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 20092 

### IRIS – UPDATE LI TERATURE 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 dos e-response assessment values (oral reference doses [RfDs]), inhala tion reference concentrations [RfCs], cancer evaluations (both weight of evid ence [WOE] and quantitative) that were posted on IRIS ten or

more years ago.

As an initial step in this goal, a literatu re search was performed to identify new and relevant information that has appeared the in th e literature since the cu rrent 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 potentia l to be toxic in humans.

The literature search was comprehensive and conducted accord ing to conventional procedures in databases listed in the scientific litera ture (specifics available upon request). The title and abstract of every citation identified in th e literature search were read and screened by the USEPA to evaluate their likelihood of offering ne w 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 pr ocess 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 cita tion 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 fo r 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 incl uding their not being directly us eful (code 5) or at all (code 8). A separate code was pr ovided 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 usef ul for establishing IR IS toxicity values

6 Studies with information on h ealth 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). "S urface epithelium of t he 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 dysfunction s, including destruction of ovarian follicles in primates. The purpose of this study wa s to determine the effects of HCB on ovary surface epithelium (SE). Gelatin capsules containing HCB mixed with glucose were given to 16 cynomolgus monke ys housed under controlled conditi ons 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 anima l was removed, fixed in glutaraldehyde, and processed by conventional methods fo r examination by transmission electron microscopy. SE from the animals in contro l group consisted of a single layer of squamous-to-cuboidal cells which possessed mi crovilli 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 gr oups, the degree of severity in creased 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 column ar, 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 observati ons 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 Meri ones 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 fo r 30 days. Morphological and morphometrical estimations were applied to quantify some structural constit uents of the testes. Testicular weight was significantly decreased in all treated groups, while no change was noted in seminal vesicle wei ght. A decrease in the spermatozoid

content of the seminiferous t ube was noted and appeared correlated with a modification of the process of spe rmatogenesis. Spermatic activity in HCBtreated animals testes decreased signific antly, particularly in the group treated with the higher dose (60+ /-3.16% vs. 88+/-4.89% in controls). Plasma testosterone levels were decreased signifi cantly 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 hex achlorobenzene in Meriones unguiculatus: effects on th yroid 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 me riones 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 tr eatment led to a pronounced hepatic hypertrophy comparatively to controls. Histological observations revealed many cytomorphological alterations. Cellular nec rosis, periportal, and centrolobular vein congestion and cytoplasmic vacuolis ation were noted and correlated with the administered doses of HCB. The high er dose of HCB induced modifications in the activities of hepatic transaminas es and on thyroid hormones levels: ALAT activity level was more pronounced in ma les (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 co ntrols). However, ASAT activity increased significantly onl y in females (259+/-29 U/l vs. 244.66+/- 18 U/l in controls). Plasma total triio dothyronine (TT3) and total thyroxine (TT4) levels seemed to be sex-dependent in in toxicated 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 c hanges in ovarian follicles of monkeys administered hexachlorobenzene." Amer ican Journal of Veterinary Research

56 (12): 1673-1677.

OBJECTIVE--To test hexachlorobenzene (HCB ), an environmental pollutant, for its potential toxicity to the ovary. DESIGN--N onhuman primates were or ally 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 that5 contained follicle-stimulating and luteinizi ng hormones to stimulate development of

