1

Literature Search Product 

for 

Hexachlorobenzene (RfD/Cancer) 

(CAS No. CASRN118-74-1) 

1997- 2009

In Support of 

The Integrated Risk Information System (IRIS) – Update Project 

Prepared by 

Syracuse Research Corporation & the IRIS – Update Project Team 

December 2009 
2

IRIS – UPDATE LITERATURE SEARCH FOR HEXACHLOROBENZENE 

(CASRN 118-74-1) (RfD/CANCER) 

INTRODUCTION – Search Strategy, Dates of Search, and Presentation of Results 

The goal of the IRIS Update Program is to re-visit all IRIS dose-response assessment 

values (oral reference doses [RfDs]), inhalation reference concentrations [RfCs], cancer 

evaluations (both weight of evidence [WOE] and quantitative) that were posted on IRIS ten or 

more years ago. 

As an initial step in this goal, a literature search was performed to identify new and 

relevant information that has appeared the in the literature since the current date of posting on 

IRIS. New and relevant information is that which may be likely to result in significant 

improvements to the scientific understanding of the agent’s potential to be toxic in humans. 

The literature search was comprehensive and conducted according to conventional 

procedures in databases listed in the scientific literature (specifics available upon request). The 

title and abstract of every citation identified in the literature search were read and screened by the 

USEPA to evaluate their likelihood of offering new and relevant information for the assessment 

under consideration. 

The literature search was assembled in two parts spanning the time since the IRIS listing 

of the hexachlorobenzene assessments, 1997 - 2009. The first part was from an existing search 

performed as an initial effort in the updating process that was inclusive of the dates when the 

original file was placed upon IRIS, from 1997 to 2003. The second part of the search was 

conducted from the end date of the first part, 2003, to July, 2009. 

Based on this reading and screening each citation was coded to the following scheme on 

how the citation and the information that it may contain could possibly affect the updated 

assessment. Separate codes were provided for areas projected to include general noncancer 

(code 1) and cancer information (codes 2 and 3) for information on pharamacokinetics (code 4) 

and on effects in young populations (code 6). Codes were also provided to accommodate 

negative evaluation of citations including their not being directly useful (code 5) or at all (code 

8). A separate code was provided to designate reviews, other assessments or general 

compilations of information (code 7). 
3

Coding Scheme for Citations Identified in IRIS-Update Literature Searches 

Code Description 

1 Potential to produce a significant change in an existing noncancer toxicity value 

2 Potential to produce a significant change in an existing cancer toxicity value 

3 Potential to produce a significant change in an existing cancer WOE designation 

4 Pharmacokinetic studies (including PBPK modeling) 

5 Other toxicity studies not directly useful for establishing IRIS toxicity values 

6 Studies with information on health effects in young populations 

7 Compilations of health effects studies 

8 Not useful 

References with the same codes were collated into groups also designated by this code. 

The results of the entire search and coding are listed below. 

PRESENTATION OF RESULTS (BY CODES) 

CODE 1 (non cancer) References: 

 Babineau, K. A., A. Singh, et al. (1991). "Surface epithelium of the ovary following oral 

administration of hexachlorobenzene to the monkey." Journal of submicroscopic 

cytology and pathology. 23(3): 457-464. 

 

Hexachlorobenzene (HCB) is a toxic and carcinogenic chemical that has been 

implicated in female reproductive dysfunctions, including destruction of ovarian follicles 

in primates. The purpose of this study was to determine the effects of HCB on ovary 

surface epithelium (SE). Gelatin capsules containing HCB mixed with glucose were 

given to 16 cynomolgus monkeys housed under controlled conditions in dosages of 0.0, 

0.1, 1.0, or 10.0 mg/kg body weight daily, for 90 days; the first group served as the 

control. At necropsy one ovary from each animal was removed, fixed in glutaraldehyde, 

and processed by conventional methods for examination by transmission electron 

microscopy. SE from the animals in control group consisted of a single layer of 

squamous-to-cuboidal cells which possessed microvilli and contained cytoplasm rich in 

organelles; the nuclei were placed in middle of the cells. Although the types of alteration 

were similar in the treated groups, the degree of severity increased with increasing dose 

levels. In the lowest dose group (0.1 mg/kg) tested, stratification of cells was observed 

in some areas. Many cells were tall columnar, highly irregular in outline, and showed 

signs of degeneration. The nuclei had migrated toward the apical surface. Cytoplasm 

contained a large number of lysosomes, and numerous vesicles, which may have been 

swollen endoplasmic reticulum. In the 10 mg/kg group the affected cells were in 

advanced stages of degeneration. These observations support the evidence that HCB is 

a potent reproductive toxicant. Further studies are required to establish the effects of 

this damage on reproductive performance. 
4

Bitri, L., W. Darragi, et al. (2008). "[Effect of hexachlorobenzene on some male 

reproductive parameters in Meriones unguiculatus]." C R Biol 331(5): 380-8. 

 Organochlorine pesticides are known to cause disturbances in many 

physiological functions. The effects of in vivo administered hexachlorobenzene 

(HCB) on the male testicular function were studied in Meriones unguiculatus. 

Three groups of sexually mature meriones were orally exposed to 1.6, 4, and 16 

mg/kg of body weight in olive oil for 30 days. Morphological and morphometrical 

estimations were applied to quantify some structural constituents of the testes. 

Testicular weight was significantly decreased in all treated groups, while no 

change was noted in seminal vesicle weight. A decrease in the spermatozoid 

content of the seminiferous tube was noted and appeared correlated with a 

modification of the process of spermatogenesis. Spermatic activity in HCBtreated animals testes decreased significantly, particularly in the group treated 

with the higher dose (60+/-3.16% vs. 88+/-4.89% in controls). Plasma 

testosterone levels were decreased significantly in the groups treated with 4 and 

16 mg[HCB]/kg BW (0.48+/-0.08 ng/ml and 0.54+/-0.07 ng/ml) comparatively to 

controls (1.08+/-0.1 ng/ml) p<0.01. 

Bitri, L., N. Dhaouadi, et al. (2007). "[Toxicity of hexachlorobenzene in Meriones 

unguiculatus: effects on thyroid and liver]." C R Biol 330(5): 410-8. 

 The effect of in vivo administered hexachlorobenzene (HCB) on liver and thyroid 

was studied on Meriones unguiculatus. HCB (1.6, 4, and 16 mg/kg of body 

weight) has been administered orally to meriones for 30 days. At the end of the 

experiment, the body weight of the animals did not show significant change. 

However, the higher dose of HCB treatment led to a pronounced hepatic 

hypertrophy comparatively to controls. Histological observations revealed many 

cytomorphological alterations. Cellular necrosis, periportal, and centrolobular 

vein congestion and cytoplasmic vacuolisation were noted and correlated with 

the administered doses of HCB. The higher dose of HCB induced modifications 

in the activities of hepatic transaminases and on thyroid hormones levels: ALAT 

activity level was more pronounced in males (170+/-24.7 U/l vs. 52.66+/-8.29 U/l 

in controls) than in females (120+/-12.47 U/l vs. 56+/-5 U/l in controls). However, 

ASAT activity increased significantly only in females (259+/-29 U/l vs. 244.66+/-

18 U/l in controls). Plasma total triiodothyronine (TT3) and total thyroxine (TT4) 

levels seemed to be sex-dependent in intoxicated animals, since TT4 decreased 

significantly in males (21.95+/-7.46 nmol/l vs. 40.59+/-1.08 nmol/l in controls) and 

TT3 in females (1.42+/-0.11 nmol/l vs. 3.96+/-0.48 nmol/l in controls). 

Bourque, A. C., A. Singh, et al. (1995). "Ultrastructural changes in ovarian follicles of 

monkeys administered hexachlorobenzene." American Journal of Veterinary Research

56(12): 1673-1677. 

OBJECTIVE--To test hexachlorobenzene (HCB), an environmental pollutant, for its 

potential toxicity to the ovary. DESIGN--Nonhuman primates were orally administered 

the pollutant at doses between 0.01 and 10 mg of HCB/kg of body weight to test viability 

of ovarian follicles. At the end of dosing period, the monkeys received a compound that 
5

contained follicle-stimulating and luteinizing hormones to stimulate development of 

follicles that would be examined by electron microscopy. ANIMALS--Twenty, 6- to 13-

year-old cynomolgus monkeys were randomly assigned to 5 groups. PROCEDURE--

The HCB, in concentrations of 0.01, 0.1, 1.0, and 10.0 mg/kg, was orally administered 

with glucose in gelatin capsules for 13 weeks. Monkeys receiving capsules containing 

glucose only served as controls. After the 13th week, monkeys were given a compound 

that contained follicle-stimulating and luteinizing hormones daily during days 2 to 7 from 

the start of menses. On day 8 of the menstrual cycle, 5,000 IU of human chorionic 

gonadotropin was administered, and 35 to 38 hours later, 1 ovary from each monkey 

was obtained during laparotomy. Approximately 1-mm cubes of tissue from each ovary 

were harvested, fixed by immersion in buffered 2% glutaraldehyde, and processed for 

transmission electron microscopy. RESULTS--Ultrastructure of ovarian follicles was 

altered in the monkeys administered HCB. Lesions were observed in the follicles from 

monkeys given the lowest concentrations of HCB, and comprised condensed 

mitochondria in the developing ova and follicular cells that contained nuclei with deep 

indentations and abnormal accumulation of cytoplasmic lipid droplets. Alterations, such 

as herniation of the ooplasm, degeneration of the follicular cells, and appearance of 

abnormal spaces between follicular cells were observed in the follicles from monkeys of 

the 0.1 to 1.0 mg of HCB/kg dosage groups. The most relevant alterations were seen in 

the mitochondrion, an organelle that appeared to be most sensitive to the compound. 

Mitochondria were condensed, with abnormal intracristal spaces in the lower-dosage 

groups, and were markedly degenerated in the 10 mg/kg group. The effect of HCB were 

dose-related. CONCLUSION--The HCB is a reproductive system toxicant, and its 

damaging effects may be a result of augmentation of lipid peroxidation, especially in the 

primary follicle, which abnormally affects cellular membranes and thus, impairs their 

permeability. 

 

Chiappini, F., L. Alvarez, et al. (2009). "Hexachlorobenzene triggers apoptosis in rat 

thyroid follicular cells." Toxicol Sci 108(2): 301-10. 

 Hexachlorobenzene (HCB) is a widespread environmental pollutant. Chronic 

exposure of humans to HCB produces a number of effects, such as triggering of 

porphyria, increased synthesis of liver microsomal enzymes, neurological 

symptoms, immunological disorders and thyroid dysfunctions. In rats, HCB 

induced hepatic porphyria, neurotoxic effects, and toxic effects on the 

reproductive system, thyroid function, and immune system. HCB is also known to 

cause tumors of the liver, thyroid and mammary gland in laboratory animals. The 

aim of this study was to investigate parameters of thyroid growth regulation, 

mainly cell proliferation and apoptosis in thyroid tissue from HCB (0.1, 1, 10, 100, 

and 500 mg/kg body weight)-treated female Wistar rats. The current study 

demonstrates that only the exposure to the highest HCB dose for 30 days, has 

adverse effects on thyroid endpoints examined related to thyroid gland 

morphology, and 3,3'5,5'-tetraiodothyronine (T(4), thyroxine) serum levels, 

without changes in thyroid-stimulating hormone concentrations or in thyroid gland 

weight. Morphological changes, included flattened epithelium and increased 

colloid size compared with control tissue. Transforming growth factor (TGFbeta1) mRNA levels, evaluated by RT-PCR, revealed a significant upregulation 
6

after exposure to HCB (1, 10, 100 mg/kg body weight). Cell proliferation 

evaluated by 5'-Br deoxiuridine incorporation into DNA, was not altered at any 

dose. HCB (1, 10, 100 mg/kg body weight) induces apoptosis, evaluated by in 

situ end labeling of fragmented DNA, terminal deoxynucleotidyl transferasemediated deoxy uridine triphosphate nick-end labeling, in rat thyroid glands. This 

process is associated with dose-dependent increases in cytochrome c release 

from the mitochondria and procaspase-9 processing to its active product. 

Caspase-8 was not activated. These studies indicate that doses of HCB that do 

not disrupt thyroid economy induce TGF-beta1 expression and apoptosis in the 

thyroid gland, involving the mitochondrial pathway. 

Courtney, K. D., J. E. Andrews, et al. (1984). "Postnatal effects of hexachlorobenzene 

(HCB) on cardia lactic dehydrogenase (LDH) and creatine kinase (CK) isozymes in CD1 mice." Toxicology Letters 22(2): 223-228. 

Pregnant CD-1 mice were treated with hexachlorobenzene (HCB) by gavage at doses 

of 0, 1, 10 and 50 mg HCB/kg body weight on days 6-17 of gestation and studied on 

day 1 or 21 postpartum (pp). Hearts of the dams and pups were assayed for lactic 

dehydrogenase (LDH) and creatine kinase (CK) activities and isozyme profiles. LDH 

and CK activities and CK isozyme profiles were not affected in the dams by HCB 

treatment, but isozyme LDH-5 was significantly depressed and isozyme LDH-3 

significantly increased at the 50 mg/kg dose of HCB on day 1 pp. Hearts of the pups 

were studied on days 1, 8, 10, 15 and 21 pp. The 50 mg/kg dose level resulted in a 

statistically significantly increased mortality in the pups. The mortality at the other doses 

showed a dose-related effect. LDH and CK activities and CK isozyme profiles were not 

affected by HCB exposure in utero. The only isozyme affected was LDH-5 with a 

statistically significant increase in the 50 mg/kg dose group on day 21 pp. 

 

Foster, W. G., A. McMahon, et al. (1995). "Alterations in circulating ovarian steroids in 

hexachlorobenzene-exposed monkeys." Reproductive Toxicology 9(6): 541-548. 

 

Hexachlorobenzene (HCB) is a global pollutant that has been identified in human serum 

and ovarian follicular fluid, and its effect on ovarian function has not been adequately 

defined. Thus, the effects of HCB on ovarian steroidogenesis and menstrual cycle 

characteristics were investigated in cynomolgus monkeys (n = 16) orally dosed by 

gelatin capsule (0.0, 0.1, 1.0, and 10.0 mg HCB/kg b.wt./d) for 90 d (approximately 

three menstrual cycles). Analysis of change in menstrual cycle length for each animal 

revealed a dose-dependent increase (P = 0.02) in cycle length. Ovulatory levels of 

estradiol (E2) were significantly reduced (P = 0.02) in the highest treatment group. 

During ovulation induction, the area under the E2 concentration curve (AUC) was 

significantly (P = 0.03) suppressed in the highest treatment group. Our data 

demonstrate that HCB treatment, under the conditions of the present study, alters both 

ovarian function and menstrual cycle characteristics with a no observable adverse effect 

level of 1.0 mg/kg. 
7

Hadjab, S., D. Maurel, et al. (2004). "Hexachlorobenzene, a dioxin-like compound, 

disrupts auditory function in rat." Hear Res 191(1-2): 125-34. 

 Hexachlorobenzene (HCB) is a dioxin-like compound widely distributed in the 

environment. In this study, we investigated the effects of HCB on the cochlea. 

Conscious free-moving rats were given HCB per os daily for 4 weeks at doses of 

0.16, 4 or 16 mg/kg in olive oil, whereas the control group received olive oil only. 

The effects of HCB were evaluated at various time intervals, by measuring 

auditory nerve acoustic thresholds and plasma thyroid hormone concentration by 

radioimmunoassay. Histological evaluation involved surface preparation and 

scanning electron microscopy observations of cochlear hair cells. At a dose of 

0.16 mg/kg, HCB induced no loss of acoustic sensitivity, whereas at 4 mg/kg, it 

induced cochlear sensitivity deficits at the mid-frequencies (2-16 kHz) with 

complete recovery once treatment was stopped. At a dose of 16 mg/kg, 

permanent threshold shifts were observed at all frequencies tested (from 1 to 32 

kHz). Morphological studies showed no cochlear hair cell loss or alteration of 

stereocilia. HCB treatment reduced circulating thyroxine concentrations. 

Thyroidectomy had no effect on cochlear sensitivity in control animals. Thus, 

HCB is a potent oto-toxicant, and its ototoxicity may be independent of its 

thyroidal effects. 

Jarrell, J. F., A. McMahon, et al. (1993). "Hexachlorobenzene toxicity in the monkey 

primordial germ cell without induced prophyria." Reproductive Toxicology 7: 41-47. 

 

Hexachlorobenzene is a persistent chlorinated organic chemical that has been detected 

in many tissues from a variety of species including human ovary and human ovarian 

follicular fluid. When administered in high dosage to nonhuman primates, 

hexachlorobenzene causes destruction of ovarian primordial germ cells in association 

with systemic toxicity. The purpose of these experiments was to assess relative ovarian 

germ cell sensitivity at much lower dosages of hexachlorobenzene that do not produce 

systemic effects and additionally to evaluate oocyte function by means of the response 

to superovulation, fertilization, and embryo cleavage during a cycle of in vitro fertilization 

in the cynomolgus monkey. Hexachlorobenzene in dosages of 0.1, 1.0, and 10.0 

mg/kg/day was administered orally by gelatin capsule for 90 days. There was a dosedependent accumulation of HCB in serum and other tissues without any change in the 

serum estradiol response to human menopausal gonadotropin, oocyte recovery, oocyte 

maturation, oocyte fertilization in vitro, and early embryo cleavage rate. There was a 

dose-related toxic effect observed in primordial germ cells at the lowest dose despite no 

evidence of systemic or hepatic effects. As there were no changes in the urinary 

porphyrin excretion, the mechanism of hexachlorobenzene ovotoxicity may be distinct 

from hexachlorobenzene-induced cytochrome P-450-dependent inhibition of 

uroporphobilinogen decarboxylase in the liver, although such intraovarian metabolism 

cannot be excluded. 

Johnson, J. D., D. Vasconcelos, et al. (2005). "Subchronic Toxicity Study Of 

Hexachlorobenzene (HCB) In Female Harlan Sprague-Dawley Rats." Toxicol Sci 84(1-

S): 242. 
8

 HCB (cas #118-74-1) is used as a fungicide and an intermediate in the 

manufacture of dyes, pentachlorophenol, and rubber. HCB has some dioxin-like 

activity thereby necessitating the need to evaluate it for potential inclusion in the 

toxic equivalency factor scheme used to assess the risk of dioxin-like 

compounds. HCB, in corn oil/1% acetone, was administered by gavage (10 

rats/group) at dosages of 0 (control), 0.03, 0.1, 0.3, 1, 3, 10, or 25 mg/kg/day, 

five days a week, for 13 weeks. HCB treatment had no effect on survival. Group 

mean BW was increased (25 mg/kg/day). Total/free T4 was decreased ( > =10 

and > =1 mg/kg/day), T3 was decreased (25 mg/kg/day), and TSH was similar to 

control. Dose-related increases in hepatic CYP1A1, CYP2B, and CYP1A2 and 

pulmonary CYP1A1 activities were observed at dosages equal to and greater 

than 1, 0.03, 0.3, and at 25 mg/kg/day, respectively. Mean maximal observed 

CYP1A1 activity was 340 pmol/min/mg (25 mg/kg/day), which is markedly lower 

than that observed previously for animals treated for 13 weeks with 100 ng 

TCDD/kg (2130 pmol/min/mg). HCB increased liver cell proliferation ( > =10 

mg/kg/day). Spleen, liver, and lung absolute and relative organ weights were 

increased ( > =3, > =10, and 25 mg/kg/day, respectively). HCB-related 

microscopic findings included hepatocellular hypertrophy ( > =3 mg/kg/day), 

pulmonary focal interstitial fibrosis and histiocytic infiltration ( > =1 mg/kg/day), 

mammary gland hyperplasia and thymic atrophy ( > =10 mg/kg/day), dermal 

suppurative inflammation and ulceration (25 mg/kg/day), and splenic 

hematopoietic cell proliferation ( > =3 mg/kg/day) and lymphoid hyperplasia ( > 

=10 mg/kg/day). These data indicate that HCB has only weak dioxin-like activity 

and also exhibits non dioxin-like effects. 

Long, P. H., R. A. Herbert, et al. (2004). "Hexachlorobenzene-induced incisor 

degeneration in Sprague-Dawley rats." Toxicol Pathol 32(1): 35-40. 

 Hexachlorobenzene (HCB) was administered to female Sprague-Dawley rats in a 

13-week toxicity study conducted for the National Toxicology Program (NTP). 

Groups of 10 rats were treated by gavage with 0.0, 0.03, 0.1, 0.3, 1.0, 3.0, 10, or 

25 mg/kg HCB in corn oil 5 days/week for 13 weeks. Dose-dependent, regionspecific, maxillary incisor degeneration was observed in animals given HCB at 

doses of 1.0 mg/kg/day and higher. Treatment with 1.0 mg/kg/day resulted in 

focal mesenchymal cell vacuolation and focal osteodentin formation within the 

pulp. Lesions were restricted to a short linear region subjacent to the odontoblast 

layer along the lateral aspect of the incisor at the level of the dentin-enamel 

interface. When observed in both incisors, lesions were bilaterally symmetric. 

Treatment with 3.0 mg/kg/day resulted in lateral and medial pulp lesions and 

focal odontoblast degeneration with dentin niche formation along the lateral 

incisor margin in some animals. Treatment with 10 mg/kg/day resulted in a higher 

incidence of lateral dentin niches and a low incidence of medial dentin niches. In 

animals treated with 25 mg/kg/day, a high incidence of bilaterally symmetric, 

lateral and medial, dentin niches were observed. The morphology and 

distribution of HCB-induced incisor lesions in rats are consistent with injury to a 

selective population of preodontoblasts. 
9

NTP (2001). Data from the NTP 2001 report: Toxicity studies of hexachlorobenzene -

Not yet available National Toxicology Program,. 

 

Sims, D. E., A. Singh, et al. (1991). "Alteration of primate ovary surface epithelium by 

exposure to hexachlorobenzene: a quantitative study." histology and Histopathology 6: 

525-529. 

 

Hexachlorobenzene (HCB) is a fungicide and a pollutant of increasing concern in 

industrialized regions of the world. Reproductive failure is one of the effects of HCB 

upon mammals. Alteration of cell shape in the ovary surface epithelium (OSE) of 

Cynomolgus monkeys following oral administration of HCB was observed in this study. 

At the lowest dose used, 0.1 mg/kg body weight, a dosage that is associated with 

follicular degeneration, HCB caused quantifiable changes in length-to-width ratios of 

OSE. Measurement of cell shape by light microscopy offers a reliable indication of OSE 

changes induced by HCB. 

 

Singh, A., D. Friesen, et al. (1990). "Hexachlorobenzene toxicity in the monkey ovary. I. 

ultrastructure induced by low (0.1 mg/kg) dose exposure." Electron microscopy 12: 282-

283. 

 

Wolfe, G. W. and S. G. Pepperl (2005). Hexachlorobenzene: Reproductive Assessment 

by Continuous Breeding When Administered to Sprague-Dawley Rats by Oral Gavage, 

Volumes 1 and 2, Govt Reports Announcements & Index (GRA&I), Issue 13, 2006: 894. 

 Final rept. 

Sponsored by National Toxicology Program, Research Triangle Park, NC. 

The National Toxicology Program generates toxicity data for chemicals of concern in 

either an industrial or consumer environment. This report summarizes the data 

generated for hexachlorobenzene (HCB). It has been estimated that airborne 

emissions of HCB in the United States are between 46,300-63,900 pounds per 

year. These emissions result primarily from pesticide use and the manufacture of 

chlorinated solvents (Report on Carcinogens, Eighth Edition). A previous study 

conducted by Nakashima et al. (1997) examined the transfer of HCB during 

lactation to suckling rats, and they concluded that a large amount of HCB was 

transferred from the dams to the nursing pups through the milk in early days after 

birth. The available data on the developmental toxicity of HCB are limited. This 

study was designed to generate data on the mammalian reproductive effects of 

HCB, examine any effects during continuous breeding over two generations, and 

define a no-effect level for reproductive and developmental toxicity. 

CODE 2 (cancer) References 

 None 

CODE 3 (WOE) References 
10

Ashley, A., M. Lohitnavy, et al. (2004). "Isolation And Enrichment Of Preneoplastic 

Hepatocytes During Malignant Cell Transformation." Toxicologist 78(1-S): 225-6. 

 We modified Ito’s medium-term liver foci bioassay by incorporating time-course 

sacrifices to study pharmacokinetics/pharmacodynamics related to the 

initiationpromotion process. In our earlier clonal growth modeling studies on a 

series of chlorobenzenes, the probable existence of two cell types in glutathioneS-trasferase (GSTP) foci became apparent. As suggested by other researchers, 

these two cell types are either susceptible or resistant to mitoinhibitory effects as 

a response to external chemical insults, and those resistant to mitoinhibitory 

effect would have a growth advantage serving as basis for malignant 

transformation. Thus, as preneoplastic GSTP foci form, isolation of GSTP 

positive (GSTP+) cells from liver across time allows capturing changing 

characteristics of an emerging malignant population. This study describes an 

attempt to isolate primary GSTP+ hepatocytes using Ito’s bioassay protocol with 

diethylnitrosamine (DEN) as an initiating agent and a 2/3 partial hepatectomy 

with concomitant dosing of hexachlorobenzene (HCB; 28.4 mg/kg/day) with and 

without coexposure to PCB 126 (9.8 μg/kg/day) as promoting agents. Male F344 

rats were sacrificed at 20, 24, 28, 47 and 56 days, and 3, 6, and 9 months 

following DEN injection. By day 56, a significant increase in liver weight was 

observed in rats coexposed to HCB and PCB 126. Either primary hepatocytes or 

liver sections were taken to analyze formation of GSTP+ foci. By treating cell 

suspension and/or culture with ethacrynic acid (EA) (Stenius et al., 

Carcinogenesis 15:1561-1566, 1994), GSTP+ hepatocytes were enriched by 

inducing toxicity to non-GSTP+ cells. In so doing, progressively more malignant 

cell populations can be subjected to cell cycle kinetic studies, genomic analyses, 

and clonal growth modeling to aid our insight into the carcinogenic process. 

Audet, R. M., S. Girard, et al. (2004). "Long Term Exposure Of Human Mammary 

Epithelial Cells To Hexachlorobenzene (HCB) Induces A Procarcinogenic Phenotype." 

Toxicologist 78(1-S): 339. 

 Organochlorines are environmental lipophilic contaminants found in breast tissue 

with a debated role in breast cancer development (BCD). HCB, a widespread 

organochlorine in the environment, is virtually present in 100% of North American 

women. Epidemiological studies indicated that some breast cancer patients have 

higher HCB levels. We observed that long term exposure of human mammary 

epithelial cells to HCB increases the phosphorylation of c-erbB2 (neu). Cells with 

such epigenetic alterations can be considered procarcinogenic taking into 

account the bad prognostic role of c-erbB2 in BCD. In order to further evaluate 

the potential of HCB in causing epigenetic changes akin to a procarcinogenic 

phenotype, cultures of a non-tumorigenic human mammary epithelial cell line, 

MCF10- A, were chronically exposed to 20 μM HCB (0.1% in DMSO) or to 

DMSO alone. Following approximately 25 passages of continuous exposure to 

HCB, an increase in proliferation was observed. These cells showed an increase 

in the phosphorylation of the integrin-linked kinase (ILK), with a decrease in 

Akt/PKB levels. ECadherin, an important cell adhesion molecule, was also 

decreased. Control cells sub-cultured on Matrigel® showed a distinctive 
11

branching pattern after 24h. However, HCB-exposed cells exhibited a rounded 

shape with minimal cellular contacts. This is suggestive of a decrease in 

intercellular communication and cell adhesion ; the latter is supported by the 

decrease in E-Cadherin expression in these cells. Moreover, after 10 d in culture 

HCB-exposed cells migrated differently into the Matrigel® layer as compared to 

controls. Overall, data suggest that HCB induces a procarcinogenic phenotype 

characterized by reduced intercellular communication and that this may result 

from overactivation of ILK, known to be a down-stream target of c-erbB2, leading 

to down-regulation of Akt, which controls E-cadherin expression. This work 

brings biological plausibility to the involvement of environmental contaminants in 

BCD. 

Bauer, M., F. Hilpert, et al. (2004). "Persistent organochlorine compounds and their role 

for the carcinogenesis of breast cancer." Geburtshilfe und Frauenheilkunde 64(7): 681-

689. 

 A review. The role of persistent organochlorine compds. in the development of 

breast cancer is controversially discussed. Used as biocides or tech. adjuvants 

for misc. applications, organochlorines have been released into the environment 

for years. Due to their highly lipophilic properties, they have been able to 

accumulate in the food chain leading to a long lasting presence in human tissues. 

The evidence that organochlorines might be involved in the carcinogenesis of 

breast cancer is based on their complex toxicol. properties: organochlorines are 

able to influence estrogen-mediated and other endocrine processes; they induce 

microsomal enzyme systems with consecutive formation of genotoxic metabolites 

and activate the Her2-protooncogene product, c-neu tyrosine kinase. Several 

epidemiol. studies have investigated the correlation between organochlorine 

exposure and the incidence of breast cancer. Although the majority of authors did 

not detect a pos. correlation, the results remain inconclusive. Due to the common 

retrospective study design as well as the selection of the control population, the 

validity of some studies is questionable; due to the wide variation of tested 

compds., many studies are hard to compare. In addn., genetically detd. and 

individually varying sensitivity to organochlorines, synergistic interactions of 

several compds., and evidence for the assocn. of organochlorine exposure with 

poor prognosis in case of malignant transformation complicate the interpretation 

of many results. However, considering the available data, the involvement of 

organochlorine compds. in the carcinogenesis of breast cancer can not be 

excluded and therefore needs further investigation. 

Biggs, M. L., M. D. Davis, et al. (2008). "Serum organochlorine pesticide residues and 

risk of testicular germ cell carcinoma: a population-based case-control study." Cancer 

Epidemiology, Biomarkers and Prevention 17(8): 2012-8. 

 Testicular germ cell carcinoma (TGCC) is the most common malignancy among 

men ages 20 to 34 years. Although the pathogenesis of TGCC is poorly 

understood, suboptimal androgen levels or impaired androgen signaling may 

play a role. Some persistent organochlorine pesticides commonly found in 

human tissue possess antiandrogenic properties. We examined whether the risk 
12

of TGCC is associated with serum levels of 11 organochlorine pesticides, 

including p,p'-DDE, and whether the p,p'-DDE-TGCC association is modified by 

CAG or GGN repeat polymorphisms in the androgen receptor gene. We 

conducted a population-based case-control study among 18- to 44-year-old male 

residents of three Washington State counties. Cases (n = 246) were diagnosed 

during 1999 to 2003 with a first, primary TGCC. Controls (n = 630) were men of 

similar age with no history of TGCC from the same population identified through 

random-digit telephone dialing. Questionnaires elicited information on 

demographic, medical, and lifestyle factors. A blood specimen provided serum 

for gas chromatography-high-resolution mass spectrometry analysis of 

organochlorine pesticide residues and DNA for genotyping. We observed no 

clear patterns between TGCC risk and concentrations of any of the 

organochlorines measured, nor did we observe that the risk associated with p,p'-

DDE was modified by androgen receptor CAG (<23 versus > or =23 repeats) or 

GGN (<17 versus > or =17 repeats) genotype. This study does not provide 

support for the hypothesis that adult exposure to organochlorine pesticides is 

associated with risk of TGCC. Due to uncertainty regarding how well 

organochlorine levels measured in adulthood reflect exposures during early life, 

further research is needed using exposure measurements collected in utero or 

during infancy. 

Burgaz, S., I. Cok, et al. (2005). "Occurrence of organochlorine pesticides in cancerous 

and non-cancerous breast tissues." Fresenius Environmental Bulletin 14(11): 1024-

1030. 

 Current data provide inconsistent evidence for linking human exposure to 

organochlorine pesticides (OCPs) and risk of breast cancer development. We 

previously demonstrated that the free radical-mediated oxidative stress is partly 

assocd. with some of the OCP residues in human breast tumors. In the current 

study, we further examd. the assocn. between OCP levels in neoplastic and 

adjacent normal human breast tissues (n = 24) during menopausal status of the 

patients, tumor grade and stage of the disease. The overall mean (±SE) values 

of OCP residues in neoplastic and adjacent normal human breast tissues of 

patients have been found found to be ?-HCH 1.20 ± 0.37; 0.27 ± 0.08 ppm 

(p<0.05), ?-HCH 4.19 ± 1.07; 3.43 ± 0.63 ppm, ?-HCH 0.69 ± 0.20; 0.26 ± 0.11 

ppm (p<0.05), HCB 0.23 ± 0.11; 0.18 ± 0.08 ppm, heptachlorepoxide (HE) 1.54 ± 

0.47; 0.40 ± 0.20 ppm (p<0.01), p.p'-DDE 5.18 ± 0.88; 5.37 ± 1.06 ppm, and 

p.p'DDT 2.02 ± 1.10; 1.89 ± 0.59 ppm, resp. resp. Certain OCP elevations in 

breast tumors, although their role for the menopausal status of the patients, and 

stage and grade of the disease could not clearly evidenced, show that these 

OCPs, to a certain extent, might play a role in breast cancer risk. 

Cantor, K. P., P. T. Strickland, et al. (2003). "Risk of non-Hodgkin's lymphoma and 

prediagnostic serum organochlorines: beta-hexachlorocyclohexane, 

chlordane/heptachlor-related compounds, dieldrin, and hexachlorobenzene." 

Environmental Health Perspectives 111(2): 179-83. 
13

 Increases in non-Hodgkin's lymphoma (NHL) incidence and mortality rates during 

the past few decades remain largely unexplained. Studies suggest that 

organochlorine pesticides may contribute to an increased risk of NHL. In 1974, 

serum samples were obtained from 25,802 participants in the Campaign Against 

Cancer and Stroke in Washington County, Maryland (USA), and cryopreserved 

for future study. We measured prediagnostic levels of chlordane, lindane 

(gamma-hexachlorocyclohexane), beta-hexachlorocyclohexane, transnonachlor, 

heptachlor, heptachlor epoxide, oxychlordane, dieldrin, and hexachlorobenzene 

in serum samples of 74 cases of NHL and 147 matched controls. Previously, we 

found an association between NHL and serum levels of total PCBs 

(polychlorinated biphenyls), but not DDT (dichlorodiphenyltrichloroethane) and 

related compounds. In this instance, there was no evidence of an association 

between NHL risk and serum levels of any of the individual lipid- and recoverycorrected organochlorines that we evaluated, nor of the summed chlordanerelated compounds (transnonachlor, heptachlor, heptachlor epoxide, 

oxychlordane). These findings do not support the hypothesis that the 

organochlorine compounds included in this study are strongly linked to the 

development of NHL. The possibility of a weak association cannot be excluded 

by these data. 

Charbonneau, M., I. Plante, et al. (2005). "Modulation Of Cell-Cell Interactions By 

Epigenetic Hepatocarcinogens." Toxicol Sci 84(1-S): 336-7. 

 Mechanisms of epigenetic carcinogenesis involve disruption of cell or tissue 

homeostasis, such as cell-cell interactions mediated by various types of 

junctions. Gap junctions are formed by channels that allow direct communication 

between cells (GJIC), while adhering junctions maintain tissue integrity by linking 

cells together. Gap and adhering junctions are physically and functionally 

interrelated membrane structures. Connexins and cadherins are key proteins in 

gap and adhering junctions, respectively. While the effects of hepatocarcinogens 

on these proteins in rodent livers are well documented and will be discussed in 

this presentation, the pathways involved in their regulation are less understood. 

Consequently, a particular emphasis will be made on hexachlorobenzene (HCB), 

an important environmental contaminant, that modulates intracellular pathway 

involved in cell junctions. HCB causes liver tumor formation and down-regulation 

of connexins and E-cadherin in the liver of female but not male rats. A sexual 

dimorphism in the activation of the ILK pathway is believed to be responsible for 

these down-regulations ; inactivation of GSK3-beta and nuclear translocation of 

both Akt and beta-catenin are important events. In vitro studies, using specific 

inhibitors and overexpression systems confirmed not only the role of ILK pathway 

in cell-cell interactions, but also the functional interrelationships between 

connexins and cadherins. Down-regulation of proteins forming gap and adhering 

junctions allow initiated cells to escape control from neighboring cells, thus 

promoting their clonal expansion. The importance of such mechanisms in 

carcinogenesis is illustrated by the fact that human tumors of various origins 

show low levels of immunoreactive connexins and cadherins. Moreover, studies 

suggest that lost of cell-cell interaction proteins is an early event in the 
14

carcinogenesis process. Overall, data support the contention that gap and 

adhering junctions are at the basis of important cell-cell interactions disruptuted 

in epigenetic hepatocarcinogenesis. 

Charlier, C., A. Albert, et al. (2003). "Breast cancer and serum organochlorine 

residues." Occup Environ Med 60(5): 348-51. 

 BACKGROUND: Controversy still exists about the breast carcinogenic properties 

in humans of environmental xenoestrogens (organochlorines), justifying new 

investigations. AIMS: To compare the blood levels of total 

dichlorodiphenyltrichloroethane (DDT) and hexachlorobenzene (HCB) in samples 

collected at the time of breast cancer discovery, in order to avoid the potential 

consequences of body weight change (after chemotherapy or radiotherapy) on 

the pesticide residue levels. METHODS: Blood levels of HCB and total DDT (we 

calculated total DDT concentrations by adding all DDT and DDE isomers) were 

compared in 159 women with breast cancer and 250 presumably healthy 

controls. Risk of breast cancer associated with organochlorine concentration was 

evaluated. RESULTS: Mean levels of total DDT and HCB were significantly 

higher for breast cancer patients than for controls. No differences in serum levels 

of total DDT or HCB were found between oestrogen receptor positive and 

oestrogen receptor negative patients with breast cancer. CONCLUSIONS: These 

results add to the growing evidence that certain persistent pollutants may occur 

in higher concentrations in blood samples from breast cancer patients than 

controls. 

Charlier, C., J. M. Foidart, et al. (2004). "Environmental dichlorodiphenyltrichlorethane 

or hexachlorobenzene exposure and breast cancer: is there a risk?" Clin Chem Lab 

Med 42(2): 222-7. 

 The carcinogenic potential of environmental xenoestrogens (i.e., 

organochlorines) is a matter of controversy. Their pathogenic role as promoters 

in breast cancer has been previously suggested. In Europe, despite their 

prohibition since the '70s, residues persist in soil and rivers resulting in a 

widespread contamination of the general population. In this study, we have 

compared the serum levels of p,p'-1,1-dichloro-2, 2-bis (4-chlorophenyl) ethylene 

(DDE) and hexachlorobenzene (HCB) in 231 women at the time of breast cancer 

discovery and in 290 age-matched healthy controls. p,p'-DDE was found in 

76.2% of cases and in 71.1% of controls but HCB was present only in 12.6% of 

cases (29 from 231) and in 8.9% of controls (26 from 290). Even if taking all 

undetectable results (recorded as "0") into consideration, mean values were 

significantly different in cases when compared to controls. The serum level of 

p,p'-DDE was 3.46 +/- 3.48 ppb (0.58 +/- 0.58 microg/g lipid) in patients and 1.85 

+/- 2.09 ppb (0.31 +/- 0.35 microg/g lipid) in controls (p < 0.0001). The HCB 

serum level was 0.66 +/-.25 ppb (0.11 +/- 0.21 microg/g lipid) in patients and 0.20 

+/- 1.02 ppb (0.03 +/- 0.17 microg/g lipid) in controls (p < 0.0001). When 

considering p,p'-DDE and HCB as binary variables (1 if higher than the limit of 

quantification, 0 if lower), the presence of both residues was significantly 

associated with an increased risk of breast cancer development (OR 2.21, 95% 
15

CI 1.41-3.48 for p,p'-DDE and OR 4.99, 95% CI 2.95-8.43 for HCB). No excess 

was observed among parous women or when familial history of breast cancer 

was considered. In the cancer group, no differences in serum levels of p,p'-DDE 

or HCB were found in relation with estrogen-receptor (ER) status, Bloom stage or 

lymph node metastasis, but the HCB level was moderately correlated with tumor 

size (p = 0.026). 

Cocco, P., P. Brennan, et al. (2008). "Plasma polychlorobiphenyl and organochlorine 

pesticide level and risk of major lymphoma subtypes." Occupational and Environmental 

Medicine 65(2): 132-40. 

 BACKGROUND: There is conflicting epidemiological evidence concerning an 

increase in risk of non-Hodgkin's lymphoma (NHL) associated with elevated 

blood levels of persistent organochlorine (OC) pesticides and 

polychlorobiphenyls (PCBs). METHODS: We measured the concentration of 17 

OC pesticides, including hexachlorobenzene (HCB), four lindane isomers (alpha-

, beta-, gamma- and delta-hexachlorocyclohexane (HCH)), two chlordane 

species (heptachlor and oxy-chlordane), four cyclodiene insecticides (aldrin, 

dieldrin, endrin and mirex), six dichloro-diphenyl-trichloroethane (DDT) isomers 

and nine PCB congeners (PCBs 28, 52, 101, 118, 138, 153, 170, 180 and 194) in 

plasma samples of 377 subjects, including 174 NHL cases and 203 controls from 

France, Germany and Spain. The risk of NHL and its major subtypes associated 

with increasing blood levels of OC pesticides and PCBs was calculated using 

unconditional logistic regression. RESULTS: Risk of NHL, diffuse large B cell 

lymphoma (DLBCL) and chronic lymphatic leukaemia (CLL) did not increase with 

plasma levels of HCB, beta-HCH, p,p'-dichloro-diphenyl-dichloroethylene (DDE), 

or total and individual PCBs or their functional groups, in the overall study 

population. Substantial heterogeneity in DLBCL risk associated with immunotoxic 

PCBs (p = 0.03) existed between the Spanish subgroup (odds ratio (OR) for 

immunotoxic PCB plasma level above the median vs below the median was 0.7, 

95% CI 0.3 to 1.6) and the French and German subgroups combined (OR 3.2, 

95% CI 0.9 to 11.5). CONCLUSION: We did not find evidence of an association 

between NHL risk and plasma level of OC pesticides and PCBs. 

De Roos, A. J., P. Hartge, et al. (2005). "Persistent organochlorine chemicals in plasma 

and risk of non-Hodgkin's lymphoma." Cancer Research 65(23): 11214-26. 

 Polychlorinated biphenyls (PCB) have been suspected as possible contributors 

to increasing non-Hodgkin's lymphoma incidence during the latter half of the 20th 

century based on their toxicologic properties and provocative epidemiologic 

reports. We investigated PCBs and other organochlorines and risk of nonHodgkin's lymphoma in a population-based case-control study in the United 

States. Congeners of PCBs (including coplanar congeners), dioxins, furans and 

pesticides or pesticide metabolites were measured in plasma of 100 untreated 

cases and 100 control subjects. We used a multiple imputation procedure to fill in 

missing values of levels determined to be below the detection limits. Risks of 

non-Hodgkin's lymphoma associated with each analyte were estimated using 

conditional logistic regression for the continuous measure, exposure quartiles, 
16

trend across quartile categories, and exposures above the 95th percentile. 

Certain PCB congeners were associated with increased risk of non-Hodgkin's 

lymphoma, including coplanar PCBs 156, 180, and 194, with odds ratios for the 

highest versus lowest quartile ranging from 2.7 to 3.5, and significant trends. 

Each of the furan congeners was associated with risk of non-Hodgkin's 

lymphoma, as were total furans, with 3.5-fold increased risk for the highest 

versus lowest quartile and a significant trend across quartiles (P = 0.006). The 

toxic equivalency quotient (TEQ), a summed metric that weights congeners by 

their dioxin-like potency, was associated with non-Hodgkin's lymphoma, with 

35% increased risk per 10 TEQ pg/g lipid (95% confidence interval, 1.02-1.79). 

Our results add to existing literature, which suggests that exposure to 

organochlorines contributes to non-Hodgkin's lymphoma risk; these risks were 

most apparent for certain PCBs and furans. 

Ebadi, A. G., M. Shokrzadeh, et al. (2005). "Relation between serum level of some 

organochlorine pesticides and breast cancer in Mazandaran province." Chemistry 

(Rajkot, India) 2(2): 73-79. 

 Concerns about the breast carcinogenic properties by environmental 

xenoestrogens (organochlorine pesticides) still exists and making new studies to 

compare the blood levels of total dichlorodiphenyl trichloroethane (DDT) and 

hexachlorobenzene (HCB) in blood samples collected at the time of breast 

cancer discovery. Blood levels of HCB and total DDT were calcd. and compared 

in 159 women with breast cancer and 250 presumably healthy controls. Risk of 

breast cancer assocd. with organochlorine concn. was evaluated. Mean levels of 

total DDT and HCB were significantly higher for breast cancer patients than for 

controls. No differences in serum levels of total DDT or HCB were found between 

estrogen receptor pos. and estrogen receptor neg. patients with breast cancer. 

These results add to the growing evidence that certain persistent pollutants may 

occur in higher concns. in blood samples from breast cancer patients than 

controls. 

Fratev, F. and E. Benfenati (2008). "A combination of 3D-QSAR, docking, local-binding 

energy (LBE) and GRID study of the species differences in the carcinogenicity of 

benzene derivatives chemicals." Journal of molecular graphics & modelling. 27(2): 147-

60. 

 A combination of 3D-QSAR, docking, local-binding energy (LBE) and GRID 

methods was applied as a tool to study and predict the mechanism of action of 

100 carcinogenic benzene derivatives. Two 3D-QSAR models were obtained: (i) 

model of mouse carcinogenicity on the basis of 100 chemicals (model 1) and (ii) 

model of the differences in mouse and rat carcinogenicity on the basis of 73 

compounds (model 2). 3D-QSAR regression maps indicated the important 

differences in species carcinogenicity, and the molecular positions associated 

with them. In order to evaluate the role of P450 metabolic process in 

carcinogenicity, the following approaches were used. The 3D models of CYP2E1 

for mouse and rat were built up. A docking study was applied and the important 

ligand-protein residues interactions and oxidation positions of the molecules were 
17

identified. A new approach for quantitative assessment of metabolism pathways 

was developed, which enabled us to describe the species differences in CYP2E1 

metabolism, and how it can be related to differences in the carcinogenic potential 

for a subset of compounds. The binding energies of the important substituents 

(local-binding energy-LBE) were calculated, in order to quantitatively 

demonstrate the contribution of the substituents in metabolic processes. 

Furthermore, a computational procedure was used for determining energetically 

favourable binding sites (GRID examination) of the enzymes. The GRID 

procedure allowed the identification of some important differences, related to 

species metabolism in CYP2E1. Comparing GRID, 3D-QSAR maps and LBE 

results, a similarity was identified, indicating a relationship between P450 

metabolic processes and the differences in the carcinogenicity. 

Hardell, K., M. Carlberg, et al. (2009). "Concentrations of organohalogen compounds 

and titres of antibodies to Epstein-Barr virus antigens and the risk for non-Hodgkin 

lymphoma." Oncol Rep 21(6): 1567-76. 

 Exposure to some pesticides and persistent organic pollutants (POPs) has been 

indicated to be a risk factor for non-Hodgkin's lymphoma (NHL). Epstein-Barr 

virus (EBV) has been associated with some subgroups of NHL. In a previous 

study we found an interaction between high concentrations of some POPs and 

titres of antibodies to EBV early antigen (EA IgG) in relation to NHL. In the 

present study we measured lipid adjusted plasma concentrations of 35 

congeners of polychlorinated biphenyls (PCB), p,p'-

dichlorodiphenyldichloroethyelene (p,p'-DDE), hexachlorobenzene (HCB), seven 

subgroups of chlordanes (cis-heptachlorepoxide, cis-chlordane, trans-chlordane, 

oxychlordane, MC6, trans-nonachlordane, cis-nonachlordane) and one 

polybrominated diphenylether (PBDE) congener (no. 47) in 99 cases with NHL 

and 99 population based controls. Odds ratios (OR) for NHL were estimated. 

Sum of PCBs > median in the controls gave odds ratio (OR) 2.0, 95% confidence 

interval (CI) 0.99-3.9. High sum of chlordanes yielded OR 2.3, 95% CI 1.2-4.5. 

An interaction with EBV EA IgG was found. High sum of PCB gave OR 5.2, 95% 

CI 1.9-14 in the group with EA IgG > 40. Similarly HCB yielded OR 5.3, 95% CI 

1.9-15, pp'-DDE gave OR 3.3, 95% CI 1.4-7.7 and sum of chlordanes yielded OR 

6.8, 95% CI 2.3-20, whereas no association was found with PBDE. In summary, 

this study confirmed an association between certain POPs and NHL with an 

interaction with titre of IgG antibody to EBV EA. 

Hardell, L., S. O. Andersson, et al. (2006). "Adipose tissue concentrations of persistent 

organic pollutants and the risk of prostate cancer." Journal of Occupational and 

Environmental Medicine 48(7): 700-7. 

 OBJECTIVE: We sought to study the concentrations of certain persistent organic 

pollutants with endocrine-disrupting properties in cases with prostate cancer and 

controls with benign prostate hyperplasia. METHODS: Adipose tissue was 

obtained from 58 cases and 20 controls. RESULTS: The median concentration 

among controls was used as cut-off in the statistical analysis. In the total 

material, a greater-than median concentration of PCB congener 153 yielded an 
18

odds ratio (OR) of 3.15 and 95% confidence interval (CI) of 1.04-9.54 and one 

chlordane type, trans-chlordane, yielded OR 3.49 (95% CI = 1.08-11.2). In the 

group of case subjects with PSA levels greater than the median level of 16.5 

ng/mL, PCB 153 was OR 30.3 (95% CI = 3.24-284), hexachlorobenzene OR = 

9.84 (95% CI = 1.99-48.5), trans-chlordane OR = 11.0 (95% CI = 1.87-64.9), and 

the chlordane-type MC6 OR = 7.58 (95% CI = 1.65-34.9). The grouping of PCBs 

according to structural and biological activity was found to produce significantly 

increased risks for enzyme and phenobarbital-inducing PCBs and lower 

chlorinated PCBs in the case group with PSA levels greater than 16.5 ng/mL. 

CONCLUSIONS: These chemicals might be of etiologic significance but need to 

be further investigated. The biological relevance of the arbitrary cut-off point of 

PSA is unclear. 

Hardell, L., B. Bavel, et al. (2006). "In utero exposure to persistent organic pollutants in 

relation to testicular cancer risk." International Journal of Andrology 29(1): 228-34. 

 Testicular cancer is the most common tumour type in young men. In Sweden the 

annual age-adjusted incidence increased significantly by 2.4% during the time 

period 1984-1993 and during 1994-2003 by 1.4%. Exposure to endocrine 

disrupting chemicals during the foetal period has been postulated to be a risk 

factor. In this investigation we studied the concentrations of chlorinated biphenyls 

(PCBs), p,p'-dichlorodiphenyl-dichloroethylene (pp'-DDE), hexachlorobenzene 

(HCB), chlordanes and polybrominated diphenylethers (PBDEs) in 58 cases with 

testicular cancer and 61 age-matched controls. Furthermore, case and control 

mothers were also asked to participate and 44 case mothers and 45 control 

mothers agreed. No significant differences were found between cases and 

controls. Case mothers had in general higher concentrations of these chemicals. 

For the sum of PCBs an odds ratio (OR) = 3.8, 95% confidence interval (CI) = 

1.4-10 was calculated using the median concentration for the controls as cut-off 

value. For HCB OR = 4.4, CI = 1.7-12 and for PBDE OR = 2.5, 95% CI = 1.02-

6.0 were obtained, whereas OR was not significantly increased for pp'-DDE and 

sum of chlordanes. The cases were born during a period with high 

concentrations of persistent organic pollutants (POPs) in humans. The decline of 

the increasing incidence of testicular cancer during recent years may reflect 

decreasing body burden of certain POPs since the 1980s. 

Hardell, L., M. Carlberg, et al. (2007). "Decreased survival in pancreatic cancer patients 

with high concentrations of organochlorines in adipose tissue." Biomedicine and 

Pharmacotherapy 61(10): 659-64. 

 We analysed adipose tissue concentrations of persistent organic pollutants 

(POPs) in 21 cases with exocrine pancreatic cancer. The comparison group 

consisted of 59 subjects. Significantly increased concentrations of 

polychlorinated biphenyls (PCBs), hexachlorobenzene (HCB), sum of chlordanes 

and polybrominated diphenylethers (PBDEs) were found in the cases. For 1,1,-

dichloro-2,2-bis(p-chlorophenyl)-ethylene (p,p'-DDE) no significant difference was 

seen. For PCBs no odds ratio (OR) could be calculated since all cases had 

concentration>median in controls used as a cut-off. HCB yielded OR=53.0, 95% 
19

confidence interval (CI)=4.64-605 and sum of chlordanes OR=18.4, 95% 

CI=2.71-124 whereas OR was not significantly increased for p,p'-DDE or PBDEs. 

Body mass index (BMI) at the time of tissue sampling was significantly lower for 

the cases. This might have influenced the results. Using BMI one year previously 

or decreasing the concentrations of POPs with the same percentage as weight 

loss among the cases did not change the results. Survival of the cases was 

shorter in the group with the concentration of POPs>median among cases, 

significantly so for the sum of PCBs (147 vs. 294 days), p,p'-DDE (134 vs. 302 

days), and sum of chlordanes (142 vs. 294 days) in the high and low group, 

respectively. The results were based on a low number of cases and should be 

interpreted with caution. 

Hardell, L. and M. Eriksson (2003). "Is the decline of the increasing incidence of nonHodgkin lymphoma in Sweden and other countries a result of cancer preventive 

measures?" Environmental Health Perspectives 111(14): 1704-6. 

 Is the decline of the increasing incidence of non-Hodgkin lymphoma (NHL) in 

Sweden and other countries a result of cancer preventive measures? The yearly 

age-standardized incidence of NHL increased significantly in Sweden during 

1971-1990, for men an average of 3.2% and for women 3.1%. The 

corresponding figures for 1991-2000 were -0.8% and -0.2%, respectively. A 

decline of the increasing incidence has also been seen in other countries, such 

as the United States, Finland, and Denmark. Immunosuppression is one 

established risk factor for NHL, possibly with interaction with Epstein-Barr virus. 

Phenoxyacetic acids and chlorophenols, both pesticides, have been associated 

with NHL. Use of these chemicals was banned in Sweden in 1977 and 1978, 

respectively. Also, persistent organic pollutants such as polychlorinated 

biphenyls, hexachlorobenzene, chlordanes, and dioxins have been shown to 

increase the risk. Exposure of the whole population occurs predominantly 

through the food chain. Exposure to such chemicals was highest in the 1960s 

and 1970s. Because of regulation in the 1970s, exposure has declined 

substantially in the population. The change in incidence of NHL in Sweden and 

other countries may serve as a good example of how prohibition and limitation of 

exposure may be reflected in cancer statistics some decades later. 

Hardell, L., G. Lindstrom, et al. (2006). "High concentrations of organochlorines in a 

patient with kidney cancer and anorexia-cachexia syndrome." Med Chem 2(6): 607-10. 

 PURPOSE: To determine persistent organic pollutants in adipose tissue in a 

patient with kidney cancer. METHODS: Adipose tissue was sampled from the 

abdominal wall during autopsy of a 75-year old man who had died from a kidney 

cancer. The concentrations of polychlorinated biphenyls (PCBs), p,p'-

dichlorodiphenyltrichloroethane (DDE), hexachlorobenzene (HCB), chlordanes 

and tetrabromodiphenyl ether (TeBDE) were determined on lipid basis. For 

comparison results from 29 male population based subjects aged 70-80 years 

were used. RESULTS: All concentrations except for TeBDE were very high in the 

patient; sum of PCBs 18 808 ng/g fat (median for controls 997), DDE 14 183 

(median for controls 751), HCB 424 (median for controls 46), and sum of 
20

chlordanes 2 389 (median for controls 62). The patient lost weight from 80 kg to 

48 kg when he died, which may have contributed wholly or partly to the very high 

concentrations of organochlorines. CONCLUSION: Changes in weight must be 

recorded in cancer patients and the concentrations of persistent organic 

pollutants should be normalized to weight. The concentrations in this patient 

were 10- to almost 40-times higher than in the controls. Such very high 

concentrations may give clinical symptoms in the final stage of a wasting cancer 

patient. 

Hardell, L., B. van Bavel, et al. (2004). "Adipose tissue concentrations of p,p'-DDE and 

the risk for endometrial cancer." Gynecol Oncol 95(3): 706-11. 

 OBJECTIVE: To evaluate in a case-control study possible risk of endometrial 

cancer associated with environmental endocrine disruptors. METHODS: We 

analyzed the adipose tissue concentrations of polychlorinated biphenyls, 

hexachlorobenzene (HCB), p,p'-dichlorodiphenyl-dichloroethylene (p,p'-DDE), 

chlordanes, and polybrominated biphenyls in 76 cases with endometrial cancer 

and 39 controls with benign endometrial hyperplasia. RESULTS: For the different 

chemicals, odds ratios (ORs) and 95% confidence intervals (CI) were close to 

unity taking the median concentration among the controls as cutoff value. 

However, for p,p'-DDE OR = 1.9, 95% CI = 0.8-4.8 was obtained. Additional 

estrogen replacement therapy yielded in this category OR = 2.3, 95% CI = 0.6-

8.6. CONCLUSION: The results suggest an interaction between p,p'-DDE and 

estrogen replacement drugs in the etiology of endometrial cancer, although no 

significant associations were found. 

Hardell, L., B. van Bavel, et al. (2003). "Increased concentrations of polychlorinated 

biphenyls, hexachlorobenzene, and chlordanes in mothers of men with testicular 

cancer." Environ Health Perspect 111(7): 930-4. 

 An increasing incidence of testicular cancer has been reported from several 

countries in the Western world during the last decades. According to current 

hypothesis, testicular cancer is initiated during the fetal period, and exposure to 

endocrine disruptors, i.e., xenoestrogens, has been of concern. In this 

investigation we studied the concentrations of the sum of 38 polychlorinated 

biphenyls (PCBs), p,p'-dichlorodiphenyl-dichloroethylene, hexachlorobenzene 

(HCB), and chlordanes, in 61 cases with testicular cancer and 58 age-matched 

controls. Furthermore, case and control mothers were also asked to participate, 

and 44 case mothers and 45 control mothers agreed. They were of similar age. 

In cases only the concentration on lipid basis of cis-nonachlordane was 

significantly increased, whereas case mothers showed significantly increased 

concentrations of the sum of PCBs, HCB, trans- and cis-nonachlordane, and the 

sum of chlordanes. Among case mothers the sum of PCBs yielded an odds ratio 

(OR) of 3.8; 95% confidence interval (CI), 1.4-10 was calculated using the 

median concentration for the control mothers as cutoff value. For HCB, OR = 4.4 

(95% CI, 1.7-12); for trans-nonachlordane, OR = 4.1 (95% CI, 1.5-11); for cisnonachlordane, OR = 3.1 (95% CI, 1.2-7.8); and for sum of chlordanes, OR = 1.9 
21

(95% CI, 0.7-5.0). No consistent different risk pattern was found for seminoma or 

nonseminoma testicular cancer. 

Hess-Wilson, J. K. and K. E. Knudsen (2006). "Endocrine disrupting compounds and 

prostate cancer." Cancer Letters 241(1): 1-12. 

 Prostate cancer is a major health concern and is treated based on its hormone 

dependence. Agents that alter hormone action can have substantial biological 

effects on prostate cancer development and progression. As such, there is 

significant interest in uncovering the potential effects of endocrine disrupting 

compound (EDC) exposure on prostate cancer. The present review is focused on 

agents that alter hormone action in the prostate and how they may impact cancer 

growth or treatment. 

Howsam, M., J. O. Grimalt, et al. (2004). "Organochlorine exposure and colorectal 

cancer risk." Environmental Health Perspectives 112(15): 1460-6. 

 Organochlorine compounds have been linked to increased risk of several 

cancers. Despite reductions in their use and fugitive release, they remain one of 

the most important groups of persistent pollutants to which humans are exposed, 

primarily through dietary intake. We designed a case-control study to assess the 

risk of colorectal cancer with exposure to these chemicals, and their potential 

interactions with genetic alterations in the tumors. A subsample of cases (n = 

132) and hospital controls (n = 76) was selected from a larger case-control study 

in Barcelona, Catalonia, Spain. We measured concentrations in serum of several 

organochlorines by gas chromatography. We assessed point mutations in K-ras 

and p53 genes in tissue samples by polymerase chain reaction/single-strand 

conformation polymorphism and assessed expression of p53 protein by 

immunohistochemical methods. An elevated risk of colorectal cancer was 

associated with higher serum concentrations of mono-ortho polychlorinated 

biphenyl (PCB) congeners 28 and 118. The odds ratio for these mono-ortho 

PCBs for middle and higher tertile were, respectively, 1.82 [95% confidence 

interval (CI), 0.90-3.70] and 2.94 (95% CI, 1.39-6.20). Alphahexachlorocyclohexane, hexachlorobenzene, and p,p'-DDE (4,4'-

dichlorodiphenyltrichloroethene) showed nonsignificant increases in risk. Risk 

associated with mono-ortho PCBs was slightly higher for tumors with mutations 

in the p53 gene but was not modified by mutations in K-ras. Mono-ortho PCBs 

were further associated with transversion-type mutations in both genes. These 

results generate the hypothesis that exposure to mono-ortho PCBs contributes to 

human colorectal cancer development. The trend and magnitude of the 

association, as well as the observation of a molecular fingerprint in tumors, raise 

the possibility that this finding may be causal. 

Ichihara, T., N. Imai, et al. (2005). "Evidence of a threshold dose for promotion of 

hepatocarcinogenesis by hexachlorobenzene in a rat medium-term liver bioassay." 

Journal of Toxicologic Pathology 18(1): 7-11. 

 The potential of hexachlorobenzene (HCB) to promote the development of 

glutathione S-transferase placental form (GST-P) pos. foci in the male 
22

F344/DuCrj (F344) rat liver was evaluated with 11 different dietary doses, 

ranging from 0.002 to 75 ppm, using a medium-term liver bioassay system. No 

mortalities caused by HCB treatment were encountered, and no clin. changes 

were apparent. The nos. and areas of GST-P pos. foci in the 0.002-40-ppm 

groups were comparable with the control values, but those in the 75-ppm HCB 

group were slightly, albeit not significantly, increased. The present results 

indicate that HCB exerts a weak promotion potential for rat liver carcinogenesis, 

but only at a dietary level of 75 ppm (5.27 mg/kg/day), thus providing evidence 

for the existence of a threshold. 

Iscan, M., T. Coban, et al. (2002). "The organochlorine pesticide residues and 

antioxidant enzyme activities in human breast tumors: is there any association?" Breast 

Cancer Research and Treatment 72(2): 173-82. 

 The levels of some organochlorine pesticides (OCP)s (hexachlorobenzene, HCB, 

alpha-hexachlorocyclohexane, alpha-HCH, beta-HCH, gamma-HCH, 

heptachlorepoxide, HE, bis (4-chlorophenyl)-1,1-dichloroethene, p.p'DDE, bis (4-

chlorophenyl)-1,1,1-trichloroethane, p.p' DDT and total DDT (E-DDT) and 

antioxidant enzyme activities namely Cu, Zn superoxide dismutase (SOD), 

catalase (CAT), selenium-dependent glutathione peroxidase (Se-GSH-Px), total 

glutathione peroxidase (T-GSH-Px), selenium independent glutathione 

peroxidase (GSH-Px II), glutathione reductase (GRd), level of reduced 

glutathione (GSH) and lipid peroxidation (LP), glutathione S-transferase (GST) 

activity toward several substrates including 1-chloro-2,4-dinitrobenzene (CDNB), 

1,2-dichloro-4-nitrobenzene (DCNB), ethacrynic acid (EAA), 1,2-epoxy-3-(pnitrophenoxy)-propane (ENPP) were measured in tumor and surrounding tumor 

free tissues of 24 female breast cancer patients and was evaluated whether 

there exist any association between the levels of OCPs and antioxidants. The 

mean levels of GSH, alpha-BHC, gamma-BHC and HE, and activities of SOD, 

Se-GSH-Px, T-GSH-Px, GSH-Px II,GRd, GST CDNB, and GST DCNB were 

significantly higher in tumors than in controls. In tumors, significant correlations 

were noted between: SOD and y-BHC; Se-GSH-Px and gamma-BHC; T-GSH-Px 

and gamma-BHC; GSH-Px II and alpha-BHC, gamma-BHC; GSH and alphaBHC, gamma-BHC, HE; GRd and alpha-BHC; CDNB GST and alpha-BHC, 

gamma-BHC. These results show that free-radical mediated oxidative stress is, 

at least partly, associated with some of these OCP residues in human breast 

tumors. 

Joffe, M. (2004). "Re: "Increased concentrations of polychlorinated biphenyls, 

hexachlorobenzenes, and chlordanes in mothers of men with testicular cancer"." 

Environ Health Perspect 112(1): A21-2; author reply A22. 

 

Khanjani, N., D. R. English, et al. (2006). "An ecological study of organochlorine 

pesticides and breast cancer in rural Victoria, Australia." Archives of Environmental 

Contamination and Toxicology 50(3): 452-61. 

 A number of studies have suggested that environmental contamination with 

organochlorine pesticides may be related to risk of breast cancer. To investigate 
23

this association in a rural part of Australia, organochlorine contamination data 

from a breast milk organochlorine study conducted in the state of Victoria in 1993 

were used. The state was divided into 11 statistical divisions. Standardized 

incidence ratios (SIRs) for the 11 regions were calculated using breast cancer 

incidence data from 1983 to 2002. During that time, 47,250 breast cancer cases 

occurred in Victoria, which had an average population of 2,147,409 women. The 

Ovens-Murray region, which was the region most contaminated with 

organochlorine pesticides, showed an elevated SIR of 1.10 (95%CI, 1.03-1.17), 

although two other regions with lower organochlorine contamination levels also 

had elevated SIRs. The rural part of the Ovens-Murray region, where the main 

pesticide use occurred, had the highest SIR, 1.15 (95%CI, 1.07-1.23). We did not 

find any significant correlation between organochlorine contamination and the 

age-standardized rate of breast cancer across all regions. But a positive doseresponse relationship using an adjusted negative binomial model was detected 

for heptachlor epoxide. Our study may provide limited support for the role of 

environmental contamination with organochlorine pesticides in the development 

of breast cancer. 

Kishima, M. O., L. F. Barbisan, et al. (2000). "Promotion of hepatocarcinogenesis by 

hexachlorobenzene in energy- restricted rats." Cancer Lett 152(1): 37-44. 

 The interaction between dietary energy restriction and low dose of the fungicide 

hexachlorobenzene (HCB) was evaluated in a rat liver medium- term bioassay 

for carcinogenesis. Male Wistar rats were fed a control or a 50% energyrestricted diet, both added or not with 50 ppm HCB, for 6 weeks. HCB exposure 

or energy restriction separately did not exert any influence on the development of 

glutathione S-transferase placental form (GST-P(+)) foci of hepatocytes. 

Simultaneous HCB exposure and energy restriction induced a significant 

increase in liver centrilobular hypertrophy and GST-P(+) foci development. Our 

findings suggest that energy restriction increases liver response to low dose of 

HCB, unmasking the promoting potential of this fungicide. 

Leao, M. B. C., A. C. Pavao, et al. (2005). "A multivariate model of chemical 

carcinogenesis." Theochem 719(1-3): 129-135. 

 In this work we have investigated electronic parameters that characterize the 

action of carcinogens, i.e descriptors such as electron affinity, ?(HOMO-LUMO), 

dipole moments, electrostatic attraction, formation heat (Hf) and permeability of 

the cellular membrane (c Log P) for selected compds. The multivariate anal. 

allows us to propose a theor. model that correlates these descriptors with the 

carcinogenic activity in a series of chem. compds. The protecting activity of 

antioxidants was analyzed by considering their competition with the DNA in the 

electron donation process and formation of chem. bond with the carcinogen. 

Lee, S. A., Q. Dai, et al. (2007). "Association of serum concentration of organochlorine 

pesticides with dietary intake and other lifestyle factors among urban Chinese women." 

Environment International 33(2): 157-63. 
24

 Concerns about the carcinogenic and endocrine-disrupting characteristics of 

organochlorine pesticides (OCPs) have led to a global ban on OCP use. 

However, OCPs persist in the environment for decades because of their long 

half-life. We evaluated serum levels of OCPs and their correlations with usual 

dietary intake and other lifestyle factors among 250 healthy women who 

participated as controls in the Shanghai Breast Cancer Study. Serum levels of 

hexachlorocyclohexane isomers (alpha-HCH, beta-HCH, gamma-HCH), dichlorodi-phenyl-trichloroethane (DDT) isomers (p,p'-DDE and p,p'-DDT), 

hexachlorobenzene (HCB), trans-nonachlor (TNC), and eight polychlorinated 

biphenyls (PCB) congeners (IUPAC no. 74, 118, 138, 153, 170, 180, 183, and 

187) were measured. Lifestyle factors and usual dietary habits over the past 5 

years were assessed through an in-person interview. With the exception of PCB, 

total OCP levels in our study population were significantly higher than those 

observed in other countries. Age, income, body mass index, waist-to-hip ratio, 

number of pregnancies, and/or total duration of breastfeeding were all 

significantly correlated with all types of OCPs. Of the 20 food groups evaluated, 

correlations with serum total OCPs were observed for eggs (r=0.13), fresh beans 

(r=-0.17), tea (r=0.14), and animal fat (r=0.18). Multiple regression analyses 

showed that age and animal fat intake were positively associated with serum 

total level OCPs, while leafy vegetable and fresh bean consumption was 

negatively associated with OCPs level. Our study suggests that dietary intake 

may be an important contributor of serum levels of OCPs in Chinese women. 

Lindstroem, G., L. Hardell, et al. (2004). "Adipose tissue concentrations of PCB, HCB, 

chlordane, PBDE, and p,p'-DDE and the risk for endometrial cancer." Organohalogen 

Compounds 66(Dioxin 2004): 3182-3187. 

 The possible risk of endometrial cancer assocd. with environmental endocrine 

disruptors was evaluated in this case-control study. The adipose tissue concns. 

of polychlorinated biphenyls, hexachlorobenzene, p,p'-DDE, chlordanes, and 

polybrominated biphenyls in 76 cases with endometrial cancer and 39 controls 

with benign endometrial hyperplasia were analyzed. For the different chem. odds 

ratios (ORs) and 95% confidence intervals (CIs) were close to unity taking the 

median concn. among the controls as cut off value. However, for p,p'-DDE OR = 

1.9, 95% CI= 0.8-4.8 was obtained. Addnl. estrogen replacement therapy yielded 

in this category OR= 2.3, 95% CI= 0.6-6.8. The results indicate an interaction 

between p,p'-DDE and estrogen replacement drugs in the etiol. of endometrial 

cancer. 

Lope, V., B. Perez-Gomez, et al. (2009). "Occupational exposure to chemicals and risk 

of thyroid cancer in Sweden." International Archives of Occupational and Environmental 

Health 82(2): 267-74. 

 PURPOSE: To explore thyroid cancer (TC) risk in the Swedish population, 

associated with occupational exposure to certain chemicals. METHODS: 

National cancer and death registries were used to follow-up (1971-1989) all 

Swedish workers employed in the 1970 census. Each combination of occupation 

and industry was linked to a Swedish job-exposure matrix (JEM), with exposure 
25

to 13 chemicals classified as "possible exposure", "probable exposure" or 

"unexposed". Relative risks were obtained using Poisson models adjusted for 

age, period and geographical area. A second analysis was performed, in which 

adjustment was additionally made for simultaneous exposure to other matrix 

chemicals and ionising radiations. RESULTS: Probable exposure to solvents 

among women displayed an increased risk (RR = 1.91; 95%CI:1.05-3.45), mainly 

due to a higher risk observed among shoe-cutters, lasters and sewers engaged 

in shoe-making. CONCLUSIONS: Exposure to solvents, used mainly in the shoe 

and leather industry, seems to be associated with excess TC among women. 

Lu, Y. (2006). "Application of physiologically based pharmacokinetic/pharmacodynamic 

(PBPK/PD) model in studying the carcinogenic potential of hexacholorobenzene, PCB 

126, and their mixture." 67(12): 7047. 

 

Lu, Y., M. Lohitnavy, et al. (2008). "Quantitative analysis of liver GST-P foci promoted 

by a chemical mixture of hexachlorobenzene and PCB 126: implication of sizedependent cellular growth kinetics." Arch Toxicol 82(2): 103-16. 

 The objectives of this study were twofold: (1) evaluating the carcinogenic 

potential of the mixture of two persistent environmental pollutants, 

hexachlorobenzene (HCB) and 3,3',4,4',5-pentachlorobiphenyl (PCB 126), in an 

initiation-promotion bioassay involving the development of pi glutathione Stransferase (GST-P) liver foci, and (2) analyzing the GST-P foci data using a 

biologically-based computer model (i.e., clonal growth model) with an emphasis 

on the effect of focal size on the growth kinetics of initiated cells. The 8-week 

bioassay involved a series of treatments of initiator, two-thirds partial 

hepatectomy, and daily oral gavage of the mixture of two doses in male F344 

rats. The mixture treatment significantly increased liver GST-P foci development, 

indicating carcinogenic potential of this mixture. Our clonal growth model was 

developed to simulate the appearance and development of initiated GST-P cells 

in the liver over time. In the model, the initiated cells were partitioned into two 

subpopulations with the same division rate but different death rates. Each 

subpopulation was further categorized into single cells, mini- (2-11 cells), 

medium- (12-399 cells), and large-foci (>399 cells) with different growth kinetics. 

Our modeling suggested that the growth of GST-P foci is size-dependent; in 

general, the larger the foci, the higher the rate constants of division and death. In 

addition, the modeling implied that the two doses promoted foci development in 

different manners even though the experimental foci data appeared to be similar 

between the two doses. This study further illustrated how clonal growth modeling 

may facilitate our understanding in chemical carcinogenic process. 

Lu, Y., M. Reddy, et al. (2004). "Development Of A PBPK Model For 

Hexachlorobenzene In The Context Of Ito's Medium-Term Liver Foci Bioassay." 

Toxicologist 78(1-S): 244-5. 

 Hexachlorobenzene (HCB) is an important environmental contaminant. Due to its 

high lipophilicity and persistence in the environment, human exposure to HCB 

has continued despite the curtailment of its usage. HCB is carcinogenic to 
26

laboratory animals with the liver as one of the primary target organs. We have 

incorporated the study of the relationship between pharmacokinetics and 

pharmacodynamics into the Ito’s medium-term liver foci bioassay. Thus, we 

describe here the development of a PBPK model for HCB in the context of Ito’s 

bioassay protocol. The model was built based on two data sets: one from a 

single intravenous dosing study (Scheufler et al. 1984) and the other from a 

single oral gavage study (Yamaguchi et al. 1986). It was then modified to 

simulate the exposure conditions in the Ito’s bioassay and verified with data from 

our laborotary. The PBPK model includes five compartments: blood, liver, fat and 

rapidly and slowly perfused tissues. As HCB can bind to red blood cells, the 

blood compartment was divided into red blood cells and plasma. The fat 

compartment was divided into two subcompartments, one with a higher perfusion 

rate and lower partitioning and the other with a lower perfusion rate and higher 

partitioning. Uptake of HCB was diffusion-limited in the fat compartments and 

flow-limited in the others. HCB was eliminated by metabolism in the liver and by 

passive transfer from plasma to the intestinal lumen. Reabsorption of HCB from 

the intestine was incorporated in the model. The resultant model adequately 

described the available data sets. This model may be linked with a clonal growth 

model to quantitatively describe the relationship between an external exposure to 

HCB and the consequent preneoplastic liver foci development. 

Mally, A. and K. Chipman (2002). "Non-genotoxic liver carcinogens: Early effects on gap 

junctions, cell proliferation and apoptosis in the rat." Toxicology 178(1): 45-46. 

 

McCready, D., J. Aronson Kristan, et al. (2004). "Breast tissue organochlorine levels 

and metabolic genotypes in relation to breast cancer risk Canada." Cancer causes & 

control : CCC 15(4): 399-418. 

 Genes that metabolize the rate of clearance of environmental carcinogens may 

be candidate genes for cancer susceptibility. There is some data to suggest that 

exposure to environmental pesticides and other organochlorine pollutants is a 

risk factor to breast cancer. It is therefore reasonable to ask if variants in the 

genes responsible for the metabolic activation of organochlorines are associated 

with different tissue burdens of organochlorines and if these variants modify the 

risk of breast cancer in the population. We conducted a case-control study of 

women who underwent an excision biopsy for suspected breast cancer in a 

Toronto hospital from 1995 to 1997. Patients are residents of the Greater Toronto 

Area and are primarily Caucasian of European descent. Cases were women with 

invasive breast cancer (n = 70) and controls (n = 69) were women diagnosed 

with benign disease, frequency matched by age to cases. Levels of 

organochlorines were measured in benign breast tissue and seven 

polymorphisms in five candidate genes were genotyped. In general, women who 

carried inactive alleles of the GSTM1 had higher levels of breast 

organochlorines, and were at modestly increased risk of breast cancer (odds 

ratio = 2.2; 95% CI = 1.1-4.4). However, multiple comparisons were made and 

generally our data do not support the hypothesis that organochlorines increase 
27

the risk of breast cancer among subgroups of women with specific metabolic 

genotypes. 

Munoz-de-Toro, M., M. Durando, et al. (2006). "Estrogenic microenvironment generated 

by organochlorine residues in adipose mammary tissue modulates biomarkers 

expression in ER?-positive breast carcinomas." Breast Cancer Research 8(4): No pp. 

 Introduction Breast cancer is the most frequent malignant disease in women. 

Exposure to estrogens throughout a woman's life is a risk factor for the 

development of breast cancer. Organochlorine compds. (OCCs), such as 

pesticides and polychlorinated biphenyls (PCBs), are persistent lipophilic chems. 

identified as endocrine disruptors mainly with estrogenic effects. To test the 

hypothesis that the amt. and quality of organochlorine residues in adipose tissue 

adjacent to breast carcinoma affect the biol. behavior of the tumor, we studied 

biomarker expression in breast carcinoma and OCCs body burden in patients 

from an urban area adjacent to Parana fluvial system, Argentina. Methods The 

studied patients were 55 women that had undergone excision biopsies of a 

breast lesion diagnosed as invasive breast carcinoma. Anal. of OCCs residues in 

breast adipose tissue was conducted by electron-capture gas liq. chromatog. 

Estrogen receptor (ER)-?, progesterone receptor (PR) and proliferative activity 

(Ki-67) were measured in paraffin embedded biopsies of breast tumors by 

immunohistochem. Results All patients had high levels of organochlorine 

pesticides in their breast adipose tissue. The most frequently detected compds. 

were p,p' dichlorodiphenyldichloroethylene (DDE), hexachlorobenzene (HCB) 

and ?-hexachlorocyclohexane (?-HCH). When the whole sample was analyzed, 

no correlation between ER? or PR expression and OCCs levels were found. 

However, in the subgroup of ER?-pos. breast carcinoma patients, there was a 

pos. correlation between PR expression (an estrogen induced protein) in the 

neoplastic cells and OCCs levels in adipose tissue surrounding the tumor. More 

significant, all the ER?-pos. breast carcinomas from postmenopausal women 

exhibited high proliferation when organochlorine levels in the surrounding 

adipose tissue reached levels higher than 2600 ppb. No assocns. were found 

between organochlorine body burden and any other marker of tumor 

aggressiveness such as node involvement or tumor size. Conclusion The present 

results support the hypothesis that organochlorine residues in adipose tissue 

adjacent to breast carcinoma generate an estrogenic microenvironment that may 

influence the biol. behavior of the tumor through ER? activation and ER?-

dependent proliferation. These findings may have therapeutic implications, since 

interference between organochlorine compds. and hormonal therapy could be 

expected to occur. 

Muscat, J. E., J. A. Britton, et al. (2003). "Adipose concentrations of organochlorine 

compounds and breast cancer recurrence in Long Island, New York." Cancer 

Epidemiology, Biomarkers and Prevention 12(12): 1474-8. 

 Several studies have measured the association between blood or adipose 

concentrations of organochlorinated compounds (OCs), such as pesticides and 

polychlorinated biphenyls (PCBs), and breast cancer. The estrogenic effects of 
28

OCs might adversely affect breast cancer recurrence. The participants were 224 

women with nonmetastatic breast cancer enrolled in a New York-based casecontrol study. Supercritical fluid extraction followed by gas chromatography was 

conducted on adipose surgical specimens to determine OC concentrations. The 

mean follow-up time from surgery was 3.6 years. Thirty women (13.4%) were 

diagnosed with a recurrence. The concentration of pesticides and PCBs was 

correlated with baseline age and body mass index, but not with cancer stage. 

The highest tertile of total PCB concentration was associated with an increased 

risk of recurrence [relative risk (RR), 2.9; 95% confidence interval (CI), 1.02-8.2 

versus the lowest tertile]. The risk for the highest tertile of the PCB congener 

Ballschmiter and Zell 118 was 4.0 (95% CI, 1.3-4.9). There was an increased risk 

for the middle level of the most abundant pesticide, 1,1-dichloro-2,2-di(4-

chlorophenyl)ethylene (RR, 2.3; 95% CI, 0.9-5.7), and for betahexachlorocyclohexane, but not for their highest levels. Self-reported home 

termiticide exposure, alcohol consumption (> or = 1 drink/day), and race were not 

associated with prognosis. The RR for current cigarette smoking at diagnosis 

was 2.1 (95% CI, 0.9-5.1). In contrast to previous data showing no relationship 

between OC exposure and risk of breast cancer in these women, adipose PCB 

concentrations were associated with tumor recurrence. Pesticide levels were not 

related to recurrence. 

NTP (2001). Data from the NTP 2001 report: Toxicity studies of hexachlorobenzene -

Not yet available National Toxicology Program,. 

 

NTP (2004). Hexachlorobenzene. Report on carcinogens. Bethesda, MD, National 

Toxicology Program. 10: 134-135. 

 

Oezden, S., T. Chen, et al. (2008). "Alteration in global DNA methylation as an early 

event in nongenotoxic carcinogenesis." Toxicology Letters (Shannon) 180(Suppl. 1): 

S55. 

 

Ou, Y. C., R. B. Conolly, et al. (2003). "Stochastic simulation of hepatic preneoplastic 

foci development for four chlorobenzene congeners in a medium-term bioassay." 

Toxicological Sciences 73(2): 301-14. 

 A combination of experimental and simulation approaches was used to analyze 

clonal growth of glutathione-S-transferase pi (GST-P) enzyme-altered foci during 

liver carcinogenesis in an initiation-promotion regimen for 1,4-dichlorobenzene 

(DCB), 1,2,4,5-tetrachlorobenzene (TECB), pentachlorobenzene (PECB), and 

hexachlorobenzene (HCB). Male Fisher 344 rats, eight weeks of age, were 

initiated with a single dose (200 mg/kg, ip) of diethylnitrosamine (DEN). Two 

weeks later, daily dosing of 0.1 mol/kg chlorobenzene was maintained for six 

weeks. Partial hepatectomy was performed three weeks after initiation. Liver 

weight, normal hepatocyte division rates, and the number and volume of GST-P 

positive foci were obtained at 23, 26, 28, 47, and 56 days after initiation. A clonal 

growth stochastic model separating the initiated cell population into two distinct 

subtypes (referred to as A and B cells) was successfully used to describe the foci 
29

development data for the four chlorobenzenes. The B cells are initiated cells that 

display a selective growth advantage under conditions that inhibit the growth of 

initiated A cells or normal hepatocytes. The simulation exercise for the four 

chlorobenzenes indicates a positive correlation between the estimated net 

growth rate of B cells during the 2-week regeneration period following partial 

hepatectomy and final foci volume at the end of the bioassay. This observation is 

consistent with the sensitivity analysis of model parameters. While TECB, PECB, 

and HCB all significantly increased foci volume, only HCB increased normal 

hepatocyte proliferation. Together, these results indicate that examining effects 

of chemicals on regenerative responses following partial hepatectomy may be a 

means for understanding the carcinogenicity potential of chlorobenzene 

compounds. 

Ou, Y. C., R. B. Conolly, et al. (2001). "A clonal growth model: time-course simulations 

of liver foci growth following penta- or hexachlorobenzene treatment in a medium-term 

bioassay." Cancer Res 61(5): 1879-89. 

 A combination of experimental and simulation approaches were used to analyze 

the clonal growth of preneoplastic, enzyme-altered foci during liver 

carcinogenesis in an initiation-promotion regimen. Male Fisher 344 rats, 8 weeks 

of age, were initiated with a single dose (200 mg/kg, i.p.) of diethylnitrosamine 

(DEN). Beginning 2 weeks later, animals were exposed to daily gavage 

consisting of 0.1 mmol/kg pentachlorobenzene (PECB) or hexachlorobenzene 

(HCB) in corn oil vehicle for 6 weeks. Partial hepatectomy was performed 3 

weeks after initiation. Experimental data including liver weight, hepatocyte 

density (number of hepatocytes/unit volume), 5-bromo-2'-deoxyuridine- labeling 

index for analysis of cell division rate, and number and volume of glutathione-Stransferase pi-positive foci were collected 23, 26, 28, 47, or 56 days after 

initiation. Model parameters describing liver growth were obtained directly from 

the experimental data. The probability of mutation/division of normal cells and the 

growth rate of initiated cells were inferred by a comparison of model outcomes 

with the observed time courses of foci development. To describe the timedependent increases in foci volume and the concomitant reduction of foci number 

observed in all treatment groups, the calibrated model for the DEN controls 

incorporated the hypothesis of two initiated cell populations (referred to as A and 

B cells) within the framework of the two-stage model. The B cells are initiated 

cells that have a selective growth advantage under conditions that inhibit the 

growth of A cells and normal hepatocytes. The parameter values defined in the 

DEN controls were used to evaluate experiments involving the administration of 

PECB or HCB. Both PECB and HCB caused a significant increase in foci volume 

compared with the DEN controls. HCB treatments resulted in increased 

proliferation of normal hepatocytes, which was not observed for PECB under the 

same treatment regimen. The best description of the data resulted from the 

model incorporating the hypothesis that PECB and HCB promoted the growth of 

foci via increased net growth rates of B cells. We present here a biologically 

based clonal growth simulation platform to describe the growth of preneoplastic 

foci under experimental manipulations of initiation-promotion studies. This 
30

simulation work is an example of quantitative approaches that could be useful for 

the analysis of other initiation-promotion studies. 

Pavuk, M., J. R. Cerhan, et al. (2003). "Case-control study of PCBs, other 

organochlorines and breast cancer in Eastern Slovakia." J Expo Anal Environ Epidemiol

13(4): 267-75. 

 This case-control study was designed to investigate association between 

polychlorinated biphenyls (PCBs) and risk of breast cancer in an area of high 

environmental exposure in the Michalovce district of eastern Slovakia. Incident 

breast cancer cases from the Michalovce district diagnosed between May 1997 

and May 1999 were recruited through the Oncology Department of the District 

Hospital. A total of 15 individual PCB congeners, 2,2'-bis(4-chlorophenyl)-1,1-

dichloroethylene (DDE), 2,2-bis(4-chlorophenyl)-1,1,1-trichloroethane (DDT), and 

hexachlorobenzene (HCB) were measured in the serum of 24 breast cancer 

patients and 88 population controls in 1998-1999. The median levels of total 

PCBs were similar in cases (2586 ng/g of lipid) and controls (2682 ng/g of lipid). 

Higher serum levels (highest vs. lowest tertile) of total PCBs (odds ratio 

(OR)=0.42, 95% CI 0.10-1.82, p-for trend=0.31), group 1 congeners (OR=0.37, 

95% CI 0.10-1.43, P-for trend=0.02), group 2 congeners (OR=0.32, 95% CI 0.07-

1.56, P-for trend=0.60), and group 3 congeners (OR=0.49, 95% CI 0.12-2.04, Pfor trend=0.51) were inversely associated with risk of breast cancer. Higher 

serum levels of DDE (OR=3.04, 95% CI 0.65-14.3, P-for trend=0.10) were 

positively associated with risk of breast cancer, while there was no association 

for DDT (OR=1.19, 95% CI 0.27-5.23, P-for trend=0.68), and an inverse 

association for HCB (OR=0.45, 95% CI 0.06-3.19, P-for trend=0.67). While 

generally not statistically significant, PCB and HCB levels were inversely 

associated with risk of breast cancer in this highly exposed population. DDE, but 

not DDT, was positively associated with risk. 

Petreas, M., D. Smith, et al. (2004). "Distribution of persistent, lipid-soluble chemicals in 

breast and abdominal adipose tissues: lessons learned from a breast cancer study." 

Cancer Epidemiology, Biomarkers and Prevention 13(3): 416-24. 

 OBJECTIVES: We sought to determine differences between concentrations of 

persistent, lipid-soluble chemical contaminants in breast and abdominal adipose 

tissues and to explore whether concentrations measured in one tissue could 

predict concentrations in the other tissue. METHODS: We analyzed surgical 

specimens and measured concentrations of prevalent dioxins, furans, 

polychlorinated biphenyls, organochlorine pesticides, and brominated diphenyl 

ethers to determine their partitioning between breast and abdominal adipose 

tissues of 21 women. The women constituted a subgroup, undergoing 

mastectomies with simultaneous breast reconstruction, of a case-control study 

evaluating links between breast cancer and body burdens of organohalogen 

contaminants. RESULTS: For every contaminant, differences between 

concentrations in breast and abdominal adipose tissues did not exceed the 

analytical error. Results indicated that, with some notable exceptions, 

measurements in breast and abdominal adipose tissues were correlated and that 
31

concentrations of target chemicals in one tissue could be derived from 

measurements in the other tissue. CONCLUSIONS: This information will allow 

comparison of results from body burden studies that used different tissues. It 

may also facilitate future breast cancer studies by allowing selection of controls 

among patients undergoing surgical procedures other than breast surgery, 

minimizing concerns about overmatching. We also observed large differences in 

the lipid content of surgical specimens. These differences underscore the need 

for lipid adjustment of concentrations to avoid misclassification. 

Plante, I., M. Charbonneau, et al. (2002). "Decreased gap junctional intercellular 

communication in hexachlorobenzene-induced gender-specific hepatic tumor formation 

in the rat." Carcinogenesis 23(7): 1243-9. 

 Hexachlorobenzene (HCB), an epigenetic carcinogen, HCB induces the 

formation of liver tumors in female rats, whereas only a small percentage of 

males are responsive. Intercellular communication via gap junctions is decreased 

in carcinogenesis. Gap junctions are composed of proteins termed connexins 

(Cxs). The objectives of this study were (i) to determine if HCB-induced tumor 

development is associated with a loss of gap junctional communication; (ii) to 

assess if HCB causes a gender- specific decrease in the expression of Cx32 and 

Cx26; and (iii) to establish if these effects result from gender differences in the 

constitutive expression of these Cxs. Rats were given HCB by gavage for five 

consecutive days. In the first experiment, control and HCB-treated female rats 

were sampled on day 100. Intercellular communication was significantly 

decreased in HCB-treated females compared to controls. To investigate if 

changes in Cx levels occur prior to day 100, experiments done using male and 

female rats sampled on day 50. Hepatic mRNA levels for Cx26 and Cx32 were 

significantly lower only in HCB-treated females as compared to controls. Cx26 

mRNA levels were 3-fold higher and Cx32 mRNA levels were 8-fold lower in 

females compared with males. In a third experiment, ovariectomy abolished any 

differences between male and female controls for both Cxs, while estradiol had a 

partial role in the regulation of Cx32. This suggests that the sexual dimorphism in 

hepatic Cx levels is determined by the ovarian hormones. However, the HCBinduced decrease in Cx32 and Cx26 mRNA levels was maintained in 

ovariectomized rats, suggesting that the HCB effects are not mediated via an 

ovary-dependent pathway. Overall results show that HCB exposure induces 

gender-specific long-term alterations in intercellular gap junctional 

communication in female rat liver. This effect appears to be a critical mechanism 

of HCB-induced liver carcinogenesis and tumor promotion. 

Plante, I., D. G. Cyr, et al. (2005). "Down-Regulation Of E-Cadherin By The IntegrinLinked Kinase Pathway (ILK) In Hepatocytes; A Possible Mechanism For 

Hexachlorobenzene-Induced Tumor Promotion." Toxicol Sci 84(1-S): 156. 

 The ILK pathway is overexpressed in tumors of various tissues. We have 

previously shown an activation of the ILK pathway in the liver of female rats given 

hexachlorobenzene (HCB), an environmental epigenetic carcinogen. This was 

accompanied by a down-regulation of E-cadherin, an adhering junction protein, 
32

and connexin32 (Cx32), a gap junction protein. The aim of this study was to 

demonstrate the role of the ILK pathway in the regulation of adhering and gap 

junctions in liver cells. MH1C1 rat hepatocytes exposed to HCB for 7 days 

showed increased levels of the inactive form of GSK3beta, i.e. phosphoGSK3beta, an important messenger of ILK activation, and a decrease in Cx32, 

as observed in vivo exposed rats. Two different GSK3beta specific inhibitors 

were used to confirm the role of the ILK pathway in Ecadherin and Cx32 

regulation. Both inhibitors (kenpaullone 5 and 10 uM, SB- 415286 125 and 150 

nM) markedly reduced GSK3beta activity and caused an approximately 50% 

decrease in E-cadherin mRNA levels, whereas Cx32 mRNA levels were 

unchanged. This suggests that in MH1C1 cells, Cx32 expression is not 

modulated by GSK3beta, but depends on either another messenger of the ILK 

pathway, such as Akt, or another pathway. Stable transfections of MH1C1 cells 

with Cx32 expression vector to increase Cx32 expression levels resulted in a 

marked increased Ecadherin mRNA levels thereby suggesting a link between 

Cx32 and E-cadherin regulation. Together, these data demonstrate that in rat 

hepatocytes E-cadherin is down-regulated by the ILK pathway via GSK3beta 

inhibition and up-regulated by Cx32 overexpression. Clearly, both Cx32 and Ecadherin are regulated differently in hepatocytes suggesting that HCB may 

modulate several signalling pathways in the promotion of hepatocarcinogenesis. 

Plante, I., D. G. Cyr, et al. (2005). "Involvement of the integrin-linked kinase pathway in 

hexachlorobenzene-induced gender-specific rat hepatocarcinogenesis." Toxicol Sci

88(2): 346-57. 

 Overexpression of the integrin-linked kinase (ILK) pathway disrupts cell-cell 

interactions, an epigenetic event leading to epithelial cell transformation. Female 

rats exposed to hexachlorobenzene (HCB) for 5 consecutive days and sampled 

45 days later show a decrease in liver gap junctional intercellular communication. 

We hypothesized that HCB also alters E-cadherin expression and that this 

alteration is mediated by the ILK pathway. Hepatic ILK levels were markedly 

increased in HCB-treated female rats. Cytoplasmic/membrane levels of protein 

kinase B (Akt), a target of ILK, and its phosphorylated active form were 

decreased in treated female rats. Flow cytometric analysis showed a concomitant 

increase in nuclear Akt levels. Both ILK and Akt can phosphorylate glycogen 

synthetase kinase-3beta (GSK3beta), rendering it inactive. PhosphorylatedGSK3beta levels were higher in treated females and resulted in a twofold 

decrease in the activity of GSK3beta. The inactivation of GSK3beta in HCBtreated female rats resulted in the nuclear translocation of beta-catenin, as 

demonstrated by both immunocytochemistry and flow cytometric analyses. 

Western blot analysis showed an 84% decrease in E-cadherin levels in HCBtreated rats as compared to controls, and this decrease was not mediated by 

Snail activation. Mimicking the activation of ILK with specific GSK3beta inhibitors 

resulted in downregulation of E-cadherin levels but had no effect on Cx32 

expression in the MH(1)C(1) cells. Overall, these results indicate that hepatic Ecadherin is downregulated as a result of an overexpression of the ILK pathway. 

The concomitant HCB-induced downregulation of intercellular communication 
33

does not occur as a result of either E-cadherin downregulation or GSK3beta 

inactivation. 

Plante, I., D. G. Cyr, et al. (2007). "Sexual dimorphism in the regulation of liver 

connexin32 transcription in hexachlorobenzene-treated rats." Toxicol Sci 96(1): 47-57. 

 Hexachlorobenzene (HCB), an epigenetic carcinogen, causes female rats to be 

more susceptible to liver tumor formation than males. HCB exposure in females 

downregulates the expression of Cx32, a gap junction protein, through the 

activation of Akt. The objectives of this study were to determine (1) the 

implication of different regions of the hepatic Cx32 promoter in the observed 

sexual dimorphism in the expression of Cx32, (2) the implication of different 

regions of the hepatic Cx32 promoter in the HCB-induced downregulation of 

Cx32 in female rat liver, and (3) if HCB exposure modulates the binding of 

transcription factors on the Cx32 promoter through Akt activation. Male and 

female rats were exposed to HCB during 5 consecutive days and sampled 45 

days later. Electrophoresis mobility shift assays showed that the intensity of only 

one nuclear protein-DNA complex differed between males and females. The 

formation of this complex requires two binding sites to be intact in a fragment of 

the basal promoter (Fr26). Following HCB exposure, the intensity of two 

complexes (Fr26 and Fr110) was decreased in females, but not in males, 

consistent with the decrease in Cx32 expression observed only in HCB-treated 

females. In vitro studies using a rat hepatocyte cell line (MH1C1) showed that the 

formation of the Fr110 protein-DNA complex appears to be controlled by Akt and 

requires the integrity of a Myb site. Overall, results suggest that both the sexual 

dimorphism and the downregulation of Cx32 in HCB-treated female rats are 

mediated by a reduction in the binding of activating transcription factors on the 

Cx32 promoter. 

Porta, M., L. Ruiz, et al. (2002). "Correlations among serum concentrations of highly 

prevalent organochlorine compounds in patients with exocrine pancreatic cancer." 

Organohalogen Compounds 55(Dioxin 2002): 307-310. 

 The correlations between the serum concns. of the most prevalent 

organochlorine compds. in patients with exocrine pancreatic cancer were 

evaluated. The correlation between DDT and DDE was stronger in cases older 

than 60 yr than in younger cases, suggesting that younger subjects incorporated 

the two compds. in a more independent manner than older ones. This indicated 

that, while in the elderly a larger proportion of the p,p'-DDE body burden would 

stem from metabolization of p,p'-DDT, the predominant source of DDE in 

younger cases would be background dietary exposure. Correlations tended to be 

higher between compds. with higher serum concns., such as the two PCB 

congeners, 138 and 153, with highest concns. The Spearman's rank correlation 

coeff. between hexachlorobenzene and b-hexachlorocyclohexane was also high 

and was the same in men and in women, as well as in older and younger 

subjects. 
34

Quintana, P. J., R. J. Delfino, et al. (2004). "Adipose tissue levels of organochlorine 

pesticides and polychlorinated biphenyls and risk of non-Hodgkin's lymphoma." 

Environmental Health Perspectives 112(8): 854-61. 

 In this nested case-control study we examined the relationship between nonHodgkin's lymphoma (NHL) and organochlorine pesticide exposure. We used a 

data set originally collected between 1969 and 1983 in the U.S. Environmental 

Protection Agency National Human Adipose Tissue Survey. Adipose samples 

were randomly collected from cadavers and surgical patients, and levels of 

organochlorine pesticide residues were determined. From the original study 

population, 175 NHL cases were identified and matched to 481 controls; 173 

controls were selected from accident victims, and 308 from cases with a 

diagnosis of myocardial infarction. Cases and controls were mainly from 

cadavers (> 96%) and were matched on sex, age, region of residence within the 

United States, and race/ethnicity. Conditional logistic regression showed the 

organochlorine pesticide residue heptachlor epoxide to be significantly 

associated with NHL [compared with the lowest quartile: third quartile odds ratio 

(OR) = 1.82, 95% confidence interval (CI), 1.01-3.28; fourth quartile OR = 3.41, 

95% CI, 1.89-6.16]. The highest quartile level of dieldrin was also associated with 

elevated NHL risk (OR = 2.70; 95% CI, 1.58-4.61), as were higher levels of 

oxychlordane, p,p'-DDE [p,p'-1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene], and 

ss-benzene hexachloride (ORs = 1.79, 1.99, and 2.47, respectively). The pvalues for trends for these associations were significant. In models containing 

pairs of pesticides, only heptachlor epoxide and dieldrin remained significantly 

associated with risk of NHL. Limitations of this study include collection of 

samples after diagnosis and a lack of information on variables affecting 

organochlorine levels such as diet, occupation, and body mass index. Given the 

persistence of pesticides in the environment, these findings are still relevant 

today. 

Raaschou-Nielsen, O., M. Pavuk, et al. (2005). "Adipose organochlorine concentrations 

and risk of breast cancer among postmenopausal Danish women." Cancer 

Epidemiology, Biomarkers and Prevention 14(1): 67-74. 

 OBJECTIVE: Exposure to environmental organochlorines has been examined as 

a potential risk factor for human breast cancer with mixed results. Our purpose 

was to examine associations between organochlorines and the development of 

breast cancer in a large prospective study using stored adipose tissue. 

METHODS: We conducted a nested case-control study of 409 postmenopausal 

women who developed breast cancer and 409 controls selected from the 29,875 

women enrolled in the Danish Diet, Cancer, and Health cohort between 1993 and 

1997. We measured concentrations of 14 pesticides and 18 polychlorinated 

biphenyls in adipose tissue, collected upon enrollment, and estimated relative 

risk (RR) of breast cancer using conditional logistic regression. RESULTS: The 

results showed no higher risk of breast cancer among women with higher levels 

of any pesticides or polychlorinated biphenyls; the RR associated with the upper 

quartile of 1,1-dichloro-2, 2-bis(p-chlorophenyl)ethylene concentration was 0.7 

[95% confidence interval (95% CI), 0.5-1.2] contrasting the lower quartile, and for 
35

the sum of polychlorinated biphenyls the similar risk was 1.1 (95% CI, 0.7-1.7). 

We observed a pattern of substantially lower risk of estrogen receptor-negative 

breast cancer in association with higher levels of most of the pesticides and 

polychlorinated biphenyls; the RR for the higher quartile of 1,1-dichloro-2,2-bis(pchlorophenyl)ethylene was 0.1 (95% CI, 0.0-0.5) and for the sum of 

polychlorinated biphenyls it was 0.3 (95% CI, 0.1-0.9). CONCLUSION: The 

results do not support that higher organochlorine body levels increase the risk of 

breast cancer in postmenopausal women. The interpretation of the inverse 

association for estrogen receptor-negative breast cancer is currently unclear. 

Randi, A. S., C. Cocca, et al. (2006). "Hexachlorobenzene is a tumor co-carcinogen and 

induces alterations in insulin-growth factors signaling pathway in the rat mammary 

gland." Toxicol Sci 89(1): 83-92. 

 Hexachlorobenzene (HCB) is a widespread environmental pollutant. Controversy 

still exists about the breast carcinogenic properties of organochlorines in 

humans. The ligands, receptors, and related signaling proteins of the insulin 

growth factor family are involved in the regulation of breast-cancer cell growth. 

The aims of this study were to determine: (1) whether HCB is co-carcinogenic in 

a medium term assay of N-nitroso N-methylurea (NMU)-induced mammary 

tumors in rats; (2) the effect of HCB on insulin receptor (IR), insulin-like growth 

factor-I receptor (IGF-IR) and insulin receptor substrate-1 (IRS-1) levels and on 

IRS-1 phosphorylation; (3) microsomal and cytosolic Protein Tyrosine Kinase 

(PTK) activities in mammary glands and NMU-induced tumors. Sprague Dawley 

rats were injected with 50 mg/kg body weight of NMU at 50, 80, and 110 days 

old. HCB (100 mg/kg body weight) was administered three times a week from 65 

to 110 days of age. Rats were separated in four groups: control, NMU, HCB, and 

NMU-HCB. HCB alone did not induce tumor development. Parameters of tumor 

development were increased in NMU-HCB compared to NMU rats. A higher 

cellular undifferentiation was observed in NMU-HCB tumors. IR, IGF-IR, and 

IRS-1 levels were higher in HCB than in controls. Conversely IGF-IR levels 

decreased in NMU-HCB vs. NMU group. The IRS-1 phosphorylation increased in 

HCB rats; however, it decreased in NMU-HCB vs. NMU. HCB decreased 

microsomal PTK activity in tumors. This study showed for the first time that HCB 

is a co-carcinogenic agent in NMU-induced mammary tumors in rats. Our results 

suggest that the IR and/or IGF-IR signaling pathway may be involved in the 

mechanism of action of HCB. 

Randi, A. S., S. Hernandez, et al. (2003). "Hexachlorobenzene-induced early changes 

in ornithine decarboxylase and protein tyrosine kinase activities, polyamines and c-Myc, 

c-Fos and c-Jun proto-oncogenes in rat liver." Toxicol Sci 76(2): 291-8. 

 Hexachlorobenzene (HCB) is a lipophilic chemical compound that is widely 

distributed in the environment. HCB is known to cause liver tumors in 

experimental animals. In the present study the in vivo effect of HCB treatment on 

ornithine decarboxylase (ODC) and protein tyrosine kinase (PTK) activities, free 

polyamine content, and c-Myc, c-Fos, and c-Jun protein levels in rat liver were 

investigated. HCB (1000 mg/kg body weight) increased hepatic 
36

immunodetectable c-Myc, c-Fos, and c-Jun levels after 6 h, and ODC activity and 

spermine and putrescine content after 18 and 24 h, while maximum stimulation of 

PTK activity occurred at 12 h. PTK and ODC activities varied in a dosedependent manner. The time-course of c-Myc, c-Fos, and c-Jun protein levels 

was different for each proto-oncogene. They were all elevated at the second day 

of treatment, while only c-Fos and c-Jun remained elevated after 10 days of HCB 

exposure. These data jointly suggest that the increase in ODC activity may be 

the consequence of proto-oncogene induction. The alterations in PTK activity 

suggest that the growth factor signal transduction pathway may be involved in 

the regulation of the proto-oncogene levels or/and ODC activity. The decrease in 

PTK activity after the first day, even in the presence of alpha-DDifluoromethylornithine (DFMO), an inhibitor of ODC activity, suggests that it is 

not regulated by polyamines. These results may be relevant to the early 

molecular events involved in HCB tumor promoter activity in rat liver. 

Raynal, N. J., M. Charbonneau, et al. (2005). "Sexual Dimorphism In DNA Methylation 

In The Liver Of Hexachlorobenzene-Treated Rat : A Possible Mechanism For Tumor 

Promotion." Toxicol Sci 84(1-S): 365. 

 Hexachlorobenzene (HCB), a widespread environmental contaminant, causes 

gender- specific liver tumor promotion in the rat where only females develop liver 

cancer. We have previously shown that in female but not male rat livers HCB 

causes significant decreases compared to controls in : i) the total number of 

expressed genes as measured by microarray analysis, ii) the mRNA and protein 

levels of the liver gap junction subunits, connexin 26 and connexin 32 (Cxs), 

which are considered to be tumor suppressive, and iii) gap junctional intercellular 

communication (GJIC). Modulation of gene expression is the hallmark of 

epigenetic carcinogens such as HCB. DNA methylation exerts mechanistic 

control of gene expression. This study aimed to assess the effects of HCB on 

DNA methylation as a mechanism responsible for the reduction of global, and 

more specifically Cx32, gene expression. Global DNA methylation was assessed 

using arbitrarily primed PCR ; total DNA was extracted (N=4), amplified by PCR 

and digested by RsaI and HpaII. HCB induced DNA hypermethylation of HpaII 

restriction site. Local DNA methylation on the Cx32 promoter was measured 

using methylation specific- PCR (MSP) of bisulfite-treated DNA (N=4). Results 

showed a 2.5-fold increase (p < 0.05) in the methylation of the Cx32 promoter in 

HCB-treated female rat livers compared to controls. Moreover, results showed a 

marked sexual dimorphism in DNA methylation, with males having lower levels (p 

< 0.05) compared to control females, which correlated with the gender-difference 

in Cx32 mRNA levels. Overall, data suggest that by inducing aberrations in 

global methylation, and more specifically in local hypermethylation of the Cx32 

promoter, HCB acts as a tumor promoter by modifying gene expression only in 

female rat livers. This work brings a better understanding of the modulation of 

DNA methylation in the reduction of gene expression by HCB in rat livers and 

strongly supports its role in rat hepatocarcinogenesis. 
37

Ritchie, J. M., S. L. Vial, et al. (2003). "Organochlorines and risk of prostate cancer." 

Journal of Occupational and Environmental Medicine 45(7): 692-702. 

 This pilot study examined the relationships of organochlorine pesticides (OCPs) 

and polychlorinated biphenyls (PCBs) with prostate cancer. Ninety-nine controls 

were frequency matched by age in 5-year increments to 58 prostate cancer 

patients. Thirty PCBs and 18 OCPs were measured in serum by gas 

chromatography. Multiple logistic regression was used to assess the magnitude 

of association. Seven organochlorines, dieldrin, p,p'-DDE, trans-nonachlor, 

oxychlordane, heptachlor epoxide, and PCBs 153 and 180 were detected in at 

least 20% of all study participants. Adjusting for age, body mass index, and a 

history of prostatitis, oxychlordane and PCB 180 were associated with an 

increased risk of prostate cancer. This study suggests that long-term, low-dose 

exposure to specific OCPs and PCBs in the general population may contribute to 

an increased risk of prostate cancer and supports further investigation in this 

area. 

Strucinski, P., J. K. Ludwicki, et al. (2002). "Hexachlorobenzene (HCB) and total 

polychlorinated biphenyls (3PCBS) in human breast lipids and breast cancer risk in 

Polish women." Organohalogen Compounds 59(Dioxin 2002): 365-368. 

 The results of the current study support the hypothesis that long-term exposure 

to organochlorine compds. may be assocd. with a small increase in the risk of 

breast cancer, esp. among postmenopausal women. 

Strucinski, P., B. Wojtyniak, et al. (2004). "Do we have to consider chemotherapy in the 

analysis of association between OCs in breast adipose tissue and the risk of female 

breast cancer?" Organohalogen Compounds 66(Dioxin 2004): 2543-2548. 

 A study of 165 samples of mammary gland's adipose tissue was performed to 

evaluate whether adipose tissue levels of selected persistent organochlorine 

pollutants might be assocd. with chemotherapy in women with breast cancer. All 

women had measurable levels of hexachlorobenzene, ?-HCH, p,p'-DDT, p,p'-

DDE (dominant analyte), and total polychlorinated biphenyls (PCBs), while p,p'-

DDD has been found in the 75% of the samples. The mean concn. of all 

compds., except p,p'-DDD, has been slightly lower in women who have 

undergone chemotherapy as compared to non treated patients. The differences 

were statistically significant for p,p'-DDE and total PCBs and at the borderline of 

statistical significance for ?-HCH. This, however, could result from the differences 

in mean age of donors in both groups, wherein women after chemotherapy were 

significantly younger than the non-treated ones. In general, the use of adipose 

tissue samples taken from patients who have undergone chemotherapy shortly 

before mastectomy does not bias exposure assessment. 

Uehara, T., M. Hirode, et al. (2008). "A toxicogenomics approach for early assessment 

of potential nongenotoxic hepatocarcinogenicity of chemicals in rats." Toxicology

250(1): 15-26. 

 For assessing carcinogenicity in animals, it is difficult and costly, an alternative 

strategy has been desired. We explored the possibility of applying a 
38

toxicogenomics approach by using comprehensive gene expression data in rat 

liver treated with various compds. As prototypic nongenotoxic 

hepatocarcinogens, thioacetamide (TAA) and methapyrilene (MP) were selected 

and 349 commonly changed genes were extd. by statistical anal. Taking both 

compds. as pos. with six compds., acetaminophen, aspirin, phenylbutazone, 

rifampicin, ?-naphthyl isothiocyanate, and amiodarone as neg., prediction anal. of 

microarray (PAM) was performed. By training and 10-fold cross validation, a 

classifier contg. 112 probe sets that gave an overall success rate of 95% was 

obtained. The validity of the present discriminator was checked for 30 chems. 

The PAM score showed characteristic time-dependent increases by treatment 

with several nongenotoxic hepatocarcinogens, including TAA, MP, coumarin, 

ethionine and WY-14643, while almost all of the noncarcinogenic samples were 

correctly predicted. Measurement of hepatic glutathione content suggested that 

MP and TAA cause glutathione depletion followed by a protective increase, but 

the protective response is exhausted during repeated administration. Therefore, 

the presently obtained PAM classifier could predict potential nongenotoxic 

hepatocarcinogenesis within 24 h after single dose and the inevitable pseudopositives could be eliminated by checking data of repeated administrations up to 

28 days. Tests for carcinogenicity using rats takes at least 2 years, while the 

present work suggests the possibility of lowering the time to 28 days with high 

precision, at least for a category of nongenotoxic hepatocarcinogens causing 

oxidative stress. 

Verner, M. A., M. Charbonneau, et al. (2008). "Physiologically based pharmacokinetic 

modeling of persistent organic pollutants for lifetime exposure assessment: a new tool in 

breast cancer epidemiologic studies." Environmental Health Perspectives 116(7): 886-

92. 

 BACKGROUND: Despite experimental evidence, most epidemiologic studies to 

date have not supported an association between exposure to persistent organic 

pollutants (POP) and breast cancer incidence in humans. This may be 

attributable to difficulties in estimating blood/tissue POP concentration at critical 

time periods of carcinogenesis. OBJECTIVES: In this work we aimed to develop 

a tool to estimate lifetime POP blood/tissue exposure and levels during any 

hypothesized time window of susceptibility in breast cancer development. 

METHODS: We developed a physiologically based pharmacokinetic (PBPK) 

model that can account for any given physiologic lifetime history. Using data on 

pregnancies, height, weight, and age, the model estimates the values of 

physiologic parameters (e.g., organ volume, composition, and blood flow) 

throughout a woman's entire life. We assessed the lifetime toxicokinetic profile 

(LTP) for various exposure scenarios and physiologic factors (i.e., breastfeeding, growth, pregnancy, lactation, and weight changes). RESULTS: 

Simulations for three POPs [hexachlorobenzene, polychlorinated biphenyl (PCB)-

153, PCB-180] using different lifetime physiologic profiles showed that the same 

blood concentration at 55 years of age can be reached despite totally different 

LTP. Aside from exposure levels, lactation periods and weight profile history 

were shown to be the factors that had the greatest impact on the LTP. 
39

CONCLUSIONS: This new lifetime PBPK model, which showed the limitations of 

using a single sample value obtained around the time of diagnosis for lifetime 

exposure assessment, will enable researchers conducting environmental 

epidemiology studies to reduce uncertainty linked to past POP exposure 

estimation and to consider exposure during time windows that are hypothesized 

to be mechanistically critical in carcinogenesis. 

Waliszewski, S. M., M. T. Bermudez, et al. (2005). "Persistent organochlorine pesticide 

levels in breast adipose tissue in women with malignant and benign breast tumors." 

Bulletin of Environmental Contamination and Toxicology 75(4): 752-9. 

 

Waliszewski, S. M., M. T. Bermudez, et al. (2005). "Persistent organochlorine pesticide 

levels in breast adipose tissue in women with malignant and benign breast tumors." 

Revista Internacional de Contaminacion Ambiental 21(3): 133-142. 

 Organochlorine pesticides have been used in Mexico in agriculture, sanitation, 

malaria programs and livestock to combat ectoparasites. Due to their chem. 

stability, persistence and lipophility, their residues bioconc. in lipid-rich tissues, 

according to the equil. pattern of internal transport and lipid tissue content. The 

studies on their role as estrogenic or antiandrogenic agents have related these 

pesticides to breast cancer. Therefore, organochlorine pesticides were detd. in 

breast adipose tissue of women subjected to surgery due to the diagnosis of 

breast abnormalities. The study pool constituted 127 women with malignant 

breast tumors, 127 with benign breast tumors and 127 in a control group without 

breast abnormalities. The pesticides detd. were: HCB, ?-HCH, pp'DDE, op'DDT, 

pp'DDT and ?-DDT. Comparing the studied groups, the highest residue levels 

were detd. in the benign breast tumor group. The detd. levels from the control 

group through malignant to benign cases increased stepwise; HCB: 0.045, 0.099, 

0.116 mg kg-1, ?-HCH: 0.163, 0.265, 0.319 mg kg-1, pp'DDE: 0.782, 0.980, 

1.761 mg kg-1, op'DDT: 0.035, 0.094, 0.176 mg kg-1, pp'DDT: 0.296, 0.351, 

0.661 mg kg-1, ?-DDT: 1.112, 1.423, 2.601 mg kg-1, resp. Paired analyses of the 

three groups revealed divergences among them and correlation of these 

pesticide levels with breast tumors. Calcd. relative risk (RR) values for the benign 

to control group and the malignant to control cases presented the following 

values: HCB: 2.11, 2.01, ?-HCH: 1.96, 1.58, pp'DDE: 2.13, 1.17, op'DDT: 4.42, 

2.27, pp'DDT: 2.33, 1.33, ?-DDT: 2.21, 1.19 resp. The obtained results indicate 

higher organochlorine pesticide residue levels in women with benign breast 

abnormalities and higher relative risk related to op'DDT presence. 

Waliszewski, S. M., M. V. Meza Hernandez, et al. (2003). "Persistent organochlorine 

pesticide levels in women with breast cancer in Veracruz, Mexico." Revista 

Internacional de Contaminacion Ambiental 19(2): 59-65. 

 The etiol. of breast cancer implicates organochlorine pesticides in the prevalence 

of the illness, due to their action as hormonal disrupters and bioaccumulation in 

the human body. During the study, 21 samples of adipose tissue adhered to 

mammary tumors and 21 control samples of abdominal adipose tissue from 

women subjected to hernia surgery were taken. The organochlorine pesticide 
40

levels were detd. by gas chromatog. The ages of the control group were 48.7 ± 

16.6 and of the breast cancer group 50.9 ± 13.4. The control group has 3.5 ± 2.6 

children while the breast cancer group only 1.4 ± 1.3. The HCB levels were 0.043 

mgkg-1 in the control group and 0.036 mgkg-1 in the breast cancer group. ?-

HCH show 0.282 mgkg-1 in the control group and 0.320 mgkg-1 in the breast 

cancers. The pp'-DDE revealed 0.746 mgkg-1 in the control group and 1.098 

mg/kg in the breast cancer women's group. The op'-DDT presented 0.041 mgkg1 in the control group and 0.141 mgkg-1 in the breast cancers. The pp'-DDT 

indicated 0.350 mgkg-1 in the control group and 0.398 mgkg-1 in the breast 

cancer patients. The DDT total values show 1.333 mgkg-1 in the control group 

and 1.638 mgkg-1 in the breast cancer women. The organochlorine pesticide 

levels are higher in the patients with breast cancer compared to the control 

group. First group presented minor birth rate. The statistical test applied indicated 

no correlation between the two groups and those tests showed a possible 

correlation of higher exposition to organochlorine pesticides and prevalence of 

breast cancer. 

CODE 4 (pharmacokinetics) References 

Abballe, A., T. J. Ballard, et al. (2008). "Persistent environmental contaminants in 

human milk: concentrations and time trends in Italy." Chemosphere 73(1 Suppl): S220-

7. 