follicles that would be exami ned by electron microscopy. ANIMALS--Twenty, 6- to 13- year-old cynomolgus monkeys were random ly 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 wee ks. 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 m enstrual cycle, 5,000 IU of human chorionic gonadotropin was administered, and 35 to 38 hour s 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 bu ffered 2% glutaraldehyde, and processed for transmission electron microscopy. RESULTS-- Ultrastructure of ovarian follicles was altered in the monkeys administered HCB. Les ions were observed in the follicles from monkeys given the lowest concentrations of HCB, and comprised condensed mitochondria in the developing ova and follic ular cells that contained nuclei with deep indentations and abnormal accumulation of cytopl asmic lipid droplets. Alterations, such as herniation of the oopl asm, degeneration of the follic ular 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 in tracristal 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 ce llular 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 widespr ead 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 ma mmary gland in laborat ory animals. The aim of this study was to investigate par ameters of thyroid growth regulation, mainly cell proliferation and apoptosis in th yroid 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'-tet raiodothyronine (T(4), th yroxine) serum levels, without changes in thyroid-stimulating horm one concentrations or in thyroid gland weight. Morphological changes, incl uded flattened epithelium and increased colloid size compared with control tissue. Transforming growth factor (TGFbeta1) mRNA levels, evaluated by RT-PCR , revealed a significant upregulation6 after exposure to HCB (1, 10, 100 mg/k g body weight). Ce ll proliferation evaluated by 5'-Br deoxiuridine incorporat ion 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, te rminal deoxynucleotidyl transferasemediated deoxy uridin e triphosphate nick-end labeling, in rat thyroid glands. This process is associated wit h 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 econom y 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 tr eated 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 signi ficantly depressed and isozyme LDH-3 significantly increased at the 50 mg/kg dos e 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 acti vities and CK isozyme profiles were not affected by HCB exposure in utero. T he 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 circ ulating ovarian steroids in hexachlorobenzene-exposed monkeys. " Reproductive Toxicology 9 (6): 541-548.

Hexachlorobenzene (HCB) is a gl obal pollutant that has been identified in human serum and ovarian follicular fluid, and its effe ct on ovarian function has not been adequately defined. Thus, the effects of HCB on ov arian steroidogenesis and menstrual cycle characteristics were investigated in cynom olgus 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 characteri stics 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-l ike compound widely distributed in the environment. In this study, we investigat ed 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 oliv e oil, whereas the control gr oup received olive oil only.

The effects of HCB were evaluated at various time intervals, by measuring auditory nerve acoustic thresholds and pl asma thyroid hormone concentration by radioimmunoassay. Histological evaluat ion 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 acousti c sensitivity, whereas at 4 mg/kg, it induced cochlear sensitivity deficits at the mid-frequencie s (2-16 kHz) with complete recovery once treatment wa s 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 co chlear hair cell loss or alteration of

stereocilia. HCB treatment reduced circ ulating 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 persist ent chlorinated organic chemical that has been detected in many tissues from a variety of spec ies including human ov ary and human ovarian follicular fluid. When administered in high dosage to nonhuman primates,

hexachlorobenzene causes destruction of ovari an primordial germ cells in association with systemic toxicity. The purpose of these ex periments 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. Hexachlor obenzene in dosages of 0.1, 1.0, and 10.0 mg/kg/day was administered orally by gelat in capsule for 90 days. There was a dosedependent accumulation of HCB in serum an d other tissues without any change in the serum estradiol response to human menopaus al gonadotropin, oocyte recovery, oocyte maturation, oocyte fertilization in vitro, and early embryo cleavage rate. There was a dose-related toxic effect observed in primordi al 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 hex achlorobenzene ovotoxic ity may be distinct from hexachlorobenzene-induced cytochr ome P-450-dependent in hibition 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 ev aluate it for potentia l inclusion in the toxic equivalency factor scheme used to assess the risk of dioxin-like compounds. HCB, in corn oil/1% ac etone, 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 tr eatment 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 (2 5 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 increas ed liver cell proliferation ( > =10 mg/kg/day). Spleen, liver, and lung abs olute and relative organ weights were increased ( > =3, > =10, and 25 mg/kg/day, respectively). HCB-related microscopic findings included hepatocellu lar hypertrophy ( > =3 mg/kg/day), pulmonary focal interstitial fibrosis and hi stiocytic 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 t he 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, or25 mg/kg HCB in corn oil 5 days/week for 13 weeks. Dose-dependent, regionspecific, maxillary incisor degeneration wa s observed in animals given HCB at doses of 1.0 mg/kg/day and higher. Treat ment with 1.0 mg/kg/day resulted in focal mesenchymal cell vacuolation and focal osteodentin formation within the pulp. Lesions were restricted to a shor t linear region subjacent to the odontoblast layer along the lateral aspect of the inci sor 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 degenerati on 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 lo w 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 studi es of hexachlorobenzene - Not yet available National Toxicology Program,.