 Breast milk monitoring studies of persistent and toxic environmental 

contaminants are of primary importance for carrying out an adequate risk 

assessment at the actual levels of human exposure and represent a major 

source of information on infant perinatal exposure. Milk specimens from mothers 

of the general population of the Venice and Rome areas were collected over the 

1998-2001 period, pooled, and analyzed for selected persistent organic 

pollutants such as polychlorodibenzodioxins (PCDDs), polychlorodibenzofurans 

(PCDFs), polychlorobiphenyls (PCBs), organochlorinated pesticides (p,p'-DDE, 

p,p'-DDT, hexachlorobenzene), and polybromodiphenyl ethers (PBDEs), and the 

heavy metals Cd, Co, Cu, Hg, Mn, Pb, Sn, and Zn. The goal was to verify 

whether mother milk from the Venice area, whose lagoon is partly under direct 

industrial impact, had a contaminant load greater than that from the Rome area, 

primarily urban. For mothers from the Venice area, the correlation between fish 

and fishery product consumption and contaminant concentrations in milk was 

also explored, with however inconclusive results. The concentrations of PCDDs, 

PCDFs, dioxin-like PCBs, and organochlorinated pesticides determined in this 

study were compared with those available from a previous analytical work carried 

out on 1987 human milk pools of domestic origin: the declining trend of the 

aforesaid contaminants in milk is confirmed to be in agreement with what was 

observed in other European countries. The breast milk content of (137)Cs and 

(40)K radionuclides was also determined and compared with data obtained in 

other research programmes carried out in Italy: the health risk for breastfed 

infants was deemed to be not significant. 
41

Arrebola, J. P., P. Martin-Olmedo, et al. (2009). "Predictors of concentrations of 

hexachlorobenzene in human adipose tissue: a multivariate analysis by gender in 

Southern Spain." Environ Int 35(1): 27-32. 

 Hexachlorobenzene (HCB) was measured in adipose tissue intraoperatively 

collected from 387 subjects over 16 years old undergoing surgery in two 

hospitals in Granada (Southern Spain). HCB was quantified in 90.7% of subjects. 

The concentrations and frequencies of HCB were similar to those reported in 

adipose tissue samples in other recent European studies. Exposure patterns 

differed between females and males: higher HCB concentrations were found in 

females than in males (geometric mean 18.3 vs. 6.8 ng/g, p<0.001). The 

relationship between HCB concentrations and exposure risk factors was 

assessed by multivariate analysis stratifying by gender. In men, HCB 

concentrations were predicted (r(2)=0.45) by age, body mass index (BMI), place 

of residence, smoking, consumption of fish, chicken and cheese, occupation 

related to agriculture, and family involvement in construction activities. In women, 

HCB concentrations were predicted (r(2)=0.50) by age, BMI, consumption of milk 

and cheese, and occupation related to industry. The finding that women had 

three-fold higher levels of HCB than the men deserves further investigation. 

Barr, D. B., P. Weihe, et al. (2003). "PCBs and organochlorine pesticide concentrations 

in a Faroe Island 14-year old cohort: measurement using new methodology and 

evaluation of correlations and patterns." Organohalogen Compounds 63: 385-388. 

 Polychlorinated biphenyls (PCB) and organochlorine pesticide patterns and 

intercorrelations were measured in serum samples of children. An accelerated 

solvent extn. and gel permeation chromatog. were followed by isotope diln. 

GC/high resoln. MS. The most highly chlorinated PCBs, esp. pentachloro and 

higher, were intercorrelated, but showed poor correlations with the lower 

chlorinated PCBs. PCBs of lower chlorination were intercorrelated with each 

other. The commonly measured PCB 153 and 180 were correlated with 

oxychlordane, trans-nonachlor, p,p'-DDE, and mirex. Hexachlorobenzene and ?-

hexachlorocyclohexane showed correlations with all of the most prevalent PCBs. 

A concn. gradient in the more highly chlorinated PCBs was found in dependence 

on the consumption of blubber. Children nursed for a shorter time had lower 

concns. of the higher mol. wt. PCBs than those nursed for a longer duration. 

Differences were found in serum PCB levels between males and females. 

Behrooz, R. D., A. E. Sari, et al. (2009). "Organochlorine pesticide and polychlorinated 

biphenyl residues in human milk from the Southern Coast of Caspian Sea, Iran." 

Chemosphere 74(7): 931-7. 

 In the present study, human milk was sampled in October 2006 from Nour and 

Noushahr cities and their countryside on the Southern Coast of Caspian Sea, 

Iran. They were analyzed for organochlorine pesticides, such as 

dichlorodiphenyltrichloroethane (DDT) and its metabolites, hexachlorobenzene 

(HCB), alpha, beta and gamma-hexachlorocycloexane (HCH) isomers and six 

PCBs congeners (IUPAC Nos. 28, 52, 101, 138, 153 and 180). Average 

concentrations of HCHs, DDTs, PCBs and HCB were 3780, 2554, 1560 and 930 
42

ng g(-1) lipid wt, respectively. There was no significant difference between the 

concentrations of investigated pollutants between the two cities and their 

countryside. No significant differences in OCPs and PCBs were found between 

primiparous and multiparous mothers. There was no correlation between levels 

of OCPs and PCBs in human milk and the age of mothers. There was a 

significant difference in the organochlorine levels, including DDTs, between 

mothers who have eaten fish once a week and those who consumed fish more 

than once (p>0.05). An analysis of the infant exposure to OCPs and PCBs via 

breast milk indicated that the daily intake rates for most of the mothers were 

above the guideline proposed by Health Canada which is definitely caused on 

children health for concern. 

Bhatnagar, V. K., R. Kashyap, et al. (2004). "Levels of DDT, HCH, and HCB residues in 

human blood in Ahmedabad, India." Bull Environ Contam Toxicol 72(2): 261-5. 

 

Billi de Catabbi, S. C., A. Faletti, et al. (2005). "Hepatic arachidonic acid metabolism is 

disrupted after hexachlorobenzene treatment." Toxicol Appl Pharmacol 204(2): 187-95. 

 Hexaclorobenzene (HCB), one of the most persistent environmental pollutants, 

can cause a wide range of toxic effects including cancer in animals, and 

hepatotoxicity and porphyria both in humans and animals. In the present study, 

liver microsomal cytochrome P450 (CYP)-dependent arachidonic acid (AA) 

metabolism, hepatic PGE production, and cytosolic phospholipase A2 (cPLA2) 

activity were investigated in an experimental model of porphyria cutanea tarda 

induced by HCB. Female Wistar rats were treated with a single daily dose of 

HCB (100 mg kg(-1) body weight) for 5 days and were sacrificed 3, 10, 17, and 

52 days after the last dose. HCB treatment induced the accumulation of hepatic 

porphyrins from day 17 and increased the activities of liver ethoxyresorufin Odeethylase (EROD), methoxyresorufin O-demethylase (MROD), and aminopyrine 

N-demethylase (APND) from day 3 after the last dose. Liver microsomes from 

control and HCB-treated rats generated, in the presence of NADPH, 

hydroxyeicosatetraenoic acids (HETEs), epoxyeicosatrienoic acids (EETs), 

11,12-Di HETE, and omega-OH/omega-1-OH AA. HCB treatment caused an 

increase in total NADPH CYP-dependent AA metabolism, with a higher response 

at 3 days after the last HCB dose than at the other time points studied. In 

addition, HCB treatment markedly enhanced PGE production and release in liver 

slices. This HCB effect was time dependent and reached its highest level after 10 

days. At this time cPLA2 activity was shown to be increased. Unexpectedly, HCB 

produced a significant decrease in cPLA2 activity on the 17th and 52nd day. Our 

results demonstrated for the first time that HCB induces both the cyclooxygenase 

and CYP-dependent AA metabolism. The effects of HCB on AA metabolism were 

previous to the onset of a marked porphyria and might contribute to different 

aspects of HCB-induced liver toxicity such as alterations of membrane fluidity 

and membrane-bound protein function. Observations also suggested that a 

possible role of cPLA2 in the early increase of AA metabolism cannot be 

excluded. However, the existence of other pathway(s) for metabolizable AA 

generation different from cPLA2 activation is also proposed. 
43

Bloom, M. S., J. E. Vena, et al. (2005). "Profiles of ortho-polychlorinated biphenyl 

congeners, dichlorodiphenyldichloroethylene, hexachlorobenzene, and Mirex among 

male Lake Ontario sportfish consumers: the New York State Angler cohort study." 

Environ Res 97(2): 178-94. 

 Great Lakes sportfish consumption is a recognized human exposure source to 

environmental organochlorine compounds. Using data collected as part of the 

New York State Angler Cohort Study, 203 males were considered with regard to 

history of Lake Ontario sportfish consumption and sera levels of 57 orthosubstituted polychlorinated biphenyl (PCB) congeners, 

dichlorodiphenyldichloroethylene, hexachlorobenzene, and Mirex. Consumption 

of six species of highly contaminated Lake Ontario sportfish during the years 

1980 to 1990 was considered. Exposure was weighted by average annual 

frequency of consumption, whole-fish PCB estimates, and meal size to determine 

a continuous index of exposure. This index was dichotomized to compare 

"consumers" to "nonconsumers" in several procedures. Recovery and lipidadjusted serum values for PCB congener IUPAC Nos. 138+163 (rsp=0.3), 183 

(rsp=0.3), 187 (rsp=0.4), and 188 (rsp=0.3) and Mirex (rsp=0.4) were significantly 

correlated with the index of fish consumption (P<0.001). A logistic regression 

model, using forward stepwise selection procedures (alpha in/out=0.002/0.004), 

was employed to account for high intercorrelations among organochlorine 

predictor variables. Mirex was the sole statistically significant predictor variable of 

"consumer/nonconsumer." A one-unit increase in log Mirex was associated with 

a 92.0% increase in the odds of having reported sportfish consumption 

(OR=1.92, 95%CI=1.43, 2.58). Age, body mass index, cigarette smoking, 

water/wildfowl consumption, and year of sampling were considered covariates. 

The results of this study support the premise that long-term dietary consumption 

of Lake Ontario sportfish, even at comparatively low levels, contributes 

significantly to the body burden of organochlorine compounds in western New 

York anglers and sportsmen. 

Bradman, A. S., J. M. Schwartz, et al. (2007). "Factors predicting organochlorine 

pesticide levels in pregnant Latina women living in a United States agricultural area." J 

Expo Sci Environ Epidemiol 17(4): 388-99. 

 Organochlorine (OC) pesticide use was restricted starting in the 1970s in 

developed countries and the 1980s and 1990s in developing countries. Current 

exposure to OC pesticides - dichlorodiphenyltrichloroethane (DDT), lindane (99% 

pure gamma-hexachlorocyclohexane (gamma-HCH)), hexachlorobenzene (HCB) 

- occurs on a limited basis. We measured para, para' (p,p')-DDE, p,p'-DDT, ortho, 

para' (o,p')-DDT, HCB, beta (beta)-HCH (the most persistent isomer of technicalgrade HCH) and gamma-HCH in serum from 426 low-income pregnant Latina 

women living in an agricultural community in California. Detection frequencies 

were 94% to 100%. Median levels (ng/g lipid) of p,p'-DDE (1,052), p,p'-DDT (13), 

beta-HCH (37) and HCB (65) were significantly higher than United States 

population levels. Multivariate analyses of p,p'-DDE, p,p'-DDT, o,p'-DDT, betaHCH and HCB indicate that time spent living outside the United States and 
44

birthplace in an area of Mexico with recent use of OC pesticides were significant 

predictors of exposure. Time spent living in the United States was associated 

with increased serum levels of p,p'-DDE and beta-HCH, but the increase for each 

year lived in the United States was lower than for each year lived outside the 

United States. There was no difference between the increase of HCB levels over 

time spent in or outside the United States, suggesting current and thus 

preventable exposure routes. However, we observed no associations between 

serum levels of any OC compound and current intake of saturated fat or 

agricultural take-home exposure risk factors. Lactation history and recent weight 

gain were negatively associated with serum levels of some, but not all OC 

compounds studied. Smoking history was borderline associated with elevated 

HCB levels. We observed no significant associations with body mass index. 

Although the weight of evidence from this study indicates that most exposure 

occurred before moving to the United States, the results for HCB indicate the 

possibility of ongoing exposure in this country. 

Burke, E. R., A. J. Holden, et al. (2003). "Organochlorine pesticide residues in human 

milk from primiparous women in Indonesia." Bulletin of Environmental Contamination 

and Toxicology 71(1): 148-55. 

 

Butler Walker, J., L. Seddon, et al. (2003). "Organochlorine levels in maternal and 

umbilical cord blood plasma in Arctic Canada." Science of the Total Environment 302(1-

3): 27-52. 

 A baseline for exposure to organochlorine and metal contaminants has been 

established for mothers and newborns in the Northwest Territories and Nunavut 

areas of Arctic Canada. Maternal and umbilical cord blood plasma 

organochlorine levels are described for Inuit, Dene, Metis, Caucasian and Other 

non-Aboriginal participants. Overall, 523 women volunteered to participate by 

giving their written informed consent between May 1994 and June 1999, resulting 

in the collection of 386 maternal blood samples, 407 cord blood samples and 351 

maternal/cord pairs. Nearly half of all the participants regularly smoked 

cigarettes, including 77% of the Inuit participants. Maternal and cord results are 

presented for PCBs (as Aroclor 1260 and 14 congeners) and organochlorine 

pesticides, including p,p'-DDT, p,p'-DDE, beta-hexachlorocyclohexane (betaHCH), hexachlorobenzene (HCB), cis and trans nonachlor, heptachlor epoxide, 

oxychlordane, mirex, dieldrin and toxaphene. Maternal PCB levels (as Aroclor 

1260) averaged 4.42 (+/-9.03) microg/l in Inuit, which was 3.3 times higher than 

those found in Dene/Metis, and 3.4 times higher than levels in Caucasians. Mean 

DDE levels were 2.8 times higher in the Other non-Aboriginal group (Chinese, 

Filipino, East Indian and multiple ethnicity) than in the Inuit group, at 3.99 

microg/l and 1.42 microg/l, respectively. Cord blood PCB levels (as Aroclor 1260) 

averaged 1.16 (+/-2.42) microg/l for Inuit participants, which was 3.3-4 fold higher 

than the other ethnic groups. PCBs, p,p'-DDE and hexachlorobenzene were 

detected in all maternal samples, and p,p'-DDE was detected in all cord samples. 

Regression coefficients for maternal/cord pairs are presented for selected 
45

organochlorines. Other results from this study, including maternal and cord 

metals data, will be presented elsewhere. 

Carrizo, D., J. O. Grimalt, et al. (2006). "Physical-chemical and maternal determinants 

of the accumulation of organochlorine compounds in four-year-old children." 

Environmental Science and Technology 40(5): 1420-6. 

 A cohort study representing a general population (Minorca Island, birth year 

1997-1998) showed that in utero transfer of organochlorine compounds (OCs) in 

children was strongly correlated with the age of the mother and, in the case of 

hexachlorobenzene (HCB), 4,4'-DDE, and 4,4'-DDT, with the maternal body 

mass index. Some of these correlations remained significant for the serum 

concentrations collected in these children at four years. No significant 

correlations with length of gestation were observed. Breastfeeding and age of 

lactation were strong determinants of most OC concentrations at four years of 

age. At this age, the body burden of these compounds was higher than at birth 

irrespective of maternal or formula feeding, but they accumulated at higher extent 

in the former case involving concentration increments in blood that surpassed the 

growth dilution effects, with the only exceptions being pentachlorobenzene 

(PeCB), HCB, and 4,4'-DDT. 4,4'-DDE exhibited the highest increase in 

association with breastfeeding, pointing to a specific accumulation pathway via 

this mode. Compounds with low K(ow) values such as betahexachlorocyclohexane showed significant accumulation in four-year-old children 

but with small differences between the groups that had been raised on either 

breast milk or formula. Compounds having low K(oa) values such as HCB 

showed decreases in concentration and small body burden variation between 

birth and four years of age, which points to their preferential elimination in these 

initial periods of infant growth. 

Charlier, C., C. Desaive, et al. (2002). "Human exposure to endocrine disrupters: 

consequences of gastroplasty on plasma concentration of toxic pollutants." International 

journal of obesity and related metabolic disorders : journal of the International 

Association for the Study of Obesity. 26(11): 1465-8. 

 BACKGROUND: Body weight loss occurring after a hypoenergetic diet or a 

gastroplasty could be followed by an increase in blood concentration of 

potentially toxic pollutants that can interfere with the hormonal system (endocrine 

disrupters). DESIGN: Thirty obese individuals recruited for gastroplasty were 

compared before and after treatment with 45 normal-weight people. 

MEASUREMENTS: Blood samples were analyzed for DDT, DDE, HCB and 

PCBs no. 28, 52, 101, 118, 138, 153 and 180, by gas chromatography-mass 

spectrometry. RESULTS: The results indicate clearly that body weight loss 

occurring after gastroplasty increases plasma concentration of lipophilic 

pollutants. CONCLUSION: Gastroplasty increases plasma concentration of 

organochlorine pesticides and PCBs, which could be a risk factor of endocrine 

disruption. Future longitudinal research will have to determine if the advantages 

of body weight loss are reduced by this potentially harmful effect. 
46

Charlier, C. J. and G. J. Plomteux (2002). "Determination of organochlorine pesticide 

residues in the blood of healthy individuals." Clinical chemistry and laboratory medicine : 

CCLM / FESCC. 40(4): 361-4. 

 Pesticide use is one of several factors that have permitted maintenance of our 

supply of food in spite of continuing increase of the population. However, the use 

of biologically active compounds poses potential problems of toxicity. If the 

compound is used at any stage of food production, residues or derivatives may 

persist in food and the entire population may be exposed to the trace amounts of 

the material. The human body burden associated with long-term exposure may 

or may not be associated with illness. Persistent environmental contaminants 

such as pesticide residues have long been suspected to be implicated in cancer 

etiology. Organochlorine chemicals are persistent, lipophilic compounds 

commonly present in the environment. Some of them demonstrated carcinogenic 

activity in laboratory animals. Controversy still exists concerning their 

carcinogenic potential in humans. To answer this question, clinical toxicology 

laboratories should propose validated methodologies able to identify and quantify 

pesticide residues in biological samples. An example of chromatographic method 

dedicated to organochlorine residues is presented here and illustrated by results 

obtained in a healthy population (104 men, 147 women). Only 17.9% of the 

samples were free from detectable amounts of pesticides and p,p'-DDE 1,1-

dichloro-2,2-bis(p-chlorophenyl)ethylene was the most frequently detected 

residue (66.5%). Hexachlorobenzene was found at detectable level in 13.5% of 

the samples. 

Cole, D. C., J. Sheeshka, et al. (2002). "Dietary intakes and plasma organochlorine 

contaminant levels among Great Lakes fish eaters." Archives of Environmental Health

57(5): 496-509. 

 Nutritional intakes and contaminant burdens should be assessed jointly in 

individuals who are at high risk of environmental exposures to contaminants 

through food. In this study, the authors used shore surveys and community 

contacts to recruit 91 individuals who frequently consumed Great Lakes fish. 

These individuals provided dietary intake information and fasting blood samples 

for lipid and contaminant analyses. Participants ate an annual median of 88 

meals of Great Lakes fish. Asian-Canadians consumed more total fish meals 

(i.e., Great Lakes, non-Great Lakes, and other) (medians = 213.0 females, 223.0 

males) than Euro-Canadians (medians = 131.0 females, 137.5 males). The 

higher total fish consumption by Asian-Canadians was associated with a lower 

percentage of energy derived from fat, higher protein and iron intakes, and higher 

plasma concentrations of omega-3 essential fatty acids (e.g., median 

docosahexaenoic acid levels [microgram/l] in Asian-Canadian females = 5.48, 

males = 4.38; in Euro-Canadian females = 2.93, males = 2.27). Plasma 

organochlorine contaminant lipid weight concentrations varied by country of 

origin and by gender (e.g., median total polychlorinated biphenyls [microgram/kg] 

in Asian-Canadian females = 490.6, males = 729.0; in Euro-Canadian females = 

339.6, males = 355.5). Age was the most consistent predictor (+ve) of 

contaminant concentrations, followed by years spent in Canada (for Asian-
47

Canadians). Associations with sport fish consumption variables were less 

consistent than for the aforementioned predictors. Given both the health benefits 

and potential risks of fish consumption, policies that address diverse 

ethnocultural groups should support continued consumption of sport fish, but 

from less-contaminated sources than are currently used. 

Covaci, A., C. Hura, et al. (2008). "Organochlorine contaminants in hair of adolescents 

from Iassy, Romania." Chemosphere 72(1): 16-20. 

 Human hair samples (n=42) from Iassy county (Eastern Romania) collected in 

2002-2003 from adolescents were analyzed for hexachlorocyclohexane (HCH) 

isomers, p,p'-DDT and its metabolites, hexachlorobenzene (HCB), chlordane and 

metabolites and 5 polychlorinated biphenyl (PCB) congeners. Very low levels 

were found for HCB and oxychlordane (0.8 and 2.5 ng g(-1)) indicating a low 

usage of these pesticide formulations in the studied area. In case of HCHs, 

gamma-HCH isomer was measured at higher median concentrations (79 ng g(-1) 

hair) compared to the beta-HCH isomer (55 ng g(-1)), which generally is the most 

prevalent from HCHs. The DDTs profile consisted in p,p'-DDE and p,p'-DDT 

which levels correspond to 81% of sum DDTs. Very high median concentrations 

measured for p,p'-DDT (192 ng g(-1)) combined with lower values for p,p'-

DDE/p,p'-DDT of 0.4 (from 0.20 to 2.0) in all hair samples suggest recent 

exposure to "fresh" DDT. When gender was considered, significantly higher 

concentrations for most of the investigated contaminants were found in girls hair 

compared to boys. Very high levels were found in the present study for HCHs 

and DDTs compared to samples from Greece, Western Europe and China. In 

case of PCBs, the levels found in Romanian samples were found to be in the 

same range compared to other previously published data. 

De Felip, E., A. di Domenico, et al. (2004). "Polychlorobiphenyls and other 

organochlorine compounds in human follicular fluid." Chemosphere 54(10): 1445-9. 

 Based on observations in animals, there is an increasing evidence that a number 

of persistent organochlorine pollutants can alter the endocrine homeostasis, this 

resulting in toxic effects in particular in the developing organism. However, the 

role of these chemicals in determining endocrine-related diseases in humans, 

and possibly a decrease of fertility, is still controversial. Exposure data 

concerning the human reproductive system are essential for risk assessment. 

Based on this, the occurrence in follicular fluid of polychlorobiphenyls (PCBs), 

2,3,7,8-chlorosubstituted polychlorinated dibenzo-p-dioxins (PCDDs) and 

dibenzofurans (PCDFs), 1,1,1-trichloro-2,2-bis(4-chlorophenyl)-ethane (p,p'-DDT) 

and its metabolites, and hexachlorobenzene (HCB) was investigated. With 

respect to PCBs, the sum of the three most abundant congeners (PCBs 138, 153 

and 180) was 1230 ng/g, lipid basis (0.37 ng/g, wet weight). Congener 

distribution profile overlapped what is usually observed in other human tissues, 

as blood and milk. PCDDs, PCDFs, p,p'-DDT and 1,1-dichloro-2,2-bis(4-

chlorophenyl)-ethane (p,p'-DDD) were below their determination limits. 1,1-

dichloro-2,2-bis(4-chlorophenyl)-ethene (p,p'-DDE) and HCB were detected in 
48

concentrations respectively in the order of 700 and 70 ng/g, lipid basis 

(approximately 0.2 and approximately 0.02 ng/g, wet weight). 

Devanathan, G., A. Subramanian, et al. (2009). "Persistent organochlorines in human 

breast milk from major metropolitan cities in India." Environ Pollut 157(1): 148-54. 

 The present study was carried out to understand the current contamination status 

of organochlorine compounds (OCs) in human breast milk from three 

metropolitan cities in India (New Delhi, Mumbai and Kolkata). Among the OCs 

analyzed, DDTs were predominant followed by HCHs and PCBs. CHLs and HCB 

levels were much lower. Contamination patterns were different in human milk 

found in our previous study in Chennai, a metropolitan city in southern India, 

indicating region specific exposure routes and variable sources. In comparison 

with previous data, levels of DDTs and HCHs generally declined with time, 

implying the effect of various bans and restrictions on their usage. No association 

between concentrations of OCs and demographic characteristics such as parity 

and age of mothers was observed which might be due to narrow range of 

mother's age. Estimated daily intake shows that some infants are exposed to 

OCs to a greater extent, particularly HCHs than the guideline standard. 

Dewailly, E., G. Mulvad, et al. (1999). "Concentration of organochlorines in human 

brain, liver, and adipose tissue autopsy samples from Greenland." Environmental Health 

Perspectives 107(10): 823-828. 

 BIOSIS COPYRIGHT: BIOL ABS. Organochlorines are persistent lipophilic 

compounds that accumulate in Inuit people living in circumpolar countries. 

Organochlorines accumulate as a result of the Inuits' large consumption of sea 

mammal fat; however, available data are limited to blood lipids, milk fat, and 

adipose tissue. We report results of organochlorine determination in liver, brain, 

omental fat, and subcutaneous abdominal fat samples collected from deceased 

Greenlanders between 1992 and 1994. Eleven chlorinated pesticides and 14 

polychlorinated biphenyl congeners were measured in tissue lipid extracts by 

high-resolution gas chromatography with electron capture detection. Mean 

concentrations of polychlorinated biphenyls, 2,2'-bis(4-chlorophenyl)-1,1-

dichloroethylene, beta-hexachlorocyclohexane, hexachlorobenzene, mirex, transnonachlor, and oxychlordane in adipose tissue samples from Greenlanders were 

3-34-fold higher than those measured using the same analytical method in 

samples from Canadians in Quebec City, Quebec. Brain lipids contained lower 

concentrations of all organochlorines than lipids extracted from other tissues. 

Organochlorine residue levels in lipid extracts from liver, omental fat, and 

subcutaneous abdominal fat samples were similar, with the exception of betahexachlorocyclohexane, which reached a greater concentration in liver lipids than 

in lipids from both adipose tissues (4-fold; p < 0.05). Comparisons with available 

international data on adipose tissue levels reveal that the organochlorine body 

burden in the Inuit population of Greenland is presently among the highest 

resulting from environmental exposure. 
49

Eggesbo, M., H. Stigum, et al. (2009). "Levels of hexachlorobenzene (HCB) in breast 

milk in relation to birth weight in a Norwegian cohort." Environ Res. 

 BACKGROUND: Hexachlorobenzene (HCB) is a ubiquitous environmental 

contaminant that, even at low doses, causes destruction of ovarian primordial 

germ cells in experimental studies. However, its potential for reproductive toxicity 

in humans exposed to background levels has not been fully evaluated. Here we 

examined the association between maternal levels of HCB and their infants' birth 

weight. METHODS: HCB was measured in milk samples from a subset of women 

in the Norwegian Human Milk Study (HUMIS), 2003-2006; 300 subjects were 

randomly chosen from the cohort and 26 from all small for gestational age (SGA) 

children. Additional information was obtained through questionnaires and the 

Medical Birth Registry. RESULTS: Overall, HCB was associated with birth weight 

(adjusted b=-90g per 8mug/kg milk fat, 95% CI-275 to 8) and with SGA (odds 

ratio 1.8, 95% CI 0.9-3.7 per 8mug/kg milk fat (difference between the 10th and 

the 90th percentile)). After stratification, however, the association was present 

only among smokers. For birth weight for past or current smokers: b=-282, CI -

467 to -98; for never smokers: b=0.5, CI -149 to 150, p-value for interaction: 0.01. 

Similar results were observed for head circumference, crown-heel length, and 

SGA. CONCLUSIONS: We saw a moderate association between HCB and 

markers of impaired fetal growth among past and current smokers. This finding 

may be non-causal and due to underlying genetic variants tied to both growth 

and breakdown of HCB or to confounding by unmeasured toxicants that coexist 

in exposure sources. It may, however, also result from HCB exposure. 

Egorov, A., G. Mikhailov, et al. (2003). "Fish consumption and breast milk 

concentrations of PCBs and chlorinated pesticides in the Astrakhan region, Russia." 

Organohalogen Compounds 64: 91-94. 

 Dietary habits and breast milk concns. of polychlorinated biphenyl (PCB) 

congeners (not including the non-ortho-substituted congeners) and chlorinated 

pesticides [dichlorodiphenyltrichloroethane (DDT) and daughter products, 

hexachlorobenzene (HCB), mirex, aldrin, heptachlor, trans-nonachlor, 

oxychlordane] were assessed in the Astrakhan region, Russia. There were 

correlations between consumption of 3 fish species (perch, carp, pikeperch) and 

breast milk concns. of sumPCBs, mono-ortho PCBs, and di-ortho PCBs. 

Consumption of meat and meat products was neg. correlated with breast milk 

concns. of the same pollutants. Education and maternal age were predictive of a 

greater birth wt. 

Erdinger, L., P. Eckl, et al. (2004). "The Aral Sea disaster--human biomonitoring of Hg, 

As, HCB, DDE, and PCBs in children living in Aralsk-and Akchi, Kazakhstan." Int J Hyg 

Environ Health 207(6): 541-7. 

 Mercury and arsenic have been measured in urine samples and HCB, DDE and 

PCBs in blood samples of children from Aralsk and Akchi, Kazakhstan. Due to 

the special situation of Aralsk in the desert left by the drying out Aral Sea, 

environmental pollution with heavy metals and organic contaminants is believed 

to be higher than elsewhere in Kazakhstan. Aralsk was formerly located at the 
50

shore of the Aral Sea and is now far away from it. Akchi is a similar village and 

was included in this study as a Kazakh reference site. Urine concentrations of 

arsenic were higher in Akchi (9.4 microg/l) than in Aralsk (5.5 microg/l) and 

compared to children from Mannheim, Germany (4.25 microg/l; Median values). 

Regarding Hg, differences between children of Aralsk and Akchi were not 

significant and concentrations were lower than reference values from Germany. 

DDE contamination of children from Aralsk (2.48 microg/l) was significantly 

higher compared to Akchi (1.35 microg/l). DDE concentrations in blood samples 

from children in both cities were also significantly higher than the German 

reference value (0.7 microg/l). HCB and PCBs levels differed significantly 

between both Kazakh groups. However, concentrations of these compounds 

were lower than German reference values and there was no significant difference 

to samples from Mannheim children. 

Escuder-Gilabert, L., R. M. Villanueva-Camanas, et al. (2009). "Permeability and 

toxicological profile estimation of organochlorine compounds by biopartitioning micellar 

chromatography." Biomed Chromatogr 23(4): 382-9. 

 This paper points out the usefulness of biopartitioning micellar chromatography 

(BMC) as a high-throughput primary screening tool providing key information 

about the oral absorption, skin permeability (K(p)), brain-blood distribution 

coefficient (BB) and ecotoxicological parameters such as median lethal 

concentration (LC(50)) and bioconcentration factors of 15 organochloride 

compounds. The retention data of compounds in BMC conditions were 

interpolated in previously developed quantitative-retention activity relationships 

by our research group. Results show that the compounds studied readily cross 

the intestinal barrier (oral absorption > 90%) and the blood-brain barrier (log BB > 

0.4). In addition, the organochlorines DDE, chlorobenzene, 1,3-dichlorobenzene 

and 1,2-dichlorobenzene are the compounds which can more quickly cross the 

skin barrier (log K(p ) > -0.74 cm/h). From a ecotoxicological point of view, it can 

be concluded that the most retained compounds, DDE, DDD, 

hexachlorobenzene and dicofol, are the most toxic and bioacumulative. 

Falco, G., A. Bocio, et al. (2004). "Dietary intake of hexachlorobenzene in Catalonia, 

Spain." Sci Total Environ 322(1-3): 63-70. 

 To assess the dietary intake of hexachlorobenzene (HCB) by the population of 

Catalonia, Spain, a total-diet study was carried out. Concentrations of HCB were 

determined in food samples randomly acquired in seven cities of Catalonia 

between June and August 2000. A total of 11 food groups were included in the 

study. HCB levels were determined by HRGC/HRMS. Estimates of average daily 

food consumption were obtained from recent studies. HCB intake was estimated 

for five population groups: children (aged 4 to 9 years), adolescents (aged 10 to 

19 years), male and female adults (aged 20 to 65 years), and seniors (aged >65 

years). In general, HCB residues in foods were rather low excepting dairy 

products with a mean concentration of 0.869 ng/g wet weight. Total dietary 

intakes of HCB (microgram per kilogram body weight/day) were the following: 

children (0.0064), adolescents (0.0031), female adults (0.0025), male adults 
51

(0.0024) and seniors (0.0019). All these values are considerably lower than the 

WHO tolerable daily intake (TDI), which is 0.17 microg kg(-1) day(-1) for noncancer effects and 0.16 microg kg(-1) day(-1) for neoplastic effects in humans. 

Falco, G., J. M. Llobet, et al. (2008). "Exposure to hexachlorobenzene through fish and 

seafood consumption in Catalonia, Spain." Sci Total Environ 389(2-3): 289-95. 

 The concentrations of hexachlorobenzene (HCB) were analyzed by 

HRGC/HRMS in 42 composite samples of the 14 most consumed marine species 

(sardine, tuna, anchovy, mackerel, swordfish, salmon, hake, red mullet, sole, 

cuttlefish, squid, clam, mussel, and shrimp) in Catalonia, Spain. The daily intake 

of HCB associated with this consumption was also estimated for four age groups 

of the population of Catalonia: children, adolescents, adults and seniors, which 

were in turn divided according to sex. The highest HCB levels were found in 

salmon and mackerel: 1.68 and 0.80 ng/g of wet weight, respectively, whereas 

the lowest HCB levels were found in cuttlefish, mussel, and shrimp (0.02, 0.03, 

and 0.04 ng/g of wet weight, respectively). In general terms, these results are 

within the range of data reported in recent years by a number of authors. The 

highest and lowest HCB intake (ng/day) corresponded to female adults (13.3) 

and girls (4.0), respectively. For most age/sex groups, salmon and sole were the 

species showing the highest contribution to HCB intake. When HCB intake was 

calculated according to the average body weight of the individuals in each group, 

the highest and lowest values corresponded to boys (0.32 ng/kg/day) and female 

adolescents (0.14 ng/kg/day). For all groups, HCB intake from fish and seafood 

consumption was considerably lower than the WHO tolerable daily intake (TDI), 

for non-cancer effects and for neoplastic effects in humans. 

Fernandez, M. F., B. Olmos, et al. (2002). "Organochlorine determination in human 

placentas from different regions." Organohalogen Compounds 58(Dioxin 2002): 301-

303. 

 This work studies the intrauterine exposure of the fetus to some organochlorine 

compds. selected for their estrogen-mimicking character, through the anal. of 

placenta samples from women in hospitals in Granada, Almeria, Turku, and 

Copenhagen. 

Focant, J. F., A. Sjodin, et al. (2004). "Measurement of selected polybrominated 

diphenyl ethers, polybrominated and polychlorinated biphenyls, and organochlorine 

pesticides in human serum and milk using comprehensive two-dimensional gas 

chromatography isotope dilution time-of-flight mass spectrometry." Analytical Chemistry

76(21): 6313-20. 

 A new method using comprehensive two-dimensional gas chromatography and 

isotope dilution time-of-flight mass spectrometry (GCxGC-IDTOFMS) for the 

simultaneous measurement of selected polychlorinated biphenyls (PCBs), 

organochlorine pesticides (OCPs), and brominated flame retardants is presented. 

In contrast to the reference methods based on classical GC/MS, a single 

injection of the extract containing all compounds of interest results in accurate 

identification and quantification. Using GCxGC ensures the chromatographic 
52

separation of most compounds, and TOFMS allows mass spectral deconvolution 

of coeluting compounds as well as the use of (13)C-labeled internal standards for 

quantification. Isotope ratio measurements of the most intense ions for both 

native and labels ensure the required specificity. The use of this new method with 

an automated sample preparation procedure developed at the Centers for 

Disease Control and Prevention (CDC) for the analysis of human serum and milk 

compared favorably to conventional isotope-dilution one-dimensional gas 

chromatography-high-resolution mass spectrometry (GC-IDHRMS) for the 

different human serum and milk pools tested. The instrumental detection limits 

ranged between 0.5 pg/microL and 10 pg/microL and the method detection limits 

ranged between 1 and 15 pg/microL (N = 59 analytes). The reproducibility of the 

method was almost as good as with GC-IDHRMS, the relative standard 

deviations ranging between 1 and 11% for OCPs measured in human serum. 

OCP, PBDE, and PCB levels measured using the two methods were highly 

correlated, and the deviations between the two methods were below 20% for 

most analytes with concentrations above 1 ng/g milk lipids. 

Foster, W. G., C. L. Hughes, et al. (2002). "Human developmental exposure to 

endocrine active compounds." Environmental Toxicology and Pharmacology 12(2): 75-

81. 

 Quantification of exposure to environmental contaminants such as endocrine 

active chemicals (EACs) during critical periods of development, particularly in 

utero, remains largely unexplored. Therefore, we tested the hypothesis that 

EACs can be detected and quantified in second trimester human amniotic fluid. 

Amniotic fluid was obtained from women (n = 175) undergoing routine 

amniocentesis between 14 and 21 weeks gestation. Samples were assayed by 

gas chromatography/mass spectrometry (GC/MS) for common organochlorine 

contaminants and dietary phytoestrogens. The DDT metabolite p,p'-DDE was 

found in approximalely 25% of amniotic fluid samples (mean +/- S.D., 0.15 +/- 

0.06 ng/mL) whereas the dietary phytoestrogens, genistein and or daidzein were 

found in 96.2% of samples tested (0.94 +/- 0.91 and 1.08 +/- 0.91 ng/mL, 

respectively). Our results demonstrate that: (1) human amniotic fluid is a suitable 

biological medium to evaluate developmental exposure to EACs, and (2) fetuses 

are exposed to biologically active levels of EACs in mid pregnancy. 

Gabrio, T., S. Broser, et al. (2005). "[Human biomonitoring investigations of 

organochlorine compounds -- PCB, DDE, HCB, beta- and gamma-HCH, PCDD/PCDF, 

Dioxin-like PCB's and polybrominated biphenyl ethers]." Gesundheitswesen 67(4): 302-

11. 

 Although PCB and PCB-containing materials are not processed for a long time, 

PCB is under discussion again and again caused by the pollution of indoor 

environments. To objectify the discussion, the dates of the PCB-biomonitoring, 

the organochlorine-compounds (DDE, HCB, beta-/gamma -HCH, PCDD/PCDF) 

and the polybrominated biphenyl ethers concerning the investigations within the 

project "Sentinel Health Departments" in Baden-Wurttemberg are represented. 

Additionally results from children from Kazakhstan (Aral-Sea area) and from 
53

teachers which are working in PCB polluted schools as well as from a long term 

investigated test person are reported. Blood concentrations of the following 

compounds decreased from 1996/97 to 2002/03: the sum of the concentration of 

PCB 138,153 and 180 decreased from 0.46 microg/L to 0.20 microg/L, DDE from 

0.32 microg/L to 0.17 microg/, HCB from 0.20 microg/L to 0.08 microg/L, betaHCH below the level of detection, I-TEQ NATO to 4.8 pg/g blood fat, TEQ WHO 

(without PCB) to 5.5 pg/g blood fat, PCB 126 to 18,8,pg/g blood fat and PCB 169 

to 12.8 pg/g blood fat. The influence of breast feeding and the gender on the 

level of the pollution is conspicious. No local correlations were found in BadenWurttemberg, but they were found in comparison with the results of Kazakhstan 

(Aral-Sea area). The difficulty to produce time series while the analyzing 

pollutants are more and more decreasing, as well as the change of the 

calculation base of the summation of parameters like I-TEQ NATO to TEQ WHO 

are discussed. 

Gladen, B. C., S. C. Monaghan, et al. (1999). "Organochlorines in breast milk from two 

cities in Ukraine." Environmental Health Perspectives 107(6): 459-462. 

 BIOSIS COPYRIGHT: BIOL ABS. Reports of environmental problems in the 

former Soviet Union, including excess use of pesticides, have led to concerns 

about high levels of contamination in humans, but little information is available to 

assess whether these concerns are warranted. Samples of breast milk from 197 

women from two cities in Ukraine were analyzed for p,p'-DDT, p,p'-DDE, endrin, 

dieldrin, heptachlor epoxide, trans-nonachlor, oxychlordane, hexachlorobenzene, 

beta-hexachlorocyclohexane (HCH), and 18 polychlorinated bip or lower than 

other reports from Europe. Concentrations from the city of Kyiv were generally 

lowerthan those from Dniprodzerzhinsk, but the magnitudes of these differences 

were modest. 

Glynn, A., M. Aune, et al. (2007). "Determinants of serum concentrations of 

organochlorine compounds in Swedish pregnant women: a cross-sectional study." 

Environmental health : a global access science source [electronic resource]. 6: 2. 

 BACKGROUND: We performed a cross-sectional study of associations between 

personal characteristics and lipid-adjusted serum concentrations of certain PCB 

congeners and chlorinated pesticides/metabolites among 323 pregnant 

primiparous women from Uppsala County (age 18-41 years) sampled 1996-1999. 

METHODS: Extensive personal interviews and questionnaires about personal 

characteristics were performed both during and after pregnancy. Concentrations 

of organochlorine compounds in serum lipids in late pregnancy were analysed by 

gas chromatography. Associations between personal characteristics and serum 

levels of organochlorine compounds were analysed by multiple linear regression. 

RESULTS: Participation rate was 82% (325 of 395 women). Serum 

concentrations of PCB congeners IUPAC no. 28, 52, 101, 105 and 167, and o, p'-

DDT and -DDE, p, p'-DDT and -DDD, oxychlordane, and gamma- and alphaHCH were in many cases below the limit of quantification (LOQ). No statistical 

analysis of associations with personal characteristics could be performed for 

these substances. Concentrations of PCB congeners IUPAC no. 118, 138, 153, 
54

156 and 180, HCB, beta-HCH, trans-nonachlor and p, p'-DDE increased with 

increased age and were highest in women sampled early during the 4 year study 

period. This shows that older women and women sampled early in the study had 

experienced the highest life-time exposure levels, probably mainly during 

childhood and adolescence. The importance of early exposures was supported 

by lower PCB concentrations and higher beta-HCH and p, p'-DDE concentrations 

among women born in non-Nordic countries. Moreover, serum concentrations of 

certain PCBs and pesticide/metabolites were positively associated with 

consumption of fatty fish during adolescence, and concentrations of CB 156, CB 

180 and p, p'-DDE increased significantly with number of months women had 

been breast-fed during infancy. Short-term changes in bodily constitution may, 

however, also influence serum concentrations, as suggested by negative 

associations between concentrations of organochlorine compounds and BMI 

before pregnancy and weight change during pregnancy. CONCLUSION: 

Although some of the associations could be caused by unknown personal 

characteristics confounding the results, our findings suggest that exposures to 

organochlorine compounds during childhood and adolescence influence the body 

burdens of the compounds during pregnancy. 

Greizerstein, H. B., C. Stinson, et al. (1999). "Comparison of PCB congeners and 

pesticide levels between serum and milk from lactating women." Environmental 

Research 80(3): 280-286. 

 BIOSIS COPYRIGHT: BIOL ABS. Samples of blood and milk were obtained from 

lactating women participating in the New York State Angler study. A total of 

seven women gave one blood and one milk sample at time intervals between 

blood and milk collection different for each woman. The time between samples 

varied from 3 to 318 days. One subject provided a second milk sample 219 days 

after the first milk sample. The samples were analyzed for 69 PCB congeners, 

DDE (a metabolite of DDT), Mirex, and hexachlorobenzene (HCB). Lipid cont 

tions varied from 0.18 to 1.66 with a mean of 0.65 | 0.49 showing no consistency 

among individuals prior to adjusting the data for lipid content. The total PCB 

levels normalized for lipid content were 320-728 ng/g of serum lipid and 239-428 

ng/g of milk lipid. The range of the lipid adjusted serum/milk ratio was 1.1 to 2.8 

and the mean | SD serum/milk ratio was 1.9 | 0.5. The ranges of lipid adjusted 

serum concentration of DDE, HCB, and Mirex were 95 to 591, 8 to 48, and 3 to 

29 

Hagmar, L., E. Wallin, et al. (2006). "Intra-individual variations and time trends 1991-

2001 in human serum levels of PCB, DDE and hexachlorobenzene." Chemosphere

64(9): 1507-13. 

 BACKGROUND: An important question is whether human serum levels of 

persistent organic pollutants has continued to decrease during the last decades. 

The aim of this study was to assess intra-individual variations over time of serum 

levels of 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153), 1,1-dichloro-2,2-bis(4-

chlorophenyl)-ethene (p,p'-DDE) and hexachlorobenzene (HCB), considering the 

impact of a number of possible determinants. METHODS: Blood samples were 
55

drawn for the same 39 subjects in 1991 and 2001. Interviews were made at both 

occasions. Lipid adjusted serum concentrations of CB-153, p,p'-DDE and HCB 

were determined in both sets of blood samples using gas chromatography-mass 

spectrometry. The fatty acid composition of the serum lipids was analyzed by 

means of gas-liquid chromatography. RESULT: The CB-153 concentrations in 

serum had averagely decreased with 34% in between 1991 and 2001 (p<0.001). 

Of individual determinants only increasing BMI was associated with decreasing 

CB-153 levels (beta=-1.0, 95% CI -1.8, -0.2, p=0.01), explaining 13% of the 

variation. The average decrease of p,p'-DDE was 55%, and could only weakly be 

associated with a relative increase of BMI (beta=-1.0, 95% CI -2.3, 0.2, p=0.09), 

explaining only 5% of the variation. The average decrease of HCB was 53%, and 

was associated only with high fish consumption in 1991, explaining 12% of the 

variation. CONCLUSIONS: The results support a continuing decrease in human 

body burdens of PCBs, DDE and HCB during the 1990s. The explanatory factors 

relative change of BMI and fish consumption explained only a minor part of the 

time-related variations in serum levels. 

Hanaoka, T., Y. Takahashi, et al. (2002). "Residuals of beta-hexachlorocyclohexane, 

dichlorodiphenyltrichloroethane, and hexachlorobenzene in serum, and relations with 

consumption of dietary components in rural residents in Japan." Sci Total Environ

286(1-3): 119-27. 

 To estimate levels of organochlorine residuals in the Japanese population and 

the contribution of dietary factors to these levels, we determined serum levels of 

beta-hexachlorocyclohexane (beta-HCH), hexachlorobenzene (HCB), p,p'-

dichlorodiphenyldichloroethane (p,p'- DDD), 1,1-dichloro-2,2-bis(p-chlorophenyl) 

ethylene (p,p'-DDE) and p,p'- dichlorodiphenyltrichloroethane (p,p'-DDT) in 41 

volunteers (14 men and 27 women) in a rural area of Northern Japan. These 

organochlorine levels were measured using gas-chromatography massspectrometry. By a self-administered dietary history questionnaire, the usual 

dietary intake was estimated. Their median levels (range) were as follows: betaHCH, 0.50 (0.05-1.50); HCB, 0.20 (0.02-0.70); and total DDT (p,p'-DDE + p,p'-

DDT), 5.0 (0.9-31.0) ng/ml serum. Levels of p,p'-DDD were detected in only 

seven subjects (0.05-0.6 ng/ml serum). The beta-HCH levels were increased with 

rice and milk intakes, but the least squares means were not simply increased 

according to the quartile of the intakes. Concerning HCB, fish intake showed a 

borderline significant correlation (0.20, P = 0.052). In terms of total DDT, intakes 

of meat, fish, vegetable and milk showed a positive relationship, although none of 

them provided statistically significant results. No other statistically significant 

relation between any organochlorines and any food intakes examined was 

observed in this study. The present study suggests that organochlorine 

compounds are transported into the human body via foods in the Japanese 

population. Their effects on health should thus be investigated and monitored. 

Hendriks, A. J., T. P. Traas, et al. (2005). "Critical body residues linked to octanol-water 

partitioning, organism composition, and LC50 QSARs: meta-analysis and model." 

Environmental Science and Technology 39(9): 3226-36. 
56

 To protect thousands of species from thousands of chemicals released in the 

environment, various risk assessment tools have been developed. Here, we link 

quantitative structure-activity relationships (QSARs) for response concentrations 

in water (LC50) to critical concentrations in organisms (C50) by a model for 

accumulation in lipid or non-lipid phases versus water Kpw. The model indicates 

that affinity for neutral body components such as storage fat yields steep KpwKow relationships, whereas slopes for accumulation in polar phases such as 

proteins are gentle. This pattern is confirmed by LC50 QSARs for different 

modes of action, such as neutral versus polar narcotics and organochlorine 

versus organophosphor insecticides. LC50 QSARs were all between 0.00002 

and 0.2Kow(-1). After calibrating the model with the intercepts and, for the first 

time also, with the slopes of the LC50 QSARs, critical concentrations in 

organisms C50 are calculated and compared to an independent validation data 

set. About 60% of the variability in lethal body burdens C50 is explained by the 

model. Explanations for differences between estimated and measured levels for 

11 modes of action are discussed. In particular, relationships between the critical 

concentrations in organisms C50 and chemical (Kow) or species (lipid content) 

characteristics are specified and tested. The analysis combines different models 

proposed before and provides a substantial extension of the data set in 

comparison to previous work. Moreover, the concept is applied to species (e.g., 

plants, lean animals) and substances (e.g., specific modes of action) that were 

scarcely studied quantitatively so far. 

Hernandez, F., T. Portoles, et al. (2009). "Searching for anthropogenic contaminants in 

human breast adipose tissues using gas chromatography-time-of-flight mass 

spectrometry." Journal of mass spectrometry : JMS. 44(1): 1-11. 

 The potential of gas chromatography-time-of-flight mass spectrometry (GC-TOF 

MS) for screening anthropogenic organic contaminants in human breast adipose 

tissues has been investigated. Initially a target screening was performed for a list 

of 125 compounds which included persistent halogen pollutants [organochlorine 

(OC) pesticides, polychlorinated biphenylss (PCBs), polybrominated diphenyl 

ethers (PBDEs)], polyaromatic hydrocarbons (PAHs), alkylphenols, and a notable 

number of pesticides from the different fungicide, herbicide and insecticide 

families. Searching for target pollutants was done by evaluating the presence of 

up to five representative ions for every analyte, all measured at accurate mass 

(20-mDa mass window). The experimental ion abundance ratios were then 

compared to those of reference standards for confirmation. Sample treatment 

consisted of an extraction with hexane and subsequent normal-phase (NP) High 

performance liquid chromatography (HPLC) or SPE cleanup. The fat-free LC 

fractions were then investigated by GC-TOF MS.Full-spectral acquisition and 

accurate mass data generated by GC-TOF MS also allowed the investigation of 

nontarget compounds using appropriate processing software to manage MS 

data. Identification was initially based on library fit using commercial nominal 

mass libraries. This was followed by comparing the experimental accurate 

masses of the most relevant ions with the theoretical exact masses with 

calculations made using the elemental composition calculator included in the 
57

software.The application of both target and nontarget approaches to around 40 

real samples allowed the detection and confirmation of several target pollutants 

including p,p'-DDE, hexachlorobenzene (HCB), and some polychlorinated 

biphenyls (PCBs) and polyaromatic hydrocarbons (PAHs). Several nontarget 

compounds that could be considered anthropogenic pollutants were also 

detected. These included 3,5-di-tert-butyl-4-hydroxy-toluene (BHT) and its 

metabolite 3,5-di-tert-butyl-4-hydroxybenzaldehyde (BHT-CHO), dibenzylamine, 

N-butyl benzenesulfonamide (N-BBSA), some naphthalene-related compounds 

and several PCBs isomers not included in the target list. As some of the 

compounds detected are xenoestrogens, the methodology developed in this 

paper could be useful in human breast cancer research. 

Herrick, R. F., J. D. Meeker, et al. (2007). "Serum PCB levels and congener profiles 

among US construction workers." Environ Health 6: 25. 

 BACKGROUND: The presence of PCB in caulking (sealant) material found in 

masonry buildings has been well-documented in several countries. A recent 

investigation of 24 buildings in the greater Boston area found that 8 buildings had 

high PCB levels in caulking materials used around window frames and in joints 

between masonry blocks. Workers removing caulking material have been shown 

to have elevated serum PCB levels. METHODS: This project compared serum 

PCB levels among male workers who installed and/or removed PCB-containing 

caulking material from buildings in the greater Boston area with reference serum 

PCB levels from 358 men from the same area. Serum PCB levels were 

measured in the same laboratory by liquid-liquid extraction, column 

chromatography clean-up and dual capillary column GC/microECD analysis. 

RESULTS: When the congener profiles were compared between the reference 

population and the construction workers, the serum levels of the more volatile, 

lighter PCBs (di-, tri-and tetrachloro, sum of IUPAC# 6-74) were substantially 

higher among the construction workers. One of the youngest workers had the 

lowest total serum PCB levels (sum of 57 congeners) of all 6 workers, but the 

contribution of more volatile (less chlorinated) PCB congeners (#16, 

26,28,33,74,66, and 60) was markedly higher than in other 5 workers and 

reference men. Only this worker was working on a job that involved removing 

PCB caulking at the time of the blood sampling. CONCLUSION: While the results 

of this pilot study are based upon small numbers (6 construction workers who 

handled PCB caulking), the serum PCB levels among the construction workers 

exceed the referents. Comparison of the congener profiles suggests that there 

are substantial differences between the construction workers and the general 

population samples. These differences, and the similarities of profiles among the 

construction workers strongly suggest that occupational contact with caulking 

material can be a major source of PCB exposure for construction workers. 

Hue, O., J. Marcotte, et al. (2007). "Plasma concentration of organochlorine compounds 

is associated with age and not obesity." Chemosphere 67(7): 1463-7. 

 It has been suggested that obese individuals, because of an increased dilution 

space (body fat) for lipophilic organochlorines compounds, may have greater 
58

levels of toxic pollutants than lean sedentary individuals. It is important to further 

examine this possibility because of the potential contribution of organochlorine 

pesticides in the development of Parkinson's disease and other neurological 

diseases. The aim of this study was to further investigate the relationship 

between the magnitude of obesity and the plasma concentration of 

organochlorines for a wide range of BMI (with participants at steady state body 

weight). Fifty-three individuals were selected on the basis of their body mass 

index (BMI): lean controls (n=16; mean BMI 22.8+/-2.2 kg/m(2); mean age 

38.8+/-9.4 years), obese individuals (n=19; mean BMI 33.4+/-3.0 kg/m(2); mean 

age 38.6+/-7.6 years) and morbidly obese individuals (n=18; mean BMI 49.3+/-

6.5 kg/m(2); mean age 44.3+/-9.2 years). Blood samples were analyzed for 

organochlorine compounds. The relationship between the total plasma 

organochlorine concentration and BMI was tested using a multiple regression 

analysis. Age was included in the model. There was no relationship between the 

total plasma organochlorine concentration and BMI. Organochlorine 

concentrations, however, were correlated with age (BMI-adjusted R(2)=0.46; 

p<0.001). At steady state body weight, toxic pollutant concentrations are not 

associated to obesity but strongly correlate with age. 

Jandacek, R. J., N. Anderson, et al. (2005). "Effects of yo-yo diet, caloric restriction, and 

olestra on tissue distribution of hexachlorobenzene." Am J Physiol Gastrointest Liver 

Physiol 288(2): G292-9. 

 Chlorinated hydrocarbons are lipophilic, toxic, and persistent in the environment 

and animal tissues. They enter the body in food and are stored in adipose tissue. 

Loss of body fat through caloric restriction mobilizes stored lipophilic xenobiotics 

and results in distribution to other tissues. We have studied the reversibility of 

this process in mice that followed a regimen of body weight cycling. Weight gain 

was followed by weight loss, a second gain, and a second loss ("yo-yo diet 

regimen"). We measured the distribution of orally gavaged 

[14C]hexachlorobenzene, which is sparingly metabolized. We found that weight 

cycling has different effects in different organs. Continued weight loss resulted in 

a threefold increase of 14C amount and concentration in the brain. After weight 

regain, 14C in the brain decreased but then increased again after a second 

weight loss. Weight loss resulted in an increase in the concentration of 14C in 

adipose tissue without changing the total amount in that tissue. Weight loss and 

regain resulted in an increase of 14C in the liver, which reflected an increase of 

fat in the liver. The regimen of weight gain and loss was repeated in mice 

gavaged with [14C]hexachlorobenzene, with one group receiving the 

nonabsorbable fat olestra in the diet. Combined dietary olestra and caloric 

restriction caused a 30-fold increase in the rate of excretion of 14C relative to an 

ad libitum diet or a reduced caloric diet alone. Distribution of 14C into the brain 

resulting from the restricted diet was reduced by 50% by dietary olestra. 

Jandacek, R. J., T. Rider, et al. (2009). "Lymphatic and portal vein absorption of 

organochlorine compounds in rats." Am J Physiol Gastrointest Liver Physiol 296(2): 

G226-34. 
59

 The route of absorption of ingested compounds is a determinant of their 

distribution and metabolism. Portal vein absorption results in direct transport to 

the liver, where metabolism may take place before extrahepatic delivery. 

Lymphatic absorption can result in delivery of parent compound to nonhepatic 

tissues. Understanding the fate of an ingested compound requires determination 

of the importance of each of these routes. Portal vein absorption can be 

estimated from the difference in concentrations of an ingested compound 

between the portal vein and peripheral vessel blood. To make these estimations, 

one must make assumptions on the basis of estimates of flow rate and dilution. 

We report here methodology that allows a direct measurement of portal vein 

absorption that is independent of these assumptions. Mesenteric lymph was 

diverted from rats by cannulation. Portal blood was sampled after duodenal 

infusion of a bolus of compound of interest along with a portal absorption marker, 

3-O-methylglucose. Since lymph was diverted, the appearance in portal blood 

was solely the result of portal absorption. Absorption was quantified by the areas 

under the curve for the compound and marker. Portal absorption was a function 

of the octanol/water partition coefficients for four organochlorine compounds: 

hexachlorobenzene, pentachlorophenol, DDT, and its metabolite 1,1,1-trichloro2,2-bischlorophenylethylene. 

Jandacek, R. J. and P. Tso (2007). "Enterohepatic circulation of organochlorine 

compounds: a site for nutritional intervention." J Nutr Biochem 18(3): 163-7. 

 Organochlorine compounds enter the body primarily as components of the diet. 

Their removal from the body is via excretion into the feces. There is evidence 

that many people are in a positive balance, with the rate of intake of 

organochlorines exceeding that of their excretion. A desirable nutritional 

approach to this problem would both reduce dietary intake and increase fecal 

excretion. Nonabsorbable dietary lipids reduce the absorption of dietary 

organochlorines and also increase the rate of their fecal excretion. 

Organochlorine compounds that are stored in the body enter the intestine both in 

bile and through a poorly understood nonbiliary mechanism. Part of the amount 

that enters the intestine is excreted, and part is reabsorbed in an enterohepatic 

circulation. There is evidence that an increase in excretion can be achieved by 

interference with the enterohepatic circulation of organochlorine compounds and 

their metabolites. Data from animals and humans show that the presence of 

nonabsorbed lipid in the intestine can increase the rate of excretion in a clinically 

significant manner. 

Jandacek, R. J., S. Zheng, et al. (2004). "Rapid clearance of hexachlorobenzene from 

chylomicrons." Lipids 39(10): 993-5. 

 Toxic organochlorines that are present in food are lipophilic and carried by 

chylomicrons. We have studied the clearance of an organochlorine, 

hexachlorobenzene, from chylomicrons. Chylomicrons were obtained from 

mesenteric lymph of rats that were intraduodenally given 14Chexachlorobenzene and 3H-triolein. The labeled chylomicrons were injected 

intravenously into recipient rats, and the clearance of isotopes was followed. 
60

Surprisingly, the hexachlorobenzene disappeared from the plasma more rapidly 

than the triolein. This unexpected result raises questions about the manner in 

which hexachlorobenzene is delivered to tissues. The tissue distribution of the 

hexachlorobenzene is consistent with its rapid uptake. 

Jaraczewska, K., J. Lulek, et al. (2006). "Distribution of polychlorinated biphenyls, 

organochlorine pesticides and polybrominated diphenyl ethers in human umbilical cord 

serum, maternal serum and milk from Wielkopolska region, Poland." Science of the 

Total Environment 372(1): 20-31. 

 The levels of organochlorinated pesticides (OCPs): p,p'-DDT and its metabolites, 

hexachlorobenzene (HCB), hexachlorocyclohexane isomers (HCHs), chlordanes 

and their metabolites, and 18 polychlorinated biphenyl (PCB) congeners were 

measured in maternal serum, umbilical cord serum and human milk collected 

from 22 mothers living in the Wielkopolska region, Poland. Additionally, 11 

polybrominated diphenyl ether (PBDE) congeners were measured in the human 

milk samples. p,p'-DDT and its major metabolite, p,p'-DDE, together with HCB, 

were found in all milk and serum samples. Median concentrations of p,p'-DDE in 

maternal serum, umbilical cord serum and milk were 343, 329 and 634ng/g lipid 

weight (lw). PCB congeners 138, 153 and 180 were the major congeners 

measured in all serum samples, while CB 170 was detected in 74% and 100% of 

umbilical cord and maternal serum, respectively. Except for CBs 74, 101 and 

105, which had a detection frequency of 77%, 23% and 82%, respectively, all 

investigated PCB congeners were measured in all human milk samples. The 

median concentrations of sum PCBs in maternal serum, umbilical cord serum 

and milk were 79, 60 and 133 ng/g lw, respectively. A good correlation 

(Spearman R(S)>0.75, p<0.001) was found for major PCBs, p,p'-DDT and p,p'-

DDE, between maternal and umbilical cord serum, while the correlation was 

weaker between milk and serum. The median of sum PBDEs in human milk was 

2.0 ng/g lw (range 0.8 to 8.4), with BDE 47 being always the most abundant 

PBDE congener and, together with BDE 153, being present in all samples. In 

general, results found in the investigated group are at the low end of the 

concentration range measured in Europe. 

Kang, J. H., H. Park, et al. (2008). "Distribution of organochlorine pesticides (OCPs) and 

polychlorinated biphenyls (PCBs) in human serum from urban areas in Korea." 

Chemosphere 73(10): 1625-31. 

 Concentrations of organochlorine pesticides (OCPs) and polychlorinated 

biphenyls (PCBs) were determined in serum samples from residents of a Korean 

urban area (Seoul). This study was performed on 40 Koreans in the general 

population, aged 27-58, who had resided in urban areas for more than 10 years 

without occupational exposure to organochlorine pollutants. To our knowledge, 

this study was the first report on serum concentrations of OCPs in Korean 

residents. p,p'-DDE, beta-HCH, p,p'-DDT, HCB, and trans-nonachlor were the 

dominant OCPs in most samples. In addition, concentrations of 22 OCPs were 

measured by the isotope dilution method with GC-HRMS, which gave accurate 

and precise data for investigations of trend and international comparisons. The 
61

dominant PCBs were PCB153, 138, 180, 187, and PCB118, which contributed 

60% to total PCBs. The median concentrations of total OCPs and total PCBs 

were 315 ng g(-1) lipid and 104 ng g(-1) lipid, respectively. In females, the serum 

concentrations of all determined organochlorine compounds except beta-HCH 

were positively correlated with age, and higher concentrations of organochlorine 

pollutants were found in males than in females. Compared to our previous 

studies, PCB concentrations in serum from urban areas have substantially 

decreased during the last decade leading to the observation that the strict 

regulation of PCBs was helpful in controlling the concentration of PCBs in the 

environment. Extensive monitoring programs are required for evaluating the 

concentrations of OCPs and PCBs in serum samples of the general population 

as an indicator of possible adverse health effects. 

Koppen, G., A. Covaci, et al. (2002). "Persistent organochlorine pollutants in human 

serum of 50-65 years old women in the Flanders Environmental and Health Study 

(FLEHS). Part 1: Concentrations and regional differences." Chemosphere 48(8): 811-

25. 

 In 1999, a campaign of the Flemish Ministry of Health, Belgium was set up to 

assess pollutant concentrations and related health effect biomarkers in humans 

living in two regions of Flanders. The study was called the 'Flemish Environment 

and Health Study' (FLEHS). One of the goals was to measure present 

concentrations of persistent organochlorine pollutants in a Flemish population 

and to compare values obtained from pooled and individual serum samples. 

Concentrations of selected organochlorine pesticides, polychlorinated biphenyls 

(PCB) and polychlorinated dibenzo-p-dioxins (PCDD) and furans (PCDF) were 

measured by gas chromatography-mass spectrometry. TEQ values were also 

assessed by Chemical-Activated LUciferase gene eXpression (CALUX) 

bioassay. The study population consisted of 200 women between 50 and 65 

years living in two areas of Flanders, Belgium. Because of the large volumes 

serum needed for all measurements, the concentrations of organochlorines were 

measured in 47 pooled serum samples originating from these women. The 

concentrations of the indicator PCBs (359.8 ng/g fat) and organochlorine 

pesticides (hexachlorobenzene, p,p'-dichlorodiphenyldichloroethylene, p,p'-

dichlorodiphenyl-trichloroethane, lindane and pentachlorophenol), were 

comparable to those found in other European countries. The concentrations of 

PCDD/PCDFs showed another picture. With a median value of 48 pg WHOTEQ/g fat, the women had 2-fold higher levels than a comparable age group from 

Germany examined in 1996. The mean total WHO-TEQ including PCDD/F, nonortho and mono-ortho PCBs was 72.7 pg WHO-TEQ/g fat, whereas the CALUXTEQ mean value was only 35.0 pg TEQ/g fat. In order to assess the pooling 

procedure, indicator PCBs and CALUX-TEQs were measured in all 200 

individuals that were integrated in the pools. The measured values were 

comparable to the pool results: 390.0 ng/g fat and 41.6 pg TEQ/g fat 

respectively. It was concluded that pooling of serum samples offers the possibility 

to measure exposure in the whole study population on a more cost-effective way. 
62

However, because of statistical power loss and no possibility of confounder 

adjustment, pooling is not the most effective way to study regional differences. 

Korrick, S. A., L. M. Altshul, et al. (2000). "Measurement of PCBs, DDE, and 

hexachlorobenzene in cord blood from infants born in towns adjacent to a PCBcontaminated waste site." J Expo Anal Environ Epidemiol 10(6 Pt 2): 743-54. 

 There are limited data on the concentrations of common contaminants-- 

polychlorinated biphenyls (PCBs), dichlorodiphenyl dichloroethene (pp'- DDE) 

and hexachlorobenzene (HCB)--in umbilical cord blood. Cord blood provides the 

primary direct measure of prenatal exposure to these contaminants, the key 

determinant of PCBs' neurodevelopmental toxicities. The objective of this study 

was to characterize cord blood levels of PCBs, pp'-DDE, and HCB among 751 

infants who were born between 1993 and 1998 to mothers residing adjacent to a 

PCB- contaminated harbor in New Bedford, Massachusetts, and for whom the 

neurodevelopmental toxicities of these compounds are being studied. We refined 

standard analytic methods to optimize the sensitivity and precision of trace-level 

PCB, p,p'-DDE, and HCB measurements in blood. Using these methods, we 

measured the concentrations of 51 individual PCBs, their sum (sum(PCB)), p,p'-

DDE, and HCB in cord serum. With correction for background contamination, the 

respective mean+/-SD cord serum concentrations of sum(PCB), p,p'-DDE, and 

HCB were 0.54+/-0.83, 0.48+/-0.94, and 0.03+/-0.04 ng/g serum. These 

concentrations were generally lower than those in most of the few published 

studies with congener-specific measures of PCBs in cord blood. However, for 

less- chlorinated PCB congeners (e.g., congeners 99 and 118), study samples 

had concentrations comparable to those in other populations, including groups at 

risk for high dietary PCB exposure. Of note, the contaminated harbor sediment 

has a relatively high proportion of less-chlorinated PCB congeners. Thus, 

although the sum(PCB) in study infants was not higher than concentrations in 

infants studied elsewhere, the relative predominance of less-chlorinated 

congeners was generally consistent with the characteristics of the contaminated 

site. 

Kunisue, T., M. Muraoka, et al. (2006). "Contamination status of persistent 

organochlorines in human breast milk from Japan: recent levels and temporal trend." 

Chemosphere 64(9): 1601-8. 

 Contamination levels of persistent organochlorines (OCs) such as 

polychlorinated dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs), biphenyls 

(PCBs), dichlorodiphenyltrichloroethane and its metabolites (DDTs), 

hexachlorocyclohexane isomers (HCHs), hexachlorobenzene (HCB), and 

chlordane compounds (CHLs) was examined in human breast milk collected 

during 2001-2004 from Fukuoka prefecture in Japan. The concentrations of OCs 

such as dioxins and related compounds, DDTs, CHLs and HCB in human breast 

milk from primiparae were comparable to or slightly higher than the data obtained 

during 1998, indicating that the levels of these contaminants in Japanese human 

breast milk have not decreased since 1998 and Japanese are continuously 

exposed to these chemicals, presumably via fish intake. In addition, OC levels in 
63

human breast milk from primiparae were significantly higher than those from 

multiparae, implying elimination of OCs via lactation. Furthermore, significant 

positive correlations were observed between levels of OCs in human breast milk 

and the age of primiparae. These results indicate that the mothers with higher 

age may transfer higher amounts of OCs to the first infant than to the infants born 

afterwards through breast-feeding, and hence the first born children might be at 

higher risk by OCs. 

Kunisue, T., M. Watanabe, et al. (2002). "PCDDS, PCDFs, PCBS and organochlorine 

insecticides in human breast milk collected from Asian developing countries: Risk 

assessment for infants." Organohalogen Compounds 58(Dioxin 2002): 285-288. 

 The contamination level of polychlorinated dibenzo-p-dioxin/dibenzofuran 

(PCDD/F), polychlorinated biphenyl, and organochlorine insecticides in human 

breast milk from dumping sites of municipal wastes and ref. sites in Asian 

developing countries was evaluated. PCDD/Fs, PCBs, and organochlorine 

insecticides were detected in all the samples of human breast milk, indicating 

that the residents around dumping sites of municipal wastes and ref. sites have 

been exposed to these contaminants. The dominant organochlorine insecticides 

in human breast milk were HCHs and DDTs. The relationship between concns. of 

toxic equivalence and organochlorines in human breast milk and the no. of 

delivery times, levels of these contaminants tended to decrease with increase in 

the no. of delivery times. 

Lackmann, G. M. (2002). "Polychlorinated biphenyls and hexachlorobenzene in full-term 

neonates. Reference values updated." Biol Neonate 81(2): 82-5. 

 OBJECTIVE: To determine actual reference values of polychlorinated biphenyls 

(PCBs) and hexachlorobenzene (HCB) in full-term neonates. PATIENTS AND 

METHODS: Cord blood samples were taken from 200 healthy, full-term neonates 

in 1998. Blood specimens were immediately centrifuged, and serum was stored 

in glass tubes at -20 degrees C up to analysis. Six PCB congeners (IUPAC No. 

28, 52, 101, 138, 153, and 180) and HCB were determined with capillary gas 

chromatography with electron capture detection. Study groups were tested on 

mean differences with Wilcoxon's test of independent samples. The 95th 

percentiles by rank were calculated as reference values. RESULTS: One sample 

was excluded from further evaluation because of unusually high PCB 

concentrations. Personal data of the remaining 199 newborns showed 106 male 

and 93 female neonates. Mean gestational age was 40 weeks (range 38-43 

weeks), mean birth weight was 3,450 g (2,300-5,060 g). The concentrations of 

the lower-chlorinated PCB congeners 28, 52, and 101 were below the detection 

limit with exception of two probes. Reference values (95th percentile by rank) of 

the higher-chlorinated PCB congeners and HCB were as follows: PCB 138, 0.5 

microg/l; PCB 153, 0.5 microg/l; PCB 180, 0.4 microg/l; and HCB, 0.5 microg/l. 

CONCLUSIONS: The results of the present study clearly demonstrate a further 

decline in the prenatal uptake of PCBs and HCB since 1994-1995. During the 

past 15 years, a 75% decline in the prenatal burden with PCBs and a 90% 

reduction in the burden with HCB could be demonstrated. 
64

Lackmann, G. M., J. Angerer, et al. (1999). "Influence of maternal age and duration of 

pregnancy on serum concentrations of polychlorinated biphenyls and 

hexachlorobenzene in full-term neonates." Biology of the Neonate 76(4): 214-219. 

 BIOSIS COPYRIGHT: BIOL ABS. Polychlorinated biphenyls (PCBs) and 

hexachlorobenzene (HCB) are ubiquitous carcinogenic and teratogenic 

compounds that are transplacentally transferred from mother to fetus during 

pregnancy. It was the aim of the present study to evaluate the possible influence 

of maternal age and duration of pregnancy on the neonatal burden with these 

substances. Blood samples were taken from 80 full-term German neonates 

within the first 12 h of life, before the first oral feeding. The serum concentrations 

of s 0.96 mug/l, HCB concentration 0.61 mug/l. All detectable PCB congeners 

and the total PCB concentration correlated significantly with the gestational age 

of the newborns (r = 0.2639; p < 0.01), with 50-140% higher serum levels in 

children born at 42 weeks of gestation as compared with neonates born in the 

38th week. HCB concentration correlated with maternal age (r = 0.249; p < 0.01), 

with 2.7-fold higher serum levels in offspring of 40-year-old as compared with 20-

year-old women. It is conclud 

Lackmann, G. M., J. Angerer, et al. (1999). "Influence of maternal age and duration of 

pregnancy on serum concentrations of polychlorinated biphenyls and 

hexachlorobenzene in full-term neonates." Biol Neonate 76(4): 214-9. 

 Polychlorinated biphenyls (PCBs) and hexachlorobenzene (HCB) are ubiquitous 

carcinogenic and teratogenic compounds that are transplacentally transferred 

from mother to fetus during pregnancy. It was the aim of the present study to 

evaluate the possible influence of maternal age and duration of pregnancy on the 

neonatal burden with these substances. Blood samples were taken from 80 fullterm German neonates within the first 12 h of life, before the first oral feeding. 

The serum concentrations of six PCB congeners (28, 52, 101, 138, 153, and 

180) and HCB were determined with capillary gas chromatography with electron 

capture detection. The concentrations of the lower chlorinated PCB congeners 

(28, 52, and 101) were below the detection limit. PCB 153 showed the highest 

serum concentration (median 0.42 microg/l), followed by PCB 138 (0. 34 

microg/l) and PCB 180 (0.17 microg/l). Total PCB concentration was 0.96 

microg/l, HCB concentration 0.61 microg/l. All detectable PCB congeners and the 

total PCB concentration correlated significantly with the gestational age of the 

newborns (r = 0.2639; p < 0.01), with 50-140% higher serum levels in children 

born at 42 weeks of gestation as compared with neonates born in the 38th week. 

HCB concentration correlated with maternal age (r = 0.249; p < 0.01), with 2.7-

fold higher serum levels in offspring of 40-year-old as compared with 20-year-old 

women. It is concluded that the neonatal burden with organochlorine compounds 

depends on maternal age and duration of pregnancy, thereby reflecting the 

increase in body pollution with these substances during human life as well as a 

continuous transplacental transfer from mother to fetus during pregnancy. 
65

Lackmann, G. M., K. H. Schaller, et al. (2004). "Organochlorine compounds in breastfed vs. bottle-fed infants: preliminary results at six weeks of age." Sci Total Environ

329(1-3): 289-93. 

 BACKGROUND: Polychlorinated biphenyls (PCBs), hexachlorobenzene (HCB), 

and 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (DDT) are ubiquitous 

compounds with carcinogenic and teratogenic properties. They are chemically 

very stable and lipophilic and, therefore, accumulate in our food-chain. They are 

prenatally transmitted from mother to foetus, and mother's milk due to its high 

lipid content is an elimination pathway of special importance. Therefore, breastfeeding has been held responsible for elevated concentrations of these 

organochlorine compounds as well as for harmful effects in children later in life. 

METHODS: Blood samples (2.5 ml) were taken from each 10 breast-fed and 

bottle-fed infants at 6 weeks of age. Blood specimens were immediately 

centrifuged, and serum was stored in glass tubes at -20 degrees C until analysis. 

Three higher chlorinated PCB congeners (IUPAC nos. 138, 153 and 180), HCB, 

and the organic metabolite of DDT, p,p << -DDE, were analysed with capillary 

gas chromatography with electron capture detection. Reliability was tested with 

gas chromatography-mass spectrometry. RESULTS: There were no differences 

between the study groups of breast-fed and bottle-fed infants with regard to sex 

distribution, gestational age, birth-weight, age of the mothers, and smoking 

behaviour of the parents. In contrast, serum concentrations of all organochlorine 

compounds were significantly higher (P < 0.0001) in breast-fed than in bottle-fed 

infants (mean): PCB 138, 0.38 vs. 0.10 microg/l; PCB 153, 0.49 vs. 0.1 microg/l; 

PCB 180, 0.31 vs. 0.04 microg/l; SigmaPCB, 1.19 vs. 0.29 microg/l; HCB, 0.13 

vs. 0.04 microg/l; p,p << -DDE, 1.05 vs. 0.18 microg/l. CONCLUSIONS: Breastfeeding significantly increases the pollution of our infants with different 

organochlorine compounds as early as at 6 weeks of age. The progress of the 

present study will show whether this pollution will further increase with longer 

duration of breast-feeding, and whether breast-feeding bears any health risks for 

our offspring. 

Link, B., T. Gabrio, et al. (2005). "Biomonitoring of persistent organochlorine pesticides, 

PCDD/PCDFs and dioxin-like PCBs in blood of children from South West Germany 

(Baden-Wuerttemberg) from 1993 to 2003." Chemosphere 58(9): 1185-201. 

 In the context of a monitoring program, persistent organic pollutants (POPs) were 

quantified in the blood of 10 year old children at four different demographic 

regions in Baden-Wuerttemberg, a highly industrialised federal state in South 

West Germany. DDE, HCB, PCB 138, PCB 153 and PCB 180 were measured in 

1996/1997, 1998/1999, 2000/2001 and 2002/2003 in individual samples of about 

400 children per year. PCDD/PCDFs and some relevant coplanar PCBs were 

determined in pooled samples from children in seven cycles from 1993 to 2003. 

Blood concentrations of the investigated compounds decreased in that time 

period by a factor of 2-4 with the exception of most PCDFs. The concentrations 

of POPs in the blood of the children were distinctly lower than the concentrations 

reported for adults. Breast feeding was associated with about 30% higher median 

concentrations of DDE, HCB, PCBs and a 30% increase for mean PCDD/PCDF 
66

concentrations. Concerning demographic differences, significant lower 

concentrations of HCB, PCBs and PCDD/PCDFs could be seen in children from 

Mannheim compared to the region of Aulendorf. About 10-20% higher 

concentrations were found in boys compared to girls for HCB, indicator PCBs 

and PCDD/PCDFs. The pattern of non-ortho and mono-ortho PCBs in the blood 

of children was similar to the pattern reported for mother's milk, and PCB 126 

and PCB 156 contributed about 70% to the toxicity of dioxin-like PCBs and about 

one-third to total TEQ including PCDD/PCDFs. 

Lu, Y., M. Lohitnavy, et al. (2005). "Alteration Of Hexachlorobenzene Disposition By 

PCB126 Coexposure And Application Of PBPK Modeling In A Mediumterm Liver Foci 

Bioassay." Toxicol Sci 84(1-S): 173. 

 Hexachlorobenzene (HCB) is a probable human carcinogen which still exists in 

the environment despite the curtailment of its production and use. Human 

exposure to HCB is often accompanied by PCB126, a dioxin-like compound and 

the most potent congener of polychlorinated biphenyls. Earlier, we observed that 

PCB126 altered the kinetics of coexposed lipophilic chemicals. Here, we report 

our studies on HCB pharmacokinetics, with or without coexposure to PCB126. 

Our experiments included two separate kinetic studies (HCB alone and 

HCB+PCB126) integrated into a time-course medium-term liver foci bioassay. In 

both studies, fat had the highest concentrations of HCB, followed by the other 

tissues. The kinetics of tissue distribution of HCB are dramatically different 

between HCB alone group and the HCB+PCB126 combination group, suggesting 

complex interaction mechanisms. Using PBPK modeling as a hypothesis-testing 

tool, we carried out computer simulations based on the assumptions that 

PCB126 induced disruption at the levels of absorption, exsorption (i.e., the 

diffusion from blood to the lumen of GI tract), and fat metabolism. We utilized a 

previously constructed PBPK model for HCB to describe these altered disposition 

patterns. The model was composed of fat, liver, erythrocytes, blood plasma, GI 

lumen, and rapidly and slowly perfused tissues and incorporated the 

physiological changes related to partial hepatectomy in the time-course medium 

term liver foci bioassay protocol. The model adequately described the 

pharmacokinetics of HCB singly and in combination with PCB126. From our 

modeling exercises, we propose that the kinetic alterations were the results of a 

combination of the modification of HCB absorption and exsorption and the 

disruption of fat metabolism by PCB126. 

Lu, Y., M. Lohitnavy, et al. (2006). "An updated physiologically based pharmacokinetic 

model for hexachlorobenzene: incorporation of pathophysiological states following 

partial hepatectomy and hexachlorobenzene treatment." Toxicol Sci 91(1): 29-41. 

 Physiologically based pharmacokinetic (PBPK) modeling is generally used for 

describing xenobiotic disposition in animals and humans with normal 

physiological conditions. We describe here an updated PBPK model for 

hexachlorobenzene (HCB) in male F344 rats with the incorporation of 

pathophysiological conditions. Two more features contribute to the distinctness of 

this model from the earlier published versions. This model took erythrocyte 
67

binding into account, and a particular elimination process of HCB, the plasma-togastrointestinal (GI) lumen passive diffusion (i.e., exsorption), was incorporated. 

Our PBPK model was developed using data mined from multiple 

pharmacokinetic studies in the literature, and then modified to simulate HCB 

disposition under the conditions of our integrated pharmacokinetics/liver foci 

bioassay. This model included plasma, erythrocytes, liver, fat, rapidly and slowly 

perfused compartments, and GI lumen. To account for the distinct characteristics 

of HCB absorption, the GI lumen was split into an upper and a lower part. HCB 

was eliminated through liver metabolism and the exsorption process. The 

pathophysiological changes after partial hepatectomy, such as alterations in the 

liver and body weights and fat volume, were incorporated in our model. With 

adjustment of the transluminal diffusion-related parameters, the model 

adequately described the data from the literature and our bioassay. Our PBPK 

model simulation suggests that HCB absorption and exsorption processes 

depend on exposure conditions; different exposure conditions dictate different 

absorption and exsorption rates. This model forms a foundation for our further 

exploration of the quantitative relationship between HCB exposure and 

development of preneoplastic liver foci. 

Lu, Y., M. Reddy, et al. (2004). "Development Of A PBPK Model For 

Hexachlorobenzene In The Context Of Ito's Medium-Term Liver Foci Bioassay." 

Toxicologist 78(1-S): 244-5. 

 Hexachlorobenzene (HCB) is an important environmental contaminant. Due to its 

high lipophilicity and persistence in the environment, human exposure to HCB 

has continued despite the curtailment of its usage. HCB is carcinogenic to 

laboratory animals with the liver as one of the primary target organs. We have 

incorporated the study of the relationship between pharmacokinetics and 

pharmacodynamics into the Ito’s medium-term liver foci bioassay. Thus, we 

describe here the development of a PBPK model for HCB in the context of Ito’s 

bioassay protocol. The model was built based on two data sets: one from a 

single intravenous dosing study (Scheufler et al. 1984) and the other from a 

single oral gavage study (Yamaguchi et al. 1986). It was then modified to 

simulate the exposure conditions in the Ito’s bioassay and verified with data from 

our laborotary. The PBPK model includes five compartments: blood, liver, fat and 

rapidly and slowly perfused tissues. As HCB can bind to red blood cells, the 

blood compartment was divided into red blood cells and plasma. The fat 

compartment was divided into two subcompartments, one with a higher perfusion 

rate and lower partitioning and the other with a lower perfusion rate and higher 

partitioning. Uptake of HCB was diffusion-limited in the fat compartments and 

flow-limited in the others. HCB was eliminated by metabolism in the liver and by 

passive transfer from plasma to the intestinal lumen. Reabsorption of HCB from 

the intestine was incorporated in the model. The resultant model adequately 

described the available data sets. This model may be linked with a clonal growth 

model to quantitatively describe the relationship between an external exposure to 

HCB and the consequent preneoplastic liver foci development. 
68

Mari, M., M. A. Borrajo, et al. (2007). "Monitoring PCDD/Fs and other organic 

substances in workers of a hazardous waste incinerator: a case study." Chemosphere

67(3): 574-81. 

 The aim of this study was to measure, 6 years after regular operations, the 

concentrations of a number of organic substances in blood and urine of 19 

workers employed at a hazardous waste incinerator (HWI) in Spain, and to 

establish the temporal variation with respect to baseline data and previously 

performed surveys. This facility was the first, and so far the only HWI in that 

country. The levels of hexachlorobenzene (HCB), polychlorinated biphenyls 

(PCB 28, 52, 101, 138, 153 and 180) and polychlorinated dibenzo-p-dioxins and 

dibenzofurans (PCDD/Fs) were analyzed in six composite plasma samples, while 

concentrations of di-, tri, and pentachlorophenols, as well those of 1-

hydroxypyrene were measured in the urine of these workers. The current mean 

PCDD/F concentration, 10.4 ng I-TEQ/kg lipid, was significantly lower than that 

found in the baseline survey, 26.7 ng I-TEQ/kg lipid and similar to that found in 

the previous (2004) study (7.7 ng I-TEQ/kg lipid). PCDD/F levels in plasma were 

similar or even lower than those recently reported for various non-exposed 

populations. For the remaining analyzed substances in plasma and urine, there 

was not any significant increase in comparison with the levels found in the 

baseline survey. On the other hand, no marked differences between the 

concentrations of organic substances in plasma or urine were found according to 

the respective workplace (plant, laboratory and administration). The results of the 

present survey indicate that after 6 years of regular operation, the workers at the 

HWI are not occupationally exposed to PCDD/Fs and other organic substances 

in their workplaces. 

Mari, M., M. Schuhmacher, et al. (2009). "Levels of metals and organic substances in 

workers at a hazardous waste incinerator: a follow-up study." Int Arch Occup Environ 

Health 82(4): 519-28. 

 PURPOSE: To determine the blood and urine concentrations of a number of 

metals and organic substances in workers at a hazardous waste incinerator 

(HWI) in Catalonia, Spain, 8 years after regular operations in the facility. To 

compare these concentrations with the baseline (1999) levels and with those 

obtained in previous (2000 and 2005) surveys. METHODS: The employees were 

divided into three groups according to their specific workplaces. Plasma analyses 

of hexachlorobenzene (HCB), polychlorinated biphenyls (PCBs 28, 52, 101, 138, 

153 and 180) and polychlorinated dibenzo-p-dioxins and dibenzofurans 

(PCDD/Fs), as well as urinary analyses of 2,4- and 2,5-dichlorophenol (DCP), 

2,4,5- and 2,4,6-trichlorophenol (TCP), pentachlorophenol (PCP) and 1-

hydroxypyrene (1-HP) were carried out. Blood concentrations of manganese and 

mercury, and urinary levels of nickel were also determined. RESULTS: For 

organic compounds in plasma, the comparison of the current levels with those of 

previous surveys did not show any significant increase for any of the compounds 

analyzed. In contrast, plasma levels of PCBs 28, 52 and 101 were significantly 

lower than the respective baseline concentrations, while especially notable was 

the significant reduction in the levels of PCDD/Fs in plasma of plant workers, 
69

which decreased from 26.7 pg I-TEQ/g lipid in the baseline survey to the current 

2.5 pg I-TEQ/g lipid. CONCLUSION: According to the results of the present 

study, there are no evident signs of occupational exposure to a number of metals 

and organic substances in the workers of the HWI. 

Marti-Cid, R., J. M. Llobet, et al. (2008). "Human dietary exposure to 

hexachlorobenzene in Catalonia, Spain." J Food Prot 71(10): 2148-52. 

 The concentrations of hexachlorobenzene (HCB) were measured in samples of 

foodstuffs widely consumed by the population of Catalonia, Spain. Food samples 

were randomly acquired in 12 cities of Catalonia between March and June of 

2006. HCB levels were determined by high-resolution gas chromatography-highresolution mass spectrometry. The dietary intake of HCB was subsequently 

estimated for the population of Catalonia, and the results were compared with 

those of a survey performed in 2000. The highest HCB concentrations were 

found in oils and fats, fish and seafood, and dairy products, with mean levels of 

0.481, 0.330, and 0.284 ng/g of fresh weight, respectively. HCB intake was 

estimated for four population groups: children, adolescents, adults, and seniors 

(aged >65 years). The highest and lowest HCB intake corresponded to children 

and seniors, respectively. Similar results were found in our 2000 survey. For a 

standard male adult of 70-kg body weight, in the 2000 study, total dietary intake 

of HCB was 166.2 ng/day (2.4 ng/kg of body weight per day), whereas in the 

current survey the intake was 71.6 ng/day (1.0 ng/kg of body weight per day). On 

a body-weight basis, it means a decrease of 57%, which was mainly due to the 

important reductions in the contribution of dairy products (mainly cheese), as well 

as those of meat and meat products and fish and seafood. All the intakes are 

considerably lower than the World Health Organization tolerable daily intake, 

which is 0.17 microg/kg/day for noncancer effects and 0.16 microg/kg/day for 

neoplastic effects in humans. 

Moser, G. A. and M. S. McLachlan (2002). "Modeling digestive tract absorption and 

desorption of lipophilic organic contaminants in humans." Environmental Science and 

Technology 36(15): 3318-25. 

 A model of the absorption and desorption of persistent lipophilic organic 

pollutants in the human gastrointestinal tract was formulated. The influence of the 

dietary intake of chemical, the chemical concentration in human tissue, the 

physical-chemical properties of the chemical, and the sorption properties of the 

feces on the predicted net mass transfer of chemical was explored and shown to 

be consistent with experimental observations. The model was parametrized and 

tested using a data set of approximately 800 measurements of net 

absorption/excretion of polychlorinated biphenyls, dibenzo-p-dioxins, and 

dibenzofurans that were obtained in experiments with 14 human volunteers. 

Overall good agreement was obtained between the predicted and measured 

values. The largest discrepancies were observed in cases of net excretion 

because the model was not able to account for the considerable individual and 

temporal variability in the sorption properties of the feces. In a sample model 

application, good agreement was found between concentrations of 
70

octachlorodibenzo-p-dioxin in blood measured in different age groups of the 

background population and values predicted by the model. 

Moser, G. A. and M. S. McLachlan (2002). "Partitioning of polychlorinated biphenyls and 

hexachlorobenzene into human faeces." Chemosphere 46(3): 449-57. 

 The dietary absorption of persistent lipophilic organic pollutants (PLOPs) in 

humans is believed to occur via partitioning of the chemical between the lumen 

and the wall of the digestive tract. As such, the partitioning properties of the 

lumen contents are a key factor governing absorption. In this study, the 

partitioning properties of faeces were measured for 11 polychlorinated biphenyls 

and hexachlorobenzene (HCB). Four volunteers participated in the study, each of 

them providing faeces from a normal diet and a vegetarian diet. The faeces/gas 

equilibrium partition coefficient K(FG) varied by over three orders of magnitude 

between the different compounds. A linear relationship between log K(FG) and 

log KOA, the octanol/air partition coefficient, was observed. The slope of the 

relationship was > 1, indicating that the solvent properties of faeces were less 

polar than those of octanol. For a given compound, KFG varied up to a factor of 

2.8 between the individuals on a normal diet. The influence of the vegetarian diet 

on K(FG) was negligible for the two volunteers who simply deleted fish and 

animal products from their normal diet, but K(FG) increased on average by a 

factor of 2 in the two individuals who increased their consumption of less readily 

digestible whole grains and vegetables in their vegetarian diet. On the basis of 

K(FG), the fugacities in the faeces were calculated. They were found to be much 

lower than the fugacities in blood. It is hypothesised that this is due to a 

temporary decrease in the fugacity in the wall of the jejunum caused by 

absorption of dietary lipids that results in equilibration between the lumen 

contents and the wall of the digestive tract at a fugacity below that present in the 

blood and the rest of the body. 

Moysich, K. B., C. B. Ambrosone, et al. (2002). "Exposures associated with serum 

organochlorine levels among postmenopausal women from western New York State." 

Am J Ind Med 41(2): 102-10. 

 BACKGROUND: Organochlorines, such as 2,2-bis (4-chlorophenyl)-1,1- 

dichloroethylene (DDE), polychlorinated biphenyls (PCBs), and 

hexachlorobenzene (HCB) are lipophilic compounds that are ubiquitous in the 

environment and may cause adverse health effects in humans. METHODS: We 

examined the correlation between epidemiological exposure variables and serum 

DDE, PCB, and HCB levels in a sample of 192 healthy, female postmenopausal 

western New York residents; a subset of the control group from a case-control 

study on breast cancer risk. Usual diet, reproductive and medical histories, and 

other lifestyle information were obtained by an extensive in person interview. 

Serum levels (ng/g) of DDE, HCB, and 69 PCB congeners were determined by 

gas chromatography with electron capture detection. Statistical analyses 

included computations of crude and age and lipid adjusted correlation 

coefficients, as well as multiple linear regression analysis. RESULTS: Results 

indicated that the strongest predictors for serum DDE levels were age, serum 
71

lipids, parity, and fruit and dairy consumption. Statistically significant predictors of 

PCB levels included age, serum lipids, parity, and fish consumption. Serum HCB 

levels were related to age, serum lipids, and fruit and red meat consumption. 

CONCLUSIONS: Our findings are consistent with previous investigations that 

reported strong associations between organochlorine levels and age and serum 

lipids. The absence of other data showing an association between fruit intake 

and organochlorine levels make the importance of this finding unclear. 

Nakai, K., T. Nakamura, et al. (2004). "Organochlorine pesticide residues in human 

breast milk and placenta in Tohoku, Japan." Organohalogen Compounds 66(Dioxin 

2004): 2537-2542. 

 Several organochlorine pesticides were analyzed in human breast milk and 

placenta from 20 mothers to identify the major pesticide compds. found in the 

cohort subjects. The concn. of organochlorine pesticides in breast milk mainly 

depends on their accumulation in the maternal fatty tissue and their subsequent 

mobilization. Since there were excellent correlations of all major pesticides 

between breast milk samples and placenta samples, placenta is also suggested 

to be the useful material to est. the maternal body burden. In addn., the concns. 

of some organochlorine pesticides such as hexachlorobenzene, oxy-chlordane, 

and trans-nonarchlor, in the placenta samples had significant neg. correlations 

with parity. This indicates that the mothers eliminate these pesticides during 

pregnancy and by breastfeeding them into their children. Considering that the 

concn. of pesticides in breast milk samples had no significant correlation with 

parity, monitoring of the placental pesticide concn. may contribute to detg. the 

prenatal exposure of infants to organochlorine pesticides. The contribution of fish 

consumption to the intake of pesticides was dependent on the kind of pesticide. 

Nakashima, Y. and S. Ikegami (2000). "Hexachlorobenzene and pentachlorobenzene 

accumulated during pregnancy is transferred to pups at the accumulation ratio in dams." 

Journal of Health Science 46(2): 89-97. 

 Hexachlorobenzene (HCB) and pentachlorobenzene (PECB) were used to clarify 

how the rate at which lipophilic environmental pollutants are metabolized will 

affect their transfer to pups. In this study, the ratio of PECB/HCB transference to 

fetuses and suckling pups was investigated in rats fed a diet containing HCB 

(35.1 nmol/100 g diet) and PECB (351 nmol/100 g diet). The amounts of HCB 

and PECB transferred to fetuses were 0.44% and 0.15% of the amounts 

consumed by their dams, respectively, and the PECB/HCB concentration ratio in 

fetuses was 3.4. In pregnant rats on the day before parturition, the PECB 

concentrations in organs and fat tissue were 3 to 4 times higher than those of 

HCB. After parturition, PECB rapidly disappeared from the body of nursing rats 

during the lactation period, especially when compared with HCB. On day 2 after 

birth, HCB and PECB concentrations in the stomach contents of suckling pups 

were highest, and the PECB concentration was 3.5 times higher than that of 

HCB. HCB in the stomach contents decreased gradually (T1/2 = 5.7 d) and 

PECB decreased rapidly (T1/2 = 2.8 d) during the 15 d after birth. These findings 
72

indicate that the PECB/HCB transferred to fetuses and suckling pups was the 

same ratio found in the blood of their dams. 

Nakashima, Y. and S. Ikegami (2003). "High-fat diet enhances the accumulation of 

hexachlorobenzene (HCB) by pregnant rats during continuous exposure to HCB." J 

Agric Food Chem 51(6): 1628-33. 

 To investigate the influence of a high-fat diet on HCB distribution and 

accumulation, pregnant rats in study 1 were fed a high-fat or control diet 

containing HCB, and, in study 2, pregnant rats were given a single HCB dose by 

intragastric gavage and HCB-free high-fat or control diet. In study 1, the high-fat 

diet group had higher HCB concentrations in fat tissues and liver than did the 

controls. In study 2, although the total amounts of HCB in the fat tissue and liver 

were greater in the high-fat diet group than in the controls, no significant 

differences in HCB concentration were observed between the two groups. The 

high-fat diet group also showed more fecal excretion of HCB. Therefore, HCB 

accumulation in rats fed a high-fat diet was enhanced more by continuous 

exposure to HCB than by administration of a single dose. 

Nakashima, Y., S. Ohsawa, et al. (1999). "High-Fat diet enhances accumulation of 

hexachlorobenzene in rat dams and delays its transfer from rat dams to suckling pups 

through milk." J Agric Food Chem 47(4): 1587-92. 

 Effect of diets on the distribution and transfer of hexachlorobenzene (HCB) from 

dams to fetuses and suckling pups was investigated. In pregnant rats, the 

amount of HCB accumulated in fat tissues of the high- fat diet group was higher 

than that of the control diet group (P < 0.05). The amounts of HCB in fetuses of 

the high-fat and control diet groups were estimated to be about 0.28 and 0.12% 

of the dam's total intake during pregnancy, respectively. In both groups, a large 

proportion of HCB in dams disappeared during lactation period and was 

transferred to their pups through the milk. In the pups of the high-fat diet group, 

the amount of HCB in stomach contents was lower immediately after birth and 

decreased slowly compared with that in the control diet group during lactation. 

These results showed that a high-fat diet reduced the speed of the transfer of 

HCB from the dams to their suckling pups through milk. 

Nakata, H., T. Nasu, et al. (2005). "Organochlorine contaminants in human adipose 

tissues from China: mass balance approach for estimating historical Chinese exposure 

to DDTs." Environmental Science and Technology 39(13): 4714-20. 

 Concentrations of persistent organochlorines (OCs), such as DDTs, 

hexachlorocyclohexanes (HCHs), hexachlorobenzene (HCB), polychlorinated 

biphenyls (PCBs), and chlordane compounds (CHLs) were determined in 34 

human adipose tissues collected from Guizhou Province, southern China, during 

2002. DDT was the predominant contaminant among OCs analyzed; 

concentrations ranged from 420 to 20 000 ng/g on a lipid wt basis (average +/- 

sd: 5700 +/- 4100 ng/g). Concentrations of DDTs and the ratio of p,p'-DDT/ 

sigmaDDT in humans in China were significantly higher than those reported for 

developed countries. DDT levels in humans in Guizhou Province were 
73

comparable to those from Shanghai City, implying the presence of significant 

sources of DDTs in inland and coastal areas in China. Age-dependent 

accumulation of HCH concentration was found in this study, possibly because of 

the considerable reduction in average dairy intake (ADI) of HCHs by Chinese 

during the recent two decades. On the basis of the information of the ADI rates, 

half-lives, and body burdens of DDTs, the magnitude of historical DDT exposures 

by Chinese was estimated. This suggested that approximately 80% of DDTs 

deposited in Chinese adipose tissues was accumulated before the 1990s. The 

monitoring of OC levels and epidemiological studies are needed in China to 

understand the status of contamination and the risks to humans. 

Needham, L. L., D. B. Barr, et al. (2005). "Concentrations of environmental chemicals 

associated with neurodevelopmental effects in U.S. population." Neurotoxicology 26(4): 

531-45. 

 Humans are exposed to many environmental chemicals, some of which can 

potentially affect neurodevelopment. Fetuses, infants, and young children are the 

most susceptible to the effects of these chemicals. As part of the National Health 

and Examination Survey, 1999-2000, the Centers for Disease Control and 

Prevention analyzed biological samples for many of these chemicals in a 

representative sampling of the U.S. population. Concentration data of selected 

metals, persistent organic pollutants, organophosphorus and carbamate 

insecticides, and cotinine are presented. For example, the 95th percentile 

estimates for serum total PCBs (whole weight) in the population aged 20 years 

and older is about 2.7 ng/g. The 95th percentile estimates for serum dioxin total 

toxic equivalence in the U.S. population aged 20 years and older is between 40 

and 50 pg/g lipid basis. In general, human levels of these chemicals are 

decreasing over time in the U.S. population. This reflects the effects of 

legislation, industry efforts, and changes in lifestyle/activity patterns in the U.S. 

population. These data will continue to be collected in 2-year cycles and thus 

allow changes in human levels to be followed. 

Noren, K., C. Weistrand, et al. (1999). "Distribution of PCB congeners, DDE, 

hexachlorobenzene, and methylsulfonyl metabolites of PCB and DDE among various 

fractions of human blood plasma." Archives of Environmental Contamination and 

Toxicology 37(3): 408-414. 

 BIOSIS COPYRIGHT: BIOL ABS. The concentrations of chlorinated biphenyls 

(CBs), 1,1-bis(4-chlorophenyl)-2,2-dichloroethene (DDE), hexachlorobenzene 

(HCB), and the methylsulfonyl metabolites of CBs (MeSO2-CBs) and DDE 

(MeSO2-DDE) were determined in human plasma samples and in the fractions 

obtained by ultracentrifugation of plasma into very-low-density (VLDL), lowdensity (LDL), high-density (HDL) lipoprotein and lipoprotein depleted (LPDP) 

fractions (containing primarily albumin). The concentrations of triacylglycerols, 

cho hylsulfonyl substituted chlorobiphenyls to the LPDP fraction was noticed. 

Among the lipoprotein fractions, LDL was the main carrier of HCB, DDE and 

CBs. MeSO2-DDE was predominantly found in HDL and MeSO82-CBs were 

distributed equally among the LDL and HDL fractions. Calculating the 
74

concentrations of organochlorine compounds in relation to the content of apoB, 

the levels were about 10 times higher in VLDL than in LDL. 

Ntow, W. J., L. M. Tagoe, et al. (2008). "Accumulation of persistent organochlorine 

contaminants in milk and serum of farmers from Ghana." Environmental Research

106(1): 17-26. 

 In the present study, the concentrations of persistent organochlorine (OC) 

pesticides such as dichlorodiphenyltrichloroethane and its metabolites (DDTs), 

hexachlorocyclohexane isomers (HCHs), hexachlorobenzene (HCB) and dieldrin 

in pooled samples of human breast milk (n=109), and serum (n=115) from 

vegetable farmers in Ghana, during 2005, were determined. Gas 

chromatography with mass spectrometry was used to quantify residue levels on 

a lipid basis of the OCs. The pattern of OCs in human fluid showed that DDTs 

was consistently the prevalent OC in milk and blood. The levels of DDTs, HCHs, 

and dieldrin in the breast milk samples were found to correlate positively with age 

of the milk sample donors (r(s)=0.606, 0.770, and 0.540, respectively). When 

blood serum levels of the OCs were compared between male and female 

farmers, no pronounced relationship for HCHs and HCB (p>0.05) was observed. 

However, DDTs and dieldrin residues were significantly higher (p<0.05) in males 

than in females. There was association between breast milk and serum residues. 

When daily intakes of DDTs and HCHs to infants through human breast milk 

were estimated, some individual farmers (in the case of DDTs) and all farmers (in 

the case of HCHs) accumulated OCs in breast milk above the threshold 

(tolerable daily intake, TDI, guidelines proposed by Health Canada) for adverse 

effects, which may raise concern on children health. 

Omori-Inoue, M., H. Fukata, et al. (2007). "The contamination levels of organochlorines 

and the pattern of gene expressions in human umbilical cords from intra-pairs of twins 

at delivery." Reprod Toxicol 23(3): 283-9. 

 In this study, we examined the contamination levels of organochlorines and the 

patterns of gene expressions using umbilical cords of twins. The contamination 

levels of total PCBs, HCB and HCHs of intra-pair of twins were close to each 

other, but that of DDTs were not so as the others. It shows that the placental or 

fetal factor may influence the transfer or the accumulation of DDTs. The patterns 

of gene expressions of intra-pair of twins were similar to each other. It may 

because the environmental factor (sharing same mother), genetic factor or the 

both of twins are similar. This study gave us some information to understand the 

fetal exposure to organochlorines. Moreover, it showed the possibility that the 

pattern of gene expression in umbilical cord reflected the intra-uterine 

environment. However, the information from general pattern of the gene 

expression is limited. Therefore, further investigation is necessary to find new 

markers not only mRNA but also protein to estimate the effects of fetal exposure 

of multiple organochlorines. 
75

Ortega Garcia, J. A., D. Carrizo Gallardo, et al. (2006). "Meconium and neurotoxicants: 

searching for a prenatal exposure timing." Archives of Disease in Childhood 91(8): 642-

6. 

 BACKGROUND: Exposure to organochlorine compounds (OCs) has been a 

subject of interest in recent years, given their potential neurotoxicity. Meconium is 

easily available and accumulates neurotoxicants and/or metabolites from the 

12th week of gestation. AIMS: To determine whether neurotoxicants, specifically 

OCs, could be detected in serially collected meconium, and to compare the 

results with those obtained in cord blood samples. METHODS: A sample of cord 

blood and three serial stool samples were analysed in 10 newborns. 

Pentachlorobenzene (PeCB), hexachlorobenzene (HCB), polychlorinated 

biphenyls (PCBs), dichlorodiphenyl trichloroethane (p,p'-DDT) and its metabolite 

dichlorodiphenyl dichloroethylene (p,p'-DDE), and hexachlorocyclohexane 

isomers (alpha-, beta-, gamma-, and delta-HCH) were analysed by gas 

chromatography. RESULTS: From serial stool collection and analysis in 

newborns, there was an increase in the concentrations of HCB, p,p'-DDE, PCBs, 

and beta-HCH between the first and last stools of the newborn. Levels of DDT 

diminished as pregnancy progressed. Concentrations in cord blood were 

positively associated with concentrations in meconium for p,p'-DDE and betaHCH. CONCLUSIONS: Meconium is a very useful instrument for the 

investigation of fetal exposure to neurotoxicants; serial collection and analysis of 

meconium should estimate the timing and degree of in utero exposure of the 

fetus to neurotoxicants. Analysis and interpretation of neurotoxicants in 

meconium results is a complex process. Measurement in meconium of a wide 

range of neurotoxic substances should facilitate early identification of harmful 

exposures, and enable rehabilitation and instigation of preventive measures. 

Petrik, J., B. Drobna, et al. (2006). "Serum PCBs and organochlorine pesticides in 

Slovakia: age, gender, and residence as determinants of organochlorine 

concentrations." Chemosphere 65(3): 410-8. 

 We measured organochlorine concentrations of 15 polychlorinated biphenyl 

congeners and six organochlorine pesticides (PCB28, 52, 101, 123(+149), 118, 

114, 153, 105, 138(+163), 167, 156(+171), 157, 180, 170, 189, alpha-, beta-, 

gamma-HCH, HCB, p,p'-DDT and p,p'-DDE) in 2047 subjects from contaminated 

and background areas of eastern Slovakia. Data were collected in 2001 and 

analyzed by high-resolution gas chromatography with electron capture detection 

in 2002-2003. Elevated levels persist in subjects from Michalovce district, site of 

former production facility, after almost 20-years since the end of the PCB 

manufacturing. Sum of 15 PCB congeners was 3105 ng/g of lipid in the 

Michalovce district versus 871 ng/g of lipid for subjects from the background 

districts of Svidnik and Stropkov. Relatively high concentration in children from 

the Michalovce district, sum PCB = 766 ng/g of lipid versus 372 ng/g of lipid in 

children from background area suggest ongoing exposure from environmental 

reservoirs and contaminated food. Consistent differences between genders in 

both contaminated and background areas are reported here. Levels in males are 

about 20% higher in both districts. Levels of organochlorine pesticides, 
76

particularly of DDT metabolite DDE and hexachlorobenzene are also elevated in 

the Michalovce district, reflecting intensive use of pesticides in agriculture in the 

past. About 30% decrease in serum organochlorine levels was observed in 

comparison with our earlier samples collected in 1998. These results suggest 

that contamination with PCBs still remains a source of relatively high 

environmental exposure for subjects in the Michalovce district. 

Polder, A., G. W. Gabrielsen, et al. (2008). "Spatial and temporal changes of chlorinated 

pesticides, PCBs, dioxins (PCDDs/PCDFs) and brominated flame retardants in human 

breast milk from Northern Russia." Science of the Total Environment 391(1): 41-54. 

 This study presents for the first time temporal changes of organochlorine 

pesticides (OCPs) and polychlorinated biphenyls (PCBs) in Russian human 

breast milk samples. Concentrations of OCPs and PCBs in samples from three 

locations in the North West of Russia in 2000-2002 (n=42), were compared to 

corresponding levels measured in 1993-1996 (n=58). In addition brominated 

flame retardants (BFRs), consisting of polybrominated diphenylethers (PBDEs) 

(including BDE-209) and hexabromocyclododecane (HBCD) were analysed in 

samples from 2000-2002 (n=37). The present levels of SigmaDDTs and 

SigmaHCHs were 5 and 10 times higher than corresponding levels in the 

neighbouring country Norway. Median concentrations of SigmaHCHs (196 

microg/kg lw), SigmaCHBs (19.7 microg/kg lw) and SigmaPCBs(16) (316 

microg/kg lw) were highest in Murmansk. The percentage of p,p'-DDT to 

SigmaDDTs and ratio DDE/DDT suggest possible ongoing use of DDT in Russia. 

Levels of PBDE were low and dominated by the congeners BDE-47 and BDE153. The deca brominated BDE-209 was detected in all analysed samples 

(median concentration 0.19 microg/kg lipid). Levels of SigmaOCPs and 

SigmaPCBs decreased 56 and 30% in Murmansk and 36 and 43% in 

Arkhangelsk during the study period. The decline of SigmaOCPs was significant 

at both locations (p<0.05-p<0.0001). For SigmaPCBs, the decreasing trend was 

only significant in Arkhangelsk (p<0.0001). In addition, a decline of Sigmatotal 

TEQs (SigmaTEQs of PCDDs/PCDFs, non-ortho- and mono-ortho PCBs) was 

observed in Murmansk and Arkhangelsk during the study period. The exposure 

of infants by PCDDs/PCDFs and dioxin-like PCBs is still exceeding the daily 

tolerable intake (TDI) in North West Russia. However, the concentrations of 

PCDDs/PCDFs and dioxin-like PCBs seem to decline very rapidly. 

Polder, A., C. Thomsen, et al. (2008). "Levels and temporal trends of chlorinated 

pesticides, polychlorinated biphenyls and brominated flame retardants in individual 

human breast milk samples from Northern and Southern Norway." Chemosphere 73(1): 

14-23. 

 Human breast milk samples from primipara women from Northern (Tromso) 

(N=10) and Southern Norway (Oslo) (N=19) collected in 2000-2001 were 

analysed with respect to hexachlorobenzene (HCB), hexachlorocyclohexane 

(HCHs), chlordanes (CHLs), DDTs, mirex, toxaphenes (CHBs), polychlorinated 

biphenyls (PCBs), polybrominated diphenylethers (PBDEs) and 

hexabromocyclododecane (HBCD). CHBs, PBDEs and HBCD were only 
77

analysed in the Tromso samples. Sum-PCBs and sum-DDTs were the major 

organochlorines (OCs) (170 and 110 ng g(-1) lipid weight (lw), respectively). 

Other OCs were found in levels of approximately 10- to 300-fold lower than sumPCBs. Overall, the concentrations of OCs followed the decreasing order of 

PCBs>DDTs>HCB>HCHs approximately CHLs>CHBs>mirex. Concentrations of 

sum-HCHs were significantly higher in breast milk from Oslo compared to 

Tromso (p<0.05). The PCB profile was dominated by PCB-153, -138 and -180. 

The PBDE pattern was dominated by PBDE-47 and PBDE-153. The median 

level of sum-PBDEs was 4.1 ng g(-1) lw. PBDE-209 was detected in all analysed 

samples (median 0.13 ng g(-1) lw). The estimated daily intake (EDI) for the 

median (range) of sum mono-ortho (mo) PCBs(8) was 3.7 (1-9) pg TEQ kg(-1) 

body weight per day for breast fed infants in Norway. This exceeded the TDI by a 

factor of 1.8 (1-4) based only on intake of mono-ortho PCBs. The present study 

shows that concentrations of OCs in primipara breast milk have decreased 50-

60% since 1991, and that this trend is continuing. 

Polischu, S. C., R. J. Norstrom, et al. (2002). "Body burdens and tissue concentrations 

of organochlorines in polar bears (Ursus maritimus) vary during seasonal fasts." 

Environmental Pollution 118(1): 29-39. 

 Lipophilic organochlorines (OCs) are ingested by mammals through their foods 

and are generally stored in adipose tissue depots. For some species, such as 

polar bears, the size of these depots can fluctuate seasonally by several-fold. 

However, the effect of these fluctuations on the fate of stored OCs in an animal 

with such labile lipid depots is unknown. We determined the whole body burden 

and tissue concentrations of OCs in free-ranging polar bears categorized by age 

(cubs-of-the-year, yearlings and adults) and sex before and after a fast averaging 

56 days. Adipose tissue, plasma, and milk samples were analysed for sum of 

chlorobenzenes (sigma-ClBzs), hexachlorocyclohexanes (sigma-HCHs), 

chlordanes (sigma-CHLORs), dichlorodiphenyltrichloroethane compounds 

(sigma-DDTs) and polychlorinated biphenyls (sigma-PCBs). Decline in body 

mass during fasting ranged from 0.2 kg/day for cubs-of-the-year to 0.9 kg/day for 

sub-adult and adult males. Although all bears showed a decline in both lipid and 

lean mass during fasting, patterns of OC whole body burden changes were not 

consistent among compounds and bear classes. The burdens of sigma-DDTs 

declined by 11-50% for most bears during fasting, those of sigma-CHLORs 

declined by 67% during fasting in sub-adult and adult males but remained 

constant for all females, indicating male-specific metabolism of sigma-CHLORs. 

As fat depots became depleted, OC concentrations in the remaining adipose 

tissue varied; sigma-DDTs and sigma-HCHs declined while those of sigmaCHLORs and sigma-PCBs generally increased. Thus. within a 3-4 month fast, 

most polar bears were able to significantly rid their adipose tissue of sigma-DDTs 

and sigma-HCHs. Burdens of sigma-CHLORs (except males), sigma-ClBzs and 

sigma-PCBs remained constant for all classes of bears, therefore there was no 

significant excretion or metabolism during the fast of the specific congeners in 

these compound classes typically found in polar bears. The ratio of 

plasma/adipose tissue and milk/adipose tissue OC concentrations was the same 
78

for before and after the fast indicating that OC concentrations in polar bears are 

probably at a steady state among various body compartments. Concentrations of 

sigma-CHLORs and sigma-PCBs in milk almost doubled during the fast. As a 

consequence of this rise in milk OC concentrations, the whole body 

concentrations of these compounds increased in nursing cubs. Since developing 

young may be susceptible to the effects of environmental contaminants, the 

increased exposure of nursing cubs to OCs during a fast by their mothers is 

noteworthy. 

Rhainds, M., P. Levallois, et al. (1999). "Lead, mercury, and organochlorine compound 

levels in cord blood in Quebec, Canada." Archives of Environmental Health 54(40-47). 

 BIOSIS COPYRIGHT: BIOL ABS. We conducted this study to evaluate blood 

levels of lead, mercury, and organochlorine compounds in newborns in the 

Province of Quebec. During 1993 to 1995, we carried out a survey in 10 hospitals 

located in southern Quebec. During that time, umbilical cord blood samples were 

obtained from 1109 newborns, and we analyzed each for lead, mercury, 14 

polychlorinated biphenyl congeners, and 11 chlorinated pesticides. We used the 

geometric mean and 95% confidence interval (Cl) to describe the results. Mean 

concentrations of lead and mercury in cord blood were 0.076 mumol/l (95% Cl = 

0.074, 0.079) and 4.82 nmol/l (95% Cl = 4.56, 5.08), respectively. The mean 

concentrations of total polychlorinated biphenyls (Aroclor 1260) and 

dichlorodiphenyl dichloroethylene were 0.514 mug/l (95% Cl =.493, 0.536) and 

0.412 mug/l (95% Cl = 0.390, 0.435), respectively. We observed a statistically 

significant relationship between maternal age and cord blood concentrations of 

(a) lead, (b) mercury 

Ribas, F., auml, et al. (2003). "Exposure To Organochlorine Compounds Through 

Breastfeeding In A Population Exposed To Airborne Hexachlorobenzene." Epidemiology

14(5 Suppl): S40. 

 Objective: Exposure to organochlorine compounds occurs both in utero and 

through breastfeeding. Levels of hexachlorobenzene (HCB) in the cord serum of 

newborns from a population located in the vicinity of an electrochemical factory in 

Spain are among the highest ever reported. We aimed to assess the degree of 

breast milk contamination in this population and the subsequent child's exposure 

to these chemicals through breastfeeding. Methods:A birth cohort including 92 

mother-infant pairs (84% of all births in the study area) was recruited between 

1997-1999 in 5 neighbouring villages. Organochlorine compounds were 

measured in cord serum, colostrum, breast milk and child's serum at 8 weeks of 

age. Results:Levels of organochlorine compounds were detected and quantified 

in all colostrum and milk samples (medians in colostrum for HCB, p,p'DDE and 

PCBs were 0.90, 1.03 and 0.61 ug/g on lipid basis, respectively). Concentrations 

of these chemicals in colostrum were significantly correlated with the 

concentrations in child's serum at 8 weeks of life. Those infants who were 

breastfed had higher concentrations of organochlorine compounds at 8 weeks of 

life than those who were formula fed (2.00 ng/ml among formula feeders vs. 2.84 

among breast feeders of HCB, 0.98 vs. 4.55 of p,p'DDE (p < 0.05), and 0.65 vs. 
79

1.62 of PCBs (p < 0.05)). After adjusting for maternal age, parity and maternal 

body mass index the differences were statistically significant for all the 

contaminants. Conclusions:Levels of HCB and p,p'DDE in colostrum in this 

population are among the highest described in the Western countries. 

Breastfeeding leads to rapid removal of these contaminants from the body and 

increases the degree of contamination among breast feeders during the first 

weeks of life. 

Ribas-Fito, N., J. O. Grimalt, et al. (2005). "Breastfeeding and concentrations of HCB 

and p,p'-DDE at the age of 1 year." Environ Res 98(1): 8-13. 

 Exposure to organochlorine compounds (OCs) occurs both in utero and through 

breastfeeding. Levels of hexachlorobenzene (HCB) in the cord serum of 

newborns from a population located in the vicinity of an electrochemical factory in 

Spain are among the highest ever reported. We aimed to assess the degree of 

breast milk contamination in this population and the subsequent exposure of 

children to these chemicals through breastfeeding. A birth cohort including 92 

mother-infant pairs (84% of all births in the study area) was recruited between 

1997 and 1999 in five neighboring villages. OCs were measured in cord serum, 

colostrum, breast milk, and children's serum at 13 months of age. Concentrations 

of OCs were detected and quantified in all colostrum and milk samples. The 

concentrations in mature milk were lower than those encountered in colostrum. 