Sims, D. E., A. Singh, et al . (1991). "Alteration of primat e ovary surface epithelium by exposure to hexachlorobenzene: a quantitat ive study." histology and Histopathology 6 : 525-529.

Hexachlorobenzene (HCB) is a fungicide and a pollutant of increasing concern in industrialized regions of the world. Reprodu ctive 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 administrat ion 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 ce ll shape by light microscopy offers a reliable indication of OSE changes induced by HCB.

Singh, A., D. Friesen, et al . (1990). "Hexachlorobenzene toxici ty in the monkey ovary. I. ultrastructure induced by low (0.1 mg/k g) dose exposure." Electron microscopy 12 : 282-

283.

Wolfe, G. W. and S. G. P epperl (2005). Hexachlorobenzene: Reproductive Assessment by Continuous Breeding When Administered to Sprague-Dawley Rats by Oral Gavage, Volumes 1 and 2, Govt Reports Announcem ents & Index (GRA&I ), Issue 13, 2006 : 894. Final rept. Sponsored by National Toxicology Pr ogram, Research Triangle Park, NC. The National Toxicology Progr am generates toxicity data for chemicals of concern in

either an industrial or c onsumer environment. This report summarizes the data generated for hexachlorobenzene (HCB). It has been estimated that airborne

emissions of HCB in the United St ates are between 46,300-63,900 pounds per year. These emissions result primarily from pesticide use and the manufacture of chlorinated solvents (Report on Carcinogen s, Eighth Edition). A previous study conducted by Nakashima et al. (1997) examined the transfer of HCB during lactation to suckling rats, and they conc luded that a large am ount of HCB was

transferred from the dams to the nursing pups through the milk in early days after birth. The available data on the development al toxicity of HCB are limited. This study was designed to generate data on t he mammalian reproductive effects of HCB, examine any effects during conti nuous breeding over two generations, and define a no-effect level for reproduc tive and developmental toxicity.



### CODE 2 (cancer) References

None

CODE 3 (WOE) References10 Ashley, A., M. Lohitnavy, et al. (2004). "Isolation And Enrichment Of Preneoplastic Hepatocytes During Malignant Ce ll 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 ear lier clonal growth modeling studies on a series of chlorobenzenes, the probable exis tence of two cell types in glutathioneS-trasferase (GSTP) foci became apparen t. As suggested by other researchers, these two cell types are either susceptible or resistant to mitoi nhibitory 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 GS TP foci form, isolation of GSTP positive (GSTP+) cells from liver ac ross time allows capturing changing characteristics of an emerging malignant population. This study describes an attempt to isolate primary GSTP+ hepatocyt es using Ito’s bioassay protocol with diethylnitrosamine (DEN) as an initia ting agent and a 2/3 partial hepatectomy with concomitant dosing of hexachl orobenzene (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 si gnificant increase in liver weight was observed in rats coexposed to HCB and PC B 126. Either prim ary hepatocytes or liver sections were taken to analyze forma tion of GSTP+ foci . By treating cell suspension and/or culture with ethacrynic acid (EA) (Stenius et al., Carcinogenesis 15:1561-1566, 1994), GS TP+ hepatocytes were enriched by inducing toxicity to non-GSTP+ cells. In so doing, progressively more malignant cell populations can be subjected to ce ll cycle kinetic studies, genomic analyses, and clonal growth modeling to aid our in sight 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 lipophili c contaminants found in breast tissue