At 13 months of age the highest concentration of OC was found for 

dichlorodiphenyl dichloroethane (p,p'-DDE), in contrast to what these children 

presented at birth, where HCB was the highest compound. Those infants who 

were breastfed had higher concentrations at the age of 1 than those who were 

formula fed (2.13 ng/mL of HCB among formula feeders vs 4.26 among breast 

feeders, and 1.95 of p,p'-DDE vs 6.00 (P<0.05)). Long-term breastfeeding leads 

to a dose-response increase of the concentrations in children's serum during the 

first year of life. 

Ribas-Fito, N., M. Sala, et al. (2002). "Association of hexachlorobenzene and other 

organochlorine compounds with anthropometric measures at birth." Pediatr Res 52(2): 

163-7. 

 The aim of the present study was to assess the association of prenatal exposure 

to hexachlorobenzene (HCB) and other organochlorine compounds with 

anthropometric measures at birth. A total of 98 mother-infant pairs (83% of all 

children born in a specific area polluted with HCB in the period 1997-1999) were 

recruited after giving written consent. Levels of organochlorine compounds were 

measured in 72 maternal serum samples at delivery and in 70 cord serum 

samples. Of the organochlorines measured in cord serum, median levels of HCB 

were higher than for the other compounds (median of HCB = 1.13 ng/mL, median 

of dichlorodiphenyl dichloroethylene = 0.85 ng/mL, and median of total 

polychlorinated biphenyls = 0.27 ng/mL). Premature newborns had higher 

concentrations of HCB [1.94 ng/mL among prematures versus 1.10 among 

nonprematures (p < 0.10)], dichlorodiphenyl dichloroethylene [2.40 versus 0.80 

(p < 0.05)], and polychlorinated biphenyls in cord serum [0.70 versus 0.14 (p < 
80

0.10)]. Those infants born with a small length for gestational age had higher 

levels of HCB in cord serum than those with an adequate length for gestational 

age [1.64 ng/mL versus 1.00 ng/mL (p < 0.05)]. In addition, HCB cord serum 

levels were negatively associated in a dose-response way with crown-heel length 

[for each doubling of the dose there was a decrease of 0.46 (SE = 0.22) cm] after 

adjusting for smoking, gestational age, and other organochlorine compounds. 

The associations of dichlorodiphenyl dichloroethylene and polychlorinated 

biphenyls with length were not significant. The results did not vary when stratified 

for prematurity. These data suggest that HCB reduces intrauterine physical linear 

growth. 

Ribas-Fito, N., J. Sunyer, et al. (2003). "[Changes in concentrations of organochloride 

compounds in women from Flix, Tarragona [Spain]]." Gac Sanit 17(4): 309-11. 

 The population of Flix (region of Ribera del Ebro, Tarragona) is highly exposed to 

hexachlorobenzene (HCB) due to the closeness of an electrochemical factory. 

Although the degree of HCB contamination in this population is still high, 

concentrations of HCB in the sera of women aged 18-40 years from 1997 to 

1999 were 61% lower than those observed in 1994 (4.1 ng/ml vs. 10.6 ng/ml). 

Concentrations of dichlorodiphenyl dichloroethane (p,p'-DDE) and betahexachlorocyclohexane (beta-HCH) also decreased, although the difference was 

not statistically significant. In contrast, concentrations of polychlorinated 

biphenyls (PCB) in the period 1997-1999 showed a nonsignificant increase 

compared with those in 1994. 

Rodolico, S., S. Parrocchia, et al. (1999). "Chlorinated compounds in human breast 

milk: Levels of contamination and infant intake." Igiene Moderna|L'igiene moderna.

111(2): 119-131. 

 BIOSIS COPYRIGHT: BIOL ABS. Levels of HCB, BHC (alpha, gamma, beta, 

delta), Heptachlor, Heptachlor epoxide, o-p'DDE, p-p'DDE, o-p'TDE, p-p'TDE, op'DDT, and p-p'DDT were analyzed in 50 samples of human colostrum drawn 

between October 1992 and November 1993 from women hospitalized in a large 

hospital of Rome. In 62% of the samples either p-p' DDE or HCB residues were 

found. In 96% of the samples p-p' DDE was found (range 1-62 mugg, average 

12,8). We compared our results with a 1983-85 study and observed a reduction 

of con 

Rusiecki, J. A., A. Baccarelli, et al. (2008). "Global DNA hypomethylation is associated 

with high serum-persistent organic pollutants in Greenlandic Inuit." Environmental 

Health Perspectives 116(11): 1547-52. 

 BACKGROUND: Persistent organic pollutants (POPs) may influence epigenetic 

mechanisms; therefore, they could affect chromosomal stability and gene 

expression. DNA methylation, an epigenetic mechanism, has been associated 

with cancer initiation and progression. Greenlandic Inuit have some of the 

highest reported POP levels worldwide. OBJECTIVE: Our aim in this study was 

to evaluate the relationship between plasma POPs concentrations and global 

DNA methylation (percent 5-methylcytosine) in DNA extracted from blood 
81

samples from 70 Greenlandic Inuit. Blood samples were collected under the 

Arctic Monitoring and Assessment Program and previously analyzed for a battery 

of POPs. METHODS: We used pyrosequencing to estimate global DNA 

methylation via Alu and LINE-1 assays of bisulfite-treated DNA. We investigated 

correlations between plasma POP concentrations and global DNA methylation 

via correlation coefficients and linear regression analyses. RESULTS: We found 

inverse correlations between percents methylcytosine and many of the POP 

concentrations measured. Linear regressions, adjusting for age and cigarette 

smoking, showed statistically significant inverse linear relationships mainly for the 

Alu assay for p,p'-DDT (1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane; beta = -

0.26), p,p'-DDE [1,1-dichloro-2,2-bis(p-chlorophenyl) ethylene; beta = -0.38], 

beta-hexachlorocyclohexane (beta = -0.48), oxychlordane (beta = -0.32), alphachlordane (beta = -0.75), mirex (beta = -0.27), sum of polychlorinated biphenyls 

(beta = -0.56), and sum of all POPs (beta = -0.48). Linear regressions for the 

LINE-1 assay showed beta estimates of similar magnitudes to those using the 

Alu assay, however, none was statistically significant. CONCLUSIONS: This is 

the first study to investigate environmental exposure to POPs and DNA 

methylation levels in a human population. Global methylation levels were 

inversely associated with blood plasma levels for several POPs and merit further 

investigation. 

Saghir, S. A., M. J. Bartels, et al. (2007). "Effect of organic carbon content, clay type, 

and aging on the oral bioavailability of hexachlorobenzene in rats." Environ Toxicol 

Chem 26(11): 2420-9. 

 Bioavailability of lipophilic chemicals is influenced by the physicochemical 

properties of soils/sediment such as particle size, pH, clay, and organic carbon 

content. The present study investigated the effects of sediment composition and 

aging on the oral bioavailability of hexachlorobenzene (HCB) in rats. Formulated 

sediments were prepared using various ratios of kaolinite and montmorillonite 

clay, sand, peat moss, and black carbon, spiked with (14)C-HCB, and orally 

administered to rats prior to and after one year of aging in dark at 10 degrees C. 

In the nonaged sediments there was a 21 to 45% reduction in the oral 

bioavailability of HCB when compared to the corn oil standard without any clear 

pattern of the impact of the sediment clay and/or organic carbon content. One 

year of aging resulted in statistically significant (p = 0.049) reduction in the oral 

bioavailability of HCB from the sediments compared to the corn oil standard and 

nonaged sediment indicating stronger interactions between HCB and sediment 

contents with aging. The mean reduction in oral bioavailability after one year of 

aging ranged from approximately 5 to 14% greater than that observed for 

nonaged sediments. The fecal elimination of the HCB-derived radioactivity from 

the one-year-aged sediments was much higher than the nonaged sediments, 

consistent with the lower absorption from the gastrointestinal tract due to lower 

desorption of HCB from the aged sediments. Increase in the fecal elimination and 

decrease in oral bioavailability of (14)C-HCB was related to the increase in clay 

and black carbon. 
82

Saito, K., M. Ogawa, et al. (2005). "Systematic analysis and overall toxicity evaluation of 

dioxins and hexachlorobenzene in human milk." Chemosphere 61(9): 1215-20. 

 A systematic method for analyzing dioxins (PCDDs, PCDFs and dioxin-like 

PCBs), hexachlorobenzene (HCB), heptachlor epoxide and betahexachlorocyclohexane (HCH) in human milk was developed to determine the 

residual amount of HCB in human milk and to evaluate the overall toxicity of both 

dioxins and HCB in human milk. The fractionation behavior of HCB on 

chromatography with silica gel, alumina, and activated carbon/silica gel, and the 

concentrated sulfuric acid decomposition method, which is widely used as a 

dioxin cleanup method, were studied in order to make the preprocessing 

operation for HCB measurement compatible with that for conventional dioxin 

measurement. HCB was found to be eluted in the 2% dichloromethane 

(DCM)/hexane 60 ml fraction from an alumina column. Heptachlor epoxide and a 

part of beta-HCH were eluted in the 10% DCM/hexane 50 ml fraction from a 

silica gel column, while the remaining beta-HCH was eluted in the 25% 

DCM/hexane 60 ml fraction from an activated carbon/silica gel column. 

Moreover, HCB showed significant correlation with dioxin congeners having high 

toxicity equivalence factors (TEFs). The results suggest that the exposure route 

to HCB and its accumulation behavior in the human body are similar to those of 

the dioxins. 

Sarcinelli, P. N., A. C. Pereira, et al. (2003). "Dietary and reproductive determinants of 

plasma organochlorine levels in pregnant women in Rio de Janeiro." Environmental 

Research 91(3): 143-50. 

 Organochlorine (OC) plasma levels and their dietary and reproductive 

determinants were investigated in 64 pregnant women from Rio de Janeiro, 

Brazil. Prenatal exposure of newborns was evaluated in a subset of these 

women in which umbilical cord blood was analyzed. To assess the influence of 

dietary factors on OC levels, a semiquantitative food frequency questionnaire 

was completed by participants. Nondietary determinants were investigated 

through a general questionnaire that addressed reproductive history, lifestyle, 

and social-demographic characteristics. Both women and their newborns had 

detectable but low levels of OCs. The most frequently detected compound was 

p,p'-DDE, the main metabolite of p,p'-DDT. This compound was found in 97% of 

the women who participated in the study and in 67% of the umbilical cord blood 

samples, with levels ranging from 0.161 to 8.03ppb and from 0.320 to 1.06ppb, 

respectively. Among the OCs detected, only p,p'-DDE showed any correlation 

with dietary and nondietary factors. There was a positive correlation between 

maternal p,p'-DDE and the consumption of fish (Pearson r=0.38,P=0.002) and 

chicken (Pearson r=0.26, P=0.042). The correlation between pork consumption 

and p,p'-DDE exhibited an inverse relationship (Pearson r=-0.25,P=0.052). Parity 

was the only nondietary factor that showed a significant correlation (Pearson r=-

0.36,P=0.004). The main determinants of p,p'-DDE levels in this group of women 

were fish consumption and parity, together explaining 28% of the variance 

(P<001), in a multivariate model. 
83

Selden, A. I., Y. Floderus, et al. (1999). "Porphyrin status in aluminum foundry workers 

exposed to hexachlorobenzene and octachlorostyrene." Arch Environ Health 54(4): 248-

53. 

 The possible interference of hexachlorobenzene and octachlorostyrene (i.e., 

thermal byproducts from hexachloroethane in aluminum degassing) with 

porphyrin metabolism was investigated in exposed workers. Urine specimens 

from 9 male aluminum foundry workers (i.e., smelters) at 6 different companies 

and from 18 controls-matched for sex, age, residence, and socioeconomic 

status-were analyzed for total porphyrins and porphyrin isomers. Workers 

exposed to hexachlorobenzene and octachlorostyrene had a statistically 

significant increase in urinary total porphyrins, compared with controls (mean +/- 

standard deviation: 13.63 +/- 11.13 micromol/mol creatinine and 6.24 +/- 3.84 

micromol/mol creatinine, respectively; p = .02). The authors attributed the results 

mainly to differences in excretion of coproporphyrins-notably coproporphyrin III. 

Erythrocyte uroporphyrinogen decarboxylase activity was similar in both groups. 

There was a high correlation between levels of hexachlorobenzene and 

octachlorostyrene, respectively, in plasma and urinary excretion of porphyrins; 

these findings, however, relied heavily on 1 subject for whom extreme values 

were obtained. The results indicated that occupational exposure to 

hexachlorobenzene and octachlorostyrene in aluminum degassing with 

hexachloroethane may affect porphyrin metabolism in a manner consistent with 

early secondary coproporphyrinuria-the first recognized step in the development 

of chronic hepatic porphyria. It was also noted that changes remained detectable 

some years after exposure ceased. 

Shen, H., K. Main, et al. (2004). "Comparison hexachlorobenzene residues in placentas 

from Finland and Denmark (1997-2001)." Organohalogen Compounds 66(Dioxin 2004): 

2791-2794. 

 Statistical anal. of placentas from Finland and Denmark showed that their lipid 

contents have nearly normal distributions. The geometric means and the av. 

values are the same for the two cohorts, however, the Danish cohort has slightly 

lower lipid content than the Finnish one. The hexachlorobenzene (HCB) concns. 

for the two cohorts do not show normal distribution, indicating that the HCB 

contents are not apparently fat correlated in the non-fatty placental tissue. The 

av. content in the Danish cohort is 1.5 times of that in the Finnish cohort on both 

lipid base and wet wt. base. The difference in geometric mean of the concns. is 

1.7-fold with difference to both, lipid and fresh wt., suggesting that that HCB 

exposure level in Danish fetuses is generally higher than in Finland. This geog. 

difference might suggest geog. difference of HCB sources. 

Shen, H., K. M. Main, et al. (2008). "Concentrations of persistent organochlorine 

compounds in human milk and placenta are higher in Denmark than in Finland." Human 

Reproduction 23(1): 201-10. 

 BACKGROUND: A significantly reduced male reproductive health status, 

including a higher prevalence of cryptorchidism and hypospadias, has been 

documented in Danish men compared with Finnish men. Exposure to 
84

environmental pollutants with endocrine disrupting activities has been suggested 

as a possible contributing factor. In this study, we investigated whether there was 

a difference in milk and placental concentrations of persistent organohalogen 

compounds, between the two countries. METHODS: Organohalogens were 

analysed by high-resolution gas chromatography-high-resolution mass 

spectrometry in human milk samples from Finland (n = 65) and Denmark (n = 65) 

and in placentas from Finland (n = 112) and Denmark (n = 168). RESULTS: 1,1-

dichloro-2,2-bis(4-chlorophenyl)ethane (p,p'-DDE) was the dominant pollutant. 

beta-Hexa-chloro-cyclohexane (beta-HCH), hexachlorobenzene (HCB), 

endosulfan-I, dieldrin, oxychlordane (OXC), cis-heptachloroepoxide (c-HE) and 

1,1,1-trichloro-2,2-bis(4-chlorophenyl)ethane (p,p'-DDT) were the other main 

organochlorines detected. Danish samples had significantly higher 

concentrations of p,p'-DDE, p,p'-DDT, beta-HCH, HCB, dieldrin, c-HE and OXC 

than did the Finnish samples. Levels of organobrominated compounds were very 

low and most were undetectable in the majority of samples. BB-153 and BB-155 

were the most abundant polybromobiphenyl congeners. BB-153 was more 

abundant in Danish milk samples compared with Finnish samples, whereas BB155 was more abundant in the Finnish milk. CONCLUSIONS: The 

organochlorine levels were higher in Danish, than in Finnish, samples, 

suggesting a higher exposure for Danish infants. 

Shen, H., K. M. Main, et al. (2005). "Prenatal organochlorine pesticides in placentas 

from Finland: exposure of male infants born during 1997-2001." Placenta 26(6): 512-4. 

 

Shen, H., K. M. Main, et al. (2007). "From mother to child: investigation of prenatal and 

postnatal exposure to persistent bioaccumulating toxicants using breast milk and 

placenta biomonitoring." Chemosphere 67(9): S256-62. 

 The exposure levels of placenta and paired breast milk samples to selected 

organochlorine compounds and pesticides from Danish and Finnish samples 

have been investigated. p,p'-DDE is the dominant pollutant, beta-HCH, 

hexachlorobenzene, endosulfan-I, dieldrin, oxychlordane, cis-heptachlor epoxide 

and p,p'-DDT being the other major constituents. Their concentrations are 

linearly correlated between milk and placenta in similar patterns for Danish and 

Finnish samples. Milk samples have higher levels of these pollutants than 

placenta on lipid base. However, the apparently not correlated compounds, such 

as alpha-HCH, pentachlorobenzene, pentachloroanisole and methoxychlor, are 

generally accumulated more in placenta, which may suggest a tissue specific 

metabolic activity. Thus, depending on the compound of interest, biomonitoring 

may be done in placenta only or in both matrices. 

Strucinski, P., K. Goralczyk, et al. (2006). "[Levels of selected organochlorine 

insecticides, polychlorinated biphenyls, phthalates and perfluorinated aliphatic 

substances in blood--Polish WWF study]." Roczniki Panstwowego Zakladu Higieny

57(2): 99-112. 

 In June 2004, blood samples of fifteen volunteers were analyzed for presence of 

selected groups of chemical contaminants. The aim of this survey organized by 
85

WWF Poland (World Wildlife Fund) was highlighting the problem of man-made, 

persistent and bioaccumulative chemicals constantly present in surrounding 

environment and in our tissues. It was a part of European WWF "Detox" 

campaign supporting proposal of a new EU regulation that should lead to the 

identification and phasing out of the most harmful chemicals (known as REACH). 

Three laboratories in Czech Republic, Sweden and Belgium have analyzed blood 

samples for presence of the following groups of contaminants: organochlorine 

compounds (pesticides and polychlorinated pesticides), phthalates and 

perfluorinated aliphatic substances. The total number of single chemicals found 

in the blood samples was 25, that represents 64% of the 39 chemicals looked for. 

The average number of compounds found in the samples was 21 (from 19 to 22). 

Among organochlorine compounds analyzed, the predominant chemical found in 

the highest concentration was p,p'-DDE (range from 130 to 1310 ng/g of fat), 

which similarly like p,p'-DDT, beta-HCH, and HCB (concentrations ranging from 

6,4 to 46 ng/g of fat) was present in every person's blood. Among analyzed 

polychlorinated biphenyls, in all samples the following congeners have been 

present: PCB-118, PCB-138, PCB-153, and PCB-180 (concentrations ranging 

from 3,7 to 61 ng/g of fat). The two predominant phtalates from total eight 

analyzed present in all samples were di(2-ethylhexyl)phthalate (DEHP) 

(concentration range from 49 to 293 ng/g of blood) and diisobutyl phthalate 

(DIBP) (concentration range from 10 to 63 ng/g of blood). Among fifteen 

perfluorinated aliphatic substances analyzed, six have been present in each 

single sample (perfluorohexanesulfonic acid - PFHxS, perfluorooctanoic acid - 

PFOA, perfluorooctane-sulfonic acid - PFOS, perfluorooctanesulfonylamide - 

PFOSA, perfluorononanoic acid - PFNA, and perfluorododecanoic acid - PFDA). 

The predominant compound in this class of contaminants was PFOS with the 

concentration ranging from 4,4 to 14 ng/ml of blood. The limited number of 

samples does not allow for making an analysis of potential impact of different 

factors on concentrations of particular contaminants in human blood. Results 

obtained in this survey confirm the ubiquitous contamination by a cocktail of 

hazardous chemicals of every person tested. Humans being a part of the 

environment are being contaminated with the same chemicals which are present 

in surrounding air, water, food, consumer articles, etc. 

Sudaryanto, A., T. Kunisue, et al. (2005). "Specific accumulation of organochlorines in 

human breast milk from Indonesia: Levels, distribution, accumulation kinetics and infant 

health risk." Environmental Pollution (Amsterdam, Netherlands) 139(1): 107-117. 

 This study detd. concns. of polychlorinated biphenyls (PCBs) and organochlorine 

compd. (OC) pesticides in the milk samples of women from the general 

population in four locations of Indonesia. The most prevalent residues of OCs 

were DDTs, PCBs and hexachlorocyclohexane isomers (HCHs), whereas other 

OCs such as chlordane compds. (CHLs), tris(4-chlorophenyl)methane and 

hexachlorobenzene were lower. The levels of OCs varied between locations and 

individuals, with DDTs higher in suburban and rural areas than urban localities, 

may be due to the differences in food habits and sources between the individuals 

and locations. Data from Purwakarta site indicated continuing DDT exposure, 
86

which may confirm recent usage of DDT in Indonesia. A pos. correlation was 

obsd. between concn. of OCs in human milk and age of mothers, primiparas 

women having higher OCs than multiparas, suggesting these parameters play an 

important role influencing the OC burdens in lactating women. Some individuals 

accumulated DDTs and HCHs in breast milk close to or even higher than the TDI 

(tolerable daily intake) guidelines proposed by Health Canada. Specific residents 

were exposed to high levels of DDTs in Indonesia. 

Sudaryanto, A., T. Kunisue, et al. (2006). "Specific accumulation of organochlorines in 

human breast milk from Indonesia: levels, distribution, accumulation kinetics and infant 

health risk." Environmental Pollution 139(1): 107-17. 

 This study determined concentrations of polychlorinated biphenyls (PCBs) and 

organochlorine compound (OC) pesticides in the milk samples of women from 

the general population in four locations of Indonesia. The most prevalent 

residues of OCs were DDTs, PCBs and hexachlorocyclohexane isomers (HCHs), 

whereas other OCs such as chlordane compounds (CHLs), tris(4-

chlorophenyl)methane and hexachlorobenzene were lower. The levels of OCs 

varied between locations and individuals, with DDTs higher in suburban and rural 

areas than urban localities, may be due to the differences in food habits and 

sources between the individuals and locations. Data from Purwakarta site 

indicated continuing DDT exposure, which may confirm recent usage of DDT in 

Indonesia. A positive correlation was observed between concentration of OCs in 

human milk and age of mothers, primiparas women having higher OCs than 

multiparas, suggesting these parameters play an important role influencing the 

OC burdens in lactating women. Some individuals accumulated DDTs and HCHs 

in breast milk close to or even higher than the TDI (tolerable daily intake) 

guidelines proposed by Health Canada. 

Sudaryanto, A., T. Kunisue, et al. (2005). "Persistent organochlorine compounds in 

human breast milk from mothers living in Penang and Kedah, Malaysia." Archives of 

Environmental Contamination and Toxicology 49(3): 429-37. 

 This study determined the concentrations of polychlorinated dibenzo-pdioxins/dibenzofurans (PCDD/Fs), polychlorinated biphenyls (PCBs), 

organochlorine (OC) pesticides, and tris(4-chlorophenyl) methane (TCPMe) in 

human breast milk samples collected in 2003 from primipara mothers living in 

Penang, Malaysia. OCs were detected in all the samples analyzed with DDTs, 

hexachlorocyclohexane isomers (HCHs), and PCBs as the major contaminants 

followed by chlordane compounds (CHLs), hexachlorobenzene (HCB), and 

TCPMe. The residue levels of DDTs, HCHs, and CHLs were comparable to or 

higher than those in general populations of other countries, whereas PCBs and 

HCB were relatively low. In addition, dioxins and related compounds were also 

detected with a range of dioxin equivalent concentrations from 3.4 to 24 pgTEQs/g lipid wt. Levels of toxic equivalents (TEQs) were slightly higher than 

those in other developing countries but still much lower than those of 

industrialized nations. One donor mother contained a high TEQs level, equal to 

the mean value in human breast milk from Japan, implying that some of the 
87

residents in Malaysia may be exposed to specific pollution sources of dioxins and 

related compounds. No association was observed between OCs concentrations 

and maternal characteristics, which might be related to a limited number of 

samples, narrow range of age of the donor mothers, and/or other external 

factors. The recently identified endocrine disrupter, TCPMe, was also detected in 

all human breast milk samples of this study. A significant positive correlation was 

observed between TCPMe and DDTs, suggesting that technical DDT might be a 

source of TCPMe in Malaysia. The present study provides a useful baseline for 

future studies on the accumulations of OCs in the general population of Malaysia. 

Sun, S. J., J. H. Zhao, et al. (2005). "Persistent organic pollutants in human milk in 

women from urban and rural areas in northern China." Environmental Research 99(3): 

285-93. 

 Human milk specimens from 55 women in Shijiazhuang urban and Tangshan 

rural areas in Hebei Province in northern China were collected and analyzed for 

persistent organic pollutants, such as p,p'-dichlorodiphenyldichloroethylene (p,p'-

DDE), hexachlorobenzene (HCB), beta-hexachlorocyclohexane (beta-HCH), and 

dioxins. We administered a questionnaire to milk donors at collection time, asking 

about lifestyle factors that potentially influence organochlorine pesticide (OCP) 

levels in human milk. We found that the concentrations of p,p'-DDE and betaHCH in human milk from the primiparous mothers in Shijiazhuang (3330 and 

108.8 ng/g fat, respectively) were higher than in samples from mothers from 

Tangshan (1916 and 21.2 ng/g fat, respectively). In addition, we found the level 

of p,p'-DDE correlated positively with a dietary history of meat consumption or 

consumption of internal organs of pigs and sheep (r=0.38 and r=0.52, 

respectively), but not with intake frequencies of vegetables and fruits in 

primiparous mothers. The higher level for p,p'-DDE may be due to a greater 

intake of contaminated fatty foods in the industrialized areas. We also showed 

that the body burden of p,p'-DDE was higher in the urban group compared to the 

values in other regions in China after 1998. However, there was no difference in 

dioxin levels between the two regions. Comprehensive monitoring of persistent 

organic pollutants in human milk and food is needed in China. 

Thomas, G. O., M. Wilkinson, et al. (2006). "Organohalogen chemicals in human blood 

from the United Kingdom." Environmental Pollution 141(1): 30-41. 

 Blood serum from 154 volunteers at 13 UK locations in 2003 were analysed for a 

range of PCBs, organochlorine pesticides and PBDEs. HCB, p,p'-DDE and p,p'-

DDT and beta-HCH were the dominant organochlorine pesticides in most 

samples. BDEs 47, 99, 100, 153, 154 and 183 were the most regularly detected 

PBDEs. This study is the first report of BDE209 in UK human blood (found in 11 

samples, range < 15-240 ng/g lipid). Concentration and age correlated for the 

less easily metabolised PCBs, p,p'-DDT and p,p'-DDE, HCB and HCHs. With 

increasing age females tended to have lower concentrations of the more 

chlorinated PCBs than males. Similar PBDE concentrations, and distributions, to 

those reported in the general population in Sweden in 2002 were found, despite 

differences in historical PBDE production and usage. There is increasing 
88

regulation to control persistent and bioaccumulative chemicals, and establishing 

human exposure will help to identify substances which should be urgently 

phased out. 

Trapp, S., L. M. Bomholtz, et al. (2008). "Coupled mother-child model for 

bioaccumulation of POPs in nursing infants." Environmental Pollution 156(1): 90-8. 

 Bioaccumulation of persistent organic pollutants (POPs) leads to high levels in 

human milk and high doses of POPs for nursing infants. This is currently not 

considered in chemical risk assessment. A coupled model for bioaccumulation of 

organic chemicals in breast-feeding mother and nursing infant was developed 

and tested for a series of organic compounds. The bioaccumulation factors 

(BAFs) in mother, breast milk and child were predicted to vary with logK(OW) 

and, for volatile compounds, with K(AW) and concentration in air. The 

concentrations of POPs in the infant body increase the first half year to about 

factor 3 above mother and decline thereafter to lower levels. The predicted 

results are close to empirical data and to an empirical regression. The new 

mother-child model is compact due to its easy structure and the analytical matrix 

solution. It could be added to existing exposure and risk assessment systems, 

such as EUSES. 

Tsydenova, O. V., A. Sudaryanto, et al. (2007). "Organohalogen compounds in human 

breast milk from Republic of Buryatia, Russia." Environ Pollut 146(1): 225-32. 

 Human breast milk samples collected during 2003/04 in Buryatia, a Russian 

autonomous republic, were analyzed in order to assess human exposure to 

organohalogen compounds including organochlorine pesticides, polychlorinated 

biphenyls (PCBs), and polybrominated diphenyl ethers (PBDEs). When 

compared with available worldwide data, levels of HCB (23-880 ng/g lipid wt.), 

PCBs (69-680 ng/g lipid wt.), and HCHs (100-3700 ng/g lipid wt.) were relatively 

high, indicating elevated human exposure to these organochlorines (OCs) in 

Buryatia. In contrast to OCs, PBDE concentrations were low (0.46-1.7 ng/g lipid 

wt.). Out of 14 BDE congeners analyzed, BDE-28, BDE-47, BDE-100, BDE-153, 

BDE-197, and BDE-207 were detected. Estimated daily intakes (EDIs) of HCHs, 

HCB, CHLs, and PCBs by infants solely from human milk for 100%, 43%, 34%, 

and 17% of the samples, respectively, exceeded guideline thresholds. Although 

high EDIs raise concern for possible toxic effects of OCs, women in Buryatia are 

recommended to breastfeed due to numerous advantages of breastfeeding for 

mother and child. 

Van Wouwe, N., A. Covaci, et al. (2004). "Levels of contamination for various pollutants 

present in Belgian human plasma." Organohalogen Compounds 66(Dioxin 2004): 2784-

2790. 

 The actual contamination's levels of various pollutants in human plasma from 

Belgium, including polychlorinated dibenzodioxin/dibenzofurans (PCDD/Fs), 

polychlorinated biphenylsand organochlorine pesticides (OCPs), as well as 

perfluorooctanesulfonate (PFOS) and related fluorochems. were assessed. 

Among the three fluorochems., PFOS was present at the highest concn., 
89

followed by PFOA. Concerning dietary habits, PFOS concn. was significantly 

influenced by meat and milk consumption. On the contrary, PCB concns. were 

not significantly explained by any food consumption. In all samples, p,p'-DDE 

was the major pesticide, followed by HCB, OxC and ?-HCH. When expressed in 

pg/g lipids, the dioxin congener profiles was dominated by higher chlorinated 

compds. such as OCDD, 1,2,3,4,5,7,8-heptaCDD and 1,2,3,6,7,8-hexaCDD. For 

furans, 2,3,4,7,8-pentaCDF was the most predominant congener, followed by 

1,2,3,4,7,8,-hexaCDF and 1,2,3,4,6,7,8-heptaCDF. None of the sample 

demonstrated any estrogen activity over the detection limit of 34.67 pg/?L ?-

estradiol equiv. using the LUMI-CELL ER. 

Verner, M. A., M. Charbonneau, et al. (2008). "Physiologically based pharmacokinetic 

modeling of persistent organic pollutants for lifetime exposure assessment: a new tool in 

breast cancer epidemiologic studies." Environmental Health Perspectives 116(7): 886-

92. 

 BACKGROUND: Despite experimental evidence, most epidemiologic studies to 

date have not supported an association between exposure to persistent organic 

pollutants (POP) and breast cancer incidence in humans. This may be 

attributable to difficulties in estimating blood/tissue POP concentration at critical 

time periods of carcinogenesis. OBJECTIVES: In this work we aimed to develop 

a tool to estimate lifetime POP blood/tissue exposure and levels during any 

hypothesized time window of susceptibility in breast cancer development. 

METHODS: We developed a physiologically based pharmacokinetic (PBPK) 

model that can account for any given physiologic lifetime history. Using data on 

pregnancies, height, weight, and age, the model estimates the values of 

physiologic parameters (e.g., organ volume, composition, and blood flow) 

throughout a woman's entire life. We assessed the lifetime toxicokinetic profile 

(LTP) for various exposure scenarios and physiologic factors (i.e., breastfeeding, growth, pregnancy, lactation, and weight changes). RESULTS: 

Simulations for three POPs [hexachlorobenzene, polychlorinated biphenyl (PCB)-

153, PCB-180] using different lifetime physiologic profiles showed that the same 

blood concentration at 55 years of age can be reached despite totally different 

LTP. Aside from exposure levels, lactation periods and weight profile history 

were shown to be the factors that had the greatest impact on the LTP. 

CONCLUSIONS: This new lifetime PBPK model, which showed the limitations of 

using a single sample value obtained around the time of diagnosis for lifetime 

exposure assessment, will enable researchers conducting environmental 

epidemiology studies to reduce uncertainty linked to past POP exposure 

estimation and to consider exposure during time windows that are hypothesized 

to be mechanistically critical in carcinogenesis. 

Verreault, J., R. J. Letcher, et al. (2009). "Dietary, age and trans-generational effects on 

the fate of organohalogen contaminants in captive sledge dogs in Greenland." 

Environment International 35(1): 56-62. 

 Studies on the fate of organohalogen contaminants (OHCs) in wild top predator 

mammals in the Arctic have often been a challenge due to important knowledge 
90

deficiencies in the life history of the sampled animals. The present study 

investigated the influence of age, dietary and trans-generational factors on the 

fate of major lipophilic chlorinated and brominated OHCs in adipose tissue of a 

potential surrogate captive species for the polar bear (Ursus maritimus), the 

sledge dog (Canis familiaris) in West Greenland. Adult female sledge dogs (P) 

and their sexually-mature (F1) and/or pre-weaning pups (F1-MLK) were divided 

into an exposed group (EXP) fed blubber from a Greenland minke whale 

(Balaenoptera acutorostrata) and a control group (CON) given commercially 

available pork fat. Large dietary treatment-related differences in summed and 

individual congener/compound adipose tissue concentrations of polybrominated 

diphenyl ethers (PBDEs), hexachlorobenzene (HCB), chlordanes (CHLs) and 

polychlorinated biphenyls (PCBs) were found between the EXP and CON groups 

for all the sledge dog cohorts. However, among the F1-MLK, F1 and P dogs in 

both of the EXP and CON groups, little or no difference existed in PBDE, HCB, 

CHL and PCB concentrations, suggesting higher state of equilibrium in adipose 

tissue concentrations from a very early stage of life. In contrast, the distribution 

pattern (proportions to the summed concentrations) of OHC classes, and the 

major congeners/compounds constituting those classes, varied on a dietary 

group- and/or cohort-dependent manner. The present captive sledge dog study 

demonstrated the importance of the confounding effects of diet composition, 

mother-pup association (maternal transfer), reproductive status (nursing), and to 

a lesser extent age in the fate of OHCs in adipose tissue of a large top carnivore 

mammal. 

Voorspoels, S., A. Covaci, et al. (2002). "Relationship between age and levels of 

organochlorine contaminants in human serum of a belgian population." Bulletin of 

Environmental Contamination and Toxicology 69(1): 22-9. 

 

Waliszewski, S. M., A. A. Aguirre, et al. (1999). "Organochlorine pesticide residues in 

human blood serum of inhabitants of Veracruz, Mexico." Bulletin of Environmental 

Contamination and Toxicology 62(4): 397-402. 

 Biosis copyright: biol abs. rrm research article human patient pollution toxicology 

organochlorine pesticide residues environmental contaminant blood serum toxin 

clinical chemistry pesticides lindane pesticide pp'ddt aldrin heptachlor op'ddt 

pp'dde pp'ddd alpha beta-endosulfan epsilon-ddt veracruz mexico 

Waliszewski, S. M., A. A. Aguirre, et al. (1999). "Comparison of organochlorine pesticide 

levels in adipose tissue and human milk of mothers living in Veracruz, Mexico." Bull 

Environ Contam Toxicol 62(6): 685-90. 

 

Waliszewski, S. M., S. Gomez-Arroyo, et al. (2003). "Comparison of organochlorine 

pesticide levels between abdominal and breast adipose tissue." Bulletin of 

Environmental Contamination and Toxicology 71(1): 156-62. 

 
91

Whitcomb, B. W., E. F. Schisterman, et al. (2005). "Relative concentrations of 

organochlorines in adipose tissue and serum among reproductive age women." 

Environmental Toxicology and Pharmacology 19(2): 203-213. 

 Much of the available literature focusing on organochlorine exposure and human 

health effects has relied upon serum for quantifying exposure despite adipose 

tissue being the purported "gold std.". The accuracy of exposure status is 

dependent upon serum being a valid and reliable proxy for adipose tissue 

regardless of compd. under study and served as the impetus for study. Serum 

and omentum fat concns. for 62 polychlorinated biphenyls (PCBs) and 7 

organochlorine pesticides (OCPs) were detd. using gas chromatog. with electron 

capture and compared to assess their relative abundance and correlation among 

15 women aged 18-40 years undergoing laparoscopy. The relation between 

concn. in serum and fat was detd. by linear regression. Of the 20 

organochlorines (OCs) (29%) present in both serum and fat samples, moderate 

linear correlations (r > 0.6) were obsd. between lipid-adjusted serum and fat 

concns. for PCBs #138, 153, 180, 188, 194, 206, and DDE. Forty-nine OCs were 

present in adipose samples but measured below the LOD in serum samples. 

These findings underscore the potential for discrepant human health results 

assocd. with OC exposure on the basis of medium used for quantification 

purposes, esp. for less ubiquitous compds. or when study samples include 

individuals with relatively low exposures. These data support earlier findings and 

argue for concerted methodol. work aimed at developing standardized lab. 

methods for epidemiol. studies. 

Wittsiepe, J., P. Schrey, et al. (2008). "Polychlorinated dibenzo-pdioxins/polychlorinated dibenzofurans (PCDD/Fs), polychlorinated biphenyls (PCBs), 

and organochlorine pesticides in human blood of pregnant women from Germany." 

Journal of toxicology and environmental health. Part A. 71(11-12): 703-9. 

 Blood samples from 226 pregnant women aged between 19 and 41 yr, living in 

an industrialized area of Germany (Duisburg birth cohort study), were collected 

between September 2000 and November 2002 and analyzed for their content of 

persistent organic pollutants (POPs). Levels of polychlorinated dibenzo-p-dioxins 

(PCDDs), polychlorinated dibenzofurans (PCDFs), and polychlorinated biphenyls 

(PCBs) were in the range of 4.34-97.3 pg WHO 1998 TEq/g(lipid base) (median: 

25.96) or 3.77-63.56 pg WHO 2005 TEq/g(lipid base) (median: 19.38), 

respectively. Whole blood volume-based concentrations of organochlorine 

pesticides and their metabolites were 0.036-0.53 microg/L (median: 0.15) 

hexachlorobenzene (HCB), 4.5-1300 ng/L (median: 67) betahexachlorocyclohexane (HCH), 0.6-520 ng/L (median: 18) 4,4'-

dichlorodiphenyltrichloroethane (DDT), and 0.1-9.1 microg/L (median: 0.54) 4,4'-

dichlorodiphenyldichloroethene (DDE). Parameters influencing the POP levels in 

human blood were examined using multiple regression models. Levels and the 

levels scatter widths of most PCDD/F and PCB congeners and HCB increased 

significantly with age. Within the multiple regression model a weak age 

dependence was also found for beta-HCH and DDT, whereas blood levels of 

alpha- and gamma- HCH and DDE were not age dependent. The total lactation 
92

period for earlier born children decreased most POP blood levels, except for 

alpha- and gamma-HCH. Over the study period of 27 mo only a low decreasing 

effect on human POP blood levels was observed. The body mass index had in 

general no or a low positive influence on contaminant levels. Because exposure 

to PCDD/F and PCB is higher in most industrialized countries in comparison to 

less industrialized ones, lower levels of these substances were detected in blood 

samples of women who had lived outside Western Europe for a longer period. In 

contrast, these women showed higher blood levels of organochlorine pesticides, 

indicating that these chemicals are still in use outside Western Europe. 

Wolkers, H., I. C. Burkow, et al. (2002). "Transfer of polychlorinated biphenyls and 

chlorinated pesticides from mother to pup in relation to cytochrome P450 enzyme 

activities in harp seals (Phoca groenlandica) from the gulf of St. Lawrence, Canada." 

Environmental Toxicology and Chemistry 21(1): 94-101. 

 Congener-specific transfer of polychlorinated biphenyls (PCBs) and chlorinated 

pesticides from female to pup was studied in harp seals from eastern Canada. 

Possible effects on hepatic cytochrome P450 enzymes (CYP450) due to 

contaminant mobilization from blubber lipids in females and ingestion of 

contaminated milk in pups were studied. Contaminant transfer from blubber to 

milk in females favored the more polar compounds (lower chlorinated PCBs, 

toxaphenes, hexachlorocyclohexanes, and hexachlorobenzene) relative to more 

lipophilic compounds (higher chlorinated PCBs, dichlorodiphenyltrichloroethane 

[DDT], chlordane). In spite of substantial contaminant mobilization from blubber 

in females and ingestion of contaminated milk by pups, CYP450 activities were 

low in all animals. Possibly, increased plasma estradiol concentrations, involved 

in breeding after lactation, suppressed CYP450 directly. Although the pups were 

exposed to contaminants in milk, CYP450 activities were low, resulting in low 

contaminant metabolism. This was confirmed by similar contaminant patterns in 

milk and pups. A strong positive relation between CYP1A-like activities and body 

weight in the pups suggested not yet fully developed CYP1A enzymes. A 

negative association between CYP3A and pesticides in females and pups was 

hypothesized to be a result of metabolic inactivation of CYP450. The CYP450 

enzyme activities were considered unsuitable indicators for contaminant 

mobilization and transfer in harp seals. 

Yu, H. F., X. D. Zhao, et al. (2006). "Continuous surveillance of organochlorine 

pesticides in human milk from 1983 to 1998 in Beijing, China." Int J Environ Health Res

16(1): 21-6. 

 A study was carried out to study the accumulative levels and dynamic changes of 

organochlorine pesticides in human milk in Beijing from 1982 to 1998, and the 

effect of prohibition and restriction on the use of DDT and BHC (666) in China in 

1983. The milk samples were collected from women during the lactation period in 

four districts of Beijing from 1982 to 1998, in 1991, 1993 and 1998, respectively. 

The contents of DDT and BHC in human milk were determined according to the 

standard method of biology-monitoring of PR China. The average fat content of 

human milk was about 3% from 1982-1998 in Beijing. The average concentration 
93

of pp-DDT and op-DDT in 1985 was less than 0.10 mg/kg and remained so until 

1998. The average concentration of pp'-DDT decreased from 1.80 mg/kg in 1982 

to 0.24 mg/kg in 1998 and that of pp-DDE descended from 5.87 mg/kg to 1.72 

mg/kg and the total concentration of DDT dropped from 7.71 mg/kg to 2.04 

mg/kg. Since prohibition of organochlorine pesticides 1983, the average 

concentration of beta-BHC and total BHC fell respectively from 9.66 mg/kg and 

10.1 mg/kg in 1983 to 1.18 mg/kg in 1998. However, the accumulative 

concentration of DDT and BHC was much higher than that of some foreign 

countries. Therefore, it was important and necessary to monitor organochlorine 

compounds in human milk continuously. 

Zietz, B. P., M. Hoopmann, et al. (2008). "Biomonitoring of polychlorinated biphenyls 

and organochlorine pesticides in human milk from mothers living in Northern Germany." 

Naunyn-Schmiedeberg's Archives of Pharmacology 377(Suppl. 1): 91. 

 

Zietz, B. P., M. Hoopmann, et al. (2008). "Long-term biomonitoring of polychlorinated 

biphenyls and organochlorine pesticides in human milk from mothers living in northern 

Germany." International Journal of Hygiene and Environmental Health 211(5-6): 624-

638. 

 Polychlorinated biphenyls (PCBs) and organochlorine pesticides are persistent 

org. pollutants that have a widespread distribution in the environment. Human 

biomonitoring is a suitable tool to assess the burden of humans with these 

substances. Over a time span of 8 years, a free anal. of their milk was offered to 

lactating mothers residing in the state of Lower Saxony, Germany. The human 

milk was analyzed for a no. of org. chems. including polychlorinated biphenyls 

(PCBs), 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (DDT), hexachlorobenzene 

(HCB) and ?-hexachlorocyclohexane (?-HCH). Factors that may influence these 

levels were investigated using a questionnaire. In total, 4314 samples were 

collected in the years 1999-2006 and analyzed for their content of these 

persistent org. pollutants (POPs). A clear downward trend of median total PCB, 

DDT, ?-HCH and HCB values in all participants and also in different selected 

subgroups could be obsd. The median values of calcd. total PCB in the year 

2006 including all participants was 0.1825 mg/kg lipid, that of DDT 0.0815 mg/kg 

lipid, ?-HCH 0.0116 mg/kg lipid and of HCB 0.0229 mg/kg lipid. There were 

redns. between 40.9% and 47.1% compared to the year 1999. Among other 

influencing factors, median concns. of total PCB, DDT, ?-HCH and HCB showed 

a clear rise with increasing age of mothers whereas an increasing no. of 

breastfed infants per mother led to a decrease. The proportions of other 

measured substances exceeding limits of quantification were as follows: dieldrin 

68.6%, ?-HCH 1.3%, ?-HCH 60.1%, heptachlor epoxide 41.5%, musk xylene 

15.6%, musk ambrette 0.4%. We conclude that the known declining trend of 

important xenobiotic substances in human milk of German mothers has 

continued. 
94

CODE 5 (not directly useful) References 

Akkina, J., J. Reif, et al. (2004). "Age at natural menopause and exposure to 

organochlorine pesticides in Hispanic women." J Toxicol Environ Health A 67(18): 1407-

22. 

 A cross-sectional study was conducted to evaluate the relationship between 

exposure to selected organochlorine pesticides (OCP) (p,p'-DDT, p',p'-DDE, 

dieldrin, hexachlorobenzene, beta-hexachlorocyclohexane [beta-HCH], 

oxychlordane, trans' nonachlor) and age at natural menopause in a sample of 

219 menopausal women participating in the Hispanic Health and Nutrition 

Examination Survey in 1982-1984. Information on age at menopause, 

reproductive history, demographic variables, and potential confounding variables 

was collected via interview. Analysis of variance was employed to compare 

adjusted mean age at natural menopause among women by category of serum 

OCP level. Serum levels of p,p'-DDT, p,p'-DDE, beta-HCH, and trans-nonachlor 

were associated with a younger age at menopause. In particular, women with 

exposure levels in the highest exposure categories (serum p,p'-DDT > or = 6ppb, 

beta-HCH > or = 4ppb, or trans-nonachlor > or = 2ppb) had an adjusted mean 

age at menopause on average 5.7, 3.4, and 5.2 yr earlier, respectively, than 

women with serum levels of these pesticides below the detection limit. Women 

with serum p,p'-DDE levels greater than 23.6 ppb (highest quintile) had an 

adjusted mean age at menopause 1.7 yr earlier than women with serump,p'-DDE 

levels less than 5.5 ppb (lowest quintile). However, no consistent dose-response 

effect was apparent across low, medium, and high exposure categories. 

Interactions were detected for p,p'-DDT in combination with beta-HCH, transnonachlor, or oxychlordane, as well as beta-HCH in combination with 

oxychlordane. 

Alvarez, L., S. Hernandez, et al. (2005). "The role of type I and type II 5' deiodinases on 

hexachlorobenzene-induced alteration of the hormonal thyroid status." Toxicology

207(3): 349-62. 

 Treatment of male Wistar rats with hexachlorobenzene (HCB) (1000 mg/kg b.w.) 

for 3-30 days decreases circulating levels of thyroxine (T4) but does not affect 

triiodothyronine (T3). Time courses were determined for 5' deiodinase type I (5' 

D-I) activity in thyroid, liver, and kidney and 5' deiodinase type II (5' D-II) activity 

in brown adipose tissue (BAT) to test the possibility that increased deiodinase 

activity might contribute to the maintenance of the serum T3 level. Specific 5' D-I 

activity was increased in the thyroid at 21 days and thereafter. No significant 

changes were observed in the liver, however, total 5' D-I activity in this tissue 

was increased at 30 days of treatment as a consequence of liver weight 

enhancement. HCB decreased kidney 5' D-I activity after 15 days, and BAT 5' DII activity after 21 days of treatment. Total body 5' D-I activity was significantly 

increased by 30 days of HCB-treatment. HCB increased the activity of hepatic T4 

uridine diphosphoglucuronosyl transferase (UDPGT) in a time-dependent 

manner, without changes in T3 UDPGT. We propose that increased T4 to T3 
95

conversion in the thyroid and in the greatly enlarged liver may account for the 

maintenance of serum T3 concentration in hypothyroxinemic HCB-treated rats. 

Alvarez, L., A. Randi, et al. (1999). "Effect of hexachlorobenzene on NADPH-generating 

lipogenic enzymes and L- glycerol-3-phosphate dehydrogenase in brown adipose 

tissue." J Endocrinol Invest 22(6): 436-45. 

 The effect of the in vivo administration of hexachlorobenzene (HCB) (100 mg/100 

g bw) for 30 days, on the activities of brown adipose tissue (BAT) lipogenic 

enzymes, i.e. malic enzyme (ME), and glucose-6- phosphate dehydrogenase 

(G6PD) and the mitochondrial non lipogenic enzyme, L-glycerol-3-phosphate 

dehydrogenase (LG3PD), was studied in male Wistar rats, submitted to various 

neurohormonal manipulations. BAT ME, G6PD and LG3PD activities showed 

significant reductions in response to HCB treatment both in euthyroid and 

surgically thyroidectomized rats, showing that the effect does not depend on the 

presence of thyroid hormones. These results differ from those obtained for 

hepatic ME and G6PD activities, which increased in HCB intoxicated rats without 

alteration in LG3PD. HCB decreased BAT ME activity under BAT denervation. 

Administration of HCB resulted in time and dose-dependent decreases in the 

activity of BAT malic enzyme. The basal activity of ME was increased in 

hypothyroid rats, while that of LG3PD was reduced. A stimulatory effect of 

receptor-saturating doses of triiodothyronine (T3) (50 microg/100 g body weight) 

was observed on BAT ME and LG3PD activities in thyroidectomized rats, 

showing that the enzymes responded to thyroid hormone stimulation in a normal 

manner. The stimulatory effect of saturating doses of T3 on ME and LG3PD was 

reduced by HCB. The results presented herein unequivocally show that brown 

adipose tissue is a specific target in HCB-induced toxicity, which in turn involves 

severe alterations in the regulation of BAT lipogenesis. 

Alvarez-Pedrerol, M., N. Ribas-Fito, et al. (2008). "Effects of PCBs, p,p'-DDT, p,p'-DDE, 

HCB and beta-HCH on thyroid function in preschool children." Occup Environ Med

65(7): 452-7. 

 OBJECTIVE: Several studies have shown that some organochlorine compounds 

(OCs) can interfere with the thyroid system. As thyroid hormones (THs) are 

essential for normal brain development, it is important to study the association 

between THs and OCs during pregnancy and childhood. We have evaluated the 

relationship between thyroid function and OCs in preschool children. METHODS: 

Children from a general population birth cohort in Menorca (n = 259), Spain were 

assessed at the age of 4 years. Concentrations of THs (free T4 and total T3), 

thyrotropin (TSH) and a range of OCs were measured in peripheral blood. 

RESULTS: Blood levels of dichlorodiphenyl trichloroethane (p,p'-DDT), betahexachlorocylcohexane (beta-HCH), polychlorinated biphenyls (congeners PCB138, PCB-153 and PCB-118) were related to lower total T3 levels (p<0.05). In 

addition, free T4 was inversely associated with PCB-118, while no relationship 

was found between TSH and any of the measured OCs. CONCLUSIONS: This 

study suggests that even at background levels of exposure, OCs may affect the 

thyroid system, particularly total T3 levels. 
96

Andrews, J. E. a. C., K. D. (1986). "Hexachlorobenzene-induced renal maldevelopment 

in CD-1 mice and CD rats 

" IARC Sci Publ

77(381-91 

). 

 

Arcaro, K. F., J. W. Staudenmayer, et al. (2005). "Analysis Of Environmental Pollutants 

In Breast Milk And DNA Damage In Breast-Milk Cells." Toxicol Sci 84(1-S): 263. 

 It has been hypothesized that increased genetic instability, resulting from 

exposure to environmental toxicants, may increase an individual’s risk of 

developing breast cancer. It is important, therefore, to determine the extent to 

which exposure to environmental pollutants results in increased genetic 

instability. We have addressed this issue by examining both the levels of 

pollutants in breast milk, and DNA damage in breast-milk cells. Breast milk 

samples collected from twenty-one women living in the Springfield, MA and 

Albany, NY areas, were analyzed for levels of 101 polychlorinated biphenyl 

(PCB) congeners and 8 organochlorine pesticides/metabolites 

(Hexachlorobenzene, oxychlordane, pp’-DDE, op’-DDE, - Chlodane, transNonachlor, Mirex, and cis-Nonachlor). Cells in the milk were separated by 

centrifugation within one hour of milk collection, and DNA damage was assessed 

using the single cell gel electrophoresis assay. Each woman completed a 

questionnaire providing information on her age, age of her nursing child, her 

cigarette smoking history and current exposure, and number of children she 

previously nursed. Mother’s age ranged from 21 to 40 years, and child’s age 

ranged from 3.5 to 67 weeks. PCBs and pesticides were detected in all 21 milk 

samples. Among women who had not previously nursed a child (n = 15), there 

were significant positive correlations between age of the woman and 1) total PCB 

level, 2) Hexachlorobenzene level, and 3) pp’-DDE level. None of these 

correlations were significant in women who had previously nursed a child (n = 6). 

All samples contained cells with detectable levels of DNA damage, but no 

significant correlations between levels of pollutants and DNA damage were 

observed. 

Ashley, A., M. Lohitnavy, et al. (2004). "Isolation And Enrichment Of Preneoplastic 

Hepatocytes During Malignant Cell Transformation." Toxicologist 78(1-S): 225-6. 

 We modified Ito’s medium-term liver foci bioassay by incorporating time-course 

sacrifices to study pharmacokinetics/pharmacodynamics related to the 

initiationpromotion process. In our earlier clonal growth modeling studies on a 

series of chlorobenzenes, the probable existence of two cell types in glutathioneS-trasferase (GSTP) foci became apparent. As suggested by other researchers, 

these two cell types are either susceptible or resistant to mitoinhibitory effects as 

a response to external chemical insults, and those resistant to mitoinhibitory 

effect would have a growth advantage serving as basis for malignant 

transformation. Thus, as preneoplastic GSTP foci form, isolation of GSTP 

positive (GSTP+) cells from liver across time allows capturing changing 
97

characteristics of an emerging malignant population. This study describes an 

attempt to isolate primary GSTP+ hepatocytes using Ito’s bioassay protocol with 

diethylnitrosamine (DEN) as an initiating agent and a 2/3 partial hepatectomy 

with concomitant dosing of hexachlorobenzene (HCB; 28.4 mg/kg/day) with and 

without coexposure to PCB 126 (9.8 μg/kg/day) as promoting agents. Male F344 

rats were sacrificed at 20, 24, 28, 47 and 56 days, and 3, 6, and 9 months 

following DEN injection. By day 56, a significant increase in liver weight was 

observed in rats coexposed to HCB and PCB 126. Either primary hepatocytes or 

liver sections were taken to analyze formation of GSTP+ foci. By treating cell 

suspension and/or culture with ethacrynic acid (EA) (Stenius et al., 

Carcinogenesis 15:1561-1566, 1994), GSTP+ hepatocytes were enriched by 

inducing toxicity to non-GSTP+ cells. In so doing, progressively more malignant 

cell populations can be subjected to cell cycle kinetic studies, genomic analyses, 

and clonal growth modeling to aid our insight into the carcinogenic process. 

Audet, R. M., S. Girard, et al. (2004). "Long Term Exposure Of Human Mammary 

Epithelial Cells To Hexachlorobenzene (HCB) Induces A Procarcinogenic Phenotype." 

Toxicologist 78(1-S): 339. 

 Organochlorines are environmental lipophilic contaminants found in breast tissue 

with a debated role in breast cancer development (BCD). HCB, a widespread 

organochlorine in the environment, is virtually present in 100% of North American 

women. Epidemiological studies indicated that some breast cancer patients have 

higher HCB levels. We observed that long term exposure of human mammary 

epithelial cells to HCB increases the phosphorylation of c-erbB2 (neu). Cells with 

such epigenetic alterations can be considered procarcinogenic taking into 

account the bad prognostic role of c-erbB2 in BCD. In order to further evaluate 

the potential of HCB in causing epigenetic changes akin to a procarcinogenic 

phenotype, cultures of a non-tumorigenic human mammary epithelial cell line, 

MCF10- A, were chronically exposed to 20 μM HCB (0.1% in DMSO) or to 

DMSO alone. Following approximately 25 passages of continuous exposure to 

HCB, an increase in proliferation was observed. These cells showed an increase 

in the phosphorylation of the integrin-linked kinase (ILK), with a decrease in 

Akt/PKB levels. ECadherin, an important cell adhesion molecule, was also 

decreased. Control cells sub-cultured on Matrigel® showed a distinctive 

branching pattern after 24h. However, HCB-exposed cells exhibited a rounded 

shape with minimal cellular contacts. This is suggestive of a decrease in 

intercellular communication and cell adhesion ; the latter is supported by the 

decrease in E-Cadherin expression in these cells. Moreover, after 10 d in culture 

HCB-exposed cells migrated differently into the Matrigel® layer as compared to 

controls. Overall, data suggest that HCB induces a procarcinogenic phenotype 

characterized by reduced intercellular communication and that this may result 

from overactivation of ILK, known to be a down-stream target of c-erbB2, leading 

to down-regulation of Akt, which controls E-cadherin expression. This work 

brings biological plausibility to the involvement of environmental contaminants in 

BCD. 
98

Billi de Catabbi, S. C., C. P. Setton-Advruj, et al. (2000). "Hexachlorobenzene-induced 

alterations on neutral and acidic sphingomyelinases and serine palmitoyltransferase 

activities. A time course study in two strains of rats." Toxicology 149(2-3): 89-100. 

 Hexachlorobenzene (HCB) induces porphyria both in humans and rodents, and 

hepatocarcinoma in rodents. In a previous work we observed that HCB produces 

a continuous decrease in hepatic sphingomyelin (SM) content in Wistar rats. A 

distinguishing characteristic of sphingolipids breakdown products is their 

participation in anti-proliferative and apoptotic processes and in the suppression 

of oncogenesis. As a first step to elucidate the role of SM decrease in the 

hepatotoxicity induced by HCB, the present study evaluates the metabolic 

causes of the continuous decrease in hepatic SM content observed in Wistar rats 

with HCB intoxication, and its relation with porphyria development. For this 

purpose, the time-course (3, 7, 15, 21 and 28 days) of the effects of HCB on 

hepatic SM levels and on some of the enzymes of SM synthesis (serine 

palmitoyltransferase, SPT) and catabolism (sphingomyelinases, SMases) was 

followed, using two strains of rats differing in their susceptibility to acquire 

porphyria: Chbb THOM (low) and Wistar (high). HCB (1 g kg(-1) b.w. per day) 

was administered by gastric intubation as an aqueous suspension. After 5 days 

of HCB treatment, animals were allowed a 2-day recovery period without HCB 

administration. Two phases in the HCB-induced damages to sphingolipid 

metabolism were observed. The first stage (7 days of treatment), common to 

both strains of rats, was characterized by a decrease in hepatic SM levels (17-

25%) and in SPT activity (50-43%), while strain differences were found for the 

later stage. In Chbb THOM rats, hepatic SM content was restored to normal 

values concomitantly with an increase in SPT activity (44%, at day 28), and 

without any increase in SM catabolism. In addition, the level of the other 

phospholipids was not altered. In Wistar rats, hepatic SM levels decreased 

continuously throughout the experiment, accompanied by increases in SPT, 

acidic sphingomyelinase (A-SMase) and neutral sphingomyelinase (N-SMase) 

activities (86, 28.5 and 78% increase, respectively). A role for glutathione (GSH) 

in the interstrain differences or a direct effect of HCB on SM metabolism was not 

found. The present study: (a) demonstrates that N-SMase, A-SMase, and SPT 

are some of the enzymes that play a role in the HCB-induced decrease of 

hepatic SM content; (b) finds that HCB-induced alterations of SM metabolism do 

not correlate with HCB-induced accumulation of hepatic porphyrins; and (c) 

proposes a link between HCB-induced alterations in phospholipid pattern and in 

SM metabolism. The increased SM hydrolysis produced as a consequence of 

SMases induction could be regarded as a cellular response to liver injury elicited 

by HCB, perhaps acting through the activation of SM signal transduction pathway 

delaying the proliferative processes observed after long-term treatment with HCB 

in some rodent species. However, such protective mechanism appears to be 

strain-dependent. 

Bilrha, H., R. Roy, et al. (2003). "In vitro activation of cord blood mononuclear cells and 

cytokine production in a remote coastal population exposed to organochlorines and 

methyl mercury." Environmental Health Perspectives 111(16): 1952-7. 
99

 Remote coastal populations that rely on seafood for subsistence often receive 

unusually high doses of organochlorines and methyl mercury. 

Immunosuppression resulting from prenatal exposure to organochlorines has 

been reported in wildlife species and humans. In this study, we assessed 

lymphocyte activation and associated cytokine secretion in 47 newborns from a 

remote maritime population living on the Mid and Lower North Shore regions of 

the St. Lawrence River (Quebec, Canada; subsistence fishing group) and 65 

newborns from nearby urban settings (reference group). Cord blood samples 

were collected for organochlorine and mercury analyses and also to isolate cord 

blood mononuclear cells (CBMCs) for the in vitro assessment of cytokine 

production and expression of surface markers after mitogenic stimulation 

(CD4(+)CD45RO(+), CD8(+)CD45RO(+), CD3(+)CD25(+), and CD8(+)HLADR(+)). Blood mercury and plasma concentrations of polychlorinated biphenyls 

(PCBs), 1,1-dichloro-2,2-bis(4-chlorophenyl)ethylene (p,p'-DDE), and 

hexachlorobenzene (HCB) were significantly higher in the subsistence fishing 

group than in the reference group (p < 0.001). No difference was observed 

between the two groups regarding subsets of lymphocytes showing markers of 

activation. In vitro secretion of cytokines by CBMCs after mitogenic stimulation 

was lower in the subsistence fishing group than in the reference group (p < 0.05). 

Moreover, we found an inverse correlation between tumor necrosis factor-alpha 

(TNF-alpha) secretion and plasma PCB, p,p'-DDE, and HCB concentrations (p < 

0.05). Our data support a negative association between TNF-alpha secretion by 

CBMCs and prenatal organochlorine exposure. If the relationship between 

organochlorine and TNF-alpha secretion is causal, it would suggest a role for this 

important proinflammatory cytokine in mediating organochlorine-induced 

immunotoxicity in infants developmentally exposed to these compounds. 

Bishop, J. B. (2002). Molecular Detection Of Chromosome Damage In Rodent Germ. 

Crisp Data Base National Institutes of Health. 

 Infertility and other untoward reproductive and developmental outcomes, such as 

spontaneous abortion, fetal and neonatal death, birth defects, and genetic 

susceptibilities to cancer and other diseases, are associated with genetic 

damage occurring in mammalian germ cells. This Project employs molecular 

biomarkers in the identification and characterization of chemicals in our 

environment that are responsible for such germ cell damage. Specifically, 

fluorescence in situ hybridization (FISH) with chromosome specific DNA markers 

are used to detect structural and numerical chromosome damage in sperm and 

early embryonic cells of rodents. These rodent sperm-FISH assays, which 

provide parallel models of similar sperm-FISH assays in humans, are being used 

for evaluating the aneugenic and clastogenic potential of environmental 

chemicals tested in NTP bioassays, as well as for addressing questions about 

dose response, differential stage sensitivity, the relationship of defects seen in 

sperm to those transmitted to the early embryo, and other important issues 

related to health-risks which cannot be addressed in human studies. During this 

past year, frozen samples of rat sperm were obtained from NTP Reproductive 

Assessment by Continuous Breeding (RACB) studies on hexachlorobenzene and 
100

tetrachloroazobenzeneare, and frozen samples of mouse sperm were obtained 

from an RACB study of AZT/ddI and from micronucleus studies of benzene, 

diazoaminobenzene, analine and cyclophosphamide. 

Blinova, V. G., D. A. Dobrynin, et al. (2003). "Prediction of chronic toxicity indexes of 

substituted benzenes using the John Stuart Mill (JSM) method for automatic generation 

of hypotheses." Nauchno-Tekhnicheskaya Informatsiya, Seriya 2: Informatsionnye 

Protsessy i Sistemy(4): 1-4. 

 Effects of substituents in the benzene ring were examd. on the chronic toxicity by 

John Stuart Mill method for automatic generation of hypotheses and quantumchem. calcns. Structural fragments responsible for high, moderate and low 

toxicity to substituted benzene derivs. were identified without chronic exptl. 

studies on the lab. animals. 

Bloksma, N. (2004). "Effects of the T cell inhibitor, cyclosporin A (CsA), on 

hexachlorobenzene (HCB)-induced immunopathology in the Brown Norway (BN) rat." 

Toxicol Sci 81(1): 253; author reply 254-5. 

 

Bloom, M. S., J. M. Weiner, et al. (2003). "Exploring associations between serum levels 

of select organochlorines and thyroxine in a sample of New York state sportsmen: the 

New York State Angler Cohort Study." Environ Res 93(1): 52-66. 

 This preliminary study investigated associations between environmental 

organochlorine compounds and thyroid function in a sample of 66 sportsmen 

selected from among participants in the New York State Angler Cohort Study. A 

cross-sectional design was employed with the primary goal of the analysis being 

the generation of specific testable hypotheses. Blood samples were analyzed for 

compounds based on a priori identified literature-cited evidence of thyroid 

disruption. These included hexachlorobenzene and polychlorinated biphenyl 

congeners 19, 28, 47, 118, 153, 169, 180, 183, and 187. Time of sample 

collection, serum triglycerides, cholesterol, high- and low-density lipoproteins, 

age, body mass index, and cigarette smoking were considered for each 

participant. Potential associations between organochlorine compounds and 

serum total thyroxine, controlling for potential confounders, were examined using 

multivariable linear regression models. The models reported consisted of all 

variates being entered ("full" model, R2=0.380, P=0.136) and stepwise selection 

of variates ("reduced" models, alpha=0.15) using the criterion of maximum partial 

correlation at each step. Several procedures were considered to address 

contaminant data below the limit of detection in the reduced models with no 

change in selected predictors. Hexachlorobenzene (beta=-0.113) and age 

(beta=0.007) were selected as predictors of serum T4 in the reduced models 

(R2=0.083, P=0.065). Power analysis suggested that by doubling the sample 

size the existing results would be statistically significant with a type I error of 0.05 

and a power of 0.80. These findings are important in the design of a new specific 

study of thyroid function and environmental contaminants. 
101

Charbonneau, M., I. Plante, et al. (2005). "Modulation Of Cell-Cell Interactions By 

Epigenetic Hepatocarcinogens." Toxicol Sci 84(1-S): 336-7. 

 Mechanisms of epigenetic carcinogenesis involve disruption of cell or tissue 

homeostasis, such as cell-cell interactions mediated by various types of 

junctions. Gap junctions are formed by channels that allow direct communication 

between cells (GJIC), while adhering junctions maintain tissue integrity by linking 

cells together. Gap and adhering junctions are physically and functionally 

interrelated membrane structures. Connexins and cadherins are key proteins in 

gap and adhering junctions, respectively. While the effects of hepatocarcinogens 

on these proteins in rodent livers are well documented and will be discussed in 

this presentation, the pathways involved in their regulation are less understood. 

Consequently, a particular emphasis will be made on hexachlorobenzene (HCB), 

an important environmental contaminant, that modulates intracellular pathway 

involved in cell junctions. HCB causes liver tumor formation and down-regulation 

of connexins and E-cadherin in the liver of female but not male rats. A sexual 

dimorphism in the activation of the ILK pathway is believed to be responsible for 

these down-regulations ; inactivation of GSK3-beta and nuclear translocation of 

both Akt and beta-catenin are important events. In vitro studies, using specific 

inhibitors and overexpression systems confirmed not only the role of ILK pathway 

in cell-cell interactions, but also the functional interrelationships between 

connexins and cadherins. Down-regulation of proteins forming gap and adhering 

junctions allow initiated cells to escape control from neighboring cells, thus 

promoting their clonal expansion. The importance of such mechanisms in 

carcinogenesis is illustrated by the fact that human tumors of various origins 

show low levels of immunoreactive connexins and cadherins. Moreover, studies 

suggest that lost of cell-cell interaction proteins is an early event in the 

carcinogenesis process. Overall, data support the contention that gap and 

adhering junctions are at the basis of important cell-cell interactions disruptuted 

in epigenetic hepatocarcinogenesis. 

Chaufan, G., M. M. Corvi, et al. (2005). "Abnormal kinetic behavior of uroporphyrinogen 

decarboxylase obtained from rats with hexachlorobenzene-induced porphyria." J 

Biochem Mol Toxicol 19(1): 19-24. 

 Uroporphyrinogen decarboxylase is an essential enzyme in all organisms and 

functions in the heme biosynthetic pathway, catalyzing the decarboxylation of the 

four acetate groups of uroporphyrinogen to form coproporphyrinogen. This work 

examines whether the four sequential decarboxylations occur at the same active 

site, and explores whether hexachlorobenzene-induced porphyria affects the 

behavior of the enzyme. For this purpose, kinetic competition studies were done 

with mixtures of uroporphyrinogen III and pentacarboxyporphyrinogen III. With 

the enzyme from normal rats, a constant velocity was obtained with all the 

mixtures, indicating that uroporphyrinogen and pentacarboxy-porphyrinogen 

react at the same active site, i.e. the first and fourth decarboxylations occur at the 

same site. In contrast, in experiments with enzyme from rats with 

hexachlorobenzene-induced porphyria, the total rate for mixtures was always 

lower than the reference rate; and a curve with a deep minimum was obtained, 
102

indicating that the two reactions occur at functionally different sites, but with 

cross-inhibition. This suggests that the modifications induced in the enzyme by 

hexachlorobenzene cause the two active sites to become nonequivalent and 

functionally different. The question is discussed how the hexachlorobenzene 

treatment may produce this abnormal kinetic behavior, and alternative 

hypotheses are considered. 

Chaufan, G., M. C. Rios de Molina, et al. (2001). "How does hexachlorobenzene 

treatment affect liver uroporphyrinogen decarboxylase?" Int J Biochem Cell Biol 33(6): 

621-30. 

 The aims of the present work were: (1) to investigate whether the strong 

decrease of liver uroporphyrinogen decarboxylase (UroD) activity observed in 

experimental porphyria cutanea tarda is due to alteration of the enzymatic protein 

and (2) to improve the knowledge about the normal liver enzyme. With these 

purposes, several physicochemical studies for enzymatic characterization were 

carried out comparatively on the 12-fold purified liver enzyme of both normal and 

hexachlorobenzene porphyric rat. The study shows that the enzyme from 

porphyric rats has a higher activation energy, lower reactivity index and lower 

optimum pH than the normal one. In addition, it did not reach the Vmax at any of 

the substrate concentrations assayed (up to 28 microM uroporphyrinogen III), 

while the normal enzyme reached the plateau around 14 microM. The porphyric 

enzyme appears to be more protected than the normal against the inhibitory 

action of several metals, particularly Cu2+ and Pb2+, and against thermal 

inactivation. Zn2+ did not affect enzymatic activity, whereas Cu2+, Hg2+, Fe2+, 

Pb2+, and Cd2+ lowered the activities of both normal and porphyric enzyme in a 

dose-related way. It was also observed that the larger the atomic radius in its 

hydrated state, the lower the effect of the metal. Neither glutathione nor 

dithiothreitol significantly altered enzymatic activity in the range of concentrations 

assayed. beta-Mercaptoethanol had diverse effects, as regards both the 

concentration assayed and the enzymatic sample used. Assays with cystine 

showed a dual behaviour of both normal and porphyric enzymatic activity. 

Western blots for both preparations revealed a single band (65 kDa) with a 

similar intensity.This study show that hexachlorobenzene treatment modifies the 

physicochemical properties of liver UroD leading to a sharp decrease of its 

activity, without affecting its antigenic reactivity probably as a consequence of 

changes at the conformational level promoted by the binding of its reported 

inhibitor. 

Chipman, J. K. (2004). "Biomarkers For Nongenotoxic Carcinogens." Toxicologist 78(1-

S): 318. 

 Nongenotoxic carcinogens are thought to act via disturbance of the balance 

between cell death and cell proliferation, leading to clonal expansion of preneoplastic cells. The precise mechanisms that can lead to this disruption are 

varied and this complicates the ability to use short term tests to predict 

nongenotoxic carcinogenic potential. Biomarkers indicative of a chemical’s ability 

to influence cell survival and proliferative advantage are important in recognising 
103

this activity in rodent studies. This may be helpful in the interpretation of rodent 

carcinogenicity that may occur in the absence of genotoxicity, and to be able to 

extrapolate to human risk assessment. The dose response relationships and 

species differences in response are critical parameters in this process. 

Biomarkers can be relatively non-specific relating to apoptosis and proliferation in 

target organs but may be optimised and more refined by interrogation of the 

modulation of specific molecules involved in key signalling processes. Both the 

modulation of connexin-mediated gap junction intercellular communication and 

the status of DNA methylation have shown particular promise as relevant 

biomarkers in conjunction with functional studies as above. For example, the 

rodent non-genotoxic hepatocarcinogens Wy-14, 643, 2, 3, 7, 8-

tetrachlorodibenzo- p-dioxin, methapyrilene and hexachlorobenzene and the rat 

kidney carcinogens chloroform and p-dichlorobenzene all disrupt gap junction 

plaques containing connexin 32 in the target organs in the absence of toxicity 

and they all cause proliferation at the carcinogenic dose. Furthermore, 

compounds that deplete glutathione such as chloroform and carbon tetrachloride 

have the ability to induce a secondary genotoxicity through oxidative stress but 

only at high concentrations. Transcriptomic analyses are leading to the 

identification of further novel potential biomarkers associated with species- and 

tissue- specific nongenotoxic carcinogenesis such as the induction of hepatic 

fibrinogen / angiopoietin-related protein by monoethylhexylphthalate. 

Cochon, A. C., N. Gonzalez, et al. (2002). "Effects of the porphyrinogenic compounds 

hexachlorobenzene and 3,5- diethoxycarbonyl-1,4-dihydrocollidine on polyamine 

metabolism." Toxicology 176(3): 209-19. 

 The naturally occurring polyamines--putrescine, spermidine and spermine- -are 

organic cations present in all living cells and essential for cell growth and 

differentiation. The aim of the present study was to extend the investigations on 

the effects of porphyrinogenic compounds on polyamine metabolism. This was 

achieved by studying putrescine, spermidine and spermine levels in a model of 

acute porphyria, i.e. 3,5- diethoxycarbonyl-1,4-dihydrocollidine (DDC)-induced 

porphyria, and in a model of non-acute porphyria, i.e. hexachlorobenzene (HCB)-

induced porphyria. HCB administration to female Wistar rats for 7, 14, 21, 28 and 

56 days did not alter polyamine levels in liver, even though rats presented clear 

signs of HCB-induced porphyria. In contrast to HCB, DDC treatment resulted in a 

remarkable increase in putrescine levels in the liver of female and male SpragueDawley rats. This increase was due, at least in part, to ornithine decarboxylase 

(ODC) activation. DDC induction of putrescine levels did not show organ 

specificity, since it could also be seen in adrenal gland. Interestingly, the 

deregulation of polyamine biosynthesis occurred concomitantly with the 

deregulation of the heme biosynthetic pathway. In addition to porphyria, it is 

known that DDC intoxication affects several proteins of the hepatocyte 

cytoskeleton. It is suggested that DDC-induced increase in ODC activity and 

putrescine levels may be an early event contributing to alter the cytoskeleton. 
104

Cochon, A. C., L. C. San Martin de Viale, et al. (1999). "Effects of hexachlorobenzene 

on phospholipid and porphyrin metabolism in Harderian glands: a time-course study in 

two strains of rats." Toxicol Lett 106(2-3): 129-36. 

 Hexachlorobenzene, one of the most persistent environmental pollutants, 

induces uroporphyria and phospholipid alterations in rat liver. Harderian glands 

produce a secretion that is rich in lipids and accumulate large amounts of 

protoporphyrin. The aim of the present study was to determine if 

hexachlorobenzene administration to rats affects phospholipid and porphyrin 

metabolisms in Harderian glands and if these effects are strain dependent. For 

this purpose, a time-course study (2, 3 and 4 weeks of hexachlorobenzene 

treatment) of phospholipid pattern and porphyrin content was performed 

comparatively in two strains of rats (Wistar and Chbb THOM) which differ in their 

susceptibility to develop HCB-induced porphyria. Hexachlorobenzene produced 

decreases in several phospholipid contents, but no changes in 

phosphatidylcholine levels. While the sphingomyelin/phosphatidylcholine molar 

ratio remained essentially constant until the third week in Chbb THOM rats, it 

showed a constant drop in Wistar rats, suggesting a more pronounced alteration 

of membrane fluidity in the later strain. In regard to porphyrin metabolism, Wistar 

rats showed an increase in the porphyrin content of the gland, while Chbb THOM 

animals showed a decrease. The study revealed that not only are the normal 

parameters of phospholipid and porphyrin metabolism in rat Harderian glands 

strain dependent, but the response to hexachlorobenzene is also. 

Cochon, A. C., L. C. San Martin de Viale, et al. (2001). "Phospholipid alterations elicited 

by hexachlorobenzene in rat brain are strain-dependent and porphyria-independent." 

Comp Biochem Physiol C Toxicol Pharmacol 130(2): 199-207. 

 Hexachlorobenzene (HCB) alters phospholipid and heme metabolisms in the 

liver and Harderian gland. The effects of HCB on phospholipid metabolism, in an 

organ considered to be non-responsive to its porphyrinogenic effects, remain to 

be studied. Therefore, as the brain is an organ with this feature, this paper 

analyzes the effects of HCB on brain phospholipid composition in order to 

investigate if there is any relationship between HCB-induced porphyrin 

metabolism disruption and phospholipid alterations. For this purpose, a timecourse study of HCB effects on brain phospholipids was performed in two strains 

of rats differing in their susceptibility to acquire hepatic porphyria: Chbb THOM 

(low); and Wistar (high). This paper shows for the first time that rat brain 

phospholipids are affected by HCB exposure. Comparative studies show that 

HCB-induced disturbances in brain phospholipid patterns are time and straindependent. Thus, whereas major phospholipids, phosphatidylcholine and 

phosphatidylethanolamine were more altered in Wistar rats, minor phospholipids, 

phosphatidylinositol and phosphatidylserine were more affected in Chbb THOM 

rats. HCB intoxication led to a sphingomyelin/phosphatidylcholine molar ratio 

lower than the normal, in both strains. As was expected, brain porphyrin content 

was not altered by HCB intoxication in either strain. It can be concluded that HCB 

is able to alter brain phospholipid metabolism in a strain-dependent fashion, and 

in the absence of alterations in brain heme metabolism. In addition, HCB-induced 
105

disturbances in brain phospholipids were not related to the degree of hepatic 

porphyria achieved by the rats. 

Codru, N., M. J. Schymura, et al. (2007). "Diabetes in relation to serum levels of 

polychlorinated biphenyls and chlorinated pesticides in adult Native Americans." Environ 

Health Perspect 115(10): 1442-7. 

 BACKGROUND: Recent research suggests that diabetes, a condition whose 

incidence is increasing, is associated with exposure to polychlorinated biphenyls 

(PCBs) and chlorinated pesticides. OBJECTIVES: We investigated the potential 

association between diabetes and serum levels of PCBs, 

dichlorodiphenyldichloroethylene (DDE), hexachlorobenzene (HCB), and mirex in 

a cross-sectional study of an adult Native-American (Mohawk) population. 

METHODS: Through a standardized questionnaire we collected demographic, 

medical, and lifestyle information from 352 adults, > or =30 years of age. We 

collected fasting serum samples that were analyzed for 101 PCB congeners, 

DDE, HCB, and mirex along with fasting glucose, triglycerides, and cholesterol. 

Participants who had fasting-glucose values > 125 mg/dL and/or who were taking 

antidiabetic medication were defined as persons with diabetes. We conducted 

logistic regression to assess the potential association between organochlorine 

serum levels and diabetes, while controlling for the potential confounding 

variables of age, body mass index (BMI), smoking, sex, and serum lipid levels. 

Organochlorine serum levels were categorized in tertiles, and the lowest tertile 

was used as the reference category. RESULTS: The prevalence of diabetes was 

20.2%. The odds ratio (OR) of having diabetes for participants in the highest 

tertile of total PCB concentration compared with the lowest tertile was 3.9 (95% 

confidence interval, 1.5-10.6). The corresponding ORs for DDE and HCB were 

even higher. Elevated serum mirex was not associated with diabetes. After 

adjustment for other analytes, the OR for HCB remained significant, whereas 

ORs for PCBs and DDE remained elevated but not statistically significant. In 

contrast, after adjustment for other analytes, the OR for mirex became 

statistically significant and indicated an inverse association. CONCLUSIONS: In 

this study of adult Native Americans, elevated serum PCBs, DDE, and HCB were 

positively associated with diabetes after controlling for potential confounders, 

whereas a negative association was observed for mirex. 

Cote, S., P. Ayotte, et al. (2006). "Plasma organochlorine concentrations and bone 

ultrasound measurements: a cross-sectional study in peri-and postmenopausal Inuit 

women from Greenland." Environmental health : a global access science source 

[electronic resource]. 5: 33. 

 BACKGROUND: Inuit women are highly exposed through their traditional 

seafood based diet to organochlorine compounds, some of them displaying 

endocrine disrupting properties. We hypothesized that this exposure might be 

related to bone characteristics that are altered in osteoporosis, because hormone 

deficiency is a known risk factor for the disease. METHODS: We measured 

quantitative ultrasound parameters (QUS) at the right calcaneum of 153 peri- and 

postmenopausal Inuit women (49-64 year old) from Nuuk, Greenland, and 
106

investigated the relation between these parameters and plasma organochlorine 

concentrations. We used high-resolution gas chromatography with electron 

capture detection to analyze plasma samples for 14 polychlorinated biphenyls 

(PCB) congeners and 11 chlorinated pesticides and metabolites. We analysed 

morning urine samples for cadmium, a potential confounder, by atomic 

absorption spectrometry. We used a validated questionnaire to document dietary 

and lifestyle habits as well as reproductive and medical histories. RESULTS: 

Concentrations of PCB 153, a surrogate of exposure to most organochlorines 

present in plasma samples, were inversely correlated to QUS parameters in 

univariate analyses (p < 0.001). However, PCB 153 concentrations were not 

associated with QUS values in multivariate analyses that comprised potential 

confounding factors such as age, body weight, former oral contraceptive use and 

current hormone replacement therapy (HRT) use, which were all significant 

predictors of bone stiffness (total R2 = 0.39; p < 0.001). CONCLUSION: Overall 

we found little evidence that organochlorines exposure is related to osteoporosis 

in Greenlandic Inuit women, but the hypothesis that exposure to dioxin-like 

compounds might be linked to decreased bone quality and osteoporosis 

deserves further attention. 

De Catabbi, S. C. B., C. Aldonatti, et al. (2000). "Heme metabolism after discontinued 

hexachlorobenzene administration in rats: possible irreversible changes and biomarker 

for hexachlorobenzene persistence." Comp Biochem Physiol C Toxicol Pharmacol

127(2): 165-75. 

 The aim of the present study was to determine whether short-term administration 

of hexachlorobenzene (HCB) (1 g/kg body wt., suspended in water, 5 

days/week), could cause and maintain marked porphyria in the absence of the 

exogenous drug, and whether porphyria parameters can be useful as biomarkers 

of HCB persistence in rats. Hepatic uroporphyrinogen decarboxylase activity, its 

inhibitor formation, porphyrin content and composition were studied in Wistar rats 

treated with the fungicide for 1, 2, 3, or 4 weeks and then withdrawn for a 20- 

week period. The time course of urinary porphyrin excretion was studied for 7 

weeks either by continuous treatment for the entire period, or a 1-week HCB 

administration. The degree of porphyria achieved by rats after 20 weeks of 

suspended HCB administration was severe, independent of the length of the 

treatment, and even higher than that observed in animals analysed immediately 

at the end of each treatment. Rats treated with HCB for 1 week showed a modest 

decrease in uroporphyrinogen decarboxylase and low inhibitor formation, and 

exhibited a greater enzyme inhibition, inhibitor formation, hepatic porphyrin 

accumulation, and an altered pattern of porphyrin composition in the absence of 

the exogenous drug. Independent of the treatment, urinary porphyrins rose after 

a delay of 5 weeks. Substantial amounts of HCB were still found in fat of rats 

treated with HCB for 1 week, after a withdrawal period of 20 weeks. These 

results suggest that the high persistence of HCB in tissues acts as a continuous 

source of the xenobiotic, and stimulus for heme biosynthesis derangement. The 

alterations induced by HCB within 1 week of treatment could be regarded as an 

initial trigger for irreversible damage on heme metabolism. Thus, abnormalities in 
107

heme biosynthesis can be considered effective markers of HCB persistence in 

rats or of irreversible HCB-induced damage. Taking into account the delayed and 

enhanced metabolic effects of HCB, it is advisable that porphyria parameters 

should be evaluated not only immediately after exposure, but also some time 

afterwards, especially in susceptible and occupationally-exposed populations. 

De Coster, S., G. Koppen, et al. (2008). "Pollutant effects on genotoxic parameters and 

tumor-associated protein levels in adults: a cross sectional study." Environ Health 7: 26. 

 BACKGROUND: This study intended to investigate whether residence in areas 

polluted by heavy industry, waste incineration, a high density of traffic and 

housing or intensive use of pesticides, could contribute to the high incidence of 

cancer observed in Flanders. METHODS: Subjects were 1583 residents aged 

50-65 from 9 areas with different types of pollution. Cadmium, lead, p,p'-DDE, 

hexachlorobenzene, PCBs and dioxin-like activity (Calux test) were measured in 

blood, and cadmium, t,t'-muconic acid and 1-hydroxypyrene in urine. Effect 

biomarkers were prostate specific antigen, carcinoembryonic antigen and p53 

protein serum levels, number of micronuclei per 1000 binucleated peripheral 

blood cells, DNA damage (comet assay) in peripheral blood cells and 8-hydroxydeoxyguanosine in urine. Confounding factors were taken into account. 

RESULTS: Overall significant differences between areas were found for 

carcinoembryonic antigen, micronuclei, 8-hydroxy-deoxyguanosine and DNA 

damage. Compared to a rural area with mainly fruit production, effect biomarkers 

were often significantly elevated around waste incinerators, in the cities of 

Antwerp and Ghent, in industrial areas and also in other rural areas. Within an 

industrial area DNA strand break levels were almost three times higher close to 

industrial installations than 5 kilometres upwind of the main industrial installations 

(p < 0.0001). Positive exposure-effect relationships were found for 

carcinoembryonic antigen (urinary cadmium, t,t'-muconic acid, 1-hydroxypyrene 

and blood lead), micronuclei (PCB118), DNA damage (PCB118) and 8-hydroxydeoxyguanosine (t,t'-muconic acid, 1-hydroxypyrene). Also, we found significant 

associations between values of PSA above the p90 and higher values of urinary 

cadmium, between values of p53 above the p90 and higher serum levels of p,p'-

DDE, hexachlorobenzene and marker PCBs (PCB 138, 153 and 180) and 

between serum levels of p,p'-DDE above the p90 and higher serum values of 

carcinoembryonic antigen. Significant associations were also found between 

effect biomarkers and occupational or lifestyle parameters. CONCLUSION: 

Levels of internal exposure, and residence near waste incinerators, in cities, or 

close to important industries, but not in areas with intensive use of pesticides, 

showed positive correlations with biomarkers associated with carcinogenesis and 

thus probably contribute to risk of cancer. In some rural areas, the levels of these 

biomarkers were not lower than in the rest of Flanders. 

Edelbrock, M. A., M. J. Fernstrom, et al. (2005). "p,p'-DDE and HCB: Mechanisms of 

toxicity to fetal and embryonic mammalian cells." Endocrine Disruptors (2nd Edition): 

101-133. 
108

 A review discusses both known and hypothetical mechanisms of toxicity of p,p'-

DDE and hexachlorobenzene (HCB). It also describes specific genotoxic and 

cytotoxic effects of these chems. on immature cells at low environmental 

concns., both sep. and as a mixt. 

Ennaceur, S., D. Ridha, et al. (2008). "Genotoxicity of the organochlorine pesticides 1,1-

dichloro-2,2- bis(p-chlorophenyl)ethylene (DDE) and hexachlorobenzene (HCB) in 

cultured human lymphocytes." Chemosphere 71(7): 1335-9. 

 The possible genotoxic potential of 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene 

(DDE), which is a metabolite of dichlorobiphenyltrichloroetane (DDT), and 

hexachlorobenzene (HCB), which are organochlorine pesticides have been 

evaluated in vitro by using human lymphocytes as test system. Genetic damage 

was determined by scoring the frequency of micronuclei (MN) in primary 

lymphocyte cultures obtained from different donors. The results indicated that, 

under the experimental conditions used, the DDT metabolite DDE was able to 

induce significant increases in the frequency of micronucleated cells, which 

indicate a certain clastogenic and/or aneugenic potential. DDE was tested in the 

range of 10-80 mM, but the only concentration producing a significant genotoxic 

effect was 80 mM. On the other hand, HCB was unable to induce a significant 

increase in the MN frequency in the range of concentrations assayed, from 0.005 

to 0.1mM. The selected concentrations of DDE and HCB were chosen according 

to their toxicity in cell blood cultures; higher concentrations reduced significantly 

cell proliferation and produced a low frequency of binucleated cells. In 

conclusion, the results indicate that a genotoxic risk is associated with the 

exposure to DDE at concentrations 80 mM and above. 

Escuder-Gilabert, L., R. M. Villanueva-Camanas, et al. (2009). "Permeability and 

toxicological profile estimation of organochlorine compounds by biopartitioning micellar 

chromatography." Biomed Chromatogr 23(4): 382-9. 

 This paper points out the usefulness of biopartitioning micellar chromatography 

(BMC) as a high-throughput primary screening tool providing key information 

about the oral absorption, skin permeability (K(p)), brain-blood distribution 

coefficient (BB) and ecotoxicological parameters such as median lethal 

concentration (LC(50)) and bioconcentration factors of 15 organochloride 

compounds. The retention data of compounds in BMC conditions were 

interpolated in previously developed quantitative-retention activity relationships 

by our research group. Results show that the compounds studied readily cross 

the intestinal barrier (oral absorption > 90%) and the blood-brain barrier (log BB > 

0.4). In addition, the organochlorines DDE, chlorobenzene, 1,3-dichlorobenzene 

and 1,2-dichlorobenzene are the compounds which can more quickly cross the 

skin barrier (log K(p ) > -0.74 cm/h). From a ecotoxicological point of view, it can 

be concluded that the most retained compounds, DDE, DDD, 

hexachlorobenzene and dicofol, are the most toxic and bioacumulative. 

Ezendam, J., I. Hassing, et al. (2004). "Hexachlorobenzene-induced Immunopathology 

in Brown Norway rats is partly mediated by T cells." Toxicol Sci 78(1): 88-95. 
109

 Hexachlorobenzene (HCB) is a persistent environmental pollutant with 

(auto)immune effects in humans and rats. The Brown Norway (BN) rat is very 

susceptible to HCB-induced immunopathology, and oral exposure causes 

inflammatory skin and lung lesions, splenomegaly, lymph node (LN) 

enlargement, and increased serum levels of IgE and anti-ssDNA IgM. The role of 

T cells in HCB-induced immunopathology is unclear and to elucidate this 

Cyclosporin A (CsA) was used. BN rats were exposed to either a control diet or a 

diet supplemented with 450 mg/kg HCB for 21 days. CsA treatment started 2 

days prior to HCB exposure and rats were injected daily with 20 mg/kg body 

weight CsA. Treatment with CsA prevented the HCB-induced immunopathology 

significantly. The onset of skin lesions was delayed and the severity was also 

strongly decreased. Furthermore, CsA prevented the HCB-induced increase in 

spleen weight partly and the increase in auricular LN weight completely. The 

increase in serum IgE and IgM against ssDNA levels was prevented completely. 

Macrophage infiltrations into the spleen and lung still occurred but infiltrations of 

eosinophilic granulocytes into the lung were prevented. Restimulation of spleen 

cells with the T-cell mitogen ConA and the macrophage activator LPS clearly 

showed that CsA inhibited T-cell activation, but not macrophage activation. 

Together, our results show that both T cells and macrophages play a prominent 

role in HCB-induced immunopathology. 

Ezendam, J., K. Kosterman, et al. (2005). "Macrophages are involved in 

hexachlorobenzene-induced adverse immune effects." Toxicol Appl Pharmacol 209(1): 

19-27. 

 Hexachlorobenzene (HCB) is a persistent environmental pollutant that causes 

adverse immune effects in man and rat. The Brown Norway (BN) rat is very 

susceptible to HCB-induced immunopathology and oral exposure causes 

inflammatory skin and lung lesions, splenomegaly, lymph node (LN) 

enlargement, and increased serum levels of IgE and anti-ssDNA IgM. T cells play 

an important role but do not account for all adverse effects induced by HCB. 

Macrophages are probably also important and the relationship between 

macrophages and T cells was further investigated. To eliminate macrophages 

clodronate-liposomes were used. Furthermore, a kinetic study was performed to 

obtain insight in the early phase of the HCB-induced immune response. Also, 

experiments were performed to detect specific memory T cells. Therefore, an 

adoptive transfer study was performed. Our results indicate that macrophages 

are indeed involved in HCB-induced skin lesions, lung eosinophilia, and elevation 

of IgM against ssDNA. Kinetics showed that both skin and lung lesions appeared 

early after exposure. Moreover, immune effects could not be adaptively 

transferred. Thus, both macrophages and T cells are involved in HCB-induced 

immune effects but HCB exposure does not lead to specific T cell sensitization. 

Presumably, HCB exposure induces macrophage activation, thereby generating 

adjuvant signals that polyclonally stimulate T cells. Together, these events may 

lead to the observed immunopathology in BN rats. 
110

Ezendam, J., F. Staedtler, et al. (2004). "Gene Expression Profiles In 

Hexachlorobenzene-Induced Toxicity." Toxicologist 78(1-S): 11. 

 Hexachlorobenzene (HCB) is a persistent environmental pollutant with toxic 

effects in man and rat. Reported adverse effects are hepatic porphyria, toxic 

effects on reproductive and immune system, and neurotoxicity. The Brown 

Norway (BN) rat is very susceptible to HCB-induced immunopathology and oral 

exposure causes enlargement of liver, spleen and lymph nodes, increased serum 

levels of IgM, IgG and IgE and inflammatory skin and lung lesions. The 

mechanisms of HCB-induced immunopathology are not clear, but both T cells 

and macrophages seem to be involved. To gain more insight in the mechanisms 

of HCB-induced toxicity, gene expression levels were studied using microarrays. 

BN rats were exposed for 4 weeks to a diet supplemented with 0, 150 or 450 

mg/kg HCB. Blood, thymus, kidney, liver, spleen and mesenteric lymph nodes 

(MLN) were collected and analysed using the Affymetrix rat RGU-34A GeneChip 

microarray. Most significant (p < 0.001) changes occurred in spleen, followed by 

liver, kidney, blood and MLN, but only a few genes were affected in thymus. This 

was to be expected since the thymus is not a target organ of HCB. Known effects 

of HCB such as immunotoxicity and induction of enzymes involved in drug 

metabolism, porphyria and reproductive system were confirmed, and in line with 

histopathology were the increased transcript levels of markers for granulocytes 

and macrophages. New findings include upregulation of genes encoding mast 

cell markers, complement, cell adhesion molecules, chemokines, 

proinflammatory cytokines, acute phase proteins and antioxidants. In general, 

gene expression data provide evidence that HCB induced a systemic 

inflammatory response, accompanied by oxidative stress and an acute phase 

response. In conclusion, this study confirms previously observed toxicological 

effects of HCB but also reveals several new and mechanistically relevant genes. 

Thus, genomics can be considered to be an important tool for hazard 

identification of this compound. 

Ezendam, J., F. Staedtler, et al. (2004). "Toxicogenomics of subchronic 

hexachlorobenzene exposure in Brown Norway rats." Environ Health Perspect 112(7): 

782-91. 

 Hexachlorobenzene (HCB) is a persistent environmental pollutant with toxic 

effects in man and rat. Reported adverse effects are hepatic porphyria, 

neurotoxicity, and adverse effects on the reproductive and immune system. To 

obtain more insight into HCB-induced mechanisms of toxicity, we studied gene 

expression levels using DNA microarrays. For 4 weeks, Brown Norway rats were 

fed a diet supplemented with 0, 150, or 450 mg HCB/kg. Spleen, mesenteric 

lymph nodes (MLN), thymus, blood, liver, and kidney were collected and 

analyzed using the Affymetrix rat RGU-34A GeneChip microarray. Most 

significant (p < 0.001) changes, compared to the control group, occurred in 

spleen, followed by liver, kidney, blood, and MLN, but only a few genes were 

affected in thymus. This was to be expected, as the thymus is not a target organ 

of HCB. Transcriptome profiles confirmed known effects of HCB such as 

stimulatory effects on the immune system and induction of enzymes involved in 
111

drug metabolism, porphyria, and the reproductive system. In line with previous 

histopathological findings were increased transcript levels of markers for 

granulocytes and macrophages. New findings include the upregulation of genes 

encoding proinflammatory cytokines, antioxidants, acute phase proteins, mast 

cell markers, complements, chemokines, and cell adhesion molecules. 

Generally, gene expression data provide evidence that HCB induces a systemic 

inflammatory response, accompanied by oxidative stress and an acute phase 

response. In conclusion, this study confirms previously observed 

(immuno)toxicological effects of HCB but also reveals several new and 

mechanistically relevant gene products. Thus, transcriptome profiles can be used 

as markers for several of the processes that occur after HCB exposure. 

Ezendam, J., I. Vissers, et al. (2003). "Immunomodulatory effects of 

tetrachlorobenzoquinone, a reactive metabolite of hexachlorobenzene." Chem Res 

Toxicol 16(6): 688-94. 

 Hexachlorobenzene (HCB) is an environmental pollutant that causes 

autoimmune-like effects in humans and rats. It is not completely clear whether T 

cells are involved and, if so, how they are stimulated after oral exposure to HCB. 

HCB as a rather inert chemical is not likely to bind covalently to macromolecules. 

The oxidative metabolite of HCB, tetrachlorobenzoquinone (TCBQ), which is in a 

redox equilibrium with tetrachlorohydroquinone (TCHQ), can bind to 

macromolecules, hence may form hapten-carrier complexes in vivo. We have 

assessed in the reporter antigen-popliteal lymph node assay whether HCB or 

TCHQ and TCBQ are able to induce a 2,4,6-trinitrophenyl (TNP) specific IgG1 

response to the T cell-independent antigen TNP-Ficoll, which is indicative of 

neoantigen specific T cell help. To this end, these compounds and silica were 

injected into the footpad of Balb/c mice. Silica was included as an inert model 

compound, which causes autoimmune-like effects by activating macrophages. 

Seven days later, cell number and TNP specific antibody-secreting cells (ASC) in 

the popliteal lymph node (PLN) were determined. Furthermore, a secondary 

PLNA was performed to find out if TCHQ was capable of eliciting a memory 

response. Silica, TCHQ, and TCBQ, but not HCB, increased PLN cellularity and 

the number of IgM-producing ASC by ELISPOT. Both oxidative metabolites were 

able to induce the formation of germinal centers as assessed by 

immunohistochemistry and an IgG1 response to TNP-Ficoll. In the secondary 

PLNA, only mice primed with TCHQ and challenged with TCHQ together with 

TNP-Ficoll showed a significant increase in TNP specific IgG1 ASC. Present data 

show that TCHQ and TCBQ are capable of inducing neoantigen specific T cell 

help and that TCHQ can induce a compound specific memory response. 

Ezendam, J., J. G. Vos, et al. (2005). "Research articles mechanisms of 

hexachlorobenzene-induced adverse immune effects in brown norway rats." J 

Immunotoxicol 1(3): 167-75. 

 Hexachlorobenzene (HCB) is an environmental pollutant that induces adverse 

immune effects in humans and rats. Brown Norway rats (BN) appear to be very 

susceptible to HCB-induced immune effects. Oral exposure causes inflammatory 
112

skin and lung lesions, enlarged spleen and lymph nodes (LN) and elevated 

humoral responses. This review describes recent experiments that were 

performed to elucidate the mechanisms underlying these adverse immune 

effects. The metabolites tetrachlorohydroquinone and tetrachlorobenzoquinone 

are capable of generating neoantigen-specific T-cells in the mouse reporter 

antigen popliteal lymph node assay with 2,4,6-trinitrophenyl-Ficoll. Additional 

experiments in BN rats have shown that T-cells are involved in the development 

of HCB-induced skin lesions, the increase in auricular LN weight, lung 

eosinophilia, and humoral responses. However, splenomegaly and macrophage 

infiltration in the spleen and lung occur independent of T-cells. Remarkably, HCB 

does not induce T-cell sensitization in BN rats, suggesting that T-cells are 

activated nonspecifically, for example by macrophages. Transcriptome profiles 

obtained after subchronic HCB exposure to BN rats reveal that HCB induces a 

systemic inflammatory response in which several innate immune cells, such as 

macrophages, and pro-inflammatory cytokines are involved. Additional 

experiments have shown that macrophages are implicated in HCB-induced skin 

lesions, in particular in the aggravation of skin effects. Also, HCB-induced lung 

eosinophilia and elevation of anti-ssDNA IgM antibodies are less pronounced 

after macrophage elimination. Presumably, HCB activates macrophages, thereby 

generating pro-inflammatory adjuvant signals that induce a systemic 

inflammatory response. Subsequently, this may lead to polyclonal activation of Tand B-cells, eosinophilia, and eventually visible clinical effects. 

Fang, H., W. Tong, et al. (2003). "Study of 202 natural, synthetic, and environmental 

chemicals for binding to the androgen receptor." Chemical Research in Toxicology

16(10): 1338-58. 

 A number of environmental and industrial chemicals are reported to possess 

androgenic or antiandrogenic activities. These androgenic endocrine disrupting 

chemicals may disrupt the endocrine system of humans and wildlife by mimicking 

or antagonizing the functions of natural hormones. The present study developed 

a low cost recombinant androgen receptor (AR) competitive binding assay that 

uses no animals. We validated the assay by comparing the protocols and results 

from other similar assays, such as the binding assay using prostate cytosol. We 

tested 202 natural, synthetic, and environmental chemicals that encompass a 

broad range of structural classes, including steroids, diethylstilbestrol and related 

chemicals, antiestrogens, flutamide derivatives, bisphenol A derivatives, 

alkylphenols, parabens, alkyloxyphenols, phthalates, siloxanes, phytoestrogens, 

DDTs, PCBs, pesticides, organophosphate insecticides, and other chemicals. 

Some of these chemicals are environmentally persistent and/or commercially 

important, but their AR binding affinities have not been previously reported. To 

the best of our knowledge, these results represent the largest and most diverse 

data set publicly available for chemical binding to the AR. Through a careful 

structure-activity relationship (SAR) examination of the data set in conjunction 

with knowledge of the recently reported ligand-AR crystal structures, we are able 

to define the general structural requirements for chemical binding to AR. 

Hydrophobic interactions are important for AR binding. The interaction between 
113

ligand and AR at the 3- and 17-positions of testosterone and R1881 found in 

other chemical classes are discussed in depth. The SAR studies of ligand 

binding characteristics for AR are compared to our previously reported results for 

estrogen receptor binding. 

Fernandez-Tome, M. C., S. C. Billi de Catabbi, et al. (2000). "Heme metabolism and 

lipid peroxidation in rat kidney hexachlorobenzene- induced porphyria: A 

compartmentalized study of biochemical pathogenic mechanisms." Kidney Blood Press 

Res 23(1): 20-6. 

 In the present study, the effects of hexachlorobenzene (HCB) on lipid 

peroxidation and heme metabolism in the different constitutive suborgans of the 

kidney were determined. For this purpose, conjugated diene and 

malondialdehyde levels, as lipid peroxidation parameters, and porphyrin 

accumulation, uroporphyrinogen decarboxylase activity, and its inhibitor 

formation, as measures of heme metabolism, were determined in renal cortex, 

medulla, and papilla. Adult Wistar rats were treated with HCB during 1, 2, 3, or 4 

weeks. A significant increase in cortical conjugated dienes was observed from 

the 1st week of treatment. The malondialdehyde levels rose by 47, 34, and 28% 

after 2, 3, and 4 weeks of intoxication, respectively. The porphyrin content 

showed a tenfold increase after 4 weeks of treatment, and the uroporphyrinogen 

decarboxylase activity was reduced by 26 and 58% with respect to control values 

after 3 and 4 weeks of treatment, respectively. The results demonstrate a direct 

correlation between the oxidative environment and the effect elicited by the drug 

on heme metabolism in the renal cortex. In contrast, in papilla and medulla, 

where the antioxidant systems were higher, HCB showed no porphyrinogenic 

effect. 

Foster, W. G., M. G. Wade, et al. (2004). "Developmental Exposure To A Complex 

Mixture Of Environmental Toxicants Interacts With Postnatal Genistein To Induce 

Changes In Reproductive Development Of Female Sprague Dawley Rats." Toxicologist

78(1-S): 220. 

 Estimates of safe exposure levels are based primarily on the results of animal 

studies employing single test chemicals, epidemiological studies, and estimates 

of potential human exposure. However, the consequences of chemical 

interactions to human reproductive and endocrine function remain unknown. The 

potential for interaction with hormonally active dietary constituents is also 

unknown. Therefore the objective of this study was to determine the effects of in 

utero exposure to a complex mixture of persistent environmental toxicants that 

have been quantified in human reproductive tissues. Pregnant Sprague-Dawley 

rats were exposed daily to a complex mixture at 1, 10, and 100 times the 

minimum risk level (MRL) or tolerable daily intake (TDI) as determined by the 

US-EPA on gestations days 9-16. The mixture used contained organochlorines 

(TCDD, PCBs, methoxychlor, DDT, DDE, dieldrin, endosulfan, 

hexachlorobenzene, hexachlorocyclohexane, mirex and heptachlor) and the 

metals lead and cadmium. Following delivery half the pups of each treatment 

group were injected subcutaneously with 10 ug genistein/g BW/day on postnatal 
114

days 2-8. Randomly selected pups from each litter were necropsied on days 21, 

60, 120 and 200 days of age. Treatments had no effect on litter size, sex ratio, 

birth weight, reproductive organ weights or reproductive endocrine outcome 

measures. Treatment with the mixture had no effect on sexual maturation in 

either sex whereas the mixture/genistein combination induced a significant delay 

in vaginal opening but had no effect on preputial separation. These data suggest 

that developmental exposure to environmental toxicants representative of 

contemporary human tissue residues is unlikely to induce additive or synergistic 

effects on the reproductive tract. However, our data suggest that exposure 

complex mixtures of toxicants can interact with dietary components to induce 

adverse effects on reproductive development in the female. 

Gocmen, A., Peters, et al. (1986). "Porphyria turcica: hexachlorobenzene-induced 

porphyria 77: 

 ." IARC Scientific Publications 77: 567-573. 

 

Gocmen, A., H. A. Peters, et al. (1989). "Hexachlorobenzene episode in Turkey 

" Biomed Environ Sci

2(1): 36-43 

 During the period 1955-1959, approximately 4000 people in southeast Anatolia 

developed porphyria due to the ingestion of hexachlorobenzene (HCB), a 

fungicide added to wheat seedlings. These HCB exposures subsequently led to 

the development of bullae on sun-exposed areas, hyperpigmentation, 

hypertrichosis, and porphyrinuria. The condition was called kara yara or "black 

sore." Many of the breast-fed children under the age of 2 years whose mothers 

had ingested HCB-treated grain died from a disease known as pembe yara or 

"pink sore." In this follow-up study of 252 patients, 20-30 years postexposure, 

there were 162 males and 90 females, with an average current age of 35.7 

years, an average of onset of 7.6 years, and a duration of 2.2 years. Many 

patients had dermatologic, neurologic, and orthopedic symptoms and signs. The 

observed clinical findings include scarring of the face and hands (83.7%), 

hyperpigmentation (65%), hypertrichosis (44.8%), pinched facies (40.1%), 

painless arthritis (70.2%), small hands (66.6%), sensory shading (60.6%), 

myotonia (37.9%), cogwheeling (41.9%), enlarged thyroid (34.9%), and enlarged 

liver (4.8%). Urine and stool porphyrin levels were determined in all patients, and 

17 have at least one of the porphyrins elevated. A total of 56 specimens of 

human milk obtained from mothers with porphyria were analyzed for HCB. The 

average value was 0.51 ppm in HCB-exposed patients compared to 0.07 ppm in 

unexposed controls. Offspring of mothers with three decades of HCB-induced 

porphyria appear normal. 

Gorman, N., H. S. Trask, et al. (2007). "Hexachlorobenzene stimulates uroporphyria in 

low affinity AHR mice without increasing CYP1A2." Toxicol Appl Pharmacol 221(2): 235-

42. 
115

 Hexachlorobenzene (HCB), a weak ligand of the aryl hydrocarbon receptor 

(AHR), causes hepatic uroporphyrin (URO) accumulation (uroporphyria) in 

humans and animals. CYP1A2 has been shown to be necessary in the 

development of uroporphyria in mice. Using mice expressing the low affinity form 

of the AH receptor (AHRd), we investigated whether the enhancement of 

uroporphyria by HCB involves an obligatory increase in CYP1A2 as measured by 

specific enzyme assays and immunoblotting. We compared the ability of HCB, in 

combination with iron dextran and the porphyrin precursor, 5-aminolevulinate 

(ALA), to cause uroporphyria in a strain of mice (C57BL/6) which expresses the 

high affinity form of the receptor (AHRb(1)), with three strains of mice (SWR and 

two 129 sublines) expressing the low affinity AHRd. In C57BL/6 mice, HCBenhanced uroporphyria was associated with a doubling of CYP1A2. HCB 

treatment produced uroporphyria in iron-loaded mice expressing AHRd, even 

though there was little or no increase in CYP1A2. Cyp1a2(-/-) mice in a 129 

background were completely resistant to HCB-induced uroporphyria, and female 

Hfe(-/-) 129 mice, in which the levels of hepatic CYP1A2 were half of those of the 

male levels, responded poorly. The effect of exogenous iron, administered in the 

form of iron dextran, on HCB enhancement of uroporphryia could be replicated 

utilizing the endogenous hepatic iron accumulated in 129 Hfe(-/-) mice. In 

conclusion, some minimal basal expression of CYP1A2 is essential for HCBmediated enhancement of uroporphyria, but increases in CYP1A2 above that 

level are not essential. 

Grassi, T. F., C. A. Tararam, et al. (2007). "Diuron lacks promoting potential in a rat liver 

bioassay." Toxicol Pathol 35(7): 897-903. 

 The promoting activity of the herbicide Diuron was evaluated in a medium-term 

rat liver carcinogenesis bioassay that uses as endpoint immunohistochemically 

identified glutathione S-transferase positive (GST-P+) foci. Male Wistar rats were 

allocated to the following groups: G1 to G6 were initiated for liver carcinogenesis 

by a single dose of diethylnitrosamine (DEN, 200 mg/kg) while groups G7 and 

G8 received only 0.9% NaCl (DEN vehicle). From the 2nd week animals were fed 

a basal diet (G1 and G7) or a diet added with Diuron at 125, 500, 1250, 2500 and 

2500 ppm (G2 to G5 and G8, respectively) or 200 ppm Hexaclorobenzene (HCB; 

G6). The animals were submitted to 70% partial hepatectomy at the 3rd week 

and sacrificed at the 8th week. The herbicide did not alter ALT or creatinine 

serum levels. No conspicuous GST-P+ foci development was registered in noninitiated rats fed Diuron at 2500 ppm. While DEN-initiated animals fed Diuron at 

1250 or 2500 ppm developed mild centrilobular hypertrophy, DEN-initiated HCBfed animals showed severe liver centrilobular hypertrophy and significant GSTP+ foci development. These findings indicate that the medium-term assay 

adopted in this study does not reveal any liver carcinogenesis initiating or 

promoting potential of Diuron in the rat. 

Hjelmborg, P. S., M. Ghisari, et al. (2006). "SPE-HPLC purification of endocrinedisrupting compounds from human serum for assessment of xenoestrogenic activity." 

Analytical and Bioanalytical Chemistry 385(5): 875-87. 
116

 Assessment of xenoestrogenic activity in human serum samples requires the 

removal of endogenous sex hormones to assure that the activity measured 

originates from xenobiotic compounds only. Serum samples representing high, 

medium and lower accumulation of persistent organic pollutants (POPs) were 

extracted using solid-phase extraction (SPE) followed by normal-phase highperformance liquid chromatography (NP-HPLC) for separation of POPs from 

endogenous hormones. The recovery of polychlorinated biphenyl (PCB) 

congeners in spiked serum samples was up to 86 %, making the extraction 

method suitable for the study. MVLN cells, stably transfected with an estrogen 

receptor (ER) luciferase reporter vector (estrogen response element chemically 

activated luciferase expression, ERE-CALUX), were exposed to the reconstituted 

SPE-HPLC extracts for determination of the integrated estrogenic activity. The 

effects of PCBs were analyzed by direct in vitro exposure of PCBs (nos. 138, 

153, 180) and by ex vivo analysis of SPE-HPLC extracts from serum spiked with 

the PCBs. Similar effects on ER transactivation were observed for the direct in 

vitro and the ex vivo analysis experiments. The ER transactivation responses 

determined for actual serum samples were in the linear range of the doseresponse curve. 17beta-Estradiol titrations showed that the xenoestrogenic 

effects were mediated via ER. Moreover, our SPE-HPLC-ERE-CALUX assay 

was demonstrated to elicit high interlaboratory correlation. In the present study 

the combination of SPE-HPLC purification and the ex vivo estrogenic responses 

measured by ERE-CALUX was validated and considered to be a valuable tool to 

assess the combined ER effect of lipophilic serum POPs where 

additive/synergistic and agonistic/antagonistic effects are integrated giving an 

overall estimate of exposure and bioactivity. 

Imbeault, P., J. Chevrier, et al. (2002). "Increase in plasma pollutant levels in response 

to weight loss is associated with the reduction of fasting insulin levels in men but not in 

women." Metabolism: clinical and experimental.|Metabolism 51(4): 482-6. 

 Environmental pollutants can act as endocrine modulators. In this study, we 

examined whether weight loss-induced changes in plasma organochlorine 

compounds (OC) were associated with those in plasma insulin levels. Fasting 

insulin and the area under the curve (AUC) of insulin after a 75-g oral glucose 

load, plasma levels of 1 commercial polychlorinated biphenyl (PCB) mixture 

(Aroclor 1260), 1 PCB congener (PCB 153), and 3 pesticides (2,2'-bis(4-

chlorophenyl)-1,1-dichloroethylene (p,p'-DDE), beta-hexachlorocyclohexane 

(beta-HCH), and hexachlorobenzene (HCB)) were measured before and after a 

15-week weight loss program induced by a caloric restriction in a sample of 

obese men and women. Both genders showed a similar reduction in body weight 

(approximately 11 kg) in response to treatment, although men lost significantly 

more fat mass than women (mean +/- SD 9.4 +/- 4.1 v 5.9 +/- 5 kg, respectively, 

P <.05). Fasting insulin and AUC of insulin significantly decreased in men and 

women after the treatment. In response to weight loss, a significant increase in 

OC was observed in both genders, and this effect was more pronounced in men. 

The greater the increase in plasma OC levels, the greater the reduction in fasting 

insulin was in response to weight loss in men (-.49 < r < -.59, P <.05), but not in 
117

women (-.22 < r <.01, not significant [NS]). In both genders, no relationship was 

observed between changes in plasma OC levels and changes in AUC of insulin 

(-.41 < r < -.08, NS). In men, relationships between changes in plasma HCB, 

Aroclor 1260, and PCB-153 concentrations and those in fasting insulin levels in 

response to weight loss remained significantly correlated after correction for fat 

mass loss (-.46 < partial r < -.51, P values ranging from.05 to.07). These results 

suggest that weight loss-induced increase in plasma pollutant levels tends to be 

independently associated with the reduction of fasting insulin levels in men, but 

not in women. Further studies are needed to verify whether these findings are 

causally related. 

Ishizuka, M., T. Takasuga, et al. (2004). "Suppression of testosterone syntheses in 

testes of wild Norway rats in Japan: Accumulation of persistent organochlorine 

pollutants and polybrominated diphenyl ether and their effect." Toxicology and Applied 

Pharmacology 197(3): 236-237. 

 

Jarrell, J., A. Gocmen, et al. (1998). "Evaluation of reproductive outcomes in women 

inadvertently exposed to hexachlorobenzene in southeastern Turkey in the 1950s 

" Reprod Toxicol

12(4): 469-76 

 in southeastern Turkey during the period of 1955-57, women were accidentally 

exposed to the fungicide hexachlorobenzene (HCB) after eating contaminated 

seed grain and developed porphyria cutanea tarda (PCT). While HCB has been 

shown to be a potent oocyte toxicant in primates and has been identified as an 

ovarian follicular fluid contaminant in women, its effect on human reproduction is 

poorly understood. This study was undertaken to evaluate the effects of HCB on 

women with a known high dose exposure. A retrospective controlled cohort 

comparison study of three groups was conducted. Group 1, those with confirmed 

PCT; Group 2, controls for the region and Group 3, controls for the country of 

Turkey, were followed-up after approximately 40 years (n=42/group). Blood 

samples were taken for analysis of serum HCB, estradiol, follicle-stimulating 

hormone (FSH) and inhibin. Frequency of HCB detection was greatest in Group 

3, while number of cases with HCB values exceeding 1 ng/mL was significantly 

greater in Groups 1 and 2. There were no differences in the other biochemical 

measures. Interviews were completed for each patient regarding reproductive 

history (number of pregnancies, live births, spontaneous abortions, still births and 

sex of live babies). Multiple comparisons of the three groups, based on Fisher's 

test found the groups were inhomogeneous. When serum HCB was analyzed 

using correlated response logistic regression, there was a strong relationship 

between serum HCB levels and risk for spontaneous abortion but not sex ratio of 

children. The following findings were made. HCB is detectable and ubiquitous in 

serum samples from women in the country of Turkey with identified and 

unidentified exposure events. Spontaneous abortion risk is not restricted to 

women with identifiable exposure to HCB but to a surrogate marker of exposure 
118

(serum HCB sample). The risk of spontaneous abortion with HCB exposure 

requires further investigation. 

Kirkland, D., M. Aardema, et al. (2005). "Evaluation of the ability of a battery of three in 

vitro genotoxicity tests to discriminate rodent carcinogens and non-carcinogens. I. 

Sensitivity, specificity and relative predictivity. [Erratum to document cited in 

CA143:243161]." Mutation Research, Genetic Toxicology and Environmental 

Mutagenesis 588(1): 70. 

 On the title page, the URL of the website address in the open star footnote 

should read: www.lhasalimited.org/cgx. This is where the appendixes have been 

posted. 

Kirkland, D., M. Aardema, et al. (2005). "Evaluation of the ability of a battery of three in 

vitro genotoxicity tests to discriminate rodent carcinogens and non-carcinogens I. 

Sensitivity, specificity and relative predictivity." Mutation research. 584(1-2): 1-256. 

 The performance of a battery of three of the most commonly used in vitro 

genotoxicity tests--Ames+mouse lymphoma assay (MLA)+in vitro micronucleus 

(MN) or chromosomal aberrations (CA) test--has been evaluated for its ability to 

discriminate rodent carcinogens and non-carcinogens, from a large database of 

over 700 chemicals compiled from the CPDB ("Gold"), NTP, IARC and other 

publications. We re-evaluated many (113 MLA and 30 CA) previously published 

genotoxicity results in order to categorise the performance of these assays using 

the response categories we established. The sensitivity of the three-test battery 

was high. Of the 553 carcinogens for which there were valid genotoxicity data, 

93% of the rodent carcinogens evaluated in at least one assay gave positive 

results in at least one of the three tests. Combinations of two and three test 

systems had greater sensitivity than individual tests resulting in sensitivities of 

around 90% or more, depending on test combination. Only 19 carcinogens (out 

of 206 tested in all three tests, considering CA and MN as alternatives) gave 

consistently negative results in a full three-test battery. Most were either 

carcinogenic via a non-genotoxic mechanism (liver enzyme inducers, peroxisome 

proliferators, hormonal carcinogens) considered not necessarily relevant for 

humans, or were extremely weak (presumed) genotoxic carcinogens (e.g. Nnitrosodiphenylamine). Two carcinogens (5-chloro-o-toluidine, 1,1,2,2-

tetrachloroethane) may have a genotoxic element to their carcinogenicity and 

may have been expected to produce positive results somewhere in the battery. 

We identified 183 chemicals that were non-carcinogenic after testing in both male 

and female rats and mice. There were genotoxicity data on 177 of these. The 

specificity of the Ames test was reasonable (73.9%), but all mammalian cell tests 

had very low specificity (i.e. below 45%), and this declined to extremely low 

levels in combinations of two and three test systems. When all three tests were 

performed, 75-95% of non-carcinogens gave positive (i.e. false positive) results 

in at least one test in the battery. The extremely low specificity highlights the 

importance of understanding the mechanism by which genotoxicity may be 

induced (whether it is relevant for the whole animal or human) and using weight 
119

of evidence approaches to assess the carcinogenic risk from a positive 

genotoxicity signal. It also highlights deficiencies in the current prediction from 

and understanding of such in vitro results for the in vivo situation. It may even 

signal the need for either a reassessment of the conditions and criteria for 

positive results (cytotoxicity, solubility, etc.) or the development and use of a 

completely new set of in vitro tests (e.g. mutation in transgenic cell lines, systems 

with inherent metabolic activity avoiding the use of S9, measurement of genetic 

changes in more cancer-relevant genes or hotspots of genes, etc.). It was very 

difficult to assess the performance of the in vitro MN test, particularly in 

combination with other assays, because the published database for this assay is 

relatively small at this time. The specificity values for the in vitro MN assay may 

improve if data from a larger proportion of the known non-carcinogens becomes 

available, and a larger published database of results with the MN assay is 

urgently needed if this test is to be appreciated for regulatory use. However, 

specificity levels of <50% will still be unacceptable. Despite these issues, by 

adopting a relative predictivity (RP) measure (ratio of real:false results), it was 

possible to establish that positive results in all three tests indicate the chemical is 

greater than three times more likely to be a rodent carcinogen than a noncarcinogen. Likewise, negative results in all three tests indicate the chemical is 

greater than two times more likely to be a rodent non-carcinogen than a 

carcinogen. This RP measure is considered a useful tool for industry to assess 

the likelihood of a chemical possessing carcinogenic potential from batteries of 

positive or negative results. 

Kishima, M. O., L. F. Barbisan, et al. (2000). "Promotion of hepatocarcinogenesis by 

hexachlorobenzene in energy- restricted rats." Cancer Lett 152(1): 37-44. 

 The interaction between dietary energy restriction and low dose of the fungicide 

hexachlorobenzene (HCB) was evaluated in a rat liver medium- term bioassay 

for carcinogenesis. Male Wistar rats were fed a control or a 50% energyrestricted diet, both added or not with 50 ppm HCB, for 6 weeks. HCB exposure 

or energy restriction separately did not exert any influence on the development of 

glutathione S-transferase placental form (GST-P(+)) foci of hepatocytes. 

Simultaneous HCB exposure and energy restriction induced a significant 

increase in liver centrilobular hypertrophy and GST-P(+) foci development. Our 

findings suggest that energy restriction increases liver response to low dose of 

HCB, unmasking the promoting potential of this fungicide. 

Kleiman de Pisarev, D. d. C. R. d. M., M; San Martin de Viale, LC. (1990). "Thyroid 

function and thyroxine metabolism in hexachlorobenzene-induced porphyria." Biochem 

Pharmacol 39(5): 817-825. 

 

Koppen, G., A. Covaci, et al. (2002). "Persistent organochlorine pollutants in human 

serum of 50-65 years old women in the Flanders Environmental and Health Study 

(FLEHS). Part 1: Concentrations and regional differences." Chemosphere 48(8): 811-

25. 
120

 In 1999, a campaign of the Flemish Ministry of Health, Belgium was set up to 

assess pollutant concentrations and related health effect biomarkers in humans 

living in two regions of Flanders. The study was called the 'Flemish Environment 

and Health Study' (FLEHS). One of the goals was to measure present 

concentrations of persistent organochlorine pollutants in a Flemish population 

and to compare values obtained from pooled and individual serum samples. 

Concentrations of selected organochlorine pesticides, polychlorinated biphenyls 

(PCB) and polychlorinated dibenzo-p-dioxins (PCDD) and furans (PCDF) were 

measured by gas chromatography-mass spectrometry. TEQ values were also 

assessed by Chemical-Activated LUciferase gene eXpression (CALUX) 

bioassay. The study population consisted of 200 women between 50 and 65 

years living in two areas of Flanders, Belgium. Because of the large volumes 

serum needed for all measurements, the concentrations of organochlorines were 

measured in 47 pooled serum samples originating from these women. The 

concentrations of the indicator PCBs (359.8 ng/g fat) and organochlorine 

pesticides (hexachlorobenzene, p,p'-dichlorodiphenyldichloroethylene, p,p'-

dichlorodiphenyl-trichloroethane, lindane and pentachlorophenol), were 

comparable to those found in other European countries. The concentrations of 

PCDD/PCDFs showed another picture. With a median value of 48 pg WHOTEQ/g fat, the women had 2-fold higher levels than a comparable age group from 

Germany examined in 1996. The mean total WHO-TEQ including PCDD/F, nonortho and mono-ortho PCBs was 72.7 pg WHO-TEQ/g fat, whereas the CALUXTEQ mean value was only 35.0 pg TEQ/g fat. In order to assess the pooling 

procedure, indicator PCBs and CALUX-TEQs were measured in all 200 

individuals that were integrated in the pools. The measured values were 

comparable to the pool results: 390.0 ng/g fat and 41.6 pg TEQ/g fat 

respectively. It was concluded that pooling of serum samples offers the possibility 

to measure exposure in the whole study population on a more cost-effective way. 

However, because of statistical power loss and no possibility of confounder 

adjustment, pooling is not the most effective way to study regional differences. 

Kumar, V., C. Majumdar, et al. (2008). "Effects of endocrine disrupting chemicals from 

leather industry effluents on male reproductive system." J Steroid Biochem Mol Biol

111(3-5): 208-16. 

 The leather tanning industry is characterized by the production of different kinds 

of effluents, generated in each step of leather processing. These effluents have 

various chemical compounds which may cause toxicity and endocrine disruption 

and are thus known as endocrine disrupting chemicals (EDC). This study was 

aimed to examine the androgenic potential of leather industry effluents collected 

from northern region of India. Hershberger assay data showed a significant 

increase (p<0.05) in the weight and structure of sex accessory tissues of 

castrated rats. Reverse transcriptase polymerase chain reaction (RT-PCR) 

analysis demonstrated a significant change (p<0.05) in the expression patterns of 

the major steroidogenic enzymes in adrenal and testes namely, cytochrome 

P450scc, 3beta-hydroxysteroid dehydrogenase, 17beta-hydroxysteroid 

dehydorgenase in castrated and intact rats. This was further supported by 
121

increased enzymatic activities measured in vitro spectrophotometrically. Serum 

hormone profile demonstrated a dose dependent increase in testicular and 

adrenal testosterone productions in intact and castrated rats, respectively. This 

was further supported by decreased level of gonadotrophic hormones (LH and 

FSH) in treated groups of animals. Further, the effluent treatment resulted in the 

development of hyperplasia in seminiferous tubules of testes in treated rats as 

evident from histopathological studies and about two-fold increases in daily 

sperm production. On analysis of water samples using GC-MS, it was found to 

contain various aromatic compounds (nonylphenol, hexaclrobenzene and several 

azo dyes) some of which independently demonstrated similar effects as shown 

by water samples. Our data suggests that the effluents from leather industry 

have potential EDC demonstrating androgenic activities. 

Langer, P., A. Kocan, et al. (2008). "Increased thyroid volume, prevalence of thyroid 

antibodies and impaired fasting glucose in young adults from organochlorine cocktail 

polluted area: outcome of transgenerational transmission?" Chemosphere 73(7): 1145-

50. 

 In 137 females (F) and 94 males (M) aged 21-35 years from organochlorines 

(OCs) polluted area (POLL) increased thyroid volume (ThV), prevalence of 

antibodies to thyroperoxidase (TPOab), thyrotropin receptor (TRab) and of 

impaired fasting glucose (IFG) was found compared to 116 F and 107 M from 

background pollution area (BCGR). In F and M from POLL also strikingly 

increased level of PCBs, DDE and HCB was found. Such findings were 

compared to the generation of their parents aged 41-55 years consisting of 

320F/213M from POLL and 406F/231M from BCGR. However, in spite of 

strikingly lower level of those OCs in young adults from POLL, they showed 

about the same prevalence of adverse health signs as the old generation. From 

such reason 44 young F and 40 young M with lowest PCBs level from POLL 

were selected to obtain nearly the same PCB level as found in all young F and M 

from BCGR. In such PCB adjusted groups the prevalence of TPOab, TRab, IFG 

and increased ThV was still significantly higher than that in all young subjects 

from BCGR. At the same time, also the level of DDE and HCB in such PCBs 

adjusted groups was considerably lower. It was concluded that such adverse 

effects in young adults from POLL possibly did not result from their actual OCs 

levels, but very likely from their exposure to high OCs levels of their mothers 

during their prenatal and perinatal life. Thus, the data may be compatible with 

present views on transgenerational transmission of endocrine disruptors action. 

Langer, P., M. Tajtakova, et al. (2006). "Multiple organochlorine pollution and the 

thyroid." Endocr Regul 40(2): 46-52. 

 OBJECTIVE: Although the biological effects of major persistent 

organochlorinated pollutants (POPs) appear to be essentially similar, some 

effects which would be specific for certain substance cannot be excluded. We 

attempted to study the thyroid volume and thyrotropin level in the population 

living in the area with multiple pollution by polychlorinated biphenyls (PCBs) and 

pesticides (DDE and hexachlorobenzene - HCB). METHODS: A total of 454 
122

adults was examined within the pilot field survey in 1998. Among them were 237 

males (age range 19-78 years, median 47) and 227 females (age range 19-78 

years, median 48). Fifteen environmentally prevalent congeners of 

polychlorinated biphenyls and also p,p-DDE (2,2-bis(4-chlorophenyl)-1,1-

dichloroethylene), p,p-DDT (2,2-bis(4-chlorophenyl)- 1,1,1-trichloro-ethane), 

hexachlorobenzene (HCB) as well as alpha-, beta- and gammahexachlorocyclohexane (HCH) were determined in serum by high resolution gas 

chromatography using microelectron capture detector and microcapillary column. 

Thyroid volume (ThV) was measured by real time sonography using the ellipsoid 

method with the aid of sonographic instrument Sonoline SI-400 (Siemens, 

Germany). The level of TSH was estimated by supersensitive immunoradiometric 

method using commercial kits by Immunotech (Marseille, France). Pearsons 

correlation coefficients after logarithmic transformation of values and Spearmans 

correlation coefficients were used for statistical evaluation. RESULTS: Significant 

positive association (p<0.01) was found between DDE and PCB, DDE and HCB, 

while that between PCB and HCB was not significant. Similar positive association 

(p<0.01) was also found between each individual organochlorine and their sum. 

Significant negative association (p<0.01) was found between ThV and TSH. 

When using categorical PCB values either >2000 (N=208) or >3000 (N=127) 

ng/g lipid, significant positive association (p<0.05 and p<0.01, respectively) was 

found between the sum of all organochlorines (PCB+DDE+HCB) and ThV, while 

that between PCB and ThV (p<0.01) was found only at the PCB levels >3000 

ng/g lipid. When using Spearmans correlation coefficients, significant negative 

association appeared between PCB and TSH (p<0.05), sum of organochlorines 

and TSH (p<0.05) and ThV and TSH (p<0.01). CONCLUSIONS: Although 

several significant positive and negative associations were found, this study, like 

several others, could not exactly define the participation level of individual POPs 

in their common toxic effects, but possibly contributed to the recognition and 

elucidation of some problems related to this task. 

Leao, M. B. C., A. C. Pavao, et al. (2005). "A multivariate model of chemical 

carcinogenesis." Theochem 719(1-3): 129-135. 

 In this work we have investigated electronic parameters that characterize the 

action of carcinogens, i.e descriptors such as electron affinity, ?(HOMO-LUMO), 

dipole moments, electrostatic attraction, formation heat (Hf) and permeability of 

the cellular membrane (c Log P) for selected compds. The multivariate anal. 

allows us to propose a theor. model that correlates these descriptors with the 

carcinogenic activity in a series of chem. compds. The protecting activity of 

antioxidants was analyzed by considering their competition with the DNA in the 

electron donation process and formation of chem. bond with the carcinogen. 

Lelli, S. M., N. R. Ceballos, et al. (2007). "Hexachlorobenzene as hormonal disruptor--

studies about glucocorticoids: their hepatic receptors, adrenal synthesis and plasma 

levels in relation to impaired gluconeogenesis." Biochem Pharmacol 73(6): 873-9. 

 In Wistar rats, hexachlorobenzene (HCB) depresses the gluconeogenic enzyme 

phosphoenolpyruvate-carboxykinase (PEPCK). In the liver, glucocorticoids (GC) 
123

normally regulate the glucose synthesis by acting on PEPCK. Thus, the aim of 

this work was to investigate, in a time-course study, the effects of HCB on 

plasma GC, its adrenal synthesis and stimulation, and the kinetic parameters of 

its hepatic receptors (GR) in relation to the gluconeogenic blockage produced by 

HCB. Plasma corticosterone (CORT) concentration, urinary porphyrins and 

hepatic PEPCK were determined after 2, 4, 6 and 8 weeks of HCB-treatment. 

The effect of HCB on kinetic parameters of GR was studied in adrenalectomized 

porphyric rats after 2, 4 and 8 weeks of treatment. Additionally, adrenal CORT 

synthesis in the same weeks was measured with or without ACTH. Results show 

that plasma CORT in intoxicated animals dropped significantly after 2 and 4 

weeks of treatment (23% and 58%, respectively), and then remained constant 

until the 8th week. HCB also promoted a reduction in the number of hepatic GR 

(50-55%) without modifying affinity. After 8 weeks, when porphyria was well 

established (40-50-fold increase in urinary porphyrins), a reduction (52%) in 

hepatic GR number, as well as a decrease in PEPCK activity (56%) were 

observed. Moreover, CORT biosynthesis in adrenals from intoxicated animals 

significantly decreased (60%) without changes in ACTH effect. Briefly, this paper 

shows that HCB causes a disruption in GC and GR. This disturbance could 

contribute to the negative effect on glucose synthesis through PEPCK regulation, 

thus modulating porphyria. These results enhance the knowledge about the 

hormonal disruption produced by chlorinated xenobiotics. 

Li, J., M. Ma, et al. (2008). "A two-hybrid yeast assay to quantify the effects of 

xenobiotics on thyroid hormone-mediated gene expression." Environmental Toxicology 

and Chemistry 27(1): 159-67. 

 Over the last few years, increasing evidence has become available that some 

chemicals may have thyroid hormone- disrupting potencies. The effects exerted 

via thyroid hormone receptors (TR) have not been studied thoroughly. The 

present study investigates chemical thyroid hormone disruption at the level of TR 

functioning. To this end the (ant)agonistic action of a series of xenobiotics was 

tested in the newly developed yeast two-hybrid assay. This assay makes use of 

recombined TRbeta gene and reporter gene yeast, which specifically expresses 

beta-galactosidase when incubated with exogenous 3,3',5-triiodo-l-thyronine 

(T(3)). Agonistic and antagonistic actions were studied in the absence and 

presence of 5 x 10(-6) mol/L T(3), which induced maximal beta-galactosidase 

activity. The compounds tested included the specific TR-antagonist amiodarone, 

as well as a series of phenols, phthalate, organochlorine pesticides (OCPs), 

polyhalogenated aromatic hydrocarbons (PHAHs) with structural similarity to 

T(3), and 3,3',5,5'-tetraiodo-l-thyronine (T(4)). The results obtained reveal that 

only 2-t-butylphenol and 2-isopropylphenol are specific agonists. Interestingly, 

some compounds showed potentiated antagonistic effects when tested in 

combination with T(3), which suggests that TR-mediated transcription may be 

disrupted in vivo. The 20% relative inhibitory concentration (RIC20) values of 

phenols, ester and OCPs were more than 10(-7) mol/L, but the values for PHAHs 

with metabolization were lower than 5 x 10(-7) g/L. These results suggest that 

PHAHs pose a serious threat to the human thyroid system. Altogether the results 
124

of the present study show that the newly developed, yeast two-hybrid assay can 

be used as a valuable tool for identification and quantification of compounds 

active in disturbing thyroid hormone homeostasis at the level of TR. The results 

are further evidence of thyroid-related effects of environmentally relevant PHAHs. 

Li, Y. F., N. Shi, et al. (2006). "[Toxicity and oxidative stress on rats by 

hexachlorobenzene]." Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi 24(10): 601-

4. 

 OBJECTIVE: To study the toxicity on rats by hexachlorobenzene (HCB), and to 

explore the role of oxidative stress in the mechanism of HCB intoxication. 

METHODS: SD female rats were fed on a powdered diet containing 0.25 per 

thousand or 2.00 per thousand HCB for 14 days. The content of 

malondialdehyde (MDA) and the activity of total-superoxide dismutase (T-SOD), 

catalase (CAT) and glutathione peroxidase (GSH-PX) in cerebral cortex, 

hippocampus, liver tissue and serum were determined. Eleven biochemical 

indicators including alkaline phosphatase (ALP) were surveyed. RESULTS: (1) 

MDA levels in cerebral cortex, hippocampus, liver and serum of the high dosage 

group rats and that in hippocampus and serum of the low dosage group were 

significantly higher than that of the control group. (2) The activity of T-SOD was 

increased in cerebral cortex and hippocampus of the rats in both groups (P < 

0.01), but decreased in the serum of the high dosage group (P < 0.01). (3) The 

activity of CAT was also increased in the hippocampus of rats in the high dosage 

group. (4) In cerebral cortex and hippocampus of the rats in the high dosage 

group and in the hippocampus of the rats in the low dosage group, the activity of 

GSH-PX was significantly higher compared with the control group. However, in 

liver of both dosage groups, the activity of GSH-PX was decreased (P < 0.01). 

(5) The activity of serum alkaline phosphatase of both dosage groups was also 

decreased, but the contents of both serum albumin and total cholesterol were 

significantly higher than those of the control group (P < 0.01). CONCLUSION: 

HCB can induce enhanced lipid peroxidation on SD rats, and the oxidative stress 

plays an important role in the mechanism of neurotoxicity and hepatotoxicity. 

Liu, G. H., K. D. Yang, et al. (2005). "[Effects of residues of organochlorine pesticides 

on reproductive endocrine in human]." Wei sheng yan jiu|Journal of hygiene 

research.|Wei sheng yan jiu : Journal of hygiene research. 34(5): 524-8. 

 OBJECTIVE: To explore effects of residues of organochlorine pesticides on 

reproductive endocrine in human. METHODS: The accumulative levels of the 

pesticides in the pregnant women's venous blood were determined and were 

grouped to understand the associations among the pesticides, hormones, and 

genes. RESULTS: (1) With the increase of blood burden of organochlorine 

pesticides, levels of the hormones such as follicle stimulating hormone (FSH), 

estradiol (E2) and progesterone (P) in the maternal blood and FSH, luteinizing 

hormone (LH) and E2 in the umbilical cord blood increased in dose-effect 

manner, respectively. However, the hormones, for example, LH in the women 

blood and P in the cords blood decreased respectively with the rising pesticides' 

levels and an obvious dose-effect relationship was found. (2) The expressional 
125

abundances of alpha-estrogen receptor (alpha-ER), beta-endorphin (beta-EP) 

and gonadotropin releasing hormone (GnRH) in the placentae and alpha-ER and 

beta-EP in the cord tissues went up respectively in dose-effect manner following 

the rising pesticides' burdens. (3) The times of the previous adverse pregnancy 

outcomes increased with the increase of the residues' burdens and there were 

significant differences between the control and various residue groups, but the 

times in the high-residue was smaller than that in the mid-residue group (P < 

0.01). The average weights of the newborn in various residue groups were 

heavier comparing to the control. There was no significant difference between 

the high residue group and the control. However, significances existed among 

the low, intermediate, and control group (P < 0.05). Moreover, the rank from high 

to low was the low-residue, mid-residue and high residue group. CONCLUSION: 

The residues of organochlorine pesticides (DDT and BHC and their metabolites) 

possess reproductive and developmental toxicities, and present mostly the 

estrogenic activity under the joint exposure in which the total BHC concentration 

was higher than that of the total DDT in maternal blood. 

Llambias, E. B., M. B. Mazzetti, et al. (2007). "Melatonin formation in pineal gland from 

rats with hexachlorobenzene experimental porphyria." Int J Toxicol 26(6): 545-51. 

 Hexachlorobenzene produces an experimental hepatic porphyria in rats, which is 

similar to human porphyria cutanea tarda, with hyperpigmentation as one of its 

characteristic features. Alterations in tryptophan metabolism have been 

previously observed in this chronic porphyria. Melatonin formation from 

tryptophan via serotonin shows diurnal rhythmicity in the pineal gland, and higher 

values are observed during the dark phase of an imposed light-dark cycle. The 

purpose of this study was to determine the contents of tryptophan and its 

metabolites in pineal gland of normal and hexachlorobenzene-treated rats in 

order to find alterations potentially related to porphyria cutanea tarda. Results 

show that in animals with this experimental porphyria some tryptophan 

metabolite levels (serotonin and 5-hydroxyindoleacetic acid) increase only during 

the light period, whereas tryptophan content remained equal to the controls. 

Hydroxyindole-O-methyltransferase activity also increases by light in pineal gland 

from hexachlorobenzene-treated rats. On the other hand, tryptophan is converted 

to melatonin in the dark period, but this route is not exacerbated in 

hexachlorobenzene porphyria. The relevance of these alterations is discussed in 

relation to hyperpigmentation, neoplastic and oxidative stress processes 

associated with this porphyria. 

Loaiza-Perez, A. I., M. T. Seisdedos, et al. (1999). "Hexachlorobenzene, a dioxin-type 

compound, increases malic enzyme gene transcription through a mechanism involving 

the thyroid hormone response element." Endocrinology 140(9): 4142-51. 

 Hexachlorobenzene (HCB) is a dioxin-type chemical that acts mainly through the 

aryl hydrocarbon receptor. Chronic exposure of rats to HCB increases the activity 

of malic enzyme (ME). In this report, we show that this increase is correlated with 

an induction of ME messenger RNA (mRNA) levels, with the maximal HCB effect 

achieved after 9 days of intoxication. This effect is specific for ME, as other liver 
126

enzymes, such as glyceraldehyde-3-phosphate dehydrogenase, phosphoenol 

pyruvate carboxykinase, and mitochondrial alpha-glycerol-3-phosphate 

dehydrogenase, are not affected by HCB. The induction of ME mRNA levels is 

accompanied by an increase in ME promoter activity, as demonstrated by 

transient transfection experiments performed in rat hepatoma H35 cells. In an 

attempt to identify the cis-regulatory elements responsible for the HCB effect, 

different promoter deletions and mutations were used. The results obtained 

localize the responsive region between positions -315 and -177. This region does 

not contain either consensus xenobiotic response or activating protein-1 

elements, the two main mediators of dioxin compounds described to date. In 

contrast, a thyroid hormone response element (TRE) is located between - 281 to 

-261. Deletions and mutations of the TRE element do not respond to HCB, 

demonstrating that this element mediates the response of this dioxin-type 

compound. As ME gene expression is regulated mainly by thyroid hormones, we 

next investigated the role of T3 receptor (T3R) in the ME gene transcriptional 

induction mediated by HCB. Using Scatchard analysis, we show that neither T3R 

binding features for its ligand nor alpha1 or beta1T3R mRNA levels are changed 

with the toxic. In gel shift assays, however, we observed that protein/DNA 

complexes formed on TRE from the ME promoter were induced by HCB. Using 

an oligonucleotide with a mutation that eliminates the TRE function, we 

demonstrate a loss of the induced protein/DNA complexes. Together, these data 

suggest that the dioxin-type compound HCB increases ME gene transcription by 

modulating the levels of still unidentified nuclear proteins that bind to the TRE 

element of the ME promoter. 

Masuda, Y., K. Haraguchi, et al. (2003). "[Peculiar remaining of some PCB congeners in 

the patients with Yusho for more than 30 years]." Fukuoka Igaku Zasshi 94(5): 136-43. 

 Concentrations of polychlorinated biphenyl (PCB) congeners, 

hexachlorobenzene (HCB) and dichloro dichlorophenyl ethylen (DDE) in the 

blood of Yusho patients (n = 28) were statistically compared with those in the 

blood of Fukuoka residents (n = 151). The PCB concentrations in the blood of 

Yusho patients were higher than those of Fukuoka controls and concentration 

ratios of Yusho/Control were various depending on PCB congeners, being 1.6 on 

2,3',4,4',5-pentaCB (# 118), 17.5 on 2,3,3',4,4',5-hexaCB (# 156) and 5.4 on total 

PCBs. Correlation coefficients between age and concentrations of 7 PCB 

congeners, HCB and DDE in the blood of Fukuoka residents were significantly 

positive each other (p < 0.001), while in Yusho patients, the correlation 

coefficients were positive but various depending on the congeners. However, 

correlation coefficient between PCB # 118 and PCB # 156 in the Yusho patients 

was remarkably low, indicating their peculiar accumulative properties in Yusho 

patients. The concentration of PCB # 118 had been markedly decreased after the 

ingestion of PCBs and would be metabolized to hydroxylated PCB, which might 

cause estrogen disturbance in the Yusho patients. 
127

Matsuoka, M., H. Ishibashi, et al. (2005). "The potential contribution of phytoestrogens 

and organochlorine pesticides in an experimental fish diet to estrogenic activity." Journal 

of Health Science 51(2): 212-219. 

 Phytoestrogens and organochlorine pesticides in the diet of lab. animals are 

possible source of interference in bioassays that assess estrogenic activity. In 

the present study, we investigate the levels of dietary phytoestrogens, 

organochlorine pesticides and the estrogenic activity of various diets for an exptl. 

fish and discuss the potential contribution of these substances to estrogenic 

activity, in comparison with those used in previous studies. After hydrolysis with 

?-glucuronidase, genistein and daidzein were detected in all of the diets, and 

there were no significant differences in the contents of these substances among 

present and previous investigations. In addn., organochlorine pesticides, such as 

hexachlorobenzene (HCB), ?-benzene hexachloride (?-BHC), ?-BHC, transnonachlor, and/or endrin, were detected in most fish diets. All of these diets 

exhibited higher levels of activation of ? estrogen receptors than with ? estrogen 

receptors in an in vitro yeast-based bioassay. These results indicate that 

phytoestrogens, such as genistein and daidzein, were the main substances 

contributing to the estrogenic activity of the diet. Moreover, some diets may exert 

estrogenic activity in in vivo tests, indicating the necessity for more careful 

selection of the feeding diet and measurement of estrogenic substances when 

performing routine screening assays for endocrine-disrupting chems. 

Mazzetti, M. B., M. C. Taira, et al. (2004). "Hexachlorobenzene impairs glucose 

metabolism in a rat model of porphyria cutanea tarda: a mechanistic approach." Arch 

Toxicol 78(1): 25-33. 

 Hexachlobenzene (HCB), one of the most persistent environmental pollutants, 

induces porphyria cutanea tarda (PCT). The aim of this work was to analyze the 

effect of HCB on some aspects of glucose metabolism, particularly those related 

to its neosynthesis in vivo. For this purpose, a time-course study on 

gluconeogenic enzymes, pyruvate carboxylase (PC), phosphoenolpyruvate 

carboxykinase (PEPCK), glucose-6-phosphatase (G-6-Pase) and on pyruvate 

kinase (PK), a glycolytic enzyme, was carried out. Plasma glucose and insulin 

levels, hepatic glycogen, tryptophan contents, and the pancreatic insulin 

secretion pattern stimulated by glucose were investigated. Oxidative stress and 

heme pathway parameters were also evaluated. HCB treatment decreased PC, 

PEPCK, and G-6-Pase activities. The effect was observed at an early time point 

and grew as the treatment progressed. Loss of 60, 56, and 37%, respectively, 

was noted at the end of the treatment when a considerable amount of porphyrins 

had accumulated in the liver as a result of drastic blockage of uroporphyrinogen 

decarboxylase (URO-D) (95% inhibition). The plasma glucose level was reduced 

(one-third loss), while storage of hepatic glucose was stimulated in a timedependent way by HCB treatment. A decay in the normal plasma insulin level 

was observed as fungicide intoxication progressed (twice to four times lower). 

However, normal insulin secretion of perifused pancreatic Langerhans islets 

stimulated by glucose during the 3rd and 6th weeks of treatment did not prove to 

be significantly affected. HCB promoted a time-dependent increase in urinary 
128

chemiluminiscence (fourfold) and hepatic malondialdehide (MDA) content 

(fivefold), while the liver tryptophan level was only raised at the longest 

intoxication times. These results would suggest that HCB treatment does not 

cause a primary alteration in the mechanism of pancreatic insulin secretion and 

that the changes induced by the fungicide on insulin levels would be an 

adaptative response of the organism to stimulate gluconeogenesis. They showed 

for the first time that HCB causes impairment of the gluconeogenic pathway. 

Therefore, the reduced levels of glucose would thus be the consequence of 

decreased gluconeogenesis, enhanced glucose storage, and unaffected 

glycolysis. The impairment of gluconeogenesis (especially for PEPCK) and the 

related variation in glucose levels caused by HCB treatment could be a 

consequence of the oxidative stress produced by the fungicide. Tryptophan adds 

its effect to this decrease in the higher phases of HCB intoxication, where its 

levels overcome the control values possibly owing to the drastic decline of UROD. This derangement of carbohydrates leads porphyric hepatocytes to have 

lower levels of free glucose. These results contribute to our understanding of the 

protective and modulatory effect that diets rich in carbohydrates have in hepatic 

porphyria disease. 

Meeker, J. D., L. Altshul, et al. (2007). "Serum PCBs, p,p'-DDE and HCB predict thyroid 

hormone levels in men." Environ Res 104(2): 296-304. 

 Polychlorinated biphenyls (PCBs) and some organochlorine pesticides, which 

continue to be measurable in a high proportion of blood samples from the 

general population, have been found to alter thyroid hormone levels in animals 

and humans. However, studies of these relationships in adult men are limited 

and results across studies have been inconsistent. In the present study, we 

measured serum levels of 57 PCB congeners, dichlorodiphenyldichloroethylene 

(p,p(')-DDE, a stable metabolite of DDT), and hexachlorobenzene (HCB), as well 

as free T(4), total T(3), and TSH, in 341 adult men recruited from an infertility 

clinic from 2000 to 2003. In multivariate linear regression, there were positive 

associations between p,p(')-DDE and both free T(4) and total T(3), and an 

inverse association between p,p(')-DDE and TSH. Conversely, for PCBs there 

was only a suggestive inverse association between PCB 153 and total T(3) when 

potential confounding variables were considered. However, when results were 

additionally adjusted for p,p(')-DDE, inverse associations with T(3) were 

significant for PCB 138, PCB 153, sum of PCBs and three different PCB 

groupings, and HCB, while the positive associations between p,p(')-DDE and 

T(3) also remained. In conclusion, serum concentrations of PCBs, p,p(')-DDE, 

and HCB were associated with circulating thyroid hormone levels in adult men. 

Abbreviations: BMI, body mass index; CYP, cytochrome P450; DDT, 1,1,1-

trichloro-2,2-bis(p-chlorophenyl)ethane; HCB, hexachlorobenzene; MDL, method 

detection limit; NHANES, national health and nutrition examination survey: p,p(')-

DDE, 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene; PCB, polychlorinated 

biphenyl; T(3), triiodothyronine; T(4), thryoxine; TSH, thyroid stimulating hormone 

(thyrotrophin); US, United States. 
129

Meydan, C., A. Kuecuekural, et al. (2008). "Discovery of Biomarkers for 

Hexachlorobenzene Toxicity Using Population Based Methods on Gene Expression 

Data." Chetty, M [Editor] 7(S). 

 Discovering toxicity biomarkers is important in drug discovery to safely evaluate 

possible toxic effects of a substance in early phases. We tried evolutionary 

classification methods for selecting the important classifier genes in 

hexachlorobenzene toxicity using microarray data. Using modified genetic 

algorithms for selection of minimum number of features for classification of gene 

expression data, we discovered a number of gene sets of size 4 that were able to 

discriminate between the control and the hexachlorobenzene (HCB) exposed 

group of Brown-Norway rats with >99% accuracy in 5-fold cross-validation tests, 

whereas classification using all of the genes with SVM and other methods 

yielded results that vary between 48.48% to 81.81%. Making use of this small 

number of genes as biomarkers may allow us to detect toxicity of substances 

with mechanisms of toxicity similar to HCB in a fast and cost efficient manner 

when there are no emerging symptoms. 

Michielsen, C., S. Boeren, et al. (2000). "The mercapturic acid biotransformation 

pathway of hexachlorobenzene is not involved in the induction of splenomegaly, or skin 

and lung lesions in the Brown Norway rat." Arch Toxicol 74(10): 609-17. 

 Involvement of the mercapturic acid pathway in the induction of splenomegaly 

and skin and lung pathology by hexachlorobenzene (HCB) in the rat was 

investigated by seeking to determine whether pentachloronitrobenzene (PCNB) 

has the same inflammatory effects as HCB, since both compounds are directly 

conjugated to glutathione, and further processed into the same mercapturic acid 

metabolites which are excreted via the urine. Female Brown Norway 

(BN/SsNO1aHsd) rats at 3 to 4 weeks of age were orally exposed to diets with or 

without supplementation with 450 mg HCB or equimolar (467 mg) or higher (934 

mg) amounts of PCNB per kilogram of diet over 4 weeks. Gross skin lesion 

development and body weight gains were assessed during exposure and spleen 

and liver weights as well as histopathologic changes in skin and lung were 

assessed after exposure. After 3 weeks of exposure, urinary metabolites of the 

mercapturic acid and oxidative biotransformation pathways were identified using 

high-performance liquid chromatography (HPLC) and liquid chromatographymass spectrometry (LC-MS). Oral exposure of the rats to 450 mg/kg HCB 

resulted in an increase in relative spleen and liver weights as well as in the 

development of skin and lung pathology in the absence of overall liver toxicity. 

Equimolar or higher concentrations of PCNB caused none of these effects. 

Urinary levels of the mercapturic acid N-acetyl-S- (pentachlorophenyl)-cysteine 

(PCP-NAC), were comparable in HCB- and PCNB-treated rats. Levels of closely 

related methylsulfide derivatives of PCP-NAC, also generated via the same 

mercapturic acid pathway, appeared to be significantly higher in PCNB- than in 

HCB-treated rats, whereas the reverse was true for the urinary levels of the 

oxidative metabolite pentachlorophenol (PCP). Thus, results indicate that 

metabolites of the mercapturic acid pathway are not involved in the induction of 

splenomegaly and skin and lung pathology caused by HCB exposure in BN rats 
130

and that the main urinary metabolite of HCB in these BN rats is PCP. Since PCP 

itself, as well as other cytochrome P450-derived metabolites from HCB, are not 

likely to be involved in the induction of splenomegaly and skin and lung 

pathology, it is suggested that either the parent compound HCB or as-yetunidentified non-P450- generated metabolites are involved in these inflammatory 

effects of HCB. 

Michielsen, C., S. Zeamari, et al. (2002). "The environmental pollutant 

hexachlorobenzene causes eosinophilic and granulomatous inflammation and in vitro 

airways hyperreactivity in the Brown Norway rat." Arch Toxicol 76(4): 236-47. 

 Based on observations that the persistent environmental pollutant 

hexachlorobenzene (HCB) induces inflammatory skin lesions and eosinophilic 

and granulomatous lung pathology as well as in vivo airways 

hyperresponsiveness to methacholine in the BN/SsNOlaHsd rat (Michielsen et 

al., Toxicol Appl Pharmacol 172:11-20, 2001), which are features of human 

Churg-Strauss syndrome (CSS), we have investigated whether HCB induced 

other features of CSS such as asthma and systemic vasculitis involving the heart 

and kidneys in this strain of rat. To this end, BN/SsNOlaHsd rats received control 

feed or feed supplemented with 450 mg/kg HCB. On days 6, 14 or 21, tracheas 

were isolated to assess non-specific in vitro airways hyperresponsiveness (AHR) 

to cumulative concentrations of arecoline and serotonin. In addition, lungs were 

lavaged to count and differentiate lavage cells, and skin, lungs, heart, kidneys, 

and lymph nodes were processed for histopathological investigation. HCB 

induced eosinophilic and granulomatous lung pathology in the BN/SsNOlaHsd 

rat, which became more severe with time and was associated with significant in 

vitro AHR to arecoline. Moreover, as in CSS-patients, systemic effects on spleen 

and lymph nodes were observed in HCB-fed BN/SsNOlaHsd rats, as well as 

development of skin lesions with vascular changes and eosinophilic infiltrates. In 

contrast, cardiac or renal involvement, frequently seen in CSS-patients, was not 

seen in HCB-fed rats. More importantly, there were no indications of necrotizing 

vasculitis, a hallmark feature of CSS, in the lungs and skin of BN/SsNOlaHsd 

rats. Thus, it is concluded that the persistent environmental pollutant HCB 

possibly induces a mild or early stage of CSS in the BN/SsNOlaHsd rat that may 

evolve into fully developed CSS after prolonged exposure to HCB. 

Michielsen, C. C., N. Bloksma, et al. (1999). "The role of thymus-dependent T cells in 

hexachlorobenzene-induced inflammatory skin and lung lesions." Toxicol Appl 

Pharmacol 161(2): 180-91. 

 The involvement of thymus-dependent T cells in the inflammatory skin and lung 

lesions and spleen effects induced by hexachlorobenzene (HCB) was 

investigated by using genetically athymic and euthymic WAG/Rij rats and Brown 

Norway (BN) rats with or without depletion of T cells by adult thymectomy, lethal 

irradiation, and bone marrow reconstitution. Rats were exposed to diets with no 

supplementation or diets supplemented with 150 or 450 mg HCB per kg diet for 4 

(BN) or 6 (WAG/Rij) weeks. Skin lesion development and body weight gains 

were assessed during exposure and spleen and liver weights as well as 
131

histopathologic changes in skin, lung, and spleen were assessed after exposure. 

Oral HCB exposure of athymic and euthymic rats of both rat strains resulted in a 

dose-dependent increase of relative liver weight at doses of 150 and 450 mg/kg 

HCB and increased relative spleen weights at a dose of 450 mg/kg. HCB 

exposure of both strains further resulted in inflammatory changes in skin, lungs, 

and splenic red pulp independent of the T cell status except for skin lesions in the 

BN strain. HCB-exposed T cell-competent BN rats showed faster skin lesion 

development than the T cell-depleted rats, although qualitatively and 

quantitatively similar skin pathology was observed at the end of the 4- week 

exposure in both groups. In the WAG/Rij strain skin lesions could not be 

comparatively assessed due to preexistent inflammatory skin pathology in the 

nude rats. This study showed that thymus-derived T cells are not required for the 

induction of skin and lung pathology and splenic changes by HCB and therefore 

it is suggested that HCB acts differently from many allergenic and 

autoimmunogenic low molecular weight compounds that trigger pathology via 

thymus-dependent mechanisms. A role for mononuclear phagocytes and, in BN 

rats, eosinophilic granulocytes, in the HCB-induced pathology is suggested since 

these cells were prominently present in the HCB-induced lesions. 

Michielsen, C. P., A. Leusink-Muis, et al. (2001). "Hexachlorobenzene-induced 

eosinophilic and granulomatous lung inflammation is associated with in vivo airways 

hyperresponsiveness in the Brown Norway rat." Toxicol Appl Pharmacol 172(1): 11-20. 

 We investigated whether the eosinophilic and granulomatous lung pathology that 

develops in Brown Norway (BN/SsNOlaHsd) rats upon feeding 

hexachlorobenzene (HCB) is associated with nonspecific in vivo airways 

hyperresponsiveness (AHR) to methacholine. To this end, female 

BN/SsNOlaHsd rats were exposed to diets with no supplementation or diets 

supplemented with 450 mg HCB per kg feed. On days 7 or 21 of exposure in vivo 

airways hyperresponsiveness to increasing concentrations of methacholine was 

assessed both by whole body plethysmography and by visual scoring. In 

addition, lungs were lavaged to count and differentiate lavage cells, and skin and 

lungs were processed for histology. Lungs of the control rats showed some 

scattered microgranulomas and by 3 weeks of control diet some rats showed 

rather extensive granuloma formation and perivascular and peribronchiolar 

infiltration of eosinophils, as well as increased responsiveness to methacholine. 

Oral exposure to HCB for 7 days caused a moderate perivasculitis, but no 

increase of total serum IgE levels and no AHR to methacholine was found. 

Prolonged HCB exposure for 21 days resulted in severe and extensive 

eosinophilic and granulomatous lung inflammation, a threefold increase of total 

serum IgE levels, and marked cholinergic AHR in all rats. Correlation analysis 

revealed a significant relation between the AHR and lung inflammation, as 

judged by granuloma formation and increased numbers of eosinophilic 

granulocytes in the lung interstitium, particularly around the bronchi and 

bronchioli. No correlation was observed between serum IgE levels and AHR. 

Data suggest that HCB induces AHR by stimulating eosinophilic lung 
132

inflammation and that the preexistent microgranulomas may predispose to 

development of the HCB-induced lung pathology. 

Mueller, P., I. Wolff, et al. (2002). "Screening toward genotoxic effects of halogenated 

hydrocarbons." Naunyn-Schmiedeberg's Archives of Pharmacology 365(Supplement 1): 

R137. 

 

Nakano, K., M. Ishizuka, et al. (2009). "Absolute requirement for iron in the development 

of chemically induced uroporphyria in mice treated with 3-methylcholanthrene and 5-

aminolevulinate." BioMetals: an International Journal on the Role of Metal Ions in 

Biology, Biochemistry, and Medicine 22(2): 345-51. 

 Accumulating evidence, including experiments using cytochrome P450 1a2 

(Cyp1a2) gene knock-out mice (Cyp1a2(-/-)), indicates that the development of 

chemically induced porphyria requires the expression of CYP1A2. It has also 

been demonstrated that iron enhances and expedites the development of 

experimental uroporphyria, but that iron alone without CYP1A2 expression, as in 

Cyp1a2(-/-) mice, does not cause uroporphyria. The role of iron in the 

development of porphyria has not been elucidated. We examined the in vivo 

effect of iron deficiency on hepatic URO accumulation in experimental porphyria. 

Mice were fed diets containing low (iron-deficient diet (IDD), 8.5 mg iron/kg) or 

normal (normal diet (ND), 213.7 mg iron/kg) levels of iron. They were treated with 

3-methylcholanthrene (MC), an archetypal inducer of CYP1A, and 5-

aminolevulinate (ALA), precursors of porphyrin and heme. We found that 

uroporphyrin (URO) levels and uroporphyrinogen oxidation (UROX) activity were 

markedly increased in ND mice treated with MC and ALA, while the levels were 

not raised in IDD mice with the same treatments. CYP1A2 levels and 

methoxyresorufin O-demethylase (MROD) activities, the CYP1A2-mediated 

reaction, were markedly induced in the livers of both ND and IDD mice treated 

with MC and ALA. UROX activity, supposedly a CYP1A2-dependent activity, was 

not enhanced in iron-deficient mice in spite of the fact of induction of CYP1A2. 

We showed that a sufficient level of iron is essential for the development of 

porphyria and UROX activity. 

Nakashima, Y. and S. Ikegami (2000). "Hexachlorobenzene and pentachlorobenzene 

accumulated during pregnancy is transferred to pups at the accumulation ratio in dams." 

Journal of Health Science 46(2): 89-97. 

 Hexachlorobenzene (HCB) and pentachlorobenzene (PECB) were used to clarify 

how the rate at which lipophilic environmental pollutants are metabolized will 

affect their transfer to pups. In this study, the ratio of PECB/HCB transference to 

fetuses and suckling pups was investigated in rats fed a diet containing HCB 

(35.1 nmol/100 g diet) and PECB (351 nmol/100 g diet). The amounts of HCB 

and PECB transferred to fetuses were 0.44% and 0.15% of the amounts 

consumed by their dams, respectively, and the PECB/HCB concentration ratio in 

fetuses was 3.4. In pregnant rats on the day before parturition, the PECB 

concentrations in organs and fat tissue were 3 to 4 times higher than those of 

HCB. After parturition, PECB rapidly disappeared from the body of nursing rats 
133

during the lactation period, especially when compared with HCB. On day 2 after 

birth, HCB and PECB concentrations in the stomach contents of suckling pups 

were highest, and the PECB concentration was 3.5 times higher than that of 

HCB. HCB in the stomach contents decreased gradually (T1/2 = 5.7 d) and 

PECB decreased rapidly (T1/2 = 2.8 d) during the 15 d after birth. These findings 

indicate that the PECB/HCB transferred to fetuses and suckling pups was the 

same ratio found in the blood of their dams. 

Ozalla, D., C. Herrero, et al. (2002). "Evaluation of urinary porphyrin excretion in 

neonates born to mothers exposed to airborne hexachlorobenzene." Environ Health 

Perspect 110(2): 205-9. 

 The existence of a link between hexachlorobenzene (HCB) and porphyria 

cutanea tarda has been known for a long time. However, the epidemiologic data 

on effects on health caused by prenatal exposure have not provided convincing 

evidence that HCB alters porphyrin metabolism. Our objectives were to analyze 

urinary porphyrin excretion and HCB in maternal serum and fetal cord blood in 

neonates born in a village (Flix) near a chlorinated solvent factory, to detect 

possible adverse effects in urinary porphyrin excretion caused by prenatal 

exposure, and to assess their relationship with HCB blood levels. We conducted 

a cross-sectional study in the Porphyria Unit at a tertiary care facility in 

Barcelona, Spain, and the Pediatric Unit of the Mora d'Ebre Hospital, the 

reference hospital of the study area. We included in the study all neonates (n = 

68) born in Mora d'Ebre Hospital 1997- 1999 and their mothers. We obtained 68 

urine specimens of singleton neonates on the third day after birth to test for 

urinary porphyrin excretion. We obtained 52 fetal cord blood and 56 maternal 

serum samples for HCB analysis. Total urinary porphyrins were quantified using 

spectrofluorometry. Porphyrin profile was determined by HPLC. Serum HCB was 

analyzed by gas chromatography coupled with electron capture detection. In total 

population, median HCB levels were 1.08 ng/mL in cord blood and 3.31 ng/mL in 

maternal serum. Total urinary porphyrin concentration was 37.87 micromol/mol 

creatinine. Coproporphyrin I and coproporphyrin III were the major porphyrins 

excreted. We found no positive relationship between urinary porphyrin excretion 

and HCB levels. However, we observed an association between maternal 

smoking and coproporphyrin excretion. Although high environmental levels of 

HCB are reported in the town of Flix, we found no alteration in urinary porphyrin 

excretion. 

Pelletier, C., E. Doucet, et al. (2002). "Associations between weight loss-induced 

changes in plasma organochlorine concentrations, serum T3 concentration, and resting 

metabolic rate." Toxicological Sciences 67(1): 46-51. 

 Organochlorine compds. are released from body fat into the bloodstream during 

wt. loss. Because these compds. may impair thyroid status, which is implicated in 

the control of resting metabolic rate (RMR), the aim of this study was to det. if the 

augmentation in plasma organochlorine concns. might be assocd. with the 

decrease in serum T3 concn. and RMR obsd. in response to body wt. loss. 

Plasma organochlorine concns., serum T3 concn., and RMR were measured 
134

before and after wt. loss in 16 obese men who followed a nonmacronutrientspecific energy-restricted diet for 15 wk. As expected, a significant decrease in 

serum T3 concn. and RMR was obsd. after the program, whereas concns. of 

most detected organochlorines were significantly increased. Changes in 

organochlorine concns. were neg. assocd. with changes in serum T3 concn. 

(significantly for p,p'-DDT, HCB, Aroclor 1260, PCB 28, PCB 99, PCB 118, and 

PCB 170) and with changes in RMR adjusted for wt. loss (significantly for HCB 

and PCB 156). In conclusion, organochlorines released in plasma during wt. loss 

are assocd. with the documented decrease in serum T3 concn. and RMR. 

Further studies are needed to verify whether these findings are causally related. 

Pelletier, G., S. Masson, et al. (2009). "Contribution of methylmercury, polychlorinated 

biphenyls and organochlorine pesticides to the toxicity of a contaminant mixture based 

on Canadian Arctic population blood profiles." Toxicology Letters 184(3): 176-85. 

 Human populations are simultaneously exposed to a variety of anthropogenic 

contaminants. However, despite extensive literature on animal exposure to single 

compounds, data on the toxicity of complex mixtures are scarce. The Northern 

Contaminant Mixture (NCM) was formulated to contain the 27 most abundant 

contaminants in the same relative proportions found in the blood of Canadian 

Arctic populations. Sprague-Dawley rat dams were dosed from the first day of 

gestation until weaning with methylmercury (MeHg), polychlorinated biphenyls 

(PCBs) or organochlorines pesticides (OCs) administered either separately or 

together in the NCM. An additional control group for hypothyroxinemia was 

included by dosing dams with the goitrogen 6-propyl-2-thiouracil (PTU). Offspring 

growth, survival, serum thyroxine and Thyroid Stimulating Hormone (TSH) levels, 

thyroid gland morphology, brain taurine content and cerebellum and 

hippocampus protein expression patterns resulting from such exposures were 

monitored. Pups' increased mortality rate and impaired growth observed in the 

NCM treatment group were attributed to MeHg, while decreased circulating 

thyroxine levels and perturbations of thyroid gland morphology were mostly 

attributable to PCBs. Interestingly, despite comparable reduction in serum 

thyroxine levels, PCBs and PTU exposures produced markedly different effects 

on pup's growth, serum TSH level and brain taurine content. Analysis of 

cerebellum and hippocampus protein expression patterns corroborated previous 

cerebellum gene expression data, as contaminant co-exposure in the NCM 

significantly masked the effects of individual components on protein twodimensional electrophoresis patterns. Identification by MALDI-TOF/TOF MS of 

differentially expressed proteins involved notably in neuronal and mitochondrial 

functions provided clues on the cellular and molecular processes affected by 

these contaminant mixtures. 

Peters, H., Johnson, SAM; Cam, S; Muftu, Y; Oral, S; Ergene, T. (1966). 

"Hexachlorobenzene-induced porphyria: Effect of chelation of the disease, porphyria, 

and metal metabolism." Am. J. Med. Sci. 251(3): 314-322. 

 
135

Peters, H., Gocmen, A; Cripps, DJ; Bryan, GT; Dobramaci, I. (1982). " Epidemiology of 

hexachlorobenzene-induced porphyria in Turkey.Clinical and laboratory follow-up after 

25 years. ." Arch. Neurol 39(12): 744-749. 

 Cutanea tarda and mixed porphyric symptoms resulted from accidental ingestion 

of hexachlorobenzene (HCB)-treated seed grain in Turkey 25 years ago and 

involved about 4,000 persons with a 10% mortality. Twenty-five years later, 161 

patients, 63 women and 98 men, with histories of HCB exposure as children or 

young adults were studied. Many patients had persistent abnormal porphyrin 

metabolism and prominent neurological, dermatologic, and orthopedic symptoms 

and signs. Thyromegaly was seen in 60% of the women and 27% of the men. 

The children born to porphyric mothers 25 years ago all died of pembe yara 

secondary to maternal milk and transplacental transfer of HCB. Current lactation 

specimens of porphyric patients show high HCB levels, up to 3.12 ppm, but the 

infant offspring appear normal. 

Peters, H., D. Cripps, et al. (1987). "Turkish epidemic hexachlorobenzene porphyria a 

30-year study 

" Annals of the New York Academy of Sciences

514: 83-190 

 

Petersen, M. S., J. Halling, et al. (2008). "Impact of dietary exposure to food 

contaminants on the risk of Parkinson's disease." Neurotoxicology 29(4): 584-90. 

 This study aimed to investigate the association of Parkinson's disease (PD) with 

dietary exposure to polychlorinated biphenyls (PCBs) and methylmercury (MeHg) 

in a community with increased exposure levels. A total of 79 clinically verified 

idiopathic PD cases and 154 controls matched by sex and age were examined in 

this case-control study in the Faroe Islands. Blood and hair samples were 

collected and a questionnaire recorded lifetime information on residence, dietary 

habits, smoking history, and occupational exposure to solvents, pesticides, and 

metals. Both unconditional and conditional logistic regression analyses were 

used to estimate the odds ratio (OR) and 95% confidence interval (CI) in regard 

to relevant exposure variables. Increased ORs for dietary intakes of whale meat 

and blubber during adult life were statistically significant. The ORs for 

occupational exposure to solvents, pesticides and metals also suggested an 

increased risk for PD. Current serum concentrations of summation operator PCB 

and related contaminants suggested slightly increased ORs, although only betahexachlorocyclohexane (beta-HCH) was statistically significant. Increased intake 

of whale meat and blubber in adult life was significantly associated with PD, thus 

suggesting a positive association between previous exposure to marine food 

contaminants and development of PD. 

Pieters, R., J. G. Vos, et al. (2005). "Immunotoxic effects the fungicide 

hexachlorobenzene." Toxicology Letters (Shannon) 158(Suppl. 1): S30. 

 
136

Plante, I., M. Charbonneau, et al. (2002). "Decreased gap junctional intercellular 

communication in hexachlorobenzene-induced gender-specific hepatic tumor formation 

in the rat." Carcinogenesis 23(7): 1243-9. 

 Hexachlorobenzene (HCB), an epigenetic carcinogen, HCB induces the 

formation of liver tumors in female rats, whereas only a small percentage of 

males are responsive. Intercellular communication via gap junctions is decreased 

in carcinogenesis. Gap junctions are composed of proteins termed connexins 

(Cxs). The objectives of this study were (i) to determine if HCB-induced tumor 

development is associated with a loss of gap junctional communication; (ii) to 

assess if HCB causes a gender- specific decrease in the expression of Cx32 and 

Cx26; and (iii) to establish if these effects result from gender differences in the 

constitutive expression of these Cxs. Rats were given HCB by gavage for five 

consecutive days. In the first experiment, control and HCB-treated female rats 

were sampled on day 100. Intercellular communication was significantly 

decreased in HCB-treated females compared to controls. To investigate if 

changes in Cx levels occur prior to day 100, experiments done using male and 

female rats sampled on day 50. Hepatic mRNA levels for Cx26 and Cx32 were 

significantly lower only in HCB-treated females as compared to controls. Cx26 

mRNA levels were 3-fold higher and Cx32 mRNA levels were 8-fold lower in 

females compared with males. In a third experiment, ovariectomy abolished any 

differences between male and female controls for both Cxs, while estradiol had a 

partial role in the regulation of Cx32. This suggests that the sexual dimorphism in 

hepatic Cx levels is determined by the ovarian hormones. However, the HCBinduced decrease in Cx32 and Cx26 mRNA levels was maintained in 

ovariectomized rats, suggesting that the HCB effects are not mediated via an 

ovary-dependent pathway. Overall results show that HCB exposure induces 

gender-specific long-term alterations in intercellular gap junctional 

communication in female rat liver. This effect appears to be a critical mechanism 

of HCB-induced liver carcinogenesis and tumor promotion. 

Plante, I., M. Charbonneau, et al. (2006). "Activation of the integrin-linked kinase 

pathway downregulates hepatic connexin32 via nuclear Akt." Carcinogenesis 27(9): 

1923-9. 

 Gap junctions mediate intercellular communication through channels composed 

of proteins termed connexins (Cxs). We have shown that Cx32 is downregulated 

in the liver of female rats exposed to hexachlorobenzene (HCB), an epigenetic 

environmental carcinogen. This is concomitant with the activation of the integrinlinked kinase (ILK) pathway, leading to the activation and nuclear translocation of 

Akt and the inactivation of glycogen synthase kinase-3beta (GSK3beta). Ecadherin, an adhering junction protein, is also downregulated in the liver of these 

female rats, owing to the inactivation of GSK3beta. Using an in vitro model, the 

aim of this study was to determine the role of the ILK pathway in the regulation of 

Cx32. In order to mimic the activation of the ILK pathway, a well-differentiated rat 

hepatoma cell line, MH1C1, was transiently transfected with an expression vector 

for ILK (ILK+ cells). ILK+ cells displayed significantly lower Cx32 mRNA levels 

and Akt was also activated and translocated into the nucleus. Using a 
137

constitutively active Akt expression vector, we showed that Akt transfected cells 

had lower Cx32 mRNA levels, indicating a role for Akt in Cx32 regulation. Finally, 

using an Akt-NES vector, a nuclear-active form of Akt, we showed that Cx32 

protein levels were reduced in transfected cells as compared with cell transfected 

with the wild-type inactive Akt vector, suggesting that the nuclear form of Akt is 

responsible for the downregulation of Cx32. Overall, these data indicate that 

Cx32 is downregulated by the ILK pathway activation in rat hepatocytes and that 

this is mediated via the activation and nuclear translocation of Akt. 

Plante, I., D. Cyr, et al. (2006). "Modulation Of Transcription Factor Binding To 

Connexin 32 Promoter By Hexachlorobenzene In Female Rats." Toxicol Sci 90(1-S): 

195. 

 Hexachlorobenzene (HCB), a widespread epigenetic environmental carcinogen, 

renders female more susceptible than male rats to development of hepatic 

tumors. We have previously shown that in female, but not male rats, HCB downregulates gene expression and causes a significant decrease in gap junctional 

intercellular communication (GJIC). The latter results in part from a decrease in 

the liver gap junction protein, connexin 32 (Cx32). This study was aimed to 

assess the mechanism of HCB-induced Cx32 down-regulation by focusing on the 

binding of transcription factors the gene promoter. Male and female rats were 

administered 100 mg/kg of HCB by gavage for five consecutive days and killed 

45 days later; control rats received corn oil alone. Liver nuclear proteins were 

isolated and incubated with labeled double stranded DNA from three regions of 

the Cx32 promoter (FR26, Fr53, Fr110) which have been shown to regulate the 

expression of hepatic Cx32. The binding protein-DNA complexes were analysed 

by Electrophoretic Mobility Shift Assay. No significant differences between 

groups were observed for the two complexes formed with Fr53; for Fr110 a 

significant 3-fold decrease in the intensity of the complex formed was observed 

between HCB-treated and control females, while no changes were observed in 

proteins isolated from male livers. Furthermore, a female-specific 5-fold decrease 

in binding was observed with Fr26. Supershift experiments are currently under 

investigation to confirm the identity of the transcription factors binding to each 

DNA fragment. Together, these data suggest that the decrease in Cx32 mRNA 

level induced by HCB in females results from a decrease in the binding of 

transcription factors which stimulate the expression of Cx32. 

Plante, I., D. G. Cyr, et al. (2003). "Overexpression of the integrin-linked-kinase pathway 

in HCB-treated female rats." Toxicological Sciences 72(S-1): 237-238. 

 

Plante, I., D. G. Cyr, et al. (2005). "Down-Regulation Of E-Cadherin By The IntegrinLinked Kinase Pathway (ILK) In Hepatocytes; A Possible Mechanism For 

Hexachlorobenzene-Induced Tumor Promotion." Toxicol Sci 84(1-S): 156. 

 The ILK pathway is overexpressed in tumors of various tissues. We have 

previously shown an activation of the ILK pathway in the liver of female rats given 

hexachlorobenzene (HCB), an environmental epigenetic carcinogen. This was 

accompanied by a down-regulation of E-cadherin, an adhering junction protein, 
138

and connexin32 (Cx32), a gap junction protein. The aim of this study was to 

demonstrate the role of the ILK pathway in the regulation of adhering and gap 

junctions in liver cells. MH1C1 rat hepatocytes exposed to HCB for 7 days 

showed increased levels of the inactive form of GSK3beta, i.e. phosphoGSK3beta, an important messenger of ILK activation, and a decrease in Cx32, 

as observed in vivo exposed rats. Two different GSK3beta specific inhibitors 

were used to confirm the role of the ILK pathway in Ecadherin and Cx32 

regulation. Both inhibitors (kenpaullone 5 and 10 uM, SB- 415286 125 and 150 

nM) markedly reduced GSK3beta activity and caused an approximately 50% 

decrease in E-cadherin mRNA levels, whereas Cx32 mRNA levels were 

unchanged. This suggests that in MH1C1 cells, Cx32 expression is not 

modulated by GSK3beta, but depends on either another messenger of the ILK 

pathway, such as Akt, or another pathway. Stable transfections of MH1C1 cells 

with Cx32 expression vector to increase Cx32 expression levels resulted in a 

marked increased Ecadherin mRNA levels thereby suggesting a link between 

Cx32 and E-cadherin regulation. Together, these data demonstrate that in rat 

hepatocytes E-cadherin is down-regulated by the ILK pathway via GSK3beta 

inhibition and up-regulated by Cx32 overexpression. Clearly, both Cx32 and Ecadherin are regulated differently in hepatocytes suggesting that HCB may 

modulate several signalling pathways in the promotion of hepatocarcinogenesis. 

Plante, I., D. G. Cyr, et al. (2005). "Involvement of the integrin-linked kinase pathway in 

hexachlorobenzene-induced gender-specific rat hepatocarcinogenesis." Toxicol Sci

88(2): 346-57. 

 Overexpression of the integrin-linked kinase (ILK) pathway disrupts cell-cell 

interactions, an epigenetic event leading to epithelial cell transformation. Female 

rats exposed to hexachlorobenzene (HCB) for 5 consecutive days and sampled 

45 days later show a decrease in liver gap junctional intercellular communication. 

We hypothesized that HCB also alters E-cadherin expression and that this 

alteration is mediated by the ILK pathway. Hepatic ILK levels were markedly 

increased in HCB-treated female rats. Cytoplasmic/membrane levels of protein 

kinase B (Akt), a target of ILK, and its phosphorylated active form were 

decreased in treated female rats. Flow cytometric analysis showed a concomitant 

increase in nuclear Akt levels. Both ILK and Akt can phosphorylate glycogen 

synthetase kinase-3beta (GSK3beta), rendering it inactive. PhosphorylatedGSK3beta levels were higher in treated females and resulted in a twofold 

decrease in the activity of GSK3beta. The inactivation of GSK3beta in HCBtreated female rats resulted in the nuclear translocation of beta-catenin, as 

demonstrated by both immunocytochemistry and flow cytometric analyses. 

Western blot analysis showed an 84% decrease in E-cadherin levels in HCBtreated rats as compared to controls, and this decrease was not mediated by 

Snail activation. Mimicking the activation of ILK with specific GSK3beta inhibitors 

resulted in downregulation of E-cadherin levels but had no effect on Cx32 

expression in the MH(1)C(1) cells. Overall, these results indicate that hepatic Ecadherin is downregulated as a result of an overexpression of the ILK pathway. 

The concomitant HCB-induced downregulation of intercellular communication 
139

does not occur as a result of either E-cadherin downregulation or GSK3beta 

inactivation. 

Porpora, M. G., E. Medda, et al. (2009). "Endometriosis and organochlorinated 

environmental pollutants: a case-control study on Italian women of reproductive age 

" Environ Health Perspect

117(7): 1070-5 

 Endometriosis is a common gynecologic disease characterized by the ectopic 

growth of endometrial tissue. In industrialized countries, it affects approximately 

10% of women of reproductive age. Its etiology is unclear, but a multifactorial 

origin is considered to be most plausible. Environmental organochlorinated 

persistent pollutants, in particular dioxins and polychlorinated biphenyls (PCBs), 

have been hypothesized to play a role in the disease etiopathogenesis. However, 

results of studies carried out on humans are conflicting. OBJECTIVE: We 

evaluated the exposure to organochlorinated persistent pollutants as a risk factor 

for endometriosis. METHODS: We conducted a case-control study in Rome on 

158 women comprising 80 cases and 78 controls. In all women, serum 

concentrations of selected non-dioxin-like PCBs (NDL-PCBs) and dioxin-like 

PCBs (DL-PCBs), 1,1-dichloro-2,2,-bis(4-chlorophenyl)-ethene (p,p'-DDE), and 

hexachlorobenzene (HCB) were determined by ion-trap mass spectrometry. DRCALUX bioassay was employed to assess the 2,3,7,8-tetrachlorodibenzo-pdioxin toxicity equivalent (TEQ) concentrations of polychlorinated dibenzo-pdioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and DL-PCBs. 

RESULTS: We found an increased risk of endometriosis for DL-PCB-118 [odds 

ratio (OR) = 3.79; 95% confidence interval (CI), 1.61-8.91], NDL-PCB-138 (OR = 

3.78; 95% CI, 1.60-8.94), NDL-PCB-153 (OR = 4.88; 95% CI, 2.01-11.0), NDLPCB-170 (OR = 3.52; 95% CI, 1.41-8.79), and the sum of DL-PCBs and NDLPCBs (OR = 5.63; 95% CI, 2.25-14.10). No significant associations were 

observed with respect to HCB or to the sum of PCDDs, PCDFs, and DL-PCBs 

given as total TEQs. CONCLUSIONS: The results of this study show that an 

association exists between increased PCB and p,p'-DDE serum concentrations 

and the risk of endometriosis. 

Ralph, J. L., M. C. Orgebin-Crist, et al. (2003). "Disruption of androgen regulation in the 

prostate by the environmental contaminant hexachlorobenzene." Environ Health 

Perspect 111(4): 461-6. 

 Hexachlorobenzene (HCB) is a persistent environmental contaminant that has 

the potential to interfere with steroid hormone regulation. The prostate requires 

precise control by androgens to regulate its growth and function. To determine if 

HCB impacts androgen action in the prostate, we used a number of methods. 

Our in vitro cell-culture-based assay used a firefly luciferase reporter gene driven 

by an androgen-responsive promoter. In the presence of dihydrotestosterone, 

low concentrations (0.5-5 nM) of HCB increased the androgen-responsive 

production of firefly luciferase and high concentrations of HCB (> 10 microM) 
140

suppressed this transcriptional activity. Results from a binding assay showed no 

evidence of affinity between HCB and the androgen receptor. We also tested 

HCB for in vivo effects using transgenic mice in which the transgene was a 

prostate-specific, androgen-responsive promoter upstream of a chloramphenicol 

acetyl transferase (CAT) reporter gene. In 4-week-old mice, the proportion of 

dilated prostate acini, a marker of sexual maturity, increased in the low HCB 

dose group and decreased in the high HCB dose mice. In the 8-week-old mice, 

there was a significant decrease in both CAT activity and prostate weight upon 

exposure to 20 mg/kg/day HCB. Therefore, in vitro and in vivo data suggest that 

HCB weakly agonizes androgen action, and consequently, low levels of HCB 

enhanced androgen action but high levels of HCB interfered. Environmental 

contaminants have been implicated in the rising incidence of prostate cancer, 

and insight into the mechanisms of endocrine disruption will help to clarify their 

role. 

Randi, A. S., S. Hernandez, et al. (2003). "Hexachlorobenzene increases ornithine 

decarboxylase activity, free polyamines content and c-Myc, c-Fos and c-Jun protein 

levels in rat liver." Toxicology Letters (Shannon) 144(Suppl. 1): s168. 

 

Randi, A. S., M. S. Sanchez, et al. (2008). "Hexachlorobenzene triggers AhR 

translocation to the nucleus, c-Src activation and EGFR transactivation in rat liver." 

Toxicol Lett 177(2): 116-22. 

 Hexachlorobenzene (HCB) is a widespread environmental pollutant. It has some 

properties that are typical for dioxin-like compounds that act mainly through the 

aryl hydrocarbon receptor (AhR) protein. Upon dioxin binding, the AhR 

translocates to the nucleus and modulates gene expression. At the same time, cSrc kinase frees from the AhR complex and thereby activates its own kinase 

activity, which acts as a trigger for the growth factor receptor signal transduction 

pathway. HCB is a weak agonist of the AhR, and the evidence that HCB toxicity 

is mediated via the AhR complex is limited and inconclusive. In the present 

study, female Wistar rats were administered HCB (1, 10 and 100mg/kg) for 30 

days. Liver cytosolic AhR was translocated to the nucleus. The activity of liver 

microsomal c-Src increased at all assayed doses. HCB induced the association 

of the EGFR with c-Src and increased the phosphorylation of EGFR at tyrosine 

845 (Tyr845), a known c-Src phosphorylation site. c-Src from WB-F344 cells 

treated with HCB exhibited increased protein levels and c-Src-pTyr416 

phosphorylation than the control cells. Again HCB induced EGFR 

phosphorylation at Tyr845. Such an effect of HCB could not be detected when cSrc activity was blocked by PP2. All together, our data demonstrates that HCB 

may induce EGFR transactivation through an c-Src-dependent pathway. 

Randi, A. S., H. A. Sancovich, et al. (2003). "Effect of in vivo administered 

hexachlorobenzene on epidermal growth factor receptor levels, protein tyrosine kinase 

activity, and phosphotyrosine content in rat liver." Biochem Pharmacol 65(9): 1495-506. 

 In the present study, the effects of hexachlorobenzene (HCB) on epidermal 

growth factor receptor (EGFR) content of liver microsomes and plasma 
141

membrane, and on EGFR-tyrosine kinase activity in the microsomal fraction were 

investigated. In addition, we studied the parameters of the tyrosine kinase 

signalling pathway such as protein tyrosine kinase (PTK) activity and 

phosphotyrosine content in microsomal and cytosolic protein. To determine 

whether the observed alterations were correlated with a manifestation of overt 

toxicity, a single very low dose of HCB (1mg/kg body wt) and two much higher 

doses (100 and 1000 mg/kg body wt), the highest being toxicologically significant 

in that it reduced serum thyroxine (T(4)) and inhibited uroporphyrinogen 

decarboxylase (URO-D) (EC 4.1.1.37) activity, were tested. Our results 

demonstrated that liver microsomes of rats treated with HCB had higher levels of 

EGFR than untreated rats; treated rats also had less EGFR present in 

hepatocyte plasma membrane fractions than did untreated rats. HCB altered the 

phosphotyrosine content and protein phosphorylation of some microsomal and 

cytosolic proteins in a biphasic dose-response relationship. At the low dose, 

phosphorylation and phosphotyrosine content of several microsomal proteins 

were increased; however, these effects were diminished or reversed at the 

higher doses. Our results suggest that chronic HCB treatment produces a downregulation of the EGFR and a dose-dependent increase in EGFR-tyrosine kinase 

activity in the microsomal fraction. This effect may contribute to the alteration of 

membrane and cytosolic protein tyrosine phosphorylation. The level of sensitivity 

encountered in our studies is extraordinary, occurring at 1/10 to 1/1000 the doses 

of HCB known to cause other toxicological lesions. 

Rios de Molina, M. B., SC; San Martin de Viale, LC. (1986). "Does feeding of 

hexachlorobenzene promote structural changes in rat liver porphyrinogen carboxylase? 

." In: Hexachlorobenzene: Proceedings of an international symposium (C.R. Morris and 

J.P.R. Cabral, Eds.) IARC: 481-486. 

 

Rios de Molina, M. C., M. B. Mazzetti, et al. (2002). "The decrease in uroporphyrinogen 

decarboxylase activity induced by ethanol predisposes rats to the development of 

porphyria and accelerates xenobiotic-triggered porphyria, regardless of hepatic 

damage." Braz J Med Biol Res 35(11): 1273-83. 

 We evaluated the porphyrinogenic ability of ethanol (20% in drinking water) per 

se, its effect on the development of sporadic porphyria cutanea tarda induced by 

hexachlorobenzene in female Wistar rats (170-190 g, N = 8/group), and the 

relationship with hepatic damage. Twenty-five percent of the animals receiving 

ethanol increased up to 14-, 25-, and 4.5-fold the urinary excretion of deltaaminolevulinate, porphobilinogen, and porphyrins, respectively. Ethanol 

exacerbated the precursor excretions elicited by hexachlorobenzene. Hepatic 

porphyrin levels increased by hexachlorobenzene treatment, while this parameter 

only increased (up to 90-fold) in some of the animals that received ethanol alone. 

Ethanol reduced the activities of uroporphyrinogen decarboxylase, deltaaminolevulinate dehydrase and ferrochelatase. In the ethanol group, many of the 

animals showed a 30% decrease in uroporphyrinogen activity; in the ethanol + 

hexachlorobenzene group, this decrease occurred before the one caused by 

hexachlorobenzene alone. Ethanol exacerbated the effects of 
142

hexachlorobenzene, among others, on the rate-limiting enzyme deltaaminolevulinate synthetase. The plasma activities of enzymes that are markers 

of hepatic damage were similar in all drug-treated groups. These results indicate 

that 1) ethanol exacerbates the biochemical manifestation of sporadic 

hexachlorobenzene-induced porphyria cutanea tarda; 2) ethanol per se affects 

several enzymatic and excretion parameters of the heme metabolic pathway; 3) 

since not all the animals were affected to the same extent, ethanol seems to be a 

porphyrinogenic agent only when there is a predisposition, and 4) hepatic 

damage showed no correlation with the development of porphyria cutanea tarda. 

Rios de Molina, M. W. d. C., R; San Martin de Viale, LC. (1980). "Investigations on the 

presence of porphyrinogen carboxylase inhibitor in the liver of rats intoxicated with 

hexachlorobenzene." Int J Biochem 12: 1027-1032. 

 

Roncaglioni, A., M. Novic, et al. (2004). "Classification of Potential Endocrine Disrupters 

on the Basis of Molecular Structure Using a Nonlinear Modeling Method." Journal of 

Chemical Information and Computer Sciences 44(2): 300-309. 

 A methodol. for the classification of endocrine disruption chems. is proposed. It is 

based on a data set of 106 substances extd. from the list of 553 chems. that 

were inspected by the European Union Commission for the scientific evidence of 

their endocrine disruption activity. The substances belong to different categories 

defined in the EU Commission report: (i) literature evidence for certainly active as 

endocrine disrupters, (ii) for potentially active, (iii) for less probable active - 

lacking evidence, and (iv) for certainty nonactive. 3D mol. coordinates were 

calcd. using the AM1 or the PM3 optimization method. From 3D coordinates an 

extensive set of mol. descriptors was calcd. The classification model based on 

the counterpropagation neural network was constructed and evaluated. This is 

the first time that the counterpropagation neural network is applied for the 

classification of compds. regarding their literature evidence for the endocrine 

disruption activity. The developed classification model is proposed as a tool for a 

preliminary assessment of potential endocrine disrupters, which would help the 

assessors to make the priority list for a large amt. of chems. that have to be 

tested with more expensive in vitro and in vivo methods. 

Ropstad, E., I. C. Oskam, et al. (2006). "Endocrine disruption induced by 

organochlorines (OCs): field studies and experimental models." Journal of toxicology 

and environmental health. Part A. 69(1-2): 53-76. 

 Long-range transport of persistent organic compounds by air and ocean currents 

from industrialized areas resulted in high levels of these pollutants in food webs 

in the Svalbard area. With the aim to test if organochlorine (OC) exposure in freeliving polar bears from Svalbard affected their plasma steroid hormone 

concentrations, it was found that polychlorinated biphenyls (PCBs) were 

associated with increased progesterone levels in females. The sum of pesticides 

(sigma pesticides) and sigma PCBs contributed significantly negative to the 

variation of the plasma testosterone in males, and the overall contribution of the 

OCs to the plasma cortisol variation was negative. A second objective was to 
143

study the effects of selected OCs (i.e., PCB 153 and PCB 126) on animal health 

as a consequence of effects on endocrine-regulated functions such as 

reproduction and immunity in a goat model focusing on long-term and low-level 

exposure during the periods of fetal development and in the neonatal period. 

Additionally, acute exposure was studied in adult mice. The results indicated that 

exposure to low doses of PCB 153 in utero and in the suckling period influenced 

reproductive functions and both PCB 153 and PCB 126 exerted 

immunomodulatory effects on the offspring, whereas acute exposure of adult 

mice had minor effects on male reproductive function. 

Roy, P., H. Salminen, et al. (2004). "Screening of some anti-androgenic endocrine 

disruptors using a recombinant cell-based in vitro bioassay." Journal of Steroid 

Biochemistry and Molecular Biology 88(2): 157-66. 

 The present work describes the development and optimization of a cell-based 

androgen reporter assay using the Chinese hamster ovarian cell line (CHO K1) in 

the 96-well format. The recent reports on increasing exposure of humans and 

wild-life to environmental endocrine disrupting chemicals (ED) prompt the need 

for high throughput screening systems for such compounds in environmental and 

biological samples. To this end, CHO cells were cotransfected with plasmids 

encoding mouse mammary tumour virus-neomycin-luciferase and human 

androgen receptor (hAR), and a stable cell line was established. After selection 

with neomycin, a highly active clone was obtained which stably expressed both 

the hAR and the androgen-responsive luciferase reporter. Stimulation of the cells 

with androgens for 24 h resulted in about 15-fold stimulation of luciferase activity, 

with the minimum effective dose of testosterone being 0.1 nmol/l. Potent steroidal 

and non-steroidal anti-androgens, such as hydroxyflutamide and cyproterone 

acetate, significantly inhibited the androgen-induced transactivation. Nonandrogenic steroids like estradiol, progesterone, dexamethasone and cortisol 

showed weak activity at high concentrations. RT-PCR and western blot 

confirmed proper transcription and translation as well as stable expression of the 

AR gene in the cells. About 60 different chemicals (mostly pesticides or their 

metabolites, and common industrial chemicals) were screened with the cell line 

for their ability to stimulate luciferase activity or inhibit that evoked by 0.1 nmol/l 

R1881, used as a positive androgenic control. About 10 highly potent antiandrogenic chemicals were identified. The most potent anti-androgenic 

compounds identified in our assay included bisphenol A, alphahexachlorocyclohexane, vinclozolin and 4,4-DDE. These compounds had alone 

either no effect or were weak agonists (with cytotoxic effects at very high 

concentrations), but none showed any significant agonistic activity. In conclusion, 

we demonstrate that the bioassay based on this cell line provides a reliable test 

for detecting androgenic and anti-androgenic compounds. The 96-well plate 

format makes the assay suitable for high throughput screening. 

Sala, M., J. Sunyer, et al. (1999). "Health effects of chronic high exposure to 

hexachlorobenzene in a general population sample." Arch Environ Health 54(2): 102-9. 
144

 Hexachlorobenzene, an organochlorine compound that accumulates in humans, 

is widespread throughout the environment. In this study, we describe the health 

status of inhabitants of a rural village that surrounds an electrochemical factory 

characterized by high levels of hexachlorobenzene in the air. During 1994, we 

conducted a cross- sectional study of 1 800 inhabitants in the south of Catalonia, 

Spain, who were older than 14 y of age. We obtained information on lifestyles 

and occupational and medical histories via questionnaire. Self-reported health 

outcomes were validated against clinical records and cancer registry data. Serum 

levels of hexachlorobenzene were very high in males who worked in the 

electrochemical factory (geometric mean = 54.6 ng/ml in randomized 

participants). Levels were lower among subjects who had never worked in the 

electrochemical factory (females, 14.9 ng/ml; males, 9.0 ng/ml). Levels of other 

organochlorine compounds (i.e., beta- hexachlorocy-clohexane, 2,2-bis[pchlorophenyl]-1,1-dichloroethylene) were in the same range found in other 

communities. Perceived health, prevalence of self-reported common chronic 

conditions, and porphyria cutanea tarda, thyroid pathology, Parkinson's disease, 

cancer, and reproductive outcomes were within the ranges observed in other 

studies. Employment in the plant, however, was associated with having any of 

the a priori selected health outcomes that were potentially related to exposure to 

hexachlorobenzene (odds ratio for cancer prevalence = 1.9; 95% confidence 

interval = 0.5, 7.6). Our population of workers and nonworkers had the highest 

levels of hexachlorobenzene ever described. The results suggest that exposure 

to hexachlorobenzene did not affect the general health status of the this 

population, but it was associated with specific health effects of the most highly 

exposed subjects. 

Schell, L. M. (2002). Mohawk culture, behavior, toxicant exposure and health. Crisp 

Data Base National Institutes of Health. New York. 

 Considerable concern exists over possible effects on human physical and 

psychological development of endocrine disrupting environmental contaminants 

such as polychlorinated biphenyls (PCBs). Native American communities are 

particularly at risk owing to subsistence systems and a cultural ethos involving 

greater contact with the physical environment. The proposed study follows-up 

220 Mohawk adolescents aged 17-21 years, who participated in a previous study 

when they were 10-16 years old. All adolescents are members of the Mohawk 

Nation at Akwesasne which is located on the St. Lawrence River, adjacent to 

hazardous waste sites where PCBs have contaminated the local ecology. The 

investigation examines the interrelationship between Mohawk cultural identity, 

traditional Mohawk customs, behaviors related to toxicant exposure and current 

toxicant burden. Serum level of PCBs will be assessed by congener specific 

analysis. The study will determine 1) the relationship of congeners and their 

hydroxylated metabolites to thyroid function (thyroid hormone levels and antithyroid antibodies), and 2) psychosocial outcomes including school behavior and 

performance, hyperactivity, and adaptation to the community. Data gathered for 

the past study will be employed to assess variation in metabolism of PCBs, as 

well as how earlier measures of cognition and hyperactivity relate to 17 year old 
145

psychosocial outcomes. Variation in susceptibility to PCB effects will be 

determined by examining the effects of concurrent toxicant exposure 

(hexachlorobenzene, Mirex, dichlorodiphenyldichloroethene, lead), diet, and 

indicators of PCB metabolism, on the focal measures of adult functioning. The 

proposed study will clarify the causal pathways between culturally identifying 

behavior, PCB exposure and body burden, thyroid functioning, cognitive 

functioning, social behavior and school functioning while identifying activities that 

are important to maintain cultural identify and unrelated to exposure. 

Schell, L. M. (2003). Mohawk culture, behavior, toxicant exposure and health. Crisp 

Data Base National Institutes of Health. New York. 

 Considerable concern exists over possible effects on human physical and 

psychological development of endocrine disrupting environmental contaminants 

such as polychlorinated biphenyls (PCBs). Native American communities are 

particularly at risk owing to subsistence systems and a cultural ethos involving 

greater contact with the physical environment. The proposed study follows-up 

220 Mohawk adolescents aged 17-21 years, who participated in a previous study 

when they were 10-16 years old. All adolescents are members of the Mohawk 

Nation at Akwesasne which is located on the St. Lawrence River, adjacent to 

hazardous waste sites where PCBs have contaminated the local ecology. The 

investigation examines the interrelationship between Mohawk cultural identity, 

traditional Mohawk customs, behaviors related to toxicant exposure and current 

toxicant burden. Serum level of PCBs will be assessed by congener specific 

analysis. The study will determine 1) the relationship of congeners and their 

hydroxylated metabolites to thyroid function (thyroid hormone levels and antithyroid antibodies), and 2) psychosocial outcomes including school behavior and 

performance, hyperactivity, and adaptation to the community. Data gathered for 

the past study will be employed to assess variation in metabolism of PCBs, as 

well as how earlier measures of cognition and hyperactivity relate to 17 year old 

psychosocial outcomes. Variation in susceptibility to PCB effects will be 

determined by examining the effects of concurrent toxicant exposure 

(hexachlorobenzene, Mirex, dichlorodiphenyldichloroethene, lead), diet, and 

indicators of PCB metabolism, on the focal measures of adult functioning. The 

proposed study will clarify the causal pathways between culturally identifying 

behavior, PCB exposure and body burden, thyroid functioning, cognitive 

functioning, social behavior and school functioning while identifying activities that 

are important to maintain cultural identify and unrelated to exposure. 

Schulte, A., J. Althoff, et al. (2002). "Two immunotoxicity ring studies according to 

OECD TG 407-comparison of data on cyclosporin A and hexachlorobenzene." Regul 

Toxicol Pharmacol 36(1): 12-21. 

 Two international ring studies were performed to develop appropriate parameters 

within standard toxicology study for screening of immunotoxicological potential of 

unknown substances. These studies followed OECD TG 407 and included a 

number of additional examinations. CSA was selected as model for its 

immunosuppressive and HCB as model for its immunostimulating effects. 
146

Reproducibility of data was defined by significant findings in at least 50% of 

participating laboratories. In-life clinical observations, values for WBC 

parameters, and changes of lymphoid organ weights suggested immune effects. 

Elevated IgM titers indicated increased antibody formation in HCB-exposed rats. 

Cellularity of T-cell compartments in thymus (medulla), spleen (PALS), and 

lymph nodes (paracortical zone of mesenteric and popliteal LN) were dose 

dependently decreased in CSA-treated rats. The numbers of follicular germinal 

centers were reduced in LN. HCB induced cellular proliferation in spleen 

marginal zones and endothelial activation in HEV of mesenteric and popliteal LN 

and GALT and in small pulmonary venules. Data obtained by specific immune 

parameters indicated immune effects; however, statistical inference was limited 

to low numbers of participating laboratories. In spleen, both substances 

decreased lymphoblast proliferation after ConA mitogen stimulation. Reduced 

numbers of antibody-forming cells in PFC assay indicated impaired T-celldependent humoral immunity by CSA, which was not seen for HCB. Altered 

fractions for B- and T-cell subpopulations were identified in spleen for both 

substances. In order to predict immunomodulatory effects of CSA or HCB, 

histomorphologic examination of lymphoid tissues resulted in the most reliable 

and sensitive data to distinguish immunosuppression and -stimulation. 

Sekihashi, K., A. Yamamoto, et al. (2002). "Comparative investigation of multiple organs 

of mice and rats in the comet assay." Mutation research. 517(1-2): 53-75. 

 Mice and/or rats are usually used to detect chemical carcinogenicity and it has 

been known that there are species differences in carcinogenicity. To know 

whether there are species difference in genotoxicity, we conducted comparative 

investigation of multiple organs of mice and rats in the comet assay. Since the 

sensitivity to xenobiotics is different for different species, we queried species 

difference in the genotoxic sensitivity at one equitoxic level but not at one 

equidose. Therefore, groups of four mice or rats were treated once 

intraperitoneally or orally with a chemical at highest dose without death and 

distinct toxic manifestation. When the death was not observed at 2000 mg/kg of a 

chemical, 2000 mg/kg was used for the comet study. The stomach, colon, liver, 

kidney, bladder, lung, brain, and bone marrow were sampled 3, 8, and 24h after 

treatment. Among chemicals tested, benzyl acetate, chlorodibromomethane and 

p-chloro-o-toluidine are carcinogenic to mice but not rats, and aniline, 

azobenzene, o-phenylphenol Na, and D-limonene are carcinogenic to rats but 

not mice. Although the two species differed in genotoxicity target organs and 

migration values, the judgement of a positive or negative response was the same 

for all chemicals studied except for 2,4-dimethoxyaniline, 2,5-diaminotoluene, 

and p,p'-DDT when chemicals with positive responses in at least one organ are 

judged to be comet assay-positive. 2,4-Dimethoxyaniline and 2,5-diaminotoluene 

that are Ames test-positive non-carcinogens in both species were positive in one 

organ (urinary bladder for 2,4-dimethoxyaniline and stomach for 2,5-

diaminotoluene) in rats, but negative in all mouse organs. p,p'-DDT, which is an 

Ames test-negative but in vitro cytogenetic test-positive hepatic carcinogen in 

mice and rats, was positive in multiple rat organs, but not in any mouse organ. 
147

These results suggest that species differences in genotoxicity at one equitoxic 

level are not consistent with species difference in carcinogenicity and that the 

use of both species is appropriate to indicate a carcinogenic potential in the 

comet assay with multiple organs, when chemicals being positive in at least one 

organ are judged to be comet assay-positive. 

Sonne, C., R. Dietz, et al. (2005). "Do organohalogen contaminants contribute to 

histopathology in liver from East Greenland polar bears (Ursus maritimus)?" 

Environmental Health Perspectives 113(11): 1569-74. 

 In East Greenland polar bears (Ursus maritimus), anthropogenic organohalogen 

compounds (OHCs) (e.g., polychlorinated biphenyls, 

dichlorodiphenyltrichloroethane, and polybrominated diphenyl ethers) contributed 

to renal lesions and are believed to reduce bone mineral density. Because OHCs 

are also hepatotoxic, we investigated liver histology of 32 subadult, 24 adult 

female, and 23 adult male East Greenland polar bears sampled during 1999-

2002. Light microscopic changes consisted of nuclear displacement from the 

normal central cytoplasmic location in parenchymal cells, mononuclear cell 

infiltrations (mainly portally and as lipid granulomas), mild bile duct proliferation 

accompanied by fibrosis, and fat accumulation in hepatocytes and pluripotent Ito 

cells. Lipid accumulation in Ito cells and bile duct hyperplasia accompanied by 

portal fibrosis were correlated to age, whereas no changes were associated with 

either sex or season (summer vs. winter). For adult females, hepatocytic 

intracellular fat increased significantly with concentrations of the sum of 

hexachlorocyclohexanes, as was the case for lipid granulomas and 

hexachlorobenzene in adult males. Based on these relationships and the nature 

of the chronic inflammation, we suggest that these findings were caused by aging 

and long-term exposure to OHCs. Therefore, these changes may be used as 

biomarkers for OHC exposure in wildlife and humans. To our knowledge, this is 

the first time liver histology has been evaluated in relation to OHC concentrations 

in a mammalian wildlife species, and the information is important to future polar 

bear conservation strategies and health assessments of humans relying on 

OHC-contaminated food resources. 

Sonne, C., P. S. Leifsson, et al. (2008). "Greenland sledge dogs (Canis familiaris) 

develop liver lesions when exposed to a chronic and dietary low dose of an 

environmental organohalogen cocktail." Environmental Research 106(1): 72-80. 

 We assessed the relationship between exposure to organohalogen polluted 

minke whale (Balaenoptera acutorostrata) blubber and liver morphology and 

function in a generational controlled study of 28 Greenland sledge dogs (Canis 

familiaris). The prevalence of portal fibrosis, mild bile duct hyperplasia, and 

vascular leukocyte infiltrations was significantly higher in the exposed group (all 

Chi-square: p<0.05). In case of granulomas, the frequency was significantly 

highest in the bitches (P generation) while the prevalence of portal fibrosis was 

highest in the F generation (pups) (both Chi-square: p<0.05). No significant 

difference between exposed and controls was found for bile acid, ALAT, and 

ALKP, while ASAT and LDH were significantly highest in the control group (both 
148

ANOVA: p<0.05). We therefore suggest that a daily intake of 50-200g 

environmentally organohalogen polluted minke whale blubber can cause liver 

lesions in Greenland sledge dogs. It is reasonable to infer that other apex 

predators such as polar bears (Ursus maritimus) and humans may suffer from 

similar impacts. 

Sugiura-Ogasawara, M., Y. Ozaki, et al. (2003). "PCBs, hexachlorobenzene and DDE 

are not associated with recurrent miscarriage." Am J Reprod Immunol 50(6): 485-9. 

 PROBLEM: A case-control study was designed to evaluate any associations 

between high exposure to polychlorinated biphenyls (PCB), hexachlorobenzene 

(HCB) and the 1,1,1,-trichloro-2,2-bis (p-chlorophenyl) ethane (DDT) metabolite 

1,1-dichloro-2,2-bis (p-chlorophenyl) ethylene (DDE) and recurrent miscarriage 

and immunoendocrine abnormalities. METHODS OF STUDY: A total of 18 kinds 

of co-planer PCBs, HCB, DDE, natural killer cell (NK) activity, antiphospholipid 

antibodies, antinuclear antibody, prolactin, progesterone, thyroid-stimulating 

hormone (TSH) and free T4 were examined in 45 patients with a history of three 

or more (3-11) consecutive first-trimester miscarriages and 30 healthy women 

with no history of live birth and infertility. RESULTS: There were no differences in 

mean +/- S.D. values in serum samples for PCBs, HCB and DDE between 

patients and controls. Hypothyroidism, hyperprolactinemia, luteal phase defects, 

NK cell activity and the presence of autoantibodies were also not associated with 

levels of any of the compounds in the patients. CONCLUSION: PCBs, HCB and 

DDE are not associated with miscarriage and immunoendocrine abnormalities in 

patients with a history of recurrent miscarriage. 

Sunyer, J., C. Herrero, et al. (2002). "Serum organochlorines and urinary porphyrin 

pattern in a population highly exposed to hexachlorobenzene." Environ Health 1(1): 1. 

 BACKGROUND: Porphyria cutanea tarda (PCT) is caused by 

hexachlorobenzene (HCB) in several species of laboratory mammals, but the 

human evidence is contradictory. In a study among adults of a population highly 

exposed to HCB (Flix, Catalonia, Spain), the prevalence of PCT was not 

increased. We aimed at analysing the association of individual urinary porphyrins 

with the serum concentrations of HCB and other organochlorine compounds in 

this highly exposed population. METHODS: A cross-sectional study on total 

porphyrins was carried out in 1994 on 604 inhabitants of the general population 

of Flix, older than 14 years. Of them, 241 subjects (comprising a random sample 

and the subgroup with the highest exposure) were included for the present study. 

The porphyrin profile was determined by high-pressure liquid chromatography. 

Serum concentrations of HCB, as well as common organochlorine compounds, 

were determined by gas chromatography coupled to electron capture detection. 

RESULTS: Coproporphyrin I (CPI) and coproporphyrin III (CPIII) were the major 

porphyrins excreted, while uroporphyrins I and III were only detected in 2% and 

36% of the subjects respectively, and heptaporphyrins I and III in 1% and 6%, 

respectively. CPI and CPIII decreased with increasing HCB concentrations (p < 

0.05). This negative association was not explained by age, alcohol, smoking, or 

other organochlorine compounds. No association was found between 
149

uroporphyrin I and III excretion, nor heptaporphyrin excretion, and HCB. CPIII 

increased with smoking (p < 0.05). CONCLUSION: HCB exposure in this highly 

exposed population did not increase urinary concentrations of individual 

porphyrins. 

Taira, M. C., M. B. Mazzetti, et al. (2004). "Glycogen metabolism and glucose transport 

in experimental porphyria." Toxicology 197(2): 165-75. 

 Hexachlorobenzene (HCB) is a fungicide of well-known porphyrinogenic ability, 

which induces an experimental porphyria that resembles human porphyria 

cutanea tarda (PCT) in several animal species. It has been demonstrated that 

high glucose ingestion prevents porphyria development, and high-fat/high-protein 

diets enhance HCB porphyrinogenic ability. On the contrary, a diet rich in 

carbohydrates reduces HCB effects. The aim of this work was to study HCB 

effects on glycogen synthesis and degradation, as well as on glucose synthesis 

and transport, in order to elucidate whether would justify the beneficial use of 

carbohydrates in this porphyria. Rats were treated with HCB dissolved in corn oil 

(five daily doses 100mg/kg body weight). Results showed that: (1) HCB caused 

an increase in glycogen content; (2) glycogen synthase activity increased three 

times, and phosphorylase activity decreased about 40% due to fungicide 

intoxication. The effect of HCB on these two activities accounted for the higher 

glycogen content observed in treated animals; (3) three gluconeogenic enzymes 

were reduced 30-50%; (4) glucose uptake in the liver decreased in all weeks 

studied. The alterations found in glucose synthesis, its uptake in liver and other 

tissues, and its release from glycogen might contribute to the biochemical 

porphyria picture and would account for the effect of glucose above mentioned. 

Wade, M. G., S. Parent, et al. (2002). "Thyroid toxicity due to subchronic exposure to a 

complex mixture of 16 organochlorines, lead, and cadmium." Toxicological Sciences

67(2): 207-18. 

 The human population in the industrialized world is ubiquitously exposed to 

complex mixtures of persistent pollutants that contaminate food, water, and air. A 

large number of these contaminants have been shown to cause significant 

toxicity to the hypothalamic-pituitary-thyroid (HPT) axis in laboratory animal 

studies, through a variety of mechanisms, although these effects occur at levels 

of exposure greatly in excess of common human exposure. While many of the 

mechanisms of thyroid toxicity of these substances are potentially 

complementary, little is known of the degree of interaction of common persistent 

contaminants on responses of the HPT axis. To investigate the potential effects 

of a complex, environmentally relevant mixture on the HPT axis, sexually mature 

male rats were administered a mixture of 16 common organochlorines 

(dichlorodiphenoxytrichloroethane [DDT], p,p'-dichlorodiphenoxydichloroethylene 

[p,p'-DDE], hexachlorobenzene [HCB], tetrachlorodibenzo-p-dioxin [TCDD], 

polychlorinated biphenyls [PCBs], methoxychlor, endosulfan, heptachlor, 

hexachlorocyclohexane, dieldrin, aldrin, mirex, and several chlorinated 

benzenes, and metal contaminants [lead, cadmium]). The doses of the mixture 

that were administered were related to minimum risk levels or tolerable daily 
150

intakes of these substances, as derived by risk assessment with the 1x, 10x, 

100x, and 1000x groups receiving mixture components at doses equivalent to 1x, 

10x, 100x, or 1000x the minimum risk level (or tolerable daily intake, reference 

dose), respectively. After 70 daily treatments by gavage, endpoints related to 

circulating thyroid hormone (serum thyroxine [T(4)], triiodothyronine [T(3)], 

thyroid stimulating hormone [TSH], and serum T(3) uptake [T(3)-up]), thyroid 

gland histomorphology (thyroid follicle cross sectional area, epithelial height, 

follicle roundness or aspect ratio, colloid/epithelial ratio) and hepatic metabolism 

of thyroid hormone (UDP-glucuronyl transferase [UGT] and outer-ring deiodinase 

[ORD]) were assessed. All examined endpoints were significantly altered by the 

mixture albeit with great variability between endpoints in the sensitivity. While 

most endpoints examined did not show significant changes at mixture doses 

below 1000x, 2 endpoints, TSH and hepatic outer ring deiodinase activity, were 

significantly increased and decreased, respectively, by 1x dose and showed 

dose-related increases in severity with increasing dose. Median thyroid follicle 

cross sectional area was also increased by the lowest dose of the mixture but 

decreased with subsequent increases in dose until, at the highest dose, this 

parameter was significantly reduced relative to control. The relative sensitivity of 

endpoints of thyroid function in detecting toxicity of the mixture was TSH = ORD 

= median follicle area >> T(3) > all other endpoints. These results demonstrate 

that low doses of ubiquitous environmental contaminants can alter HPT 

physiology in sexually mature males. 

Weiss, B. (2006). "Endocrine disruptors as a factor in mental retardation." Davidson, 

PW [Editor]; Myers, GJ [Editor]; Weiss, B [Editor]. International Review of Research in 

Mental Retardation: 195-223. 

 

Woods, A. S., S. C. Moyer, et al. (2003). "Interaction of chlorisondamine with the 

neuronal nicotinic acetylcholine receptor." J Proteome Res 2(2): 207-12. 

 An epitope was found on the alpha2-nicotinic isoform of the neuronal nicotinic 

acetylcholine receptor that would likely form salt bridges with quaternary 

ammonium compounds and a cation-pi interaction with the pi-cloud of an 

aromatic ring. Chlorisondamine, a nicotinic antagonist, exerts a long-lasting, if not 

permanent, blockade of the ion channel gated by acetylcholine. Blocking of the 

ion channel prevents nicotine from exerting its rewarding effect on the CNS. 

Chlorisondamine contains two quaternary ammonium groups and a 

tetrachloroisoindoline ring. We propose that chlorisondamine interacts with an 

epitope on the alpha2 isoform of the rat neuronal nicotinic receptor (residues 

388-402, GEREETEEEEEEEDE), where one or both of the quaternary 

ammonium groups of chlorisondamine form a salt bridge with dither a glutamic 

acid side chain or a phosphate group, whereas the tetrachlorobenzene portion of 

the tetrachloroisoindoline ring interacts with the guanidinium group of arginine in 

a cation-pi association: In this work, a new way of probing the interaction of a 

receptor epitope (alpha2) with organic molecules (chlorisondamine and 

hexachlorobenzene) was undertaken using matrix assisted laser 

desorption/ionization mass spectrometry. 
151

CODE 6 (young populations) References 

Akita, M., M. Kato, et al. (2002). "Teratogenic effects of organohalogen contaminants 

extracted from small cetacean products on in vitro rat embryos during organogenesis." 

Organohalogen Compounds 55(Dioxin 2002): 421-423. 

 The teratogenic effects of the contaminants extd. from whale bacon products on 

gestation day 11.5 rat embryos cultured for 48 h in the in vitro whole embryos 

culture system were evaluated. High and low contaminated groups had no 

significant change on heart rate, embryonic blood circulation and total no. of 

somites. Crown-rump length of embryos reduced considerably in the both 

contaminated groups. Rat embryos in high contaminated medium showed 

malformations with incidence of 100%, while cultured embryos in low 

contaminated medium showed the weak anomalies of cacogenesis to 

telencephalon or mandibla and hematoma of cranioface or fore limbs with 50% 

incidence, suggesting that the organohalogen contaminants from whale products 

show the teratogenicity to rat embryos during organogenesis in a dosedependent manner. The teratogenic effect occurred at environmentally relevant 

concns. of these compds. 

Alvarez, L., A. Randi, et al. (2000). "Reproductive effects of hexachlorobenzene in 

female rats." J Appl Toxicol 20(1): 81-7. 

 Hexachlorobenzene (HCB) is a polyhalogenated aromatic hydrocarbon widely 

distributed in the environment. In animal testing, HCB has been shown to be a 

reproductive toxin. Previous investigations of the effects of HCB on ovarian 

function have yielded equivocal results. Thus, the effects of chronic 

administration of HCB (1 g kg(-1) body wt.) on the ovary and pituitary hormone 

levels, hepatic and uterine oestradiol receptors, ovarian histopathological 

changes and oestrus cycle characteristics were investigated in spontaneously 

cycling rats. Our data demonstrate that HCB treatment, under the conditions of 

the present study, reduced circulating levels of oestradiol and prolactin without 

differences in serum concentrations of progesterone. Follicle- stimulating 

hormone serum levels were elevated. Hexachlorobenzene treatment resulted in 

irregularity of cycles, characterized mainly as prolonged periods of oestrus with a 

reduced number of ova recovered. In addition, HCB administration resulted in 

significantly decreased uterine nuclear oestrogen receptor levels. 

Histopathological examination revealed degenerative changes of the ovarian 

follicles and germinal epithelium and increased numbers of atresic follicles. 

Anas, M. K., C. Guillemette, et al. (2005). "In utero and lactational exposure to an 

environmentally relevant organochlorine mixture disrupts reproductive development and 

function in male rats." Biology of Reproduction 73(3): 414-26. 

 We hypothesized that in utero and lactational exposure of male rats to a mixture 

of more than 15 organochlorines, resembling that found in blubber from northern 
152

Quebec seals, alters reproductive development and function. Female rats were 

gavaged with either corn oil (controls) or the organochlorine mixture in increasing 

doses (low, medium, and high) for 5 wk before mating and through gestation. 

Developmental effects were monitored in the male offspring from Postnatal Day 

(PND) 2 until PND 90. The high-dose mixture reduced the number of pups per 

litter, percentage of live offspring, and pup weights (P < 0.05). Because only 

three rats from the high-dose treatment survived, data from this group beyond 

PND 2 were not included in the statistical analyses. As assessed by the time of 

preputial separation, puberty was delayed in the pups from treated dams (P < 

0.05). Testes weights in the medium-dose group were greater than those in 

controls on PND 21 (P < 0.05). Ventral prostate weights were lower for the 

medium-dose group on PND 60 (P < 0.05). On PND 90, weights of the 

epididymis, ventral prostate, and seminal vesicle of the medium-dose rats were 

reduced compared to those of controls (P < 0.05). On PND 90, sperm motility 

parameters assessed by computer-assisted sperm analysis were altered in the 

low- and medium-dose groups (P < 0.05). Testicular and epididymal morphology 

was severely affected in rats exposed to the high dose of the mixture. Serum 

testosterone, LH, FSH, prolactin, and total thyroxine levels did not differ because 

of organochlorine treatment. Therefore, in utero and lactational exposure to an 

environmentally relevant organochlorine mixture adversely affects the 

reproductive system of male rats, perhaps via antiandrogenic effects during testis 

development, suggesting a possible reproductive health hazard for humans and 

other species. 

Babineau, K. A., A. Singh, et al. (1991). "Surface epithelium of the ovary following oral 

administration of hexachlorobenzene to the monkey." Journal of submicroscopic 

cytology and pathology. 23(3): 457-464. 

 

Bailey, J. L. (2002). "Organochlorines and male reproductive function: Is there a link?" 

Proceedings of International Symposium on Spermatology, 9th, Cape Town, South 

Africa, Oct. 6-11, 2002: 185-190. 

 The authors use the pig model to test the hypothesis that exposure to an 

organochlorine (OC) mixt. alters reproductive function. Four groups of prepubertal female pigs were fed increasing doses of OC through puberty, breeding, 

gestation and lactation. Offspring body length decreased with increasing OCs; 

birth wts., ano-genital distance and testosterone levels of male piglets were 

reduced in treated groups. At puberty, sperm motility was less in boars from 

sows receiving the highest OCs. Autopsy showed that testicular wts. decreased 

in a dose-dependent manner. The authors suggest reproductive development via 

endocrine disruption and testicular function are compromised by maternal 

exposure to OCs. In vitro studies reveal that the same OCs reduce sperm 

function and embryonic competence, likely through some other mechanism. 

Barnett, J. B., L. Barfield, et al. (1987). "The effect of in utero exposure to 

hexachlorobenzene on the developing immune response of BALB/C mice." Toxicology 

Letters 39: 263-274. 
153

 

Bilrha, H., R. Roy, et al. (2004). "Effects of gestational and lactational exposure to 

organochlorine compounds on cellular, humoral, and innate immunity in swine." 

Toxicological Sciences 77(1): 41-50. 

 Few studies have characterized the immunotoxic potential of complex mixtures of 

organochlorines (OCs) that bear environmental relevance. We monitored 

immune parameters in male piglets exposed in utero and through lactation to an 

OC mixture which was designed to approximate that found in the traditional diet 

of Arctic aboriginal populations. Prepubertal sows were administered orally either 

corn oil (control group) or the OC mixture in increasing doses (low, medium, and 

high). The sows were inseminated with the semen from an untreated boar and 

OC treatment was continued throughout gestation and lactation (21 days). Blood 

was collected from the sows at delivery and monthly from piglets until 8 months 

of age for the determination of plasma OC concentrations and parameters of 

innate, cellular, and humoral immunity. Treatment with the OC mixture had no 

dose-dependent effect on the proportion of CD4+ and CD8+ T-cell subsets, and 

did not modulate the functional activity of the complement component C2. The 

proportion of CD4+CD8+ cells, CD8+DR+ cells, and the mitogenic 

lymphoproliferative response increased in OC-treated, 4-month-old piglets. At 6 

months, the lymphoproliferative response to mitogen and the proportion 

CD4+CD8+ cells were still elevated in the OC-treated piglets, but the proportion 

of CD8+DR+ cells was decreased as compared to the controls. Animals in the 

high-dose group also exhibited a slight increase in polymorphonuclear leukocyte 

phagocytic activity at 8 months of age. Furthermore, the high dose decreased the 

antibody response to Mycoplasma hyopneumoniae. Our results indicate that 

developmental exposure to an environmentally relevant OC mixture alters the 

immune function in swine. 

Bloom, M. S., M. Buck-Louis Germaine, et al. (2009). "Changes in maternal serum 

chlorinated pesticide concentrations across critical windows of human reproduction and 

development." Environmental Research 109(1): 93-100. 

 Investigators often employ a single cross-sectional measure of in utero exposure 

when evaluating associations between organochlorine (OCs) 

pesticides/metabolites and adverse reproductive outcomes. Few data are 

available on the stability of exposures to OCs over critical windows of human 

reproduction and development inclusive of the periconception window. Our 

objective was to measures changes in OC concentrations prior to conception and 

throughout pregnancy or after 12 unsuccessful months attempting pregnancy. 

Seventy-nine women planning pregnancy were prospectively enrolled and 

followed for up to 12 menstrual cycles. Blood specimens were obtained for 

toxicologic analysis of seven OCs from participating women at baseline 

(preconception, n=79), at the first prenatal visit following a positive pregnancy 

test leading to a live birth (n=54) or after pregnancy loss (n=10), at approximately 

6 weeks post-partum (n=53), and after 12 unsuccessful cycles (n=9). Overall and 

daily rate of change in OCs concentration (ng/gserum) were estimated adjusting 

for serum lipids and baseline concentration. Significant (P<0.05) decreases in the 
154

overall and daily rate of change in OCs concentrations (ng/mLserum) were 

observed from baseline to pregnancy for HCB (-0.032, -0.001, respectively) and 

trans-nonachlor (-0.050, -0.002, respectively) while oxychlordane demonstrated 

an increase during this critical window (0.029, 0.001, respectively). Significant 

decreases in aldrin (-0.002, -1.47x10(-4), respectively), HCB (-0.069, -0.003, 

respectively), and trans-nonachlor (-0.045, -0.002, respectively), and an overall 

increase for oxychlordane (0.015) were seen for women with pregnancy losses. 

Significant decreases also were observed among infertile women for aldrin (-

0.003, -3.52x10(-6), respectively), DDE (-0.210, -4.29x10(-4), respectively), and 

HCB (-0.096, -2.03x10(-4), respectively), along with an increase for transnonachlor (0.034, 7.59x10(-5), respectively). These data, though limited by 

sample size and the possibility of laboratory measurement error, suggest that OC 

concentrations may change over critical windows. This underscores the 

importance of timing biospecimen collection to critical windows for development 

in the assessment of reproductive and/or developmental effects. 

Bourque, A. C., A. Singh, et al. (1995). "Ultrastructural changes in ovarian follicles of 

monkeys administered hexachlorobenzene." American Journal of Veterinary Research

56(12): 1673-1677. 

 

Bowers, W. J., J. S. Nakai, et al. (2004). "Early developmental neurotoxicity of a 

PCB/organochlorine mixture in rodents after gestational and lactational exposure." 

Toxicological Sciences 77(1): 51-62. 

 The developmental and neurobehavioral effects of gestational and lactational 

exposure to a mixture of 14 polychlorinated biphenyls (PCBs) and 11 

organochlorine pesticides was examined and compared against the commercial 

PCB mixture Aroclor 1254. The mixture was based on blood levels reported in 

Canadian populations living in the Great Lakes/St. Lawrence basin. Pregnant 

Sprague-Dawley rats were dosed orally with 0.013, 0.13, 1.3, or 13 mg/kg of the 

chemical mixture or 15 mg/kg of Aroclor 1254 from gestation day (GD) 1 to 

postnatal day (PND) 23. The highest mixture dose decreased maternal gestation 

and lactation body weight, and produced high mortality rates (80% overall) and 

reductions in offspring weight that persisted to adulthood. Aroclor 1254 produced 

smaller but persistent decreases in offspring weight without affecting maternal 

weight or offspring mortality. Aroclor 1254 and 13 mg/kg of the mixture produced 

comparable decreases in maternal and offspring serum T4 levels and 

comparable alterations to maternal thyroid morphology. Aroclor 1254 delayed the 

righting reflex and ear opening, accelerated eye opening, and reduced grip 

strength at PNDs 10-14. The mixture at 13 mg/kg delayed negative geotaxis in 

addition to delaying righting reflex and ear opening and reducing grip strength but 

had no effect on eye opening. Lower mixture doses (0.13 and 1.3 mg/kg) also 

delayed ear opening but affected no other parameters. Developmental exposure 

to the chemical mixture was found to be more toxic than exposure to Aroclor 

1254 and produced a different profile of effects on early neurodevelopment. This 

PCB/organochlorine pesticide mixture affects mortality, growth, thyroid function, 

and neurobehavioral development in rodents. 
155

Buck, G. M., J. E. Vena, et al. (2002). "PCB congeners and pesticides and female 

fecundity, New York State Angler Prospective Pregnancy Study." Environmental 

Toxicology and Pharmacology 12(2): 83-92. 

 Consumption of PCB-contaminated sport fish from Lake Ontario has been 

reported to be associated with diminished female fecundity. To identify 

Polychlorinated biphenyl (PCB) congeners and other pesticides that might be 

associated with reduced fecundity, we followed 102 women aged 20-34 years 

attempting pregnancy who completed daily diaries for 12 at risk menstrual cycles. 

Fecundity referred to time-to-pregnancy (TTP) or the number of at risk menstrual 

cycles required for pregnancy. Blood specimens were obtained for 88 (86%) 

women and were analyzed using gas chromatography and electron capture for 

66 PCB congeners and seven pesticides. Laboratory values were recovery, 

background and fat corrected prior to natural log transformation. Using stepwise 

discriminant analysis, congeners IUPAC #205 and #206 and hexaclorobenzene 

were significantly and positively associated with increasing TTP when women 

were categorized as becoming pregnant in the first or first three at risk menstrual 

cycles, respectively. Congeners #205 and #206 are reported to have (anti) 

estrogenic structural activity. 

Campagna, C., C. Guillemette, et al. (2002). "An environmentally relevant 

organochlorine mixture impairs sperm function and embryo development in the porcine 

model." Biology of Reproduction 67(1): 80-7. 

 We evaluated the effects of an environmentally relevant mixture of more than 15 

organochlorines on the development of pig oocytes and sperm during in vitro 

fertilization (IVF). Oocytes were cocultured with sperm in IVF medium containing 

increasing concentrations of an organochlorine mixture, similar to that found in 

women of highly exposed populations. Exposure to the organochlorine mixture 

diminished oocyte penetration rates and polyspermy in a linear manner. The 

mixture did not affect rates of cleavage nor development to multicell embryos. 

However, rates of development to the blastocyst stage were lower at the highest 

concentration at which oocyte penetration was observed. The same experiment 

was performed using oocytes that were preexposed during in vitro maturation. 

This greater exposure to the mixture also reduced penetration in a doseresponse manner and affected polyspermy. Frozen-thawed pig sperm were also 

cultured in IVF medium containing the same organochlorine concentrations. 

Sperm motility parameters were immediately reduced in a dose-dependent 

manner by the organochlorines, followed by diminished viability 2 h later. From 

these results, it appears that reduced sperm quality would account for decreases 

in fertilization, polyspermy, and blastocyst formation. These results suggest that 

exposing porcine oocytes and sperm to an environmentally pertinent 

organochlorine mixture in vitro disrupts the oocyte block to polyspermy, sperm 

fertility, and further embryonic development, and supports recent concerns that 

such pollutants harm reproductive health in humans and other species. 
156

Carreno, J., A. Rivas, et al. (2007). "Exposure of young men to organochlorine 

pesticides in Southern Spain." Environmental Research 103(1): 55-61. 

 It has been hypothesized that endocrine disruptors and especially synthetic 

estrogenic environmental contaminants (xenoestrogens) are etiologic factors in 

the global decrease of sperm counts and other problems of the male 

reproductive tract, including cryptorchidism, hypospadias, and testicular cancer. 

This possibility has prompted research into the current and historical incidence of 

these diseases. The largest area of intensive greenhouse agriculture in Europe is 

near the Mediterranean coast of Southern Spain, where this activity has greatly 

expanded since the 1960s. We determined and compared levels of 14 

organochlorine pesticides in the blood of 220 young males in Southern Spain. 

Aldrin, dieldrin, endrin, lindane, methoxychlor, endosulfans, and DDT and its 

metabolites were identified. Detectable concentrations of p,p'-DDE were found in 

96% of serum samples. Among the remaining DDTs, o,p'-DDD was the most 

prevalent, detected in 65% of serum samples. Detectable concentrations of 

endosulfan I or II or their metabolites endosulfan-diol, or -sulfate were found in all 

samples; endosulfan-diol was the most frequently detected metabolite (92%) 

followed by sulfate. Results indicate that men of reproductive age in Southern 

Spain have been and are exposed to organochlorine pesticides. Because many 

of these chemicals have estrogenic and anti-androgenic activity, further research 

is warranted to interpret the male reproductive health consequences of this 

exposure. 

Carrizo, D., J. O. Grimalt, et al. (2008). "Pentachlorobenzene, hexachlorobenzene, and 

pentachlorophenol in children's serum from industrial and rural populations after 

restricted use." Ecotoxicol Environ Saf 71(1): 260-6. 

 The study of a population of 4-year-old children born between 1997 and 1999 in 

an urban area under strong inputs of pentachlorobenzene (PeCB) and 

hexachlorobenzene (HCB) suggested that the measured concentrations of 

pentachlorophenol (PCP) in serum may essentially result from metabolism of 

these chlorinated hydrocarbons. In contrast, examination of a rural population of 

children where the same compounds were present at relatively low levels points 

to other inputs besides transformation of PeCB and HCB being responsible for 

the measured PCP concentrations. In both populations, the results showed that a 

major proportion of the organochlorine compounds present in these children's 

serum at 4 years of age was incorporated during the lactation period. 

Chevrier, J., B. Eskenazi, et al. (2008). "Effects of exposure to polychlorinated biphenyls 

and organochlorine pesticides on thyroid function during pregnancy." Am J Epidemiol

168(3): 298-310. 

 In this study, the authors' objective was to determine whether serum 

concentrations of polychlorinated biphenyls (PCBs), hexachlorobenzene, p,p'-

dichlorodiphenyl trichloroethane (DDT), o,p'-DDT, and p,p'-dichlorodiphenyl 

dichloroethylene (DDE) are associated with thyroid function during pregnancy. 

These compounds, as well as thyroid-stimulating hormone, total thyroxine, and 

free thyroxine, were measured in serum samples collected between October 
157

1999 and October 2000 from 334 pregnant women living in the Salinas Valley, 

California. Data were analyzed by multivariate linear regression. After adjustment 

for covariates, seven of the 19 PCB congeners detected in more than 75% of 

participants and the sum of those congeners were negatively associated with 

free thyroxine concentrations. PCBs 44, 52, and 183 remained significant after 

the exclusion of two outliers. Hexachlorobenzene concentrations were negatively 

associated with both free thyroxine and total thyroxine. PCB and 

hexachlorobenzene concentrations were strongly correlated, which hampered 

the authors' ability to identify their independent associations with thyroid function. 

None of the exposures under study were associated with thyroid-stimulating 

hormone. Results suggest that exposure to PCBs and/or hexachlorobenzene at 

background levels may affect thyroid function during pregnancy. These findings 

are of particular significance, since thyroid hormones of maternal origin may play 

an essential role in fetal neurodevelopment. 

Chu, I., W. J. Bowers, et al. (2008). "Toxicological effects of in utero and lactational 

exposure of rats to a mixture of environmental contaminants detected in Canadian 

Arctic human populations." Journal of toxicology and environmental health. Part A.

71(2): 93-108. 