with a debated role in breast cancer development (BCD). HCB, a widespread organochlorine in the environment, is virtual ly present in 100% of North American women. Epidemiological studi es indicated that some br east cancer patients have higher HCB levels. We observed that long term exposure of human mammary epithelial cells to HCB increases the phos phorylation of c-er bB2 (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 epigenet ic 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 pa ssages of continuous exposure to HCB, an increase in proliferation was obs erved. These cells showed an increase in the phosphorylation of t he integrin-linked kinase (I LK), with a decrease in Akt/PKB levels. ECadherin, an important cell adhesion molecule, was also

decreased. Control cells sub-cultur ed on Matrigel® showed a distinctive11 branching pattern after 24h. However, HCB-exposed cells exhibited a rounded shape with minimal cellular contacts. Th is is suggestive of a decrease in

intercellular communication and cell adhes ion ; the latter is supported by the decrease in E-Cadherin expression in thes e cells. Moreover, a fter 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 co mmunication 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 contro ls E-cadherin expression. This work brings biological plausibility to the invo lvement of environmental contaminants in

BCD.

Bauer, M., F. Hilpert, et al. (2004). "Persistent organochlorine compounds and their role for the carcinogenesis of breast c ancer." Geburtshilfe und Frauenheilkunde 64 (7): 681-

689. A review. The role of persistent organoc hlorine compds. in the development of breast cancer is controversially discuss ed. Used as biocides or tech. adjuvants for misc. applications, organochlorines have been released into the environment for years. Due to their highly lipophi lic 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 to xicol. properties: organochlorines are able to influence estrogen-mediated and ot her 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 t he correlation between organochlorine exposure and the incidence of breast canc er. 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 co mpare. In addn., genetically detd. and individually varying sensitivity to organoc hlorines, synergistic interactions of several compds., and evidence for the asso cn. of organochlorine exposure with poor prognosis in case of malignant trans formation complicate the interpretation of many results. However, considering the available data, the involvement of organochlorine compds. in the carci nogenesis of breast cancer can not be

excluded and therefore needs further investigation.

Biggs, M. L., M. D. Davis, et al. (2008). "Serum or ganochlorine 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 organochl orine pesticides commonly found in human tissue possess antiandrogenic properti es. We examined whether the risk12 of TGCC is associated with serum le vels of 11 organochlorine pesticides, including p,p'-DDE, and whether the p,p' -DDE-TGCC association is modified by CAG or GGN repeat pol ymorphisms in the andr ogen receptor gene. We conducted a population-based case-control st udy among 18- to 44-year-old male residents of three Washington State count ies. Cases (n = 246) were diagnosed during 1999 to 2003 with a firs t, primary TGCC. Controls (n = 630) were men of similar age with no history of TGCC from the same popu lation identified through random-digit telephone dialing. Q uestionnaires elicited information on demographic, medical, and lifestyle fact ors. A blood specimen provided serum for gas chromatography-high-resoluti on 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 obser ve that the risk a ssociated with p,p'- DDE was modified by androgen receptor CAG (<23 versus > or =23 repeats) or GGN (<17 versus > or =17 repeats) genot ype. This study does not provide support for the hypothesis that adult expos ure to organochlorine pesticides is

associated with risk of TGCC. Due to uncertainty regarding how well organochlorine levels measur ed 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). "Occurrenc e of organochlorine pest icides in cancerous

and non-cancerous breast tissues." Fr esenius 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 adj acent 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. Cert ain OCP elevations in breast tumors, although their role for the menopausal status of the patients, and stage and grade of the disease could not cl early evidenced, show that these OCPs, to a certain extent, might pl ay a role in breast cancer risk.

Cantor, K. P., P. T. Strickland, et al. (2003). "Risk of non-Hodgkin's lymphoma and prediagnostic serum organochlori nes: 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. Studi es 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 C ounty, Maryland (USA), and cryopreserved for future study. We measured predi agnostic levels of chlordane, lindane (gamma-hexachlorocyclohexane), beta- hexachlorocyclohexane, transnonachlor, heptachlor, heptachlor epoxide, oxychlor dane, 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, t here was no evidence of an association between NHL risk and serum levels of any of the individual lipid- and recoverycorrected organochlorines that we ev aluated, nor of t he 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 Ce ll-Cell Interactions By Epigenetic Hepatocarci nogens." Toxicol Sci 84 (1-S): 336-7. Mechanisms of epigenetic carcinogenesis involve disruption of cell or tissue homeostasis, such as cell-cell intera ctions mediated by various types of junctions. Gap junctions are formed by c hannels that allow direct communication between cells (GJIC), while adher ing junctions maintain tissue integrity by linking cells together. Gap and adhering junctions are physically and functionally

interrelated membrane structures. Connexi ns and cadherins are key proteins in gap and adhering junctions, respectively. Wh ile the effects of hepatocarcinogens on these proteins in rodent livers ar e 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 hexachl orobenzene (HCB), an important environmental contaminant, t hat 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 pat hway 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 vitr o studies, using specific inhibitors and overexpression systems confir med not only the role of ILK pathway in cell-cell interactions, but also t he functional interrelationships between connexins and cadherins. Down-regulati on of proteins forming gap and adhering junctions allow initiated cells to e scape control from neighboring cells, thus promoting their clonal ex pansion. The importance of such mechanisms in carcinogenesis is illustrated by the fact that human tumors of various origins

show low levels of immunoreactive c onnexins and cadherins. Moreover, studies suggest that lost of cell-cell interact ion proteins is an early event in the14 carcinogenesis process. Overall, data support the content ion 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 canc er and serum organochlorine residues." Occup Environ Med 60 (5): 348-51. BACKGROUND: Controversy still exists abo ut the breast carcinogenic properties in humans of environmental xenoestrogens (organochlorines), justifying new investigations. AIMS: To compar e the blood levels of total dichlorodiphenyltrichloroethane (DDT) and hexachlorobenzene (HCB) in samples

collected at the time of breast cancer di scovery, in order to avoid the potential consequences of body weight change (a fter chemotherapy or radiotherapy) on the pesticide residue levels. METHODS: Bl ood 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 c ancer and 250 presumably healthy

controls. Risk of breast cancer associat ed with organochlorine concentration was

evaluated. RESULTS: Mean levels of total DDT and HCB were significantly higher for breast cancer patients than for co ntrols. No differences in serum levels

of total DDT or HCB were found between oestrogen receptor positive and oestrogen receptor negative patients with breast canc er. CONCLUSIONS: These results add to the growing evidence that certain persistent pollutants may occur in higher concentrations in blood samp les from breast c ancer patients than

controls.

Charlier, C., J. M. Foidart, et al. (2004). "Environmental di chlorodiphenyltrichlorethane or hexachlorobenzene exposure and breast cancer: is there a risk?" Clin Chem Lab

Med 42 (2): 222-7. The carcinogenic potential of env ironmental xenoestrogens (i.e., organochlorines) is a matter of controve rsy. Their pathogenic role as promoters in breast cancer has been previously s uggested. In Europe, despite their prohibition since the '70s, residues persi st 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-dic hloro-2, 2-bis (4-c hlorophenyl) ethylene (DDE) and hexachlorobenzene (HCB) in 231 wom en 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 cont rols (26 from 290). Even if taking all undetectable results (recorded as "0") in to consideration, mean values were significantly different in cases when co mpared 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 contro ls (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 contro ls (p < 0.0001). When considering p,p'-DDE and HCB as binary va riables (1 if higher than the limit of quantification, 0 if lower), the presence of both re sidues was significantly

associated with an increased risk of breas t 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 leve l was moderately correlated with tumor size (p = 0.026).