 As part of the program to investigate mixture effects of environmental pollutants, 

this study describes clinical, biochemical, and histopathological effects in rats 

perinatally exposed to a mixture of persistent organochlorine pollutants and 

methylmercury that simulates the blood contaminant profile of humans residing in 

the Canadian Arctic. Groups of pregnant rats were administered orally 0, 0.05, 

0.5, or 5 mg/kg body weight (bw)/d of a reconstituted mixture of organochlorine 

pollutants (referred to as mixture hereafter) from gestational day (GD) 1 to 

postnatal day (PND) 23. Positive and vehicle controls were given Aroclor 1254 

(Aroclor hereafter, 15 mg/kg bw) and corn oil (vehicle), respectively. After 

parturition, the pups were colled to 8 per litter on PND 4, and killed on PND 35, 

77, or 350, when tissues were collected for analysis. Gestational and lactational 

exposure of rats to mixture up to 5 mg/kg bw produced adverse effects in the 

offspring, including growth suppression, decreased spleen and thymic weights, 

increased serum cholesterol and liver microsomal enzyme activities, lower liver 

retinoid levels, and histological changes in the liver, thyroid, and spleen. 

Histological changes in the liver consisted of hepatic inflammation, vacuolation, 

and hypertrophy, while alterations in the thyroid were characterized by 

hypertrophy and hyperplasia of follicles. The hepatic and thyroidal effects were 

mild even at the highest dose. The spleen showed a dose-dependent atrophy in 

the lymphoid nodules and periarteriolar lymphatic sheath regions. Aroclor 

produced effects similar to those seen in the highest mixture group. In summary, 

this study demonstrates that exposure to the reconstituted mixture at 5 mg/kg bw 

produced growth suppression, changes in organ weights, and biochemical and 

histopathological changes in liver, thyroid, and spleen. This study also 

demonstrated that the blood level in rats given the 5-mg/kg dose, where most of 

the effects were observed, is 100-fold higher than the blood level in the 0.05-
158

mg/kg group, which is comparable to that found in humans living in the Canadian 

Arctic region. 

Courtney, K. D., J. E. Andrews, et al. (1984). "Postnatal effects of hexachlorobenzene 

(HCB) on cardia lactic dehydrogenase (LDH) and creatine kinase (CK) isozymes in CD1 mice." Toxicology Letters 22(2): 223-228. 

 

Courtney, K. D., M. F. Copeland, et al. (1976). "The effects of pentachloronitrobenzene, 

hexachlorobenzene, and related compounds on fetal development." Toxicology and 

Applied Pharmacology 35: 239-256. 

 

Dallaire, R., E. Dewailly, et al. (2008). "Effects of prenatal exposure to organochlorines 

on thyroid hormone status in newborns from two remote coastal regions in Quebec, 

Canada." Environmental Research 108(3): 387-92. 

 BACKGROUND: Several prospective studies have revealed that prenatal 

exposure to polychlorinated biphenyls (PCBs) and other organochlorine 

compounds (OCs) affect neurodevelopment during infancy. One of the 

mechanisms by which PCBs might interfere with neurodevelopment is a deficit in 

thyroid hormone (TH) concentrations. OBJECTIVES: We investigated the 

potential impact of transplacental exposure to PCBs and hexachlorobenzene 

(HCB) on TH concentrations in neonates from two remote coastal populations 

exposed to OCs through the consumption of seafood products. METHODS: 

Blood samples were collected at birth from the umbilical cord of neonates from 

Nunavik (n=410) and the Lower North Shore of the St. Lawrence River (n=260) 

(Quebec, Canada) for thyroid parameters [thyroid-stimulating hormone (TSH), 

free T4 (fT4), total T3 (tT3), and thyroxine-binding globuline (TBG)] and 

contaminants analyses. RESULTS: In multivariate models, umbilical cord plasma 

concentrations of PCB 153, the predominant PCB congener, were not associated 

with TH and TSH levels in both populations. Prenatal exposure to HCB was 

positively associated with fT4 levels at birth in both populations (Nunavik, 

beta=0.12, p=0.04; St. Lawrence, beta=0.19, p<0.01), whereas TBG 

concentrations were negatively associated with PCB 153 concentrations (beta=-

0.13, p=0.05) in the St. Lawrence cohort. CONCLUSION: OCs levels were not 

associated to a reduction in THs in neonates from our two populations. Essential 

nutrients derived from seafood such as iodine may have prevented the negative 

effects of OCs on the thyroid economy during fetal development. 

Damgaard, I. N., N. E. Skakkebaek, et al. (2006). "Persistent pesticides in human breast 

milk and cryptorchidism." Environmental Health Perspectives 114(7): 1133-8. 

 INTRODUCTION: Prenatal exposure to some pesticides can adversely affect 

male reproductive health in animals. We investigated a possible human 

association between maternal exposure to 27 organochlorine compounds used 

as pesticides and cryptorchidism among male children. DESIGN: Within a 

prospective birth cohort, we performed a case-control study; 62 milk samples 

from mothers of cryptorchid boys and 68 from mothers of healthy boys were 

selected. Milk was collected as individual pools between 1 and 3 months 
159

postpartum and analyzed for 27 organochlorine pesticides. RESULTS: Eight 

organochlorine pesticides were measurable in all samples (medians; nanograms 

per gram lipid) for cases/controls: 1,1-dichloro-2,2-bis(4-chlorophenyl) ethylene 

(p,p -DDE) : 97.3/83.8; beta-hexachlorocyclohexane (beta-HCH) : 13.6/12.3; 

hexachlorobenzene (HCB) : 10.6/8.8; alpha-endosulfan: 7.0/6.7; oxychlordane: 

4.5/4.1; 1,1,1-trichloro-2,2-bis(4-chlorophenyl) ethane (p,p -DDT) : 4.6/4.0; 

dieldrin: 4.1/3.1 ; cis-heptachloroepoxide (cis-HE) : 2.5/2.2. Five compounds 

[octachlorostyrene (OCS); pentachlorobenzene, 1,1-dichloro-2,2-bis(4-

chlorophenyl) ethane(p,p -DDD) ; o,p -DDT ; mirex] were measurable in most 

samples (detection rates 90.8-99.2%) but in lower concentrations. For 

methoxychlor, cis-chlordane, pentachloroanisole (PCA), gamma-HCH, 1,1-

dichloro-2-(2-chlorophenyl) -2,2(4-chlorophenyl) ethane, trans-chlordane, alphaHCH, and o,p -DDE, both concentrations and detection rates were low (26.5-

71.5%). Heptachlor, HCH (lc delta, epsilon), aldrin, beta-endosulfan and transheptachloroepoxide were detected at negligible concentrations and low detection 

rates and were not analyzed further. Seventeen of 21 organochlorine pesticides 

[p,p -DDT, p,p-DDE, p,p-DDD, o,p-DDT, HCH (alpha, beta, gamma), HCB, PCA, 

alpha-endosulfan, cis-HE, chlordane (cis-, trans-) oxychlordane, methoxychlor, 

OCS, and dieldrin] were measured in higher median concentrations in case milk 

than in control milk. Apart from trans-chlordane (p = 0.012), there were no 

significant differences between cryptorchid and healthy boys for individual 

chemicals. However, combined statistical analysis of the eight most abundant 

persistent pesticides showed that pesticide levels in breast milk were significantly 

higher in boys with cryptorchidism (p = 0.032). CONCLUSION: The association 

between congenital cryptorchidism and some persistent pesticides in breast milk 

as a proxy for maternal exposure suggests that testicular descent in the fetus 

may be adversely affected. 

den Tonkelaar, E. M., H. G. Verschuuren, et al. (1978). "Hexachlorobenzene toxicity in 

pigs." Toxicology and Applied Pharmacology 43: 137-145. 

 

Denham, M., L. M. Schell, et al. (2005). "Relationship of lead, mercury, mirex, 

dichlorodiphenyldichloroethylene, hexachlorobenzene, and polychlorinated biphenyls to 

timing of menarche among Akwesasne Mohawk girls." Pediatrics 115(2): e127-34. 

 BACKGROUND: Children are commonly exposed at background levels to 

several ubiquitous environmental pollutants, such as lead and persistent organic 

pollutants, that have been linked to neurologic and endocrine effects. These 

effects have prompted concern about alterations in human reproductive 

development. Few studies have examined the effects of these toxicants on 

human sexual maturation at levels commonly found in the general population, 

and none has been able to examine multiple toxicant exposures. The aim of the 

current investigation was to examine the relationship between attainment of 

menarche and levels of 6 environmental pollutants to which children are 

commonly exposed at low levels, ie, dichlorodiphenyldichloroethylene (p,p'-DDE), 

hexachlorobenzene (HCB), polychlorinated biphenyls (PCBs), mirex, lead, and 

mercury. METHODS: This study was conducted with residents of the Akwesasne 
160

Mohawk Nation, a sovereign territory that spans the St Lawrence River and the 

boundaries of New York State and Ontario and Quebec, Canada. Since the 

1950s, the St Lawrence River has been a site of substantial industrial 

development, and the Nation is currently adjacent to a US National Priority 

Superfund site. PCB, p,p'-DDE, HCB, and mirex levels exceeding the US Food 

and Drug Administration recommended tolerance limits for human consumption 

have been found in local animal species. The present analysis included 138 

Akwesasne Mohawk Nation girls 10 to 16.9 years of age. Blood samples and 

sociodemographic data were collected by Akwesasne community members, 

without prior knowledge of participants' exposure status. Attainment of menses 

(menarche) was assessed as present or absent at the time of the interview. 

Congener-specific PCB analysis was available, and all 16 PCB congeners 

detected in >50% of the sample were included in analyses (International Union of 

Pure and Applied Chemistry numbers 52, 70, 74, 84, 87, 95, 99, 101 [+90], 105, 

110, 118, 138 [+163 and 164], 149 [+123], 153, 180, and 187). Probit analysis 

was used to determine the median age at menarche for the sample. Binary 

logistic regression analysis was used to determine predictors of menarcheal 

status. Six toxicants (p,p'-DDE, HCB, PCBs, mirex, lead, and mercury) were 

entered into the logistic regression model. Age, socioeconomic status (SES), and 

BMI were tested as potential cofounders and were included in the model at P < 

.05. Interactions among toxicants were also evaluated. RESULTS: Toxicant 

levels were measured in blood for this sample and were consistent with longterm exposure to a variety of toxicants in multiple media. Mercury levels were at 

or below background levels, all lead levels were well below the Centers for 

Disease Control and Prevention action limit of 10 microg/dL, and PCB levels 

were consistent with a cumulative, continuing exposure pattern. The median age 

at menarche for the total sample was 12.2 years. The predicted age at menarche 

for girls with lead levels above the median (1.2 microg/dL) was 10.5 months later 

than that for girls with lead levels below the median. In the logistic regression 

analysis, age was the strongest predictor of menarcheal status and SES was 

also a significant predictor but BMI was not. The logistic regression analysis that 

corrected for age, SES, and other pollutants (p,p'-DDE, HCB, mirex, and 

mercury) indicated that, at their respective geometric means, lead (geometric 

mean: 0.49 microg/dL) was associated with a significantly lower probability of 

having reached menarche (beta = -1.29) and a group of 4 potentially estrogenic 

PCB congeners (E-PCB) (geometric mean: 0.12 ppb; International Union of Pure 

and Applied Chemistry numbers 52, 70, 101 [+90], and 187) was associated with 

a significantly greater probability of having reached menarche (beta = 2.13). 

Predicted probabilities at different levels of lead and PCBs were calculated on 

the basis of the logistic regression model. At the respective means of all toxicants 

and SES, 69% of 12-year-old girls were predicted to have reached menarche. 

However, at the 75th percentile of lead levels, only 10% of 12-year-old Mohawk 

girls were predicted to have reached menarche; at the 75th percentile of E-PCB 

levels, 86% of 12-year-old Mohawk girls were predicted to have reached 

menarche. No association was observed between mirex, p,p'-DDE, or HCB and 

menarcheal status. Although BMI was not a significant predictor, we tested BMI 
161

in the logistic regression model; it had little effect on the relationships between 

menarcheal status and either lead or E-PCB. In models testing toxicant 

interactions, age, SES, lead levels, and PCB levels continued to be significant 

predictors of menarcheal status. When each toxicant was tested in a logistic 

regression model correcting only for age and SES, we observed little change in 

the effects of lead or E-PCB on menarcheal status. CONCLUSIONS: The 

analysis of multichemical exposure among Akwesasne Mohawk Nation 

adolescent girls suggests that the attainment of menarche may be sensitive to 

relatively low levels of lead and certain PCB congeners. This study is 

distinguished by the ability to test many toxicants simultaneously and thus to 

exclude effects from unmeasured but coexisting exposures. By testing several 

PCB congener groupings, we were able to determine that specifically a group of 

potentially estrogenic PCB congeners affected the odds of reaching menarche. 

The lead and PCB findings are consistent with the literature and are biologically 

plausible. The sample size, cross-sectional study design, and possible 

occurrence of confounders beyond those tested suggest that results should be 

interpreted cautiously. Additional investigation to determine whether such low 

toxicant levels may affect reproduction and disorders of the reproductive system 

is warranted. 

Eggesbo, M., H. Stigum, et al. (2009). "Levels of hexachlorobenzene (HCB) in breast 

milk in relation to birth weight in a Norwegian cohort." Environ Res. 

 BACKGROUND: Hexachlorobenzene (HCB) is a ubiquitous environmental 

contaminant that, even at low doses, causes destruction of ovarian primordial 

germ cells in experimental studies. However, its potential for reproductive toxicity 

in humans exposed to background levels has not been fully evaluated. Here we 

examined the association between maternal levels of HCB and their infants' birth 

weight. METHODS: HCB was measured in milk samples from a subset of women 

in the Norwegian Human Milk Study (HUMIS), 2003-2006; 300 subjects were 

randomly chosen from the cohort and 26 from all small for gestational age (SGA) 

children. Additional information was obtained through questionnaires and the 

Medical Birth Registry. RESULTS: Overall, HCB was associated with birth weight 

(adjusted b=-90g per 8mug/kg milk fat, 95% CI-275 to 8) and with SGA (odds 

ratio 1.8, 95% CI 0.9-3.7 per 8mug/kg milk fat (difference between the 10th and 

the 90th percentile)). After stratification, however, the association was present 

only among smokers. For birth weight for past or current smokers: b=-282, CI -

467 to -98; for never smokers: b=0.5, CI -149 to 150, p-value for interaction: 0.01. 

Similar results were observed for head circumference, crown-heel length, and 

SGA. CONCLUSIONS: We saw a moderate association between HCB and 

markers of impaired fetal growth among past and current smokers. This finding 

may be non-causal and due to underlying genetic variants tied to both growth 

and breakdown of HCB or to confounding by unmeasured toxicants that coexist 

in exposure sources. It may, however, also result from HCB exposure. 

Ennaceur, S., N. Gandoura, et al. (2008). "Distribution of polychlorinated biphenyls and 

organochlorine pesticides in human breast milk from various locations in Tunisia: levels 
162

of contamination, influencing factors, and infant risk assessment." Environmental 

Research 108(1): 86-93. 

 The concentrations of dichlorodiphenytrichloroethane and its metabolites (DDTs), 

hexachlorobenzene (HCB), hexachlorocyclohexane isomers (HCHs), dieldrin, 

and 20 polychlorinated biphenyls (PCBs) were determined in 237 human breast 

milk samples collected from 12 locations in Tunisia. Gas chromatography with 

electron capture detector (GC-ECD) was used to identify and quantify residue 

levels on a lipid basis of organochlorine compounds (OCs). The predominant 

OCs in human breast milk were PCBs, p,p'-DDE, p,p'-DDT, HCHs, and HCB. 

Concentrations of DDTs in human breast milk from rural areas were significantly 

higher than those from urban locations (p<0.05). With regard to PCBs, we 

observed the predominance of mid-chlorinated congeners due to the presence of 

PCBs with high K(ow) such as PCB 153, 138, and 180. Positive correlations 

were found between concentrations of OCs in human breast milk and age of 

mothers and number of parities, suggesting the influence of such factors on OC 

burdens in lactating mothers. The comparison of daily intakes of PCBs, DDTs, 

HCHs, and HCB to infants through human breast milk with guidelines proposed 

by WHO and Health Canada shows that some individuals accumulated OCs in 

breast milk close to or higher than these guidelines. 

Fenster, L., B. Eskenazi, et al. (2006). "Association of in utero organochlorine pesticide 

exposure and fetal growth and length of gestation in an agricultural population." 

Environmental Health Perspectives 114(4): 597-602. 

 From 1940 through the 1970s, organochlorine compounds were widely used as 

insecticides in the United States. Thereafter, their use was severely restricted 

after recognition of their persistence in the environment, their toxicity in animals, 

and their potential for endocrine disruption. Although substantial evidence exists 

for the fetal toxicity of organochlorines in animals, information on human 

reproductive effects is conflicting. We investigated whether infants' length of 

gestation, birth weight, and crown-heel length were associated with maternal 

serum levels of 11 different organochlorine pesticides: p,p -

dichlorodiphenyltrichloroethane (p,p -DDT), p,p -dichlorodiphenyldichloroethylene 

(p,p -DDE), o,p -dichlorodiphenyltrichloroethane (o,p -DDT), hexachlorobenzene 

(HCB), gamma-hexachlorocyclohexane (gamma-HCCH), gammahexachlorocyclohexane (gamma-HCCH), dieldrin, heptachlor epoxide, 

oxychlordane, trans-nonachlor, and mirex. Our subjects were a birth cohort of 

385 low-income Latinas living in the Salinas Valley, an agricultural community in 

California. We observed no adverse associations between maternal serum 

organochlorine levels and birth weight or crown-heel length. We found decreased 

length of gestation with increasing levels of lipid-adjusted HCB (adjusted gamma 

= -0.47 weeks; p = 0.05). We did not find reductions in gestational duration 

associated with any of the other organochlorine pesticides. Our finding of 

decreased length of gestation related to HCB does not seem to have had clinical 

implications for this population, given its relatively low rate of preterm delivery 

(6.5%). 
163

Foster, W. G., A. McMahon, et al. (1992). "Hexachlorobenzene (HCB) suppresses 

circulating progesterone concentrations during the luteal phase in the Cynomolgus 

monkey." Journal of Applied Toxicology 12(1): 13-17. 

 

Foster, W. G., A. McMahon, et al. (1995). "Alterations in circulating ovarian steroids in 

hexachlorobenzene-exposed monkeys." Reproductive Toxicology 9(6): 541-548. 

 

Gladen, B. C., Z. A. Shkiryak-Nyzhnyk, et al. (2003). "Persistent organochlorine 

compounds and birth weight." Annals of epidemiology. 13(3): 151-7. 

 PURPOSE: To determine whether weight at birth is related to prenatal exposure 

to persistent organochlorine compounds. METHODS: Birth weight was obtained 

for 197 singleton infants drawn from the general population born in two cities in 

Ukraine in 1993 to 1994. Concentrations of seven organochlorine pesticides 

(p,p'-DDT, p,p'-DDE, beta-hexachlorocyclohexane, hexachlorobenzene, transnonachlor, oxychlordane, heptachlor epoxide) and 11 polychlorinated biphenyl 

congeners measured in maternal milk taken at four or five days after birth were 

used as an index of prenatal exposure. RESULTS: The greatest differences were 

seen for beta-hexachlorocyclohexane, with a pattern not suggestive of doseresponse; infants in the lowest tertile were small, those in the central tertile were 

large, and those in the upper tertile were average. Adjustment for gestational age 

and other potential confounders had little effect on these patterns. Infants in the 

two upper tertiles for p,p'-DDE were larger than those in the lower tertile, with the 

effect being more striking after adjustment for gestational age. Adjustment for 

potential confounders made the pattern disappear. Other chemicals showed no 

convincing evidence of effects. CONCLUSIONS: Prenatal exposure to the 

chemicals studied, at concentrations currently seen in this population, does not 

impact weight at birth. 

Grant, D. L., F. Iverson, et al. (1974). "Effects of hexachlorobenzene on liver porphyrin 

levels and microsomal enzymes in the rat." Environmental Physiology and Biochemistry

4: 159-165. 

 

Grant, D. L., W. E. J. Phillilps, et al. (1977). "Effect of hexachlorobenzene on 

reproduction in the rat." Archives of Environmental Contamination and Toxicology 5(2): 

207-216. 

 

Hansen, L. G., R. M. Teske, et al. (1979). "Hexachlorobenzene and feline reproduction: 

effectsof ground pork contaminated by dietary exposure to spiked with purified HCB." 

Veterinary and Human Toxicology 21: 248-253. 

 

Hardell, L., B. van Bavel, et al. (2003). "Increased concentrations of polychlorinated 

biphenyls, hexachlorobenzene, and chlordanes in mothers of men with testicular 

cancer." Environ Health Perspect 111(7): 930-4. 

 An increasing incidence of testicular cancer has been reported from several 

countries in the Western world during the last decades. According to current 

hypothesis, testicular cancer is initiated during the fetal period, and exposure to 
164

endocrine disruptors, i.e., xenoestrogens, has been of concern. In this 

investigation we studied the concentrations of the sum of 38 polychlorinated 

biphenyls (PCBs), p,p'-dichlorodiphenyl-dichloroethylene, hexachlorobenzene 

(HCB), and chlordanes, in 61 cases with testicular cancer and 58 age-matched 

controls. Furthermore, case and control mothers were also asked to participate, 

and 44 case mothers and 45 control mothers agreed. They were of similar age. 

In cases only the concentration on lipid basis of cis-nonachlordane was 

significantly increased, whereas case mothers showed significantly increased 

concentrations of the sum of PCBs, HCB, trans- and cis-nonachlordane, and the 

sum of chlordanes. Among case mothers the sum of PCBs yielded an odds ratio 

(OR) of 3.8; 95% confidence interval (CI), 1.4-10 was calculated using the 

median concentration for the control mothers as cutoff value. For HCB, OR = 4.4 

(95% CI, 1.7-12); for trans-nonachlordane, OR = 4.1 (95% CI, 1.5-11); for cisnonachlordane, OR = 3.1 (95% CI, 1.2-7.8); and for sum of chlordanes, OR = 1.9 

(95% CI, 0.7-5.0). No consistent different risk pattern was found for seminoma or 

nonseminoma testicular cancer. 

Iatropoulos, M. J., W. Hobson, et al. (1976). "Morphological effects of 

hexachlorobenzene toxicity in female Rhesus monkeys." Toxicology and Applied 

Pharmacology 37: 433-444. 

 

Jarrell, J. F., A. McMahon, et al. (1993). "Hexachlorobenzene toxicity in the monkey 

primordial germ cell without induced prophyria." Reproductive Toxicology 7: 41-47. 

 

Joffe, M. (2004). "Re: "Increased concentrations of polychlorinated biphenyls, 

hexachlorobenzenes, and chlordanes in mothers of men with testicular cancer"." 

Environ Health Perspect 112(1): A21-2; author reply A22. 

 

Khanjani, N. and M. R. Sim (2006). "Reproductive outcomes of maternal contamination 

with cyclodiene insecticides, hexachlorobenzene and beta-benzene hexachloride." 

Science of the Total Environment 368(2-3): 557-64. 

 The effects of organochlorines on human reproduction have been recently under 

scrutiny. Some negative effects on animal reproduction have been reported. In 

this study we aimed to evaluate the effect of maternal contamination with a 

certain group of organochlorines, which are cyclodienes, HCB 

(hexachlorobenzene) and beta-BHC (beta-hexachlorocyclohexane) on human 

reproduction. Breast milk samples from 815 eligible Victorian mothers were used 

for measuring maternal contamination and the reproductive outcomes such as 

birth weight, head circumference and prematurity were taken from health files. 

Our study did not show any significant negative effect on outcomes such as birth 

weight, small for gestation age, previous miscarriage or still birth, head 

circumference or sex ratio. An inconsistent increase across oxychlordane 

exposure levels for prematurity was found. We also found an inverse association 

between the highest levels of HCB and oxychlordane with previous miscarriage 

or still birth; but this was based on small numbers and may be explained by loss 

of contaminants through the aborted fetus. These results suggest that the 
165

declining contamination levels of these chemicals do not impose a threat to 

human reproduction. 

Khera, K. S. (1974). "Teratogenicity and dominant lethal studies on hexachlorobenzene 

in rats." Food and Cosmetics Toxicology 12: 471-477. 

 

Kitchin, K. T., R. E. Linder, et al. (1982). "Offspring mortality and maternal lung 

pathology in female rats fed hexachlorobenzene." toxicology 23: 33-39. 

 

Lackmann, G. M. (2002). "Polychlorinated biphenyls and hexachlorobenzene in full-term 

neonates. Reference values updated." Biol Neonate 81(2): 82-5. 

 OBJECTIVE: To determine actual reference values of polychlorinated biphenyls 

(PCBs) and hexachlorobenzene (HCB) in full-term neonates. PATIENTS AND 

METHODS: Cord blood samples were taken from 200 healthy, full-term neonates 

in 1998. Blood specimens were immediately centrifuged, and serum was stored 

in glass tubes at -20 degrees C up to analysis. Six PCB congeners (IUPAC No. 

28, 52, 101, 138, 153, and 180) and HCB were determined with capillary gas 

chromatography with electron capture detection. Study groups were tested on 

mean differences with Wilcoxon's test of independent samples. The 95th 

percentiles by rank were calculated as reference values. RESULTS: One sample 

was excluded from further evaluation because of unusually high PCB 

concentrations. Personal data of the remaining 199 newborns showed 106 male 

and 93 female neonates. Mean gestational age was 40 weeks (range 38-43 

weeks), mean birth weight was 3,450 g (2,300-5,060 g). The concentrations of 

the lower-chlorinated PCB congeners 28, 52, and 101 were below the detection 

limit with exception of two probes. Reference values (95th percentile by rank) of 

the higher-chlorinated PCB congeners and HCB were as follows: PCB 138, 0.5 

microg/l; PCB 153, 0.5 microg/l; PCB 180, 0.4 microg/l; and HCB, 0.5 microg/l. 

CONCLUSIONS: The results of the present study clearly demonstrate a further 

decline in the prenatal uptake of PCBs and HCB since 1994-1995. During the 

past 15 years, a 75% decline in the prenatal burden with PCBs and a 90% 

reduction in the burden with HCB could be demonstrated. 

Lackmann, G. M., K. H. Schaller, et al. (2004). "Organochlorine compounds in breastfed vs. bottle-fed infants: preliminary results at six weeks of age." Sci Total Environ

329(1-3): 289-93. 

 BACKGROUND: Polychlorinated biphenyls (PCBs), hexachlorobenzene (HCB), 

and 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (DDT) are ubiquitous 

compounds with carcinogenic and teratogenic properties. They are chemically 

very stable and lipophilic and, therefore, accumulate in our food-chain. They are 

prenatally transmitted from mother to foetus, and mother's milk due to its high 

lipid content is an elimination pathway of special importance. Therefore, breastfeeding has been held responsible for elevated concentrations of these 

organochlorine compounds as well as for harmful effects in children later in life. 

METHODS: Blood samples (2.5 ml) were taken from each 10 breast-fed and 

bottle-fed infants at 6 weeks of age. Blood specimens were immediately 
166

centrifuged, and serum was stored in glass tubes at -20 degrees C until analysis. 

Three higher chlorinated PCB congeners (IUPAC nos. 138, 153 and 180), HCB, 

and the organic metabolite of DDT, p,p << -DDE, were analysed with capillary 

gas chromatography with electron capture detection. Reliability was tested with 

gas chromatography-mass spectrometry. RESULTS: There were no differences 

between the study groups of breast-fed and bottle-fed infants with regard to sex 

distribution, gestational age, birth-weight, age of the mothers, and smoking 

behaviour of the parents. In contrast, serum concentrations of all organochlorine 

compounds were significantly higher (P < 0.0001) in breast-fed than in bottle-fed 

infants (mean): PCB 138, 0.38 vs. 0.10 microg/l; PCB 153, 0.49 vs. 0.1 microg/l; 

PCB 180, 0.31 vs. 0.04 microg/l; SigmaPCB, 1.19 vs. 0.29 microg/l; HCB, 0.13 

vs. 0.04 microg/l; p,p << -DDE, 1.05 vs. 0.18 microg/l. CONCLUSIONS: Breastfeeding significantly increases the pollution of our infants with different 

organochlorine compounds as early as at 6 weeks of age. The progress of the 

present study will show whether this pollution will further increase with longer 

duration of breast-feeding, and whether breast-feeding bears any health risks for 

our offspring. 

Lopez-Espinosa, M. J., A. Granada, et al. (2007). "Organochlorine pesticides in 

placentas from Southern Spain and some related factors." Placenta 28(7): 631-8. 

 During pregnancy, lipophilic xenobiotics stored in maternal adipose tissue can be 

mobilized and enter her blood circulation and reach the placenta. This study 

measured residues of oestrogen-mimicking organochlorine pesticides (OCs) in 

150 placenta samples from women in Southern Spain. OCs were extracted from 

placenta by solid-liquid technique and purified by preparative liquid 

chromatography. Gas chromatography/electron-capture detection and mass 

spectrometry were used to identify and quantify p,p'-DDT and 

congeners/metabolites, endosulphan and congeners/metabolites, lindane, 

aldrin/dieldrin/endrin, hexachlorobenzene, methoxychlor and mirex. A mean of 

eight pesticides per placenta were detected (range, 3-15 pesticides). 

Endosulphan-ether, endosulphan-diol, endosulphan-I, p,p'-DDE, o,p'-DDD, p,p'-

DDT, o,p'-DDT and lindane were detected in >or=50% of samples; p,p'-DDE was 

the most frequent (96.03%), followed by endosulphan-diol (76.86%) and lindane 

(74.17%). Presence of more pesticides was significantly associated with lower 

birth weight. Mean concentration of p,p'-DDE was 2.37+/-2.80 ng/g of placenta or 

76.62+/-104.85 ng/g of lipid. Higher maternal body mass index was significantly 

associated with higher endosulphan concentrations in placenta, and greater 

maternal weight gain was significantly associated with higher p,p'-DDE 

concentrations. Prenatal exposure to OC xenoestrogens may be a causative 

factor in adverse reproductive health trends, and further studies are required to 

identify and describe pathways of this exposure to enhance preventive 

measures. 

Madeddu, A. and S. Sciacca (2008). "[Biological tracking on the presence of Hg, PCB 

and HCG in milk and hair of women resident in a region with high incidence of children 

born with malformation (Augusta)]." Ann Ig 20(3 Suppl 1): 59-64. 
167

 Following the findings of some studies that have found the presence of Hg, HCB 

and PCBs in fish from the bay of Augusta and showed a strong association 

between the consumption of local fish and the increased risk of children born 

malformed among women of the same city, the authors, in collaboration with the 

judicial authorities, have initiated a study on the tracking of these substances in 

biological tissues of mothers exposed to risk of contamination because resident 

in the Syracusan industrial area. The study showed differences in excess, and 

statistically significant, among mothers of Augusta respect to a sample of 

Controls selected in another Sicilian region not exposed to the same risk of 

contamination, thereby reinforcing the idea that some substances from industrial 

source found in the environment and in the body of the mothers of Augusta have 

been able to contribute to the higher incidence of congenital malformations and 

abortions in the examined region, and leading a company petrochemicals to 

recognize the families of born malformed an economic compensation. 

Nakashima, Y. and S. Ikegami (2000). "Hexachlorobenzene and pentachlorobenzene 

accumulated during pregnancy is transferred to pups at the accumulation ratio in dams." 

Journal of Health Science 46(2): 89-97. 

 Hexachlorobenzene (HCB) and pentachlorobenzene (PECB) were used to clarify 

how the rate at which lipophilic environmental pollutants are metabolized will 

affect their transfer to pups. In this study, the ratio of PECB/HCB transference to 

fetuses and suckling pups was investigated in rats fed a diet containing HCB 

(35.1 nmol/100 g diet) and PECB (351 nmol/100 g diet). The amounts of HCB 

and PECB transferred to fetuses were 0.44% and 0.15% of the amounts 

consumed by their dams, respectively, and the PECB/HCB concentration ratio in 

fetuses was 3.4. In pregnant rats on the day before parturition, the PECB 

concentrations in organs and fat tissue were 3 to 4 times higher than those of 

HCB. After parturition, PECB rapidly disappeared from the body of nursing rats 

during the lactation period, especially when compared with HCB. On day 2 after 

birth, HCB and PECB concentrations in the stomach contents of suckling pups 

were highest, and the PECB concentration was 3.5 times higher than that of 

HCB. HCB in the stomach contents decreased gradually (T1/2 = 5.7 d) and 

PECB decreased rapidly (T1/2 = 2.8 d) during the 15 d after birth. These findings 

indicate that the PECB/HCB transferred to fetuses and suckling pups was the 

same ratio found in the blood of their dams. 

Noakes, P. S., P. Taylor, et al. (2006). "The relationship between persistent organic 

pollutants in maternal and neonatal tissues and immune responses to allergens: A novel 

exploratory study." Chemosphere 63(8): 1304-11. 

 BACKGROUND: Modern persistent organic pollutants (POPs) contamination are 

logical candidates in the investigation of the, as yet, unexplained association 

between allergic disease and progressive industrialisation. POPs have been 

detected in human cord blood, placental tissues and breast milk, and the 

reported association between cord blood IgE levels and cord/placental POP 

levels has raised concerns about potential immunological effects in early life. 

METHODS: The initial aim of this study was to determine if POPs were 
168

detectable in maternal blood, cord blood, placental tissues, adipose tissue and 

breast milk samples from randomly selected Western Australian women (n = 31), 

where allergic disease is epidemic. Gas chromatography was used to detect 

polychlorinated biphenyl compounds [PCBs] (as Aroclor 1232, 1254, 1260) and 

organochlorine (OC) pesticides, including p,p'-DDT, p,p'-DDE, 

hexachlorobenzene (HCB), lindane, heptachlor epoxide, dieldrin and chlordane. 

Secondly, we assessed the relationship between POP levels detected in vivo and 

maternal and neonatal responses (cytokine and lymphoproliferation) to allergens 

and mitogens. RESULTS: Low level POP contamination was detected in adipose 

tissue and breast milk (but not in cord blood, maternal blood or placental tissues). 

The most ubiquitous compound found in over 90% of adipose tissues samples 

was a OC metabolite of DDT, p,p'-DDE (median 0.07 mg/kg; interquartile range 

[IQR] 0.05-0.12). However, the majority of other OC compounds were not 

detectable and PCB were not detectable in any samples. The three main 

residues detected in breast milk were p,p'-DDE (0.003 mg/l; 0.001-0.009), 

dieldrin (0.001 mg/l; 0.001-0.046) and HCB (0.001 mg/l; 0.001-0.001). These 

levels are significantly lower than reported over 20 years ago. There were no 

consistent relationships between POP levels in vivo and maternal or infant 

responses, with the exception of a significant inverse association (Spearman 

rank correlation: r = -0.406, p = 0.049) between maternal adipose tissue levels of 

OC p,p'-DDE and maternal T helper cell Type 1 interferon [IFN] gamma to 

mitogens. CONCLUSION: This study provides the first evidence (in Australia) 

since the early 1990's that adipose OC levels have continued to fall. The 

negligible levels in this randomly selected group are significantly lower than those 

previously recorded, suggesting that POP contamination (at biologically relevant 

levels) is not likely to be a major contributing factor in the increasing rates of 

allergy in Western Australia. However, the relationship between Th1 immune 

function and OC contamination is consistent with other reports and is worth 

investigating as a relevant factor in populations where OC contamination is 

greater. 

Ozalla, D., C. Herrero, et al. (2002). "Evaluation of urinary porphyrin excretion in 

neonates born to mothers exposed to airborne hexachlorobenzene." Environ Health 

Perspect 110(2): 205-9. 

 The existence of a link between hexachlorobenzene (HCB) and porphyria 

cutanea tarda has been known for a long time. However, the epidemiologic data 

on effects on health caused by prenatal exposure have not provided convincing 

evidence that HCB alters porphyrin metabolism. Our objectives were to analyze 

urinary porphyrin excretion and HCB in maternal serum and fetal cord blood in 

neonates born in a village (Flix) near a chlorinated solvent factory, to detect 

possible adverse effects in urinary porphyrin excretion caused by prenatal 

exposure, and to assess their relationship with HCB blood levels. We conducted 

a cross-sectional study in the Porphyria Unit at a tertiary care facility in 

Barcelona, Spain, and the Pediatric Unit of the Mora d'Ebre Hospital, the 

reference hospital of the study area. We included in the study all neonates (n = 

68) born in Mora d'Ebre Hospital 1997- 1999 and their mothers. We obtained 68 
169

urine specimens of singleton neonates on the third day after birth to test for 

urinary porphyrin excretion. We obtained 52 fetal cord blood and 56 maternal 

serum samples for HCB analysis. Total urinary porphyrins were quantified using 

spectrofluorometry. Porphyrin profile was determined by HPLC. Serum HCB was 

analyzed by gas chromatography coupled with electron capture detection. In total 

population, median HCB levels were 1.08 ng/mL in cord blood and 3.31 ng/mL in 

maternal serum. Total urinary porphyrin concentration was 37.87 micromol/mol 

creatinine. Coproporphyrin I and coproporphyrin III were the major porphyrins 

excreted. We found no positive relationship between urinary porphyrin excretion 

and HCB levels. However, we observed an association between maternal 

smoking and coproporphyrin excretion. Although high environmental levels of 

HCB are reported in the town of Flix, we found no alteration in urinary porphyrin 

excretion. 

Pelletier, G., S. Masson, et al. (2009). "Contribution of methylmercury, polychlorinated 

biphenyls and organochlorine pesticides to the toxicity of a contaminant mixture based 

on Canadian Arctic population blood profiles." Toxicology Letters 184(3): 176-85. 

 Human populations are simultaneously exposed to a variety of anthropogenic 

contaminants. However, despite extensive literature on animal exposure to single 

compounds, data on the toxicity of complex mixtures are scarce. The Northern 

Contaminant Mixture (NCM) was formulated to contain the 27 most abundant 

contaminants in the same relative proportions found in the blood of Canadian 

Arctic populations. Sprague-Dawley rat dams were dosed from the first day of 

gestation until weaning with methylmercury (MeHg), polychlorinated biphenyls 

(PCBs) or organochlorines pesticides (OCs) administered either separately or 

together in the NCM. An additional control group for hypothyroxinemia was 

included by dosing dams with the goitrogen 6-propyl-2-thiouracil (PTU). Offspring 

growth, survival, serum thyroxine and Thyroid Stimulating Hormone (TSH) levels, 

thyroid gland morphology, brain taurine content and cerebellum and 

hippocampus protein expression patterns resulting from such exposures were 

monitored. Pups' increased mortality rate and impaired growth observed in the 

NCM treatment group were attributed to MeHg, while decreased circulating 

thyroxine levels and perturbations of thyroid gland morphology were mostly 

attributable to PCBs. Interestingly, despite comparable reduction in serum 

thyroxine levels, PCBs and PTU exposures produced markedly different effects 

on pup's growth, serum TSH level and brain taurine content. Analysis of 

cerebellum and hippocampus protein expression patterns corroborated previous 

cerebellum gene expression data, as contaminant co-exposure in the NCM 

significantly masked the effects of individual components on protein twodimensional electrophoresis patterns. Identification by MALDI-TOF/TOF MS of 

differentially expressed proteins involved notably in neuronal and mitochondrial 

functions provided clues on the cellular and molecular processes affected by 

these contaminant mixtures. 
170

Pierik, F. H., M. A. Klebanoff, et al. (2007). "Maternal pregnancy serum level of 

heptachlor epoxide, hexachlorobenzene, and beta-hexachlorocyclohexane and risk of 

cryptorchidism in offspring." Environ Res 105(3): 364-9. 

 Prenatal exposure to environmental endocrine disrupters has been postulated to 

cause adverse effects on male reproductive health. Exposure to organochlorine 

pesticides with anti-androgenic and estrogenic potency has been shown to 

interfere with the sex-hormone-dependent process of testicular descent in animal 

models. We examined the relation between serum levels of the pesticides 

heptachlor epoxide (HCE), hexachlorobenzene (HCB), and betahexachlorocyclohexane (beta-HCCH) in pregnant women, and the occurrence of 

cryptorchidism in their sons. These three pesticides were previously suggested 

as risk factors for cryptorchidism. In a nested case-control design, we compared 

serum levels between mothers of cases (n = 219) and controls (n = 564), 

selected from the Collaborative Perinatal Project, a US birth cohort study of 

pregnancies in 1959-1966. The offspring of mothers with HCE levels above the 

90th percentile compared to those below the 10th percentile had an adjusted 

odds ratio of cryptorchidism of 1.2 (95% confidence interval 0.6-2.6); for betaHCCH the odds ratio was 1.6 (0.7-3.6). For HCB the adjusted odds ratio was 

near one. These results provide little support for an association of cryptorchidism 

with exposure to low levels of HCE or HCB. For beta-HCCH the findings were 

somewhat suggestive of an association but were inconclusive. 

Ribas-Fito, N., M. Sala, et al. (2003). "Organochlorine compounds and concentrations of 

thyroid stimulating hormone in newborns." Occupational and Environmental Medicine

60(4): 301-3. 

 AIMS: To assess the association between prenatal exposure to organochlorine 

compounds and thyroid status in newborns from an area with high levels of 

hexachlorobenzene (HCB). METHODS: A total of 98 mother-infant pairs (83.1% 

of all children born during the period 1997-99 in a specific area polluted with 

HCB) were recruited. Levels of organochlorine compounds were measured in 70 

cord serum samples. Concentrations of thyroid stimulating hormone (TSH) were 

measured in plasma of all newborns three days after birth. RESULTS: All 

newborns had concentrations of TSH within the range of normal reference values 

(<25 mU/l). Dichlorodiphenyl dichloroethylene (p,p'DDE), betahexachlorocyclohexane (beta-HCH), polychlorinated biphenyl (PCB) 138 and 118 

were related to higher concentrations of TSH, although only significant for betaHCH. Levels of HCB were not associated with TSH. CONCLUSIONS: Although 

this community is highly exposed to HCB, no association was found between this 

organochlorine and TSH concentrations at birth. 

Ribas-Fito, N., M. Torrent, et al. (2007). "Exposure to hexachlorobenzene during 

pregnancy and children's social behavior at 4 years of age." Environ Health Perspect

115(3): 447-50. 

 BACKGROUND: Hexachlorobenzene (HCB) is an organochlorine chemical that 

has been used in agriculture and industrial processes. Behavioral impairment 

after HCB exposure has been described in animal models, but little information is 
171

available in humans. OBJECTIVES: Our goal was to study the association of 

prenatal exposure to HCB with the social behavior of preschool children. 

METHODS: Two birth cohorts in Ribera d'Ebre and Menorca (Spain) were set up 

between 1997 and 1999 (n = 475). The California Preschool Social Competence 

Scale and the Attention-Deficit Hyperactivity Disorder (ADHD) were scored by 

each 4-year-old child's teacher. Organochlorine compounds were measured in 

cord serum. Children's diet and parental sociodemographic information were 

obtained through questionnaire. RESULTS: Children with concentrations of HCB 

> 1.5 ng/mL at birth had a statistically significant increased risk of having poor 

Social Competence [relative risk (RR) = 4.04; 95% confidence interval (CI), 1.76-

9.58] and ADHD (RR = 2.71; 95% CI, 1.05-6.96) scores. No association was 

found between HCB and the cognitive and psychomotor performance of these 

children. CONCLUSIONS: Prenatal exposure to current concentrations of HCB in 

Spain is associated with a decrease in the behavioral competence at preschool 

ages. These results should be considered when evaluating the potential 

neurotoxicologic effects of HCB. 

Ropstad, E., I. C. Oskam, et al. (2006). "Endocrine disruption induced by 

organochlorines (OCs): field studies and experimental models." Journal of toxicology 

and environmental health. Part A. 69(1-2): 53-76. 

 Long-range transport of persistent organic compounds by air and ocean currents 

from industrialized areas resulted in high levels of these pollutants in food webs 

in the Svalbard area. With the aim to test if organochlorine (OC) exposure in freeliving polar bears from Svalbard affected their plasma steroid hormone 

concentrations, it was found that polychlorinated biphenyls (PCBs) were 

associated with increased progesterone levels in females. The sum of pesticides 

(sigma pesticides) and sigma PCBs contributed significantly negative to the 

variation of the plasma testosterone in males, and the overall contribution of the 

OCs to the plasma cortisol variation was negative. A second objective was to 

study the effects of selected OCs (i.e., PCB 153 and PCB 126) on animal health 

as a consequence of effects on endocrine-regulated functions such as 

reproduction and immunity in a goat model focusing on long-term and low-level 

exposure during the periods of fetal development and in the neonatal period. 

Additionally, acute exposure was studied in adult mice. The results indicated that 

exposure to low doses of PCB 153 in utero and in the suckling period influenced 

reproductive functions and both PCB 153 and PCB 126 exerted 

immunomodulatory effects on the offspring, whereas acute exposure of adult 

mice had minor effects on male reproductive function. 

Rush, G. F., J. H. Smith, et al. (1983). "Perinatal hexachlorobenzene toxicity in the 

mink." Environmental Research 31: 116-124. 

 

Salmon, M. L., S. G. Madanagopal, et al. (2002). "Effects of hexachlorobenzene on 

embryonic mammalian cells." Toxicol In Vitro 16(5): 539-48. 

 Hexachlorobenzene (HCB) is a persistent organic pollutant that has been found 

to be bioaccumulating in several Arctic regions of the world. The response of 
172

embryonic cells to HCB exposure has been evaluated for several different 

cytotoxic responses, including genotoxic effects. NIH 3T3 (mouse) and WS1 

(human) embryonic cells were exposed to HCB at 1 and 10 times the average 

newborn cord blood concentrations of Alaska Arctic natives. Assays were then 

performed to determine the subsequent effects of HCB on overall cell number, 

viability, cell growth fraction and long-term survival, as well as specific 

biochemical and molecular responses. Exposure of both cell types to HCB 

results in cell membrane damage, a short-term decrease in cell number, 

increased DNA strand breaks, and a long-term decrease in colony survival. WS1 

cells also undergo cell-cycle arrest and modulations in glutathione concentration 

after exposure to HCB. In addition, NIH 3T3 cells exhibit an increased number of 

transformed foci after repeated exposure to HCB. This study demonstrates that 

relevant environmental concentrations of HCB have significant effects on 

mammalian embryonic cells in culture. 

Schell, L. M., M. V. Gallo, et al. (2004). "Thyroid function in relation to burden of PCBs, 

p,p'-DDE, HCB, mirex and lead among Akwesasne Mohawk youth: a preliminary study." 

Environmental Toxicology and Pharmacology 18(2): 91-99. 

 The effects of endocrine disrupting environmental contaminants such as 

polychlorinated biphenyls (PCBs), hexachlorobenzene (HCB), p,p'-

dichlorophenyldichloroethylene (p,p'-DDE), mirex, and lead, are examd. in a 

sample of youth of the Akwesasne Mohawk Nation who are 10-16.9 years of age 

(n = 115). The Akwesasne community is located adjacent to hazardous waste 

sites where PCBs and other toxicants have contaminated the local ecol. This 

study examines the relationship between measures of thyroid function and 

endocrine disrupting environmental toxicants. Both with and without statistical 

adjustment for other toxicants, as well as age, sex, and lipid levels, several 

indicators of PCB burden are significantly, neg. related to levels of free thyroxine 

and total thyroxine, and pos. to TSH. The lead level was pos. related to 

triiodothyronine. Future testing of nonlinear relationships is warranted. Despite 

the linear assocns. with TSH and free and total thyroxine, PCBs were not related 

to the increased occurrence of these hormones outside the clin. normal range for 

the testing lab. 

Schell, L. M., M. V. Gallo, et al. (2008). "Relationship of thyroid hormone levels to levels 

of polychlorinated biphenyls, lead, p,p'- DDE, and other toxicants in Akwesasne 

Mohawk youth." Environmental Health Perspectives 116(6): 806-13. 

 BACKGROUND: It is well documented that acute exposure to high levels of 

persistent organic pollutants, such as polychlorinated biphenyls (PCBs), p,p'-

dichlorophenyldichloroethylene (p,p'-DDE), and hexachlorobenzene (HCB), can 

affect human health including thyroid function. Chronic exposure to multiple 

toxicants is common but difficult to analyze, and most prior studies have focused 

on adults or newborns, creating a gap in our understanding of multitoxicant 

effects among adolescents. OBJECTIVE: We investigated whether levels of 

PCBs, p,p'-DDE, HCB, mirex, lead, and mercury reflecting past chronic exposure 

are associated with alterations in levels of thyroid-stimulating hormone (TSH), 
173

triiodothyronine (T(3)), total thyroxine (TT(4)), and free thyroxine (FT(4)) among 

older children and adolescents. METHODS: The sample consists of youth from 

the Akwesasne Mohawk Nation (n=232) who reside in proximity to several 

industries that have contaminated the local environment. We used multiple 

regression analysis to examine the effect of PCB groupings, p,p'-DDE, HCB, 

lead, and mercury on thyroid hormones after adjusting for sociodemographic 

covariates and controlling for all other toxicants. RESULTS: Exposure to PCBs 

affects the thyroid hormone profile in adolescents. The group of persistent PCBs 

was positively associated with TSH but inversely related to FT(4). Nonpersistent 

PCBs were significantly and negatively related to FT(4) only. HCB was negatively 

associated with T(4), and lead was positively associated with T(3). Breast-fed 

adolescents had higher levels of persistent PCBs and p,p'-DDE but not of 

nonpersistent PCBs or any other toxicant when compared with non-breast-fed 

adolescents. Though having lower levels of persistent PCBs and p,p'-DDE, nonbreast-fed adolescents exhibited significant relationships between persistent 

PCBs and TSH and FT(4), but breast-fed adolescents did not. It appears that 

PCBs from breast milk obscure the relationship between prenatal PCB exposure 

and thyroid function by adding random variation in PCB levels. CONCLUSION: 

Our results demonstrate a reduction in thyroid function in adolescents in relation 

to their current serum levels of PCBs. These observations are consistent with the 

hypothesis that pre-natal exposure to PCBs alters thyroid function in a longlasting manner but does not exclude the possibility that postnatal exposure is 

influential also. 

Sims, D. E., A. Singh, et al. (1991). "Alteration of primate ovary surface epithelium by 

exposure to hexachlorobenzene: a quantitative study." histology and Histopathology 6: 

525-529. 

 

Singh, A., D. Friesen, et al. (1990). "Hexachlorobenzene toxicity in the monkey ovary. I. 

ultrastructure induced by low (0.1 mg/kg) dose exposure." Electron microscopy 12: 282-

283. 

 

Singleton, H., R. F. Mervis, et al. (2002). "Developmental Exposure to 

Hexachlorobenzene (Hcb) in the Rat Results in Ectopic and Dysmorphic Cerebellar 

Purkinje Cells [Abstract]." Society for Neuroscience Abstract Viewer and Itinerary 

Planner 2002: Abstract No. 

 Hexachlorobenzene (HCB) is a dioxin-like organochlorine compound that binds 

to the aryl hydrocarbon receptor (Ah). HCB may impair thyroid metabolism. HCB 

is widespread in the environment and accumulates in biological systems. It is 

transplacentally transferred from mother to fetus during pregnancy and through 

breast milk. Neurotoxic consequences of HCB exposure on the developing brain 

are, however, poorly documented. HCB (2.5 mg/kg/day) was administered by 

gavage to Sprague-Dawley female rats starting two weeks before pregnancy until 

the pups were weaned. Controls received corn oil. Pups were sacrificed when 22 

days-old and cerebella were stained using the Golgi-Cox method. There were 

seven male subjects per group. Using coded slides, from each subject seven 
174

randomly selected Purkinje cells (PCs) were evaluated for soma size and areal 

extent of their dendritic arbor. There were no differences between groups for PCs 

that had correctly migrated and were located in the Purkinje cell layer. However, 

there were also a significant number of neurons with Purkinje cell-like 

characteristics that had improperly migrated into the molecular cell layer. These 

highly dysmorphic PCs had dendritic areas 90% smaller, and somas 75% 

smaller, than normal. Since thyroid function influences critical aspects of 

cerebellar development, the abnormal migration of PCs and their dysmorphic 

development may reflect the neurotoxic impact of HCB exposure on thyroid 

function. 

Smink, A., N. Ribas-Fito, et al. (2008). "Exposure to hexachlorobenzene during 

pregnancy increases the risk of overweight in children aged 6 years." Acta Paediatr

97(10): 1465-9. 

 AIM: To determine whether prenatal exposure to hexachlorobenzene (HCB) has 

potential adverse effects on child's weight and body mass index (BMI) in a 

general population with no local pollution sources. METHODS: Starting from mid 

1997, all mothers presenting for antenatal exposure in Menorca were recruited. 

Subsequently, 482 children were enrolled. HCB was measured in cord blood. 

Weight and height were measured at birth and at age 6.5 years. RESULTS: 

Children with HCB levels higher than 1.03 ng/mL in cord blood were 1.14 kg 

(0.38) heavier and had a higher BMI (beta= 0.80 (0.34)) than children with HCB 

levels lower than 0.46 ng/mL. No statistically significant associations were found 

in height. Children in the higher exposure group of HCB had an increased risk of 

2.5 and 3.0 of being overweight and obese. Children from normal weight mothers 

also presented an increased risk of having higher BMI with increasing 

concentrations of HCB in cord serum. CONCLUSION: Prenatal exposure to HCB 

is associated with an increase in BMI and weight at age 6.5 years. Further 

studies with larger samples and longer follow-up are needed to confirm these 

results. 

Sunyer, J., M. Alvarez-Pedrerol, et al. (2008). "Urinary porphyrin excretion in children is 

associated with exposure to organochlorine compounds." Environmental Health 

Perspectives 116(10): 1407-10. 

 BACKGROUND: Hexachlorobenzene (HCB) and other organochlorines induce 

porphyria cutanea tarda (PCT) in animal studies. Evidence in humans, however, 

is contradictory. In neonates and adults from a population historically highly 

exposed to HCB (Flix, Catalonia, Spain), no relation with PCT or with porphyrin 

excretion was found. OBJECTIVES: We aimed to analyze the association 

between urinary porphyrin excretion and exposure to HCB and other 

organochlorinated compounds in children 4 years of age. METHODS: Our birth 

cohort included all newborns from Flix and the five surrounding towns (where no 

airborne pollution occurred). Among the 68 children with porphyrins we 

measured in cord blood, 52 children 4 years of age provided blood to measure 

organochlorine compounds, hair for methylmercury, and urine for porphyrin 

excretion pattern. RESULTS: Quantitative porphyrin excretion was within the 
175

normal values. However, total porphyrins, coproporphyrin I (CPI), and 

coproporphyrin III (CPIII) adjusted to creatinine excretion increased with 

increasing levels of HCB, 1,1-dichloro-2,2-bis(4-chlorophenyl)ethylene (p,p'-

DDE), 1,1,1-trichloro-2,2-bis(4-chlorophenyl)ethane (p,p'-DDT), and 

polychlorinated biphenyl congener 153 (PCB-153). We found no association with 

methylmercury. When we fitted multiple pollutant models, p,p'-DDE had the 

strongest association. We found these associations in children from both Flix and 

other towns, and they were independent of breast-feeding and of organochlorine 

and porphyrin levels at birth. CONCLUSION: HCB at current levels did not 

induce porphyria or increase uroporphyrins. However, the increase of urinary 

coproporphyrins suggests an incipient toxic effect of the organochlorines, 

especially for p,p'-DDE, on the hepatic heme-synthesis pathway that differs from 

the major effects seen in PCT. 

Takser, L., D. Mergler, et al. (2005). "Thyroid hormones in pregnancy in relation to 

environmental exposure to organochlorine compounds and mercury." Environmental 

Health Perspectives 113(8): 1039-45. 

 Polychlorinated biphenyls (PCBs), chlorinated pesticides, and mercury are global 

environmental contaminants that can disrupt the endocrine system in animals 

and humans. However, there is little evidence that they can interfere with 

endocrine status in pregnant women and neonates at low levels of exposure. The 

aim of this study was to examine thyroid hormone levels during pregnancy and in 

cord blood in relation to blood concentrations of organochlorine compounds 

(OCs) and Hg in healthy women recruited during pregnancy. We found a 

significant negative correlation between maternal total triiodothyronine levels and 

three non-coplanar congeners (PCB-138, PCB-153, and PCB-180), three 

pesticides (p,p -DDE, cis-nanochlor, and hexachlorobenzene), and inorganic Hg 

independently, without any other changes in thyroid status. No significant 

relationships were observed between OCs and cord serum thyroid hormones. 

Cord serum free thyroxin was negatively correlated with inorganic Hg. These 

results suggest that at even low levels of exposure, persistent environmental 

contaminants can interfere with thyroid status during pregnancy. 

Tenenbaum, D. J. (2008). "Obesity: Childhood BMI Rises with Prenatal Exposure to 

Hexachlorobenzene." Environmental Health Perspectives 116(12): A520. 

 Fulltext: 

A prospective study published in the October 2008 issue of Acta Paediatrica has found an 

association between prenatal exposure to hexachlorobenzene (HCB) and being 

overweight or obese in childhood. The study was the first prospective look at prenatal 

exposure of HCB in a general population, says corresponding author Agnes Smink, now 

a research coordinator at consultancy SHL Group–Breda. The study relied on body mass 

index (BMI), a common gauge of overweight and obesity. 

HCB is one of many organochlorine compounds restricted or banned by the Stockholm 

Convention on Persistent Organic Pollutants, which was signed in 2001. The compound 

was widely used, starting in 1933, to kill fungi on crop seeds and in some manufacturing 
176

processes. Its commercial use in the United States ceased in 1965. HCB bioaccumulates 

in fat and breaks down slowly. 

In humans, prenatal exposure to HCB has been shown to affect age at menarche and menopause, 

asthma, and fertility, as well as increase the relative risk of attention deficit/hyperactivity 

disorder. Other organochlorine compounds, including DDT and the polychlorinated 

biphenyls (PCBs), have also been implicated in causing damage in utero. 

In 1997, the research group began recruiting expectant mothers on the Spanish Mediterranean 

island of Minorca. They measured HCBs, PCBs, the pesticide DDT, and the DDT 

metabolite DDE in umbilical cord blood of 405 children. The children’s height and 

weight was measured at birth and at age 6.5 years. 

Analysis showed that each doubling in cord blood HCB levels was associated with a weight 

increase of 1.14 kg (2.5 lb), but the children’s height did not differ significantly. The 

relative risk of being overweight was a statistically significant 1.7 times higher per 

doubling in cord blood HCB level, and the relative risk for obesity was a nonsignificant 

2.0 times higher. The association between HCB concentration and elevated BMI was 

independent of maternal socioeconomic status, weight, or education, or child’s birth order 

or birth weight. There was no observed correlation between elevated BMI and PCBs, 

DDT, or DDE. 

“This study provides an important piece of evidence that obesity may be related not only to junk 

food and lack of exercise but also to halogenated compounds or endocrine disruptors,” 

says Wilfried Karmaus, a professor of epidemiology at the University of South Carolina. 

In his study of Michigan women who ate large quantities of home-caught fish, maternal 

levels of DDE did correlate with BMI and weight in the women’s adult children aged 20 

to 50. That study, which relied on historic analyses of blood samples in which HCB had 

not been measured, will be published in a forthcoming issue of Occupational and 

Environmental Medicine. 

The fact that different studies find different correlations between organochlorines and childhood 

obesity is troubling, Karmaus admits. “It bothers me a little bit that the Spanish found [a 

link with] HCB and we found [one with] DDE,” he says. “But they are both endocrine 

disruptors, and they may work on a comparable mechanism. There is some indication that 

these substances may disrupt normal development or the metabolism of fat, but we don’t 

know which substance and which mechanism.” 

Smink cautions that the new study does not suggest that HCB, or indeed any other 

organochlorine, is the sole explanation for overweight and obesity, which are estimated 

by the World Health Organization to affect at least 1 billion and 300 million people, 

respectively, worldwide. “It is important to keep in mind that a lot of factors are involved 

in the obesity epidemic,” she says. “I think that the proportion of the ongoing obesity 

epidemic is minimal when it comes to HCB exposure. However, it is important to reduce 

prenatal exposure to toxicants like HCB to prevent health problems like overweight. It is 

not clear if the observed effects on body weight remain after the age of six years.” 

Because most HCB exposure comes through diet, especially meat, “a mother can prevent 

exposure by paying attention to where the local pollution sources are located and avoid 

eating food which has been grown there,” Smink says. 

“Pregnancy is a really important time for development,” says Karmaus. “During pregnancy, you 

are exposed to [all the toxicants] your mother has collected in twenty or thirty years.” 
177

Prevention is key, he says, because “as a fetus you can't decide not to live under these 

conditions.” 

Torres-Arreola, L., G. Berkowitz, et al. (2003). "Preterm birth in relation to maternal 

organochlorine serum levels." Ann Epidemiol 13(3): 158-62. 

 PURPOSE: To evaluate the associations of serum levels of p,pacute;-DDE and 

two other persistent organochlorine pesticides, beta-HCH and HCB, in relation to 

preterm birth. METHODS: During 1995 we performed a case-cohort study and 

233 mothers were recruited at three large maternity hospitals in Mexico City. 

Serum levels were obtained shortly after delivery. RESULTS: A non-significant 

increased risk of preterm birth in relation to serum p,p'-DDE levels was observed. 

There was also a suggestion of an increased risk of preterm birth among women 

in the highest tertile of beta-HCH (adjusted odds ratio 1.85, 95% CI = 0.94-3.66, 

p value for test of trend p = 0.08) compared with the lowest tertile. No association 

was found between HCB serum levels and preterm births. CONCLUSIONS: 

These findings suggest that p,pacute;-DDE and other organochlorine pesticides 

may pose a risk to preterm birth in countries that continue to use such 

insecticides for malaria control. 

Verhulst, S. L., V. Nelen, et al. (2009). "Intrauterine exposure to environmental 

pollutants and body mass index during the first 3 years of life." Environmental Health 

Perspectives 117(1): 122-6. 

 OBJECTIVE: We investigated the association between body mass index (BMI) 

standard deviation score (SDS) and prenatal exposure to hexachlorobenzene, 

dichlorodiphenyldichloroethylene (DDE), dioxin-like compounds, and 

polychlorinated biphenyls (PCBs). METHODS: In this prospective birth cohort 

study, we assessed a random sample of mother-infant pairs (n = 138) living in 

Flanders, Belgium, with follow-up until the children were 3 years of age. We 

measured body mass index as standard deviation scores (BMI SDS) of children 

1-3 years of age as well as pollutants measured in cord blood. RESULTS: DDE 

correlated with BMI SDS, with effect modification by maternal smoking and the 

child's age. At 1 year, children of smoking mothers had higher BMI SDS than did 

children of nonsmoking mothers. At 3 years, this difference was reduced 

because of the faster rate of decline in BMI SDS in the former group. This 

relationship held except for children with high levels of DDE. DDE had a small 

effect on BMI SDS at 3 years of age in children of nonsmoking mothers 

(difference in BMI SDS for DDE concentrations between the 90th and 10th 

percentiles = 0.13). On the other hand, smoking enhanced the relation between 

DDE and BMI SDS at 3 years (difference in BMI SDS for DDE concentrations 

between the 90th and 10th percentiles = 0.76). Increasing concentrations of 

PCBs were associated with higher BMI SDS values at all ages (parameter 

estimate = 0.003 +/- 0.001; p = 0.03). CONCLUSION: In this study we 

demonstrated that intrauterine exposure to DDE and PCBs is associated with 

BMI during early childhood. Future studies are warranted to confirm our findings 
178

and to assess possible mechanisms by which these pollutants could alter energy 

metabolism. 

Villeneuve, D. C., L. G. Panopio, et al. (1974). "Placental transfer of hexachlorobenzene 

in the rabbit." Environmental Physiology and Biochemistry 4: 112-115. 

 

CODE 7 (compilations) References 

Agency for Toxic Substances and Disease Registry (2002). "Toxicological profile for 

hexachlorobenzene." Public Health Service, Agency for Toxic Substances and Disease 

Registry, Division of Toxicology, Toxicology Information Branch 29(30333). 

 Contents: quick reference for health care providers; public health statement; 

health effects; chemical and physical information; production, import, use and 

disposal; potential for human exposure; analytical methods; regulations and 

advisories; glossary. Health hazards include: immunotoxic effects; embryotoxic 

effects; porphyria cutanea tarda (skin lesions, arthritis, liver toxicity, neurological 

effects, gastric disorders); liver damage; thyroid disorders; neurotoxic effects; 

bone diseases; renal damage; haematotoxic effects; endocrine disorders; 

carcinogenic effects. Update of CIS 97-213. 

Anonymous (2002). "Toxicological profile for Hexachlorobenzene (update)." Agency for 

Toxic Substances and Disease Registry U.S. Public Health Service 350. 

 

Bishop, J. B. (2002). Molecular Detection Of Chromosome Damage In Rodent Germ. 

Crisp Data Base National Institutes of Health. 

 Infertility and other untoward reproductive and developmental outcomes, such as 

spontaneous abortion, fetal and neonatal death, birth defects, and genetic 

susceptibilities to cancer and other diseases, are associated with genetic 

damage occurring in mammalian germ cells. This Project employs molecular 

biomarkers in the identification and characterization of chemicals in our 

environment that are responsible for such germ cell damage. Specifically, 

fluorescence in situ hybridization (FISH) with chromosome specific DNA markers 

are used to detect structural and numerical chromosome damage in sperm and 

early embryonic cells of rodents. These rodent sperm-FISH assays, which 

provide parallel models of similar sperm-FISH assays in humans, are being used 

for evaluating the aneugenic and clastogenic potential of environmental 

chemicals tested in NTP bioassays, as well as for addressing questions about 

dose response, differential stage sensitivity, the relationship of defects seen in 

sperm to those transmitted to the early embryo, and other important issues 

related to health-risks which cannot be addressed in human studies. During this 

past year, frozen samples of rat sperm were obtained from NTP Reproductive 

Assessment by Continuous Breeding (RACB) studies on hexachlorobenzene and 

tetrachloroazobenzeneare, and frozen samples of mouse sperm were obtained 
179

from an RACB study of AZT/ddI and from micronucleus studies of benzene, 

diazoaminobenzene, analine and cyclophosphamide. 

Ezendam, J., J. G. Vos, et al. (2004). "Mechanisms of hexachlorobenzene-induced 

adverse immune effects in Brown Norway rats." Journal of immunotoxicology 1(3-4): 

167-175. 

 A review. Hexachlorobenzene (HCB) is an environmental pollutant that induces 

adverse immune effects in humans and rats. Brown-Norway rats (BN) appear to 

be very susceptible to HCB-induced immune effects. Oral exposure causes 

inflammatory skin and lung lesions, enlarged spleen and lymph nodes (LN), and 

elevated humoral responses. This review describes recent expts. that were 

performed to elucidate the mechanisms underlying these adverse immune 

effects. The metabolites tetrachlorohydroquinone and tetrachlorobenzoquinone 

are capable of generating neoantigen-specific T-cells in the mouse reporter 

antigen popliteal lymph node assay with 2,4,6-trinitrophenyl-Ficoll. Addnl. expts. 

in BN rats have shown that T-cells are involved in the development of HCBinduced skin lesions, the increase in auricular LN wt., lung eosinophilia, and 

humoral responses. However, splenomegaly and macrophage infiltration in the 

spleen and lung occur independent of T-cells. Remarkably, HCB does not induce 

T-cell sensitization in BN rats, suggesting that T-cells are activated 

nonspecifically, for example by macrophages. Transcriptome profiles obtained 

after subchronic HCB exposure to BN rats reveal that HCB induces a systemic 

inflammatory response in which several innate immune cells, such as 

macrophages, and pro-inflammatory cytokines are involved. Addnl. expts. have 

shown that macrophages are implicated in HCB-induced skin lesions, in 

particular in the aggravation of skin effects. Also, HCB-induced lung eosinophilia 

and elevation of anti-ssDNA IgM antibodies are less pronounced after 

macrophage elimination. Presumably, HCB activates macrophages, thereby 

generating pro-inflammatory adjuvant signals that induce a systemic 

inflammatory response. Subsequently, this may lead to polyclonal activation of Tand B-cells, eosinophilia, and eventually visible clin. effects. 

Fan, A. M., R. A. Howd, et al. (2004). "Risk Assessment For Drinking Water 

Contaminants: Asbestos, Barium, Beryllium, Chlorobenzene, 1, 1- Dichloroethane, 

Diethylhexyladipate, Ethylene Dibromide, Hexachlorobenzene, Silvex, 1, 1, 2, 2- 

Tetrachloroethane And Toxaphene." Toxicologist 78(1-S): 152. 

 Risk assessments were performed for 11 chemicals for development of public 

health goals (PHGs) in drinking water. PHGs are non-regulatory concentrations 

in water that are not anticipated to produce adverse health effects following a 

lifetime exposure, based on health considerations. Toxicological evaluations 

included both animal and human studies, and carcinogenic and non-carcinogenic 

endpoints. The PHGs established based on carcinogenic endpoints are: 

Asbestos, 7E6 fibers/L ( > 10 um), mice; 1, 1-dichloroethane, 3 ppb, rats; 

ethylene dibromide, 10 ppb, rats and mice; hexachlorobenzene, 0.03 ppb, rats; 1, 

1, 2, 2-tetrachloroethane, 0.1 ppb, mice; and toxaphene, 0.03 ppb, mice. PHGs 

based on non-cancer endpoints are: Barium, 2000 ppb, absence of 
180

cardiovascular effects (hypertension), human; beryllium, 1 ppb, gastrointestinal 

tract lesions, dog; diethylhexyladipate, 200 ppb, fetotoxicity, rat; chlorobenzene, 

200 ppb, liver pathology, dog; and silvex, 25 ppb, liver pathology, dogs. The 

assessments included the consideration of sensitive populations, cancer potency 

values, relative source contribution, uncertainty factors, and water consumption 

intake. These PHGs were finalized September 2003 after extensive periods for 

scientific peer review and public input. 

Huijbregts, M. A., L. J. Rombouts, et al. (2005). "Human-toxicological effect and 

damage factors of carcinogenic and noncarcinogenic chemicals for life cycle impact 

assessment." Integr Environ Assess Manag 1(3): 181-244. 

 Chemical fate, effect, and damage should be accounted for in the analysis of 

human health impacts by toxic chemicals in life-cycle assessment (LCA). The 

goal of this article is to present a new method to derive human damage and 

effect factors of toxic pollutants, starting from a lognormal dose-response 

function. Human damage factors are expressed as disability-adjusted life years 

(DALYs). Human effect factors contain a disease-specific and a substancespecific component. The disease-specific component depends on the probability 

of disease occurrence and the distribution of sensitivities in the human 

population. The substance-specific component, equal to the inverse of the ED50, 

represents the toxic potency of a substance. The new method has been applied 

to calculate combined human damage and effect factors for 1,192 substances. 

The total range of 7 to 9 orders of magnitude between the substances is 

dominated by the range in toxic potencies. For the combined factors, the typical 

uncertainty, represented by the square root of the ratio of the 97.5th and 2.5th 

percentile, is a factor of 25 for carcinogenic effects and a factor of 125 for 

noncarcinogenic effects. The interspecies conversion factor, the (non)cancer 

effect conversion factor, and the average noncancer damage factor dominate the 

overall uncertainty. 

Korrick, S. A. and S. K. Sagiv (2008). "Polychlorinated biphenyls, organochlorine 

pesticides and neurodevelopment." Curr Opin Pediatr 20(2): 198-204. 

 PURPOSE OF REVIEW: Although environmental levels of polychlorinated 

biphenyls and certain organochlorine pesticides--hexachlorobenzene, 

dichlorodiphenyl trichloroethane and its primary metabolite, dichlorodiphenyl 

dichloroethene--are generally on the decline, early-life exposures to these 

prevalent contaminants continue. The review will describe current understanding 

of the potential neurodevelopmental consequences of low-level exposures to 

these contaminants. RECENT FINDINGS: Animal models suggest that early-life 

exposures to polychlorinated biphenyls, dichlorodiphenyl 

trichloroethane/dichlorodiphenyl dichloroethene or hexachlorobenzene are 

associated with decreased cognitive or behavioral function in later development. 

Despite almost 30 years of research, however, results of human studies are 

inconsistent regarding the nature of the observed effects and their persistence 

over time. Overall, epidemiologic studies support modest associations of 

primarily prenatal polychlorinated biphenyl exposures with differences in 
181

neuromotor development, decrements in cognition and behavioral deficits, 

particularly regarding attention and impulse control. There are limited published 

human data regarding potential neurodevelopmental toxicities of early-life 

exposures to dichlorodiphenyl trichloroethane/dichlorodiphenyl dichloroethene 

and hexachlorobenzene. SUMMARY: Exposures to polychlorinated biphenyls, 

dichlorodiphenyl trichloroethane/dichlorodiphenyl dichloroethene and 

hexachlorobenzene are likely detrimental to neurodevelopment. Effective control 

of exposure is complicated by variable exposure sources and variable 

contaminant levels in food, particularly fish, for which it is important to balance 

the risk of contaminants with nutritional benefits. 

Langer, P. (2008). "Persistent organochlorinated pollutants (PCB, DDE, HCB, dioxins, 

furans) and the thyroid--review 2008." Endocr Regul 42(2-3): 79-104. 

 

Mariussen, E. and F. Fonnum (2006). "Neurochemical targets and behavioral effects of 

organohalogen compounds: an update." Crit Rev Toxicol 36(3): 253-89. 

 Organohalogen compounds (OHCs) have been used and still are used 

extensively as pesticides, flame retardants, hydraulic fluids, and in other 

industrial applications. These compounds are stable, most often lipophilic, and 

may therefore easily biomagnify. Today these compounds are found distributed 

both in human tissue, including breast milk, and in wildlife animals. In the late 

1960s and early 1970s, high levels of the polychlorinated biphenyls (PCBs) and 

the pesticide dichlorodiphenyl trichloroethane (DDT) were detected in the 

environment. In the 1970s it was discovered that PCBs and some chlorinated 

pesticides, such as lindane, have neurotoxic potentials after both acute and 

chronic exposure. Although the use of PCBs, DDT, and other halogenated 

pesticides has been reduced, and environmental levels of these compounds are 

slowly diminishing, other halogenated compounds with potential of toxic effects 

are being found in the environment. These include the brominated flame 

retardants, chlorinated paraffins (PCAs), and perfluorinated compounds, whose 

levels are increasing. It is now established that several OHCs have 

neurobehavioral effects, indicating adverse effects on the central nervous system 

(CNS). For instance, several reports have shown that OHCs alter 

neurotransmitter functions in CNS and Ca2+ homeostatic processes, induce 

protein kinase C (PKC) and phospholipase A2 (PLA2) mobilization, and induce 

oxidative stress. In this review we summarize the findings of the neurobehavioral 

and neurochemical effects of some of the major OHCs with our main focus on 

the PCBs. Further, we try to elucidate, on the basis of available literature, the 

possible implications of these findings on human health. 

McGovern, V. (2004). "Hexachlorobenzene exposure: widespread toxicant produces 

pervasive effects." Environ Health Perspect 112(7): A416. 

 

Reed, L., V. Buchner, et al. (2007). "Environmental toxicology and health effects 

associated with hexachlorobenzene exposure." Rev Environ Health 22(3): 213-43. 
182

 The synthetic industrial chemical hexachlorobenzene (HCB) is a white crystalline 

solid compound. The substance is a bioaccumulative, persistent, and toxic 

pollutant. Historically HCB was commonly used as a pesticide and fungicide. 

Although HCB production and use has ceased in many countries, the compound 

is still generated inadvertently, as a byproduct and/or impurity in the manufacture 

of various chlorinated compounds, and released into the environment. 

Hexachlorobenzene is ubiquitous in air, water, soil, and biological matrices, as 

well as in major environmental compartments. Exposure to this substance is a 

public health concern because of its association with a wide range of adverse 

health effects. The International Agency for Research on Cancer and the United 

States Environmental Protection Agency classify HCB as a probable human 

carcinogen. Although globally the consumption of HCB-contaminated food is the 

principal source of environmental exposure, exposure can also occur through the 

inhalation of HCB-contaminated air, by dermal contact, or through in utero 

exposure and breast milk. In addition to cancer, the human health effects 

associated with HCB exposure involve systemic impairment (thyroid, liver, bone, 

skin), as well as damage to the kidneys and blood cells and the immune, 

endocrine, developmental, and nervous systems. In this review, we discuss the 

sources of HCB and the potential for human exposure, as well as systemic, 

carcinogenic, and teratogenic health effects. 

Sjostrom, M., A. Kolman, et al. (2008). "Estimation of human blood LC50 values for use 

in modeling of in vitro-in vivo data of the ACuteTox project." Toxicology in Vitro 22(5): 

1405-11. 

 The main aim of the ACuteTox project, under EU 6th Framework programme, is 

to investigate whether animal toxicity tests for acute systemic toxicity could be 

replaced by a combination of alternative assays. Data for 97 reference chemicals 

was collected in the ACuteTox database (Acutoxbase), designed to handle invitro 

and invivo (human and animal) lodged data. The principal basis for 

demonstration of the applicability of invitro tests is the invitro-invivo modeling, by 

using statistical correlation between invitro IC50 molar values (the 50% inhibitory 

concentration for the endpoints measured) and human blood molar 

concentrations LC50 (50% lethal concentrations). The LC50 values were 

calculated from time-related sub-lethal and lethal blood concentrations 

determined from human acute poisoning cases. The 3T3 standard NRU assay 

(3T3 NRU) was chosen, among the various basal cytotoxicity assays, applied in 

the ACuteTox project, to demonstrate the applicability of the IC50/LC50 values 

for invitro-invivo modeling. Linear regression analysis between IC50 (x) and 

LC50 (y) gave an explained variance R2=0.56 for the 67 reference chemicals, for 

which both sets of data were available. The results demonstrated usefulness of 

human LC50 values for invitro-invivo evaluation of the predictability of basal 

cytotoxicity assays for human acute systemic toxicity. The R2 value of 0.56 

shows, as in the MEIC study, that additional organ-specific and biokinetic tests 

are needed in order to improve the predictability. 
183

Tanabe, K. and T. Matsumoto (2002). "Prediction of carcinogenicity of chlorinecontaining organic compounds by neural network." Journal of Computer Chemistry, 

Japan 1(1): 23-28. 

 A neural network was applied to the prediction of the carcinogenicity of 41 kinds 

of org. chlorine- contg. compds. Seven kinds of structural and quantum-chem. 

descriptors: mol. wt., log P. Gibbs free energy, ionization potential, LUMO 

energy, HOMO-LUMO energy gap, and Connolly vol. were detd. These 

descriptors were entered into the input layer of a three-layered neural network, 

and carcinogenicity data from the NTP database were entered into the output 

layer as teaching data. The network was trained with an error-back-propagation 

method, and a leave-one-out test showed a correct classification rate of 93%. 

Vos, J. G. and C. F. Kuper (2004). "Chemically-induced immunopathology and immune 

functional changes." Journal of Toxicologic Pathology 17(2): 137-146. 

 A review. Toxicol. pathol. of lymphoid organs plays an important role in the risk 

assessment process of immunotoxicants. Identification of chems. that have the 

potential to cause injury to the immune system is of considerable public health 

significance because of the role of the immune system in infectious diseases, 

hypersensitivity reactions, and autoimmune diseases. In assessing 

immunotoxicity, a two-tier testing system is usually employed in rodents in which 

the first tier is a general screen for (immuno)toxicity including enhanced 

histopathol. of lymphoid organs and the second tier consists of more specific 

immune function studies including host resistance tests or mechanistic studies. 

Studies with the potent immunotoxicants TCDD, TBTO, HCB, azathioprine, and 

cyclosporin A are discussed, which provide data correlating histopathol. with 

immune function changes. This is followed by a discussion of the outcomes of 

enhanced histopathol. investigation in the interlab. validation studies with 

azathioprine, cyclosporin A, and HCB in the rat, as well as the results of a recent 

evaluation of enhanced histopathol. in the mouse as an indicator of 

immunotoxicity. From these studies, that have been the basis for a no. of 

regulatory activities, the following conclusions can be drawn: (1) the consistency 

between histopathol. and functional tests, (2) the complimentary information of 

pathol. and immunol. observations, and (3) the dependence on standardized 

protocols and trained toxicol. pathologists to accurately identify and grade 

microscopical changes in lymphoid organs and tissues. 

CODE 8 (not useful) References 

(1999). Behavior of pesticides in tomatoes during commercial and home preparation. 

AU - ABOU-ARAB A AK. 

 BIOSIS COPYRIGHT: BIOL ABS. Monitoring of pesticide residues in Egyptian 

tomatoes and its products was studied. The average contents of HCB, lindane, 

dieldrin, heptachlor epoxide and DDT derivatives were detected at levels 0.009, 

0.003, 0.006, 0.008 and 0.083 mg/kg, respectively. On the other hand, the levels 

of dimethoate, profenofos and pirimiphos-methyl were 0.461, 0.206 and 0.114 

mg/kg, respectively. In ketchup and paste samples, most organochlorine and 
184

organophosphorus pesticide residues were not detectable. The distr eling, were 

necessary to remove pesticide residues in the skin. Cooking of tomatoes 

(including processing tomato to paste) helped to eliminate most pesticide 

residues from contaminated tomatoes. 

(2000). "Atmospheric deposition of toxic substances to the Great Lakes: IADN results to 

1996." /u0103. 

 The primary objective of this document is to report biennial loadings estimates for 

the atmospheric deposition of toxic substances to the Great Lakes for 1995-96. 

Three deposition processes are considered: Wet deposition by precipitation, dry 

particle deposition by sedimentation, and net diffusive gas exchange that 

combines the effects of absorption from air to water with volatilization from water 

to air. The estimates presented are based on measurements taken largely at the 

Integrated Atmospheric Deposition Network master stations, of which there is 

one per lake. Toxic substances measured include dieldrin, DDT, polychlorinated 

biphenyls, polycyclic aromatic hydrocarbons, lead, arsenic, hexachlorobenzene, 

and chlordane. Discussion of the findings considers three fundamental issues: 

The magnitude of the loadings, the manner in which each loading component 

contributes to the total, and the variation or trends in the loadings across the 

Great Lakes Basin and over many years. 

(2000). "C-56 Monitoring Data from the Michigan State Office of Toxic Materials Control 

with Cover Letter Dated 010981." EPA/OTS; Doc #40-8149021. 

 

(2000). "Contaminants in water and precipitation from the Canadian Great Lakes: 10 

years of monitoring levels." 

 Great Lakes fact sheet. Text in English and French (Bilingual). French ed. on the 

same fiche. This fact sheet describes the spatial & temporal concentration 

patterns of eight persistent toxic substances that historically have been reported 

to threaten or potentially threaten human health & aquatic life in the Great 

Lakes. These substances include hexachlorobenzene, organochlorine pesticides, 

octachlorostyrene, Mirex, polychlorinated biphenyls, and polycyclic aromatic 

hydrocarbons. Ambient concentrations are also compared to water quality 

objectives. 

(2000). "Determination of level of quantification for measuring HCB and PCDD/PCDF in 

soil -- Draft. Draft." 

 Text in English and French (Bilingual). French ed. (Determination des niveaux de 

dosage...) on the same fiche. Environment Canada has included 

hexachlorobenzene (HCB) and polychlorinated dibenzo-p-dioxins & 

dibenzofurans (PCDD/PCDF) in its list of toxic substances that are persistent, 

bioaccumulative, and anthropogenic. Virtual elimination of substances in this list 

from the environment is the main objective of the dept.'s Toxic Substance 

Management Policy. The level of quantification (LoQ) prescribed in this report will 

be used as a baseline to assist in establishing a virtual elimination target for HCB 

and PCDD/PCDF. The LoQ is defined as the lowest concentration of a target 
185

compound that can be quantified confidently. The report summarizes the study 

design & experiments for determining the LoQ for HCB & PCDD/PCDF, based on 

analyses of eight types of reference soils fortified with known quantities of the 

two substances. Results of the 10 replicate analyses are presented suggesting 

an estimated LoQ for each toxic substance. 

(2000). "Final Report on the Toxic Substances Survey of Lakes Michigan, Superior, and 

Tributary Streams." EPA/OTS; Doc #40-8390045. 

 

(2000). "Letter to Usepa Concerning the Enclosed Document for the Initial List of 100 

Chemicals Grouped in 4 Sets of 25 for Evaluation in Atsdr/Epa Toxicological Profiles 

with Attachment." EPA/OTS; Doc #110-871004. 

 

(2002). "Toxicological Profile for Hexachlorobenzene (September 2002)." 

 See also PB97-121065. 

Abou-Arab, A. A. K., M. S. Kawther, et al. (1999). "Quantity estimation of some 

contaminants in commonly used medicinal plants in the Egyptian market." Food 

Chemistry 67(4): 357-363. 

 BIOSIS COPYRIGHT: BIOL ABS. Pesticide residues, heavy metal contents and 

aflatoxins were estimated in five medicinal plants frequently used by both infants 

and adults (peppermint, chamomile, anise, caraway and tilio). Samples were 

collected from different sources in the Egyptian market. Results showed that 

malathion, dimethoate and profenofos predominated in most of the analysed 

samples. On the other hand, the lowest mean levels were detected with aldrin, 

dieldrin, chlordane and lindane. Chlorpyrifos, parathion, diazinon and endosulfan 

were not detectable in most of the samples under investigation. The results 

indicated that some of the collected samples contained some types of 

organophosphorus and orgnochlorine pesticide residues, within the limits of The 

Egyptian Organization for Standardization and Quality Control (EOS) maximum 

limits for pesticide residues on medicinal aromatic plants (1991) and 

Pharmeuropa (19 93). Heavy metal contents in the collected samples, i.e. Fe, 

Cu, Mn, Zn, Pb, Cd, Cr, Co, Sn and Ni,were found at different levels. The highest 

mean levels of Pb, Zn, Cu, and Fe were found in chamomile flower samples, 

while those of Cd, Cr and Mn, were detected in peppermint and of Ni, Co and Sn 

in caraway samples. The results also showed that the most frequently isolated 

fungi were penicillium sp., A. niger and Fusarium sp. Nevertheless, the finding of 

natural mycotoxin contamination was negative in all samples. 

Adeyeye, A. and O. Osibanjo (1999). "Residues of organochlorine pesticides in fruits, 

vegetables and tubers from Nigerian markets." Science of the Total Environment 231(2-

3): 227-233. 

 BIOSIS COPYRIGHT: BIOL ABS. Residue levels of organochlorine pesticides 

have been determined in raw fruits, vegetables and tubers from markets in 

Nigeria. In the fruits, total HCH, aldrin and total DDT were detected in 77, 38 and 

30% of all samples, respectively. In the vegetables, total HCH, HCB, total DDT 
186

and aldrin were detected from 95, 53, 50 and 30%, respectively, of all samples. 

Aldrin + dieldrin, total HCH, and total DDT were detected from 98, 79 and 49%, 

respectively, of all tuber samples. Other pesticides were be 

Ahmad, N., G. Bugueno, et al. (1999). "Determination of organochlorine and 

organophosphate pesticide residues in fruits, vegetables and sediments." Journal of 

Environmental Science and Health. Part B: Pesticides, Food Contaminants, and 

Agricultural Wastes 34(5): 829-848. 

 BIOSIS COPYRIGHT: BIOL ABS. A method is described for the determination of 

organochlorine and organophosphate pesticide residues in fruits, vegetables and 

sediments. The concentrated solvent extract was sealed in a polymeric 

membrane tube, dialysed in cyclohexane and the solvent replaced with hexane. 

The organophosphates were analysed on a specific thermionic detector without 

further clean-up. For the organochlorine pesticides the extract was eluted 

through 3 g of alumina and analysed on GC. The clean-up for sediment e 

ulphate, which was 0.01 mg/kg. The detection limit for oganochlorine pesticides 

in sediment, with the final volume of 2 mL, was less than 1 mug/kg and for 

organophosphate pesticides less than 10 mug/kg when the final volume was 

made to 0.5 mL. At the detection limits the method produced a very high 

coefficient of variation for both organochlorine and organophosphate pesticides. 

Alcock, R. E. and K. C. Jones (1999). "New Directions: "New" organic compounds in the 

environment." Atmospheric Environment 33(10): 1645-1646. 

 Biosis copyright: biol abs. rrm journal article climatology pollution air pollution 

organic compounds environment persistent organic pollutants pollutant pcbs 

aldrin chlordane pcdds pcdfs ddt dieldrin endrin heptachlor hexabromobiphenyl 

hexachlorobenzene mirex toxaphene 

Angulo, R., I. Costabeber, et al. (1999). "Organochlorinated residue in milk processed 

with L. acidophilus." Acta Alimentaria 36: 51-53. 

 BIOSIS COPYRIGHT: BIOL ABS. Currently the nourishment and the health are 

intimately related, therefore appears a new fermented or added milk generation 

of live microorganisms that produce beneficial effects on the health of the 

consumer. In spite of this, the milk can convey with his fat environmental toxic 

(residues organochlorine persistent) that with difficulty our organisation can 

demote and it is therefore it can produce negative effects on our health. In the 

present study it is consideres to know if a live microorgan CB, DDT and 

biphenyls congeners no. 28, 52, 153 and 180) by L. acidophilus. Because of this 

and by that they are scarce the existing publications in this regard, we believe 

necessary to accomplish investigations that help to obtain added milk of live 

microorganisms that produce effects more sound and healthy with respect to 

environmental pollutants as organochlorine residues persistent. 

Anonymous (1999). "Health-related indicators for the Great Lakes Basin population: 

numbers 1 to 20." NTIS Technical Report (NTIS/MIC-99-01741) 1999;:156 pp.
187

 Presents a series of indicators which, as a whole, serve to monitor human health 

as it relates to the Great Lakes environment. Three categories of indicators are 

presented: Indicators of health effects, which relate human exposure to 

environmental contaminants to measurable effects on health or health risk; 

indicators of exposure, either contaminant levels measured in human tissues or 

body fluids, or estimates of daily intake of persistent contaminants by the Great 

Lakes population; and patterns and trends in disease incidence that can show 

geographic and time variations in the rates of diseases such as cancer and birth 

defects. 

Anonymous (2004). "Safety assessment of MIBK (Methyl Isobutyl Ketone)." Int J Toxicol

1(2004): 29-57. 

 MIBK is an aliphatic ketone that functions as both a denaturant and solvent in 

cosmetic products. One method of production is acetone condensation, followed 

by catalytic hydrogenation. MIBK may contain the following impurities: dimethyl 

heptane, methyl isobutyl carbinol, mesityloxide, acetic acid, 4-methyl-2-

hydroxypentane, and methyl n-butyl ketone. According to the Chemical 

Manufacturers Association, MIBK producers indicated in 1999 that MIBK (known 

neurotoxin) is either not found in MIBK or is found in trace amounts (typically 

0.01 to 0.06% and always less than 0.1%). Frequency of use data provided by 

FDA in 1998 indicate that MIBK is used in two cosmetic products. However, use 

concentration data provided by CTFA in 2000 indicate that MIBK is used in one 

nail correction pen (volume = 3 ml) at a concentration of 21%. According to 

regulations established by the Bureau of Alcohol, Tobacco, and Firearms, the 

maximum concentration of MIBK that is listed for use as a denaturant of alcohol 

is 4.0%. MIBK is also listed in the National Formulary as an alcohol denaturant 

that is used as an excipient for drugs. The metabolites, 4-hydroxy-4-methyl-2-

pentanone (MIBK oxidation product) and 4-methyl-2-pentanol (4-MPOL) (MIBK 

reduction product) were detected in blood samples from guinea pigs injected 

intraperitoneally with MIBK. Values for the serum half-life and total clearance 

time for MIBK that have been deter-mined are 66 min and 6 h, respectively. 

Hydroxylation products of MIBK, such as 4-MPOL, are expected either to be 

conjugated with sulfate or glucuronic acid and excreted in the urine or to enter 

intermediary metabolism to be converted to carbon dioxide. In a study in which 

MIBK was administered orally or by in-halation exposure to groups of guinea 

pigs, the amount of MIBK detected in the plasma and liver was proportional to 

the administered dose. The metabolite, 4-hydroxy MIBK was detected in the 

plasma regardless of the route of exposure. 4-MPOL was detected in the plasma 

after inhalation exposure, but not after oral doses of MIBK were administered. 4-

MPOL and 4-hydroxy-4-methyl-2-pentanone were the principal MIBK metabolites 

in mice dosed intraperitoneally with MIBK. The percutaneous absorption of MIBK 

was demonstrated in 'a study involving guinea pigs. A maximum percutaneous 

uptake rate of 1.1 umol/min/cm2 was observed at 10 to 45 min after the initiation 

of exposure. Both gross and microscopic evidence of lung damage have been 

reported in acute inhalation toxicity studies in which mice and guinea pigs were 

exposed to MIBK. Increased pulmonary arterial pressure was noted in acute 
188

inhalation toxicity studies in which cats or dogs were exposed to MIBK. 

Bronchoconstriction was also observed in cats that inhaled MIBK. Acute oral 

LD50 values of 4.6 (3.932-5.382) g/kg and 2.08 (1.91-2.27) g/kg have been 

reported for MIBK in studies involving rats. An acute oral LD50 of 1.5 ml/kg 

(mice) for MIBK has also been reported. In an acute dermal toxicity study, 

undiluted MIBK was applied to the skin of two rabbits for 10 h either by flooding 

the test site or placement of a cotton pad impregnated with the test substance. 

Signs of systemic effects were not noted and no treatment-related pathologic 

changes were observed at microscopic examination of internal organs. The 

following acute intraperitoneal LD50 values for MIBK have been reported: 1.14 

ml/kg (rats), 0.59 f 0.23 g/kg (mice), and 0.919 ml/kg (guinea pigs). 

Intraperitoneal injection of MIBK was associated with pulmonary vascular effects 

in cats. Increased pulmonary arterial pressure, but not bronchoconstriction, was 

induced in cats dosed intravenously with MIBK. In short-term exposure 

experiments, male and female Fischer-344 rats inhaled MIBK (concentrations up 

to ca. 2000 ppm) 6 h per day over a period of 9 days to 2 weeks. Concentrations 

of approximately 500 or 2000 ppm induced hyaline droplet formation in the 

kidneys of malt rats, and epithelial re-generation of the proximal convoluted 

tubules was also noted at the highest concentration. Increases in liver and kidney 

weight were also observed at these concentrations. B6C3F1 mice ex-posed to 

MIBK according to the same procedure bad increased liver weight (ca. 2000 

ppm, females only). An increase (females) and decrease (males) in kidney 

weight was-also noted at this concentration. No changes in kidney weight 

occurred after exposure to ca. 500 ppm. In another short-term test, monkeys, 

dogs, mice, and rats were exposed continuously (inhalation) to 100 or 200 ppm 

MIBK over a period of 2 weeks. Increased kidney weight and microscopic 

evidence of toxic nephrosis of the proximal tubules were reported only for rats, 

and this finding was noted at both concentrations of exposure. Increased liver 

weight (rats) was also noted after exposure to 200 ppm. Other study results 

indicated increased adrenal weight only in female albino rats exposed to MIBK at 

a concentration of 4.53 mg/L of air 5 days per week (6 h/day) for 4 weeks. No 

"clear-cut" test substance-related abnormalities were noted at gross necropsy. 

No evidence of gross pathologic effects was observed in Wistar female rats that 

ingested MIBK at concentrations of 0.5% and 1.0% MIBK in drinking water for 7 

days. In a short-term dermal toxicity study, seven applications of undiluted MIBK 

(3 ml/kg each, 5 to 12 h) were made to the shaved skin of two rabbits over a 

period of 15 to 21 days. Local skin changes consisted of polymorphonuclear 

infiltration in the upper dermis. No systemic effects were noted. The subchronic 

inhalation toxicity of MIBK was evaluated using groups of male and female F-344 

rats. The animals were exposed to concentrations ranging from 50 to 1000 ppm 

5 days per week (6 h/day) for 90 days. Increased liver weight was noted following 

exposure to 1000 ppm; however, hepatic lesions were not observed at gross or 

microscopic examination. Groups ex-posed to 250 or 1000 ppm MIBK had 

increased numbers of hyaline droplets in proximal tubule cells, which may be 

specific to the male rat. Malt B6C3F1 mice exposed to MIBK bad in-creased liver 

weight following exposure to 250 or 1000 ppm, but hepatic lesions were not 
189

observed at gross or microscopic examination. Increased liver and kidney weight 

was observed in male Wistar albino rats exposed to 410 mg/m3 MIBK for 90 

days. At microscopic examination, hyaline droplet degeneration of the proximal 

tubules was observed in kidneys from each of the 100 rats. Kidney damage was 

completely reversed in rats ob-served up to 60 days post exposure. In the same 

study (same dose and exposure duration), gross examination revealed no 

differences in tissues examined between test dogs and monkeys and controls. 

Liver function test results (dogs only) also indicated no differences between test 

and control dogs. Nephrotoxicity and increased liver and kidney weight, but no 

evidence of hepatic lesions, was observed in male and female Sprague-Dawley 

rats dosed orally with 1000 mg/kg MIBK daily for 13 weeks. The 50-mg/kg dose 

(lowest dose) was considered the NOEL. No significant gross lesions and renal 

tubule cell hyperplasia were reported in a study involving rats that received daily 

oral doses of 1.04 g/kg MIBK (in drinking water) for 120 days. In a subchronic 

dermal toxicity study, MIBK (in sunflower oil) was applied to white rats (lower 2/3 

of tail) daily at doses of 300 or 600 mg/kg for 4 months. Skin changes included 

reduced mitotic activity in hair follicles and increased thickness of horny and 

granular cell layers of the epidermis. Changes in the spleen included a decrease 

in the number of reactive centers in follicles and an increase in the number of 

iron-containing pigments in the area of the red pulp. A reduction in the lipid 

content of the cortical layer was noted in the adrenal glands. Inhalation exposure 

of Sprague-Dawley rats to MIBK (up to 3020 ppm) did not cause any 

modifications in serum GLDH activity. However, preexposure of rats to MIBK 

caused a dose-related increase in DCB-induced GLDH activity. In this study, the 

mitochondrial enzyme, GLDH was assessed in serum as, a quantitative sign of 

hepatic necrosis. In other studies (oral dosing), the hepatotoxicity of chloroform in 

Sprague-Dawley rats was enhanced after the administration of MIBK or its major 

metabolites, 4-MPOL and 4-hydroxymethyl isobutyl ketone (minimally effective 

dose of each = 5 mmol/kg), and the hepatotoxicity of carbon tetrachloride was 

also enhanced after MIBK administration (dose response; doses up to 20 

mmol/kg). The dermal administration of MIBK in sunflower oil to white rats (lower 

2/3 of tail) at daily doses of 300 or 600 mg/kg for four months caused an increase 

in the number of binuclear hepatocytes, reduced mitotic activity of these cells, 

and an increase in the number of hepatocytes with pathology. Neither histologic 

evidence of liver damage nor lipid deposition was observed in mature guinea 

pigs injected intraperitoneally with a single dose of 500 or 1000 mg/kg MIBK. 

MIBK bad an additive effect on the hepatotoxicity of 1,2-dichlorobenzene, 

chloroform, hexachlorobenzene, and carbon tetrachloride. Neuropathological 

changes in the most distal portions of the tibial and ulnar nerves were observed 

in young adult rats ex-posed (inhalation) to 1500 ppm MIBK for up to 5 months. 

The neuropathological changes observed may have been related to the presence 

of 3% methyl n-butyl ketone in the commercial grade of MIBK that was tested. No 

differences in the performance of schedule-controlled operant behavior were 

noted between Sprague-Dawley rats exposed to MIBK (inhalation) at 

concentrations up to 1500 ppm for 13 weeks and control rats. At gross 

examination, no test substance-related changes were noted. In a 7-day study in 
190

which the effect of inhaled MIBK (25 to 75 ppm) on the behavior of young 

baboons was evaluated, it was concluded that MIBK did not impair each animal's 

ability to discriminate or remember stimuli presented in a match-to-sample 

discrimination task. The oral dosing of rats with 601 mg/kg MIBK five times per 

week for 55 weeks had no effect on the maximum motor-fiber conduction velocity 

in the tail nerve. MIBK did not induce peripheral neuropathy in groups of 

Sprague-Dawley albino rats injected intraperitoneally with MIBK (10% in corn oil) 

at doses up to 100 mg/kg for 2 weeks. The intravenous infusion of female 

Sprague-Dawley rats with MIBK (in an emulsion) resulted in depression of the 

vestibulooculomotor reflex. The threshold limit for this effect was 0.2 mM/L (20 

ppm) at an infusion rate of 30 uM/kg/min. Based on the results of an 

electromyographic examination; neurotoxicity was not observed in male Beagle 

dogs injected with MIBK (300 mg/kg) daily for 11 months. No evidence of 

systemic toxicity or neurotoxicity was observed in dogs injected subcutaneously 

with MIBK (150 mg/kg) twice daily for a year. Tissue samples from the brainstem, 

nerves, and muscles were examined at necropsy. The test substance (98% pure) 

contained 0.9% methyl n-butyl ketone and trace amounts of 4-methyl-2-

hydroxypentane. In another study, MIBK containing 0.9% methyl n-butyl ketone 

was injected subcutaneously (150 mg) into cats five times per week for up to 8.5 

months. The analysis of biopsy specimens from the hind feet indicated no 

detectable damage to nerve tissues. MIBK (0.5%) induced widespread cell death 

in a clonal line of neuroblastoma cells (Neuro 2aE) derived from a spontaneously 

occurring murine tumor (C1300). No discernible cytopathological changes and 

depressed growth rate were reported after exposure to concentrations of 0.1% 

and 0.2% MIBK, respectively. The results of ocular irritation studies involving 

albino rabbits indicate that undiluted MIBK is an ocular irritant. Single 24-h match 

applications of undiluted MIBK induced reactions ranging from slight to moderate 

skin irritation in rabbits and slight skin irritation in guinea pigs. Repeated 

applications (seven) of undiluted MIBK over a 15- to 21-day period caused dig of 

the skin and exfoliation in rabbits. In another study, repeated applications of 

MIBK to guinea pigs (daily for 31 days) resulted in desquamation. The immersion 

of a rabbit's ear and tails from mice in pure MIBK for 2 h caused pronounced 

inflammation and necrosis. The threshold concentration of MIBK for the inhibition 

of bacterial growth (Pseudomonas putida) was 275 mg/L in a 16-h study. MIBK 

was not mutagenic in the Ames test (Salmonella typhimurium strains) or in the 

mitotic gene conversion assay (Saccharomyces cerevisiae strain) with or without 

metabolic activation. Mammalian mutagenicity test results (with or without 

metabolic activation) for MIBK in the following assays were also negative: mouse 

lymphoma, unscheduled DNA synthesis, micronucleus, cell transformation, and 

chromosome damage. MIBK is among the chemicals that have been approved 

by the NTP for testing in a toxicology/carcinogenesis study. MIBK did not induce 

any treatment-related increases in embryotoxicity or fetal malformations in 

pregnant Fischer 344 rats or CD-1 mice that inhaled MIBK at concentrations of 

300, 1000, or 3000 ppm. There was evidence of treatment-related maternal 

toxicity only at the highest concentration tested. In another study, MIBK was 

applied to the skin (lower 2/3 of tail) of an unspecified number of male white rats 
191

daily (4 h/day) at doses of 300 or 600 mg/kg for four months. Changes in the 

testes included a reduction in the number of spermatocytes, spermatids, and 

spermatozoa. Blood and breath samples were obtained from subjects who 

inhaled MIBK during six 20-min exposure sessions. Results at 90 min post 

exposure indicated that most of the absorbed MIBK had been eliminated from the 

body. In another group of subjects exposed to MIBK (inhalation) for 2 h during 

light physical exercise, the apparent blood clearance was 1.6 L/h/kg at all 

exposure concentrations. Only 0.04% of the total dose was eliminated 

unchanged in the urine within 3 h post exposure. MIBK was detected in the 

following tissues of subjects who died following exposure to several volatile 

organic solvents during spray painting: brain, liver, lung, vitreous fluid, kidney, 

and blood. The threshold for MIBK-induced irritation of the lungs of human 

subjects was 0.03 to 0.1 mg/L after 1 min of respiration. Ocular irritation was 

noted in 12 volunteers exposed to 200 ppm MIBK (inhalation) for 15 min. Nasal, 

ocular, and throat irritation were experienced by no more than four of six 

volunteers subjected to six 20-min exposures (inhalation) to MIBK at 

concentrations ranging from 0.402 to 2.827 mg/L. In another inhalation study, 

irritation of the nose and throat were the most common symptoms reported by 

three of the eight volunteers ex-posed to MIBK at concentrations up to 48.8 ppm 

during light physical exercise for 2 h. Ocular irritation, nausea, and sore throat 

were experienced by approximately half of the 19 workers exposed to MIBK daily 

at concentrations up to 500 ppm for 30 min and 80 ppm for the remainder of the 

day. Slightly enlarged livers and nonspecific colitis were reported for 4 and 6 

workers, respectively. In an-other study, symptoms of either nausea or 

respiratory irritation were reported by workers exposed to 100 ppm MIBK. Complaints were reduced substantially when the level of exposure was reduced to 20 

ppm. Exposure to 100 ppm MIBK for 4 h did not induce neurobehavioral effects 

in either of the 23 human subjects tested. In another study, the potential narcotic 

impact of MIBK on CNS function was evaluated using two groups of six subjects 

exposed to 10 mg/m3 (control) and 200 mg/m3 MIBK, respectively, for 2 h. No 

consistent exposure-related effect on heart rate was identified, and the results of 

the simple reaction time performance test indicated no exposure-related 

differences in performance. In a case report, a 40-year-old worker (with contact 

dermatitis) at a chemical factory had a negative patch test reaction to undiluted 

MIBK. Findings in another case report indicated persistent cognitive deficits in a 

44-year-old employee at an indoor solvent extraction facility who did not wear a 

protective breathing device. The most recent occupational limits from the ACGIH 

recommended a TLV-TWA of 50 ppm and a TLV-STEL of 75 ppm for 

atmospheric exposure to MIBK. Discussion. MIBK is used as a solvent and 

denaturant in cosmetic products. The Panel expressed concern over the 

neurotoxicity potential of this ingredient, based on published data indicating that 

MnBK (methyl n-butyl ketone, a known neurotoxin) is present as an impurity in 

MIBK at concentrations-as high as 3.0%. Ac-cording to the Chemical 

Manufacturers Association, MIBK producers indicated in 1999 that MnBK is 

either not found in MIBK or is found in trace amounts (typically 0.01% to 0.06% 

and al-ways less than 0.1 %). After considering the new impurities data, data 
192

indicating that the only reported use of MIBK in cosmetics is in a nail correction 

pen (total volume of pen = 3 ml; 21% MIBK), and the observation that significant 

dermal absorption of the nail correction fluid would not be likely under normal use 

conditions, the Panel agreed that MIBK could be used safely as a solvent in nail 

polish removers in a controlled application system. However, given the known 

neurotoxic effects of MnBK, the Panel stressed the importance of continued 

efforts to limit the concentration of this impurity in MIBK. Furthermore, the Panel 

stressed the importance of avoiding inhalation exposure to MIBK, based on 

evidence of lung, kidney, or liver damage in animal studies and respiratory 

irritation or liver effects reported in human occupational exposure studies on 

MIBK. Though one of the reported uses of MIBK in cosmetics is that of a 

denaturant, product data indicative of this function have not been provided. 

However, after noting that MIBK has been approved for use as a denaturant for 

alcohol, in keeping with the regulations established by the Bureau of Alcohol, 

Tobacco, and Firearms (27CFR2121), the Panel agreed that MIBK could be 

considered safe for use as a denaturant in cosmetics at concentrations up to the 

maximum concentration of MIBK (4%) that is listed for use as a denaturant of 

alcohol. It is important to note that because of the established regulations, the 

Panel assumes that cosmetic product formulators use MIBK as a denaturant at 

concentrations that do not exceed 4.0%. The Expert Panel is aware of an 

ongoing carcinogenicity stud on MIBK that is being conducted by the National 

Toxicology Program, and agreed that the results will be reviewed by the Panel 

after the report has been made available to the public. Conclusion. Based on the 

available animal and clinical data in this report, the CIR Expert Panel concludes 

that MIBK is safe as used in nail polish removers and as an alcohol denaturant in 

cosmetic products. 

Armitage, J. M., I. T. Cousins, et al. (2007). "Empirical evaluation of spatial and nonspatial European-scale multimedia fate models: results and implications for chemical 

risk assessment." J Environ Monit 9(6): 572-81. 

 Multimedia environmental fate models are commonly-applied tools for assessing 

the fate and distribution of contaminants in the environment. Owing to the large 

number of chemicals in use and the paucity of monitoring data, such models are 

often adopted as part of decision-support systems for chemical risk assessment. 

The purpose of this study was to evaluate the performance of three multimedia 

environmental fate models (spatially- and non-spatially-explicit) at a European 

scale. The assessment was conducted for four polycyclic aromatic hydrocarbons 

(PAHs) and hexachlorobenzene (HCB) and compared predicted and median 

observed concentrations using monitoring data collected for air, water, sediments 

and soils. Model performance in the air compartment was reasonable for all 

models included in the evaluation exercise as predicted concentrations were 

typically within a factor of 3 of the median observed concentrations. Furthermore, 

there was good correspondence between predictions and observations in regions 

that had elevated median observed concentrations for both spatially-explicit 

models. On the other hand, all three models consistently underestimated median 

observed concentrations in sediment and soil by 1-3 orders of magnitude. 
193

Although regions with elevated median observed concentrations in these 

environmental media were broadly identified by the spatially-explicit models, the 

magnitude of the discrepancy between predicted and median observed 

concentrations is of concern in the context of chemical risk assessment. These 

results were discussed in terms of factors influencing model performance such 

as the steady-state assumption, inaccuracies in emission estimates and the 

representativeness of monitoring data. 

Arnold, D. L., F. R. Bryce, et al. (2000). "Dosing via gavage or diet for reproduction 

studies: a pilot study using two fat-soluble compounds-hexachlorobenzene and aroclor 

1254." Food Chem Toxicol 38(8): 697-706. 

 The choice of a dosing route for in vivo toxicological tests is often dictated by 

practical constraints. Reproduction studies are particularly challenging in this 

regard since the determination of no- effect levels and allowable daily intakes 

from reproduction data encompasses exposure of the dam to the test xenobiotic 

prior to pregnancy, during gestation and during lactation. The fetus/infant can be 

exposed to the xenobiotic as well as the dam's metabolic products of the test 

xenobiotic during gestation and lactation. We initiated a series of two-litter, pilot 

reproduction studies with Sprague-Dawley and Fischer 344 rats to specifically 

ascertain the amount of xenobiotic and its metabolites ingested by the nursing 

neonate on lactation days 4, 7, 12, 17 and 21, when its dam received the 

xenobiotic via its diet or by gavage. The xenobiotics studied in this initial series of 

experiments were hexachlorobenzene (HCB) and Aroclor(R) 1254 

(polychlorinated biphenyls; PCBs). The dams were dosed for 28 days, mated to 

untreated males and then remated approximately 2 weeks after weaning their 

first litter to a second untreated male. Dietary levels of 10 ppm HCB or 10 ppm 

PCBs, and gavage doses of 0.9 mg HCB or 0.8 mg PCBs/kg body weight/day 

were chosen and resulted in similar doses of HCB and PCBs per unit of the body 

weight of the dam during the premating period. There were no apparent 

toxicological effects regarding the dam nor were any of the reproduction 

parameters (feed consumption, dam weight, litter size, pup weight, external 

anomalies and day 4 viability index) significantly different from control values. 

Following impregnation, the body weight of the dam increased appreciably during 

gestation, but its feed consumption increased only slightly. During lactation, the 

dam's feed consumption increased markedly while its body weight increased 

slightly. Consequently, when dams received the xenobiotic in their diet they 

consumed slightly less xenobiotic per unit of body weight during gestation when 

compared to the gavaged dams, whereas the situation was dramatically reversed 

during lactation. While the greater consumption of xenobiotic by the dietarydosed dams during lactation did result in more HCB (P</=0.0001 for both litters) 

and PCBs/metabolites (litter one: P=0.05; litter two: P</=0.0001) in the suckling 

neonate's stomach contents in both generations, there was no evidence of any 

differences between the two litters when each sampling date was assessed 

separately, except for the day 4-HCB results when the litter one pups had more 

HCB in their stomachs (P=0.018). For the PCBs, the F344 neonates were found 

to have more PCBs in their stomachs (litter one P=0.0015; litter two P=0.002) 
194

than the Sprague-Dawley neonates. In addition, the amount of HCB, PCBs and 

fat in the neonates' stomachs decreased during lactation, as the pups age 

increased (P</=0.035). These preliminary results suggest that analogous 

amounts of HCB and PCBs given via diet or gavage may not result in similar 

lactational exposure by the suckling neonate. 

Atkinson, R., R. Guicherit, et al. (1999). "Transformations of pesticides in the 

atmosphere: A state of the art." Water, Air, and Soil Pollution 115(1-4): 219-243. 

 BIOSIS COPYRIGHT: BIOL ABS. The current knowledge about transformation 

rates and products of pesticides in the atmosphere is reviewed. Reactive species 

and their concentrations in the atmosphere are presented. Reactions of 

pesticides with these species (including photolysis) in the gas and the particulate 

phase are evaluated from available experimental data. The potential of 

estimation methods is discussed. Experimental techniques for laboratory and 

outdoor measurements are reviewed. Finally, an estimation is made of 

uncertainties in atmospheric lifetimes due to chemical or physical reactions. It is 

concluded that the most important transformation of pesticides in the atmosphere 

is due to reaction with OH radicals. Very few experimental data for pesticides are 

available though. The levels of uncertainty in OH radical concentrations are 

acceptable, however, for a proper estimation of atmospheric removal rates due to 

reactions with OH radicals of those pesticides for which experimental 

transformation rates (of homologues) are available. 

Atlas, E. and C. S. Giam (1981). "Global Transport of Organic Pollutants: Ambient 

Concentrations in the Remote Marine Atmosphere." Science 211(4478): 163-165. 

 Concentrations of organic pollutants in the air and in precipitation have been 

measured at Enewetak Atoll in the North Pacific Ocean. These data from a site 

removed from industrial and human activity indicate the present concentrations of 

synthetic organic pollutants in the atmosphere and establish the long-range 

atmospheric transport of organic pollutants to remote marine areas. 

Hexachlorobenzene and hexachlorocyclohexane isomers are present in the 

remote marine atmosphere. Polychlorobiphenyls, total DDT, dieldrin, chlordane, 

and two phthalate ester plasticizers were also found in the samples. The 

concentrations of pollutants in the atmosphere remote from continental sources 

are good measures of the minimum concentrations of air pollutants on Earth. 

Atuma, S. S. and M. Aune (1999). "Method for the determination of PCB congeners and 

chlorinated pesticides in human blood serum." Bulletin of Environmental Contamination 

and Toxicology 62(1): 8-15. 

 Biosis copyright: biol abs. rrm research article human pcb congeners 

determination toxin polychlorinated biphenyl blood serum chlorinated pesticides 

pesticide organochlorine compounds xenobiotic toxin determination technique 

toxicology methodology blood and lymphatics validity toxicology method 

reproducibility development sweden europe 
195

Bainy, A. C., B. R. Woodin, et al. (1999). "Elevated levels of multiple cytochrome P450 

forms in tilapia from Billings Reservoir-Sao Paulo, Brazil." Aquatic Toxicology 44(4): 

289-305. 

 BIOSIS COPYRIGHT: BIOL ABS. Cytochrome P4501A (CYP1A) levels in tissues 

of fish inhabiting polluted areas have been used extensively in biomonitoring 

studies in Europe and North America. However, little information is available 

about the extent of CYP1A expression in fish from South American waters, nor 

on the expression of other CYP proteins in fish from polluted sites. The content of 

total cytochrome P450 and b5 and of proteins cross-reactive with antibodies to 

teleost (scup) CYP1A-, CYP2B- and CYP3A-like proteins, as well as rates of 

alkoxy-resorufin-O-dealkylases (ARODs) with methoxy-, ethoxy-, pentoxy- and 

benzyloxyresorufin substrates, were analyzed in liver and kidney microsomes 

from tilapia (Oreochromis niloticus) from a reference site (Estacao de Piscicultura 

de Pindamonhangaba, Sao Paulo) and a polluted site (Billings Reservoir, Sao 

Paulo, Brazil). Levels of total microsomal P450 and b5 were elevated 1.8- and 

3.3-fold, respectively, in liver and 4.3- and 2.4-fold in kidney of tilapia fro 

Bakker, D. J., A. J. Gilbert, et al. (1999). "Implementing atmospheric fate in regulatory 

risk assessment of pesticides: (How) can it be done?" Water, Air, and Soil Pollution

115(1-4): 257-266. 

 BIOSIS COPYRIGHT: BIOL ABS. Atmospheric fate of pesticides and their 

possible effects in ecosystems beyond the immediate surrounding of the 

application site are not actively considered in currently used regulatory risk 

assessment schemes. Concern with respect to atmospheric transport and 

subsequent deposition of pesticides in non-target areas is however growing. In 

this article the results of discussions on the possibilities of implementing 

atmospheric fate in regulatory risk assessment are presented. It is concluded that 

implementing atmospheric fate in regulatory risk assessment schemes is 

possible and that, from a scientific point of view, these schemes should 

distinguish between pesticides on the basis of both their possibility/probability to 

reach non-target areas and on their toxicity. This implies that application of the 

precautionary principle or use of intrinsic pesticide properties alone is not 

considered justifiable. It is recommended that the risk assessment scheme 

should follow a tiered approach. Thefirst tier should be entered only if the existing 

regulatory risk assessment procedure, including a local PEC:PNEC calculation, 

has been passed and involves a test for the pesticide's total atmospheric 

emission potential, i. e. its potential for becoming airborne during and after 

application. The second tier, which is only entered if the total emission potential 

is higher than a certain trigger value, should consist of a PEC:PNEC calculation 

of regional off-site areas (10-50 km) (tier 2A). If the pesticide's atmospheric 

transport potential is expected to exceed a certain value, the PEC:PNEC ratio 

should also be calculated for more remote areas ( > 1000 km) (tier 2B). 

Balaam, J. L., P. H. Roberts, et al. (2009). "Identification of non-regulated pollutants in 

North Sea produced water discharges." Environ Toxicol Chem: 1. 
196

 Produced water collected from the United Kingdom Continental Shelf was 

characterized for non-regulated pollutants through the use of an effects-directed 

analysis (EDA) procedure. Produced water samples were characterized for the 

presence of arylhydrocarbon receptor (AhR) and estrogen receptor (ER) agonists 

using the DR-CALUX and yeast estrogen screen (YES) bioassays. The AhR and 

ER agonists were then isolated by normal phase high performance liquid 

chromatography (HPLC) and identified using gas chromatography coupled to 

mass spectrometry (GC-MS) in a number of formats. The identified compounds 

were cross referenced with those compounds routinely analysed and regarded 

as priority hazardous substances by the Oslo and Paris (OSPAR) Commission 

for the North East Atlantic. The occurrence in produced water of a number of 

non-regulated compounds with demonstrable potential environmental effects is 

presented for the first time. These include persistent organic contaminants such 

as hexachlorobenzene, decachlorobiphenyl and octachlorodibenzofuran. 

Balasanmugam, K., S. K. Viswanadham, et al. (1989). "Solid state chemical ionization 

for characterization of organic compounds by laser mass spectrometry." Talanta 36(1-

2): 117-24. 

 A new technique involving the addition of a compound to the analyte to serve as 

a source of "reagent" ions has been developed for negative-ion laser mass 

spectrometry. This "solid state chemical ionization" leads to ions characteristic of 

the analyte, owing to ion-molecule reactions between the "reagent" ion and the 

neutral analyte in the laser-generated plume. Polycyclic aromatic hydrocarbons 

show formation of an ion corresponding to (M + O - H)(-) in their negative-ion 

laser mass spectra when mixed with compounds such as sym-trinitrobenzene, 

sodium nitrate and sodium peroxide. NO(-)(2), O(-), and O(-)(2) serve as 

"reagent" ions in these compounds. Formation of (M + Cl)(-) is seen in the laser 

mass spectra of glycosides mixed with hexachlorobenzene. Chloride serves as 

the "reagent" ion in this case. 

Barber, J. L., A. J. Sweetman, et al. (2005). "Hexachlorobenzene in the global 

environment: emissions, levels, distribution, trends and processes." Sci Total Environ

349(1-3): 1-44. 

 Hexachlorobenzene (HCB) is considered here as a 'model persistent organic 

pollutant.' Data on its sources, emissions, environmental levels and distributions 

and trends are compiled and used to assess its fate and behaviour in the global 

environment. Consideration is given as to the extent to which it has undergone 

repeated air-surface exchange or 'hopping' to become globally dispersed, the 

balance between primary and secondary sources in maintaining ambient levels, 

and its ultimate sinks in the environment. Global production exceeded 100,000 

tonnes and primary emissions to atmosphere probably peaked in the 1970s. 

There has been a consistent downward trend in the environment over the past 20 

years. Temporal trends of HCB in the environment vary, dependent on time 

period measured, media studied and study location, but the average half-life from 

all the studies is approximately 9 years. Estimates are made of the contemporary 

burden in the environment; these range between 10,000 and 26,000 tonnes and 
197

are dominated by the loadings in treated and background soils, sediments and 

oceans. Estimates of the trends of HCB emissions from treated soils are derived. 

At its peak, the amount of HCB emitted from soil to air may have been in the 

hundreds to thousands of tonnes per year, which would have made it a 

significant source of HCB to the environment. Whilst the amount of HCB being 

emitted from contemporary soil is much lower, only a small amount of reemission of HCB from soil to air is required to maintain contemporary air 

concentrations under the current primary emission scenario. 

Bates, M. N., S. J. Buckland, et al. (2004). "Persistent organochlorines in the serum of 

the non-occupationally exposed New Zealand population." Chemosphere 54(10): 1431-

43. 

 Concentrations of polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated 

dibenzofurans (PCDFs), polychlorinated biphenyls (PCBs), and organochlorine 

pesticides were measured in the serum of a sample of the New Zealand 

population aged 15 years and older. This was the first study to obtain 

representative measures of PCDDs, PCDFs and PCBs in the adult population of 

an entire country. Serum samples were obtained in 1996-1997. Potentially 

occupationally exposed individuals were excluded. Serum samples were pooled 

according to stratification criteria for area of residence, ethnicity, age, and sex. Of 

the 80 possible strata, sufficient serum for chemical analysis was available for 

60, to which 1,834 individual samples contributed. For the PCDDs and PCDFs, 

most 2,3,7,8-chlorinated congeners were measured in all strata, with a mean 

toxic equivalents concentration across all strata of 12.8 ng TEQ kg(-1) lipid. 

Seven PCB congeners were frequently measured, including the coplanar 

congeners #126 and #169, quantified in all strata. Of the pesticides and their 

metabolites, only beta-HCH, dieldrin and pp'-DDE were consistently detected 

across strata. There was a general trend of increasing concentration with age. 

There were no consistent differences between the sexes, or between people of 

Maori (the indigenous people of New Zealand) and non-Maori ethnicity. 

Concentrations of PCDDs and PCDFs tended to increase in a North-South 

direction, possibly reflecting greater levels of industrialization and population 

concentration, and concentrations of the pesticide products were highest in the 

South, possibly reflecting historical use patterns. Results were consistent with a 

recent study of concentrations of these compounds in the milk of first-time 

mothers. 

Behrooz, R. D., A. Esmaili-Sari, et al. (2009). "Organochlorine pesticide and 

polychlorinated biphenyl in feathers of resident and migratory birds of South-west iran." 

Arch Environ Contam Toxicol 56(4): 803-10. 

 Persistent organochlorine pesticides (OCPs), such as 

dichlorodiphenyltrichloroethane (DDT) and its metabolites, hexachlorobenzene 

(HCB), alpha-, beta-, and gamma-hexachlorocyclohexane (HCH) isomers, 

together with polychlorinated biphenyl (PCB) congeners (IUPAC Nos. 28, 52, 

101, 138, 153, and 180) were determined in tail feathers from 35 birds belonging 

to 15 species, all originating from the southwest of Iran (Khuzestan, coast of the 
198

Persian Gulf) and kept in museum collections. The patterns of organochlorine 

contaminants (OCs) in birds varied depending on their migratory behavior. 

Resident birds contained higher median PCB concentrations (<LOQ-151 ng/g 

feather) than HCHs, DDTs, and HCB. Locally migrating birds had higher median 

concentrations of HCHs (19-83 ng/g feather). In contrast, long-distance migrants 

had lower concentrations of HCB and HCHs. A positive correlation was observed 

among OCs in these birds, suggesting that trophic level, feeding strategy, and 

taxonomic group are influencing factors for the OC concentrations in bird 

feathers. An estimate of the risk associated suggests that levels of OCPs and 

PCBs were lower or close to the threshold reported to affect reproduction in 

1990s. 

Belles-Isles, M., P. Ayotte, et al. (2002). "Cord blood lymphocyte functions in newborns 

from a remote maritime population exposed to organochlorines and methylmercury." 

Journal of toxicology and environmental health. Part A. 65(2): 165-82. 

 The consumption of fish and sea mammals can be an important source of 

exposure to organochlorine compounds (OCs) and heavy metals in populations 

relying on seafood for subsistence. Exposure to these substances, especially 

during the prenatal period, has been shown to induce immunotoxic effects in 

mammals. Immunological status was assessed in 48 newborns from a remote 

maritime population living on the Lower and Mid North Shore of the St. Lawrence 

River (subsistence fishing group) and 60 newborns from the coastal urban center 

of Sept-Iles (reference group). Women were recruited upon arrival at Sept-Iles 

regional hospital to give birth. Cord blood samples were collected for 

organochlorine and heavy metal analyses and to isolate lymphocytes for 

immunological assays (proportions and functional responses of the main cellular 

subsets T, B, and NK (natural killer) cells. Concentrations of polychlorinated 

biphenyls (PCBs) and mercury were respectively three- and twofold higher, 

significantly greater, in the subsistence fishing group than in the reference group. 

Compared to the reference group, the subsistence fishing group showed 

significant decreases in the proportion of the naive helper T-cell subset 

CD4+CD45RA, T-cell proliferation following an in vitro mitogenic stimulation, and 

plasma immunoglobulin M (IgM) level, while plasma IgC level was increased. NK 

cytolytic activities were similar in both groups. The proportion of CD4+CD45RA 

cells was inversely correlated to mercury and PCBs, while T-cell clonal 

expansion was negatively associated with PCBs and p,p'-DDE. Mercury was 

inversely correlated to plasma IgM. Data show that subtle functional alterations of 

the developing human immune system may result from in utero exposure to OCs 

and mercury. Epidemiological studies are needed to determine the relevance of 

these alterations in predicting detrimental health effects in the developing child. 

Benn, S., P. Brown, et al. (2009). "A commentary on decision-making and 

organisational legitimacy in the Risk Society." J Environ Manage 90(4): 1655-62. 

 Key concepts of Risk Society as elaborated by Ulrich Beck and others (Beck, U., 

1992 (trans. Mark Ritter). The Risk Society. Sage Publications, London. Beck, U., 

1995, Ecological Politics in the Age of Risk. Polity Press, Cambridge. Beck, U., 
199

1999, World Risk Society. Polity Press, Cambridge. Giddens, A., 1994, Beyond 

Left and Right. Polity Press, Oxford. Beck, U., Giddens, A. and Lash, S., 1994, 

Reflexive Modernisation: Politics, Tradition and Aesthetics in the Modern Social 

Order. Stanford University Press, Stanford. Beck, U., Bonss, W. and Lau, C., 

2003, Theory, Culture & Society 2003, Sage, London, 20(2), pp. 1-33.) are 

illuminated though a case study of managed environmental risk, namely the 

hexachlorobenzene (HCB) controversy at Botany, a southeast suburb of Sydney. 

We observe the way multiple stakeholder decision-making plays out a number of 

Risk Society themes, including the emergence of 'unbounded risk' and of highly 

'individualised' and 'reflexive' risk communities. Across several decades, the 

events of the HCB story support Risk Society predictions of legitimacy problems 

faced by corporations as they harness technoscientific support for innovation in 

their products and industrial processes without due recognition of social and 

environmental risk. Tensions involving identity, trust and access to expert 

knowledge advance our understanding of democratic 'sub-political' decisionmaking and ways of distributing environmental risk. 

Benn, S. and R. Jones (2009). "The role of symbolic capital in stakeholder disputes: 

decision-making concerning intractable wastes." J Environ Manage 90(4): 1593-604. 

 This paper examines almost 30 years of disputation concerning the disposal of 

the world's largest stockpile of the toxic organochlorine, hexachlorbenzene. It 

describes the study of a chemicals company in its attempt to manage the 

disposal of the toxic waste in a collaborative fashion with government, 

environmentalists and the local community. The study describes the new 

processes and structures specifically designed to address the decision-making 

and the issues of stakeholder perception and identity construction which have 

influenced the outcomes. Decision-making in such disputes is often theorized 

from the perspective of the emergence of highly individualized and reflexive risk 

communities and changing modes and expectations of corporate responsibility 

as a result of detraditionalization. We argue that the stakeholder interaction in 

this study reflects competing discourses in which corporate actors prioritize the 

building and maintaining of identity and symbolic capital rather than an active 

collaboration to solve the ongoing issue of the waste. As well, issues of access to 

expert knowledge highlight the relationship between conditions of uncertainty, 

technoscientific expertise and identity. The events of the study highlight the 

challenges faced by contemporary technoscientific corporations such as 

chemicals companies as they must deliver on requirements of transparency and 

openness, while maintaining technoscientific capacity and strong internal identity. 

We conclude that the study demonstrates the co-existence of social processes of 

individualization and detraditionalization with quasi-traditions which maintain 

authority, thus challenging the radical distinctions made in the literature between 

modernity and late or reflexive modernity. 

Bennett, D. H., W. E. Kastenberg, et al. (1999). "General formulation of characteristics 

time for persistent chemicals in multimedia environment." Environmental Science and 

Technology 33(3): 502-509. 
200

 BIOSIS COPYRIGHT: BIOL ABS. A simple yet representative method for 

determining the characteristic time a persistent organic pollutant remains in a 

multimedia environment is presented. The characteristic time is an important 

attribute for assessing long-term health and ecological impacts of a chemical. 

Calculating the characteristic time requires information on decay rates in multiple 

environmental media as well as the proportion of mass in each environmental 

medium. We explore the premise that using a steady-state distribution of the 

mass in the environment provides a means to calculate a representative estimate 

of the characteristic time while maintaining a simple formulation. Calculating the 

steady-state mass distribution incorporates the effect of advective transport and 

nonequilibrium effects resulting from the source terms. Using several chemicals, 

we calculate and compare the characteristic time in a representative multimedia 

environment for dynamic, steady-state, and equilibrium multimedia 

Bervoets, L., J. Voets, et al. (2005). "Use of transplanted Zebra mussels (Dreissena 

polymorpha) to assess the bioavailability of microcontaminants in Flemish surface 

waters." Environ Sci Technol 39(6): 1492-505. 

 Zebra mussels (Dreissena polymorpha) were translocated in cages to 56 water 

bodies in Flanders (Belgium) during summer 2001. After six weeks, 

concentrations of polychlorinated biphenyls (PCBs), hexachlorobenzene (HCB), 

p,p'-DDE, and trace metals were measured in the transplanted mussels. It was 

investigated whether total dissolved water and sediment pollutant levels or 

bioaccumulation factors (BAFs) and biota-sediment accumulation factors 

(BSAFs) were predictive for mussel tissue levels. The sample sites covered a 

broad range both in terms of the type and concentration of the pollutants, and 

this was reflected in large differences in tissue concentrations of all pollutants 

among the sites. The highest pollutant levels in mussels were among the highest 

reported in the literature. For Cd and Zn levels up to 33 and 1994 microg/g dry 

wt. respectively were found. The lowest levels were comparable to those from 

uncontaminated sites in Europe and the U.S. For Cd and Zn respectively 51 and 

75% of the variation in tissue levels was described. For both metals, dissolved 

and particulate metal contributed to the variation in accumulation. For other 

pollutants, relationships between tissue concentration and water or sediment 

concentration were weak or nonsignificant. Then the measured environmental 

factors (dissolved calcium, pH, oxygen, organic carbon and clay content in the 

sediment) were taken into account applying multiple regression analysis, and no 

increase in the described variation of pollutant accumulation was observed. The 

BAF and BSAF for all pollutants varied up to 1000-fold even after TOCnormalization. Clear negative relationships were found between BAFs/ BSAFs 

and environmental levels. However, even at constant environmental 

concentrations a 10- to 100-fold variation in BAFs/BSAFs was observed. This 

study illustrated the need for biological monitoring since neither environmental 

Bidleman, T. F. and R. L. Falconer (1999). "Using enantiomers to trace pesticide 

emissions: This novel approach provides clues to sources of pesticides found in the 

atmosphere." Environmental Science & Technology 33(9): 206-209. 
201

 Biosis copyright: biol abs. rrm using enantiomers to trace pesticide emissions: 

this novel approach provides clues to sources of pesticides found in the 

atmosphereyjournal article pollution toxicology pesticides un environmental 

program environmental contamination ddt pollutant atmospheric emissions 

enantiomers pesticide chlordane heptachlor aldrin dieldrin endrin toxaphene 

mirex hexachlorobenzene environmental monitoring government agency 

Binelli, A., F. Ricciardi, et al. (2004). "Present status of POP contamination in Lake 

Maggiore (Italy)." Chemosphere 57(1): 27-34. 

 In the last decade, Lake Maggiore has been subject to heavy DDT contamination 

due to a chemical plant located near the main influent of the Baveno Bay. The 

freshwater bivalve zebra mussel (D. polymorpha) was used as a bioindicator of 

several POPs (DDTs, PCBs, HCB, HCHs) to follow their concentration trend after 

a heavy flood in autumn 2000. Sampling of mollusc specimens were carried out 

monthly from April 2001 to October 2002 at two different stations in and outside 

the bay. Results showed worsening of DDT pollution due to the transport of 

insecticide from contaminated sediments and soils still present in the closed 

chemical plant site. Levels of about 4.5 microg/g lipids in soft tissues of 

specimens from the most contaminated site and 2.0 microg/g lipids outside it 

were found, which are twice those measured before the flood. HCHs and HCB 

values were always very low, but it was noticed since winter 2001-2002 a sharp 

increase of PCB pollution, with values of about 3-4 microg/g lipids, not due to the 

2000 flood, but probably to improper discharge or release of contaminated 

sediments from numerous dams located in the watershed. Concentrations of total 

dioxin-like PCBs reached dangerous levels for the water community. Fish 

consumption may be a risk for human health especially for resident population, 

bearing in mind that fish usually have a higher POP concentration than zebra 

mussel. 

Binelli, A., F. Ricciardi, et al. (2005). "Screening of POP pollution by AChE and EROD 

activities in Zebra mussels from the Italian Great Lakes." Chemosphere 61(8): 1074-82. 

 The increase of ethoxyresorufin dealkylation (EROD) and the inhibition of 

acetylcholinesterase (AChE) as biomarkers have been commonly used in 

vertebrates for the persistent organic pollutants (POPs) biomonitoring of aquatic 

environments, but very few studies have been performed for invertebrates. 

Previous researches demonstrated the interference due to some chemicals on 

EROD and AChE activities of the freshwater bivalve Zebra mussel (Dreissena 

polymorpha) in laboratory and field studies, showing its possible use for the 

screening of POP effects. We investigated the contamination of the Italian subalpine great lakes (Maggiore, Lugano, Como, Iseo, Garda) by the biomarker 

approach on Zebra mussel specimens collected at 17 sampling sites with 

different morphometric characteristics and anthropization levels. Results showed 

a homogeneous contamination of AChE inhibitors in Lake Garda, Maggiore, 

Como and Iseo with values ranging from 0.5 to 3 nmol/min/mg proteins and with 

an average inhibition of about 66% to controls. The planar compounds pollution, 

able to activate the EROD activity, seems higher in some sampling stations of 
202

Lake Garda, Como and Iseo (2-4 pmol/min/mg proteins) than that measured in 

Lake Lugano (1.5-3 pmol/min/mg proteins). On the contrary, the enzyme activity 

in Lake Maggiore showed an interesting opposite effect of AhR-binding 

compounds and trace metals. Finally, the possible use of Zebra mussel 

specimens maintained at laboratory conditions as controls against the selection 

of the less polluted sampling site is discussed. 

Binelli, A., C. Riva, et al. (2007). "Biomarkers in Zebra mussel for monitoring and quality 

assessment of Lake Maggiore (Italy)." Biomarkers 12(4): 349-68. 

 Three different biomarkers (acetylcholinesterase (AChE), ethoxy resorufin-Odeethylase (EROD) and DNA strand breaks) were measured in Zebra mussel 

(Dreissena polymorpha) specimens collected in April 2005 at six different 

sampling sites on Lake Maggiore, the second largest Italian lake in terms of 

depth and volume, in order to assess the spatial variation of exposure to manmade contaminants. Mussels maintained at fixed laboratory conditions were 

used as controls to eliminate potential interference due to environmental factors. 

Biomarker data were also supported by the analysis of several chemicals (six 

dichlorodiphenyltrichloroethane (DDTs), 23 polychlorinated biphenyls (PCBs), 14 

polybrominated diphenyl ethers (PBDEs), 11 polycyclic aromatic hydrocarbons 

(PAHs) and hexachlorobenzene (HCB)) measured in the mussel soft tissues by 

gas chromatographic analyses. We found a negative correlation between 

temperature and AChE activity, while any measured environmental or 

physiological factor seemed to influence EROD activity and DNA strand breaks. 

A positive relationship was found between EROD activity and all of the measured 

chemicals, except for PAHs, which correlated with the amount of DNA strand 

breaks. Significant differences were noted for all biomarkers, both among 

sampling stations and between control and experimental data, even if the general 

level of variability was low. The biomarkers showed a distinct pattern of spatial 

variation, but the evaluation of DNA strand breaks was the strongest 

discriminating power between sites. In addition, the comparison between AChE 

and EROD activity measured in 2005 was compared with results obtained in a 

previous study carried out over the same sampling period in 2003. Results 

indicated a strong influence of temperature on AChE activity and probable 

interference of substrate inhibition of EROD activity, pointing out the need to take 

care in the interpretation of data comparisons. The results obtained with two 

different metrics used for the measure of DNA strand breaks is also discussed, 

as well as the relationship between EROD activity data and potential 

genotoxicity. 

Bishop, C. A., N. A. Mahony, et al. (1999). "Reproductive success and biochemical 

effects in tree swallows (Tachycineta bicolor) exposed to chlorinated hydrocarbon 

contaminants in wetlands of the Great Lakes and St. Lawrence River Basin, USA and 

Canada." Environmental Toxicology and Chemistry 18(2): 263-271. 

 BIOSIS COPYRIGHT: BIOL ABS. Reproduction and biochemical indicators 

(vitamin A, ethoxyresorufin-O-deethylase (EROD), highly carboxylated 

porphyrins) of contaminant effects, and concentrations of organochlorine 
203

residues were measured in tree swallows from wetlands within the watersheds of 

the Great Lakes and the St. Lawrence River, USA and Canada. To assess the 

vitamin A sources in the tree swallow diets, insects were collected, by ligature, 

from nestlings at four of these sites. Diet samples were analyzed for retinol and 

alpha- and beta-carotene. Marked differences were found in chlorinated 

hydrocarbon residues in eggs and nestlings among sites; however, we did not 

find any significant differences in hatching or fledging success. The maximum 

polychlorinated biphenyl (PCB) concentration found was 11.1 mug/g in eggs from 

Akwesasne Reserve, New York, USA, on the St. Lawrence River, whereas the 

highest p,p'-DDE concentration of 2.57 mug/g was found in eggs from Mud 

Creek, Ontario, Canada, in the Lake 

Boehme, F., K. Welsch-Pausch, et al. (1999). "Uptake of airborne semivolatile organic 

compounds in agricultural plants: Field measurements of interspecies variability." 

Environmental Science and Technology 33(11): 1805-1813. 

 BIOSIS COPYRIGHT: BIOL ABS. The accumulation of semivolatile organic 

compounds (SOCs) in plants is important because plants are the major vector of 

these compounds into terrestrial food chains and because plants play an 

important role in scavenging SOCs from the atmosphere and transferring them to 

the soil. Agricultural plants are of particular interest because they are a key link in 

the atmosphere-fodder-milk/beef food chain that accounts for much of 

background human exposure to persistent lipophilic organic pollutants su 

developed interpretive framework was employed to analyze the data, and it was 

established whether the accumulation of a given compound was due primarily to 

equilibrium partitioning, kinetically limited gaseous deposition, or particle-bound 

deposition. The interspecies variability in uptake was then examined, and it was 

found that for those compounds which had accumulated primarily via kinetically 

limited gaseous deposition and particle-bound deposition the variation among the 

10 

Booij, K., J. R. Hoedemaker, et al. (2003). "Dissolved PCBs, PAHs, and HCB in pore 

waters and overlying waters of contaminated harbor sediments." Environ Sci Technol

37(18): 4213-20. 

 Aqueous concentrations of polychlorinated biphenyls (PCBs), polyaromatic 

hydrocarbons (PAHs), pentachlorobenzene, and hexachlorobenzene (HCB) were 

determined by exposing low-density polyethylene (LDPE) strips to the pore 

waters and the overlying water in two contaminated harbors. LDPE strips were 

also exposed in the laboratory to sediment slurries and to stagnant sediments 

collected at the same locations. Surprisingly short equilibration time scales (1-60 

days for log K(ow) < 7) were observed for the exposures to sediment slurries. 

This was a result of a profound decrease in transport resistance, due to the 

presence of particles in the aqueous boundary layer. Concentrations in the pore 

water were calculated from the initial uptake rates and the dissipation rates of 

performance reference compounds. Good correspondence existed with 

concentrations estimated from the equilibrium amounts in the strips and LDPEwater partition coefficients. Sediment-water partition coefficients for PAHs were 
204

higher than for PCBs and chlorobenzenes by approximately 1 order of 

magnitude. A one-dimensional diffusion model was used to describe contaminant 

uptake by LDPE strips from stagnant sediments. The results indicated that 95% 

of the PAHs and 50% of the PCBs were immobile on a time scale of two months. 

A comparison of concentrations in pore waters and water columns indicated that 

a fair degree of equilibrium existed for PCBs and that one sediment was a 

potential source of PAHs. Concentrations of HCB near a former discharge site 

were higher by a factor of 6 compared to reference locations. 

Booij, K., R. van Bommel, et al. (2007). "Air-water distribution of hexachlorobenzene 

and 4,4'-DDE along a North-South Atlantic transect." Mar Pollut Bull 54(6): 814-9. 

 

Borga, K., H. Hop, et al. (2007). "Selective bioaccumulation of chlorinated pesticides 

and metabolites in Arctic seabirds." Environ Pollut 145(2): 545-53. 

 Chlorinated pesticides and metabolites (CPs) were quantified in the seabird 

species: little auk (Alle alle), Brunnich's guillemot (Uria lomvia), black guillemot 

(Cepphus grylle) and black-legged kittiwake (Rissa tridactyla). The purpose was 

to evaluate avian accumulation of selected CPs based on their concentrations 

and relative patterns, their relation to dietary descriptors (stable isotopes of 

carbon and nitrogen), to enzymes involved in biotransformation, as well as CPs' 

accumulation potential relative to the recalcitrant polychlorinated biphenyl PCB153. In all species, the CP pattern was dominated by p,p'-

dichlorodiphenyltrichloroethane (DDE) and hexachlorbenzene (HCB). Except for 

HCB, concentrations were not related to trophic position. Most CPs were 

quantified in black guillemot, indicating a slower elimination compared to other 

seabird species. Brunnich's guillemot showed efficient elimination of chlordanes, 

whereas the opposite was found for little auk. Kittiwake showed higher 

accumulation of persistent CP and metabolites than auks, whereas accumulation 

of less recalcitrant CPs was low. 

Borrell, A. and A. Aguilar (2007). "Organochlorine concentrations declined during 1987-

2002 in western Mediterranean bottlenose dolphins, a coastal top predator." 

Chemosphere 66(2): 347-52. 

 We collected blubber samples from bottlenose dolphins stranded on Spain's 

Mediterranean coasts over a 25-year period (1978-2002). Samples were 

analyzed to determine time trends in levels of: HCB (hexachlorobenzene), PCB 

(polychlorinated biphenyls) and tDDT (dichlorodiphenyltrichloroethane and its 

metabolites). Overall, levels were high relative to other areas. This reflects both 

the ubiquity of organochlorine pollution in the western Mediterranean and the 

sampled species' coastal habit. There was a significant decline over the study 

period in the concentrations of all the compounds analyzed. However, the 

DDE/tDDT, which is indicative of DDT ageing, significantly increased. This 

suggests there has been no significant use of HCB, DDT or PCB in the region for 

a long time. It also indicates that the pollutant loads in the environment are 

gradually being reduced; either by degradation or by migration of the compounds 

to other regions. A comparison with dolphin species that have an oceanic 
205

distribution suggests that PCB decline at a comparable pace in coastal and 

offshore water bodies. However, the decline of tDDT is faster near the coast. 

Braune, B. M. (2007). "Temporal trends of organochlorines and mercury in seabird eggs 

from the Canadian Arctic, 1975-2003." Environ Pollut 148(2): 599-613. 

 Organochlorine pesticides, PCBs, total mercury and selenium were measured in 

eggs of thick-billed murres, northern fulmars and black-legged kittiwakes 

collected from Prince Leopold Island in the Canadian High Arctic between 1975 

and 2003. The primary organochlorines found were SigmaPCB, p,p'-DDE, 

oxychlordane, and hexachlorobenzene (HCB). Most of organochlorines analyzed 

showed either significant declines or no significant change between 1975 and 

2003 in all three species. However, significant increases were observed for 

SigmaHCH in the kittiwakes and fulmars, and beta-HCH in the murres and 

fulmars. Mercury increased significantly in eggs of murres and fulmars, whereas 

mercury in the kittiwakes did not change significantly over the study period. 

Statistical analyses included stable-nitrogen isotope ratios (delta(15)N) to control 

for any variation in trophic level over time. Although the contaminant 

concentrations reported in this study are below published threshold values, 

mercury and beta-HCH concentrations continue to increase suggesting that 

continued monitoring is warranted. 

Breivik, K., R. Alcock, et al. (2004). "Primary sources of selected POPs: regional and 

global scale emission inventories." Environ Pollut 128(1-2): 3-16. 

 During the last decade, a number of studies have been devoted to the sources 

and emissions of Persistent Organic Pollutants (POPs) at regional and global 

scales. While significant improvements in knowledge have been achieved for 

some pesticides, the quantitative understanding of the emission processes and 

emission patterns for "non-pesticide" POPs are still considered limited. The key 

issues remaining for the non-pesticide POPs are in part determined by their 

general source classification. For industrial chemicals, such as the 

polychlorinated biphenyls (PCBs), there is considerable uncertainty with respect 

to the relative importance of atmospheric emissions from various source 

categories. For PCBs, temperature is discussed as a potential key factor 

influencing atmospheric emission levels and patterns. When it comes to the 

unintentional by-products of combustion and industrial processes (PCDD/Fs), 

there is still a large uncertainty with respect to the relative contribution of 

emissions from unregulated sources such as backyard barrel burning that 

requires further consideration and characterisation. For hexachlorobenzene 

(HCB), the relative importance of primary and secondary atmospheric emissions 

in controlling current atmospheric concentrations remains one of the key 

uncertainties. While these and other issues may remain unresolved, knowledge 

concerning the emissions of POPs is a prerequisite for any attempt to understand 

and predict the distribution and fate of these chemicals on a regional and global 

scale as well as to efficiently minimise future environmental burdens. 
206

Brown, P. (2009). "Toxic waste in our midst: towards an interdisciplinary analysis." J 

Environ Manage 90(4): 1559-66. 

 Intractable industrial legacies present new challenges to governance. Amongst 

the persistent organic pollutants, now managed internationally under the 

Stockholm Convention, hexachlorobenzene (HCB) stands out in all three classes 

of chemicals (pesticides, industrial chemicals and unintended by-products). This 

paper introduces twelve interdisciplinary papers contributing to our understanding 

of decision-making processes using a case study of HCB and industrycommunity relations in Sydney's industrial heartland. In this collection, authors 

align new political theory and emerging management theory, and they analyse 

the case study from several disciplines. Disputes such as that over HCB 

destablilise the political/administrative/technoscientific regime that is the modern 

state. Citizens engage in 'sub-political' processes which require recognition of 

what Ulrich Beck and others have termed 'individualisation'. This sees decisionforming and decision-making functions push outwards into community-driven 

structures. There we find new styles of public participation, resolution of 

asymmetries between knowledge and expertise, and new corporate behaviour. 

Brown, P. and S. Benn (2009). "Toxic risk and governance: the case of 

hexachlorobenzene." J Environ Manage 90(4): 1557-8. 

 

Bruder, M. C., S. Spanhaak, et al. (1999). "Intestinal T lymphocytes of different rat 

strains in immunotoxicity." Toxicol Pathol 27(2): 171-9. 

 In order to study the intestinal mucosal immune cells, with emphasis on single T 

lymphocytes, an inventory was made of single and organized lymphocytes in the 

epithelium and lamina propria of the small intestines of untreated Wistar, Fischer 

344, and Lewis rats. The single and organized lymphocytes were examined 

microscopically. In addition, the single lymphocytes in the epithelium (IEL) and 

lamina propria (LPL) were analyzed by flow cytometry. Next, the use of flow 

cytometry analysis was explored to detect changes in the IEL T-lymphocyte 

population in subacute oral studies with the immunomodulating agents 

azathioprine and hexachlorobenzene. Untreated random-bred Wistar rats 

exhibited a large interindividual variability in IEL composition, while the variability 

was small in inbred Fischer 344 and Lewis rats. The explorative study with the 2 

model immunomodulating compounds demonstrated that hexachlorobenzene 

increased the number of intraepithelial T lymphocytes with CD8+ phenotype at 

the cost of T cells with CD4+ phenotype in Lewis rats. Azathioprine did not 

induce distinct effects on the percentages of IEL. The data indicate that the 

intraepithelial lymphocytes in the intestines are a potential target for orally 

administered immunomodulating compounds and should therefore receive more 

attention in toxicologic pathology studies. 

Bruhn, R., N. Kannan, et al. (1999). "Persistent chlorinated organic contaminants in 

harbour porpoises from the North Sea, the Baltic Sea and Arctic waters." Science of the 

Total Environment 237-238: 351-361. 
207

 BIOSIS COPYRIGHT: BIOL ABS. Individual chlorinated biphenyls (CBs) and 

chlorinated pesticides (p,p'-DDT and metabolites, HCHs and HCB) were 

determined in blubber samples of 40 harbour porpoises (Phocoena phocoena) of 

different age and sex from the North Sea, the Baltic Sea and Greenland coastal 

waters. Polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated 

dibenzofurans (PCDFs) were analysed in a selected group of animals. SIGMACB 

concentrations (medians) in North Sea immature specimens were similar (14.9 

mug/g lipi The North Sea and Baltic Sea populations were identified as distinctly 

separate on the basis of levels and compositions of these contaminants. The 

ecological risk associated with dioxin-like toxicity was dominated by the CB 

congeners 118 and 170; the PCDDs were playing only a minor role. 

Bustnes, J. O., K. E. Erikstad, et al. (2006). "Anti-parasite treatment removes negative 

effects of environmental pollutants on reproduction in an Arctic seabird." Proc Biol Sci

273(1605): 3117-22. 

 Recent studies have shown that the detrimental effects of anthropogenic 

pollutants may be worse if organisms are exposed to natural stress. In this study, 

we examined whether negative effects of organochlorines (OCs) could be 

influenced by parasites. In two breeding seasons, we administered an antihelminthic drug to groups of breeding glaucous gulls (Larus hyperboreus), 

whereas control groups were placebo treated. In all birds, blood residues of the 

most important OCs in the study population (hexachlorobenzene, oxychlordane, 

p,p'-dichlorodiphenyldichloroethylene and polychlorinated biphenyl), were 

measured. The relationships between OCs and fitness components (i.e. nesting 

success and return rate between breeding seasons) were then compared 

between the birds receiving anti-parasite treatment and the controls. Among 

untreated males, higher blood residues of OCs were associated with lowered 

nesting success, while in males receiving anti-parasite treatment, there was no 

detrimental effect of OCs on fitness. Return rate was not affected by treatment or 

OCs. Our findings suggest that parasites may be an important factor in triggering 

reproductive effects of such pollutants, and that relatively low levels of OCs may 

have serious reproductive consequences in natural populations when stress from 

other sources is high. 

Bustnes, J. O., O. Miland, et al. (2005). "Relationships between ecological variables and 

four organochlorine pollutants in an artic glaucous gull (Larus hyperboreus) population." 

Environ Pollut 136(1): 175-85. 

 The Arctic has become a sink for organochlorine contaminants (OCs) from lower 

latitudes, and relatively high levels have been found in different biota. Recent 

studies of the glaucous gull, Larus hyperboreus, a top predator in the arctic food 

web, have documented that high blood residues of various OCs are related to 

lower reproductive performance and reduced adult survival. Here we provide 

additional evidence that OCs are having ecological effects in the glaucous gull 

population at Bear Island in the Norwegian Arctic, and compare the effects of the 

four major OCs found in the glaucous gulls: HCB, oxychlordane, DDE and PCBs, 

which made up >95% of measured OCs. Firstly; it has previously been shown 
208

that gulls with high levels of PCBs in their blood spent more time away from the 

nest site during incubation than gulls with low levels. Here we reanalyzed the 

data and found that PCBs (P<0.02) and oxychlordane (P<0.05) were positive and 

significantly related to time away from the nest site, while DDE and HCB were 

not related to this trait. Secondly, among females which bred in an area where 

fish dominated the diet, and thus had high flight costs during feeding, early chick 

growth was negatively related to maternal levels of all four OCs, especially HCB 

and DDE (P<0.01). On the contrary, among females breeding in an area where 

the diet was dominated by eggs and young from nearby seabird colonies, and 

thus feeding costs were low, there were no effects of OC levels on early chick 

growth. This indicates that additional stress may be fundamental in causing 

reproductive effects of OCs in this population. Finally, during three breeding 

seasons we examined the probability of adults returning to the breeding grounds 

in the subsequent season, as a function of blood concentration of the four OCs. 

Overall, return rate from one year to the next was negatively related to blood 

residues of oxychlordane (P=0.02), but not significantly related to the other three 

compounds. Further support for the importance of oxychlordane was that a 60% 

drop in the blood levels between 1997 and 2000 led to a significant increase in 

return rate between these two years. 

Carson, L. (2009). "Deliberative public participation and hexachlorobenzene stockpiles." 

J Environ Manage 90(4): 1636-43. 

 This paper is concerned with the quality of citizen involvement in relation to the 

governance of industrial risks. Specifically, it explores the hexachlorobenzene 

(HCB) case relative to best practice public participation, which is consistent with 

deliberative democratic theory. The case could be judged a public participation 

failure given that the community committee in combination with the corporate 

sponsor was unable to agree on a mutually acceptable technological pathway. 

This stalemate might have been attributable in part to the time spent on the task 

of review. A diligent participation working party could have created a much more 

effective public participation plan, grounded in the core values of professional 

public participation practice. 

Carvalho, F. P., S. Montenegro-Guillen, et al. (1999). "Chlorinated hydrocarbons in 

coastal lagoons of the Pacific Coast of Nicaragua." Archives of Environmental 

Contamination and Toxicology 36(2): 132-139. 

 BIOSIS COPYRIGHT: BIOL ABS. A screening for persistent chlorinated 

hydrocarbons was carried out in December 1995 in the main coastal lagoons on 

the Pacific side of Nicaragua, where most of the country's agriculture and 

pesticide use has been taking place for decades. Results for a wide range of 

organochlorine pesticides in lagoon sediments show levels that generally were 

very low in Estero Real, Estero Padre Ramos, and estuary of San Juan del Sur. 

For example, total DDTs in these lagoons averaged 4.5 3.4 ng g-1 dry weight, 

which may be considered a baseline level for the region. Other compounds such 

as HCHs, BHC, endosulfan, heptachlor, endrin, toxaphene, and aroclors were 

present in concentrations even lower, generally below 1 ng g-1 dry weight. 
209

However, sediments of the Esteros Naranjo-Paso Caballos system at 

Chinandega district contained pesticide residues in much higher levels, attaining 

maximum values of 1,420 ng g-1 and 270 ng g-1 dry weight, respectively, for 

toxaphene and total DDTs. Oth MH - ECOLOGY 

Cerrillo, I., P. Molinero, et al. (2002). "Development of a bioassay for thyroid disruption 

in patients exposed to endocrine disrupting chemicals." Organohalogen Compounds

56(Dioxin 2002): 103-105. 

 The authors present a new bioassay that investigates the inhibitory effects of 

chems. on the activity of 5'-deiodinase type II enzyme. The authors also 

quantified endocrine disrupters from the cervical fat tissue of patients with 

different thyroid diseases. 

Chai, Y., J. W. Davis, et al. (2008). "Effects of aging and sediment composition on 

hexachlorobenzene desorption resistance compared to oral bioavailability in rats." 

Chemosphere 72(3): 432-41. 

 Studies were conducted to assess the effects of black carbon, clay type and 

aging (1-1.5yr) on desorption and bioavailability of hexachlorobenzene (HCB) in 

spiked artificial sediments. Tenax (a super sorbent)-mediated desorption was 

used to examine the effects of these parameters on the physicochemical 

availability of HCB. The Tenax-mediated desorption of HCB from the four aged 

artificial sediments exhibited biphasic kinetics. The fast desorbing fractions 

ranged from 64.8% to 22.3%, showing reductions of 4.0-18.9% compared with 

freshly-spiked sediments. Statistical analysis on the fast desorbing fractions 

showed that all three treatment effects (i.e., montmorillonite clay, black carbon 

content, and aging) were significant. Two sediments with higher black carbon 

content exhibited much greater aging effects (i.e., greater reduction in fast 

desorbing fraction) than the other two sediments without the addition of black 

carbon. For both freshly-spiked and aged sediments, the desorption resistant 

sediment-bound HCB (i.e., slow desorbing fraction) correlated reasonably well to 

previously reported rat fecal elimination of HCB, which is a measure of the nonbioavailable fraction of sediment-bound HCB. A similar correlation was also 

observed between fast desorbing fraction and previously reported accumulation 

of HCB in the rat body (carcass+skin). These observations suggest that 

physicochemical availability, as defined by the desorption of HCB from 

sediments, provides a reasonable prediction of the oral bioavailability of 

sediment-bound HCB to rats. These results showed that montmorillonite clay, 

black carbon and aging reduced physicochemical availability and ultimately 

bioavailability of sediment-bound HCB. 

Charlier, C., M. T. Closon, et al. (2003). "Does radiotherapy have consequences on 

plasma concentration of toxic pollutants?" Bull Environ Contam Toxicol 70(1): 17-21. 

 

Chaufan, G., A. Juarez, et al. (2006). "Toxicity of hexachlorobenzene and its 

transference from microalgae (Chlorella kessleri) to crabs (Chasmagnathus 

granulatus)." Toxicology 227(3): 262-70. 
210

 The aim of this work was to study the transference of hexachlorobenzene from a 

green alga (Chlorella kessleri) to an estuary crab (Chasmagnathus granulatus), 

and to analyze the toxic effects that the xenobiotic has on the latter. The effect of 

hexachlorobenzene uptake was evaluated measuring oxidative stress, 

Uroporphyrinogen decarboxylase activity and morphometric parameter alteration, 

and also performing a histological analysis of crab hepatopancreas. Results 

demonstrated that hexachlorobenzene enters the alga, is accumulated in it, and 

then transferred into the crab, causing a decrease in Uroporphyrinogen 

decarboxylase activity in both organisms. The high malondialdehyde levels 

detected in crab hepatopancreas after the toxic treatment suggested the 

existence of hexachlorobenzene-induced lipid peroxidation. Antioxidant defenses 

such as superoxide dismutase activity and reduced glutathione content fell below 

normal values on the fourth week of treatment. At the same time, the 

hepatosomatic index, used as a morphometric parameter, reduced 20% with 

respect to the control. The histological analysis revealed epithelium 

disorganization in hepatopancreas tubules, confirming the existence of structural 

damage caused by hexachlorobenzene. 

Chen, W., A. T. Kan, et al. (1999). "Adsorption-desorption behaviors of hydrophobic 

organic compounds in sediments of Lake Charles, Louisiana, USA." Environmental 

Toxicology and Chemistry 18(8): 1610-1616. 

 BIOSIS COPYRIGHT: BIOL ABS. Neutral organic contaminants commonly 

reside on the solid portion of soils and sediments. The extent of desorption from 

these solids determines the fate, reactivity, and toxicity. Numerous researchers 

have observed that, after an initial exposure of a few days, desorption takes 

place in two phases, namely, an initial rapid release followed by a long-term 

resistant phase. Resistant desorption has been highly unpredictable. In this 

research, the adsorption and desorption of chlorobenzenes, hexachl ld 

reasonably be interpreted using a single irreversible isotherm. Consequences of 

these results interms of sediment quality criteria (SQC) are also discussed. 

Finally, an index of fractional irreversible adsorption is proposed and tested. 

Chen, X., A. Christopher, et al. (2002). "Crystal structure of the F87W/Y96F/V247L 

mutant of cytochrome P-450cam with 1,3,5-trichlorobenzene bound and further protein 

engineering for the oxidation of pentachlorobenzene and hexachlorobenzene." J Biol 

Chem 277(40): 37519-26. 

 We reported previously that the F87W/Y96F/V247L mutant of cytochrome P450cam (CYP101) from Pseudomonas putida catalyzed the rapid oxidation of 

lightly chlorinated benzenes, but pentachlorobenzene oxidation was slow (Jones, 

J. P., O'Hare, E. J., and Wong, L. L. (2001) Eur. J. Biochem. 268, 1460-1467). In 

the present work, we determined the crystal structure of this mutant with bound 

1,3,5-trichlorobenzene. The substrate was bound to crystallographically 

independent CYP101 molecules in at least three different orientations, which 

were distinguished by the angle between the benzene ring and the porphyrin, 

and one orientation contained an Fe-Cl interaction. In another orientation, the 

substrate was almost parallel to the heme, with a C-H bond closest to the iron. 
211

The enzyme/substrate contacts suggested that the L244A mutation should 

promote the binding of pentachlorobenzene and hexachlorobenzene by creating 

space to accommodate the extra chlorines. The F87W/Y96F/L244A/V247L 

mutant thus designed was found to oxidize pentachlorobenzene at a rate of 82.5 

nmol (nmol CYP101)(-1) min(-1), 45 times faster than the F87W/Y96F/V247L 

parent mutant. The rate of hexachlorobenzene oxidation was increased 200-fold, 

to 2.0 min(-1). Both substrates are oxidized to pentachlorophenol, which is 

degraded by micro-organisms. In principle, the F87W/Y96F/L244A/V247L mutant 

could have applications in the bioremediation of polychlorinated benzenes. 

Choi, J. W., M. Matsuda, et al. (2001). "Accumulation profiles of persistent 

organochlorines in waterbirds from an estuary in Korea." Arch Environ Contam Toxicol

41(3): 353-63. 

 Persistent organochlorine pollutants (POPs), such as polychlorinated dibenzo-pdioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), polychlorinated 

biphenyls (PCBs), and organochlorine (OC) pesticides such as DDTs 

(dichlorodiphenyltrichloroethane), HCHs (hexachlorocyclohexane isomers), CHLs 

(chlordane compounds) and HCB (hexachlorobenzene), were measured in 

subcutaneous fat of resident and migratory birds collected from the Nakdong 

River estuary (NRE) in Korea. Black-tailed gull, a resident bird from the NRE, 

contained greater concentrations of PCDD/Fs and PCBs than the migratory birds 

collected in the estuary. For example, mean concentrations of PCDD/Fs in blacktailed gull (395.5 pg/g fat weight) were higher than those in migratory birds, such 

as greenshank (198.3 pg/g fat weight), common gull (90.9 pg/g fat weight) blackheaded gull (84.2 pg/g fat weight), and common tern (47.1 pg/g fat weight). 

However, concentrations of DDTs and/or HCHs were great in some migratory 

species, such as little tern (mean DDT 6,200 ng/g fat weight) and black-necked 

grebe (HCHs 475 ng/g fat weight). This suggested that contamination of 

PCDD/Fs and PCBs in resident gulls are due to intake of locally contaminated 

fish near the NRE. Elevated OC pesticide levels in migratory birds indicated that 

these birds have been exposed to DDTs and HCHs during their migration in 

Southeast Asian countries where chlorinated pesticides are still used. 2,3,7,8-

Tetrachloro dibenzo-p-dioxin equivalents (TEQs) were calculated using the toxic 

equivalency factors (TEFs) reported by World Health Organization in 1998. Four 

of the 2,3,7,8-substituted congeners of PCDD/Fs contributed over 90% of the 

TEQs. 

Cincinelli, A., T. Martellini, et al. (2009). "Organochlorine pesticide air-water exchange 

and bioconcentration in krill in the Ross Sea." Environ Pollut 157(7): 2153-8. 

 Mean hexachlorobenzene (HCB) and hexachlorocyclohexane (HCH) 

concentrations, measured in seawater and air samples, confirmed the decline in 

levels of these compounds in Antarctic air and water. However, low 

alpha/gamma-HCH ratios in air at the beginning of the sampling period suggest a 

predominance of fresh lindane entering the Antarctic atmosphere during the 

Austral spring probably due to current use in the Southern Hemisphere. Water-air 

fugacity ratios demonstrate the potential for HCH gas deposition to coastal 
212

Antarctic seas, while the water-air fugacity ratios for HCB imply that volatilization 

does not account for the observed decrease of HCB in surface seawater. HCH 

concentrations found in krill samples were correlated with seawater 

concentrations indicative of bioconcentration of HCHs from seawater. 

Clemons, E., M. R. Arkoosh, et al. (1999). "Enhanced superoxide anion production in 

activated peritoneal macrophages from English sole (Pleuronectes vetulus) exposed to 

polycyclic aromatic compounds." Marine Environmental Research 47(1): 71-87. 

 BIOSIS COPYRIGHT: BIOL ABS. As in mammals, macrophages play a vital role 

in the destruction of infective organisms in fish. The current study was done to 

determine if exposure to polycyclic aromatic compounds (PACs), a group of 

chemical contaminants commonly found in the sediments of urban marine areas, 

alters the ability of peritoneal macrophages (Mphis) from English sole 

(Pleuronectes vetulus) to produce cytotoxic reactive oxygen intermediates 

(ROIs). Initially, assay conditions including concentration of Mphis, type of in vitro 

stimulant, tissue culture media, and incubation time were optimized to measure 

production of superoxide anion (O2-, the progenitor ROI, in English sole Mphis. 

English sole were then injected with an organic solvent extract of a PACcontaminated sediment equivalent to 20 g sediment (about 860 mug selected 

PACs) per kg fish, via their dorsal lymphatic sinus. Peritoneal Mphis were 

harvested on days 1, 3, 7, and 14 post-injection. Elicited peritoneal Mphis from 

English sole 

Colume, A., S. Cardenas, et al. (1999). "Semiautomatic method for the screening and 

determination of 23 organochlorine pesticides in horticultural samples by gas 

chromatography with electron-capture detection." Journal of Chromatography a 849(1): 

235-243. 

 BIOSIS COPYRIGHT: BIOL ABS. A rapid, simple, efficient device for the 

extraction-preconcentration of 23 organochlorine pesticides currently applied to 

vegetables is proposed. Pesticide residues are extracted from chopped samples 

by using a mixture of distilled water and light petroleum (1:1, v/v). After phase 

separation, an aliquot of the organic layer is continuously evaporated to dryness 

under a N2 stream as it is dropped into a glass tube containing distilled water. 

The aqueous phase, containing the analytes, is then pa ge relative standard 

deviation at the low nanogram-per-millilitre level is 5.3%. The potentialof the 

proposed method was realized by applying it to the screening/determination of 

organochlorine pesticides in horticultural commodities. 

Cook, J., M. Engel, et al. (1999). "Multiresidue screening of pesticides in foods using 

retention time locking, GC-AED, database search, and GC-MS identification." Journal of 

Aoac International 82(2): 313-326. 

 BIOSIS COPYRIGHT: BIOL ABS. Fruit and vegetable extracts were screened for 

over 400 pesticides by gas chromatography with atomic emission detection (GCAED) and an experimental database. A technique called retention time locking 

was used to match GC-AED and GC with mass spectrometry (MS) retention 

times to those of the database. Samples were analyzed for sulfur, nitrogen, 
213

phosphorus, and chlorine by GC-AED. Possible pesticides were suggested by 

database search and identified by GC. Forty-four pesticide standards were 

analyzed to determine the precision of retention time matching and the accuracy 

of the database search. Analytical retention times matched database retention 

times within 0.32 min. Using elemental criteria, the database search identified the 

correct compound for 41 of 44 pesticide standards. For blind spikes of fruit and 

vegetable extracts, the database suggested 22 of 26 spiked pesticides as 

matche s. Nineteen were identified by GC/MS. The combination of retention time 

locking, GC-AED, database search, and GC/MS can be a powerful tool for 

identifying pesticides in a complex matrix./METHODS 

Cornelissen, G., M. Van Der Pal, et al. (1999). "Competitive effects on the slow 

desorption of organic compounds from sediments." Chemosphere 39(11): 1971-1982. 

 BIOSIS COPYRIGHT: BIOL ABS. Experiments were carried out concerning 

competition effects in slow desorption. Excess lab-added 1,2,4-trichlorobenzene 

(TCB) decreased the slowly desorbing amounts of aged in situ polychlorinated 

biphenyls (PCBs) and chlorobenzenes in sediment from Lake Ketelmeer (KM), 

The Netherlands, after 14 d of TCB-sediment contact time (factor of 1.2-2.7). 

Another experiment showed that the presence of large quantities of in situ oil (15 

g/kg) and polycyclic aromatic hydrocarbons (PAHs; 1.5 g/kg) strongly n indicates 

that the number of slow sorption sites is limited. This is in accordance with the 

recent finding that part of the sorption of organic compounds in soils and 

sediments occurs in a nonlinear way, the slowly desorbing fractions showing this 

nonlinear sorption. 

Corsolini, S., A. Covaci, et al. (2006). "Occurrence of organochlorine pesticides (OCPs) 

and their enantiomeric signatures, and concentrations of polybrominated diphenyl 

ethers (PBDEs) in the Adelie penguin food web, Antarctica." Environ Pollut 140(2): 371-

82. 

 Concentrations and enantiomeric signatures of organochlorine pesticides were 

determined in Antarctic krill, emerald rockcod and Adelie penguin from the Ross 

Sea, Antarctica. HCB and DDTs were prevalent contaminants in penguin eggs. 

The highest concentrations of SigmaHCHs (1.35 +/- 0.72 ng/g) were found in the 

rockcod muscle, where gamma-HCH (1.23 +/- 0.67 ng/g) was the principal 

isomer. The ratio gamma-HCH/alpha-HCH was evaluated. Enantioselective gas 

chromatography was used for the evaluation of enantiomeric fractions (EFs) for 

alpha-HCH and oxychlordane. An increase of 14% in the (+)alpha-HCH 

enantiomer was found from krill through penguin, suggesting the enantioselective 

biotransformation increased proportionately with trophic level. Polybrominated 

diphenyl ethers (PBDEs) were measured and their concentrations were 5.6 +/- 

1.12, 5.81 +/- 2.32, 4.57 +/- 0.17 and 3.06 +/- 3.27 ng/g lipids in krill, rockcod 

muscle, rockcod homogenate and penguin eggs, respectively. The detection of 

BDE28, BDE47, BDE99 and BDE100 in Antarctic organisms confirmed their 

global transport and distribution; the detection of lower brominated congeners 

suggested a potential long-range transport. 
214

Corsolini, S., G. Sara, et al. (2007). "HCB, p,p'-DDE and PCB ontogenetic transfer and 

magnification in bluefin tuna (Thunnus thynnus) from the Mediterranean Sea." Environ 

Sci Technol 41(12): 4227-33. 

 The bluefin tuna, Thunnus thynnus (Linnaeus 1758), is biologically and 

economically important in the Atlantic--Mediterranean ecosystems. Bluefin tuna 

feed on diverse food items depending on their age, thus they occupy different 

trophic levels during their lifespan. Hexachlorobenzene (HCB), p,p'-DDE and 

polychlorinated biphenyls (PCBs) are well-known persistent organic pollutants 

(POPs) in the Mediterranean basin. The relationship between stable isotopes of 

nitrogen (N) and the POP residue levels in tissues has recently increased 

knowledge on the link between the trophic levels and the contaminant 

accumulation. Trophic levels were estimated by using 15N/14N ratio (delta15N) 

and HCB, p,p'-DDE, and forty-three PCBs were quantified in bluefin tuna from 

the southern Tyrrhenian Sea. Results showed that changes in PCB and p,p'-DDE 

concentrations were a function of size and trophic level, while no correlations 

were observed for HCB. Apart from HCB and PCB nos. 101, 207, 95, 158, and 

60 + 56, which did not show any significant increase per trophic level, the other 

PCBs and the p,p'-DDE increased significantly. The ontogenetic magnification 

factor of PCBs was 6.6 +/- 0.5, which was significantly (12 times) higher (p < 

0.05) than the values found for p,p'-DDE (1.4) and HCB (1.4). 

Couillard, C. M. and P. Nellis (1999). "Organochlorine contaminants in mummichog 

(Fundulus heteroclitus) living downstream from a bleached-kraft pulp mill in the 

Miramichi Estuary, New Brunswick, Canada." Environmental Toxicology and Chemistry

18(11): 2545-2556. 

 BIOSIS COPYRIGHT: BIOL ABS. Mummichog, a small-sized sentinel fish 

species, has been proposed for use in environmental effects monitoring 

programs conducted by pulp mills that release their effluent in marine waters. In 

order to evaluate the suitability of mummichog as a sentinel species and to 

support the interpretation of biological effects data, tissue concentrations of 

polychlorinated dibenzo-p-dioxins and dibenzofurans, (PCDDs), chlorophenolic 

compounds (CPs), polychlorinated biphenyls (PCBs), and chlorinated pestic -pdioxin toxic equivalent concentrations were slightly above the threshold for 

ethoxy resorufin O-deethylase induction. Multivariate analyses on congener 

profiles revealed that the contamination by PCDD/Fs and CPs originated both 

from the BKM and from a former wood-preservation plant and that PCDD/Fs and 

CPs typical of the BKM were transported 40 km downstream from the mill. 

Patterns and levels of persistent contaminants differed between sites within the 

Estuary, indicating that the fish did no esence of multiple sources of 

contamination. 

Cousins, I. T., A. J. Beck, et al. (1999). "A review of the processes involved in the 

exchange of semi-volatile organic compounds (SVOC) across the air-soil interface." 

Science of the Total Environment 228(1): 5-24. 

 BIOSIS COPYRIGHT: BIOL ABS. The exchange of semi-volatile organic 

compounds (SVOC) across the air-soil interface is one of the most important 
215

processes determining the environmental fate and human exposure of these 

compounds. The main processes contributing to air-soil exchange of SVOC are 

dry deposition (both by vapour adsorption and in association with particles), wet 

deposition (by precipitation scavenging of vapour- and particle-sorbed chemicals) 

and volatilisation from the soil. These processes are reviewed and evalua 

Crane, M. and M. Babut (2007). "Environmental quality standards for water framework 

directive priority substances: challenges and opportunities." Integr Environ Assess 

Manag 3(2): 290-6. 

 The recently published Daughter Directive on priority substances is the 

culmination of several years of effort by the European Commission to develop 

consistent, Europe-wide environmental quality standards (EQS) that are 

scientifically based and protective of Europe's surface waters. This commentary 

describes progress to date in deriving EQS under the Water Framework Directive 

and identifies some remaining challenges and opportunities. In the Daughter 

Directive, annual average EQS are set for surface waters for all 33 priority 

substances. No sediment standards are included, and biota EQS are proposed 

for methyl-mercury, hexachlorobenzene and hexachlorobutadiene. Important 

remaining questions include whether the standard chemical risk assessment 

methodology is appropriate for deriving water column EQS and whether it would 

be appropriate to derive EQS for sediment or biota or to adopt alternative 

strategies. Moreover, some cross-cutting issues about the cessation of 

discharges of naturally occurring or ubiquitous substances and the advantages 

and disadvantages of member states setting their own EQS are briefly 

addressed. 

Crivelli, A. J., L. Marsili, et al. (1999). "Organochlorine compounds in pelicans 

(Pelecanus crispus and Pelecanus onocrotalus) nesting at lake Mikri Prespa, North 

Western Greece." Bulletin of Environmental Contamination and Toxicology 62(4): 383-

389. 

 Biosis copyright: biol abs. rrm research article pelecanus crispus pelecanus 

onocrotalus dalmatian pelican great white pelican egg pollution toxicology pp'dde 

chlorinated hydrocarbon toxin pollutant environmental contaminant pp'ddd pp'ddt 

lindane hcb eggshell reproductive system embryonic structure reproductive 

system thickness nesting area north-western lake mikri prespa greece 

Crouch Edmund, A. C. and C. Green Laura "Comment on "Persistent organic pollutants 

in 9/11 world trade center rescue workers: reduction following detoxification" by James 

Dahlgren, Marie Cecchini, Harpreet Takhar, and Olaf Paepke [Chemosphere 69/8 

(2007) 1320-1325]." Chemosphere 69(8): 1330-2; discussion 1333-6. 

 

Custer, T. W., C. M. Custer, et al. (1999). "Organochlorine contaminants and 

reproductive success of double-crested cormorants from Green Bay, Wisconsin, USA." 

Environmental Toxicology and Chemistry 18(6): 1209-1217. 

 In 1994 and 1995, nesting success of double-crested cormorants (Phalacrocorax 

auritus) was measured at Cat Island, in southern Green Bay, Lake Michigan, 
216

Wisconsin, USA. Sample eggs at pipping and unhatched eggs were collected 

and analyzed for organochlorines (including total polychlorinated biphenyls 

(PCBs) and DDE), hepatic microsomal ethoxyresorufin-O-dealkylase (EROD) 

activity in embryos, and eggshell thickness. Of 1,570 eggs laid, 32% did not 

hatch and 0.4% had deformed embryos. Of 632 chicks monitored from hatching 

to 12 d of age, 9% were missing or found dead; no deformities were observed. 

The PCB concentrations in sample eggs from clutches with deformed embryos 

(mean = 10.2 ug/g wet weight) and dead embryos (11.4 ug/g) were not 

significantly higher than concentrations in sample eggs from nests where all eggs 

hatched (12.1 ug/g). A logistic regression of hatching success versus DDE, 

dieldrin, and PCB concentrations in sibling eggs identified DDE and not dieldrin 

or PCBs as a significant risk factor. A logistic regression of hatching success 

versus DDE and eggshell thickness implicated DDE and not eggshell thickness 

as a significant risk factor. Even though the insecticide DDT was banned in the 

early 1970s, we suggest that DDE concentrations in double-crested cormorant 

eggs in Green Bay are still having an effect on reproduction in this species. 

Czaja, K., J. K. Ludwicki, et al. (1999). "Effect of changes in excretion of persistent 

organochlorine compounds with human breast milk on related exposure of breast-fed 

infants." Archives of Environmental Contamination and Toxicology 36(4): 498-503. 

 BIOSIS COPYRIGHT: BIOL ABS. This study was an attempt to identify if there 

are any trends in excretion of 1,2,3,4,5,6-hexachlorocyclohexane (HCH) isomers 

alpha-, beta-, and gamma-, hexachlorobenzene (HCB), (1,1,1-trichloro-2,2-bis(4-

chlorophenyl)ethane) (p,p'-DDT), (1,1-dichloro-2,2-bis(4-chlorophenyl)ethane) 

(p,p'-DDD), (1,1-dichloro-2,2-bis(4-chlorophenyl)ethylene) (p,p'-DDE), and 

polychlorinated biphenyls (PCBs) with human milk during lactation. The shortest 

lactation studied took 16 weeks, and the longest 84 weeks. Thr to those 

compounds decreases or increases as breast-feeding continues. 

Dallinga, J. W., E. J. Moonen, et al. (2002). "Decreased human semen quality and 

organochlorine compounds in blood." Human Reproduction 17(8): 1973-9. 

 BACKGROUND: Various studies have been performed in which potential effects 

of xenoestrogens on fertility or sperm parameters were investigated by 

comparing groups of subjects exposed to different levels of these chemicals. 

METHODS: In our study we used an alternative approach, as we selected one 

group of men with very poor semen quality and another group with normal semen 

quality and determined the blood organochlorine contents in order to determine 

whether a difference in these levels could be established. Organochlorine 

compounds, including polychlorinated biphenyls (PCB) and PCB metabolites, 

were detected using gas chromatography. The concentrations were compared 

between both groups, and related to semen parameters. RESULTS: A 

comparison of both groups did not reveal significant differences in organochlorine 

levels. Linear relationships were found when PCB and metabolite concentrations 

were related to the age of the volunteers. Focusing on the subgroup of men with 

normal semen quality showed that sperm count and sperm progressive motility 

were inversely related to the concentrations of PCB metabolites within this group. 
217

CONCLUSIONS: The finding of a significantly decreased sperm count in relation 

to an elevated PCB metabolite level within the subgroup of men with normal 

semen quality is important. This is the first time that a correlation between 

exposure to environmental pollutants with endocrine-disrupting capacity and 

human sperm quality has been observed. 

Daly, G. L., Y. D. Lei, et al. (2007). "Pesticides in western Canadian mountain air and 

soil." Environ Sci Technol 41(17): 6020-5. 

 The distribution of organochlorine pesticides (OCP; in past and current use) in 

the mountains of western Canada was determined by sampling air, soil, and 

lichen along three elevational transects in 2003-2004. Two transects west of the 

Continental Divide were located in Mount Revelstoke and Yoho National Park, 

while the Observation Peak transect in Banff National Park is east of the divide. 

XAD-based passive air samplers, yielding annually averaged air concentrations, 

were deployed, and soils were collected at all 22 sampling sites, whereas lichen 

were only sampled in Revelstoke. Back trajectory analysis showed limited air 

mass transport from the Prairies to the east, but a high frequency of air arriving 

from the southwest, which includes agricultural regions in British Columbia and 

Washington State. Endosulfan, dieldrin, and a-hexachlorocyclohexane were the 

most prevalent OCPs in air and soil; hexachlorobenzene was only abundant in 

air; chlorothalonil, dacthal, and pentachloronitrobenzene were also consistently 

present. OCP air concentrations were similar across the three transects, 

suggesting efficient atmospheric mixing on a local and regional scale. Soil 

concentrations and soil/air concentration ratios of many OCPs were significantly 

higher west of the Continental Divide. The soil and lichen concentrations of most 

OCPs increased with altitude in Revelstoke, and displayed maxima at 

intermediate elevations at Yoho and Observation Peak. These distribution 

patterns can be understood as being determined by the balance between 

atmospheric deposition to, and retention within, the soils. Higher deposition, due 

to more precipitation falling at lower temperatures, likely occurs west of the divide 

and at higher elevations. Higher retention, due to higher soil organic matter 

content, is believed to occur in soils below the tree line. Highest pesticide 

concentrations are thus found intemperate mountain soils that are rich in organic 

matter and receive large amounts of cold precipitation. 

Daniel, V., W. Huber, et al. (2001). "Associations of blood levels of PCB, HCHS, and 

HCB with numbers of lymphocyte subpopulations, in vitro lymphocyte response, plasma 

cytokine levels, and immunoglobulin autoantibodies." Environmental Health 

Perspectives 109(2): 173-178. 

 Pentachlorophenol (PCP), hexachlorocyclohexane-[alpha], -beta, and -[gamma] 

(HCH-[alpha], -beta, and -[gamma]), polychlorinated biphenyls (PCBs), and 

hexachlorobenzene (HCB) are widely distributed industrial chemicals. They are 

suspected to induce immunologic impairments in exposed individuals. We 

examined dose-response relationships of blood levels of these chemicals with 

cellular (numbers of lymphocyte subpopulations, in vitro lymphocyte response) or 

humoral (plasma cytokine levels, immunoglobulin autoantibodies) immunologic 
218

dysfunctions. We studied 146 patients who had been occupationally exposed 

primarily to PCBs for more than 6 months. Lymphocyte subpopulations, in vitro 

responses to mitogens and allogeneic stimulator cells, plasma neopterin, 

cytokines, soluble cytokine receptors, soluble adhesion molecules, anti-Ig 

autoantibodies, and liver transaminases were determined. Blood levels of the 

different compounds were strongly correlated with one another. There were only 

weak dose-response relationships between blood levels of PCBs with cellular 

immune parameters, and of HCHs and HCB with humoral immune parameters. 

An exception was the statistically significant negative association of HCB with 

interferon-[gamma] (IFN-[gamma]), indicating that HCB has a significant impact 

on Th1 lymphocytes. Patients with HCB blood levels above the mean of 1,109 

ng/L more often had undetectable IFN-[gamma] blood levels than patients below 

the mean. Patients with increased PCB 138 (> 710 ng/L) had more frequently 

undetectable interleukin-4 blood levels than patients with PCB 138 below the 

mean, and patients with increased PCB 101 (> 31 ng/L) more often had low DR+ 

cell counts in the blood (< 190/microL) than patients with PCB 101 below the 

mean. To assess possible cumulative effects, we compared patients who had 

blood levels of all compounds below background with patients who had blood 

levels of all compounds above background. Patients with low or absent blood 

levels of the compounds studied had higher IFN-[gamma] plasma levels, 

providing some evidence for a cumulative effect of several weakly active 

compounds. In conclusion, exposure to PCBs, HCB, or HCHs is associated with 

weak immunologic abnormalities. These results contrast with those obtained in 

earlier studies of blood levels of PCP, which showed a strong dose-dependent 

relationship with immunologic impairments. Our data suggest that long-term 

exposure of patients to HCB suppresses IFN-[gamma] production. 

Datta, S., K. Ohyama, et al. (1999). "Evidence for organochlorine contamination in 

tissues of salmonids in Lake Tahoe." Ecotoxicology and Environmental Safety 42(1): 

94-101. 

 BIOSIS COPYRIGHT: BIOL ABS. To evaluate the extent of organochlorine 

pollution in the Sierra Nevada ecosystem, residues of certain organochlorines in 

lake trout and Kokanee fish from Lake Tahoe, an alpine lake located between the 

Sierra Nevada Mountain Range and the Carson Range of California and Nevada, 

were analyzed. Multiresidue analysis in fish muscle revealed wet weight 

concentrations of total polychlorinated biphenyls (PCBs) in the range 18 to 430 

ppb and of p,p'-DDE in the range 5 to 85 ppb in the two fish species studied. In 

one large lake trout sample (6.6 kg), which was studied in more detail as 

compared with others, residue levels of PCB (267 ppb), toxaphene (154 ppb), a 

chlordane mixture (78 ppb), and a DDT mixture (154 ppb) were found in muscle. 

Full spectra of specific PCB congeners and pp'-DDE were obtained from fish fat 

tissues and their identities were confirmed using gas chromatography/mass 

spectrometry (GC-MS). The results of total PCB analysis indicated that residues 

found in f 
219

de Catabbi, S. B., R. W. de Calmanovici, et al. (1999). "Porphyria-induced hepatic 

porphyrinogen carboxy-lyase inhibitor and its interaction with the active site(s) of the 

enzyme." Biochem Mol Biol Int 47(6): 945-56. 

 Porphyrinogen carboxy-lyase is an enzyme that sequentially decarboxylates 

uroporphyrinogen III (8-COOH) to yield coproporphyrinogen III (4-COOH). In 

mammals this enzyme activity is impaired by hexachlorobenzene treatment, 

through generation of an enzyme inhibitor. The interaction of porphyrinogen 

carboxy-lyase inhibitor, extracted from the liver of hexachlorobenzene-treated 

rats, with substrate decarboxylation sites on the enzyme, was studied using four 

different carboxylated substrates belonging to the isomeric III series of naturallyformed porphyrinogens containing 8-,7-,6- and 5- COOH. Similar inhibitor effects 

were elicited against all the substrates assayed, with the exception of 

pentacarboxyporphyrinogen III in which decarboxylation was not inhibited to 

same extent. Enzyme protection assays in the presence of the different 

substrates, indicated that each porphyrinogen protects its own decarboxylation 

from inhibitor action. Preincubation of the inhibitor with normal enzyme increased 

its inhibitory effect. On the other hand, preincubation of both enzyme and 

inhibitor with superoxide dismutase or mannitol, did not alter inhibitory activity. 

Preincubation of the inhibitor with a number of amino acids showed that only 

arginine and its derivative N alpha-Benzoyl-L-Arginine ethyl ester interact with 

the inhibitor, noticeably reducing its ability to inhibit porphyrinogen carboxy-lyase. 

Albumin, histidine, serine, cysteine and imidazol, were unable to quench inhibitor 

activity. The present results indicate that the inhibitor acts at the binding site of 

each porphyrinogen. Taking into account that arginine is related to enzyme 

activity, and that histidine is found at the binding site of the substrates, the results 

suggest that the inhibitor could bind to arginine residues, blocking the access of 

substrates to histidine and altering the adequate orientation for decarboxylation 

by masking the positively charged active site necessary for porphyrinogen 

binding to the enzyme. In addition an indirect effect of the inhibitor mediated 

through free radicals could be discarded. 

De Felip, E. and A. M. Ingelido (2004). "Levels of persistent toxic substances in the 

general population in Italy." Annali dell'Istituto Superiore di Sanita 40(4): 411-5. 

 Human exposure to persistent toxic substances (PTS) occurs daily, mainly 

through diet. As a consequence of continuous exposure, and because of their 

biological persistence, PTS are virtually present in all individuals, stored in their 

fatty tissues. The exposure of the Italian general population to PTS is a fact of 

relevance from a public health perspective, because of the number of toxic 

effects associated to these compounds, possibly occurring even at the current 

background level of exposure. In spite of this, data on PTS concentrations in 

humans, considered the best dose metric to carry out an adequate risk 

assessment, are scarce, as shown by the overview of available information we 

hereafter present. The Convention of Stockholm on persistent organic pollutants 

(POP), a group of highly toxic PTS, has entered into force last May. This will 

oblige parties to develop national implementation plans, thus creating a new 
220

opportunity to develop more efficient policies to control POP and other PTS 

present in food, humans and the environment. 

de Roode, D. F., A. V. Klomp, et al. (2002). "Effects of an extract of oystercatcher 

(Haematopus ostralegus) eggs from the Zeehavenkanaal in The Netherlands, and of its 

major contaminant, hexachlorobenzene, on the chicken embryo." Environmental 

Toxicology and Pharmacology 12(3): 147-56. 

 Oystercatchers (Haematopus ostralegus) foraging on the canal 'Zeehavenkanaal' 

in the Netherlands have been shown to accumulate appreciable amounts of 

contaminants, especially hexachlorobenzene. The present study was performed 

to assess the embryotoxic effects of the present contaminants. To this end, a two 

step approach was followed. In step one, the toxic effects of hexachlorobenzene 

were studied in the chicken embryo bioassay, using concentrations realistic for 

the field situation. In step two, yolks of oystercatcher eggs were extracted and 

the embryotoxic potency of this extract was studied in the same bioassay, using 

doses of 1, 10 and 100% of the contaminant load in one average egg. The 

extract contained hexachlorobenzene and PCBs. However, presence of other 

compounds could not be excluded, since these were not analysed. 

Hexachlorobenzene induced a nonsignificant decrease in lymphocyte density in 

the bursa of Fabricius. The egg extract caused a 3.5 fold induction of EROD 

activity at the highest dose applied, and decreased lymphocyte density in the 

bursa of Fabricius. 

Dell'Anno, A., F. Raffaelli, et al. (2008). "Cytotoxic effects induced by 

hexachlorobenzene in Squilla mantis (L.) (Crustacea, Stomatopoda)." Environ Toxicol

23(1): 9-14. 

 Contamination of marine environments by hexachlorobenzene (HCB) represents 

a serious concern for potential consequences on ecosystem and human health. 

Despite this, information on cytotoxic effects on marine organisms is still largely 

lacking. In this study, we investigated cytotoxic effects induced by HCB on 

gonads and muscular tissue of Squilla mantis by analysing Na(+)/K(+)-ATPase 

activity and plasma membrane fluidity. This crustacean species was selected as 

a model for its habitat, trophic level, feeding behavior, and commercial 

exploitation for human consumption. Time course experiments revealed that low 

concentrations of HCB (i.e. 50 nM) determine an exponentially decrease of 

Na(+)/K(+)-ATPase activity and a significant modification of cellular membrane 

fluidity. Significant negative relationships between Na(+)/K(+)-ATPase activity 

and membrane fluidity were observed, suggesting that changes in the structure 

and packing of cellular membranes induced by HCB may be the primary factor 

affecting the activity of essential bilayer-associated enzymes. Overall these 

findings suggest that even small concentrations of HCB may determine important 

changes on cell metabolism with potential cascade effects on recruitment of this 

commercial species. 

Dewailly, E., P. Ayotte, et al. (2000). "Susceptibility to infections and immune status in 

Inuit infants exposed to organochlorines." Environ Health Perspect 108(3): 205-11. 
221

 We investigated whether organochlorine exposure is associated with the 

incidence of infectious diseases in Inuit infants from Nunavik (Arctic Quebec, 

Canada). We compiled the number of infectious disease episodes during the first 

year of life for 98 breast-fed and 73 bottle-fed infants. Concentrations of 

organochlorines were measured in early breast milk samples and used as 

surrogates to prenatal exposure levels. Immune system parameters were 

determined in venous blood samples collected from infants at 3, 7, and 12 

months of age. Otitis media was the most frequent disease, with 80. 0% of 

breast-fed and 81.3% of bottle-fed infants experiencing at least one episode 

during the first year of life. During the second follow-up period, the risk of otitis 

media increased with prenatal exposure to p,p'-DDE, hexachlorobenzene, and 

dieldrin. The relative risk (RR) for 4- to 7-month-old infants in the highest tertile of 

p, p'-DDE exposure as compared to infants in the lowest tertile was 1. 87 [95% 

confidence interval (CI), 1.07-3.26]. The RR of otitis media over the entire first 

year of life also increased with prenatal exposure to p,p'-DDE (RR, 1.52; CI, 

1.05-2.22) and hexachlorobenzene (RR, 1.49; CI, 1.10-2.03). Furthermore, the 

RR of recurrent otitis media ( [Greater/equal to] 3 episodes) increased with 

prenatal exposure to these compounds. No clinically relevant differences were 

noted between breast-fed and bottle-fed infants with regard to immunologic 

parameters, and prenatal organochlorine exposure was not associated with 

immunologic parameters. We conclude that prenatal organochlorine exposure 

could be a risk factor for acute otitis media in Inuit infants. 

D'Have, H., J. Scheirs, et al. (2007). "Non-destructive pollution exposure assessment in 

the European hedgehog (Erinaceus europaeus): IV. Hair versus soil analysis in 

exposure and risk assessment of organochlorine compounds." Environ Pollut 145(3): 

861-8. 

 Few ecotoxicological studies on mammals use non-destructive methodologies, 

despite the growing ethical concern over the use of destructive sampling 

methods. In the present study we assessed exposure of hedgehogs (Erinaceus 

europaeus) to polychlorinated biphenyls (PCBs), dichloro-diphenyltrichloroethanes (DDTs), hexachlorocyclohexanes (HCHs) and 

hexachlorobenzene (HCB), by investigating concentrations of these compounds 

in soils and hedgehog hair from seven study sites around the urban area of 

Antwerp, Belgium. No relationships were observed between organochlorine 

compound concentrations in soils and hair from the different study areas. 

Furthermore, the individual variation of contamination levels in hair within study 

sites was high, especially for HCHs and HCB, and hair and soil had different 

relative profiles for PCBs, DDTs and HCHs. Our results show that concentrations 

of organochlorine compounds in soils alone are not predictive of the risk of these 

pollutants to hedgehogs and that tissue analyses are preferred to soil analyses in 

exposure and risk assessment studies. 

Domingo, J. L., M. Schuhmacher, et al. (2001). "Levels of metals and organic 

substances in blood and urine of workers at a new hazardous waste incinerator." Int 

Arch Occup Environ Health 74(4): 263-9. 
222

 OBJECTIVE: To assess baseline concentrations of a number of metals and 

organic compounds in blood and urine of 28 workers employed at a new 

hazardous waste incinerator (HWI), before operation of the plant. METHODS: 

Plasma analyses of hexachlorobenzene (HCB), polychlorinated biphenyls (PCB 

28, 52, 101, 138, 153 and 180), benzene, toluene, ethylbenzene, m-xylene, and 

polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) were carried 

out. The urinary levels of 2,4- and 2,5-dichlorophenol (DCPs), 2,4,5- and 2,4,6-

trichlorophenol (TCPs) and pentachlorophenol (PCP), as well as those of 1-

hydroxypyrene (1-HP) were also measured. Beryllium (Be), manganese (Mn), 

mercury (Hg) and lead (Pb) concentrations were determined in total blood, while 

the levels of arsenic (As), cadmium (Cd), chromium (Cr), nickel (Ni) and 

vanadium (V) were measured in urine. RESULTS: The levels of benzene, 

toluene, ethylbenzene and m-xylene were under their respective detection limits. 

The concentrations of HCB, PCBs and PCDD/Fs in plasma of the HWI workers, 

chlorophenols (CLPs) and 1-HP urinary concentrations, as well as those of 

metals in blood and urine are shown. PCDD/F concentrations in plasma of the 

new HWI workers ranged between 13.4 and 84.0 pg international toxic 

equivalents (I-TEQ)/g lipid, with a geometric mean value of 24.4 pg I-TEQ/g lipid. 

DISCUSSION: PCDD/F levels, as well as the concentrations of PCBs were of the 

same order of magnitude as those recently obtained for non- occupationally 

exposed populations of Catalonia (Spain). No significant gender differences were 

found for the levels of HCB, PCBs and PCDD/Fs. Although the present results 

showed a notable variability in the levels of CLPs, geometric mean values of 

these compounds were similar or even lower than those considered as potential 

reference values. Metal concentrations in blood and urine were also of the same 

order of magnitude than previously reported metal levels in the same area. 

CONCLUSION: The present results should be useful in future surveys in which 

internal exposure of the HWI workers will be determined. 

Donald, D. B., J. Syrgiannis, et al. (1999). "Delayed deposition of organochlorine 

pesticides at a temperate glacier." Environmental Science & Technology 33(11): 1794-

1798. 

 BIOSIS COPYRIGHT: BIOL ABS. Many of the organochlorine pesticides that 

were once widely used have either been banned or uses have been restricted in 

Canada and the United States. Near areas of high pesticide use at mid-latitudes 

in eastern North America, environmental levels of some of these pesticides 

peaked in the 1960s, and all have declined at least since the late 1970s. We 

determined depositional trends in a mid-latitude temperate glacier in Alberta, 

western Canada (52ˆ N, 117ˆ W). In contrast to trends in eastern Nor nd positive 

trend (r2 = 0.17, p < 0.03) was evident for hexachlorobenzene with maximum flux 

occurring in the 1990s. Lindane and chlordane had a distinct bimodal 

depositional pattern with peak concentrations occurring about 1960 and again in 

1989. Meltwater from glaciers may contribute high concentrations of pesticides to 

cold aquatic ecosystems for decades or centuries. 
223

Donaldson, G. M. and B. M. Braune (1999). "Sex-related levels of selenium, heavy 

metals, and organochlorine compounds in American white pelicans (Pelecanus 

erythrorhyncos)." Archives of Environmental Contamination and Toxicology 37(1): 110-

114. 

 BIOSIS COPYRIGHT: BIOL ABS. Liver tissue from male and female adult 

American white pelicans (Pelecanus erythrorhyncos) were individually analyzed 

for organochlorine compounds and trace elements. Levels of most 

organochlorines, specifically SIGMADDT, SIGMAPCB, SIGMAchlordane, 

SIGMAmirex, dieldrin, and SIGMACBz, were significantly higher in male pelicans 

compared to females. Only concentrations of SIGMAHCH were not significantly 

different between sexes. Male livers also contained higher concentrations of 

mercury, cadmium, an heir wintering areas may be influencing sex-related 

differences. 

Donaldson, G. M., J. L. Shutt, et al. (1999). "Organochlorine contamination in bald eagle 

eggs and nestlings from the Canadian Great Lakes." Archives of Environmental 

Contamination and Toxicology 36(1): 70-80. 

 BIOSIS COPYRIGHT: BIOL ABS. Unhatched eggs and plasma samples from 

prefledged bald eagles (Haliaeetus leucocephalus) from a recovering population 

in the Canadian Great Lakes Basin were contaminated with organochlorine 

compounds at levels comparable to those reported for eagle populations in 

several areas of the United States. PCBs were among the most commonly 

detected contaminants and occurred at high concentrations in plasma. Plasma 

PCB concentrations in Lake Erie nestlings were significantly higher than in chicks 

from Lake Nipigon (0.130 and 0.047 mg/kg wet weight, respectively). Blood 

levels of mirex were higher in nestlings from Lake Superior compared to those 

from Lake Erie (0.0012 and 0.0006 mg/kg wet weight, respectively). Migration 

routes and over-winter locations of avian prey that constitute a part of the bald 

eagle chick's diet are likely to contribute to these spatial contaminant patterns in 

plasma. Atmospheric deposition and a cold condensation effect for chlordane 

compounds may have 

Dvorska, A., G. Lammel, et al. (2008). "Kosetice, Czech Republic--ten years of air 

pollution monitoring and four years of evaluating the origin of persistent organic 

pollutants." Environ Pollut 156(2): 403-8. 

 The regional observatory Kosetice is a central European background station. 

Unique continuous monitoring from 1988 on is held here. POP (persistent 

organic pollutant) concentration values of air samples from Kosetice taken 

between 1996 and 2005 were statistically processed. Values of Czech ambient 

air quality standards were not exceeded. Concentrations of polycyclic aromatic 

hydrocarbons reached two maxima, in 1996 and 2001-2002. Polychlorinated 

biphenyls concentrations reached the highest values in 1997 and 1998 and 

hexachlorocyclohexanes concentrations in 1998. DDTs, hexachlorobenzene and 

pentachlorobenzene were analysed as well. Long-range transport of pollutants 

between 2002 and 2005 was evaluated using the Potential Source Contribution 

Function hybrid receptor model. Indicated potential source areas of PCBs 
224

coincide with many well-known urban and industrialised areas, while the 

indicated potential source areas of HCHs and DDTs coincide with many 

agricultural and/or forested regions and the potential source areas of HCB 

comprise all land use types. 

Edwards, F. G., E. Egemen, et al. (1999). "Ranking of Toxics Release Inventory 

chemicals using a Level III fugacity model and toxicity." Water Science and Technology

39(10-11): 83-90. 

 BIOSIS COPYRIGHT: BIOL ABS. In an effort to lessen the environmental impact 

of chemicals discharged by industry, some countries rank chemicals according to 

mass released each year and then set environmental protection policy based 

upon this ranking. These rankings have driven industries and companies to 

change their process configurations and their chemical releases to reduce the 

release of higher ranking chemicals. But, chemicals that are higher ranked due to 

mass release may not be particularly toxic nor persistent in the environment; 

conversely, lower ranked chemicals may be substantially more toxic and 

persistent in the environment. The physical/chemical properties of forty five 

organic chemicals from the EPA's Toxic Release Inventory were used as inputs 

to a Level III fugacity model to estimate fate, transport, and steady state 

concentrations of chemicals in the environment. The resulting concentrations in 

the air and water, for each chemical, were determined using the fugacity model 

and were then compared with toxicity data, the ratio was used as an indication of 

the environmental impact of the release of each chemical. The chemicals were 

then ranked according to the degree of environmental impact and the results 

were compared to other ranking systems reported in the literature. MH - 

ECOLOGY 

Elliott, J. E., C. J. Henny, et al. (1999). "Chlorinated hydrocarbons in livers of American 

mink (Mustela vison) and river otter (Lutra canadensis) from the Columbia and Fraser 

River basins, 1990-1992." Environmental Monitoring and Assessment 57(3): 229-252. 

 BIOSIS COPYRIGHT: BIOL ABS. We investigated chlorinated hydrocarbon 

contaminants in aquatic mustelid species on the Fraser and Columbia Rivers of 

northwestern North America. Carcasses of river otter (Lutra canadensis) (N=24) 

and mink (Mustela vison) (N=34) were obtained from commercial trappers during 

the winters of 1990-91 and 1991-92. Pooled liver samples were analyzed for 

organochlorine pesticides, polychlorinated biphenyls (PCBs), including non-ortho 

congeners, polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofuran 79 and 

1990-92. PCBs were present in all samples. PCB concentrations in otter livers 

collectedfrom the lower Columbia were ten-fold lower than measured a decade 

previously; nevertheless, a sample taken near Portland had a mean 

concentration of 1500 mug/kg, within a range of concentrations associated with 

reproductive effects in captive mink. Concentrations of 2,3,7,8-TCDD and TCDF 

were generally below detection limits, except for one otter collected near a pulp 

mill at Castlegar 
225

Environmental Protection Agency. Great Lakes National Program Office. Environment 

Canada (2005). Greak Lakes Binational Toxics Strategy Assessment of Level 1 

Substances, Summary, Govt Reports Announcements & Index (GRA&I), Issue 20, 

2006: 68. 

 Prepared in cooperation with Environment Canada, Toronto (Ontario). 

The Great Lakes Binational Toxics Strategy (GLBTS) was signed by the United States 

and Canada (the Parties) in 1997 to advance the goals of Article II(a) of the 

Great Lakes Water Quality Agreement (GLWQA). The Strategy focus has been 

on persistent toxic substances in the Great Lakes ecosystem, in particular those 

chemicals that bioaccumulate up the food chain. 

Environmental Protection Agency. Great Lakes National Program Office. Environment 

Canada (2006). Great Lakes Binational Toxics Strategy: Canada -- United States 

Strategy for the Virtual Elmination of Persistent Toxic Substances in the Great Lakes, 

Govt Reports Announcements & Index (GRA&I), Issue 20, 2006: 26. 

 Prepared in cooperation with Environment Canada, Toronto (Ontario). 

The Great Lakes Binational Toxics Strategy (GLBTS) was signed by the United States 

and Canada (the Parties) in 1997 to advance the goals of Article II(a) of the 

Great Lakes Water Quality Agreement (GLWQA). The Strategy focus has been 

on persistent toxic substances in the Great Lakes ecosystem, in particular those 

chemicals that bioaccumulate up the food chain. 

EU (2003). "[Regulation (EC) No. 304/2003 of the European Parliament and of the 

Council of 28 Jan. 2003 concerning the export and import of dangerous chemicals 

[European Union]]." Official Journal of the European Union Journal officiel de l'Union 

europé 46(L): 1-26. 

 This Regulation repeals and replaces Regulation 2455/92/EEC (see CIS 93-

1426) on the same topic. It concerns hazardous chemicals subject to the prior 

informed consent (PIC) procedure of the Rotterdam Convention, certain other 

hazardous chemicals banned or restricted within the EU or a Member State, and 

all chemicals when exported insofar as their classification, packaging and 

labelling is concerned (however, narcotics, radioactive substances, wastes, 

chemical weapons, foods and food additives, feeding stuffs, genetically modified 

organisms and medicinal products are on the whole excluded). Contents: 

definitions; designated national authorities; participation of the EU in the 

Convention; chemicals subject to export notification, PIC notification and PIC 

procedure; information and other requirements associated with the export and 

import of dangerous chemicals; technical assistance; monitoring and reporting. In 

annexes: lists of chemicals subject to the export notification procedure, qualifying 

for PIC notification and subject to the PIC procedure; notification requirements of 

banned or severely restricted chemicals; export notifications; list of chemicals 

subject to export ban (cosmetic soaps containing mercury, and the following 

persistent organic pollutants: aldrin, chlordane, dieldrin, DDT, endrin, heptachlor, 

hexachlorobenzene, mirex, toxaphene, PCBs). 
226

Fang, M. D., F. C. Ko, et al. (2008). "Seasonality of diffusive exchange of 

polychlorinated biphenyls and hexachlorobenzene across the air-sea interface of 

Kaohsiung Harbor, Taiwan." Sci Total Environ 407(1): 548-65. 

 Gaseous and dissolved concentrations of polychlorinated biphenyls (PCBs) and 

hexachlorobenzene (HCB) were measured in the ambient air and water of 

Kaohsiung Harbor lagoon, Taiwan, from December 2003 to January 2005. 

During the rainy season (April to September), gaseous PCB and HCB 

concentrations were low due to both scavenging by precipitation and dilution by 

prevailing southwesterly winds blown from the atmosphere of the South China 

Sea. In contrast, trace precipitation and prevailing northeasterly winds during the 

dry season (October to March) resulted in higher gaseous PCB and HCB 

concentrations. Instantaneous air-water exchange fluxes of PCB homologues 

and HCB were calculated from 22 pairs of air and water samples from Kaohsiung 

Harbor lagoon. All net fluxes of PCB homologues and HCB in this study are from 

water to air (net volatilization). The highest net volatile flux observed was +172 

ng m(-)(2) day(-1) (dichlorobiphenyls) in December, 2003 due to the high wind 

speed and high dissolved concentration. The PCB homologues and HCB fluxes 

were significantly governed by dissolved concentrations in Kaohsiung Harbor 

lagoon. For low molecular weight PCBs (LMW PCBs), their fluxes were also 

significantly correlated with wind speed. The net PCB and HCB fluxes suggest 

that the annual sums of 69 PCBs and HCB measured in this study were mainly 

volatile (57.4 x 10(3) and 28.3 x 10(3) ng m(-2) yr(-1), respectively) and 

estimated yearly, 1.5 kg and 0.76 kg of PCBs and HCB were emitted from the 

harbor lagoon surface waters to the ambient atmosphere. The average tPCB flux 

in this study was about one-tenth of tPCB fluxes seen in New York Harbor and in 

the Delaware River, which are reported to be greatly impacted by PCBs. 

Farrar, N. J., K. Prevedouros, et al. (2006). "Continental scale passive air sampling of 

persistent organic pollutants using rapidly equilibrating thin films (POGs)." Environ Pollut

144(2): 423-33. 

 A novel design of rapidly equilibrating passive air sampler was deployed at 38 

sites across 19 European countries to investigate short-term spatial variability of 

persistent organic pollutants (POPs). Devices were sealed in airtight containers 

to eliminate the possibility of contamination during transit and couriered to 

recipients with deployment instructions. Exposure times of 7days permitted the 

use of back trajectory analysis to further understand the factors responsible for 

influencing the large-scale spatial distribution of PCBs, PBDEs, PCNs, PAHs, 

lindane and HCB. Following sampler harvest, devices were sealed and returned 

for analysis. Comparison of sequestered levels showed that PAHs exhibited the 

greatest spatial variability (by a factor of 30) with higher levels often associated 

with greater population density. In contrast, HCB values were much more 

uniform, reflecting its well mixed distribution in the atmosphere. Spatial variation 

was strongly influenced by air mass origin, with lower levels being observed at 

most sites impacted by maritime air masses. 
227

Felipe-Sotelo, M., R. Tauler, et al. (2008). "Assessment of the environmental and 

physiological processes determining the accumulation of organochlorine compounds in 

European mountain lake fish through multivariate analysis (PCA and PLS)." Sci Total 

Environ 404(1): 148-61. 

 The presence of organochlorine compounds (OCs)-namely hexachlorobenzene 

(HCB), hexachlorocyclohexanes (HCH), polychlorobiphenyls (PCBs #28, 52, 

101, 118, 138, 153 and 180), dichlorodiphenyltrichloroethane (DDT) and 

dichlorodiphenyldichloroethane (DDE)-was examined in various fish tissues 

(muscle and liver) sampled in 23 mountain lakes in Europe. The dependence of 

these organochlorine compounds on geographical parameters (altitude, 

longitude, latitude and temperature) and physiological parameters (lipid content, 

age, weight and size) was assessed. Principal components analysis (PCA) and 

partial least squares (PLS) models were used for the analyses. PCA results 

showed that organochlorine compound concentrations in fish tissues increased 

with increasing altitude and decreasing temperatures. This trend appeared to be 

more marked for the less volatile compounds. Some differences were found 

between the muscle and liver in the effects of the percentage of lipids on the 

accumulation of organochlorine compounds and the behaviour of HCB. 

Moreover, PCBs tended to accumulate more in liver rather than in muscle. PCA 

scores clearly differentiated samples according to the lake of origin. PLS models 

confirmed that temperature and altitude were the main factors influencing the 

accumulation of most organochlorine compounds in the lipids of the fish tissue. 

Ferrante, M. C., T. Cirillo, et al. (2007). "Polychlorinated biphenyls and organochlorine 

pesticides in seafood from the Gulf of Naples (Italy)." J Food Prot 70(3): 706-15. 

 Seven target polychlorinated biphenyls (PCBs; IUPAC nos. 28, 52, 101, 118, 

138, 153, and 180) and the organochlorine pesticides (OCPs) 

hexachlorobenzene (HCB) and dichlorodiphenyltrichloroethane (DDT) and its 

related metabolites (p,p'-DDT, p,p'-DDE, and p,p'-DDD) were quantified in edible 

tissues from seven marine species (European hake, red mullet, blue whiting, 

Atlantic mackerel, blue and red shrimp, European flying squid, and 

Mediterranean mussel) from the Gulf of Naples in the southern Tyrrhenian Sea 

(Italy). PCBs 118, 138, and 153 were the dominant congeners in all the species 

examined. The concentrations of all PCBs (from not detectable to 15,427 ng g(-

1) fat weight) exceeded those of all the DDTs (from not detectable to 1,769 ng g(-

1) fat weight) and HCB (not detectable to 150.60 ng g(-1) fat weight) in the 

samples analyzed. The OCP concentrations were below the maximum residue 

limits established for fish and aquatic products by the Decreto Ministerale 13 May 

2005 in all the samples analyzed; therefore the OCPs in the southern Tyrrhenian 

Sea species are unlikely to be a significant health hazard. Conversely, the mean 

concentrations of PCBs exceeded (greatly in some cases) the current limits (200 

ng(-1) fat weight) set by the European Union for terrestrial foods. Although the 

manufacture and use of PCBs are banned or highly restricted, these compounds 

still are important persistent chemical contaminants in the Gulf of Naples. 
228

Fillmann, G., L. Hermanns, et al. (2007). "Accumulation patterns of organochlorines in 

juveniles of Arctocephalus australis found stranded along the coast of Southern Brazil." 

Environ Pollut 146(1): 262-7. 

 The present study was conducted to elucidate the specific distributions of 

organochlorine (OC) compounds in various tissues and organs of juveniles of the 

South American fur seal (Arctocephalus australis) found stranded on beaches in 

southern Brazil. The OC residue concentrations occurred in the following order: 

PCBs>DDTs>CHLs>HCHs>HCB. OC concentrations in blubber were higher than 

other tissues (e.g. PCBs, 2480 ng g(-1) wet weight; DDTs, 660 ng g(-1) wet 

weight) indicating a positive association with lipid content (except for HCB). 

However, the poor nutritional status of these animals, possibly following a 

starvation period, is likely to have allowed the remobilization of organochlorines 

stored in lipids to other tissues throughout the body, increasing their vulnerability 

to toxic effects and possibly affecting their survival capability. 

Fischer, L. J., M. A. Wagner, et al. (1999). "Potential involvement of calcium, CaM 

kinase II, and MAP kinases in PCB- stimulated insulin release from RINm5F cells." 

Toxicol Appl Pharmacol 159(3): 194-203. 

 Polychlorinated biphenyls (PCBs) are environmental contaminants that induce 

release of insulin in rat insulinoma cells, RINm5F (Fischer et al., Life Sci. (1996) 

59, 2041-2049). In the present study the mechanisms of this effect were 

investigated using noncytotoxic concentrations (10 microg/ml) of a PCB mixture, 

Aroclor-1254, and the pure PCB congeners 2,2',4,4'-tetrachlorobiphenyl and 

2,2',4,4',5, 5'- hexachlorobiphenyl. Treatment of RINm5F cells with each of these 

agents resulted in a rapid increase in intracellular free calcium. The presence of 

extracellular calcium was required for PCB-induced insulin release because 

removal of calcium from the medium attenuated the effect. In addition, 

pretreatment of RINm5F cells with the calcium channel blocker verapamil also 

blocked PCB-induced insulin release. To determine whether PCB-related insulin 

release could be associated with the enzyme, calcium/calmodulin-dependent 

kinase II (CaM kinase II), RINm5F cells were pretreated with the CaM kinase II 

inhibitor KN-93. PCB-induced insulin release was completely blocked by KN-93. 

Under similar treatment conditions, PCBs also induced the activity of mitogenactivated protein kinases (MAPK) 1 and 2. However, inhibition of MAPK 

activation by a specific inhibitor, PD-98059 (10.0 microM) did not prevent insulin 

release induced by PCBs. The results of the present investigation suggest a role 

for calcium and CaM kinase II in PCB- induced insulin release. Furthermore, the 

results suggest that insulin release by PCBs is independent of the activation of 

MAPKs. 

Fisher, B. E. (1999). "Most unwanted." Environ Health Perspect 107(1): 18-23. 

 Persistent organic pollutants (POPs) can travel thousands of miles, accumulate 

in the food chain, and persist in the environment, taking as long as centuries to 

degrade. POPs are known to play a role in birth defects, cancer, immune system 

dysfunction, and reproductive problems in wildlife. While the effects of POPs on 

human health are unclear, many researchers believe that long-term exposure 
229

contributes to increasing rates of birth defects, fertility problems, greater 

susceptibility to disease, diminished intelligence, and certain cancers. Twelve 

POPs have been identified by the United Nations Environment Programme as 

requiring urgent regulatory attention. They include the pesticides aldrin, 

chlordane, DDT, dieldrin, endrin, heptachlor, hexachlorobenzene, mirex, and 

toxaphene. Of the remaining three POPs, polychlorinated biphenyls are industrial 

products (used in electrical transformers), and dioxins and furans are 

unintentional by- products of industrial processes. 

Fitzgerald, E. F., S. A. Hwang, et al. (2001). "The association between local fish 

consumption and DDE, mirex, and HCB concentrations in the breast milk of Mohawk 

women at Akwesasne." J Expo Anal Environ Epidemiol 11(5): 381-8. 

 A study was conducted to assess the extent to which the consumption of local 

fish contaminated with p,p'-dichlorodiphenyl dichloroethylene (p,p'-DDE), mirex, 

and hexachlorobenzene (HCB) has impacted the concentrations of these 

compounds in the milk of nursing Mohawk women residing along the St. 

Lawrence River. From 1986 to 1992, 97 Mohawk women were interviewed, and 

each donated a one-time sample of at least 50 ml of breast milk. The comparison 

population consisted of 154 Caucasians from other rural areas in New York 

State. After adjustment for potential confounders, Mohawk mothers who gave 

birth from 1986 to 1990 had significantly higher geometric mean p,p'-DDE milk 

concentrations than did the control group, but no significant differences were 

observed from 1991 to 1992. In contrast, mirex was significantly elevated among 

the Mohawks throughout the study period, while HCB showed no difference at 

any point. Mohawk women with the greatest estimated cumulative lifetime 

exposure to p,p'-DDE from local fish consumption had a significantly higher 

geometric mean milk level of that compound relative to control women, but no 

differences in mirex or HCB concentrations in breast milk by local fish 

consumption were found. The reduction in breast milk p,p'-DDE concentrations 

among the Mohawk women from 1986 to 1990 parallels a corresponding 

decrease in local fish consumption, and may be the result of the advisories that 

have been issued over the past decade recommending against the consumption 

of local fish by pregnant and nursing Mohawk women. Elevations in the 

concentrations of mirex in the breast milk of the Mohawks are consistent with the 

fact that it is a common contaminant in the region and throughout the Lake 

Ontario-St. Lawrence River Basin. 

Fleischer, O., H. Wichmann, et al. (1999). "Release of polychlorinated dibenzo-p-dioxins 

and dibenzofurans by setting off fireworks." Chemosphere 39(6): 925-932. 

 BIOSIS COPYRIGHT: BIOL ABS. Selected pyrotechnic articles were set off 

under laboratory conditions. Residues and vapors of smoke as well as unburnt 

charges were analyzed for polychlorinated dibenzo-p-dioxins, dibenzofurans 

(PCDD) and their precursors chlorinated benzenes and phenols. The 

contamination of the selected products with these organic xenobiotics proved to 

be very variable. Remains of fireworks contained octachlorinated dioxins and 

furans up to 142 ng I-TEQ/kg as well as hexachlorobenzene in the range of 0.05 
230

t high temperatures during the deflagration of black powder charges could not 

suppress the formationof PCDD/F from appropriate precursors. 

Fomin, A., A. Paschke, et al. (1999). "Assessment of the genotoxicity of mine-dump 

material using the Tradescantia-stamen hair (Trad-SHM) and the Tradescantiamicronucleus (Trad-MCN) bioassays." Mutation Research. 426(2): 173-181. 

 BIOSIS COPYRIGHT: BIOL ABS. The Tradescantia-stamen hair (Trad-SHM) 

and -micronucleus (Trad-MCN) bioassays were used to determine the 

genotoxicity of two eluates derived from mine tailings. The goal was to test the 

suitability of the Tradescantia bioassays as screening tools for this kind of waste 

material. Leachates obtained using the current standard German leaching test 

methods (S4 eluate) as well as leachates obtained using a new eluation method 

(pHstat4) were tested and compared. Concentration of heavy metals in the p ed 

increased mutation rates when solutions containing more than 32% eluate were 

used. The low pH of the pHstat4 eluate was not responsible for the genotoxicity 

observed using both bioassays, as indicated by the lack of significant mutation 

rates in the nitric acid controls. This demonstrates that the Tradescantia 

bioassays can be used as tools to assess the genotoxic potential of 

environmental samples with a wide range of pH values, without the need for 

sample modification. 

Foster, W. G., E. V. Younglai, et al. (2004). "Mammary gland morphology in SpragueDawley rats following treatment with an organochlorine mixture in utero and neonatal 

genistein." Toxicological Sciences 77(1): 91-100. 

 In a related reproductive toxicology study designed to investigate the effects of in 

utero exposure to environmental toxicants and potential interaction with postnatal 

genistein, gross enlargement of thoracic mammary glands was observed in 

female offspring at 200 days of age. Therefore, the objective of this study was to 

analyze the effect of in utero exposure to a mixture of toxicants on mammary 

gland morphology. Time-mated Sprague-Dawley rats were treated on days 9-16 

of gestation with vehicle or a mixture of environmental toxicants at 1x the 

acceptable daily intake. Furthermore, it is unclear whether postnatal exposure to 

phytoestrogens in soy formulas poses breast cancer benefit or risk, and potential 

interactions with environmental toxicants are unknown. Therefore, half the female 

pups from each treatment group received either subcutaneous vehicle or 

genistein (10 microg/g body weight [bw]/day) on postnatal days 2-8. Following 

necropsy at 200 days of age, a pathologist, blinded to treatment groups, 

examined mammary gland histopathology. Only mild histological changes were 

found in mammary glands of rats exposed to the mixture in utero while 

pronounced ductal hyperplasia, lactational changes, and fibrosis were observed 

in mammary glands from the genistein group and were more prominent in the 

mixture + genistein group. Mammary glands of the control group were 

histologically normal. Collectively, our results reveal that postnatal exposure to 

pharmacological levels of genistein induces profound morphological changes in 

the mammary glands of adult female rats, and that high levels of phytoestrogens 

possess the potential to modulate the toxicological effects of toxicant mixtures. 
231

Gagne, F., M. Pardos, et al. (1999). "Toxicity evaluation of organic sediment extracts 

resolved by size exclusion chromatography using rainbow trout hepatocytes." 

Chemosphere 39(9): 1545-1570. 

 BIOSIS COPYRIGHT: BIOL ABS. The (geno)toxicity of sediment 

dichloromethane extracts and fractions obtained by size exclusion 

chromatography were evaluated to investigate effects based on size 

fractionation. In this study, three sediments were selected according to their 

incremental contamination in PAHs and in PCBs: Hamilton harbour, Toronto bay 

and lake St. Clair sediments. Heavy metals, total sulfur and elemental sulfur (S8) 

were also determined in the (un)fractionated sediment extracts. The liver cells 

were exposed to c mental sulfur (S8) accounted for 14-41% of extractable sulfur 

and were found to elute in the post-column volume (PCV) fraction despite its 

molecular weight of 256 amu. Heavy metals were found mainly in the HMW (i.e 

the > 2000 amu) fraction and LMW fractions and very few or none were observed 

in the PCV fractions. In sediment extracts, sublethal effects were present 

principally by the HMW and LMW fractions suggesting that some chemicals were 

also associated with high molecular weight compounds of s. Considering the 

cytotoxic responses, the best toxicity ranking in respect to contaminant levels in 

sediment extract was obtained with the LMW and PCV fractions which accounted 

for most of the toxic responses in the chromatographic fractions. Moreover, the 

shielding effect could be explained, in part, by the association of LMW 

contaminants to large macromolecules. 

Galarini, R., M. N. Haouet, et al. (2002). "Heavy metals, HCB and p,p'-DDE in Ictalurus 

melas Raf. from Trasimeno and Corbara lakes, Italy." Bull Environ Contam Toxicol

68(2): 230-6. 

 

Gan, P., Y. Fan, et al. (2001). "[Experiment of biodegradation of chlorobenzenes]." 

Huan Jing Ke Xue 22(3): 93-6. 

 Four strains of microorganisms which were able to grow at the presence of 1,4-

dichlorobenzene 1,2,4-trichlorobenzene and hexachlorobenzene were isolated 

from the sludge collected from two different sites after incubating about 2 

months. During the growth of the mixed microorganisims on chlorobenzenes, the 

accumulating consumption of oxygen, the microbial population curve and the 

concentration of released Cl- were investigated. The result showed that the 

mixed microorganisms were able to utilize 1,4-dichlorobenzen and 1,2,4- 

trichlorobenzene as sole carbon source and energy source. The concentration of 

released Cl- may depend strongly on the activity of the living cells. The order in 

which the chlorobenzenes were readily degraded was 1,4-

dichlorobenzenez[356.7 micrograms/(L.d)] > 1,2,4- trichlorobenzene[110.4 

micrograms/(L.d)] > hexachlorobenzene[approximately 6 micrograms/(L.d)]. The 

number of the substituted chlorine on the chlorobenzenes directly resulted in the 

resistance to biodegradation. 
232

Gao, X., W. Wang, et al. (2009). "Dechlorination reaction of hexachlorobenzene with 

calcium oxide at 300-400 degrees C." J Hazard Mater. 

 Hexachlorobenzene (HCB) was thermally treated with calcium oxide (CaO) at 

300-400 degrees C. Analyses of chloride ions and residual HCB confirmed that a 

dechlorination reaction had occurred. The dechlorination mechanism was 

investigated with a series of analytical methods including X-ray fluorescence 

(XRF), X-ray diffraction (XRD), Raman spectroscopy, and X-ray photoelectron 

spectroscopy (XPS). The final products detected were CaCO(3) by XRD and 

Raman spectroscopy, amorphous carbon by Raman spectroscopy, and CaCl(2) 

by XPS. The newly produced species of CaCO(3) and amorphous carbon were 

thought to be the ultimate fate of the C element of HCB. After identification of the 

final dechlorination products, we can conclude that the reaction of HCB with CaO 

at 300-400 degrees C is through a dechlorination/polymerization pathway, which 

is induced by electron transfer. An overall reaction formula for HCB reaction with 

CaO was proposed and was energetically quite favorable. The results are helpful 

for the further comprehension of the reaction mechanism for thermal 

dechlorination of PCDD/Fs in CaO rich matrices. 

Gerhard, I., B. Monga, et al. (1999). "Chlorinated hydrocarbons in infertile women." 

Environmental Research 80(4): 299-310. 

 BIOSIS COPYRIGHT: BIOL ABS. This study was conducted to investigate the 

hypothesis that chlorinated hydrocarbons (CHC) may affect fertility in women. In 

489 infertile women, CHC levels were measured in whole blood. Different 

anamnestic and clinical parameters were obtained or investigated in order to 

detect possible associations to CHC concentrations. CHC levels were correlated 

to the women's age, body mass index, and nationality. Especially in women with 

uterine fibroids, endometriosis, miscarriages, persistent infertilit 

Glynn, A. W., K. Michaelsson, et al. (2000). "Organochlorines and bone mineral density 

in Swedish men from the general population." Osteoporos Int 11(12): 1036-42. 

 Persistent organochlorines (POCs), such as polychlorinated biphenyls (PCBs) 

and DDT, are present at relatively high concentrations in food and show 

estrogenic, anti-estrogenic or anti-androgenic activity in biological test systems. 

Because bone mineral density (BMD) in men is influenced by sex hormones, we 

looked for associations between BMD and serum concentrations of POCs in 115 

men (mean age 63 years, range 40-75 years) from the general Swedish 

population. Ten PCB congeners, five DDT isomers, hexachlorobenzene, three 

hexachlorocyclohexane isomers, trans- nonachlor and oxychlordane were 

analyzed by gas chromatography. Quantitative bone measurements were 

performed by dual-energy X-ray absorptiometry at three sites: whole body, the 

L2-L4 region of the lumbar spine, and the neck region of the proximal femur, as 

well as by quantitative ultrasound on the left os calcis (broadband ultrasound 

attenuation (BUA) and speed of sound (SOS)). After adjustment for confounding 

factors in linear regression analyses we found no strong association between 

serum concentrations of single POCs and the five BMD and ultrasound variables. 

When POCs were grouped according to hormonal activity (estrogenic, anti-
233

estrogenic, anti-androgenic) and the study subjects were divided into 

organochlorine concentration quartiles, a weak association was indicated 

between increased serum concentrations of p,p'-DDE (antiandrogenic) and 

decreased BMD, BUA and SOS. This may suggest that p,p'-DDE could cause 

negative effects on bone density, but the findings might also be due to chance 

since multiple comparisons were made in the statistical analysis. Overall our 

results do not suggest that the studied POCs caused major effects on bone 

density in our study group. 

Glynn, A. W., L. Wernroth, et al. (2000). "PCB and chlorinated pesticide concentrations 

in swine and bovine adipose tissue in Sweden 1991-1997: spatial and temporal trends." 

Sci Total Environ 246(2-3): 195-206. 

 Results from the Swedish control programme regarding organochlorines in food 

were used to determine time trends of organochlorine concentrations in adipose 

tissues from swine (4-8 months old) and bovines (non-dairy, 12-36 months) 

slaughtered between 1991 and 1997. Moreover, possible regional differences in 

concentrations were studied, as well as differences in concentrations depending 

on sex and age of the slaughtered animals. Multiple linear regression indicated 

that the concentrations of PCB, p,p'-DDE, HCB and alpha-HCH decreased by 4-

17% per year, suggesting that the decline in organochlorine concentrations in the 

Swedish environment and biota reported during the 1970s-1990s also has 

occurred in meat-producing animals during the 1990s. The concentrations of 

PCB, DDE and HCB in bovines and PCB and DDE in swine were 1.4-3.8-fold 

higher in the southern parts of Sweden than in the northern parts of the country, 

indicating a regional difference in exposure of the animals. The organochlorine 

concentrations were higher in bovines than in swine, and declined faster in swine 

than in bovines. Moreover, the concentrations of CB 153 and p,p'-DDE were 

similar in bovines, but in swine the average concentrations of the two compounds 

differed two-fold. Apart from possible species differences in metabolism of 

organochlorines, this may be due to differences in the age at slaughter between 

swine and bovines, and differences in husbandry of the animals. In the latter 

case, swine are generally kept inside during their whole life span, whereas 

bovines are kept outside grazing during the summer period. Finally, a sexdependent difference in concentrations was indicated in swine, but not in 

bovines. Our study shows that a lot of information can be 'extracted' from control 

program results. 

Gomez-Gutierrez, A., E. Garnacho, et al. (2007). "Assessment of the Mediterranean 

sediments contamination by persistent organic pollutants." Environ Pollut 148(2): 396-

408. 

 A compilation of information about levels of selected persistent organic 

pollutants, namely polychlorinated biphenyls (PCBs), 

dichlorodiphenyltrichloroetane and its degradation products (DDTs) and 

hexachlorobenzene (HCB), in Mediterranean sediments, including data published 

from 1971 to 2005, has been conducted in order to assess their main drivers and 

pressures in the environment. The application of mapping tools (GIS) and 
234

statistical instruments enabled the assessment of geographical and temporal 

trends. Chemical contamination mainly originates from land-based sources, and 

decreases significantly when moving off-shore. Contamination hot spots are 

generally located along the Northern coastline. The data for open sea sediments 

enabled the establishment of background levels of contamination for the region. 

A decreasing temporal trend in concentrations was found, more evident in the 

case of DDTs probably due to a more efficient regulation of this chemical. Finally, 

some gaps in reliable data were also identified which were related to the lack of 

information in the southern and eastern parts of the Mediterranean as well as the 

variety of analytical methodologies used. 

Gomez-Gutierrez, A. I., E. Jover, et al. (2006). "Organic contaminant loads into the 

Western Mediterranean Sea: estimate of Ebro River inputs." Chemosphere 65(2): 224-

36. 

 Annual input estimates for several organic contaminants from the Ebro River into 

the Northwestern Mediterranean Sea were carried out on the basis of monthly 

sampling from November 2002 to October 2003. Some organochlorine 

compounds (DDT and its degradation products, DDD and DDE, PCBs (9 

congeners), HCB and gamma-HCH) were selected due to their reported 

occurrence in the river. Furthermore, some polar pesticides used in the Ebro 

Delta were also determined (atrazine, simazine, diazinon, fenitrothion and 

molinate). Concentrations ranged from 0.4 to 19.5 ng l(-1) for the organochlorine 

compounds (sum of particulate and dissolved phases) and from not detected 

(ND) to 170 ng l(-1) for the more polar pesticides, which were only found in the 

dissolved phase. The sum of PCB congeners (mean 8.9 ng l(-1)) showed the 

highest concentrations among the organochlorine compounds and atrazine 

(mean 82 ng l(-1)) among the polar pesticides. Based on the contaminant 

concentrations and on hydrological data, contaminant discharges into the sea 

were estimated amounting in total to 167 and 1,258 kg year(-1) of organochlorine 

compounds and polar pesticides, respectively. Furthermore, it was observed that 

PCBs, DDTs and HCB inputs were basically influenced by spate periods due to 

an increase in suspended particulate matter associated to runoff and sediment 

resuspension. Whereas for more water soluble contaminants, such as the 

agrochemicals, their seasonal use had a higher incidence in contaminant fluxes. 

Bulk chemical parameters such as SPM, DOC, POC, %OC, %ON and C/N ratio 

provided additional information on the organic matter sources. This provides a 

better understanding of the temporal variability of the contaminant 

concentrations. 

Gouin, T., D. Mackay, et al. (2004). "Evidence for the "grasshopper" effect and 

fractionation during long-range atmospheric transport of organic contaminants." Environ 

Pollut 128(1-2): 139-48. 

 Although there is indisputable evidence that long-range atmospheric transport 

(LRAT) of organic contaminants occurs on a global scale, uncertainties remain 

about the detailed mechanism and extent of this phenomenon as well as the 

physical-chemical properties which facilitate LRAT. In this study, we discuss how 
235

mass balance models and monitoring data can contribute to a fuller 

understanding of the mechanism and extent of LRAT. Specifically we address 

the issues of "grasshopping" or "hopping" (the extent to which molecules are 

subject to multiple hops as distinct from a single emission-deposition event) and 

"global fractionation" (the differing behavior of chemicals as they are 

transported). It is shown that simple mass balance models can be used to assist 

the interpretation of monitoring data while also providing an instrument that can 

be used to assess the LRAT potential and the extent of hopping that organic 

substances may experience. The available evidence supports the notion that 

many persistent organic pollutants experience varying degrees of "hopping" 

during their environmental journey and as a consequence become fractionated 

with distance from source. 

Grace, D. (2009). "Errant corporations, diffuse responsibilities, and the environment: 

ethical issues in the Orica case study." J Environ Manage 90(4): 1622-7. 

 The papers in this volume deal with various aspects of the HCB legacy at the 

Orica plant at Botany. Whether explicitly or implicitly, they are concerned with 

questions of ethics; with the just distribution of burdens and benefits; with just 

processes for disposing of dangerous industrial waste; and with a just 

custodianship of the Botany environment. These ethical issues illustrate the 

difficulty of securing corporate accountability, and the elusiveness of 

responsibility within organisations. This paper reflects on some of the issues for 

ethics raised by the Orica case and their significance for corporate ethics. 

Gregoraszczuk, E. L., K. Milczarek, et al. (2008). "Steroid secretion following exposure 

of ovarian follicular cells to three different natural mixtures of persistent organic 

pollutants (POPs)." Reproductive Toxicology 25(1): 58-66. 

 This study investigated in vitro endocrine disrupting effects of three mixtures of 

POPs: 'Marine mix' extracted from Atlantic cod liver, and two mixtures extracted 

from burbot liver, 'Mjosa mix' and 'Losna mix'. The POP mixtures were chemically 

characterized. Co-culture of theca and granulosa cells, were exposed for 48h 

with different doses of 'Marine mix', 'Mjosa mix' or 'Losna mix'. As an end point 

cell viability was determinated by LDH test, steroid analysis by EIA and caspase3 by colorimetric substrate. Chemical characterization of the mixtures 

demonstrated that the 'Marine mix' contained high levels of DDTs and PCBs. In 

the 'Mjosa mix', the dominant pollutants were BDEs and HBCD. The 

concentrations of POPs measured in the 'Losna mix' were considerably lower. All 

mixtures used in the present study had a stimulatory effect on testosterone and 

estradiol secretion with 'Marine mix'>'Mjosa mix'>'Losna mix'. These results show 

that even a mixture containing background concentrations of POPs significantly 

affected steroid secretion. A higher steroidogenic response in low dose ranges, 

compared with high dose ranges indicated xenobiotic-conditioning hormesis. This 

could complicate predictions of effects in risk assessments. 

Grimalt, J. O., P. Fernandez, et al. (2001). "Trapping of organochlorine compounds in 

high mountain lakes." ScientificWorldJournal 1: 609-11. 
236

 High mountain areas have recently been observed to be polluted by 

organochlorine compounds (OC) despite their isolation. These persistent 

pollutants arrive at these remote regions through atmospheric transport. 

However, the mechanisms involving the accumulation of these compounds from 

the atmospheric pool to the lacustrine systems still need to be elucidated. These 

mechanisms must be related to the processes involving the transfer of these 

pollutant from low to high latitudes as described in the global distillation effect. 

Grochowalski, A., C. Lassen, et al. (2007). "Determination of PCDDs, PCDFs, PCBs 

and HCB emissions from the metallurgical sector in Poland." Environ Sci Pollut Res Int

14(5): 326-32. 