Cocco, P., P. Brennan, et al. (2008). "Pla sma polychlorobiphenyl and organochlorine pesticide level and risk of major lymphoma s ubtypes." Occupational and Environmental

Medicine 65 (2): 132-40. BACKGROUND: There is conflicting epi demiological evidence concerning an increase in risk of non-Hodgkin's ly mphoma (NHL) associated with elevated blood levels of persistent organochlorine (OC) pesticides and polychlorobiphenyls (PCBs). METHODS: We measured the concentration of 17 OC pesticides, including hexachlorobenzen e (HCB), four lindane isomers (alpha- , beta-, gamma- and delta-hexachlor ocyclohexane (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 pes ticides and PCBs was calculated using unconditional logistic regression. RESU LTS: Risk of NHL, diffuse large B cell lymphoma (DLBCL) and chronic lymphatic l eukaemia (CLL) did not increase with plasma levels of HCB, beta-HCH, p,p'-d ichloro-diphenyl-dichloroethylene (DDE),

or total and individual PCBs or their functional groups, in the overall study population. Substantial heter ogeneity in DLBCL risk associated with immunotoxic PCBs (p = 0.03) existed between the Spanish subgroup (odds ratio (OR) for immunotoxic PCB plasma level above t he 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 organoc hlorine chemicals in plasma and risk of non-Hodgkin's lym phoma." Cancer Research 65 (23): 11214-26. Polychlorinated biphenyls (PCB) have been suspected as possible contributors to increasing non-Hodgkin's lymphoma incid ence during the latter half of the 20th century based on their toxicologic proper ties and provocative epidemiologic reports. We investigated PCBs and other organochlorines and risk of nonHodgkin's lymphoma in a population-bas ed case-control study in the United States. Congeners of PCBs (including copl anar congeners), diox ins, furans and pesticides or pesticide metabolites were measured in plasma of 100 untreated cases and 100 control subjects. We used a mu ltiple imputation procedure to fill in missing values of levels determined to be below the detection limits. Risks of non-Hodgkin's lymphoma associated wit h 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 coplan ar PCBs 156, 180, and 194, with odds ratios for the highest versus lowest quartile ranging fr om 2.7 to 3.5, and significant trends. Each of the furan congeners was a ssociated 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 su mmed metric that weights congeners by their dioxin-like potency, was associ ated 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-Hodgk in'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 carci nogenic properties by environmental xenoestrogens (organochlorine pesticides) still exists and making new studies to compare the blood levels of total di chlorodiphenyl trichloroethane (DDT) and hexachlorobenzene (HCB) in blood sample s 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 pr esumably healthy controls. Risk of breast cancer assocd. with organochlorine concn. was evaluated. Mean levels of total DDT and HCB were significantly hi gher 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 samp les from breast cancer patients than

controls.

Fratev, F. and E. Benfenati (2008). "A comb ination of 3D-QSAR, docking, local-binding energy (LBE) and GRID study of the specie s 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 bas is 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 regressi on 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 followin g approaches were used. The 3D models of CYP2E1 for mouse and rat were built up. A docki ng study was applied and the important ligand-protein residues interactions and oxid ation positions of the molecules were17 identified. A new approach for quantitative assessment of metabolism pathways was developed, which enabled us to descri be 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 en ergies of the important substituents (local-binding energy-LBE) were calc ulated, in order to quantitatively

demonstrate the contribution of the s ubstituents 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 identif ication 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 persi stent organic pollutants (POPs) has been