 BACKGROUND: The aim of the project was to measure the actual emissions of 

PCDD/F, PCBs and HCB from 20 selected metallurgical installations in Poland, 

in order to update the national inventory of dioxin emission from metallurgical 

industry for developing a strategy for dioxins and furans emission abatement 

from the subject facilities (UNEP 2005). METHODS: Sampling methodology used 

in this work was developed at the Cracow University of Technology because of 

the complexity of simultaneous sampling and determining PCDFs, PCDDs, PCB 

and HCB. For the determination a GC-MS/MS system was used. RESULTS AND 

DISCUSSION: Results from the work indicate that the highest dioxins and PCB 

concentrations were recorded for iron ore sintering plants at 1.10-1.32 ng total1 

TEQ/Nm3 followed by aluminium scrap melting at 0.03-0.66 ng total TEQ/Nm3. 

The highest HCB concentrations at 613-1491 ng/Nm3 were also recorded fo iron 

ore sintering plants, whereas at aluminium plants the HCB concentrations were 

in the range of only 10.1-22.7 ng/Nm3. CONCLUSIONS: The above 

investigations indicate that secondary aluminium production is the most 

significant dioxins source, if calculated as emission factor values. However, iron 

ore sintering plants are operating at much higher production capacity, causing 

this process to become the major source of dioxins, PCB and HCB pollution to 

the atmosphere in Poland. RECOMMENDATIONS AND PERSPECTIVES: 

Based on the performed tests and the environmental reviews of selected plants 

several recommendations were formulated for the reduction of generation or of 

emission of these pollutants from iron ore sintering plants, electric arc furnace 

steel production processes, hot-blast furnace operations, secondary aluminium 

smelting and primary zinc production from zinc cathodes. 

Guerzoni, S., P. Rossini, et al. (2007). "POPs in the Lagoon of Venice: budgets and 

pathways." Chemosphere 67(9): 1776-85. 

 Dioxins and furans (PCDD/Fs), polychlorobiphenyls (PCBs) and 

hexachlorobenzene (HCB) in the ecosystem of the Lagoon of Venice were 

studied, in order to provide a general picture of conditions in the lagoon in terms 

of contamination by persistent organic pollutants (POPs). We present here novel 

data on atmospheric deposition, water, sediment and clam samples collected in 

the lagoon during the period January 2001-December 2004. Atmospheric 

deposition was sampled monthly at six sites located both close and far from large 

industrial and urban sources. Water samples were collected monthly from fifteen 
237

stations, and twenty-five samples of sediments and clams (Tapes philippinarum) 

were collected in four areas where clams are farmed and harvested inside the 

lagoon. All samples were analysed for PCDD/Fs, PCBs and HCB by 

HRGC/HRMS in the same laboratory. All samples examined (atmospheric 

deposition and water) substantially confirmed the spatial pattern reported in 

previously published data on sediments and atmospheric deposition: the zone 

surrounding the Porto Marghera petrochemical plant always had the highest 

levels of POPs (i.e., PCDD/Fs: atmosphere approximately 6 pg of 2,3,7,8-TCDD 

equivalents (I-TE) m(-2)d(-1); water 0.37 pg I-TEl(-1); sediment: 300 ng kg(-1); 

clam 2.8 pg I-TE g(-1)), and the minima were found at points on the margins of 

the lagoon (PCDD/Fs: atmosphere approximately 1 pg I-TEm(-2)d(-1); water 0.05 

pg I-TEl(-1); sediment: approximately 5 ng kg(-1); clam approximately 0.2 pg I-TE 

g(-1)). Intermediate values were often encountered in the historical city centre of 

Venice and in the central part of the lagoon. To confirm this, new data on 

correlation between levels of PCDD/F in sediments and clams are reported, both 

for absolute values and for the PCDD/F "fingerprint". There is always a clear 

fingerprinting signature (PCDF/PCDD>1) for samples collected near Porto 

Marghera, and the opposite (PCDF/PCDD<1) in the rest of the lagoon. 

Guillette, L. J., Jr., J. W. Brock, et al. (1999). "Serum concentrations of various 

environmental contaminants and their relationship to sex steroid concentrations and 

phallus size in juvenile American alligators." Archives of Environmental Contamination 

and Toxicology 36(4): 447-455. 

 BIOSIS COPYRIGHT: BIOL ABS. Recent studies have reported a number of 

abnormalities in the hatchling and juvenile alligators of Lake Apopka, FL (USA). 

These abnormalities include modifications of plasma concentrations of sex 

steroids in males and females as well as abnormalities in gonadal morphology, 

gonadal enzyme activity, and steroidogenesis. Embryonic exposure to 

environmental contaminants in the eggs has been hypothesized to be the causal 

agent for these changes. However, posthatchling exposure can also contribute to 

, dieldrin, endrin, mirex, oxychlordane, SIGMADDTs, and SIGMAPCBs compared 

to juveniles from the other lakes. Further, we observed no correlations between 

serum contaminant concentrations and sex steroid concentrations (estradiol17beta and testosterone). However, serum testosterone was significantly lower in 

males from Lake Apopka and Orange Lake compared to Lake Woodruff NWR. 

We did not observe relationships between phallus size or other body parameters 

and serum contaminant le 

Gunatilleka, A. D. and C. F. Poole (1999). "Models for estimating the non-specific 

aquatic toxicity of organic compounds." Analytical Communications 36(6): 235-242. 

 BIOSIS COPYRIGHT: BIOL ABS. The solvation parameter model is used to 

construct models for estimating the non-specific aquatic toxicity of organic 

compounds to the fathead minnow, guppy, golden orfe, water flea and the 

prokaryote Vibrio fischeri. Size is the characteristic solute property promoting 

toxicity and solute hydrogen-bond basicity in reducing it. Interspecies differences 

in toxicity result from differences in the above properties and also because of 
238

significant differences in the hydrogen-bond basicity and dipolar ies, such as the 

tadpole and guppy. 

Gustafson, D. L., M. E. Long, et al. (2000). "Comparative hepatocarcinogenicity of 

hexachlorobenzene, pentachlorobenzene, 1,2,4,5-tetrachlorobenzene, and 1,4- 

dichlorobenzene: application of a medium-term liver focus bioassay and molecular and 

cellular indices." Toxicol Sci 53(2): 245-52. 

 Of the twelve different chlorobenzene isomers, a thorough evaluation of 

carcinogenicity has only been assessed on monochlorobenzene, 1,2-, and 1,4-

dichlorobenzene, and hexachlorobenzene. In the studies presented here, we 

measured the ability of 1,4-dichlorobenzene (DCB), 1,2,4,5- tetrachlorobenzene 

(TeCB), pentachlorobenzene (PeCB), and hexachlorobenzene (HCB) to promote 

glutathione S-transferase pi (GSTP1- 1) positive preneoplastic foci formation in 

rat liver, following diethylnitrosamine (DEN) initiation. The results from these 

studies show that TeCB, PeCB, and HCB all promote the formation of GSTP1-1 

positive foci and that DCB does not. The numbers and area of foci were greatest 

following HCB promotion, and TeCB and PeCB were approximately equal in their 

promoting ability. Levels of hepatic CYP1A2, CYP2B1/2, non-focal GSTP1-1, 

and c-fos were measured in response to treatment with the 4 chlorobenzene 

isomers, as were reduced glutathione (GSH) and oxidized glutathione (GSSG) 

levels. Results from these studies show that induction of CYP1A2 and CYP2B1/2 

have correlation with both the presence and degree of GSTP1-1 foci promotion 

by the 4 chlorobenzenes. Alterations in GSH and GSSG levels were similar in 

PeCB- and TeCB- treated animals in that GSSG levels were significantly 

decreased, whereas HCB and DCB did not have this effect, although HCB 

treatment led to a significant increase in GSH levels. We conclude that induction 

of CYP1A2 or CYP2B1/2 by chlorobenzene isomers may indicate promotional 

ability, and that this property might be exploited to predict the 

hepatocarcinogenicity of other chlorobenzene isomers. 

Gutleb, A. C., I. A. T. M. Meerts, et al. (2005). "T-Screen as a tool to identify thyroid 

hormone receptor active compounds." Environmental Toxicology and Pharmacology

19(2): 231-238. 

 The T-Screen represents an in vitro bioassay based on thyroid hormone 

dependent cell proliferation of a rat pituitary tumor cell line (GH3) in serum-free 

medium. It can be used to study interference of compds. with thyroid hormone at 

the cellular level, thus bridging the gap between limitations of assays using either 

isolated mols. (enzymes, transport proteins) or complex in vivo expts. with all the 

complex feedback mechanisms present. Compds. are tested both in the absence 

and presence of thyroid hormone (EC50 concn. of T3) to test for both agonistic 

and antagonistic potency. Thyroid hormones (3,3'-5-triiodothyronine: T3 and 

3,3',5,5'-tetraiodothyroxine: T4) and compds. resembling the structure of thyroid 

hormones (3,3'-5-triiodothyroacetic acid: Triac; 3,3',5,5'-tetraiodothyroacetic acid: 

Tetrac) induced cell growth, with the rank order Triac > T3 > Tetrac > T4 (relative 

potency = 1.35>1 > 0.29>0.07), which is identical to published affinities of these 

compds. for nuclear thyroid hormone receptors. Exposure to 5,5'-
239

diphenylhydantoin (DPH) in the presence of 0.25 nM T3 resulted in up to 60% 

decreased cell growth at 200 ?M DPH. No effect of DPH on basal metabolic 

activity of GH3 cells was obsd. at this concn. Fentinchloride (IC50 = 21 nM) 

decreased cell growth induced by 0.25 nM T3, whereas parallel exposure to 

these concns. in the absence of T3 did not alter basal metabolic activities of GH3 

cells. Apolar sediment exts. from the Dommel (34%) and Terneuzen (14%) 

decreased cell growth in the presence of 0.25 nM T3, whereas the ext. from 

Hoogeveen increased cell growth (26%) and the ext. from North Sea Channel 

had no effect. The T-Screen proved to be a fast and functional assay for 

assessing thyroid hormone receptor active potencies of pure chems. or 

environmental mixts. 

Hall, A. J., C. D. Duck, et al. (1999). "Organochlorine contaminants in Caspian and 

harbour seal blubber." Environmental Pollution (Series A). Ecological and Biological

106(2): 203-212. 

 BIOSIS COPYRIGHT: BIOL ABS. Organochlorine contaminants (pesticides and 

individual polychlorinated biphenyl congeners, PCBs) were measured in Caspian 

(Phoca caspica) seal blubber and compared with concentrations in Harbour 

(Phoca vitulina) seal blubber. Concentrations of total 

dichlorodiphenyltrichloroethane (DDT) and its metabolites were significantly 

higher in Caspian seal than Harbour seal samples, whereas PCB congeners 

were significantly higher in Harbour than Caspian seals. Our finding suggests 

that Caspian seals are 

Hardell, E., M. Eriksson, et al. (2001). "Case-control study on concentrations of 

organohalogen compounds and titers of antibodies to Epstein-Barr virus antigens in the 

etiology of non-Hodgkin lymphoma." Leuk Lymphoma 42(4): 619-29. 

 A rapid increase in incidence of non-Hodgkin lymphoma (NHL) has been 

reported from many countries. Exposure to certain pesticides and 

organochlorines has been shown to be risk factors. Epstein-Barr virus (EBV) is a 

human herpesvirus that has been associated with some subgroups of NHL, such 

as Burkitt lymphoma and lymphomas related to severe immunosuppression. In 

this study, we measured lipid adjusted blood concentrations of 36 congeners of 

polychlorinated biphenyls (PCBs), p,p'-dichlorodiphenyl-dichloroethylene (p,p'-

DDE), hexachlorobenzene (HCB), four different subgroups of chlordanes (transnonachlordane, cis-nonachlordane, MC6 and oxychlordane) and 2,2',4,4'- 

tetrabrominated diphenyl ether (TBDE) in incident cases of NHL and controls 

from the general population. Titers of antibodies to the Epstein-Barr early antigen 

(EA) were correlated to concentrations of organochlorines. We found a significant 

difference in lipid adjusted blood concentrations of total PCBs and TBDE 

between cases and controls. Titers of antibodies to EA IgG > 80 were correlated 

to an increased risk for NHL with odds ratio (OR) = 1.9, 95% confidence interval 

(CI) =0.94-3.8. This risk was further increased in those with a level above the 

median value of "sum of PCBs" (OR=4.0, CI=1.2-14), HCB (OR=5.3, CI=1.6-19), 

sum of chlordanes (OR=4.0, CI=1.2-14) and TBDE (OR=21, CI=4.6-124), 

suggesting an interaction between EBV and a higher concentration of these 
240

chemicals. Also for the "sum of immunotoxic PCBs" increased risk was found in 

that group (OR=6.4, CI=1.9-24). Subdivision of NHL in histological types yielded 

highest risks for low- grade B-cell NHL. 

Hardell, L., G. Lindstrom, et al. (2002). "Is DDT exposure during fetal period and breastfeeding associated with neurological impairment?" Environ Res 88(3): 141-4. 

 The concentration of certain persistent organic pollutants was determined in a 

family including both parents and one son with neurological impairment 

suggested to be Attention Deficit-Hyperactivity Disorder (ADHD). For comparison 

control subjects from other ongoing studies were used. They were of the same 

sex and age group as the respective family member. For polychlorinated 

biphenyls, hexachlorobenzene, and chlordanes similar results were found in the 

study groups. The concentration of DDE, the main metabolite of DDT, was 

increased in the mother, 782 ng/g lipid, compared with mean 403, median 259 

(range 51-1354) for the female controls. Also, the son had an increased 

concentration of 259 ng/g lipid, compared with mean 104, median 72 (range 46-

349) for controls. A low concentration was found in the father, 127 ng/g lipid. As a 

child and as a teenager to the age of 17, the mother was exposed to DDT in her 

home environment. We discuss the potential of fetal and breast-feeding exposure 

of the son. Neurodevelopmental impairment has been reported for dioxins and 

PCBs, but DDT seems to have been less investigated in this respect. 

Hauser, B. and P. Popp (1999). "Membrane extraction combined with 

thermodesorption/gas chromatography and mass selective detection for the analysis of 

volatile organic compounds in water." Journal of High Resolution Chromatography and 

Chromatography Communications: HRC & CC|Journal of High Resolution 

Chromatography and Chromatography Communications 22(4): 205-212. 

 BIOSIS COPYRIGHT: BIOL ABS. The range of application of a commercial 

thermodesorption-cryo-focussing unit connected to a gas chromatograph/mass 

selective detector was extended to water analysis by using it in conjunction with 

membrane extraction. A flow of nitrogen passes through a silicone hollow fiber 

immersed in the water sample and extracted volatile organic compounds are 

enriched in a sorption tube mounted on top of the extraction cell. The sorption 

tube is then placed in the thermodesorption unit and analyzed by GC ts were 

found to be 0.02-0.1 mug/L for cis/trans-1,2-dichloroethene, benzene, 

trichloroethene, chlorobenzene, bromobenzene, ethylbenzene, 1,1,2,2-

tetrachloroethane, and 1,2/1,4-dichlorobenzene. The method was found to be 

suitable for compounds with boiling points up to 220ˆC as memory effects 

increased considerably from dichloro- to hexachlorobenzene. Highly 

contaminated groundwater samples were analyzed. Quantitative results 

corresponded well with those achieved with conventional 

Hellstrom, A., H. Kylin, et al. (2004). "Distribution of some organochlorine compounds in 

pine needles from Central and Northern Europe." Environ Pollut 128(1-2): 29-48. 

 Levels of selected organochlorine compounds in pine needles were measured in 

two sampling series. The first series collected in 1989 covered Southern 
241

Germany to Northern Scandinavia, and the second collected in 1990 covered 

Czechoslovakia to Estonia. The levels of alpha-hexachlorocyclohexane (alphaHCH) and hexachlorobenzene (HCB) were relatively uniform throughout Europe, 

while the levels of gamma-hexachlorocyclohexane (gamma-HCH) and the DDT 

group show higher levels in the southern parts of the investigated area. The 

deposition patterns of all compounds except alpha-HCH indicate a dependence 

on fresh release from diffuse or point sources rather than global fractionation. 

The analytes accumulate in the needles until senescence starts and, generally, 

the oldest needles have the highest concentrations. The accumulation rate of the 

analytes in mountain pine needles is about half that of Scots pine needles 

indicating the importance of species differences. 

Henry, T. R. and S. P. Bradbury (1999). "Fish tissue residue-based toxicity reference 

values for chlordane, DDT, dieldrin, endrin, hexachlorobenzene, mercury, and PCBS for 

piscivorous wildlife." 218th National Meeting of the American Chemical Society, Parts 1 

and 2, New Orleans, Louisiana, USA, August 22-26, 1999.Yabstracts of Papers 

American Chemical Society; 218 (1-2).1999.Agro 122. 218(1-2). 

 Biosis copyright: biol abs. rrm fish tissue residue-based toxicity reference values 

for chlordane, ddt, dieldrin, endrin, hexachlorobenzene, mercury, and pcbs for 

piscivorous wildlifeymeeting abstract belted kingfisher river otter mink 

bioindicator pollution toxicology environmental monitoring environmental 

contamination chlordane pesticide pollutant tissue residue toxicity reference 

values ddt dieldrin endrin hexachlorobenzene mercury heavy metal pcbs 

polychlorinated biphenyls freshwater ecology risk assessment water quality great 

lakes north america mh - congresses 

Henschler, R., K. E. Appel, et al. (2001). "Proliferation and differentiation of murine 

haemopoietic progenitor cells in stroma-free culture in the presence of metabolites of 

chlorinated pesticides." Toxicol In Vitro 15(1): 31-7. 

 We have studied the influence of metabolites of chlorinated pesticides (lindane, 

pentachlorophenol, hexachlorobenzene) on proliferation and differentiation in two 

stroma-free murine bone marrow culture models, a multipotent progenitor cell 

line (FDCP-mix) and primary lineage- depleted bone marrow cells. 

Tetrachlorohydroquinone (Cl(4)pHQ), tetrachloro-p-benzoquinone (Cl(4p)BQ), 

but not their positional isomers, tetrachlorocatechol (Cl(4)oHQ) and tetrachloro-obenzoquinone (Cl(4)oBQ), nor 2,4,6-trichlorophenol (2,4,6-Cl(3)P), were much 

more toxic to FDCP-mix cells cultured under conditions which lead to selfrenewal than under conditions which lead to granulocyte-macrophage 

differentiation. Under the latter conditions, Cl(4)pHQ and Cl(4p)BQ even 

stimulated growth at intermediate concentration levels. In the primary cell 

cultures, pronounced differences were observed in the sensitivity between 

individual developmental pathways and between the different compounds. The 

percent of cells differentiating into the granulocytic lineage was increased at high 

concentration levels of each test compound. However, stimulatory effects on the 

macrophage lineage were observed at intermediate concentration levels of 

Cl(4)pHQ, Cl(4p)BQ and 2,4,6-Cl(3)P, and differentiation into erythrocytes was 
242

stimulated at low concentrations of 2,4,6-Cl(3)P. It is concluded that chlorinated 

monocyclic pesticides, after biotransformation to quinoid metabolites, may 

interact directly with haemopoietic progenitor cells with differential effects on selfrenewal and differentiation. These mechanisms could lead to myeloplastic 

disorders. 

Hillier Oam, N., J. Gennissen, et al. (2009). "Our battle with hexachlorobenzene: citizen 

perspectives on toxic waste in Botany." J Environ Manage 90(4): 1605-12. 

 The perspectives of residents are brought together in this assembly of 

statements concerning the management of hexachlorobenzene waste in Botany, 

a southeastern suburb of Sydney. The paper indicates how residents have 

responded as participants in public participation exercises, and the contribution 

made by lay experts in the search for a negotiated solution to the problems of 

legacy wastes. Resident comments on the role of independent scientific experts, 

on legal liability, and on the State Government sponsored Commission of Inquiry, 

indicate the deficit of resources faced by the local community. The paper 

provides insights into the status of citizen knowledge in environmental 

controversies and the pitfalls of participatory processes. 

Holsbeek, L., C. R. Joiris, et al. (1999). "Heavy metals, organochlorines and polycyclic 

aromatic hydrocarbons in sperm whales stranded in the southern North Sea during the 

1994-1995 winter." Marine Pollution Bulletin 38(4): 304-313. 

 BIOSIS COPYRIGHT: BIOL ABS. Seven male sperm whales stranded on the 

southern North Sea coast during the 1994/95 winter were analysed for stable 

pollutant concentrations in muscle, liver, kidney and blubber: heavy metals (total 

and organic Hg, Se, Zn, Pb, Ni, Cd, Fe, Cr, Cu and Ti), organochlorines (PCBs 

and pesticides) and polycyclic aromatic hydrocarbons (PAHs). High 

concentrations of Cd (up to 300 mug/g dw in kidney), Hg (up to 130 mug/g dw in 

liver) and PCBs (up to 5 mug/g dw in blubber) were detected, but not considere 

Horvath, M. E., S. P. Faux, et al. (2001). "Lipid and DNA oxidative damage in 

experimentally induced hepatic porphyria in C57BL/10ScSn mice." Z Gastroenterol

39(6): 453-5. 

 Patients with porphyria cutanea tarda (PCT) develop hepatocellular carcinoma as 

a late consequence. Pre-loading of C57BL/10ScSn mice with iron greatly 

sensitizes them to the induction of hepatic porphyria caused by 

hexachlorobenzene (HCB). HCB will also cause liver tumors in experimental 

animals. Elevated liver iron stores are implicated in the development of some 

human liver cancers in connection with its known catalytic role in generation of 

highly reactive activated oxygen species. The aim of this study was to determine 

the lipid and DNA oxidative damage in iron and HCB-induced porphyric mice. 

C57BL/10ScSn mice received i.p. injections of dextran sulfate (control), iron 

(Imferon) or combined iron and HCB. 6 weeks after treatment plasma ALT levels 

and hepatic free iron, porphyrin, lipid peroxides and 8- hydroxyguanosine (8-

OHdG) levels were analyzed. Hepatic porphyrin level was significantly (p < 

0.001) increased following combined iron/HCB treatment as compared to control 
243

mice. The level of lipid peroxides increased 9-fold (p = 0.001) and 35-fold (p < 

0.001) after iron and iron/HCB treatment respectively, whereas the level of 8-

OHdG was increased 2.5-fold (p = 0.002) and 7.5-fold (p < 0.001) after iron and 

iron/HCB treatment respectively as compared to control mice. The authors 

conclude that iron overload in conjugation with HCB induce lipid and DNA 

oxidative damage in C57BL/10ScSn mice. DNA oxidative damage may be 

important in the early events of hepatic carcinogenesis in experimental porphyria. 

Horvath, M. E., S. P. Faux, et al. (2001). "Vitamin E protects against ironhexachlorobenzene induced porphyria and formation of 8-hydroxydeoxyguanosine in 

the liver of C57BL/10ScSn mice." Toxicol Lett 122(1): 97-102. 

 The effect of vitamin E treatment on total porphyrin content, lipid peroxidation 

(LOOH) and 8-hydroxydeoxyguanosine (8-OHdG) was studied in the livers of 

C57BL/10ScSn mice following hexachlorobenzene (HCB) and iron treatment. 

HCB was administered i.p. (totalling 300 mg/kg) twice, with 1 week interval. 

Three days after the first HCB injection iron- dextran was given i.p. (500 mg Fe 

per kg). Vitamin E was administered weekly (20 mg/kg) by s.c. injection. Both 

total hepatic porphyrin and LOOH levels were significantly (P<0.001) increased in 

the HCB-iron treated group as compared with the control group. Mice treated 

additionally with vitamin E had significant (P<0.001) lower levels as compared 

with the HCB-iron group. Similarly, the levels of 8-OHdG were significantly 

(P<0.001) increased above controls after HCB-iron treatment and this increase 

was reduced after co-treatment with vitamin E (P<0.02). The data support the 

hypothesis that the mechanism of hepatic porphyrinogenicity of HCB with iron 

overload is an oxidative free radical process. 

Hosie, S., S. Loff, et al. (2000). "Is there a correlation between organochlorine 

compounds and undescended testes?" Eur J Pediatr Surg 10(5): 304-9. 

 Some pesticides and synthetic chemicals are known to act as hormonal 

modulators, often possessing oestrogenic activity (xenooestrogens). They are 

persistent and accumulate in fatty tissue. Aim of our study is to address the 

question, whether a selection of such compounds is to be found in the fatty tissue 

of children undergoing surgical procedures and whether there are differences in 

values obtained from patients with or without undescended testes. Fat samples 

of 48 patients, 18 of whom had undescended testes, were examined by highresolution gas chromatography and mass spectrometry for DDT and metabolites, 

polychlorinated biphenyls (PCB), toxaphenes, hexachlorocyclohexane (HCH), 

chlorinated cyclodienes and chlorinated benzenes. We were able to find 

accumulation of all substances in every patient. Statistical analysis revealed a 

highly significant difference between patients from the control group and those 

from the undescended testes group for two compounds, namely 

heptachloroepoxide (HCE) and hexachlorobenzene (HCB), increased values 

being found in the patients with undescended testes. Since the aetiology of this 

entity is unknown in most of the cases, prenatal exposure to exogenous 

oestrogens is an attractive and plausible hypothesis. In order to confirm this, 

some questions will have to be answered in further studies: effect of exposure to 
244

xenooestrogens during a specific period of development, probable role of other 

substances with proven or suspected hormonal activity, potential synergism of 

such compounds and differences in individual susceptibility. 

Houtman, C. J., C. P. Swart, et al. (2002). "DR- and ER-CALUX assays as tools to 

direct toxicity identification and evaluation of endocrine disrupting chemicals." 

Organohalogen Compounds 58(Dioxin 2002): 349-352. 

 The authors present the development of a toxicity identification and evaluation 

(TIE) method for dioxin-like and estrogenic compds. of sediments, directed by 

responses generated in dioxin responsive (DR)- and estrogen responsive (ER)-

CALUX (Chem. Activated Luciferase Gene Expression) assays. 

Howe, T. S., S. Billings, et al. (2004). "Sources of polycyclic aromatic hydrocarbons and 

hexachlorobenzene in spruce needles of eastern Alaska." Environ Sci Technol 38(12): 

3294-8. 

 The concentrations of phenanthrene, anthracene, fluoranthene, pyrene, 

benzo[a]anthracene, chrysene, and hexachlorobenzene (HCB) were measured in 

spruce needles at 36 sites in eastern Alaska during early spring. Concentrations 

of each polycyclic aromatic hydrocarbon (PAH) varied by an order of magnitude. 

Samples taken from near the city of Fairbanks had higher concentrations than 

samples taken from more rural areas. Anthropogenic activities near Fairbanks 

are most likely a source of PAHs. Variation in the concentration ratios of isomeric 

PAHs indicates the relative importance of combustion and petrogenic sources. 

The relative combustion contribution is largest in coastal samples and smallest 

near Fairbanks. In contrast, the concentration of HCB varied by only a factor of 2. 

Lipid content of needles and distance from the coast were the major factors 

correlated with the concentration of HCB. 

Hyland, J. L., R. F. Van Dolah, et al. (1999). "Predicting stress in benthic communities of 

southeastern U.S. estuaries in relation to chemical contamination of sediments." 

Environmental Toxicology and Chemistry 18(11): 2557-2567. 

 BIOSIS COPYRIGHT: BIOL ABS. Matching data on sediment contaminants and 

macroinfaunal community structure from 231 subtidal stations in southeastern 

U.S. estuaries were used to develop a framework for evaluating risks of benthic 

impacts from multiple-contaminant exposure. Sediment contamination was 

expressed as the mean ratio of individual contaminant concentrations relative to 

corresponding sediment quality guidelines, that is, to effects range-median 

(ERM) values, probable effects level (PEL) values, or an aggregate of th 

quotients > 0.077. Seventy-three to 78% of stations with values in these upper 

ranges had degraded benthic assemblages, while 22 to 27% had healthy 

assemblages. Only four stations (three with degraded, one with healthy 

assemblages) had mean ERM or PEL quotients > 1.0, which is the beginning of 

the range associated with a high probability of mortality in short-term laboratory 

toxicity tests using amphipods. 
245

Jager, T. (2004). "Modeling ingestion as an exposure route for organic chemicals in 

earthworms (Oligochaeta)." Ecotoxicol Environ Saf 57(1): 30-8. 

 Earthworms take up chemicals from both soil pore water and food, but the 

quantitative contribution of each route is unclear. In this paper, a model is 

presented for the accumulation of organic chemicals in earthworms, including a 

compartment for the gut contents. A Monte Carlo screening method is used to 

calibrate the model simultaneously to four experimental data sets for 

hexachlorobenzene (HCB) in the compost worm (Eisenia andrei). The calibration 

procedure shows that the dominant route of exposure is across the gut wall. 

Nevertheless, predicted body residues of HCB are generally no more than 20% 

higher than the estimate based on equilibrium partitioning (EP), independent of 

the uncertainties in all of the model parameters. The deviation from EP is mainly 

related to the digestive efficiency of the earthworm. Body residues are not 

expected to exceed the EP estimate by more than 50% for other chemicals or 

other earthworm species. The model is particularly useful when the organism's 

food source is specifically contaminated and EP cannot be applied. 

James, P. (2009). "The supervision of environmental risk: the case of HCB waste or 

Botany/Randwick?" J Environ Manage 90(4): 1576-82. 

 The governance activities of capital and the state include attempts to control the 

timing and spacing of social activities such as the production of environmental 

risks and settlement of different social groups. The supervisory activities that 

have shaped the environmental and social history of the Botany/Randwick area 

are identified here, to examine how the HCB waste risk developed in that 

community. The analysis shows that multiple environmental risks and an 

ethnically diverse, working class community have been brought together in space 

to create environmental injustice. Analysing the governance of one 

environmental risk like hexachlorobenzene (HCB) waste may not increase 

understanding about communities facing multiple environmental risks or the 

supervisory processes that lead to the unfair accumulation of risks for particular 

places or social groups. Lessons from the environmental justice movement 

suggest that reframing problems like HCB waste management at 

Botany/Randwick as distributive justice issues may contribute to governance 

arrangements that better manage multiple risks and pollution sources in space 

affecting marginalised communities. 

Jan, J., M. Vrecl, et al. (1999). "Tissue distribution of planar and non-planar 

chlorobiphenyls, 4,4'-DDE and hexachlorobenzene in sheep and lambs." Chemosphere

38(11): 2607-12. 

 The bioconcentration and distribution pattern of individual PCB congeners 

(IUPAC Nos: -54, -80, -155 and -169) and organochlorine pesticides (HCB and 

4,4'-DDE) in blood, adipose tissue, liver and brain were examined in sheep two 

months after administration and in their offspring continuously exposed during 

the two months lactation period. Analyses were performed by high resolution gas 

chromatography. The levels of individual organochlorines varied significantly 

between tissues; the tissue/blood ratio (on a fat basis) varied by two orders of 
246

magnitude for individual congeners. The bioconcentration of the toxic planar 

PCB-169 congener was the highest in the liver and the lowest in the brain of the 

sheep. 

Jan, J., M. Vrecl, et al. (2001). "Bioconcentration of lipophilic organochlorines in ovine 

dentine." Arch Oral Biol 46(12): 1111-6. 

 The bioconcentration of lipophilic organochlorines in ovine dentine in comparison 

to adipose tissue was examined. Sheep were given a single dose (0.2-1.4 mg/kg 

body wt) of individual polychlorobiphenyl (PCB) congeners (tetrachlorobiphenyls 

IUPAC Nos. 54 and 80, and hexachlorobiphenyls IUPAC Nos. 155 and 169) and 

organochlorine pesticides 1,1-bis(4-chlorophenyl)-2,2-dichloroethene) (4,4'-DDE) 

and hexachlorobenzene (HCB). They were killed 2 months after the dose and 

teeth and adipose tissue were collected. For the extraction of organochlorines, 

dentine was treated ultrasonically with sulfuric acid and hexane. The 

concentration of organochlorines in dentine and adipose tissue was determined 

by high-resolution gas chromatography with electron-capture detection. The 

bioconcentration of 'planar' compounds (PCB-169, HCB) in dentine, compared to 

adipose tissue, was lower than that of 'non-planar' (PCB-155, 4,4'-DDE). Ratios 

of the non-planar to planar compounds PCB-155/-169 and 4,4'-DDE/HCB in 

dentine were 1.4 and 7.2, and in adipose tissue 0.5 and 2.4, respectively. The 

dentine:adipose tissue bioconcentration ratios (on a lipid basis) of PCB-54, -80, -

155, -169, 4,4'-DDE and HCB were 47, 16, 0.3, 0.1, 3.2 and 1.0, respectively. 

The results indicate that the bioconcentration of organochlorines in different 

tissues cannot be based on lipid content only. It is suggested that the 

physicochemical properties of individual organochlorines, i.e. lipophilicity (K(ow)), 

diffusivity, metabolism and tissue-specific interactions, play a part in the different 

bioconcentrations of individual organochlorine pollutants in dentine compared to 

adipose tissue. 

Jantunen, L. M. and T. F. Bidleman (2006). "Henry's law constants for 

hexachlorobenzene, p,p'-DDE and components of technical chlordane and estimates of 

gas exchange for Lake Ontario." Chemosphere 62(10): 1689-96. 

 The Henry's law constants (HLC) for trans- and cis-chlordane (TC, CC), transnonachlor (TN), hexachlorobenzene (HCB) and p,p'-DDE were determined by the 

gas-stripping method over a temperature range of 5-35 degrees C. The HLC 

variation versus temperature (K) was described by logH=m/T+b. Parameters of 

this equation were (with standard deviations) TC: m=-1524+/-158, b=6.58+/-0.54; 

CC: m=-1786+/-209, b=7.42+/-0.71; TN m=-2068+/-284, b=8.44+/-0.97; HCB: 

m=-3013+/-174, b=11.60+/-0.59 and p,p'-DDE: m=-2043+/-240, b=8.37+/-0.82. 

The HLCs (Pa m3 mol(-1)) at 25 degrees C (298.15 K) were: TC=29; CC=27; 

TN=32; p,p'-DDE=33 and HCB=35. These HLCs values were used to calculate 

fugacity ratios from paired air and water data from Lake Ontario, July 1998. The 

resulting fugacity ratios predict that volatilization was occurring for all compounds 

during that month. 
247

Jarrell, J. F., A. Gocmen, et al. (2002). "Hexachlorobenzene exposure and the 

proportion of male births in Turkey 1935-1990." Reprod Toxicol 16(1): 65-70. 

 Hexachlorobenzene (C(6)Cl(6), HCB) is a chemical that has been associated 

with significant immediate and long term adverse health effects in humans. It has 

been associated with both porphyria cutanea tarda and spontaneous abortions 

among survivors of widespread exposure in the 1950s in southeastern Turkey. 

HCB binds to the Ah receptor, albeit with lower affinity than dioxin. Dioxin 

exposure has been reported to lower human secondary sex ratio, putatively 

through a male mediated effect. We therefore wished to evaluate the impact of 

the HCB environmental event on the sex ratio of the progeny of the survivors. We 

undertook an assessment of 1) the effects of HCB exposure on the proportion of 

male births of individual subjects who had survived, 2) variables that significantly 

predicted the proportion of males among these individuals, and 3) the trend of 

the population sex ratio born in Turkey from 1935 to 1990. Women known to 

have been exposed to HCB in the 1950s did not have offspring with a 

significantly different sex ratio when compared to control populations. However, 

subjects reporting exposure at the peak of the episode (1955-57) had a 

significantly lower lifetime proportion of males than those exposed at a later date. 

The lifetime reported spontaneous abortion rate of these women also significantly 

predicted the percent males per subject. The available national data 

demonstrated a significant reduction in the calculated proportion of males from 

1935 to 1970 that stabilized from 1970 to 1990. These data indicate that HCB 

exposure that was sufficient to induce clinical porphyria cutanea tarda may also 

have reduced the proportion of males in subjects over their reproductive lifespan. The HCB episode does not explain the pattern of the national trend from a 

population perspective. 

Jensen-Lee, C. (2009). "When unequals are treated equally: the 2002 commission of 

inquiry into Orica's Geomelt proposal." J Environ Manage 90(4): 1613-21. 

 This paper deals with the Commission of Inquiry (COI) established by the NSW 

Department of Planning to examine Orica's proposal to build a Geomelt plant at 

its Botany site to destroy its stockpile of Hexachlorobenzene. The Inquiry is 

analysed in light of the literature on democracy/democratisation. The paper 

argues that the standard operating procedures of the Inquiry ensured that all 

stakeholders were treated equally. However, this equality was found to be purely 

formal, and drawing on the critique of formal equality dating back to Aristotle, it is 

argued that treating unequals equally results in the circumvention of deliberative 

democratic ideals by perpetuating entrenched structural inequalities while 

nonetheless giving the superficial appearance of fair play. 

Jones, K. C. and P. De Voogt (1999). "Persistent organic pollutants (POPs): State of the 

science." Environmental Pollution (Series A). Ecological and Biological 100(1-3): 209-

221. 

 BIOSIS COPYRIGHT: BIOL ABS. The environmental chemistry and 

ecotoxicology of persistent organic pollutants (POPs) are fascinating areas of 

scientific research. Our objective in this paper is to provide a brief, focussed 
248

overview of what constitutes a POP, highlight the harmful effects they may have 

on biota, make some comments on their environmental sources and analysis, 

their environmental trends and processes, their movement through foodchains 

and highlight some important regional-and global-scale environmental transport 

Juhler, R. K., M. G. Lauridsen, et al. (1999). "Pesticide residues in selected food 

commodities: Results from the Danish National Pesticide Monitoring Program 1995-

1996." Journal of Aoac International 82(2): 337-358. 

 BIOSIS COPYRIGHT: BIOL ABS. The paper presents results of analyses of 

4182 samples collected from January 1995 to December 1996 for the Danish 

National Pesticide Monitoring Program. The program basis is a random sample 

control supplemented with a target control. The objectives of the control are to 

monitor consumer exposure to health hazards and to enforce national and 

European Community regulations. The Danish Veterinary and Food 

Administration is responsible for establishing methods, data manipulation, and 

evaluation, but actual analyses are performed at 4 regional laboratories. In 

addition to a description of the Danish National Pesticide Monitoring Program on 

food, the effects of lowering the reporting limits are discussed. Pesticides 

included are those in current use as well as chlorinated pesticides like lindane, 

DDT, and HCB, occurring in food now primarily as a result of environmental 

contamination. Commodi ties analyzed are fruits, vegetables, cereals, bran, fish, 

and animal products such as meat, butter,cheese, fat, and eggs. In fruits and 

vegetables, residues were detected in 10% of 2515 samples, with higher 

incidences of detection for foreign commodities. Violation rate was 0.6%. In food 

of animal origin, low levels of organochlorine pesticides were detected in most 

fish samples and in more than half of the animal product samples. However, no 

results exceeding maximum residue limits were found. No residues of organophosphorus pesticides were detected in the 231 meat samples analyzed. 

Kacmar, P., J. Pistl, et al. (1999). "Immunotoxicology and veterinary medicine." Acta 

Veterinaria Brno 68(1): 57-79. 

 BIOSIS COPYRIGHT: BIOL ABS. Immunotoxicology investigates unwanted 

adverse effects of xenobiotics (pesticides, heavy metals from emissions, new 

DNA-recombinant products, immune response modulators, monoclonal 

antibodies, drugs and others) on the immune system of man and animals. 

Immunotoxicology in veterinary medicine deals mostly with the problems of 

dominant ecological toxicants, such as pesticides. Therefore, the veterinary 

immunotoxicology can be referred to as ecoimmunotoxicology. DNA-recombinant 

biopreparations and d enobiotic should be supported by a complex set of tests 

rather than limited number of them. The extent of functional and non-functional 

immunity tests should be determined on the basis of knowledge about the 

mechanism of the toxic effects of xenobiotics in animals. This knowledge can be 

supplied by biochemistry, toxicology, pharmacology and histopathology 

(histochemistry and immunohistochemistry). The up-to-date knowledge about 

immunosuppressive effects of pesticides and their po 
249

Kahl, M. D., C. L. Russom, et al. (1999). "Saturation units for use in aquatic bioassays." 

Chemosphere 39(3): 539-551. 

 BIOSIS COPYRIGHT: BIOL ABS. Methods were developed for preparing 

liquid/liquid and glass wool column saturators for generating chemical stock 

solutions for conducting aquatic bioassays. Exposures have been conducted 

using several species of fish, invertebrate, and mollusks in static and flowthrough conditions using these methods. Stock solutions for 82 organic 

chemicals were prepared using these saturation units. The primary purpose of 

stock generation was to provide a continuous and consistent amount of toxicant 

laden so mparison purposes to water solubility values available in the literature. 

Literature solubility values from a database by Yalkowsky et al. (1) provided 

information on temperatures and data quality which allowed comparison to 

values obtained from the present study. Twenty four compounds were identified 

and analyzed for the comparison of maximum obtainable solubility levels. 

Maximum saturator stock water concentrations were generally lower (R=0.98) but 

were in close agreement with 

Kannan, K., M. Kawano, et al. (1999). "Extractable organohalogens (EOX) in sediment 

and biota collected at an estuarine marsh near a former chloralkali facility." 

Environmental Science and Technology 33(7): 1004-1008. 

 BIOSIS COPYRIGHT: BIOL ABS. Extractable, organically bound chlorine 

(EOCI), which is determined by neutron activation analysis (NAA), has been 

used as a measure of pollution by chlorinated organics. In this study, the 

concentrations and distribution of extractable organohalogens (EOX = EOCI + 

EOBr + EOI) were measured in sediment, blue crab, fishes, birds, and terrapin 

collected at an estuarine marsh and a nearby creek contaminated by the disposal 

of wastes from a former chloralkali facility. The concentrations of the orga th its 

elevated proportions relative to the concentrations of EOBr or EOI in biota 

suggest that wastes from the chloralkali processes are a potential source of 

chlorinated organics present in the environment. The relative proportion of known 

(such as, polychlorinated biphenyls (PCBs), dibenzo-p-dioxins/dibenzofurans 

(PCDDss), polychlorinated naphthalenes (PCNs), and organochlorine pesticides) 

to unknown organochlorines in sediment, blue crab, fishes, birds, and terrapin 

was, on a 

Karmaus, W., E. P. DeKoning, et al. (2001). "Early childhood determinants of 

organochlorine concentrations in school- aged children." Pediatr Res 50(3): 331-6. 

 We investigated whether early childhood factors such as breast-feeding, parity, 

and smoking contribute to the variation of organochlorine compounds (OC: 

dichlorodiphenyldichloroethene, hexachlorobenzene, betahexachlorocyclohexane, and the sum of polychlorinated biphenyls including the 

congeners 101, 118, 138, 153, 170, 180, 183, and 187) at approximately 7 y of 

age. OC were measured in whole blood of 350 children. Pregnancy 

characteristics and the child's living conditions were gathered by questionnaires 

administered to the parents and interviews with the mother. Height and weight 

were determined during the medical examination. Exclusion of incomplete data 
250

and nonbiologic children of the mothers yielded a sample of 337 children. We 

applied regression analysis with indicator variables, controlling for confounders. 

No systematic association was detected for birth order or maternal smoking 

during pregnancy. The OC concentrations are diluted in children with a higher 

body mass index (>18 kg/m(2)). We found a strong, dose-dependent relationship 

between the duration of breast- feeding (none, 1-4 wk, 5-8 wk, 9-12 wk, >12 wk) 

and the concentration of all five OCs. Of the potential determinants analyzed, 

more of the variance of the OC concentration is accounted for by breast-feeding 

than by any other variable. Exclusive breast-feeding beyond 12 wk was 

associated with a doubling of OC whole blood concentration compared with 

bottle-fed children (dichlorodiphenyldichloroethene, 0.28 microg/L versus 0.55 

microg/L; beta-hexachlorocyclohexane, 0.05 microg/L versus 0.14 microg/L; 

hexachlorobenzene, 0.14 microg/L versus 0.25 microg/L; sum of polychlorinated 

biphenyls, 0.25 microg/L versus 0.55 microg/L). These findings indicate that 

breast-feeding can lead to an extended duration of increased OC exposure in 

childhood. 

Karmaus, W., J. Kuehr, et al. (2001). "Infections and atopic disorders in childhood and 

organochlorine exposure." Arch Environ Health 56(6): 485-92. 

 The authors investigated whether organochlorine exposure is associated with 

prevalence of otitis media, pneumonia, pertussis, asthma, and increased 

immunoglobulin E levels in children. Organochlorine concentrations and histories 

of infection and atopic manifestation were available for 343 children, and 

immunoglobulin E levels were available for 340 children. The authors applied 

logistic and linear regressions and controlled for confounders. In general, the 

prevalence of infections in children was not related to organochlorine exposure. 

However, for the combined effect of dichlorodiphenyldichloroethene with 

polychlorinated biphenyls or hexachlorobenzene, a significantly increased 

relative risk (odds ratios = 3.70 and 2.38, respectively) was found for otitis media. 

Exposure to dichlorodiphenyldichloroethene resulted in a significantly higher 

odds ratio for asthma (odds ratio = 3.71; 95% confidence interval = 1.10, 12.56) 

and in immunoglobulin E concentrations above 200 kU/l (odds ratio = 2.28; 95% 

confidence interval = 1.20, 4.31). This is the first study in which 

dichlorodiphenyldichloroethene has been identified as a substantial risk factor for 

asthma and for increased immunoglobulin E blood levels. 

Khim, J., K. Kannan, et al. (1999). "Characterization and distribution of trace organic 

contaminants in sediment from Masan Bay, Korea. 1. Instrumental analysis." 

Environmental Science and Technology 33(23): 4199-4205. 

 BIOSIS COPYRIGHT: BIOL ABS. Masan Bay, located on the southeast coast of 

Korea, is a long and narrow inlet of a semi-closed bay that receives industrial and 

municipal wastewaters from the cities of Masan and Changwon. In this study, 

sediments collected from 28 locations on Masan Bay were analyzed for total 

organic carbon (TOC), nonylphenol (NP), octylphenol (OP), bisphenol A (BPA), 

organochlorine pesticides (HCB, HCHs, CHLs, and DDTs), individual 

polychlorinated biphenyl (PCB) congeners, and 16 polycyclic aromatic 
251

hydrocabons (PAHs) to characterize their spatial distribution and contamination 

status. Concentrations of NP in sediment ranged from 113 to 3890 ng/g on a dry 

weight basis (dry wt), whereas concentrations of OP and BPA were, on average, 

20-110-fold less than those of NP. PAHs were predominated by 4-6-ring 

compounds with concentrations in the range of 54.1-1100 ng/g dry wt. 

Concentrations of PCBs in sedime nt, which were predominated by tetra- and 

pentachlorobiphenyl congeners, ranged from 10.3 to 148 ng/g, dry wt. Among 

different OC pesticides analyzed, concentrations of DDTs were the greatest, 

ranging from 0.4 to 12.6 ng/g dry wt. NP concentrations were greater at coastal 

locations proximal to the discharges of creeks from inland areas, whereas the 

concentrations of PCBs and PAHs were greater near the sites of industrial and 

shipping activities. Concentrations of target analytes were not related to TOC. 

Although the mean concentrations of PCBs and PAHs in sediments were less 

than the suggested sediment quality guidelines (SQG), their concentrations in 

some locations were close to or above the SQG for toxic effects in benthic 

organisms. 

Khim, J. S., D. L. Villeneuve, et al. (1999). "Alkylphenols, polycyclic aromatic 

hydrocarbons, and organochlorines in sediment from Lake Shihwa, Korea: Instrumental 

and bioanalytical characterization." Environmental Toxicology and Chemistry 18(11): 

2424-2432. 

 BIOSIS COPYRIGHT: BIOL ABS. Lake Shihwa is an artificial lake, located on the 

west coast of Korea, that has experienced environmental deterioration since 

1994, when it was formed by construction of a sea dike. This study used 

instrumental analysis and in vitro bioassays to characterize organic contaminants 

in sediment collected from 11 stations on Lake Shihwa. Alkylphenol (AP) 

concentrations in Lake Shihwa sediment ranged from 20.2 to 1,820 ng/g 

nonylphenol and from 4.69 to 50.5 ng/g octylphenol, on a dry weight basis. Max 

ignificant dioxinlike activity was associated with fractions containing classic aryl 

hydrocarbon receptor agonists, such as PCBs, but the mid-polarity fractions 

containing PAHs and most polar fractions yielded significant dioxinlike activity. 

Overall, most of the in vitro bioassay responses appear to have been caused by 

unidentified and/or undetectable compounds associated with Lake Shihwa 

sediment. 

Kleivane, L., T. Severinsen, et al. (2000). "Biological transport and mammal to mammal 

transfer of organochlorines in Arctic fauna." Mar Environ Res 49(4): 343-57. 

 Ringed seal (Phoca hispida) is assumed to be the most important and common 

prey of polar bears (Ursus maritimus). However, during a scientific survey in the 

ice area of the northern Barents Sea east of Svalbard in June 1995, an 

unexpectedly high number of polar bears were observed feeding on harp seal 

(Phoca groenlandica) carcasses. Samples of both harp and ringed seals were 

obtained and organochlorine (OC) occurrence and pattern in these two potential 

polar bear prey species were determined. Significantly higher OC concentrations 

were found in harp seals, as compared to the ringed seals. All animals in the 

northern harp seal group were lean specimens in late moult. The industrial 
252

chemicals, polychlorinated biphenyls (PCBs) and hexachlorobenzene (HCB), and 

the OC pesticides bis-2,2,(chlorophenyl)- 1,1,1-trichloroethanes (DDTs), 

hexachlorocyclohexanes (HCHs), and chlordanes (CHLORs) were analysed in 

blubber. The concentrations of sigma PCB (sum of concentrations of 16 PCB 

congeners) and sigma DDT (sum of concentrations of p,p'-DDT and p,p'-DDE) in 

the northern harp seal group ranged from 2093 to 20,382 and 1460 to 10,381 ng 

g-1 lipid weight, with mean concentrations of 11,133 and 6847 ng g-1 lipid 

weight, respectively. The mean concentrations of the CHLORs, oxychlordane 

and trans-nonachlor, were 1311 and 3743 ng g-1 lipid weight, respectively, while 

the mean concentrations of HCB and HCH isomers (alpha-, beta- and gammaHCH) were all < 500 ng g-1 lipid weight. No significant difference was found in 

the mean total blubber mass between the two seal species when collected in 

June. This indicates that polar bears preying on harp seals instead of ringed 

seals at this time of the year could accumulate significantly higher PCB 

concentrations. We suggest that polar bears feeding along the ice- edge east of 

Svalbard in May and June preferentially prey on harp seals instead of ringed 

seals, and that this may partly explain the variation in PCB concentrations among 

polar bears from the Norwegian Arctic. An hypothesis is that the harp seal may 

function as a transport vector of OCs into the high Arctic environment. 

Klopman, G. and S. K. Chakravarti (2003). "Structure-activity relationship study of a 

diverse set of estrogen receptor ligands (I) using MultiCASE expert system." 

Chemosphere 51(6): 445-59. 

 The MultiCASE expert system was used to construct a quantitative structureactivity relationship model to screen chemicals with estrogen receptor (ER) 

binding potential. Structures and ER binding data of 313 chemicals were used as 

inputs to train the expert system. The training data set covers inactive, weak as 

well as very powerful ER binders and represents a variety of chemical 

compounds. Substructural features associated with ER binding activity 

(biophores) and features that prevent receptor binding (biophobes) were 

identified. Although a single phenolic hydroxyl group was found to be the most 

important biophore responsible for the estrogenic activity of most of the 

chemicals, MultiCASE also identified other biophores and structural features that 

modulate the activity of the chemicals. Furthermore, the findings supported our 

previous hypothesis that a 6 A distant descriptor may describe a ligand-binding 

site on an ER. Quantitative structure-activity relationship models for the 

chemicals associated with each biophore were constructed as part of the expert 

system and can be used to predict the activity of new chemicals. The model was 

cross validated via 10 x 10%-off tests, giving an average concordance of 

84.04%. 

Kortenkamp, A. and R. Altenburger (1999). "Approaches to assessing combination 

effects of oestrogenic environmental pollutants." Science of the Total Environment

233(1-3): 131-140. 

 BIOSIS COPYRIGHT: BIOL ABS. Concerns about possible combination effects 

of environmental chemicals with estrogenic activity have motivated the search for 
253

synergisms between such agents. However, much published work has taken no 

account of the concepts and methods for analysing combination effects, which 

were developed in toxicology and pharmacology. In the present communication, 

we draw attention to conceptual frameworks relevant for a sound analysis of the 

effects of mixtures of oestrogenic compounds. A model calculation duce effects 

in in vitro assay systems and their low concentrations in the environment. 

Kosmala, A., S. Charvet, et al. (1999). "Impact assessment of a wastewater treatment 

plant effluent using instream invertebrates and the Ceriodaphnia dubia chronic toxicity 

test." Water Research 33(1): 266-278. 

 BIOSIS COPYRIGHT: BIOL ABS. The purpose of this study was to assess the 

specific impact of a wastewater treatment plant (WWTP) effluent on the receiving 

water. A combination of a field survey and laboratory toxicity tests was used to 

detect a possible cause-effect relationship between the plant discharge and the 

receiving water quality. In addition to biological and chemical quality of the river 

upstream and downstream from the WWTP outfall, we assessed Hydropsychid 

life cycle as a field bio-indicator. Laboratory experiments were carried out using 

the 7-day Ceriodaphnia dubia chronic toxicity test. Field and laboratory studies 

were performed simultaneously almost every month from March 1995 to 

February 1996. Throughout the year, we observed a biological degradation at 

downstream site compared to upstream site based on biological indices, while 

we detected a constant chronic toxicity from C. dubia test. Field and laboratory 

indicators showed that the effect of the WWTP effluent on organisms was at 

Kryukov, V. I. (1999). "Effect of chemical pollution of ecosystems in the Kafirnigan and 

Kyzylsu River Valleys on the frequency of chromosome aberrations in house mice." 

Ekologiya (Moscow) 0(4): 309-312. 

 Biosis copyright: biol abs. rrm effect of chemical pollution of ecosystems in the 

kafirnigan and kyzylsu river valleys on the frequency of chromosome aberrations 

in house miceyresearch article mus musculus pollution pesticides pollutant 

chromosomes bone marrow aberration spectrum blood and lymphatics immune 

system kafirnigan river valley kyzylsu river valley tajikistan 

Kuchen, A., F. Muller, et al. (1999). "Pesticides and other chemical residues in Swiss 

total diet samples." Mitteilungen aus Lebensmitteluntersuchung und Hygiene = Travaux 

de chimie alimentaire et d'hygiene. 90(1): 78-107. 

 BIOSIS COPYRIGHT: BIOL ABS. Foodstuffs contribute to the total exposure of 

man to pesticides and other contaminants. To estimate the mean daily intake of 

such substances in Switzerland, during the period 1991 to 1996 a total of 36 

ready-to-eat food samples representative for daily nutrition were analyzed with a 

multi residue method capable of detecting more than 300 contaminants. 66 

different pesticides and pesticide metabolites, 8 plasticizers and 6 PCBcongeners were found and quantitatively determined. For most pesticides and 

organochlorine contaminants the estimated daily intake was found to be much 

less than 1% of the corresponding ADI values. Among the investigated 

plasticizers, the results obtained for phthalates are of particular interest. The 
254

highest value being 10 % of the ADI was found for bis-n-butyl-phthalate. This 

finding indicates that more attention should be drawn to this class of substances 

in fut ure. Interesting is the fact that the intake of fungicides from fruits is more 

important than from salad. This observation is in contrast to the opinion that 

salad in wintertime is the main source. 

Kurpios, M. and A. Nowosielski (1999). "Chlorinated hydrocarbon derivative residues in 

the organism of three fish species from the Szczecin Bay." Bromatologia I Chemia 

Toksykologiczna 32(1): 87-91. 

 BIOSIS COPYRIGHT: BIOL ABS. The muscular tissue and the livers of three 

fresh-water fish species: roach (Rutilus rutilus), perch (Perca fluviatilis), and 

bream (Abramis abrama) collected from the Szczecin Bay were studied. One of 

the aim of the work was to determine the residues of gamma-HCH, DDT and its 

metabolites, HCB, and five main chlorinated biphenyl derivatives. The 

concentrations of the studied chemicals in the muscles were below 15 ng/g, while 

for the liver the corresponding figure was 60 ng/g. The results of stat s of the 

chemicals in the muscles of roach observed in our work constitute a 

characteristic feature of that fish species. 

Lackmann, G. M., J. Angerer, et al. (2000). "Parental smoking and neonatal serum 

levels of polychlorinated biphenyls and hexachlorobenzene." Pediatr Res 47(5): 598-

601. 

 Polychlorinated biphenyls (PCB) and hexachlorobenzene (HCB) are ubiquitous 

compounds that have tumor-promoting properties if applied together with 

tobacco-specific carcinogens. It was the purpose of the present study to 

investigate whether parental smoking by itself will increase the prenatal uptake of 

such organochloric compounds. With the informed consent of the parents, blood 

samples were taken from 80 full- term neonates before the first oral feeding. Six 

PCB congeners (PCB 28, 52, 101, 138, 153, and 180) and HCB were analyzed 

with capillary gas chromatography. Information about parental smoking behavior, 

the geographic origin of the parents, and their actual and previous working 

places was recorded. We composed three study groups for statistical analyses: 

active smoking mothers (n = 12), passive smoking mothers (n = 33), and 

nonsmoking families (n = 35). Neonates born to active smoking mothers had the 

highest PCB and HCB concentrations compared with children of passive or 

nonsmoking mothers. These differences were statistically significant (p < 0.01) in 

the cases of PCB 138, total PCB, and HCB. Newborns of passive smoking 

mothers had higher PCB and HCB concentrations than children of nonsmoking 

families but lower values than those of active smoking mothers. These 

differences were statistically significant for all compounds with the exception of 

PCB 180. It is concluded that active and passive maternal smoking increases the 

neonatal burden with PCB and HCB. 

Lagueux, J., D. Pereg, et al. (1999). "Cytochrome P450 CYP1A1 enzyme activity and 

DNA adducts in placenta of women environmentally exposed to organochlorines." 

Environmental Research 80(4): 369-382. 
255

 BIOSIS COPYRIGHT: BIOL ABS. Organochlorine compounds bioaccumulate in 

fishing and hunting products included in the daily diet of many coastal 

populations. Prenatal and perinatal exposure to large doses of PCBs and PCDFs 

was shown to be deleterious on fetal and neonatal development, but information 

is scarce regarding possible effects of chronic low-dose exposure. This study 

investigates biomarkers of early effects in newborns from women exposed to 

organochlorines through the consumption of species from marine food chains, 

natal organochlorine exposure was determined by measuring these compounds 

in umbilical cord plasma. The amount of bulky polycyclic aromatic hydrocarbon 

(PAH)-related DNA adducts was significantly greater in the Lower-North-Shore 

group than in the reference group. Placental EROD activity and the amount of 

less bulky (OC-related) DNA adducts were significantly higher in the Nunavik 

group than in the reference group. For both biomarkers, smoking was found to be 

an important confound 

Lamoureux, E. M. and B. J. Brownawell (2004). "Influence of soot on hydrophobic 

organic contaminant desorption and assimilation efficiency." Environ Toxicol Chem

23(11): 2571-7. 

 Soot, soot-amended sediment, and unamended sediment spiked with 

hydrophobic organic contaminants (HOC) were subjected to laboratory 

desorption and assimilation efficiency experiments in an effort to assess and 

compare the importance of soot in controlling HOC desorption and depositfeeder assimilation efficiency. Three contaminants, naphthalene (NAP), 

benzo[a]pyrene (BaP), and hexachlorobenzene (HCB) were sorbed to 

sediments, sediments amended with soot (2-4% dry wt), and soot for a period of 

34 d. Desorption of all three contaminants into seawater from the three prepared 

sorbates was then monitored, and Nereis succinea assimilation efficiency 

experiments on the BaP- and HCB-contaminated sorbates were conducted. Both 

NAP and BaP desorption rates for soot and soot-amended sediments were 

reduced by at least a factor of two relative to unamended sediment. 

Hexachlorobenzene desorption rates were similar for both the soot-amended and 

the unamended sediments. Results of N. succinea assimilation efficiency 

experiments indicate a trend similar to the desorption experiments: higher 

assimilation of BaP from unamended relative to soot-amended sediment and little 

difference in assimilation between treatments for HCB. However, soot was more 

effective in reducing BaP desorption than assimilation efficiency, which would be 

consistent with the hypothesis that the gut fluid dissolution by deposit feeders 

may partially decouple biological availability from chemical availability. 

Lee, M. H. and P. D. Ryu (1999). "Sanitation and tissue residue problems in high quality 

pork." Asian-Australasian Journal of Animal Sciences 12(2): 233-243. 

 BIOSIS COPYRIGHT: BIOL ABS. Food safety or sanitation are terms broadly 

applicable to procedures designed to ensure that food quality is high and free of 

factors which may adversely affect human health. These factors include zoonotic 

diseases and acute and chronic effects of ingesting natural and human-made 

xenobiotics. Use of drugs in animal production for the treatment and control of 
256

animal diseases, to promote growth rate, and to improve feed conversion 

efficiency has expanded year by year, thus increasing the possibilities for 

occurrences in animal products of residues harmful to humans. Governmental 

agencies have made efforts to control or prevent residue problems. The Korean 

Food and Drug Administration (KFDA) is charged with the responsibility of 

establishing tolerances for veterinary drugs, pesticides, and mycotoxins and 

other non-pharmaceutical substances. The Department of Veterinary Service is 

responsible for establishing guidelines regarding withdrawal times of drugs, 

approval of drugs 

Lewis, R. G., C. R. Fortune, et al. (1999). "Distribution of pesticides and polycyclic 

aromatic hydrocarbons in house dust as a function of particle size." Environmental 

Health Perspectives 107(9): 721-726. 

 BIOSIS COPYRIGHT: BIOL ABS. House dust is a repository for environmental 

pollutants that may accumulate indoors from both internal and external sources 

over long periods of time. Dust and tracked-in soil accumulate most efficiently in 

carpets, and the pollutants associated with dust and soil may present an 

exposure risk to infants and toddlers, who spend significant portions of their time 

in contact with or in close proximity to the floor and who engage in frequent 

mouthing activities. The availability of carpet dust for e ameter, and each fraction 

was analyzed for 28 pesticides and 10 polycyclic aromatic hydrocarbons (PAHs). 

Over 20% of the fractionated dust sample consisted of particles < 25 mum in 

diameter. Fourteen pesticides and all 10 of the target PAHs were detected in one 

or more of the seven size-fractionated samples. Sample concentrations reported 

range from 0.02 to 22 mug/g; the synthetic pyrethroids cis- and trans-permethrin 

were the most abundant pesticide residue. The concentrations of nearly all of 

Liu, T., Z. L. Chen, et al. (2007). "Monitoring bioaccumulation and toxic effects of 

hexachlorobenzene using the polyurethane foam unit method in the microbial 

communities of the Fuhe River, Wuhan." J Environ Sci (China) 19(6): 738-44. 

 Hexachlorobenzene (HCB) is a chlorinated aromatic hydrocarbon that was widely 

used for seed dressing in prevention of fungal growth on crops, and also as a 

component of fireworks, ammunition, and synthetic rubbers. Because of its 

resistance to degradation and mobility, HCB is widely distributed throughout the 

environment and is accumulated through food chains in different ecosystems. In 

this study, a preliminary investigation was carried out on the bioaccumulation and 

the toxic effects of HCB in the microbial (protozoan in particular) communities in 

the Fuhe River, Wuhan, a water body receiving industrial wastewaters containing 

HCB and other pollutants, using the standardized polyurethane foam units (PFU) 

method. Field samples were taken from eight stations established along the Fuhe 

River in January and August 2006. The concentration ratios of HCB in microbial 

communities and in water were 9.66-18.64, and the microbial communities 

accumulated 13.29-56.88 [ig/L of HCB in January and 0.82-10.25 microg/L HCB 

in August. Correlation analysis showed a negative correlation between the HCB 

contents in the microbial assemblage, and the number of species and the 

diversity index of the protozoan communities. This study demonstrated the 
257

applicability of the PFU method in monitoring the effects of HCB on the level of 

microbial communities. 

Liu, W., P. Li, et al. (2005). "Short-term toxic effects of chlorobenzenes on broadbean 

(Vicia faba) seedlings." Sci China C Life Sci 48 Suppl 1: 33-9. 

 The root growth, changes in superoxide dismutase (SOD, EC 1.15.1.1) activity, 

malonyldialdehyde (MDA) and total soluble protein level of broadbean (Vicia 

faba) seedlings were researched at different soil concentrations of 

chlorobenzene (CB), 1,2,4-trichlorobenzene (TCB) and hexachlorobenzene 

(HCB). The results showed that root growth of seedlings was interrupted after 5 d 

of 50-200 microg x g(-1) TCB treatment. During a 3 d recovery period, root 

growth was, however, restored to some extent although there was a delay in 

returning to the control level. The total soluble protein content in seedlings 

increased with TCB concentration and duration of exposure. Effect of TCB stress 

on SOD activity in seedlings displayed a significant dose-effect relationship for 1-

5 d of 50-200 microg x g(-1) treatment. When broadbean seedlings were placed 

in clean tap water for 3 d following exposure to 5 d of TCB stress to clear tap 

water for 3 d, SOD activity at 50 microg x g(-1) TCB recovered towards control 

level (P>0.05) while a significant increase in SOD activity was observed at 100 

and 200 microg x g(-1) TCB compared to control (P<0.05). The experiments also 

revealed that a significant increase of MDA level in seedlings occurred after 3 

and 5 d of 100 and 200 microg x g(-1) TCB treatment (P<0.05 and P<0.01), and 

there was a positive correlation between TCB concentration and MDA level. All 

the above results showed that SOD activity and MDA level of broadbean 

seedlings might be proposed as the biomarkers for short-term TCB 

contamination in soil. Compared to TCB, the toxicity of 50-1000 microg x g(-1) 

CB or HCB in soil to broadbean seedlings was not observed after a 3 d 

exposure. 

Liu, W., Y. S. Yang, et al. (2004). "Root growth inhibition and induction of DNA damage 

in soybean (Glycine max) by chlorobenzenes in contaminated soil." Chemosphere

57(2): 101-6. 

 The cytotoxic and genotoxic effects of 1,2,4-trichlorobenzene (TCB), 

chlorobenzene (CB), and hexachlorobenzene (HCB) on root growth and DNA 

strand breakage damage of soybean nuclei in the test soil were studied using the 

comet assay. Results indicated that the root growth was significantly inhibited, 

and DNA strand breaks and the comet tail in the root tip nuclei were both induced 

after 48 h exposure with TCB concentrations of 50, 100, 200, 300 microg g(-1) in 

the soil. DNA strand breakage was more sensitive to the TCB than the root 

growth. There was a significant dose-response relationship between the TCB 

exposure and DNA strand breakage in the soybean nuclei. Thus it is possible for 

DNA strand breakage to be used as a biomarker of soybean exposed to TCB 

contamination. Significant cytotoxic threshold concentration of the TCB exposure 

on the root growth inhibition was determined as 61 microg g(-1) in the soil. The 

toxicity of 100-1,000 microg g(-1) CB and HCB to the soybean seedlings in the 

soil were not observed after 48 h or longer exposure. 
258

Liu, X., G. Zhang, et al. (2009). "Seasonal patterns and current sources of DDTs, 

chlordanes, hexachlorobenzene, and endosulfan in the atmosphere of 37 Chinese 

cities." Environ Sci Technol 43(5): 1316-21. 

 China has a history of large scale production and application of organochlorine 

pesticides (OCPs) although, data on their nationwide distribution and seasonal 

variations in the atmosphere is still sparse. Passive air samplers (PAS) were 

therefore utilized to obtain seasonal data from 37 Chinese cities and three 

background sites in 2005. Concentrations and spatial and seasonal distribution of 

dichlorodiphenyltrichloroethanes (DDTs), chlordanes (CHLs), 

hexachlorobenzene (HCB), and endosulfans (Endo) are presented in this paper, 

and their potential sources are discussed based on the dataset. It is estimated 

that ca. 95% of DDTs present in the atmosphere of Chinese cities was still from 

technical DDT, while only ca. approximately 5% was "dicofol-type of DDT". DDT 

application for public health control and DDT activated antifouling paint for fishing 

ships may be the two most important current sources of technical DDT. The DDT 

concentrations in several Chinese cities seem to match well with the reported 

DDT concentrations in human breast milk. A low TC/CC ratio was observed 

across China in the winter to spring, which may provide a fingerprint of Chinese 

chlordane emission. It was suggested that "weathered" chlordane emitted from 

urban construction foundations in winter may give the distinctively low TC/CC 

ratio. The data showed that China is an important global source for HCB. Higher 

HCB concentrations were observed in winter and spring, and in colder cities, 

highlighting an important contribution from combustion sources. Samples with 

higher endosulfan concentrations occurred in the cotton production areas, 

indicating its major use in killing cotton pests. 

Lloyd-Smith, M. (2009). "Information, power and environmental justice in Botany: the 

role of community information systems." J Environ Manage 90(4): 1628-35. 

 In the environmental conflict that surrounds the sighting of hazardous waste 

facilities there is usually a volatile mix of disparities in power, expertise and 

information access as well as differing views on risk, which are all played out 

amidst commercial arrangements and environmental justice concerns. In recent 

times, the volatility of this mix has been further compounded by the growing 

climate of public concern and distrust surrounding scientific developments and 

technology. While there is no 'quick fix' to the complex conflict that this entails, 

community information systems (CISs) based on participatory models can help 

address the outstanding issues of capacity, information access, power inequities 

and environmental justice. CISs are an effective response to the five crucial 

elements of a toxic dispute, that is, the dialogue, capacity building, information 

access, evaluation of hazards and risk, and expertise. This paper will review the 

role of community accessible information systems in the dispute in Botany over 

the management and destruction of Orica Australia's stockpile of the persistent 

organic pollutant, hexachlorobenzene (HCB). It will focus on the role of CIS in 

responding to the challenges for expert information delivery, and in addressing 

the disparity of informational power within the toxic dispute. 
259

Lloyd-Smith, M. E. and L. Bell (2003). "Toxic disputes and the rise of environmental 

justice in Australia." Int J Occup Environ Health 9(1): 14-23. 

 The paper examines the rise of environmental justice issues in Australia, evident 

in two toxic disputes; the first, in a Perth outer suburb in Western Australia where 

residents faced both a hazardous waste dump and the nation's biggest chemical 

fire; and the second, in the Sydney suburb of Botany where residents were 

confronted with the destruction of what is thought to be, the world's largest 

stockpile of hazardous hexachlorobenzene (HCB) waste. The paper reviews the 

range of factors that impacted the local communities' fight for environmental 

justice. It explores the limitations of risk assessment and risk-based policies, as 

well as the problematic role of the expert and the communication of risk. The 

informational inequity and resource disparities so evident in toxic disputes are 

highlighted. The case studies confirmed the inequitable distribution of chemical 

risk as a failure to secure environmental justice for all Australians. 

Lopez-Carrillo, L., M. Lopez-Cervantes, et al. (2002). "Serum levels of betahexachlorocyclohexane, hexachlorobenzene and polychlorinated biphenyls and breast 

cancer in Mexican women." Eur J Cancer Prev 11(2): 129-35. 

 Information on the association between exposure to betahexachlorocyclohexane (beta-HCH), hexachlorobenzene (HCB) or 

polychlorinated biphenyls (PCBs) and the incidence of breast cancer is 

inconclusive. However, exposure to such compounds is a public health concern 

in Mexico and is subject to recent regulation. Serum levels of beta-HCH, HCB 

and PCBs were analysed in 95 histologically confirmed breast cancer cases and 

95 hospital controls, 20-79 years of age, from Mexico City, enrolled between 

March 1994 and April 1996. After adjusting for established risk factors, there was 

no evidence of a relationship between beta-HCH, HCB and PCBs and breast 

cancer risk (OR for beta-HCH tertile 3 versus tertile 1: 1.05 95% CI 0.46-2.40; 

OR for HCB tertile 3 versus tertile 1: 0.46 95% CI 0.20-1.07; OR for PCBs 1.31 

95% CI 0.33-5.21 for the high category of exposure). This study lends no support 

to the case for a role for beta-HCH, HCB or PCBs in breast cancer aetiology. 

Lunsman, T. D. and W. Lick (2005). "Sorption of hydrophobic organic chemicals to 

bacteria." Environ Toxicol Chem 24(9): 2128-37. 

 The toxicity and time-dependent sorption of three hydrophobic organic chemicals 

to Rhodococcus rhodochrous bacteria were investigated. In experiments, 

environmentally relevant concentrations of pentachlorophenol (PCP), 

hexachlorobenzene (HCB), and dichlorobiphenyl (DPCB) were applied to living 

(both growing and nongrowing) bacteria as well as to dead bacteria. For PCP (an 

ionizing chemical), bacterial growth decreased, and bacterial death increased, as 

the PCP concentration increased. In sorption experiments with PCP, the partition 

coefficient was affected by the active uptake of PCP by living but not by dead 

bacteria, by the death of the living bacteria because of PCP toxicity, and by 

saturation of site-specific sorption as the PCP concentration increased. 

Hexachlorobenzene (a nonionizing chemical) did not affect bacterial growth or 
260

death at all HCB concentrations investigated. In sorption experiments with HCB, 

the partition coefficient depended on the rate of bacterial growth relative to the 

sorption rate. The sorption rate depended on the state of bacterial aggregation, 

and this changed with time. Results for DPCB (a nonionizing chemical with an 

equilibrium partition coefficient similar to that of HCB) were similar to those for 

HCB. 

Ma, J., S. Venkatesh, et al. (2003). "Evidence of the impact of ENSO events on 

temporal trends of hexachlorobenzene air concentrations over the Great Lakes." Sci 

Total Environ 313(1-3): 177-84. 

 This study presents an evidence for association of the air concentrations of HCB 

measured in the Great Lakes region with the El Nino-Southern Oscillation 

(ENSO) during the 1990s. The measured HCB concentrations in the atmosphere 

collected by the Integrated Atmospheric Deposition Network (IADN) program in 

the Great Lakes during the 1990s show strong correlations with the Multivariate 

ENSO index (MEI) during winter (December-February) and spring (March-May) 

seasons. These correlations are stronger in the western upper Great Lakes than 

in the eastern portion of the Great Lakes ecosystem (lake Ontario), and 

correspond well to the spatial variability of the surface air temperature in North 

America during El Nino years. Departures of HCB air concentrations for each 

winter during 1992-1999 from that averaged over all winters of 1992-1999, i.e. 

the anomaly, also show the same temporal trend as that of the MEI during the 

same period. In the same time period, it has been reported that direct HCB 

emissions from application of HCB in agriculture, from industrial sources in North 

America and in the rest of the world have decreased substantially compared to 

those in the 1970s and could not by themselves account for observed HCB air 

concentrations around the Great Lakes since the 1990s. Interannual fluctuations 

of HCB concentrations are caused most likely by reemission due to volatilization 

of HCB from the soil contaminated from past use, followed by long-range 

transport associated with ENSO events. In addition to the high correlation 

(R(2)=0.61) between winter HCB air concentrations averaged over the Great 

Lakes region and the MEI the atmospheric circulation patterns associated with 

ENSO events are conducive to the long-range transport of HCB into the Great 

Lakes region. 

Ma, X. and M. M. Havelka (2009). "Phytotoxicity of chlorinated benzenes to Typha 

angustifolia and Phragmites communis." Environ Toxicol 24(1): 43-8. 

 Healthy growth of plants is a prerequisite for successful application of 

phytoremediation technologies. Typha angustifolia and Phragmites communis 

are common wetland plants and have shown potential for phytoremediation of 

hexachlorobenzene (HCB). However, the lack of phytotoxicity data impedes their 

application in field sites. This study investigated the phytotoxicity of HCB, and its 

two metabolites: 1,3,5-trichlorobenzene (1,3,5-TCB) and 1,4-dichlorobenzene 

(1,4-DCB) to Typha and the phytotoxicity of 1,3,5-TCB to Phragmites. The 

phytotoxicity of 1,3,5-TCB is species-dependent, with Typha demonstrating 

significantly higher tolerance than Phragmites. The concentration of 1,3,5-TCB 
261

causing zero growth of Phragmites was determined to be 1575 mg TCB/kg dry 

sediment. The concentration has to be doubled to completely inhibit the growth of 

Typha. Adverse effects of chlorinated benzenes in sediments on Typha 

increased with decreasing chlorine atoms. The concentrations causing zero 

growth of Typha are 5765 mg HCB/kg dry soil, 3157 mg 1,3,5-TCB/kg dry soil, 

and 1325 mg 1,4-DCB/kg dry soil. The higher toxicity of 1,4-DCB than 1,3,5-TCB 

and HCB in sediment was ascribed to its higher availability and easiness to be 

taken up by plants. The conclusion was supported by both growth rate 

calculations and plant height measurements. (c) 2008 Wiley Periodicals, Inc. 

Environ Toxicol, 2009. 

Macleod, M. and D. Mackay (1999). "An assessment of the environmental fate and 

exposure of benzene and the chlorobenzenes in Canada." Chemosphere 38(8): 1777-

1796. 

 BIOSIS COPYRIGHT: BIOL ABS. Systematic modelling of the fate of benzene 

and the chlorobenzenes is presented which follows a four-stage process of 

chemical classification, quantifying discharge rates and environmental 

concentrations, evaluative assessment of fate and regional mass balance 

modelling has been carried out for the southern Ontario region. The EQC model 

was applied to determine the principal transport and transformation processes 

experienced by this group of chemicals, which vary considerably in volatility and 

hydrophobicity. Observed environmental concentrations are in satisfactory 

agreement with the predictions of the steady state Level III ChemCAN model of 

chemical fate. A multiple pathway human exposure model which estimates intake 

of contaminants by residents of southern Ontario has been developed and 

applied to these chemicals. A novel method of deducing maximum tolerable 

environmental concentrations is presented. Results suggest that benzene and 

1,4-dichlorobenzene are present in 

Malmquist, C., R. Bindler, et al. (2003). "Time trends of selected persistent organic 

pollutants in lake sediments from Greenland." Environ Sci Technol 37(19): 4319-24. 

 Sediments from seven lakes in West Greenland were used as natural archives to 

study past and present levels of PCBs (polychlorinated biphenyls, tri- to 

decachlorinated), tetra-BDE #47 (2,2',4,4'-bromodiphenyl ether), chlordane (cisand trans-octachlordane) and HxCBz (hexachlorobenzene). The concentrations 

found are lower than or comparable to concentrations found in sediments from 

other Arctic regions and one to 2 orders of magnitude lower than concentrations 

typically found in sediments at lower latitudes. The observed temporal trends 

(direct and indirect dating) show a decreasing total PCB concentration. Even 

though local contamination sources exist, the POP deposition in the studied area 

is most likely a result from long-range transport. The hypothesis about "cold 

condensation" suggests a latitudinal fractionation to occur between different 

volatile compounds during the transport toward the pole. In this study a time 

delay in the deposition for the low-chlorinated PCBs (tri- and tetrachlorinated), 

compared to their emission histories and compared to higher chlorinated PCBs, 

was indicated. Although very low tetra-BDE #47 concentrations are observed in 
262

this study, there are indications for an increasing concentration in recent 

sediment layers that may reflect increasing environmental concentrations at 

lower latitudes. The investigated pesticides are still in use at lower latitudes, 

however neither chlordane nor HxCBz show any distinct temporal trend of 

increasing or decreasing concentration toward the sediment surface. 

Mansour, M., E. A. Feicht, et al. (1999). "Determination photostability of selected 

agrochemicals in water and soil." Chemosphere 39(4): 575-585. 

 BIOSIS COPYRIGHT: BIOL ABS. The photolysis of selected pesticides in 

aqueous solutions has been investigated. The photolysis produced different 

intermediate substances, which were also found to be soil and microbial 

degradation products. The phototransformation in the presence of TiO2 and 

humic substances leads to a disappearance of these compounds. The reaction 

rate is dependent on the semiconductor oxide and concentration. Photoproducts 

were isolated and characterized by different spectroscopic methods. Results 

from this 

Marti-Cid, R., A. Bocio, et al. (2007). "Intake of chemical contaminants through fish and 

seafood consumption by children of Catalonia, Spain: health risks." Food and Chemical 

Toxicology 45(10): 1968-74. 

 The intake of arsenic (As), cadmium (Cd), mercury (Hg), lead (Pb), 

polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs), polychlorinated 

biphenyls (PCBs), polychlorinated naphthalenes (PCNs), polybrominated 

diphenylethers (PBDEs), polychlorinated diphenylethers (PCDEs), 

hexachlorobenzene, and polycyclic aromatic hydrocarbons through fish and 

seafood consumption by children of Catalonia, Spain, was assessed. In 2005, 

samples of the 14 most consumed marine species in Catalonia were randomly 

acquired in various cities of the country. Analysis of the above chemical 

contaminants were determined according to the appropriate analytical techniques 

and the daily intakes were estimated. For most pollutants, intake was higher in 

boys than in girls. Average exposure of children to contaminants through fish and 

seafood consumption did not exceed the respective tolerable daily intake of 

those pollutants for which it has been already established (metals, PCDD/Fs plus 

dioxin-like PCBs, HCB, and PAHs). In relation to body weight, intake by children 

of most contaminants was higher than that found for other age groups of the 

general population of Catalonia. 

Marvin, C., S. Painter, et al. (2004). "Spatial and temporal trends in surface water and 

sediment contamination in the Laurentian Great Lakes." Environ Pollut 129(1): 131-44. 

 Data from recent sediment and surface water surveys have been collated and 

mapped to illustrate the spatial distribution of contaminants across the entire 

Great Lakes basin. Information from historical surveys, together with data from 

surface water monitoring programs in three major connecting channels, has also 

been collated in order to evaluate temporal trends. In general, Lakes Superior 

and Michigan exhibited the lowest levels of sediment contamination while Lake 

Ontario had the highest. Contaminants such as gamma-HCH (lindane) and 
263

dieldrin were ubiquitous in surface waters across the entire basin, which was 

indicative of atmospheric sources. The distribution of other compounds including 

hexachlorobenzene, octachlorostyrene and mirex indicated the presence of local 

sources within the watersheds of the connecting channels. Surficial sediment 

contamination was found to have decreased markedly since the late 1960s and 

1970s. Similarly, surface water contamination decreased over the period 1986-

1997 with concentrations of dieldrin, hexachlorobenzene, octachlorostyrene and 

mirex reduced by over 50%. However, the spatial distributions of both sediment 

and surface water contamination indicate that further effort is warranted in 

reducing local sources of contaminants, particularly in Lake Ontario. 

Mayer, P., J. Wernsing, et al. (1999). "Establishing and controlling dissolved 

concentrations of hydrophobic organics by partitioning from a solid phase." 

Environmental Science and Technology 33(13): 2284-2290. 

 BIOSIS COPYRIGHT: BIOL ABS. Bioavailable concentrations of hydrophobic 

organic substances in aqueous tests often decrease as a result of (bio)sorption, 

volatilization, or degradation. In the present study, partitioning driven 

administering (PDA) is introduced as an approach to maintain constant exposure 

levels of hydrophobic organics in aqueous tests. The working principle of PDA is 

to control dissolved concentrations by partitioning from a dominating solid phase. 

For this purpose, test compounds are loaded on an octadecyl ocess was 

demonstrated, and PDA was successfully applied to dose 1,3,5-tribromobenzene 

and hexachlorobenzene in algal toxicity tests. Finally, the feasibility to administer 

concentrations up to aqueous solubility, to administer mixtures, and to dominate 

the fugacity of multicompartment systems is discussed. 

McGeer, J. C., K. V. Brix, et al. (2003). "Inverse relationship between bioconcentration 

factor and exposure concentration for metals: implications for hazard assessment of 

metals in the aquatic environment." Environ Toxicol Chem 22(5): 1017-37. 

 The bioconcentration factor (BCF) and bioaccumulation factor (BAF) are used as 

the criteria for bioaccumulation in the context of identifying and classifying 

substances that are hazardous to the aquatic environment. The BCF/BAF 

criteria, while developed as surrogates for chronic toxicity and/or biomagnification 

of anthropogenic organic substances, are applied to all substances including 

metals. This work examines the theoretical and experimental basis for the use of 

BCF/BAF in the hazard assessment of Zn, Cd, Cu, Pb, Ni, and Ag. As well, 

BCF/BAFs for Hg (methyl and inorganic forms) and hexachlorobenzene (HCB) 

were evaluated. The BCF/BAF data for Zn, Cd, Cu, Pb, Ni, and Ag were 

characterized by extreme variability in mean BCF/BAF values and a clear inverse 

relationship between BCF/BAF and aqueous exposure. The high variability 

persisted when even when data were limited to an exposure range where chronic 

toxicity would be expected. Mean BCF/BAF values for Hg were also variable, but 

the inverse relationship was equivocal, in contrast with HCB, which conformed to 

the BCF model. This study illustrates that the BCF/BAF criteria, as currently 

applied, are inappropriate for the hazard identification and classification of 

metals. Furthermore, using BCF and BAF data leads to conclusions that are 
264

inconsistent with the toxicological data, as values are highest (indicating hazard) 

at low exposure concentrations and are lowest (indicating no hazard) at high 

exposure concentrations, where impacts are likely. Bioconcentration and 

bioaccumulation factors do not distinguish between essential mineral nutrient, 

normal background metal bioaccumulation, the adaptive capabilities of animals to 

vary uptake and elimination within the spectrum of exposure regimes, nor the 

specific ability to sequester, detoxify, and store internalized metal from metal 

uptake that results in adverse effect. An alternative to BCF, the accumulation 

factor (ACF), for metals was assessed and, while providing an improvement, it 

did not provide a complete solution. A bioaccumulation criterion for the hazard 

identification of metals is required, and work directed at linking chronic toxicity 

and bioaccumulation may provide some solutions. 

McLachlan, M. S. (1999). "Framework for the interpretation of measurements of SOCs 

in plants." Environmental Science and Technology 33(11): 1799-1804. 

 BIOSIS COPYRIGHT: BIOL ABS. Plant uptake of semivolatile organic 

compounds (SOCs) occurs primarily from the atmosphere via one of three 

processes: equilibrium partitioning between the vegetation and the gas phase, 

kinetically limited gaseous deposition, or wet and dry particle-bound deposition. 

Each of these processes depends on different atmospheric concentrations, plant 

properties, and environmental variables. Hence, in interpreting measurements of 

SOCs in plants, it is imperative that the major process responsible for t nt (KOA) 

of the chemical. The mathematical analysis leads to two interpretive tools, both 

log-logplots, one of the quotient of the vegetation and gas-phase concentrations 

vs KOA and one of the quotient of the vegetation and particle-bound 

concentrations vs the quotient of the particle-bound and gaseous concentrations. 

Each of these plots contains three distinct and easily recognizable segments, 

and each segment corresponds to one of the three deposition processes. When 

the experi 

McNellis, R. P., J. D. Fallon, et al. (2001). "Water-Quality Assessment of Part of the 

Upper Mississippi River Basin, Minnesota and Wisconsin: Organochlorine Compounds 

in Streambed Sediments and Fish Tissues, 1995-97." 

 Water-resources investigations. This document is color dependent and/or in 

landscape layout. It is currently only available on CD-ROM. Streambed 

sediments and fish tissues were collected in part of the Upper Mississippi River 

Basin to assess the presence and distribution of organochlorine compounds 

(OC's) including PCBs. A total of 13 OC's were detected among 14 of 27 

streambed sediment sampling locations. In fish tissues pnalyzed, 9 OC's were 

detected among 17 of 24 sites sampled. Eight OC's were detected in both fish 

and streambed sediment samples, they were: cis-chlordane, o,p'-DDD; p,p-DDE; 

p,p-DDT; hexachlorobenzene; transnonachlor; and PCBs. The most frequently 

detected OC's were: p,p-DDE; and p,p-DDD in streambed sediment and p,p-DDE 

and PCBs in fish tissues. No OC's were detected in streambed sediment at 

agricultural sites; however, the agricultural sites had 17 detections of OC's in fish 

tissue. Urban streams had concentrations of total DDT and metabolites in 
265

streambed sediment that exceed guidelines for classification of sites with high 

probabilities of adverse effects to aquatic organisms. Total DDT was the only OC 

within an urban land use that exceeded guidelines for piscivorous wildlife. 

Meijer, S. N., W. A. Ockenden, et al. (2003). "Spatial and temporal trends of POPs in 

Norwegian and UK background air: implications for global cycling." Environ Sci Technol

37(3): 454-61. 

 Data are presented for PCBs and HCB measured by passive air samplers 

(SPMDs) along a latitudinal transect from the south of the UK to the north of 

Norway during 1998-2000. This work is part of an ongoing air sampling campaign 

in which data were previously gathered for 1994-1996. Comparisons of the 

masses of chemicals sequestered by the SPMDs during these different time 

intervals are used to investigate spatial and temporal trends. Results are 

discussed in the context of sources, long-range atmospheric transport, 

fractionation/cold condensation, and global clearance processes controlling 

ambient levels of POPs. Spatial trends show a decrease in absolute sequestered 

amounts of PCBs with increasing latitude i.e., with increasing distance from the 

source area. However, relative sequestered amounts of the homologue groups 

(expressed as a ratio to penta-PCB) show a clear latitudinal trend, with the 

relative contribution of the lighter congeners increasing with increasing latitude, 

providing evidence of latitudinal fractionation. Absolute amounts of HCB increase 

with latitude, suggesting this compound is undergoing cold condensation. 

Sequestered amounts of PCBs generally decreased between the two sampling 

periods by a factor 2-5 over 4 years, suggesting half-lives on the order of 1.7-4 

years. The relative rates of decline (1998-2000 data as a percentage of the 1994-

1996 data) were compared for different congeners and latitudes. No clear 

latitudinal trends were found, with all sites/congeners showing a similar marked 

decline over time to ca. 30% of the former value. We discuss the interpretation of 

these observations and conclude they imply that the underlying trends of current 

ambient levels of PCBs in European background air are still largely controlled by 

primary emissions, rather than recycling/secondary emissions from the major 

environmental repositories such as soils or water bodies. 

Meijer, S. N., W. A. Ockenden, et al. (2003). "Global distribution and budget of PCBs 

and HCB in background surface soils: implications for sources and environmental 

processes." Environ Sci Technol 37(4): 667-72. 

 This paper presents data from a survey of polychlorinated biphenyls (PCBs) and 

hexachlorobenzene (HCB) concentrations in 191 global background surface (0-5 

cm) soils. Differences of up to 4 orders of magnitude were found between sites 

for PCBs. The lowest and highest PCB concentrations (26 and 97,000 pg/g dw) 

were found in samples from Greenland and mainland Europe (France, Germany, 

Poland), respectively. Background soil PCB concentrations were strongly 

influenced by proximity to source region and soil organic matter (SOM) content 

Most (>80%) of the estimated soil PCB burden remains in the "global source 

region" of the Northern Hemisphere (NH) temperate latitudes (30-60 degrees N) 

or in the OM-rich soils just north of that %SOM correlated with PCB and HCB in 
266

the global data set, with the correlation coefficients being greater for HCB and 

the lighter PCBs than for heavier homologues. OM-rich soils in the NH 

consistently contained the highest burdens; such soils are a key global 

compartment for these compounds. Evidence for global fractionation of PCBs 

was found in the subset of soils from latitudes north of the global source region 

but was not discerned with the global data set The full data set was used to 

estimate the burden for individual congeners/homologues in surface background 

soils and a global soil total PCB burden of 21,000 t. The significance of the 

inventory is briefly discussed in relation to the latest estimates of global 

production and atmospheric emission. 

Metcalfe, T. L., P. J. Dillon, et al. (2008). "Effects of formulations of the fungicide, 

pentachloronitrobenzene on early life stage development of the Japanese medaka 

(Oryzias latipes)." Chemosphere 71(10): 1957-62. 

 Quintozene is a fungicide containing the active ingredient, 

pentachloronitrobenzene (PCNB) that is used to control "snow mold" on golf 

courses in temperate regions of North America. In this study, quintozene and a 

formulation of quintozene widely used on golf courses, FFII were tested for 

toxicity to early life stages of the Japanese medaka, Oryzias latipes. For medaka 

exposed in static non-renewal assays to quintozene for 17d from the fertilized 

egg stage to yolk resorption at the fry stage, the LC(50) for mortality was a 

nominal concentration of 707 microgl(-1) and the effective concentration for 50% 

hatch (i.e. EC(50)) was a nominal concentration of 71 microgl(-1). Eggs and fry 

showed developmental abnormalities, including ocular malformations and 

retarded development of the brain, notochord, organs and body segmentation, 

which were interpreted as teratogenic responses to exposure to PCNB. For 

medaka exposed to quintozene, the LOECs for abnormalities of the eye and all 

other developmental abnormalities were 750 and 100 microgl(-1), respectively. In 

medaka exposed to the FFII formulation, similar patterns of mortalities, reduced 

hatching success and developmental abnormalities were observed, but at higher 

test concentrations that were consistent with the proportion of quintozene in the 

formulation. For medaka exposed to the formulation, the LOECs for 

abnormalities of the eye and all other developmental abnormalities were 10,000 

and 1,000microgl(-1), respectively. Overall, these data indicate that studies 

should be conducted to assess the risk of exposure of early life stages of fish to 

quintozene in watersheds impacted by golf courses. 

Miller, C. A., 3rd (1999). "A human aryl hydrocarbon receptor signaling pathway 

constructed in yeast displays additive responses to ligand mixtures." Toxicol Appl 

Pharmacol 160(3): 297-303. 

 An optimized signal transduction pathway that reproduces the response of 

human aryl hydrocarbon (Ah) receptor to ligands has been established in 

Saccharomyces cerevisiae. Ligand treatment induced a 50-fold increase in betagalactosidase activity from a reporter plasmid in yeast engineered to express 

human Ah receptor and Ah nuclear translocator (Arnt) proteins. The archetypal 

Ah receptor ligand, 2,3,7,8-tetrachlorodibenzo(p)dioxin, activated Ah receptor 
267

and induced lacZ reporter activity at concentrations of >/=0.3 nM. Mixtures of 

halogenated and nonhalogenated Ah receptor ligands produced additive 

signaling responses in this yeast bioassay. These results were consistent with 

the existence of a common binding site and mechanism of ligand-mediated Ah 

receptor activation. Although yeast have no natural counterpart to the Ah 

receptor pathway, expression of human Ah receptor and Arnt under the 

appropriate conditions provides a functional model system for studying Ah 

receptor activation and signal transduction. 

Miniero, R., G. Ceretti, et al. (2006). "Persistent and toxic substances in the Venice 

lagoon biota: an approach for quantitative data analysis for risk management." Ann Ist 

Super Sanita 42(4): 453-60. 

 An approach based on hypothesis testing for the management of persistent 

inorganic and organic toxic chemicals (PTS/POPs) detected in clams and 

mussels from the Venice lagoon is presented. The chemicals of interest for this 

evaluation were the polychlorinated biphenyls (PCBs), dibenzodioxins (PCDDs), 

and dibenzofurans (PCDFs), hexachlorobenzene (HCB), and the heavy metals 

cadmium (Cd), mercury (Hg), and lead (Pb). Two statistically different 

populations of data for PCDDs+PCDFs (TEQs), HCB, Cd, and Pb, associated 

with biota samples collected respectively in the lagoon central district and in the 

southern and northern districts were identified. The central district is under the 

impact of the Porto Marghera industrial settlement and the city of Venice, 

whereas the southern and northern districts are subject to a general impact. Of 

the aforementioned chemicals, those with more discriminating power were found 

to be HCB and PCDDs+PCDFs. 

Miyoshi, K., T. Nishio, et al. (2004). "Detoxification of hexachlorobenzene by 

dechlorination with potassium-sodium alloy." Chemosphere 55(11): 1439-46. 

 Dechlorination of hexachlorobenzene (HCB) was achieved by a liquid potassiumsodium (K-Na)-alloy. HCB in a cyclohexane/benzene solution (22 mmol/l, 4.67 g/l 

as chlorine) was dechlorinated by almost 100% after a 30-min reaction, indicating 

high reactivity of K-Na alloy and high proton donating power of cyclohexane. 

Decreasing orders of chlorobenzenes identified after a 15-min reaction, by 

amount were 1,2,3,4->1,2,3,5->1,2,4,5- for tetrachlorobenzenes, 1,2,4->1,2,3-

>1,3,5- for trichlorobenzenes, and 1,4->1,3->1,2- for dichlorobenzenes. It was 

hypothesized that once one chlorine atom in HCB was replaced with a proton, 

the adjacent chlorine atom to the proton tended to be replaced with another 

hydrogen atom. A total of 63 PCBs formed via the Wurtz-Fittig reaction were 

identified as by-products in the sample after a 15-min reaction. Among PCBs 

found, 2,3',4',5-tetrachlorobiphenyl, which was a product from 1,2,4-

trichlorobenzene formed via the Wurtz-Fittig reaction, was detected in relatively 

high concentration (48.9 nmol/ml). The sample obtained from a reaction mixture 

after 30 min contained only 14 PCBs in trace amounts, indicating that the PCBs 

formed were also further dechlorinated by K-Na alloy. Non-chlorinated 

compounds--such as methylbenzene, dimethylbenzene, dimer of tetrahydrofuran, 

and dicyclohexyl (dimer of cyclohexane)--were also identified in the samples. A 
268

method using K-Na alloy developed in the present study dechlorinated 

satisfactorily HCB at room temperature. 

Monagheddu, M., G. Mulas, et al. (1999). "Reduction of polychlorinated dibenzodioxins 

and dibenzofurans in contaminated muds by mechanically induced combustion 

reactions." Environmental Science and Technology 33(14): 2485-2488. 

 BIOSIS COPYRIGHT: BIOL ABS. Some selected results are reported from an 

ongoing study concerning mechanochemical dehalogenation reactions carried 

out under autopropagating high-temperature regimes. Our work shows that 

instantaneous burning reactions can be ignited in highly exothermic systems 

involving chloroorganics when subjected to intensive mechanical treatments. A 

reference trial using calcium hydride-hexachlorobenzene is first presented. No 

residual traces of the organohalide compound were found in the reacted powders 

or in the gaseous phase sampled from the headspace of the milling reactor. The 

solid products of the reaction were restricted to CaHCl and CaCl2 salts and 

graphite. Similar combustion-like phenomena were observed when contaminated 

mud samples were added to initial reactants. The contaminated mud was 

obtained from a waste site and contained traces of polychlorodibenzodioxins and 

polychlorodibenzof urans. It was observed that an effective chemical oven was 

created which caused the thermochemicalbreakdown of the hazardous 

compounds. A transformation yield greater than 99.6% was obtained with a 

decrease of the toxic equivalent concentration from 2492 to 0.788 mug/kg. Unlike 

conventional incineration methods, the mechanically induced burst processes run 

under a strictly confined environment and controlled conditions. 

Monirith, I., H. Nakata, et al. (1999). "Persistent organochlorine residues in marine and 

freshwater fish in Cambodia." Marine Pollution Bulletin 38(7): 604-612. 

 BIOSIS COPYRIGHT: BIOL ABS. Concentrations of persistent organochlorines 

(OCs) such as PCBs (polychlorinated biphenyls), DDT compounds (DDTs), HCH 

(hexachlorocyclohexanes) isomers (HCHs), chlordane compounds (CHLs) and 

HCB (hexachlorobenzene) were determined in 27 species of marine and 

freshwater fish collected from Cambodia. DDT and its derivatives were the 

predominantly detected compounds in both marine and freshwater fish. PCBs 

were the second highest followed by HCHs, CHLs and HCB. Freshwater fish 

contained higher conc ed that Cambodia has kept "Clean Environment" among 

Asian and Oceanic countries. 

Montone, R. C., S. Taniguchi, et al. (2005). "PCBs and chlorinated pesticides (DDTs, 

HCHs and HCB) in the atmosphere of the southwest Atlantic and Antarctic oceans." Mar 

Pollut Bull 50(7): 778-82. 

 

Moser, G. A. and M. S. McLachlan (1999). "A non-absorbable dietary fat substitute 

enhances elimination of persistent lipophilic contaminants in humans." Chemosphere

39(9): 1513-1521. 

 BIOSIS COPYRIGHT: BIOL ABS. For individuals contaminated with persistent 

lipophilic pollutants, there is an urgent need for a therapy to enhance 
269

contaminant elimination from the body and hence reduce long term exposure. 

This study investigated the possibility of enhancing the excretion of native 

chemical via the faeces by augmenting the lipophilic properties of the faeces with 

the non-absorbable lipid substitute olestra. The faecal excretion of 

polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDDs), polychlorinated 

the food additive. Using 2,3,7,8-Cl4DD as an example, it was estimated that 

ingestion of 25 g/d of olestra would more than double the overall rate of 

elimination of this compound from the body. It is concluded that regular 

consumption of olestra may provide a therapeutic approach for reducing the body 

burden of persistent lipophilic contaminants. 

Mu, H., C. Wesen, et al. (1999). "Response factors of organochlorine compounds in the 

electrolytic conductivity detector." Journal of Chromatography a 849(1): 285-292. 

 BIOSIS COPYRIGHT: BIOL ABS. In our previous studies we have used 

electrolytic conductivity detection (ELCD) in the selective analysis of chlorinated 

fatty acids in marine samples. In order to determine the chlorinated fatty acids 

quantitatively, we studied the ELCD response factors (RFs) of chlorinated fatty 

acids and compared them with those of other chlorinated compounds. We also 

studied the effect of reactor temperature and total gas flow-rate on the RFs. The 

ELCD RFs of different organochlorine compounds varied signifi lower RFs than 

compounds without nitrogen, owing to a neutralization of hydrogen chloride by 

ammonia. 

Mueller, J. F., D. Haynes, et al. (1999). "PCDDs, PCDFs, PCBs and HCB in marine and 

estuarine sediments from Queensland, Australia." Chemosphere 39(10): 1707-1721. 

 BIOSIS COPYRIGHT: BIOL ABS. Concentrations of 2,3,7,8-chlorine substituted 

PCDDs, PCDFs, selected PCB congeners and HCB were determined in 

sediment samples collected from sites along the east coast of Queensland in 

northern Australia. PCDDs were detectable in all sediment samples while 

PCDFs, PCBs and HCB were mainly found in sediment samples collected from 

sites in the Brisbane metropolitan area. The results provide evidence that an 

unidentified source for higher chlorinated PCDDs exists along the Queensland 

coast. 

Muir, D., B. Braune, et al. (1999). "Spatial and temporal trends and effects of 

contaminants in the Canadian Arctic marine ecosystem: A review." Science of the Total 

Environment 230(1-6): 83-144. 

 BIOSIS COPYRIGHT: BIOL ABS. Recent studies have added substantially to our 

knowledge of spatial and temporal trends of persistent organic pollutants and 

heavy metals in the Canadian Arctic marine ecosystem. This paper reviews the 

current state of knowledge of contaminants in marine biota in the Canadian Arctic 

and where possible, discusses biological effects. The geographic coverage of 

information on contaminants such as persistent organochlorines (OCs) (PCBs, 

DDT- and chlordane-related compounds, hexachlorocyclohexanes, t seals have 

only been studied recently at one location. Contaminant measurements in 

bearded seal, harbour seal, bowhead whale and killer whale tissues from the 
270

Canadian Arctic are very limited or non-existent. Many of the temporal trend data 

for contaminants in Canadian Arctic biota are confounded by changes in 

analytical methodology, as well as by variability due to age/size, or to dietary and 

population shifts. Despite this, studies of OCs in ringed seal blubber at Holman 

Island 

Murayama, H., Y. Takase, et al. (2003). "Seasonal change of persistent organic 

pollutant concentrations in air at Niigata area, Japan." Chemosphere 52(4): 683-94. 

 The concentrations of persistent organic pollutants (POPs), such as HCB, alpha-, 

beta-, gamma- and delta-HCH, trans- and cis-chlordane (t-CHL, c-CHL), DDE, 

DDD and DDT, in ambient air have been measured at five sampling points in 

Niigata area, Japan (Niigata, Maki, Tsubame, Jouzo and Yahiko) during the 

period from September 1999 to November 2001. HCB, alpha-HCH, t-CHL and cCHL showed higher concentrations than the other chemicals in all locations. All 

the POPs except t-CHL and c-CHL collected at urban sites of the Niigata Plain 

was almost the same in their concentration levels. Higher concentrations of tCHL and c-CHL in residential areas should be attributed to the past usage of the 

chemical as a termiticide. At Yahiko (remote site), most of the POPs showed 

lower concentrations than those measured at the other sampling sites, although 

alpha-HCH and gamma-HCH were comparable with the concentrations found at 

the other sampling sites. All POPs except alpha-HCH and gamma-HCH tend to 

decrease 41-80% in their concentrations from 2000 to 2001. The lower POPs 

concentrations in winter and the higher POPs concentrations in summer at every 

sampling point can be partly explained by temperature differences. Applying the 

equation of the logarithm of the POP partial pressure in air versus reciprocal 

temperature (lnPa=m/T+b) to our data, linear relations were observed. HCB gave 

a poor linearity and the smallest slope, while beta-HCH, t-CHL and c-CHL gave 

good linearities and large slopes in the equation. The results suggest that HCB 

level is influenced by not only the emission from terrestrial sources but the 

global-scale background pollution. A peculiar observation is that beta-HCH 

concentration measured in our study showed large temperature dependence, 

indicating there could be a source of contamination in the surrounding areas. 

Nakatsu, N., T. Nakamura, et al. (2007). "Evaluation of action mechanisms of toxic 

chemicals using JFCR39, a panel of human cancer cell lines." Molecular Pharmacology

72(5): 1171-80. 

 We previously established a panel of human cancer cell lines, JFCR39, coupled 

to an anticancer drug activity database; this panel is comparable with the NCI60 

panel developed by the National Cancer Institute. The JFCR39 system can be 

used to predict the molecular targets or evaluate the action mechanisms of the 

test compounds by comparing their cell growth inhibition profiles (i.e., 

fingerprints) with those of the standard anticancer drugs using the COMPARE 

program. In this study, we used this drug activity database-coupled JFCR39 

system to evaluate the action mechanisms of various chemical compounds, 

including toxic chemicals, agricultural chemicals, drugs, and synthetic 

intermediates. Fingerprints of 130 chemicals were determined and stored in the 
271

database. Sixty-nine of 130 chemicals ( approximately 60%) satisfied our criteria 

for the further analysis and were classified by cluster analysis of the fingerprints 

of these chemicals and several standard anticancer drugs into the following three 

clusters: 1) anticancer drugs, 2) chemicals that shared similar action 

mechanisms (for example, ouabain and digoxin), and 3) chemicals whose action 

mechanisms were unknown. These results suggested that chemicals belonging 

to a cluster (i.e., a cluster of toxic chemicals, a cluster of anticancer drugs, etc.) 

shared similar action mechanism. In summary, the JFCR39 system can classify 

chemicals based on their fingerprints, even when their action mechanisms are 

unknown, and it is highly probable that the chemicals within a cluster share 

common action mechanisms. 

Newsome, W. H. and J. J. Ryan (1999). "Toxaphene and other chlorinated compounds 

in human milk from northern and southern Canada: A comparison." Chemosphere

39(3): 519-526. 

 BIOSIS COPYRIGHT: BIOL ABS. Human milk from residents of northern 

Canada (Keewatin) was compared to that in national surveys of southern 

Canada with respect to residues of toxaphene, PCBs, PCDDs, chlordane, and 

several other persistant organic compounds. Concentrations of toxaphene were 

approximately ten-fold higher in specimens from Keewatin than from the south. 

Toxaphene concentrations in samples from the Great Lakes Basin collected in 

1992 were not significantly (p < 0.05) different from those of the rest of Canada; 

Norstrom, R. J., T. P. Clark, et al. (2007). "ABAM, a model for bioaccumulation of POPs 

in birds: validation for adult herring gulls and their eggs in Lake Ontario." Environ Sci 

Technol 41(12): 4339-47. 

 An Avian BioAccumulation Model (ABAM) of persistent organic pollutant (POP) 

uptake and elimination in adult life-stage of birds was validated by simulation of 

concentrations of DDE, dieldrin, mirex, and HCB in herring gull eggs in Lake 

Ontario for the years 1985, 1990, and 1992. These chemicals represented a 

range of whole-body half-lives of 82-265 days in the gull. Dietary intake of POPs 

by a female gull was simulated by a dynamic bioenergetics model which included 

dependence on temperature, photoperiod, egg production, and feeding chicks. 

Concentrations in the two main prey fish of the gull in Lake Ontario were used for 

POP exposure. Clearance from the female was based on a two compartment 

toxicokinetic model. Egg concentrations were estimated from egg/whole body 

female concentration ratios. Simulated concentrations were compared to 

measured concentrations in gull eggs from 4 different colonies in the northern 

part of Lake Ontario. Simulations using a diet of 81% fish and 19% 

uncontaminated food resulted in the best fit with least variance among predicted 

and measured data. The mean ratio of predicted to measured concentrations in 

eggs was 1.0 +/- 0.27 among chemicals, years, and colonies for this exposure 

scenario. This result was in excellent agreement with field assessments of 

herring gull diet composition in Lake Ontario of 80-82% fish. The ability to 

perform accurate a priorisimulations for the range of test conditions employed in 

the validation constituted a rigorous test of the soundness of the model's 
272

structure and parameterization. With species-specific adjustments, ABAM can be 

regarded as a general model for lipophilic POPs bioaccumulation in birds. 

Nowakowska, M. and K. Szczubialka (1999). "Photosensitized dechlorination of 

polychlorinated benzenes. 1. Carbazole-photosensitized dechlorination of 

hexachlorobenzene." Chemosphere 39(1): 71-80. 

 BIOSIS COPYRIGHT: BIOL ABS. Photosensitized dechlorination of 

hexachlorobenzene (HCBz) in hexane and in acetonitrile (MeCN) solutions as 

well as in aqueous solutions of poly(sodium styrenesulfonate-co-Nvinylcarbazole) (PSSS-VCz) copolymer has been studied. It was found that the 

reaction was photosensitized by both molecular and polymeric carbazole (Cz) 

chromophores. The products have been identified using GC, NMR and MS 

analyses. The detected products were: pentachlorobenzene, 

tetrachlorobenzenes, trichlorobenzenes, dichl ution was considerably higher than 

in organic solvents. 

Nygard, T. (1999). "Long term trends in pollutant levels and shell thickness in eggs of 

merlin in Norway, in relation to its migration pattern and numbers." Ecotoxicology 8(1): 

23-31. 

 BIOSIS COPYRIGHT: BIOL ABS. Forty-one eggs of merlin (Falco columbarius) 

collected in Norway between 1978 and 1994 were analyzed for persistent 

environmental pollutants. The mean levels of p,p'-DDE and PCBs were 9.4 

(range 1.8-39.9) mug/g and 1.5 (range 0.25-6.6) mug/g fresh weight, 

respectively. HCB, HCHs, dieldrin and chlordanes all had mean levels of 

approximately 0.1 mug/g, mercury 0.25 mug/g, whereas mirex only had 0.005 

mug/g. Migration counts indicated that the Fennoscandian merlin population 

declined from the 1950' he egg. Pesticide levels were generally decreasing 

during the period covered by the study, and a parallel improvement in shell 

thickness was observed. Ringing recoveries indicated that different wintering 

areas were used by merlins from northern and southern Norway. This was a 

possible contributing factor for the observed regional variation in pollutant 

concentrations. 

O'Hara, T. M., M. M. Krahn, et al. (1999). "Organochlorine contaminant levels in Eskimo 

harvested bowhead whales of arctic Alaska." J Wildl Dis 35(4): 741-52. 

 Organochlorine (OC) levels in liver and blubber of 20 bowhead whales (Balaena 

mysticetus) collected during the Eskimo subsistence harvest at Barrow (Alaska, 

USA) in 1992 and 1993 are presented. Liver sum DDT (lipid weight) was 

significantly greater in male whales than in females. Most of the organochlorines 

measured were at higher levels in longer (older) than in shorter (younger) males. 

For female bowhead whales, hexachlorobenzene and lipid levels decreased and 

other OC levels did not change significantly with increasing length. Most 

organochlorine contaminants have low concentrations in tissues of the bowhead 

whale compared to concentrations in tissues of other cetaceans, especially 

Odontocetes. Based on allowable daily intakes (ADI) levels established by the 

Canadian Northern Contaminants Program (Ottawa, Ontario, Canada) "safe" 
273

levels of blubber to consume were calculated. Chlordane levels in bowhead 

whale blubber results in the most restrictive consumption amount (50 g 

blubber/day). We expect no adverse effects related to these organochlorine 

contaminants to occur in bowhead whales or in consumers of their tissues. 

However, investigation of low level chronic exposure effects and a more rigorous 

assessment of histopathology, biomarkers, and immune status in the bowhead 

whale would be required to conclude "no effect" with more certainty. 

Olea, N., F. Olea-Serrano, et al. (1999). "Inadvertent exposure to xenoestrogens in 

children." Toxicology and Industrial Health 15(1-2): 151-158. 

 BIOSIS COPYRIGHT: BIOL ABS. This article reviews previous studies and 

presents new data on pesticide exposure in order to provide some indications of 

the extent and significance of childhood exposure to xenoestrogens, including 

pesticides, epoxy resins, and polycarbonates. After more than four decades of 

pesticide use, little is known about their adverse effects on health. There is a 

need to address the potential risks associated with the current contamination of 

water, soils, and foods in many agricultural areas. In south endrin, endosulfan, 

o,p'-DDE, and o,p'-DDD, among others. Of the 113 samples studied, 43 were 

positive for one or more pesticides, some of which have estrogenic activity. The 

number of new substances that mimic the action of endogenous estrogens is 

increasing rapidly. These endocrine-disrupting chemicals are not restricted to 

pesticides. Several different compounds used in the food industry, in plasticizers, 

and in dental restorations are also estrogenic. The few studies that hav 

Olsson, A., M. Vitinsh, et al. (1999). "Halogenated environmental contaminants in perch 

(Perca fluviatilis) from Latvian coastal areas." Sci Total Environ 239(1-3): 19-30. 

 The environmental contamination situation in coastal areas of the former Soviet 

Union has up to now been more or less unknown. This study on perch (Perca 

fluviatilis), collected at three locations along the coast of Latvia during 1994 and 

1995, provides concentrations of several ubiquitous environmental contaminants 

(PCBs, HCB, HCHs, 4,4'- DDT, 4,4'-DDE, 4,4'-DDD, trans-Nonachlor, 2,2',4,4'-

tetrabromodiphenyl ether). The concentrations of total PCB were similar at all 

study locations [0.7-1.4 ppm on a lipid weight (l.w.) basis], although a site close 

to the City of Riga indicated the presence of a local PCB contamination source. 

The contamination source was identified mainly by a higher relative content of 

lower chlorinated PCB congeners in the samples. Local pollution sources were 

also indicated for HCH and DDT. A large variation in the HCH isomer 

composition between 1994 and 1995 at one location demonstrates short halflives of HCHs in the environment. The brominated flame retardant compound 

2,2',4,4'-tetrabromdiphenyl ether was present in the range of 6.4-10 ng/g l.w. in 

the perch. The clean-up method applied in this study allowed for quantification of 

two semi-polar contaminants frequently overlooked in Baltic biota, namely 

Dieldrin and bis(4-chlorophenyl) sulfone (BCPS). Concentrations of BCPS were 

remarkably high, i.e. in the same magnitude as the most abundant PCB 

congeners. The results presented shows that the contamination of, e.g. PCB in 
274

an area of the former Soviet Union, the Gulf of Riga, is similar to that observed in 

other parts of the Baltic area. 

Oskam, I. C., E. Ropstad, et al. (2003). "Organochlorines affect the major androgenic 

hormone, testosterone, in male polar bears (Ursus maritimus) at Svalbard." Journal of 

toxicology and environmental health. Part A. 66(22): 2119-39. 

 Normal sexual development and subsequent reproductive function are 

dependent on appropriate testosterone production and action. The regulation of 

steroid hormones, including androgens, can be influenced by both biological and 

environmental factors, including environmental chemicals. Concentrations of 

organochlorines are considerably greater in Svalbard polar bears than in polar 

bears from other regions. Between 1995 and 1998, samples were collected from 

121 male polar bears (Ursus maritimus) from the Svalbard area. In this study, 

testosterone concentration variations were described for male polar bears during 

different seasons and for all age groups. To study possible relationships between 

plasma testosterone concentrations and biological factors, such as age, axial 

girth, and extractable plasma fat, and organochlorine contaminants including 

hexachlorocyclohexanes, hexachlorobenzene, chlordanes, p,p'-DDE, and 16 

individual polychlorinated biphenyl (PCB) congeners, identical statistical analyses 

were performed on the total population and a subsample of reproductively active 

adults. Of the biological factors, axial girth showed a significant positive 

relationship and percentage extractable fat and a significant negative relationship 

with the testosterone concentrations. Both the epsilon pesticides and epsilon 

PCBs made significant negative contributions to the variation of the plasma 

testosterone concentration. The continuous presence of high concentrations of 

organochlorines in male polar bears throughout their life could possibly 

aggravate any reproductive toxicity that may have occurred during fetal and early 

postnatal development. 

Paasivirta, J., S. Sinkkonen, et al. (1999). "Estimation of vapor pressures, solubilities 

and Henry's law constants of selected persistent organic pollutants as functions of 

temperature." Chemosphere 39(5): 811-832. 

 BIOSIS COPYRIGHT: BIOL ABS. An internally consistent set of temperature 

dependent physical-chemical property data was derived for 73 persistent organic 

pollutants, including polychlorinated biphenyls, diphenylethers, dibenzo-pdioxins, and dibenzofurans, organochlorinated pesticides and polycyclic aromatic 

hydrocarbons. Measured data reported in the literature were expanded by 

different estimation and regression methods. Temperature dependent vapor 

pressures were estimated from relative gas chromatographic retention times of 

the type log property = A - B / T. Octanol-water partition coefficients of the same 

compounds at25 ˆC were also compiled and estimated. A comparison of the 

estimated data with literature values showed fair agreement. The estimated 

property values may serve as interim input values to models of the fate of 

persistent organic pollutants under variable climatic conditions. 
275

Paez-Osuna, F., A. C. Ruiz-Fernandez, et al. (2002). "Concentrations of selected trace 

metals (Cu, Pb, Zn), organochlorines (PCBs, HCB) and total PAHs in mangrove oysters 

from the Pacific Coast of Mexico: an overview." Mar Pollut Bull 44(11): 1303-8. 

 

Payne, J. P. and A. Kortenkamp (1999). "Combination effects of a mixture of four 

weakly oestrogenic environmental pollutants." Annual Congress of the British 

Toxicology Society, Stoke on Trent, England, Uk, April 18-21, 1999.Yhuman & 

Experimental Toxicology 18(8): 522. 

 Biosis copyright: biol abs. rrm combination effects of a mixture of four weakly 

oestrogenic environmental pollutantsymeeting abstract mcf-7 cell line 

proliferation o,p'-ddt environmental pollutant mitogenic effects toxicity p,p'-dde 

hexachlorobenzene beta-hexachlorocyclohexane toxicology estrogen 

Pereira, W. E. and T. J. Leiker (1999). "Distribution and transport of selected 

anthropogenic lipophilic organic compounds associated with Mississippi River 

suspended sediment, 1989-1990. AU - ROSTAD CE." Archives of Environmental 

Contamination and Toxicology 36(3): 248-255. 

 BIOSIS COPYRIGHT: BIOL ABS. In the first study on this scale, distribution and 

transport of selected hydrophobic halogenated organic compounds associated 

with suspended sediment from the lower Mississippi River and its principal 

tributaries were determined during two spring and two summer cruises. Lipophilic 

organic compounds identified on the suspended sediment included 

hexachlorobenzene, pentachlorobenzene, pentachloroanisole, dacthal, 

chlordane (cis- and trans-), nonachlor (trans-), chlorthalonil, and penta-, hexa-, 

hep class, PCBs, was estimated at 6,750 kg per year. 

Pohl, H. R., P. R. McClure, et al. (2001). "Public health assessment of 

hexachlorobenzene." Chemosphere 43(4-7): 903-8. 

 Recently, hexachlorobenzene (HCB) was proposed for inclusion in the system of 

toxicity equivalency factors (TEFs) currently used for dioxin- like compounds. In 

this paper, we explore the practical implications of the proposition to the Agency 

for Toxic Substances and Disease Registry (ATSDR) programs by comparing 

respective health guidance values for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) 

and HCB (expressed as total toxicity equivalents [TEQs]), reviewing possible 

interactions between HCB and dioxin-like chemicals, and by providing 

information on actual co-existence of HCB and dioxin-like chemicals at 

hazardous waste sites. We found a good correlation between the TEF-adjusted 

oral exposure guidance values for HCB and guidance values for TCDD. The 

combination of HCB and other dioxin-like compounds was not found in soil, air, 

or water media at hazardous waste sites. Based on this fact, it is not necessary 

to include HCB in the total TEQ count at hazardous waste sites at this time. 

Pontius, F. W. (1999). "Complying with future water regulations: With regulatory activity 

picking up momentum into 2000, utilities must anticipate and strategically plan for 

compliance." Journal of the American Water Works Association 91(3): 46-58. 
276

 BIOSIS COPYRIGHT: BIOL ABS. To comply with future regulations, water 

utilities will need to anticipate and strategically plan for upcoming regulatory 

requirements. Existing regulations set by the US Environmental Protection 

Agency under the Safe Drinking Water Act have been previously reviewed. This 

article reviews current regulatory trends that water utilities should consider in 

strategic planning so that they can comply with new rules within the required time 

frames. 

Porta, M., M. B. de Basea, et al. (2008). "Differences in serum concentrations of 

organochlorine compounds by occupational social class in pancreatic cancer." Environ 

Res 108(3): 370-9. 

 BACKGROUND: The relationships between social factors and body 

concentrations of environmental chemical agents are unknown in many human 

populations. Some chemical compounds may play an etiopathogenic role in 

pancreatic cancer. OBJECTIVE: To analyze the relationships between 

occupational social class and serum concentrations of seven selected 

organochlorine compounds (OCs) in exocrine pancreatic cancer: 

dichlorodiphenyltrichloroethane (p,p'-DDT), dichlorodiphenyldichloroethene (p,p'-

DDE), 3 polychlorinated biphenyls (PCBs), hexachlorobenzene, and betahexachlorocyclohexane. METHODS: Incident cases of exocrine pancreatic 

cancer were prospectively identified, and interviewed face-to-face during hospital 

admission (n=135). Serum concentrations of OCs were analyzed by highresolution gas chromatography with electron-capture detection. Social class was 

classified according to occupation. RESULTS: Multivariate-adjusted 

concentrations of all seven compounds were higher in occupational social 

classes IV-V (the less affluent) than in classes I-II; they were higher as well in 

class III than in classes I-II for four compounds. Concentrations of six OCs were 

higher in manual workers than in non-manual workers (p<0.05 for PCBs). Social 

class explained statistically between 3.7% and 5.7% of the variability in 

concentrations of PCBs, and 2% or less variability in the other OCs. 

CONCLUSIONS: Concentrations of most OCs were higher in the less affluent 

occupational social classes. In pancreatic cancer the putative causal role of 

these persistent organic pollutants may not be independent of social class. There 

is a need to integrate evidence on the contribution of different social processes 

and environmental chemical exposures to the etiology of pancreatic and other 

cancers. 

Postupalsky, S., K. D. Hughes, et al. (1999). "Organochlorine contaminant residues and 

shell thickness of eggs from known-age female ospreys (Pandion haliaetus) in Michigan 

during the 1980s. AU - EWINS PJ." Environmental Pollution 104(2): 295-304. 

 BIOSIS COPYRIGHT: BIOL ABS. Eggs have been widely used as indicators of 

exposure to lipophilic contaminants in wild birds, but very few studies have 

examined the relationship between female age and egg contaminant 

concentrations. Organochlorine contaminant (OC) levels and eggshell thickness 

were determined for 25 addled eggs laid by female ospreys (Pandion haliaetus), 

3-15 years old, in Michigan during the 1980s. A wide range of OCs was detected, 
277

but there was no significant variation in wet weight concentrations of any 

compound with female age or year. Similarly, eggshell thickness did not vary 

significantly with female age or year. Among PCB congeners, neither the degree 

nor the positioning of chlorine substitution on the biphenyl ring, nor the degree of 

hydrophobicity, had any significant influence on contaminant bioaccumulation as 

birds aged. Eggs from females sampled in more than one year indicated 

considerable annual variation in OC levels, presumably reflecting differences in 

recent exposur 

Provini, A. and S. Galassi (1999). "Polychlorinated biphenyls and chlorinated pesticides 

in bird eggs from Calabria (Southern Italy)." Ecotoxicology and Environmental Safety

43(1): 91-97. 

 BIOSIS COPYRIGHT: BIOL ABS. Polychlorinated biphenyl (PCB) and chlorinaed 

pesticide levels in eggs of two terrestrial (kestrel and sparrowhawk) and two 

aquatic (heron and mallard) birds were determined in inhabited areas and 

woodlands of Calabria. The eggs of the two terrestrial raptors were more polluted 

than those of the aquatic birds. Among the raptors, the kestrel demonstrated the 

highest level of pollution because it lives close to villages, whereas sparrowhawk 

lives in forests. The highest PCB and DDT residue concent 

Prudente, M., H. Ichihashi, et al. (1999). "Butyltins, organochlorines and metal levels in 

green mussel, Perna viridis L. from the coastal waters of the Philippines." Fisheries 

science : FS. 65(3): 441-447. 

 BIOSIS COPYRIGHT: BIOL ABS. Contamination by butyltins (BTs), 

organochlorine compounds (OCs) and heavy metals was examined in green 

mussels collected along the coastal areas of the Philippines in 1994 and 1997. 

Significant BTs concentrations revealed widespread contamination along 

nearshore marine waters. Relatively high BTs concentrations were observed in 

samples collected from areas with high boating activities, suggestive that the 

source of TBT (tributyltin) is coming from antifouling paints. While TBT levels 

were found the future. Concentrations of OCs in green mussels were less than 

BTs. Among OCs, PCBs concentrations were found to be relatively high 

particularly in mussels from Manila Bay. Moreover, metal concentrations found 

suggest that the anthropogenic loading of Hg, Pb and Cd to the coasts is 

relatively low, suggestive that the green mussels from these coastal waters are 

not adversely affected by these metal toxicants and pose no risk for human 

health. To our knowledge, this is the first comprehensive r 

Rae, I. and P. Brown (2009). "Managing the intractable: communicative structures for 

management of hexachlorobenzene and other scheduled wastes." J Environ Manage

90(4): 1583-92. 

 This paper explores issues of governance and decision-making structures 

associated with the problem of hexachlorobenzene (HCB) waste at Botany in 

New South Wales. From a government perspective, the problem is 'downstream' 

of a well-known national controversy over whether Australia should have a hightemperature incinerator (HTI) to 'dispose' of such scheduled wastes. The 1992 
278

decision not to proceed with HTI followed an extensive process of public 

consultation, which, against the expectations of industry and government, saw 

the emergence of Australia-wide community opposition. Alternative national 

management plans were formulated for the treatment of several types of 

organochlorine waste, with the scheme of these plans first approved in 1993 by 

the Australian and New Zealand Environment and Conservation Council 

(ANZECC). The HCB Management Plan is one of three such plans (the others 

being for PCBs and organochlorine pesticides). With this, ANZECC established 

the Scheduled Waste Management Group comprising government officials, and 

the National Advisory Body (NAB) made up of stakeholders. Officially the NAB 

had oversight of the HCB problem until 2002 when it was disbanded. As a result 

of the HTI experience, new community consultation protocols were introduced in 

association with the alternative management plans. For HCBs, which are 

confined almost entirely to Orica's Botany site in southeastern Sydney, this led to 

the establishment of the Community Participation and Review Committee 

(CPRC), a representative body with review and advisory functions. This paper 

draws conclusions from this history about government processes of decision 

making, the role of individual and institutional actors, the central importance of 

trust, and the democratisation of risk management. Using concepts delineated by 

McDonell [1991. Toxic waste management in Australia: why did policy reform 

fail? Environment 33(6), 11-13, 33-39; 1997. Scientific and everyday knowledge: 

trust and the politics of environmental initiatives. Social Studies of Science 27, 

819-863.] we identify swings towards, then away from institutionalised trust. 

Across two decades, government and industry have placed faith in centrally 

controlled mechanisms for public participation, hoping to garner trust and 

legitimate privileged technological solutions. On the 'backswings', these 

processes have seen public trust dissipate in the face of government 

misunderstanding of the opportunities for effective bureaucratic interventions. 

Ribes, A., J. O. Grimalt, et al. (2002). "Temperature and organic matter dependence of 

the distribution of organochlorine compounds in mountain soils from the subtropical 

Atlantic (Teide, Tenerife Island)." Environ Sci Technol 36(9): 1879-85. 

 Surface soil samples from Teide mountain (Canary Islands) have been analyzed 

for polychlorobiphenyls (PCBs), DDTs, hexachlorocyclohexanes (HCHs), 

hexachlorobenzene (HCB), and pentachlorobenzene. The samples were situated 

between 10 and 3400 m above sea level being distributed below, at, and above 

the permanent inversion layer system characteristic of the subtropical Atlantic. All 

OC concentrations were, in general, low when compared with the data from 

urban, agricultural, or woodland soils reported elsewhere. Typical ranges were 

0.04-9.2, 0.01-40, 0.001-1, or 0.01-3.2 ng x g(-1) dry weight for total PCBs, 

DDTs, HCHs, or HCB, respectively. These compounds exhibited a high 

dependence from the soil total organic carbon (TOC), showing high coefficients 

in the log(OC) versus log(TOC) correlations. The slopes of the curve fitted 

straight lines were, in turn, highly correlated to the log-transformed octanol-air 

coefficients of the compounds. This overall OC distribution points to steady-state 

conditions for the concentrations of these compounds in these mountain soils, in 
279

equilibrium with TOC. The equilibrium conditions are reached, despite the 

restrictions to convective air movement associated to the permanent atmospheric 

inversion layer at these latitudes. In addition, the log-transformed TOCnormalized concentrations of most PCBs, HCB, and pentachlorobenzene exhibit 

a good correlation with the reciprocal of average annual atmospheric 

temperatures also showing a temperature dependence for their distribution in the 

high mountain system. The calculated pseudo-enthalpies for this dependence, 

120-160 kJ x mol(-1), exhibit higher values than those of octanol-air phase 

change calculated from laboratory experiments in previous studies, 66-93 kJ x 

mol(-1). The difference suggests a higher affinity of OC to soils than that 

corresponding to simple adsorption mechanisms. 

Richardson, B. J. and G. J. Zheng (1999). "Chlorinated hydrocarbon contaminants in 

Hong Kong surficial sediments." Chemosphere 39(6): 913-923. 

 BIOSIS COPYRIGHT: BIOL ABS. Twenty surficial sediments were sampled from 

nearshore Hong Kong waters during 1997-1998, and analyzed for a range of 

chlorinated pesticides and polychlorinated biphenyls (PCBs). Results showed 

that concentrations (on a dry weight basis) of total HCHs were in the range 0.1 - 

16.7 ng g-1, and total DDTs 0.3 - 14.8 ng g-1. PCBs, measured as an Aroclor 

1242, 1248, 1254, 1260 (1:1:1:1) mixture, were found to be in a range of 0.5 - 

97.9 ng g-1, and were at highest concentrations in Victoria Harbour. arl River 

Delta, and to a lesser extent developments around the Shenzhen Special 

Economic Zone), these inputs are also thought to be likely sources of 

contamination. 

Risoul, V., C. Pichon, et al. (1999). "Thermogravimetric study of thermal 

decontamination of soils polluted by hexachlorobenzene, 4-chlorobiphenyl, 

naphthalene, or n-decane." J Hazard Mater 64(3): 295-311. 

 To determine decontamination behavior as affected by temperature, shallow 

beds of a clay-rich, a calcerous, and a sedimentary soil, artificially polluted with 

hexachlorobenzene, 4-chlorobiphenyl, naphthalene, or n-decane, were 

separately heated at 5 degrees C min-1 in a thermogravimetric analyzer. 

Temperatures for deep cleaning of the calcerous and the sedimentary soil 

increased with increasing boiling point (bp) of the aromatic contaminants, but 

removal efficiencies still approached 100% well below the bp. Decontamination 

rates were therefore modelled according to a pollutant evaporation-diffusion 

transport model. For the calcerous and sedimentary soils, this model reasonably 

correlated removal of roughly the first 2/3 of the naphthalene, but gave only fair 

predictions for hexachlorobenzene and 4-chlorobiphenyl. It was necessary to 

heat the clay soil above the aromatics bp to achieve high decontamination 

efficiencies. Weight loss data imply that for temperatures from near ambient to as 

much as 150 degrees C, interactions of each aromatic with the clay soil, or its 

decomposition products, result in lower net volatilization of the contaminated vs. 

neat clay. A similar effect was observed in heating calcerous soil polluted with 

hexachlorobenzene from near ambient to about 140 degrees C. Decontamination 

mechanisms remain to be established, although the higher temperatures needed 
280

to remove aromatics from the clay may reflect a more prominent role for surface 

desorption than evaporation. This would be consistent with our estimates that the 

clay can accommodate all of the initial pollutant loadings within a single surface 

monolayer, whereas the calcerous and sedimentary soils cannot. 

Riva, C., A. Binelli, et al. (2008). "Evaluation of several priority pollutants in zebra 

mussels (Dreissena polymorpha) in the largest Italian subalpine lakes." Environ Pollut

151(3): 652-62. 

 Zebra mussel (Dreissena polymorpha) has been used for the biomonitoring of 

several POPs (PCBs, DDTs, HCB and HCHs) in the largest Italian subalpine 

great lakes (Lake Maggiore, Garda, Como, Iseo and Lugano). Samplings were 

carried out in April 2003 at 15 locations selected according to industrial and 

anthropic levels of lakes. Results have pointed out high DDT levels in D. 

polymorpha specimens from Lake Maggiore (700-1400 ng/g lipids, 5-9 times 

higher than those measured in mussels of other Italian lakes), due to a 

contamination from a chemical plant located on one of the main lake inlet that 

occurred in 1996. On the contrary, PCB levels (400-2509 ng/g lipids) highlighted 

an overall pollution, with some sporadic peaks of contamination. Data showed a 

moderate increase trend compared to those found in a previous monitoring 

campaign carried out in 1996. Future monitoring is needed in order to confirm 

this tendency. 

Rodan, B. D., D. W. Pennington, et al. (1999). "Screening for persistent organic 

pollutants: Techniques to provide a scientific basis for POPs criteria in international 

negotiations." Environmental Science and Technology 33(20): 3482-3488. 

 BIOSIS COPYRIGHT: BIOL ABS. The United Nations Environment Programme 

(UNEP) is currently coordinating negotiations to develop a binding global 

agreement by late in the year 2000 to prohibit, restrict, or reduce the production, 

use, or release of certain persistent organic pollutants (POPs). POPs are a small 

subset of organic chemicals whose characteristics of persistence in the 

environment, accumulation in biological organisms, and toxicity make them 

priority pollutants and environmental risks to humans and ecosystems. Und of 

persistence, bioaccumulation, toxicity, and long-range transport in a policy 

context. The theoretical, empirical, and multimedia modeling approaches used 

reveal that guidance for setting POPs screening criteria can be developed using 

a combination of science and policy input. These approaches suggest that 

criteria adopted under regional POPs agreements in North America and Europe 

are reasonable and tend to isolate a limited number of clearly hazardous POPs 

from the majority of organic chemica 

Rodas-Ortiz, J. P., V. Ceja-Moreno, et al. (2008). "Vitellogenin induction and increased 

plasma 17beta-estradiol concentrations in male Nile tilapia, Oreochromis niloticus, 

exposed to organochlorine pollutants and polycyclic aromatics hydrocarbons." Bull 

Environ Contam Toxicol 81(6): 543-7. 

 Vitellogenin (Vtg), 17beta-estradiol (E2) and testosterone (T) were used as 

biomarkers of endocrine disruption in mature male nile tilapia (Oreochromis 
281

niloticus) from three lakes (Rio, Enmedio and Limon) in Chiapas, Mexico. 

Vitellogenesis induction was found in tilapias from Rio and Limon, moderately 

high E(2) levels in Rio and Limon tilapias, compared with controls (cultured 

tilapias). Significant correlations between benzo(a)pyrene (BaP) metabolites and 

hexachlorobenzene (HCB) with Vtg and E(2) were found. The results of this 

study indicate that endocrine disruption exists in tilapias from Rio and Limon 

lakes, and that exposure to HCB and BaP could be causing these alterations. 

Rossini, P., S. Guerzoni, et al. (2005). "Atmospheric fall-out of POPs (PCDD-Fs, PCBs, 

HCB, PAHs) around the industrial district of Porto Marghera, Italy." Sci Total Environ

349(1-3): 190-200. 

 In order to estimate the importance of atmospheric fall-out of persistent organic 

pollutants (POPs) around the industrial district of Porto Marghera, Italy, 

atmospheric depositions of POPs were collected using bulk samplers inside the 

Lagoon of Venice. Seventy-seven atmospheric deposition samples were 

collected monthly over a 12-month period (March 2003-March 2004) at seven 

sites located close to the industrial area of Porto Marghera. Samples were 

analysed by HRGC/HRMS for PCDD-Fs, PCBs, HCB and PAHs. Differences in 

mean daily fluxes of all organic pollutants between industrial, urban and lagoonal 

stations were clear, atmospheric depositions at industrial sites being higher than 

target values for dioxin deposition recommended by the EU strategy on dioxins, 

furans and polychlorobiphenyls. In order to calculate atmospheric loadings of 

POPs around the industrial district, we considered an area defined by a distance 

of 10 km from the hypothetical centre-point of the main sources of atmospheric 

emissions from Porto Marghera. The calculated loadings, compared with the 

previous estimates, show that annual loadings of POPs are 12, 510, 90 and 130 

kg of PCDD-Fs, PCBs, HCB and PAHs, respectively, corresponding to 350-500 

mg TEQ, thus indicating a slight decrease in PCBs and a great decrease in HCB 

with respect to 1998-99. The input coming from the atmosphere is of the same 

order of magnitude of that due to the watershed runoff and approximately onehalf of the direct industrial discharges. 

Russell, R. W., F. A. P. Gobas, et al. (1999). "Role of chemical and ecological factors in 

trophic transfer of organic chemicals in aquatic food webs." Environmental Toxicology 

and Chemistry 18(6): 1250-1257. 

 BIOSIS COPYRIGHT: BIOL ABS. Trophic transfer of chlorinated organic 

contaminants was investigated in an aquatic community composed of 

zooplankton, benthic invertebrates, and fish. Biomagnification, measured as the 

increase in lipid-based chemical concentrations in predator over that in prey, was 

observed for high-Kow chemicals (log Kow > 6.3). Low-Kow chemicals (log Kow 

< 5.5) did not biomagnify in the food web, and chemicals with log Kow between 

5.5 and 6.3 showed some evidence of biomagnification. Trophic level differenc c 

interactions play a crucial role in the distribution of high-Kow chemicals but not 

for low-Kow chemicals and that (2) contaminant distributions provide a means to 

determine structure in aquatic communities. 
282

Russell, R. W., F. P. Gobas, et al. (1999). "Maternal transfer and in ovo exposure of 

organochlorines in oviparous organisms: A model and field verification." Environmental 

Science and Technology 33(3): 416-420. 

 BIOSIS COPYRIGHT: BIOL ABS. Because early life stages of many species 

exhibit a greater toxicological sensitivity to contaminants than the adult life 

stages, knowledge of the exposure of contaminants during embryonic 

development is a crucial prerequisite for toxicological risk assessment. This study 

presents a chemical equilibrium model for estimating the maternal transfer and 

resulting exposure of developing embryos in eggs of several classes of oviparous 

organisms to hydrophobic organic chemicals. The model is tested against (i) the 

results of a field study, including the analysis of 44 chemicals in eggs and 

maternal tissues of 6 fish species and snapping turtles, and (ii) literature data for 

8 additional fish and 3 bird species. Lipid normalization of egg and maternal 

concentrations reduces the variability in observed egg-to-maternal tissue 

concentration ratios between species by approximately 20-fold. The majority of 

observed lipid normalized egg/maternal tissue concentration ratios for indivi 

Russo, J. and L. Lagadic (2000). "Effects of parasitism and pesticide exposure on 

characteristics and functions of hemocyte populations in the freshwater snail Lymnaea 

palustris (Gastropoda, Pulmonata)." Cell Biol Toxicol 16(1): 15-30. 

 Morphological characteristics and functions of hemocytes were used to compare 

the immunological effects of biological and chemical stress in the freshwater snail 

Lymnaea palustris. Animals were either infected by a trematode parasite 

(Metaleptocephalus sp.), or exposed to environmental contaminants, namely 

atrazine and hexachlorobenzene (HCB). Three populations of circulating 

hemocytes, morphologically and cytochemically distinct (round cells, 

hyalinocytes, granulocytes), were identified in both control and parasitized or 

pesticide-exposed snails. After 6 h of exposure, HCB and atrazine resulted in 8-

fold increases in the mean total number of hemocytes, whereas only a 2.2-fold 

increase was observed 6 h after cercaria emission in parasitized snails. The 

impact of HCB was limited to the first 24 h of exposure, whereas long- lasting 

effects of atrazine were observed. Hyalinocytes and, to a lesser extent, round 

cells contributed most to the increases in hemocyte density in pesticide-exposed 

snails. Parasitism and atrazine treatment resulted in significant increases of 

lectin-stained hemocytes, whereas exposure to HCB did not affect the 

percentages of stained and unstained cells. Hemocyte phagocytic activity 

increased in HCB-exposed snails but with no concomitant change of the 

oxidative burst. Opposite results were obtained in atrazine-treated snail 

hemocytes, with unchanged phagocytosis and decreased phorbol 12- myristate 

13-acetate-stimulated production of reactive oxygen intermediates. No increase 

in phagocytosis, or in the production of reactive oxygen intermediates, was 

observed in hemocytes from parasitized snails. Infection with the immunologically 

compatible trematode parasite Metaleptocephalus sp. and exposure to atrazine 

generated similar reactions from circulating hemocytes, whereas a different 

response pattern was observed in HCB-exposed snails. 
283

Sala, M., N. Ribas-Fito, et al. (2001). "Levels of hexachlorobenzene and other 

organochlorine compounds in cord blood: exposure across placenta." Chemosphere

43(4-7): 895-901. 

 Hexachlorobenzene (HCB) is an organochlorine compound widespread in the 

environment, highly lipophilic, that accumulates in biological systems. It has been 

suggested that it should be classified as a dioxin-like compound. Newborns are 

exposed to organochlorine compounds across the placenta and through 

breastfeeding. Although HCB is one of the most common organochlorine 

compounds, the transplacental transference of HCB from mother to fetus during 

pregnancy has been scarcely documented. This study reports the levels of HCB, 

dichlorodiphenyl trichloroethane (DDT) and its metabolite p,p'DDE, 

polychlorinated biphenyls (PCBs), and beta-hexachlorocyclohexane (beta-HCH) 

in 72 maternal blood samples at delivery and in 69 cord blood samples, from 

which 62 corresponded to mother infant pairs born between May 1997 and 

September 1999 in a rural area highly exposed to HCB. Results show that all 

newborns presented detectable levels of HCB, PCBs, and p,p'DDE, and, to a 

lesser extent, of beta-HCH, the HCB levels being the highest. The geometric 

mean of HCB was 1.1 ng/ml, ranging from 0.3 to 5.7 ng/ml. Concentrations of 

HCB levels in cord blood (log ng/ml) were positively associated with 

concentrations in maternal blood (log ng/ml) (coefficient = 0.45, P < 0.01). 

Gestational age was not associated with the transplacental transfer of HCB. 

Maternal p,p'DDE and beta-HCH levels were also associated with newborn 

levels, but levels of PCBs were not. We conclude that HCB, similar to other 

organochlorinated compounds, has a transplacental transfer. 

Sala, M., J. Sunyer, et al. (2001). "Association between serum concentrations of 

hexachlorobenzene and polychlorobiphenyls with thyroid hormone and liver enzymes in 

a sample of the general population." Occup Environ Med 58(3): 172-7. 

 OBJECTIVES: Hexachlorobenzene (HCB) is a highly lipophilic organochlorine 

compound of widespread environmental occurrence, that accumulates in the 

biological system. It affects the porphyrine metabolism, thyroid hormones, and 

the liver function in animals. Although HCB is one of the most common 

organochlorine compound in humans, little investigation on its health effects has 

been done. Polychlorobiphenyls (PCBs) are also widespread toxic environmental 

contaminants. The aim of the present study was to investigate the association of 

serum HCB and PCB concentrations with thyroid hormone status and liver 

enzymes in human. METHODS: Thyroid stimulating hormone (TSH), total and 

free thyroxine (T4), aspartate aminotransferase (AST), alanine aminotransferase 

(ALT) and gamma-glutamyltransferase (GGT) were measured as biological 

markers of thyroid and liver function in a rural population sample older than 14 

years (n=192, except for TSH with n=608) highly exposed to HCB. Serum 

concentrations of HCB were measured by gas chromatography coupled to 

electron capture detection. RESULTS: After adjustment for confounding 

variables, there was a significant negative association between serum HCB 

concentrations and total T4 (a decrease of 0.32 microg/dl per each unit, ln ng/ml, 

of increase of HCB) and a positive association with GGT (a relative increase of 
284

10 % per each ln unit of increase of HCB), although most subjects (92%) were 

within the normal range for both T4 and GGT. These associations were not 

modified after adjustment for total lipid content or for other organochlorine 

compounds. The association of T4 and GGT with PCB was smaller although 

significant. No association was found with the other biochemical markers. 

CONCLUSIONS: These results suggest that the internal dose of HCB of this 

population may reflect a subtle metabolic effect on thyroid function and an 

enzymatic induction activity. Further studies are needed to evaluate the health 

impact of these effects in more susceptible populations, such as infants. 

Sala, M., J. Sunyer, et al. (1999). "Organochlorine in the serum of inhabitants living near 

an electrochemical factory." Occupational and Environmental Medicine 56(3): 152-158. 

 BIOSIS COPYRIGHT: BIOL ABS. Objectives-To measure the impact of 

occupational and lifestyle factors on concentrations of organochlorine 

compounds in a general population sample living near an electrochemical factory 

with a high airborne concentration of hexachlorobenzene (HCB). Methods-Serum 

samples from 608 people (328 selected from a random sample) were collected in 

1994. Information on lifestyles, occupation, and medical condition was obtained 

by questionnaire. Results-HCB and polychlorinated biphenyls (PCBs) were 

detected in all samples (means 36.7 ng/ml and 4.3 ng/ml respectively), followed 

by dichlorodiphenyl dichloroethane (DDE) and beta-hexachlorocyclohexane 

(beta-HCH), found in 98.7% and 87.3% of the samples respectively (means 4.6 

ng/ml and 2.5 ng/ml, respectively). Concentrations of HCB were the highest ever 

reported. Occupation in the factory was the main determinant of the variation in 

concentrations of HCB (regression coefficients 1.52 (SEM 0.14) in ln (HCB) for 

workers in the product 

Scharenberg, W. and B. Struwe-Juhl (2006). "White-tailed eagles (Haliaeetus albicilla) 

in Schleswig-Holstein no longer endangered by organochlorines." Bull Environ Contam 

Toxicol 77(6): 888-95. 

 

Schell, L. M. (2000). "Mohawk Culture, Behavior, Toxicant Exposure and Health." Crisp 

Data Base National Institutes of Health. 

 Considerable concern exists over possible effects on human physical and 

psycholo gical development of endocrine disrupting environmental contaminants 

such as pol ychlorinated biphenyls (PCBs). Native American communities are 

particularly at r isk owing to subsistence systems and a cultural ethos involving 

greater contact with the physical environment. The proposed study follows-up 

220 Mohawk adolesce nts aged 17-21 years, who participated in a previous 

study when they were 10-16 years old. All adolescents are members of the 

Mohawk Nation at Akwesasne which i s located on the St. Lawrence River, 

adjacent to hazardous waste sites where PCB s have contaminated the local 

ecology. The investigation examines the interrelat ionship between Mohawk 

cultural identity, traditional Mohawk customs, behaviors related to toxicant 

exposure and current toxicant burden. Serum level of PCBs wi ll be assessed by 

congener specific analysis. The study will determine 1) the re lationship of 
285

congeners and their hydroxylated metabolites to thyroid function ( thyroid 

hormone levels and anti-thyroid antibodies), and 2) psychosocial outcome s 

including school behavior and performance, hyperactivity, and adaptation to th e 

community. Data gathered for the past study will be employed to assess variati 

on in metabolism of PCBs, as well as how earlier measures of cognition and 

hyper activity relate to 17 year old psychosocial outcomes. Variation in 

susceptibilit y to PCB effects will be determined by examining the effects of 

concurrent toxic ant exposure (hexachlorobenzene, Mirex, 

dichlorodiphenyldichloroethene, lead), d iet, and indicators of PCB metabolism, 

on the focal measures of adult functionin g. The proposed study will clarify the 

causal pathways between culturally identi fying behavior, PCB exposure and 

body burden, thyroid functioning, cognitive fun ctioning, social behavior and 

school functioning while identifying activities th at are important to maintain 

cultural identify and unrelated to exposure. 

Schwab, B. W. (1999). "The TEF approach for hexachlorobenzene." Environ Health 

Perspect 107(4): 183-4. 

 

Schwartz, S. M. (1999). "Phytoestrogens, Organochlorines, and Fibroid Risk." Crisp 

Data Base National Institutes of Health. 

 Phytoestrogens (such as isoflavones and lignans) and organochlorine 

compounds (such as pesticides and polychlorinated biphenyls) are two broad 

classes of putative endocnne disruptors -- chemicals that may have the capability 

to alter a woman's hormonal milieu. The U.S. population is exposed to dietary 

sources of phytoestrogens through intake of soy foods, grains, and to a lesser 

extent fruits and vegetables. In addition, residues of organochlorine compounds 

can be detected in the tissue of a large proportion of the population. Mthough 

phytoestrogens and organochlorine compounds are suspected of being important 

environmental determinants of hormone-related neoplasia, there are few 

epidemiologic studies testing these hypotheses. Uterine fibroids are benign 

tumors whose growth is highly dependent on ovarian hormones, and are among 

the most frequently diagnosed neoplasms among women. As such, fibroids 

represent an ideal setting in which to test the hypothesis that environmental 

endocrine disruptors affect the risk of important female health outcomes. We 

propose to conduct a population-based case-control study to determine whether 

biomarkers of exposure to phytoestrogens and organochlorine compounds are 

related to a woman's risk of uterine fibroids. The study will be an ancillary 

investigation to The Uterine Leiomyomata Epidemiology Project (TULEP), an ongoing study ended by the National Institutes of Child Health and Human 

Development. TULEP is being conducted within the population of Group Health 

Cooperative (GHC) of Puget Sound, a large pre-paid health plan. TULEP data 

collection includes an extensive in-person interview to assess medical, 

reproductive, menstrual, contraceptive, and other characteristics. For the 

proposed study, we will enroll from TULEP a subset of 175 premenopausal 

women with new, ultrasound-confirmed uterine fibroids (cases) and 175 

premenopausal controls, frequency matched on age and race. From each of 
286

these women we will obtain a serum sample (for organochlorine analyses), an 

overnight urine sample (for phytoestrogen analyses), and food frequency 

questionnaires. In addition, in a sub-sample of 20 cases and 20 controls we will 

conduct an inter-method reliability study to compare phytoestrogen excretion in 

an overnight urine sample against a 24-hour urine sample. Serum samples will 

be analyzed for organochlorine residues (e.g., total PCBs, DDE, heptachlor 

epoxide, oxychlordane, frans-nonachlor, dieldrin, HCB, and beta-BHC) and total 

lipids using standard methods. Urine samples will be analyzed for excretion of 

isoflavones (daidzein, genistein, equol, and O-desmethylangolensin) and lignans 

(enterodiol and enterolactone) and urinary creatinine. Phytoestrogen excretion 

and organochlorine residues in cases and controls will be compared using 

multivariate unconditional logistic regression models. 

Schymura, M. J. (1999). "Core--Epidemiology/Biostatistics." Crisp Data Base National 

Institutes of Health. 

 An Epidemiology/Biostatistics Core is proposed to oversee all data collection 

activities at Akwesasne, to provide outreach tot he mohawk community, to serve 

as a resource to the individual research projects of the Program, and to build 

upon our previous work regarding PCB exposures, body burdens, and health 

effects among Native Americans residing near a Superfund hazardous waste 

site. Working with the Mohawk community and relying upon nearly 10 years of 

experience at Akwesasne, this Core Unit will enroll study participants from 400 

Mohawk families over a five year period. Adults over the age of 35 years will be 

emphasized, given their greater likelihood of exposure. All adult participants will 

be administered a core interview to assess dietary, residential, and occupational 

exposures, together with relevant background variables. The 

Epidemiology/Biostatistics Core also will coordinate data collection for two 

human health research projects. In addition, it will serve as a liaison with the 

Laboratory Services Core, with responsibility for indoor air, dust and tap water 

monitoring for PCBs and blood sampling for 68 PCB congeners, p,p'-DDE, mirex, 

hexachlorobenzene, thyroxine, triiodothyronine, thyrotropin, testosterone, and 

beta-estradiol from all study participants. This Core Unit will assess in vivo 

cytochrome P-4501 A2 activity in selected Mohawk adults through a caffeine 

breath test, a safe and non- invasive procedure that measures the rate at which 

labelled carbon dioxide is exhaled as an indirect monitor. Outreach will consist of 

transmitting the results to study participants, assisting the Mohawk community in 

developing health education and promoting programs, and evaluating mortality, 

morbidity, and risk factors patterns at Akwesasne using vital records, cancer 

registry reports, hospital discharge data, laboratory analyses and the core 

interview. The Epidemiology/Biostatistics Core will provide technical expertise to 

the human health projects and will furnish all students and projects in the 

program with statistical support. Using its familiarity with exposure assessment, 

Geographic Information Systems, epidemiologic and statistical methods, and 

public health, this Core unit will assess the exposure status of adult mohawk 

participants to PCBs for all relevant sources, and determine the relationship of 

exposure to body burdens, cytochrome p-450 activity, and alteractions in 
287

endocrine hormones. Economy of effort will be achieved by having these 

functions performed by one central unit. This coordinated approach was 

recommended by the Mohawk community, and has been endorsed by our Expert 

Advisory Panel to minimize duplication and disruption. 

Schymura, M. J. (2000). "Core--Epidemiology/Biostatistics." Crisp Data Base National 

Institutes of Health. 

 An Epidemiology/Biostatistics Core is proposed to oversee all data collection 

activities at Akwesasne, to provide outreach tot he mohawk community, to serve 

as a resource to the individual research projects of the Program, and to build 

upon our previous work regarding PCB exposures, body burdens, and health 

effects among Native Americans residing near a Superfund hazardous waste 

site. Working with the Mohawk community and relying upon nearly 10 years of 

experience at Akwesasne, this Core Unit will enroll study participants from 400 

Mohawk families over a five year period. Adults over the age of 35 years will be 

emphasized, given their greater likelihood of exposure. All adult participants will 

be administered a core interview to assess dietary, residential, and occupational 

exposures, together with relevant background variables. The 

Epidemiology/Biostatistics Core also will coordinate data collection for two 

human health research projects. In addition, it will serve as a liaison with the 

Laboratory Services Core, with responsibility for indoor air, dust and tap water 

monitoring for PCBs and blood sampling for 68 PCB congeners, p,p'-DDE, mirex, 

hexachlorobenzene, thyroxine, triiodothyronine, thyrotropin, testosterone, and 

beta-estradiol from all study participants. This Core Unit will assess in vivo 

cytochrome P-4501 A2 activity in selected Mohawk adults through a caffeine 

breath test, a safe and non- invasive procedure that measures the rate at which 

labelled carbon dioxide is exhaled as an indirect monitor. Outreach will consist of 

transmitting the results to study participants, assisting the Mohawk community in 

developing health education and promoting programs, and evaluating mortality, 

morbidity, and risk factors patterns at Akwesasne using vital records, cancer 

registry reports, hospital discharge data, laboratory analyses and the core 

interview. The Epidemiology/Biostatistics Core will provide technical expertise to 

the human health projects and will furnish all students and projects in the 

program with statistical support. Using its familiarity with exposure assessment, 

Geographic Information Systems, epidemiologic and statistical methods, and 

public health, this Core unit will assess the exposure status of adult mohawk 

participants to PCBs for all relevant sources, and determine the relationship of 

exposure to body burdens, cytochrome p-450 activity, and alteractions in 

endocrine hormones. Economy of effort will be achieved by having these 

functions performed by one central unit. This coordinated approach was 

recommended by the Mohawk community, and has been endorsed by our Expert 

Advisory Panel to minimize duplication and disruption. 

Selden, A. I., C. Lundholm, et al. (2008). "Polychlorinated biphenyls (PCB), thyroid 

hormones and cytokines in construction workers removing old elastic sealants." Int Arch 

Occup Environ Health 82(1): 99-106. 
288

 OBJECTIVES: To estimate the internal PCB level in Swedish workers 

specialised in PCB abatement in buildings and to measure possible effects of 

PCB on thyroid function and aspects of the immune system. METHODS: Thirty 

six of 40 eligible workers (90%) removing old elastic sealants containing PCB 

and 33 control construction workers provided blood samples for determination of 

19 PCB congeners and some other organochlorine compounds 

(hexachlorobenzene and p,p'-DDE), thyroid function hormones and a set of 

cytokines. The PCB exposed group was reinvestigated after 10 months for a 

trend assessment. RESULTS: The sum of 19 PCB congeners in blood plasma 

from the occupationally PCB-exposed group was twice the level in the controls 

(geometric mean 580 vs. 260 ng/g lipid; P < 0.001), and there was also some 

difference in p,p'-DDE between the groups while the lipid-adjusted 

hexachlorobenzene levels were of the same magnitude. No statistically 

significant increase in overall PCB levels was observed in the abatement workers 

at follow-up and some congeners even declined. Thyroid function was not 

associated with PCB exposure at the current levels and this applied also to the 

cytokines investigated. CONCLUSIONS: Swedish workers removing old elastic 

sealants with PCB have a higher internal PCB load than unexposed colleague 

construction workers, tentatively secondary to historical exposure. A system of 

protective measures seemed to be efficient since no further increase was noted 

after a longish period of additional exposure. There was no evidence of thyroid 

function or immune system involvement, as expressed by a set of cytokines, at 

the low PCB levels recorded. 

Senthilkumar, K., K. Kannan, et al. (1999). "Bioaccumulation profiles of polychlorinated 

biphenyl congeners and organochlorine pesticides in Ganges River dolphins." 

Environmental Toxicology and Chemistry 18(7): 1511-1520. 

 BIOSIS COPYRIGHT: BIOL ABS. Isomer-specific concentrations of 

polychlorinated biphenyls (PCBs) including non-, mono-, and di-ortho-substituted 

congeners, DDT and its metabolites, hexachlorocyclohexane (HCH) isomers, 

chlordane compounds, and hexachlorobenzene (HCB) were determined in river 

dolphin blubber and prey fishes collected during 1993 through 1996 from the 

River Ganges in India. Concentrations of organochlorines were also measured in 

the milk and liver of dolphins, benthic invertebrates, and sediments. The DDTs 

and ,3,4,4',5'-) was the most abundant in dolphin blubber and prey fishes. The 

isomer/congener patternof PCBs and organochlorine pesticides suggested that 

there is less metabolism due to cytochrome P450 enzymes in Ganges river 

dolphins than in marine or terrestrial mammals. The mean 2,3,7,8-

tetrachlorodibenzo-p-dioxin equivalents (TEQs) estimated in river dolphin blubber 

was greater than those that can cause adverse effects in mink. Comparison of 

organochlorine concentrations in rive 

Snedaker, S. C., R. J. Araujo, et al. (1999). "Organochlorine compounds in subtropical 

and tropical marine organisms: A meta-analysis." Toxicology and Industrial Health 15(1-

2): 214-230. 
289

 BIOSIS COPYRIGHT: BIOL ABS. A search of the published and unpublished 

literature was conducted for analytical data on organochlorine compounds in 

tissues of subtropical and tropical marine organisms. The search was limited to 

reports of analyte concentrations in whole body or muscle tissue that were 

minimally determined by chromatographic procedures. A total of 1564 sample 

analyses consisting of 4431 analyte determinations were obtained for hard and 

soft corals, sponges, benthic seagrasses and algae, gastropods, fish and s nits, 

the data were pooled by organochlorine-compound class (i.e., chlorinated 

cyclodienes, chlorinated aliphatics, chlorinated phenols, and chlorinated 

terpenes, hexachlorocyclohexanes, and polychlorinated biphenyls). A metaanalysis of the resulting database yielded a mean analyte concentration of 1594 | 

8768 ng g-1 (dry weight), a median concentration of 23 ng g-1 (dry weight), and a 

mean of 2.89 analytes per sample; the corresponding mean tissue burden is 

4608 ng g-1 (dry wei 

Sochova, I., J. Hofman, et al. (2007). "Effects of seven organic pollutants on soil 

nematode Caenorhabditis elegans." Environ Int 33(6): 798-804. 

 Caenorhabditis elegans is a free-living soil nematode that is commonly used as a 

model for toxicity tests. The aim of this study was to investigate the toxicity of 

seven organic pollutants: four azaarenes (quinoline, acridine, phenazine, and 

1,10-phenanthroline), short-chain chlorinated paraffins, and two 

organochlorinated pesticides (toxaphene and hexachlorobenzene). The exposure 

to all chemicals was carried out in three test media (soil, agar, and aquatic 

medium), and adult mortality was evaluated after 24 and 48 h. Toxaphene was 

the most toxic substance with LC(50) (48 h) of 379 mg/kg in the soil and 0.2 mg/L 

in the aquatic medium. Quinoline was the most toxic chemical in agar test with 

LC(50) (48 h) of 10 mg/L. HCB showed a very low toxicity in all tests, maybe due 

to its very low water solubility. Longer than 24-h test duration was found 

necessary for getting more correct data on toxicity. In comparison with other 

studies, C. elegans was less sensitive than other soil invertebrates. Different 

response might be attributed to different exposure routes and shorter test 

duration. Equilibrium partitioning theory was used to calculate K(oc) from results 

of soil and aquatic tests but this approach was found not working. Our results 

suggest that the tests with nematode C. elegans should be included to the 

battery of tests for risk assessment of POPs in soil. 

Song, S. B., Y. Xu, et al. (2006). "Effects of hexachlorobenzene on antioxidant status of 

liver and brain of common carp (Cyprinus carpio)." Chemosphere 65(4): 699-706. 

 Hexachlorobenzene (HCB)-induced oxidative damages have been published in 

rats while the effects have not yet been reported in fishes. Juvenile common 

carps (Cyprinus carpio) were exposed to waterborne HCB from 2 to 200 microg l1 for 5, 10 or 20 days. Liver and brain were analyzed for various parameters of 

oxidative stress. There were no significant changes of glutathione (GSH) content 

and superoxide dismutase (SOD) activity in liver after 5 or 10 days exposure, 

whereas obvious drops were observed at higher concentrations after 20 days 

exposure. Significant decreases of GSH content and SOD activity in brain were 
290

found during all the exposure days. In brain, HCB also significantly elevated the 

contents of reactive oxygen species (ROS), thiobarbituric acid- reactive 

substances (TBARS, as an indicator of lipid peroxidation products), glutathione 

disulfide (GSSG), and activities of nitric oxide synthase (NOS), glutathione 

peroxidase (GPx), and glutathione reductase (GR), and inhibited activities of 

acetylcholinesterase (AchE) and glutathione S-transferase (GST). The results 

clearly demonstrated that environmentally possible level of HCB could result in 

oxidative stress in fish and brain was a sensitive target organ of HCB toxicity. 

Song, W.-L., Q.-G. Huang, et al. (1999). "beta-cyclodextrin (beta-CD) influence on the 

biotoxicities of substituted benzene compounds and pesticide intermediates." 

Chemosphere 38(4): 693-698. 

 BIOSIS COPYRIGHT: BIOL ABS. The acute toxicities of 19 substituted benzene 

compounds and intermediates of pesticides to Photobacterium phosphoreum in 

beta -CD aqueous solution (5 g) were studied and compared with those in water 

through luminescent bacteria toxicity test, and 15 min-EC50 values were 

obtained. The presence of beta -CD significantly reduce biotoxicities of the lowpolarity compounds, while for the higher-polarity compounds, such effect was 

slight. The differences of biotoxicities were correlated with Log10Kow 

(octanol/water partition coefficients). A significant linear relationship was obtained 

with some abnormal data picked out. Some explanations concerning molecular 

structure of chemicals as well as beta -CD were given for the relationship. 

Stocker, J., M. Scheringer, et al. (2007). "Modeling the effect of snow and ice on the 

global environmental fate and long-range transport potential of semivolatile organic 

compounds." Environ Sci Technol 41(17): 6192-8. 

 Snow and ice have been implemented in a global multimedia box model to 

investigate the influence of these media on the environmental fate and longrange transport (LRT) of semivolatile organic compounds (SOCs). Investigated 

compounds include HCB, PCB28, PCB180, PBDE47, PBDE209, alpha-HCH, 

and dacthal. In low latitudes, snow acts as a transfer medium taking up 

chemicals from air and releasing them to water or soil during snowmelt. In high 

latitudes, snow and ice shield water, soil, and vegetation from chemical 

deposition. In the model version including snow and ice (scenario 2), the mass of 

chemicals in soil in high latitudes is between 27% (HCB) and 97% (alpha-HCH) 

of the mass calculated with the model version without snow and ice (scenario 1). 

Amounts in Arctic seawater in scenario 2 are 8% (alpha-HCH) to 21% (dacthal) 

of the amounts obtained in scenario 1. For all investigated chemicals except 

alpha-HCH, presence of snow and ice in the model increases the concentration 

in air by a factor of 2 (HCB)to 10 (PBDE209). Because of reduced net deposition 

to snow-covered surfaces in high latitudes, LRT to the Arctic is reduced for most 

chemicals whereas transport to the south is more pronounced than in scenario 1 

("southward shift"). The presence of snow and ice thus considerably changes the 

environmental fate of SOCs. 
291

Storelli, M. M. and G. O. Marcotrigiano (2000). "Chlorobiphenyls, HCB, and 

organochlorine pesticides in some tissues of Caretta caretta (Linnaeus) specimens 

beached along the adriatic sea, italy." Bull Environ Contam Toxicol 64(4): 481-8. 

 

Storelli, M. M. and G. O. Marcotrigiano (2001). "Persistent organochlorine residues and 

toxic evaluation of polychlorinated biphenyls in sharks from the Mediterranean Sea 

(Italy)." Mar Pollut Bull 42(12): 1323-9. 

 Persistent organochlorines such as polychlorinated biphenyls including coplanar 

congeners, DDT compounds and HCB were measured in different tissues 

(muscle, liver and eggs) of two Mediterranean shark species: namely 

Centrophorus granulosus and Squalus blainvillei. The concentrations of 

organochlorines in the tissues and organs of both species were in the order 

DDTs > PCBs > HCB. The highest values of DDTs, PCBs and HCB were found 

in liver followed by eggs and muscle. Among DDTs the compound found in 

greatest concentration was p,p'-DDE. The PCB profiles were dominated by 

congeners 138, 153, and 180. The isomers with higher TEQs values were nonand mono-ortho congeners than di-ortho ones in muscle, liver and eggs of both 

species. Among the non- ortho, PCB 126 was the major contributing individual to 

the total TEQs in both species. 

Storelli, M. M., R. G. Stuffler, et al. (2003). "Polycyclic aromatic hydrocarbons, 

polychlorinated biphenyls, chlorinated pesticides (DDTs), hexachlorocyclohexane, and 

hexachlorobenzene residues in smoked seafood." J Food Prot 66(6): 1095-9. 

 Smoked seafoods were screened for the presence of polycyclic aromatic 

hydrocarbons (PAHs), polychlorinated biphenyls (PCBs), and other 

organochlorine compounds. Total PAH concentrations ranged from 46.5 ng/g 

(wet weight) for smoked swordfish to 124.0 ng/g (wet weight) for smoked herring. 

Among the carcinogenic PAHs, benzo(a)pyrene ranged from undetectable levels 

for several smoked fish to 0.7 ng/g for Scottish salmon, dibenzo(ah)anthracene 

was not present in any of the samples analyzed, and benzo(a)anthracene was 

found in all samples and at particularly high levels in salmon (23.2 ng/g). 

Benzo(a)pyrene concentrations were below the tolerance limit for all samples. 

PCB concentrations for the different samples ranged from 2 to 30 ng/g. 

Chlorinated pesticides (DDTs: p,p'-DDE, p,p'-DDT, o,p'-DDT, p,p'-DDD, and o,p'-

DDD) were detected at levels ranging from 0.2 ng/g (wet weight) in bluefin tuna 

to 17.5 ng/g (wet weight) in salmon. Hexachlorocyclohexane isomers (alphaHCH 

+ betaHCH + gammaHCH) were present in higher amounts in eels (6.5 ng/g) 

than in the other smoked fish. For 40% of the samples, PCB concentrations 

exceeded the limit fixed by the European Union, while pesticide levels were 

below the maximum acceptable limit proposed by the Food and Agriculture 

Organization. 

Strandberg, B., C. Bandh, et al. (2000). "Organochlorine compounds in the Gulf of 

Bothnia: sediment and benthic species." Chemosphere 40(9-11): 1205-11. 

 Surface sediment, amphipods (Monoporeia affinis), isopods (Saduria entomon) 

and fourhorn sculpins (Oncocottus quadricornis) were collected at two coastal 
292

stations in the Gulf of Bothnia, one in the Bothnian Bay and the other in the 

Bothnian Sea. The objective was to study the concentrations, composition 

profiles, bioaccumulation features and spatial differences of organochlorine 

compounds such as hexachlorocyclohexanes (HCHs), DDTs, 

hexachlorobenzene (HCBz), chlordanes (CHLs), dieldrin, Mirex and 

polychlorinated biphenyls (PCBs). All groups of compounds were found in every 

sample investigated, with the exception of Mirex that was not detected in the 

sediment samples. The concentrations for e.g. PCBs and CHLs ranged from 700 

to 2400 and 70 to 400 ng/g lipid in the specimens. For the corresponding 

sediments the results were 9.0-9.3 ng/g dw for PCBs and 0.54-0.57 ng/g dw for 

CHLs, respectively. Bioaccumulation differences between the species with 

regard to both degree of and type of compound were observed. The highest 

accumulation potential was found for the cyclodiene compounds including CHLs 

and Mirex in isopod. Finally, there were only small concentration and 

bioaccumulation differences between the two stations. 

Stroebe, M., M. Scheringer, et al. (2004). "Measures of overall persistence and the 

temporal remote state." Environ Sci Technol 38(21): 5665-73. 

 The overall persistence, Pov, has been suggested as an indicator that integrates 

single media half-lives and phase partitioning. However, the application of this 

indicator is hindered by the fact that there are different definitions of Pov and that 

the most common measure of Pov, the residence time at steady state, depends 

heavily on the release pattern. Here, different measures are compared that can 

be used to compute Pov from the mass of a chemical in the environment as a 

function of time in a dynamic multimedia model. These measures include the 

equivalence width, which corresponds to the residence time at steady state, the 

mean value of the function of mass vs time ("mean time"), and the clearance 

time. The temporal remote state is defined as the state of the model system long 

after the stop of emissions; it is independent of the release pattern of a chemical. 

The mean time in the temporal remote state reflects the long-term removal rate 

of a chemical and is used as a persistence benchmark. Correlations of the three 

measures of Pov to the persistence benchmark are analyzed. The maximum 

equivalence width, which is obtained with release to one of the media air, water, 

or soil, is a good approximation of the mean time in the temporal remote state. 

Because the maximum equivalence width is identical to the maximum residence 

time at steady state, the mean time in the temporal remote state can be 

estimated with existing steady-state models. 

Su, Y., H. Hung, et al. (2006). "Spatial and seasonal variations of 

Hexachlorocyclohexanes (HCHs) and hexachlorobenzene (HCB) in the Arctic 

atmosphere." Environ Sci Technol 40(21): 6601-7. 

 Weekly high-volume air samples were collected between 2000 and 2003 at six 

Arctic sites, i.e., Alert, Kinngait, and Little Fox Lake (LFL) in Canada, Point 

Barrow in Alaska, Valkarkai in Russia, and Zeppelin in Norway. 

Hexachlorocyclohexanes (HCHs) and hexachlorobenzene (HCB) were quantified 

in all samples. Comparison showed that alpha-HCH and HCB were 
293

homogeneously distributed in the circumpolar atmosphere and uniform 

throughout the seasons. However, significantly higher atmospheric 

concentrations of alpha-HCH and HCB and strongertemperature dependence of 

alpha-HCH and gamma-HCH were found at LFL in Yukon (YK), which is unique 

among the sites by virtue of its high altitude and low latitude, resulting in higher 

precipitation rates and summer temperatures. Strong temperature dependence of 

alpha- and gamma-HCH at this location suggests that secondary emissions, i.e., 

re-evaporation from surfaces, were more important at this site than others. It is 

hypothesized that a higher precipitation rate at LFL facilitated the transfer of 

alpha-HCH from the atmosphere to surface media when technical HCH was still 

in use worldwide. On the other hand, higher temperature at LFL enhanced 

reevaporation to the atmosphere after the global ban of technical HCH. In 

contrast to alpha-HCH and HCB, larger spatial and seasonal differences were 

seen for gamma-HCH (a currently used pesticide), which likely reflect the 

influence of different primary contaminant sources on different Arctic locations. 

Fugacity ratios suggest a net deposition potential of HCB from air to seawater, 

whereas seawater/air exchange direction of alpha-HCH varies in the circumpolar 

environment. 

Sunyer, J., M. Torrent, et al. (2005). "Prenatal dichlorodiphenyldichloroethylene (DDE) 

and asthma in children." Environ Health Perspect 113(12): 1787-90. 

 Prevalence of asthma increases with increasing dichlorodiphenyldichloroethylene 

(DDE) levels. However, the effect of early-life exposure, the fundamental window 

of exposure, is unknown. We assessed the association between prenatal DDE 

and other organochlorine compounds, and atopy and asthma during infancy. All 

women presenting for antenatal care in Menorca (Spain) over 12 months starting 

in mid-1997 were invited to take part in a longitudinal study; 482 children were 

subsequently enrolled, and 468 (97.1%) provided complete outcome data up to 

the fourth year of study. Prenatal exposure of organochlorine compounds was 

measured in cord serum in 405 (83%) children. Asthma was defined on the basis 

of wheezing at 4 years of age, persistent wheezing, or doctor-diagnosed asthma. 

We measured specific immunoglobulin-E (IgE) against house dust mite, cat, and 

grass in sera extracted at 4 years of age. DDE (median = 1.03 ng/mL) was 

detected in all children, as well as hexachlorobenzene (0.68 ng/mL) and 

polychlorobiphenyls (0.69 ng/mL). Wheezing at 4 years of age increased with 

DDE concentration, particularly at the highest quartile [9% in the lowest quartile 

(< 0.57 ng/mL) vs. 19% in the highest quartile (1.90 ng/mL); relative risk = 2.63 

(95% confidence interval 1.19-4.69), adjusting for maternal asthma, breastfeeding, education, social class, or other organochlorines]. The association was 

not modified by IgE sensitization and occurred with the same strength among 

nonatopic subjects and among those with persistent wheezing or diagnosed 

asthma. DDE was not associated with atopy alone. Prenatal exposure to DDE 

residues may contribute to development of asthma. 
294

Takahashi, M., T. Negishi, et al. (2009). "Alterations in gene expression of glutamate 

receptors and exocytosis-related factors by a hydroxylated-polychlorinated biphenyl in 

the developing rat brain." Toxicology 257(1-2): 17-24. 

 Polychlorinated biphenyls (PCBs), major environmental hormonally active 

agents, are metabolized into hydroxylated PCBs in the liver to facilitate excretion. 

Some of hydroxylated PCBs also have potencies disturbing endogenous 

hormonal activities at least in vitro. Hormonal activities of hydroxylated PCBs 

raise a possibility of their interfering with normal brain development which is 

strictly regulated by endogenous hormones. We investigated whether and how 

prenatal exposure to a congener of hydroxylated PCBs (4-OH-2',3,3',4',5'-penta 

CB; 4-OH-PCB106) having activities to disrupt thyroid hormone-dependent 

signals in vitro could perturb normal gene expression in the developing brain in 

vivo. Pregnant rats were exposed to 4-OH-PCB106 subcutaneously at the dose 

of 1.0mg/(kgday) from day 7 of gestation to postnatal day 1. Then three brain 

regions (cerebral cortex, hippocampus and striatum) were obtained from 

offspring on postnatal day 1 and subjected to further gene expression analyses. 

Comprehensive analyses of mRNA expression by oligo DNA microarrays and 

subsequent validations by quantitative RT-PCR revealed that prenatal exposure 

to 4-OH-PCB106 affected mRNA expression of glutamate receptors as well as 

that of thyroid hormone-responsive genes in region-specific manners. 

Concomitantly 4-OH-PCB106 exposure increased mRNA expression of genes 

related to exocytosis in the three brain regions. These results raise the possibility 

that prenatal exposure to some hydroxylated PCBs with thyroid hormonedisrupting potencies leads to abnormal brain development via perturbations on 

the expression of genes involved in glutamatergic neurotransmission. 

Tavares, T. M., M. Beretta, et al. (1999). "Ratio of DDT in the All Saints Bay, Brazil and 

its use in environmental management." Chemosphere 38(6): 1445-1452. 

 BIOSIS COPYRIGHT: BIOL ABS. DDT degrades to DDE and the ratio of DDT 

can be used as a rough estimate of the period of its application, if the half-life of 

DDT for the specific environment is known. A cross-sectional survey was 

conducted in SH summer 1994/95 for several organochloride (OC) residues in 13 

intertidal sites of the All Saints Bay, using sediments, crabs and three species of 

local bivalves with different feeding habits as indicators. The quantified 

compounds were: DDT, DDE, DDD, HCB, gamma-HCH, Aldrin, Dieldrin and 

Endrin. All concentrations found were below limit of regulatory action. Highest 

levels were found in the Aratu Industrial Centre area, in the Subae estuary and 

the Itaparica Channel, where palm oil nursery exists. From the eight compounds 

DDE presented the highest levels (44 ng/g wet wt in B. exustus) and B. exustus 

the highest bioconcentration factors. Comparing these data with equivalent ones 

of 1985, increases have been observed at all sites, except where an oil refinery 

ten Hulscher, T. E., B. A. Vrind, et al. (2005). "Influence of long contact times on 

sediment sorption kinetics of spiked chlorinated compounds." Environ Toxicol Chem

24(9): 2154-9. 
295

 The desorption kinetics of hexachlorobenzene (HCB) and 2,4,4'-

trichlororbiphenyl (PCB 28) spiked to a field sediment were studied using a gaspurge technique. A contact time of up to 1,461 d was used to assess long-term 

changes in desorption kinetics. Purge-induced desorption experiments lasted 

from 300 to more than 4,000 h. Fast-, slow-, and very-slow-desorbing fractions 

could be distinguished. The desorption patterns changed with contact time from 

mainly fast- and slow-desorbing fractions toward the domination of slow- and 

very-slow-desorbing fractions. The desorption pattern for HCB after a contact 

time of 1,461 d became comparable to previously reported desorption patterns 

observed for in situ contaminants. An additional spike of HCB, PCB 28, 2,4,6-

trichlorobiphenyl, and 2,2',4,5'-tetrachlorobiphenyl applied to the sediment 

purged for more than 4,000 h showed that very slow sites were accessible for 

these compounds within a few hours. Only very small fast-desorbing fractions 

could be detected after a contact time of just 48 h. These results indicate that 

domination of very slow desorption is caused not only by long contact times but, 

perhaps, also by the accessibility of specific sites within the sediment matrix. 

Tilbury, K. L., N. G. Adams, et al. (1999). "Organochlorines in stranded pilot whales 

(Globicephala melaena) from the coast of Massachusetts." Archives of Environmental 

Contamination and Toxicology 37(1): 125-134. 

 BIOSIS COPYRIGHT: BIOL ABS. Pilot whales strand periodically along the U.S. 

coast, and these strandings offer an opportunity for the collection of tissues for 

biomonitoring of contaminant exposure in cetaceans, as well as for specimen 

archiving. Concentrations of organochlorine (OC) contaminants (e.g., PCB 

congeners, pesticides, DDTs) were measured in tissue samples from pilot 

whales that stranded in 1986 and 1990 along the Massachusetts coast. Adult 

and fetal samples of blubber, liver, brain, and kidney were collected, as p,p'-

DDE) and these differences may be partially due to contaminants being 

transferred by the female whales during gestation and lactation. The 

concentrations of OCs in different tissues were similar when based on total lipid 

weight, except for the brain, which contained the lowest lipid-normalized OC 

concentrations. The low concentrations in brain may be related to the disparate 

lipid compositions in this tissue as well as the presence of the blood-brain barrier. 

The availabilit 

To-Figueras, J., C. Barrot, et al. (2000). "Excretion of hexachlorobenzene and 

metabolites in feces in a highly exposed human population." Environ Health Perspect

108(7): 595-8. 

 A set of 53 individuals from a population highly exposed to airborne 

hexachlorobenzene (HCB) were selected to study the elimination kinetics of this 

chemical in humans. The volunteers provided blood, 24-hr urine, and feces 

samples for analysis of HCB and metabolites. The serum HCB concentrations 

ranged from 2.4 to 1,485 ng/mL (mean +/- SD, 124 +/- 278), confirming that this 

human population has the highest HCB blood levels ever reported. All analyzed 

feces samples contained unchanged HCB (range, 11-3,025 ng/g dry weight; 

mean +/- SD, 395 +/- 629). The HCB concentration in feces strongly correlated 
296

with HCB in serum (r = 0.85; p < 0.001), suggesting an equilibrium in 

feces/serum that is compatible with a main pulmonary entrance of the chemical 

and low intestinal excretion of nonabsorbed foodborne HCB. The equilibrium is 

also compatible with a nonbiliary passive transfer of the chemical to the intestinal 

lumen. Two HCB main metabolites, pentachlorophenol (PCP) and 

pentachlorobenzenethiol (PCBT), were detected in 51% and 54% of feces 

samples, respectively. All urine samples contained PCP and PCBT, confirming 

the conclusions of a previous study [Environ Health Perspect 105:78-83 (1997)]. 

The comparison between feces and urine showed that whereas daily urinary 

elimination of metabolites may account for 3% of total HCB in blood, intestinal 

excretion of unchanged HCB may account for about 6%, thus showing the 

importance of metabolism in the overall elimination of HCB. The elimination of 

HCB and metabolites by both routes, however, appears to be very small (< 

0.05%/day) as compared to the estimated HCB adipose depots. Features of HCB 

kinetics that we present in this study, i.e., nonsaturated intestinal elimination of 

HCB and excretion in feces and urine of inert glutathione derivatives, may 

explain, in part, the absence of porphyria cutanea in this human population 

heavily exposed to HCB. 

Toyoshiba, H., H. Sawada, et al. (2009). "Similar compounds searching system by using 

the gene expression microarray database 

Obesity: Childhood BMI Rises with Prenatal Exposure to Hexachlorobenzene." 

Toxicology Letters 186(1): 52-7. 

 Numbers of microarrays have been examined and several public and commercial 

databases have been developed. However, it is not easy to compare in-house 

microarray data with those in a database because of insufficient reproducibility 

due to differences in the experimental conditions. As one of the approach to use 

these databases, we developed the similar compounds searching system 

(SCSS) on a toxicogenomics database. The datasets of 55 compounds 

administered to rats in the Toxicogenomics Project (TGP) database in Japan 

were used in this study. Using the fold-change ranking method developed by 

Lamb et al. [Lamb, J., Crawford, E.D., Peck, D., Modell, J.W., Blat, I.C., Wrobel, 

M.J., Lerner, J., Brunet, J.P., Subramanian, A., Ross, K.N., Reich, M., 

Hieronymus, H., Wei, G., Armstrong, S.A., Haggarty, S.J., Clemons, P.A., Wei, 

R., Carr, S.A., Lander, E.S., Golub, T.R., 2006. The connectivity map: using 

gene-expression signatures to connect small molecules, genes, and disease. 

Science 313, 1929-1935] and criteria called hit ratio, the system let us compare 

in-house microarray data and those in the database. In-house generated data for 

clofibrate, phenobarbital, and a proprietary compound were tested to evaluate 

the performance of the SCSS method. Phenobarbital and clofibrate, which were 

included in the TGP database, scored highest by the SCSS method. Other high 

scoring compounds had effects similar to either phenobarbital (a cytochrome 

P450s inducer) or clofibrate (a peroxisome proliferator). Some of high scoring 

compounds identified using the proprietary compound-administered rats have 

been known to cause similar toxicological changes in different species. Our 

results suggest that the SCSS method could be used in drug discovery and 
297

development. Moreover, this method may be a powerful tool to understand the 

mechanisms by which biological systems respond to various chemical 

compounds and may also predict adverse effects of new compounds. 

Tricklebank, K. A., M. J. Kingsford, et al. (2002). "Organochlorine pesticides and 

hexachlorobenzene along the central coast of New South Wales: multi-scale 

distributions using the territorial damselfish Parma microlepis as an indicator." Environ 

Pollut 116(2): 319-35. 

 Concentrations of 10 organochlorine pesticides and hexachlorobenzene (HCB) 

were determined in the territorial damselfish Parma microlepis at three urban 

locations and three reference locations centred on the Sydney region. Dieldrin, 

HCB and DDE were the most frequently detected organochlorines, occurring in 

70-100% of samples collected. Alpha and gamma chlordane were also 

reasonably common and occurred in more than 30% of the samples. Each 

organochlorine compound investigated had a distinct spatial pattern of 

distribution. Related chemicals such as alpha and gamma chlordane, and DDT, 

DDE and DDD tended to have similar patterns of distribution. There were clear 

differences in patterns of distribution in organochlorines between urban and 

reference locations shown using non-parametric multivariate techniques. Relative 

variability of samples from urban locations was higher than at reference locations 

in 1993, but there was no consistent pattern of differences in the dispersions of 

samples among urban and reference locations in 1994. Age and condition 

indices (K) showed no association with total concentrations of organochlorine 

residues in fish. Significant, but weak associations were found between 

organochlorine residues and size, gonad somatic and liver somatic indices. 

Tsuji, L. J., B. C. Wainman, et al. (2005). "The Mid-Canada Radar Line and First 

Nations' people of the James Bay region, Canada: an evaluation using log-linear 

contingency modelling to analyze organochlorine frequency data." J Environ Monit 7(9): 

888-98. 

 Abandoned radar line stations in the North American arctic and sub-arctic 

regions are point sources of contamination, especially for PCBs. Few data exist 

with respect to human body burden of organochlorines (OCs) in residents of 

communities located in close proximity to these radar line sites. We compared 

plasma OC concentration (unadjusted for total lipids) frequency distribution data 

using log-linear contingency modelling for Fort Albany First Nation, the site of an 

abandoned Mid-Canada Radar Line station, and two comparison populations 

(the neighbouring community of Kashechewan First Nation without such a radar 

installation, and Hamilton, a city in southern Ontario, Canada). This type of 

analysis is important as it allows for an initial investigation of contaminant data 

without imputing any values. The two-state log-linear model (employing both nondetectable and detectable concentration frequencies and applicable to PCB 

congeners 28 and 105 and cis-nonachlor) and the four-state log-linear model 

(using quartile concentration frequencies for Aroclor 1260, PCB congeners 

[99,118,138,153,156,170,180,183,187], beta-HCH, p,p'-DDT +p,p'-DDE, HCB, 

mirex, oxychlordane, and trans-nonachlor) revealed that the effects of subject 
298

gender were inconsequential. Significant differences (p < 0.05) between the 

groups examined were attributable to the effect of location on the frequency of 

detection of OCs or on their differential distribution among the concentration 

quartiles. In general, people from Hamilton had higher frequencies of nondetections and of concentrations in the first quartile (p < 0.05) for most OCs 

compared to people from Fort Albany and Kashechewan (who consume a 

traditional diet of wild meats that does not include marine mammals). An 

unexpected finding was that, for Kashechewan males, the frequency of many 

OCs was significantly higher (p < 0.05) in the 4th concentration quartile than that 

predicted by the four-state log-linear model, but significantly lower than expected 

in the 1st quartile for beta-HCH. The levels of PCBs found for women in Fort 

Albany and Kashechewan were greater than those reported for Dene (First 

Nation people) and Metis (mixed heritage) of the western Northwest Territories 

(NWT) who did not consume marine mammals, and for Inuit living in the central 

NWT (occasional consumers of marine mammals). Moreover, the levels of total 

p,p'-DDT were greater for Fort Albany and Kashechewan women compared to 

these same aboriginal groups. 

Tuomisto, J. and L. Hagmar (1999). "Environmental health in the east Baltic region: 

Pesticides and persistent organic compounds." Scandinavian Journal of Work 

Environment and Health 25(Suppl 3): 65-72. 

 BIOSIS COPYRIGHT: BIOL ABS. Exposure to, and the potential effects of, 

pesticides and persistent organic pollutants in the East Baltic region are 

reviewed. Exposure of the average population to chlorinated compounds seems 

lower than in most of western Europe, and current pesticide use is very low. 

However, due to infrastructure failures and poor management controls, industrial 

hot spots and inadequate storage sites exist that cause high risks to small 

population fractions. The low exposure of the general population is indi pesticide 

residues and persistent organic compounds in the Baltic countries and 

northwestern Russiais low, but local sites of concern exist. 

Umino, Y., S. Tsuji, et al. (2002). "[Determination and survey of hexachlorobenzene in 

food red nos. 104 (phloxine) and 105 (rose bengale) by GC/MS]." Kokuritsu Iyakuhin 

Shokuhin Eisei Kenkyusho Hokoku(120): 107-11. 

 The contents of hexachlorobenzene (HCB) in Food Red Nos. 104 and 105 

samples certified in fiscal years 1998-2001 were determined by GC/MS. All 32 

samples contained HCB ranging from 0.2 to 32.9 mg/kg. The daily intakes of 

HCB based on the production of food colors was estimated to be from 0.018 to 

1.456 ng, and their average (0.441 ng) corresponded to 0.0052% of the ratio for 

the Tolerable Daily Intake (8.5 micrograms for 50 kg body weight) of HCB 

developed by the IPCS. 

UnivofCincinnati (2000). "Mortality Study of Montague, Michigan Plant-Hooker Chemical 

with Cover Letter Dated 110981 from Hooker Chem Corp to Epa." EPA/OTS; Doc #40-

8149014. 

 
299

Valters, K., A. Olsson, et al. (1999). "Polychlorinated biphenyls and some pesticides in 

perch (Perca fluviatilis) from inland waters of Latvia." Chemosphere 38(9): 2053-2064. 

 BIOSIS COPYRIGHT: BIOL ABS. Polychlorinated biphenyls (PCBs), DDTrelated substances, hexachlorocyclohexane (HCH) isomers and 

hexachlorobenzene (HCB) were analysed in perch (Perca fluviatilis) from Latvian 

lakes and rivers. DDE is present in the highest concentrations in all samples; 62-

170 ng/g lipid weight in perch from rural areas and 460 ng/g in perch from the 

Riga area. Individual dominating PCB congeners were in the range 16-45 ng/g 

and 200-210 ng/g, respectively. The degree of contamination of rural areas in 

Latvia of these organohalogen substances is in the same range as in background 

areas in Sweden. Riga, the major urban area in Latvia, is shown to be more 

polluted with PCBs than other areas in Latvia. 

Valters, K., A. Olsson, et al. (1999). "Contamination sources in Latvia: Levels of 

organochlorines in perch (Perca fluviatilis) from Rivers Daugava and Lielupe." Ambio

28(4): 335-340. 

 BIOSIS COPYRIGHT: BIOL ABS. This study was aimed to search for potential 

sources of polychlorinated biphenyls (PCBs) contributing to the PCB input to the 

Gulf of Riga, as part of the Baltic Sea. PCBs, DDT and related compounds, 

hexachlorobenzene (HCB), bis(4-chlorophenyl) sulfone (BCPS) and two 

hexachloro-cyclohexane (HCH) isomers were quantified in perch (Perca 

fluviatilis) from the rivers Daugava and Lielupe in Latvia. Local PCB 

contamination was indicated in Lielupe with the most likely origin being the 

Jelgava urban ar rom other areas in the Baltic Sea region; e.g. PCB levels of 

250-1100 ng g-1 l.w. were determined. 

van der Wal, L., T. Jager, et al. (2004). "Solid-phase microextraction to predict 

bioavailability and accumulation of organic micropollutants in terrestrial organisms after 

exposure to a field-contaminated soil." Environ Sci Technol 38(18): 4842-8. 

 The risk posed by soil contaminants strongly depends on their bioavailability. In 

this study, a partition-based sampling method was applied as a tool to estimate 

bioavailability in soil. The accumulation of organic micropollutants was measured 

in two earthworm species (Eisenia andrei and Aporrectodea caliginosa) and in 

30-microm poly(dimethylsiloxane) (PDMS)-coated solid-phase micro extraction 

(SPME) fibers after exposure to two field-contaminated soils. Within 10 days, 

steady state in earthworms was reached, and within 20 days in the SPME fibers. 

Steady-state concentrations in both earthworm species were linearly related to 

concentrations in fibers over a 10,000-fold range of concentrations. Measured 

concentrations in earthworms were compared to levels calculated via equilibrium 

partitioning theory and total concentrations of contaminants in soil. In addition, 

freely dissolved concentrations of contaminants in pore water, derived from 

SPME measurements, were used to calculate concentrations in earthworms. 

Measured concentrations in earthworms were close to estimated concentrations 

from the SPME fiber measurements. Freely dissolved concentrations of 

contaminants in pore water, derived from SPME measurements, were used to 

calculate bioconcentration factors (BCF) in earthworms. A plot of log BCFs 
300

against the octanol-water partition coefficient (log Kow) was linear up to a log 

Kow of 8. These results show that measuring concentrations of hydrophobic 

chemicals in a PDMS-coated fiber represents a simple tool to estimate internal 

concentrations of chemicals in biota exposed to soil. 

van Drooge, B. L., J. O. Grimalt, et al. (2004). "Atmospheric semivolatile organochlorine 

compounds in European high-mountain areas (central Pyrenees and high Tatras)." 

Environ Sci Technol 38(13): 3525-32. 

 Atmospheric samples from two European high-mountain areas showed similar 

composition of semivolatile organochlorine compounds (SOC), such as 

polychlorobiphenyls (PCBs), DDTs, endosulfans, hexachlorobenzene (HCB), and 

hexachlorocyclohexanes (HCHs). Nearly all compounds were predominantly 

found in the gas phase and only the less volatile such as some PCBs (e.g., 149, 

118, 153, 138, and 180) were found in higher abundance in the particulate 

phase. HCB, 49-85 pg m(-3), is the dominant SOC. This compound is only found 

in the gas phase exhibiting uniform concentrations irrespective of season and air 

mass origin. SOC of present use, like HCHs and endosulfans, were found in 

higher concentrations in the warm periods, 32-46 and 4-10 pg m(-3) in the gas + 

particulate phases, respectively, reflecting their seasonal pattern of use in many 

European countries. PCB and 4,4'-DDE, 39-42 and 4-6 pg m(-3) in the gas + 

particulate phases, respectively, also showed a seasonal trend despite neither 

the former nor the precursor of the latter (4,4'-DDT) being manufactured with 

their use drastically restricted since the 1980s. The seasonal differences are 

mainly due to a higher occurrence of air masses with strong continental inputs in 

the warm than in the cold periods. In this respect, samples whose air masses 

traveled at the high troposphere (backward air mass trajectories >6000 m) have 

been observed to carry considerably smaller PCB and 4,4'-DDE loads (9.3 +/- 

2.8 and 0.4 +/- 0.05 pg m(-3), respectively) than overall average. 

Van Jaarsveld, J. A. and W. A. Van Pul (1999). "Modelling of atmospheric transport and 

deposition of pesticides." Water, Air, and Soil Pollution 115(1-4): 167-182. 

 BIOSIS COPYRIGHT: BIOL ABS. Modelling of atmospheric transport and 

deposition of pesticides is presented and discussed. Modelling on regional scale 

builds on the existing knowledge gained in other air pollution fields. An overview 

of current modelling studies on transport and deposition on a regional scale 

(typically 30-3000 km) is given. From these studies it is concluded that the 

models are capable in simulating the spatial distribution of the concentrations 

and depositions. However, large uncertainties are present in this type of 

modelling and are for the greater part induced by the uncertainty in the emissions 

and subsequently in the exchange process parameterisations and the 

physicochemical properties needed in the parameterisations. Many more 

measurement data are needed to validate the models. 

Van Oostdam, J., A. Gilman, et al. (1999). "Human health implications of environmental 

contaminants in Arctic Canada: A review." Science of the Total Environment 230(1-3): 

1-82. 
301

 BIOSIS COPYRIGHT: BIOL ABS. This paper assesses the impact on human 

health of exposure to current levels of environmental contaminants in the 

Canadian Arctic, and identifies the data gaps that need to be filled by future 

human health research and monitoring. The concept of health in indigenous 

groups of the Arctic includes social, cultural, and spiritual dimensions. The 

harvesting, sharing and consumption of traditional foods are an integral 

component to good health among Aboriginal people influencing both physical 

health t. For the Inuit, the OCs of primary concern at this time from the point of 

view of exposure are chlordane, toxaphene, and PCBs. Exposures are higher in 

the eastern than in the western region of the North. For Deneetis, exposure to 

OCs is in general below a level of concern. However, estimated intake of 

chlordane and toxaphene has been found to be elevated for certain groups and 

is a cause for concern if exposures are elevated on a regular basis. The 

developing foetus and breastVan Pul, W. A., T. F. Bidleman, et al. (1999). "Atmospheric transport and deposition of 

pesticides: An assessment of current knowledge." Water, Air, and Soil Pollution 115(1-

4): 245-256. 

 BIOSIS COPYRIGHT: BIOL ABS. The current knowledge on atmospheric 

transport and deposition of pesticides is reviewed and discussed by a working 

group of experts during the Workshop on Fate of pesticides in the atmosphere; 

implications for risk assessment, held in Driebergen, the Netherlands, 22-24 

April, 1998. In general there is a shortage of measurement data to evaluate the 

deposition and reemission processes. It was concluded that the mechanisms of 

transport and dispersion of pesticides can be described similarly to those for 

other air pollution components and these mechanisms are rather well-known. 

Large uncertainties are present in the exchange processes at the interface 

between air and soil/water/vegetation. In all process descriptions the uncertainty 

in the physicochemical properties play an important role. Particularly those in the 

vapour pressure, Henry's law constant and its temperature dependency. More ac 

curate data on physicochemical properties and particularly the temperature 

dependencies is needed. 

Vandebriel, R. J., C. Meredith, et al. (2000). "Interleukin-10 is an unequivocal Th2 

parameter in the rat, whereas interleukin-4 is not." Scand J Immunol 52(5): 519-24. 

 Exposure of Wistar rats to the immunotoxic compounds hexachlorobenzene 

(HCB), bis(tri-n-butyltin)oxide, and benzo(a)pyrene was previously found to affect 

mRNA expression of interleukin (IL)-2, IL-2R alpha- chain, and interferon (IFN)-

gamma, the prototypic Th1 cytokine. In contrast, the mRNA expression of IL-4, 

the prototypic Th2 cytokine, was unaffected. This latter finding suggested that the 

IL-4 mRNA expression may not be an unequivocal parameter for Th2 responses 

in the rat. In order to obtain such a parameter the present study was performed, 

consisting of two types of experiments. Expression and production of IL- 4 as 

well as IL-10, a second Th2 cytokine, were measured. First, Lewis (Th1 prone) 

and Brown Norway (BN; Th2 prone) rats were exposed to HCB. Exposure was 

previously found to increase the serum immunoglobulin (Ig)E levels, an IL-4-
302

dependent response, in BN but not Lewis rats, and in Lewis rats to aggravate 

experimental allergic encephalomyelitis (EAE), severity being inversely related to 

IL-10 levels. Secondly, BN rats were infected with Trichinella spiralis, an infection 

previously found to induce IL-4 production. HCB exposure did not affect IL-4 

mRNA expression in either strain, while IL-4 production was decreased in Lewis 

and unaffected in BN rats. In Lewis rats both the mRNA expression and the 

production of IL-10 were decreased. The T. spiralis infection induced IL-4 and IL10 mRNA expression, as well as IL-10 production. In contrast, the IL-4 

production was strongly reduced. Thus, both the IL- 10 mRNA expression and 

production correlated with the EAE development and T. spiralis infection. In HCB 

exposed Lewis rats and T. spiralis infected BN rats the IL-4 mRNA expression 

correlated with IgE levels and T. spiralis infection, respectively, whereas the IL-4 

production lacked correlation in all cases. Collectively, these results suggest that 

IL-10 is an unequivocal Th2 parameter in the rat, whereas IL-4 is not. 

VelsicolChemCorp (2000). "1,2,3,4,7,7-Hexachloronorbornadiene Response to the 13th 

Interagency Testing Committee Report(48 Fr 55681) with Cover Letter Dated 101183." 

EPA/OTS; Doc #40-8483021. 

 

Verbruggen, E. M., H. J. C. Klamer, et al. (1999). "Gradient elution reversed-phase 

high-performance liquid chromatography for fractionation of complex mixtures of organic 

micropollutants according to hydrophobicity using isocratic retention parameters." 

Journal of Chromatography A 835(1-2): 19-27. 

 BIOSIS COPYRIGHT: BIOL ABS. Gradient elution RP-HPLC is used as a 

suitable method to infer the hydrophobicity values (log Kow) of components in 

complex samples. In this study, the slope (S) and the intercept (log kw) of the 

linear relationship between the logarithm of the retention factor (log k) and the 

percentage methanol of the eluent (phi) were first obtained by isocratic runs for a 

set of micropollutants with diverse structures, similar to the contaminants to 

which the method will be applied. Both S and log kw obtaine ydrophobicity. 

Vilas, G. L., C. Aldonatti, et al. (1999). "Effect of alpha lipoic acid amide on 

hexachlorobenzene porphyria." Biochem Mol Biol Int 47(5): 815-23. 

 The aim of this work is to study the effect of thioctamide--the commercial form of 

alpha lipoic acid amide--on the porphyrinogenic action of hexachlorobenzene 

(HCB). For this purpose, porphyria was induced in rats by chronic HCB 

treatment, with or without simultaneous thioctamide administration. Two different 

groups of rats were used as reference: one treated with vehicle (control) and the 

other treated with thioctamide (TO). Urine delta aminolevulic acid, 

porphobilinogen, and porphyrin excretions were lower in the HCB + TO treated 

group than in the HCB group, and the same happened with liver uroporphyrin 

accumulation. On the other hand, the second stage of uroporphyrinogendecarboxylase activity was significantly higher in the HCB + TO group than in the 

HCB group. delta aminolevulic acid synthase activity was higher in the HCB 

group. Hepatic thiobarbituric acid reactive substances were lower in HCB + TO 

group than in HCB group. Thus, we might suggest that TO would decrease HCB 
303

effects by means of its free radical scavenging ability, and by having a direct 

effect on uroporphyrinogen-decarboxylase activity. 

Vives, I., J. O. Grimalt, et al. (2005). "Age dependence of the accumulation of 

organochlorine pollutants in brown trout (Salmo trutta) from a remote high mountain 

lake (Redo, Pyrenees)." Environ Pollut 133(2): 343-50. 

 Polychlorobiphenyls (PCBs), hexachlorocyclohexanes (HCHs), 

hexachlorobenzene (HCB) and DDT were examined in the muscle of brown trout 

(Salmo trutta) from a high mountain lake located in the Pyrenees (Catalonia, 

Spain) that was used as a model of these lacustrine environments. Results 

indicate that fish age is the main factor of variability among specimens in this 

population that is subjected to atmospheric inputs of the organochlorine 

compounds (OC). Increases of 2- and 20-fold between fish aged 1 year and 15 

years old are found. The observed pattern cannot be explained in terms of fish 

size, condition factor, or muscle lipid content. Higher molecular weight 

compounds (higher lipophilicity) are better correlated with fish age than low 

molecular weight compounds. A transformation from 4,4'-DDT to 4,4'-DDE 

occurs in fish after ingestion; this results in amplified age-dependent signals, 

especially in male specimens. In contrast, PCB congener #180 has lower age 

dependence than the general OC group, which could be due to its high 

hydrophobicity (log K(ow) > 7). In any case, selective accumulation of 

hydrophobic compounds is already observed among younger fish (age, 1 year). 

Due to this effect, the relative OC composition does not reflect the main OC 

pollutants in the lake waters. 

Vorkamp, K., F. F. Riget, et al. (2008). "Levels and trends of persistent organic 

pollutants in ringed seals (Phoca hispida) from Central West Greenland, with particular 

focus on polybrominated diphenyl ethers (PBDEs)." Environ Int 34(4): 499-508. 

 Polybrominated diphenyl ethers (PBDEs) and the organochlorine compounds 

polychlorinated biphenyls (PCBs), DDTs, HCB, chlordane-related pesticides, 

HCH and toxaphene were analysed in blubber of juvenile ringed seals from 

Central West Greenland collected between 1982 and 2006. The longest time 

series could be established for PBDEs, partly based on archived material, while 

PCBs and DDTs covered a study period from 1994-2006. All organochlorines 

showed decreasing trends, most pronounced for DDT and HCH with an annual 

change of 8%. BDE-47 had a significantly increasing trend of 5% annually. It was 

the only BDE congener consistently above the detection limit, with annual 

median concentrations between 0.78 ng/g lw to 3.54 ng/g lw, i.e. about 10 times 

lower than values from East Greenland observed in a similar time trend study on 

ringed seal blubber [Riget F, Vorkamp K, Dietz R, Rastogi SC. Temporal trend 

studies on polybrominated diphenyl ethers (PBDEs) and polychlorinated 

biphenyls (PCBs) in ringed seals from East Greenland. J Environ Monit 2006; 8: 

1000-5]. A clear East>West difference was also found for PCBs and DDTs, but 

not for chlordanes, toxaphene or HCHs. Sigma 10-PCB, Sigma DDT and Sigma 

Chlordanes had similar annual median concentrations, typically exceeding 

SigmaPBDE by two orders of magnitude. The concentrations of HCH and 
304

toxaphene were in an intermediate group, with highest annual median 

concentrations of 135 ng/g lw and 20 ng/g lw, respectively. For most compound 

groups, the circumpolar trend previously established under for example the Arctic 

Monitoring and Assessment Programme was confirmed, but apparently, more 

data are needed for chlordane-related compounds and toxaphene. Statistical 

analyses of the compound patterns in the ringed seal samples revealed 

significantly greater differences between seals from East and West than between 

different sampling years. Higher proportions of PCBs and DDTs and lower 

proportions of chlordanes and HCHs were found in seals from East Greenland 

than in those from West Greenland. Based on principal component analysis of 

individual congener and compounds, seals from East Greenland were found to 

contain higher proportions of the higher chlorinated CB congeners. Varying 

patterns between sampling locations may be caused by different exposure 

situations related to contaminant emissions and transport, but different feeding 

habits may also affect the contaminant composition. 

Vos, J. G. (2000). "Health effects of hexachlorobenzene and the TEF approach." 

Environ Health Perspect 108(2): A58. 

 

Wagman, N., B. Strandberg, et al. (1999). "Organochlorine pesticides and 

polychlorinated biphenyls in household composts and earthworms (Eisenia foetida)." 

Environmental Toxicology and Chemistry 18(6): 1157-1163. 

 BIOSIS COPYRIGHT: BIOL ABS. Three indoor, household composts and the 

earthworms living in them were analyzed for their congener-specific content of 

polychlorinated biphenyls (PCBs) and organochlorine pesticides, including DDTs, 

chlordanes, dieldrin, and penta- and hexachlorobenzene. The concentrations of 

the chlordanes were 0.01 to 0.2 ng/g dry weight (dw) in compost and 0.03 to 0.06 

ng/g wet weight (ww) in the worms. Of all the pesticides, the DDTs and 

chlorobenzenes were found in the highest concentrations. The levels of 

Waliszewski, S. M., S. Gomez-Arroyo, et al. (2004). "Persistent organochlorine pesticide 

levels in bovine fat from Mexico." Food Addit Contam 21(8): 774-80. 

 Organochlorine pesticides have been used in Mexico in agriculture as a seed 

dresser, in sanitation, in malaria control programmes and in livestock to combat 

ectoparasites. The pesticides applied drift to areas where cattle graze and plants 

grow. Because of their chemical stability, they accumulate in the lipid-rich tissues 

of the body. In the body, they circulate throughout all compartments and 

accumulate in adipose fat. The aim was to monitor the organochlorine pesticide 

levels in bovine muscle fat and kidney fat from cows living in an endemic malaria 

zone, where the environmental contamination can be suspected as being higher. 

Two hundred samples (100 muscle fat, 100 kidney fat) were analysed by gas 

chromatography. From the pesticides, only hexachlorobenzene (HCB), betahexachlorocyclohexane (HCH), gamma-HCH, pp'-1.1.1-trichloro-2,2-bis(4-

chlorophenyl)ethane (DDT), op'-DDT and pp'-DDE, were detected frequently and 

at levels above the detection limits. The HCB mean level was low at 0.009 mg 

kg(-1) on a fat basis. From the HCH isomers, beta-HCH mean concentration was 
305

0.039 mg kg(-1) and gamma-HCH was 0.025 mg kg(-1) on a fat basis. Among 

DDTs, pp'-DDT was the major constituent (0.032 mg kg(-1) on a fat basis) 

followed by pp'-DDE (0.025 mg kg(-1) on a fat basis) and op'-DDT (0.023 mg kg(-

1) on a fat basis). The DDT total (sigma DDT) level was 0.067 mg kg(-1) on a fat 

basis. Comparing the previous study (1994) and the present one (2002-03), 

organochlorine pesticide levels were decreased. HCB decreased 3.7 times from 

0.033 to 0.009 mg kg(-1) on a fat basis; beta-HCH decreased 3.8 times from 

0.149 to 0.039 mg kg(-1) on a fat basis; pp'-DDE did not reveal a significant 

difference at 0.026 versus 0.025 mg kg(-1) on a fat basis. However, pp'-DDT 

decreased substantially, 6.7 times from 0.215 to 0.032 mg kg(-1) on a fat basis. 

The DDT total decreased 3.5 times from 0.236 to 0.067 mg kg(-1) on a fat basis. 

The tendency for reduced concentrations in organochlorine pesticide levels in 

Mexican cows is caused by their substitution with pyrethroids used in agriculture 

and by the Mexican Ministry of Health in sanitary programmes. 

Waliszewski, S. M., R. Villalobos-Pietrini, et al. (2003). "Persistent organochlorine 

pesticide levels in cow's milk samples from tropical regions of Mexico." Food Addit 

Contam 20(3): 270-5. 

 Organochlorine pesticides have been used in agriculture as a seed dresser, in 

sanitation, in malaria control programmes and in livestock to combat 

ectoparasites. Their residues accumulate in lipid-rich tissues due to their 

chemical stability and persistence. In the body they circulate throughout all 

compartments, deposit themselves in adipose fat and can be excreted during 

lactation. These pesticides are applied in tropical zones and drift to areas where 

cattle graze. Therefore, analyses of cow's milk samples can serve as an indicator 

of environmental and cows' exposure to them. One hundred and fifty milk 

samples were taken each year in 1998 and 2001 and analysed to determine 

concentrations of HCB, beta-HCH, pp"-DDE, op'-DDT and pp'-DDT. Results 

obtained indicate that beta-HCH is one of the main contaminants (0.106 and 

0.087 mg x kg(-1) on fat basis) followed by pp'-DDT (0.078 and 0.037 mg x kg(-1) 

on fat basis) and pp'-DDE (0.051 and 0.033 mg x kg(-1) on fat basis). The HCB 

and op'-DDT were detected in lower quantities respectively (0.008 and 0.006 mg 

x kg(-1), and 0.031 and 0.010 mg x kg(-1) on fat basis). When comparing the 

results obtained with those from the previous study, it was noted that DDT levels 

decreased significantly in 2001 as a result of the substitution of the 

organochlorine insecticides with pyrethroids sprayed by the Mexican Ministry of 

Health to combat malaria since 1999. 

Walker, S. L. and F. A. P. Gobas (1999). "An investigation of the application of the 

Canadian water quality guidelines." Environmental Toxicology and Chemistry 18(6): 

1323-1328. 

 BIOSIS COPYRIGHT: BIOL ABS. The Canadian water quality guidelines for the 

protection of aquatic life assume that (1) the external water concentration is an 

effective measure of the concentration at the active site in organisms, which is 

ultimately responsible for a toxic response, and that (2) the safety factor accounts 

for any differences between laboratory and field conditions as well as the 
306

extrapolation from the effect concentration to a long-term no-effect concentration. 

This study examines these assumptions and asses bioaccumulation model show 

that a high probability (62-100%) exists that safe internal concentrations are 

exceeded for polychlorinated biphenyls, 1,2,4,5-tetrachlorobenzene, and 

hexachlorobenzene in Lake Ontario when the aqueous concentrations are at the 

water quality guideline values. This is due to field bioaccumulation factors being 

greater than the bioaccumulation factors in laboratory toxicity tests used for the 

water quality guideline development. Factors contributing to th 

Wang, J., L. Guo, et al. (2007). "Passive air sampling of DDT, chlordane and HCB in the 

Pearl River Delta, South China: implications to regional sources." J Environ Monit 9(6): 

582-8. 

 The Pearl River Delta (PRD) is one of the largest fast-developing economic 

zones in China. Hong Kong and the mainland part of the PRD differed in socioeconomic development history and chemical management policies. Polyurethane 

foam (PUF)-passive air sampling (PAS) was deployed at 21 regional air quality 

monitoring stations across the PRD in summer and winter, respectively. Dichlorodiphenyl-trichloroethane (DDT), chlordane and hexachlorobenzene (HCB) were 

analyzed with GC-MS. High total DDT (240-3700 pg m(-3)) and chlordane (100-

2600 pg m(-3)) concentrations were observed. Concentrations of DDTs and 

chlordane were higher in summer than winter; HCB vice versa. Spatially, the 

mainland part of the PRD generally displayed higher DDT concentrations than 

Hong Kong. Antifouling paint for fishing ships in coastal China was suggested to 

be an important current DDT source in the coast. The reason is unknown for the 

very low trans-/cis-chlordane (TC/CC) ratios (0.27) found in the mainland in 

winter. HCB concentrations were relatively uniform across the PRD, and long 

range transport of HCB from inland/North China to the PRD in winter was 

suggested. 

Wania, F. (1999). "On the origin of elevated levels of persistent chemicals in the 

environment." Environmental Science and Pollution Research|Environmental Science 

and Pollution Research International 6(1): 11-19. 

 BIOSIS COPYRIGHT: BIOL ABS. In general, contamination levels tend to be 

highest close to sources of a chemical and decline with increasing distance as a 

result of dilution, dispersion and degradation. However, contrary to this, 

circumstances have been described when contamination levels are higher further 

away from sources than at the sources themselves. Examples are elevated 

levels of persistent, hydrophobic, organic chemicals in the Arctic, in mountain 

regions and in forest soils. In order to address the questions of why volume or 

temperature, and 3. dynamic or kinetic effects. These principles are illustrated 

with several examples. The case can be made that understanding, quantifying 

and predicting these causes could provide a general conceptual framework for 

studying the fate of chemicals in the environment. 

Waters, M. D., H. F. Stack, et al. (1999). "Genetic toxicology data in the evaluation of 

potential human environmental carcinogens." Mutation Research. 437(1): 21-49. 
307

 BIOSIS COPYRIGHT: BIOL ABS. In 1969, the International Agency for Research 

on Cancer (IARC) initiated the Monographs Programme to evaluate the 

carcinogenic risk of chemicals to humans. Results from short-term mutagenicity 

tests were first included in the IARC Monographs in the mid-1970s based on the 

observation that most carcinogens are also mutagens, although not all mutagens 

are carcinogens. Experimental evidence at that time showed a strong correlation 

between mutagenicity and carcinogenicity and indicated that short-te C Genetic 

Activity Profile (GAP) database over nearly 15 years are summarized and 

reviewed here withregard to their IARC carcinogenicity classifications. The 

evidence of mutagenicity or nonmutagenicity based on a 'defining set' of test 

results from three genetic endpoints (gene mutation, chromosomal aberrations, 

and aneuploidy) is examined. Recommendations are made for assessing 

chemicals based on the strength of evidence from short-term tests, and the 

implications of this approach in identifyin 

Webster, E., D. Mackay, et al. (2004). "Regional differences in chemical fate model 

outcome." Chemosphere 55(10): 1361-76. 

 The fate of anthropogenic substances in the environment is increasingly 

determined using multimedia mass balance models. It is, therefore, critical to fully 

understand how such models work and what their limitations are. The effects of 

uncertainty and variation in the chemical properties, discharges, and landscape 

parameters on model outcome have been examined by other researchers. Here, 

the role of landscape properties in controlling region-to-region differences in 

chemical fate is examined. Specifically, regions of Canada and the ChemCAN 

model are used to explore the region-to-region difference in fate for 

benzo[a]pyrene, hexachlorobenzene, tetrachloroethylene, alphahexachlorocyclohexane, 2,2',5,5'-tetrachlorobiphenyl (PCB 52), and atrazine 

emitted individually to air, water, and soil. To facilitate the same analysis in other 

places a description of the model and the methods for obtaining the landscape 

parameters used here are given. Differences in fate are the unique result of 

combining the input parameters of chemical properties, emission data, and 

landscape parameters. While region-to-region differences are small compared to 

the chemical-to-chemical differences that may span many orders of magnitude 

for physical-chemical or degradation properties, chemical fate is not the same for 

regions of differing landscape parameters. It is therefore concluded that the 

quality of results obtained from regional environmental fate models can be 

improved by the use of region-specific landscape parameters. 

Welp, G. and G. W. Bruemmer (1999). "Effects of organic pollutants on soil microbial 

activity: The influence of sorption, solubility, and speciation." Ecotoxicology and 

Environmental Safety 43(1): 83-90. 

 BIOSIS COPYRIGHT: BIOL ABS. The Fe(III) reduction test was used to measure 

the toxicity of 12 organic chemicals (dichlorophenoxyacetic acid (2,4-D), 

trichlorophenoxyacetic acid (2,4,5-T), atrazine, picloram, 4-chlorobenzeneamine, 

pentachlorophenol (PCP), hexachlorobenzene (HCB), 1,1-bis-4-chlorophenyl2,2,2-trichloroethane (DDT), trichloroethene, benzene, phenol, linear 
308

alkylbenzenesulfonate (LAS)). The different inherent toxicity of the pollutants is 

strongly modified by interactions with the soils. The total amounts that hemical 

(effective concentrations, EC10, EC50, EC90) also vary considerably. For 

somechemicals the influence of soil pH on their speciation in the soil solution is 

mainly responsible for this, e.g., the transformation from anionic to nonionic 

species with decreasing pH. The nonionic species of 2,4-D, 2,4,5-T, and PCP 

formed under acidic conditions are more toxic than the anionic species. Thus, 

depending on the chemical parameters of the soils that determine the degree of 

sorption 

Woodburn, K. B., T. A. Marino, et al. (2008). "Determination of the dietary absorption 

efficiency of hexachlorobenzene with the channel catfish (Ictalurus punctatus)." 

Ecotoxicol Environ Saf 71(2): 419-25. 

 This study was designed to experimentally measure the assimilation efficiency of 

hexachlorobenzene (HCB) in a warm-water, benthic-feeding fish species, the 

channel catfish (Ictalurus punctatus). Catfish were exposed to (14)C-radiolabeled 

HCB in catfish food over a 28-day exposure period, followed by a 14-day 

clearance period. Over the experimental period, the total (14)C residues were 

measured in fish tissue and a simple two-box kinetic model was applied to the 

data to simulate uptake and clearance dynamics. No detectable metabolism of 

HCB by catfish was found. A two-box kinetic model effectively modeled the 

uptake and clearance of (14)C-HCB in catfish, with a calculated assimilation 

efficiency of the chemical into the whole catfish of 67% (growth corrected). The 

growth-corrected pseudo first-order elimination half-life of (14)C-HCB from whole 

catfish was determined to be 29 days (k(2)=0.024 day(-1)). 

Wu, W. Z., B. S. Zhou, et al. (1999). "Cytological and biochemical alterations in 

Carassius auratus hepatocytes from exposure to sediment containing dioxins and 

related compounds." Archives of Environmental Contamination and Toxicology 37(3): 

358-363. 

 BIOSIS COPYRIGHT: BIOL ABS. Cytological and biochemical alterations of 

crucial carp (Carassius auratus) hepatocytes were characterized after exposure 

to sediments from a lake contaminated with dioxins and other industrial 

chemicals. Carp were exposed in 20 L water containing 25, 50, or 100 g of 

contaminated sediment for 2 and 4 weeks. Ultrastructural changes in the liver 

were characterized by severe enlargement of hepatocytes. Alterations in the cell 

included formation of condensed and irregular cell nucleus, polynuclei, d ex was 

significantly increased in experimental groups at 2 and 4 weeks as compared 

with the control group. EROD enzyme activities were strongly induced in liver. A 

trend from rough endoplasmic reticulum (RER) to SER was observed. Our 

results suggest that the dioxin-like compounds bound by sediment were 

bioavailable to C. auratus and cause sublethal effects. 

Yasuhara, A., H. Shiraishi, et al. (1999). "Organic components in leachates from 

hazardous waste disposal sites." Waste Management and Research 17(3): 186-197. 
309

 BIOSIS COPYRIGHT: BIOL ABS. Organic compounds and inorganic elements 

were determined in leachates from 11 landfill sites in Japan. With regard to the 

inorganic elements, the concentration of boron was found to be fairly high. More 

than 100 organic compounds were detected and several important compounds 

such as organic phosphates, 1,4-dioxane, phthalates, and bisphenol A were 

present at high concentrations. Waste plastics are a possible origin for these 

compounds. The ratio of characterized compounds to total organic carbon 

Yeh, D. H. and S. G. Pavlostathis (2001). "Development of hexachlorobenzenedechlorinating mixed cultures using polysorbate surfactants as a carbon source." Water 

Sci Technol 43(2): 43-50. 

 The use of three nonionic polysorbate surfactants--Tween 60, 61 or 65-- as the 

sole carbon source to sustain methanogenesis and dechlorination, as well as the 

effect of long-term exposure of enriched cultures to these surfactants, was 

investigated through the development of three sediment-derived cultures. Over a 

one-year period, the carbon source in these cultures was gradually switched from 

glucose and methanol to surfactant only, while the surfactant concentration was 

increased from an initial concentration of 100 mg/L to 400 mg/L. In each feeding 

cycle, the surfactants were partially degraded and converted to methane. 

Transition from glucose to Tween surfactants as the electron donor did not affect 

the rate, extent, and pathway of HCB transformation. These surfactants 

sustained the reductive dechlorination of HCB even after one year of continuous 

addition to the enriched cultures. This study demonstrated that reductive 

dechlorination of HCB sustained by the fermentation of Tween surfactants is 

feasible. The results support the use of anaerobically degradable Tween 

surfactants for the biotransformation of polychlorinated organic compounds. In 

principle, these surfactants could be used to simultaneously increase the 

bioavailability of subsurface contaminants while serving as the carbon and 

electron source for microbial reductive dechlorination. 

Yeh, D. H., K. D. Pennell, et al. (1999). "Effect of Tween surfactants on methanogenesis 

and microbial reductive dechlorination of hexachlorobenzene." Environmental 

Toxicology and Chemistry 18(7): 1408-1416. 

 BIOSIS COPYRIGHT: BIOL ABS. The effect of nine Tween surfactants 

(polyoxyethylene sorbitan fatty acid esters) on methanogenesis and the microbial 

reductive dechlorination of hexachlorobenzene (HCB) was examined using three 

anaerobic, HCB-dechlorinating mixed cultures, one glucose fed and two lactate 

fed, that were derived from contaminated estuarine sediments. The two lactatefed cultures differed significantly in their metabolic activity, especially with respect 

to the rate and extent of HCB reductive dechlorination. The e lactate-fed culture, 

which exhibited a high metabolic activity. Tween-61 and -65 exhibited the lowest 

inhibition of HCB dechlorination at initial surfactant concentrations of 200 and 

1,000 mg. On the other hand, the Tween surfactants, especially Tween-81 and -

85, enhanced the rates of both methanogenesis and HCB dechlorination when 

the low metabolic activity lactate-fed culture was used. The observed rate 

enhancements may be attributed to bacterial cell membrane modification by 
310

Yuan, S., M. Tian, et al. (2006). "Electrokinetic movement of hexachlorobenzene in 

clayed soils enhanced by Tween 80 and beta-cyclodextrin." J Hazard Mater 137(2): 

1218-25. 

 This study describes the comparative behavior of hexachlorobenzene (HCB) 

contaminated clayed soils in an electrokinetic (EK) system enhanced by Tween 

80 and beta-cyclodextrin (beta-CD). The pH of the soils was controlled by 

Na2CO3/NaHCO3 buffer. Negligible HCB movement was observed when NaOH 

or Na2CO3/NaHCO3 buffer was used as anodic flushing solution. While Tween 

80 or beta-CD was introduced to Na2CO3/NaHCO3 buffer, obvious HCB 

movement was achieved. Although beta-CD led to a less desorption of HCB from 

kaolin than Tween 80, the removal of HCB with beta-CD was much higher than 

that with Tween 80 in the EK system. Tween 80 could be sorped by kaolin more 

than beta-CD, which was responsible for the result. The mechanism of the 

movement of HCB was proposed as the enhanced desorption of HCB from soil, 

the dissolving of HCB in the soil pore fluid and the movement of HCB with the 

electroosmotic flow. Obvious movement of HCB was also observed in the EK 

treatment of real HCB-contaminated clayed soil enhanced by beta-CD. It is an 

alternative approach to use facilitating agents such as beta-CD to enhance the 

EK movement of HCB in the contaminated clayed soils. 

Yuan, S. Y., C. J. Su, et al. (1999). "Microbial dechlorination of hexachlorobenzene in 

anaerobic sewage sludge." Chemosphere 38(5): 1015-1023. 

 BIOSIS COPYRIGHT: BIOL ABS. From this study of the dechlorination of 

hexachlorobenzene (HCB) in municipal sewage sludge by an anaerobic mixed 

culture, we determined the dechlorination rate to be 0.29 mg/day under the 

optimal incubation conditions of pH 7.0, 30ˆC temperature, and a concentration 

of total solids at 26.8 g/L. In addition, we found that dechlorination did not occur 

during agitation. Biotransformation occurred along a pathway of HCBpentachlorobenzene (QCB)-1,2,3,4-tethlorobenzene (TeCB)+1,2,3,5-TeCB-1,2,4-

trichlorobenzene (TCB) + 1,2,3-TCB + 1,3,5-TCB - 1,2-dichlorobenzene 

(DCB)+1,4-DCB. Sequential dechlorination was observed within a substrate 

concentration range of 2-50 me, but slowed down significantly at concentrations 

of 50 mg/L or higher. High-to-low dechlorination mtes under three reducing 

conditions were identified as methanogenic conditions (0.30 mg/L/day) > sulfatereducing conditions (0.12 mg/L/day) > denitryfying conditions (0.08 mg/L/day). 

Zakikhani, M., M. S. Dortch, et al. (2004). Risk Characterization for Future Training 

Scenarios at the Massachusetts Military Reservation (MMR), Govt Reports 

Announcements & Index (GRA&I), Issue 23, 2004: 88. 

 Final rept. 

The original document contains color images. All DTIC reproductions will be in black 

and white. 

This study was conducted to evaluate potential human and ecological health risks 

associated with emission of pyrotechnic compounds during future training 

exercises at the Massachusetts Military Reservation. Air dispersion modeling 
311

was used to determine air concentrations and deposition rates for emissions. 

Annual average and spatially averaged air concentrations and deposition rates 

were used to perform the risk assessments. The Army Risk Assessment 

Modeling System (ARAMS) was used to conduct the human health risk 

assessment, which evaluated a site visitor or trespasser exposed to air and soil 

using air concentrations and deposition rates from the air dispersion modeling. 

ARAMS was also used to evaluate the time for deposited compounds to reach 

groundwater and the peak concentration upon contact with the water table. Of 

the 24 compounds evaluated, only Cr(VI), with an incremental cancer risk of 2.4 

x 10(exp -6), posed a potential concern for human health with the maximum 

exposure and effect through the air inhalation pathway/route. None of the 

compounds are suspected to cause a groundwater problem. Computed soil 

concentrations were compared to soil screening toxicity benchmarks for the 

ecological risk assessment for the purpose of retaining or eliminating chemicals 

from the assessment. Toluene and hexachlorobenzene were the only 

compounds that exceeded the soil toxicity benchmarks. However, because of the 

slight exceedence and its nonbio-accumulating properties, toluene is not 

considered to be a chemical of potential concern. Although hexachlorobenzene 

exceeded the toxicity benchmark, uncertainties and conservative assumptions 

associated with the modeled soil concentrations and conservative soil 

benchmarks should be recognized. 

Zakikhani, M., M. S. Dortch, et al. (2005). Risk Characterization for Future Training 

Scenarios at the Massachusetts Military Reservation (MMR), Final Results, Govt 

Reports Announcements & Index (GRA&I), Issue 06, 2006: 84. 

 Final rept. 

The original document contains color images. Prepared in cooperation with U.S. Army 

Center for Health Promotion and Preventive Medicine, Aberdeen Proving 

Ground, MD. 

This study was conducted to evaluate potential human and ecological health risks 

associated with emission of pyrotechnic compounds during future training 

exercises at the Massachusetts Military Reservation. Air dispersion modeling 

was used to determine air concentrations and deposition rates for emissions. 

Annual average and spatially averaged air concentrations and deposition rates 

were used to perform the risk assessments. The Army Risk Assessment 

Modeling System (ARAMS) was used to conduct the human health risk 

assessment, which evaluated a site visitor or trespasser exposed to air and soil 

using air concentrations and deposition rates from the air dispersion modeling. 

ARAMS was also used to evaluate the time for deposited compounds to reach 

groundwater and the peak concentration upon contact with the water table. Of 

the 24 compounds evaluated, only Cr(VI), with an incremental cancer risk of 2.4 

x 10(exp -6), posed a potential concern for human health with the maximum 

exposure and effect through the air inhalation pathway/route. None of the 

compounds are suspected to cause a groundwater problem. Computed soil 

concentrations were compared to soil screening toxicity benchmarks for the 

ecological risk assessment for the purpose of retaining or eliminating chemicals 
312

from the assessment. Toluene and hexachlorobenzene were the only 

compounds that exceeded the soil toxicity benchmarks. However, because of the 

slight exceedence and its nonbio-accumulating properties, toluene is not 

considered to be a chemical of potential concern. Although hexachlorobenzene 

exceeded the toxicity benchmark, uncertainties and conservative assumptions 

associated with the modeled soil concentrations and conservative soil 

benchmarks should be recognized. 

Zapata-Perez, O., R. Sima-Alvarez, et al. (2000). "Toxicity of sediments from Bahia de 

Chetumal, Mexico, as assessed by hepatic EROD induction and histology in nile tilapia 

Oreochromis niloticus." Mar Environ Res 50(1-5): 385-91. 

 The effect of environmental pollutants present in sediments obtained from Bahia 

de Chetumal, a bay on the border between Mexico and Belize, was studied in 

nile tilapia (Oreochromis niloticus) intraperitoneally injected with sediment 

extracts from six different sites of the Bay. Sediment samples used for the study 

contained a variety of organic chemicals such as organochlorine pesticides, 

polychlorinated biphenyls (PCBs) and polynuclear aromatic hydrocarbons 

(PAHs). Total cytochrome P- 450 and EROD activity were measured in fish liver. 

Haematological and histological analyses were also carried out. Hepatic P-450 

content in treated fish increased from 43 to 240%, and EROD activity from 85 to 

160% compared to controls. Extracts from two sampling sites inhibited EROD 

activity. There were positive significant correlations between P- 450 content and 

the levels of PCBs 44 and 128. EROD activity correlated to HCB, op'-DDE, pp'-

DDE, pp'-DDD, mirex and PCB 18 concentrations. Blood examination showed 

cell degeneration and binucleated leukocytes with abnormal chromatin. Extract 

treatment also resulted in foci of hyperplasia on the basement of gill lamellae, 

hypertrophy and oedema in gills and liver necrosis. Control fish showed no 

abnormalities. The results demonstrate that sediments from Bahia of Chetumal 

have the potential to cause histopathological, haematological and biochemical 

alterations in fish. The administration of sediment extracts to fish may serve as a 

useful test to screen the toxicity of sediments from different areas. 

Zhan, W., Y. Xu, et al. (2000). "Endocrine disruption by hexachlorobenzene in Crucian 

carp (Carassius auratus gibelio)." Bull Environ Contam Toxicol 65(5): 560-6. 

 

Zhang, J. J., B. Wen, et al. (2008). "Effect of microbial activity, soil water content and 

added copper on the temporal distribution patterns of HCB and DDT among different 

soil organic matter fractions." Environ Pollut 152(1): 245-52. 

 Temporal changes in the distribution of exogenous HCB and DDT among 

different soil organic matter fractions were studied under sterile and non-sterile 

conditions, different soil water contents, and different concentrations of added 

Cu(2+). The residence time was 311days. Soil organic matter was fractionated 

into fulvic acid (FA), humic acid (HA), bound-humic acid (BHA), lipid, and 

insoluble residue (IR) fractions by a methyl isobutyl ketone (MIBK) method. 

Results revealed that there is a mass transfer tendency of DDT and HCB from 

FA, HA and BHA to IR and lipid fractions with increasing residence time. 
313

Microbial activity accelerated the mass transfer, while the addition of Cu(2+) 

slowed it down. The HCB and DDT transfer rate decreased as the soil moisture 

increased from 1.9% to 60%, but increased when soil moisture increased further 

to 90%. A two-compartment first order kinetic model was used to describe the 

mass transfer from FA, HA and BHA. 

Zhang, J. J., B. Wen, et al. (2007). "Temporal change in the distribution patterns of 

hexachlorobenzene and dichlorodiphenyltrichloroethane among various soil organic 

matter fractions." Environ Pollut 150(2): 234-42. 

 Residence time-dependent distribution patterns of hexachlorobenzene (HCB) 

and dichlorodiphenyltrichloroethane (DDT) among different soil organic matter 

fractions of three Chinese soils were investigated. Soil organic matter (SOM) was 

fractionated into fulvic acid (FA), humic acid (HA), bound-humic acid (BHA), lipid, 

and insoluble residue (IR) fractions using methyl isobutyl ketone (MIBK) method. 

Results revealed that as the residence time prolonged, the amounts of HCB and 

DDT in the FA, HA and BHA fractions decreased, while those in the lipid and IR 

fractions increased. One- and two-compartment first order, and one- and twoparameter pore-diffusion kinetic models were used to describe the mobility of 

HCB and DDT from the FA, HA and BHA fractions. The results suggest that 

excellent agreements were achieved between the experimental data and fits to 

the two-compartment first order kinetic model (R2>0.97). The transfer rates of 

HCB and DDT followed the order FA>HA>BHA. 

Zheng, T., T. R. Holford, et al. (1999). "Environmental exposure to hexachlorobenzene 

(HCB) and risk of female breast cancer in Connecticut." Cancer Epidemiol Biomarkers 

Prev 8(5): 407-11. 

 Earlier studies have provided inconclusive results relating hexachlorobenzene 

(HCB), an organochlorine fungicide, to female breast cancer risk. The current 

study, with a total of 304 breast cancer cases and 186 controls recruited in 

Connecticut between 1994 and 1997, examined the association by directly 

comparing breast adipose tissue levels of HCB between incident breast cancer 

cases and noncancer controls. The cases and controls were patients who had 

breast biopsies or surgery at the Yale-New Haven Hospital (New Haven, CT) and 

histologically diagnosed either as breast cancer or benign breast disease. 

Information on major known or suspected risk factors for breast cancer was 

obtained through in-person interview by trained interviewers. No significant 

difference in mean breast adipose tissue levels of HCB was observed between 

breast cancer patients (21.0 ppb) and controls (19.1 ppb) in this large casecontrol study. The risk also did not vary significantly by menopausal status, 

estrogen or progesterone receptor status of the breast cancer cases, breast 

cancer histology, stage of diagnosis, or type of benign breast disease. Among 

parous women who reported ever breast feeding, an odds ratio (OR) of 0.5 [95% 

confidence interval (CI), 0.2-1.4] was observed when the highest quartile was 

compared with the lowest quartile. However, no association was observed 

among parous women who reported never breast feeding (OR = 0.7; 95% CI, 

0.3-1.7 for the fourth quartile). For nulliparous women, the adjusted OR was 2.1 
314

(95% CI, 0.5-8.8) for the third tertile when compared with the lowest based on 

few subjects. Therefore, our study does not support a positive association 

between environmental exposure to HCB and risk of breast cancer. 

Zrostlikova, J., S. J. Lehotay, et al. (2002). "Simultaneous analysis of 

organophosphorus and organochlorine pesticides in animal fat by gas chromatography 

with pulsed flame photometric and micro-electron capture detectors." Journal of 

Separation Science 25(8): 527-537. 

 A method using simultaneous pulsed flame photometric (PFPD) and microelectron capture detection (?ECD) in gas chromatog. (GC) was developed and 

validated for the anal. of 23 organophosphorus (OP) and 17 organochlorine (OC) 

pesticides in animal fat. The method entailed the extn. of animal tissue (mixed 

with twice the sample wt. of sodium sulfate) with 7 mL Et acetate per 1 g tissue. 

After the blending step, the ext. was centrifuged and 3 mL cyclopentane was 

added to a 7 mL portion of the ext. A 2.5 mL portion was injected into a 2 cm ID × 

22.5 cm Biobeads S-X3 gel permeation chromatog. column (4.5 mL/min flow rate 

of 70/30 Et acetate/cyclopentane). A 36 mL fraction (from 8 to 16 min) was 

collected, evapd., and solvent-exchanged to 1 mL final vol. in iso-octane. The 

GC/PFPD+?ECD system used a single injector and column, but the flow was 

split after the chromatog. sepn. to the two detectors. The final ext. was injected (2 

?L) into the GC/PFPD+?ECD system for simultaneous anal. of the OP and OC 

analytes. The PFPD was used in the phosphorus-only mode to detect OPs and 

the ?ECD mainly detected halogenated pesticides but a few N-contg. OPs could 

be sensitively detected with it as well. Recoveries were 60-70% for the bulk 

majority of pesticides except for methamidophos, acephate, and omethoate 

which are more difficult in GC anal. due to their more polar nature. Fenthion and 

phorate also gave more variable recoveries, presumably due to their degrdn. to 

sulfones and sulfoxides. In fortification recovery expts. at several different 

concns. over multiple days, reproducibilities of 10-20% relative std. deviation 

were achieved, and limits of quantitation were typically 10-20 ng/g.