indicated to be a risk factor for non-H odgkin's lymphoma (NHL). Epstein-Barr virus (EBV) has been associated with some subgroups of NHL. In a previous study we found an interaction between hi gh 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 adj usted plasma concentrations of 35 congeners of polychlorinated bi phenyls (PCB), p,p'- dichlorodiphenyldichloroethyelene (p,p '-DDE), hexachlorobenzene (HCB), seven subgroups of chlordanes (c is-heptachlorepoxide, cis-ch lordane, trans-chlordane, oxychlordane, MC6, trans-nonac hlordane, cis-nonachlordane) and one polybrominated diphenylether (PBDE) c ongener (no. 47) in 99 cases with NHL and 99 population based controls. Odds rati os (OR) for NHL were estimated. Sum of PCBs > median in the controls gav e odds ratio (OR) 2.0, 95% confidence interval (CI) 0.99-3.9. High sum of chlo rdanes 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. Si milarly 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 chlo rdanes yielded OR 6.8, 95% CI 2.3-20, whereas no associ ation 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 conc entrations of certain persistent organic pollutants with endocrine-disrupt ing 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 t he statistical analysis. In the total material, a greater-than median concent ration of PCB congener 153 yielded an18 odds ratio (OR) of 3.15 and 95% confidenc e 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 m edian 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 ac tivity was found to produce significantly increased risks for enzyme and phenobarbi tal-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 rele vance of the arbitrar y 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 J ournal 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-dichlor oethylene (pp'-DDE), hexachlorobenzene (HCB), chlordanes and polybrominated di phenylethers (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 di fferences were found between cases and controls. Case mothers had in general hig her 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 t he 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 polluta nts (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 pancr eatic cancer. The comparison group consisted of 59 subjects. Significa ntly increased concentrations of polychlorinated biphenyls (PCBs), hexac hlorobenzene (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) c ould 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 significant ly increased for p,p'-DDE or PBDEs. Body mass index (BMI) at the time of ti ssue sampling was significantly lower for the cases. This might have influenced the results. Usi ng BMI one year previously or decreasing the concentrations of POPs with the same percentage as weight loss among the cases did not change the re sults. Survival of the cases was shorter in the group with the concent ration 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. Er iksson (2003). "Is t he decline of the increasing incidence of nonHodgkin lymphoma in Sweden and other countri es a result of cancer preventive measures?" Environmental Health Perspectives 111 (14): 1704-6. Is the decline of the increasing inci dence 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, Fi nland, and Denmark. Immunosuppression is one established risk factor for NHL, possibly wi th interaction with Epstein-Barr virus. Phenoxyacetic acids and chlorophenols, both pesticides, have been associated

with NHL. Use of these chemicals wa s 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 w hole population occurs predominantly through the food chain. Exposure to su ch chemicals was highest in the 1960s and 1970s. Because of regulation in the 1970s, exposure has declined substantially in the population. The c hange in incidence of NHL in Sweden and other countries may serve as a good exampl e of how prohibition and limitation of exposure may be reflected in cancer statistics some decades later.

Hardell, L., G. Lindstrom, et al. (2006). "High concentrati ons of organochlorines in a patient with kidney cancer and anorex ia-cachexia syndrome." Med Chem 2 (6): 607-10. PURPOSE: To determine persistent or ganic 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'- dichlorodiphenyltrichlor oethane (DDE), hexachlorobenzene (HCB), chlordanes and tetrabromodiphenyl ether (TeBDE) we re determined on lipid basis. For comparison results from 29 male popul ation 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 (medi an for controls 46), and sum of20 chlordanes 2 389 (median for controls 62). T he patient lost weight from 80 kg to 48 kg when he died, which may have contribut ed wholly or partly to the very high concentrations of organochlorines. CONCL USION: Changes in weight must be recorded in cancer patients and the c oncentrations of persistent organic pollutants should be normalized to weight. The concentrations in this patient

were 10- to almost 40-ti mes higher than in the cont rols. 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). "A dipose tissue concentrations of p,p'-DDE and the risk for endometrial cancer." Gynecol Oncol 95 (3): 706-11.

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

cancer associated with environmental endocrine disruptors. METHODS: We analyzed the adipose tissue concentrati ons of polychlorinated biphenyls, hexachlorobenzene (HCB), p,p'-dichlorodip henyl-dichloroethylene (p,p'-DDE), chlordanes, and polybrominated biphenyls in 76 cases with endometrial cancer and 39 controls with benign endometrial hyper plasia. RESULTS: For the different chemicals, odds ratios (ORs) and 95% confidence intervals (CI) were close to unity taking the median concentration am ong the controls as cutoff value. However, for p,p'-DDE OR = 1.9, 95% CI = 0.8-4.8 was obt ained. Additional estrogen replacement therapy yielded in th is 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 etiol ogy of endometrial cancer, although no significant associations were found.

Hardell, L., B. van Bavel, et al. (2003). "Increased concentrations of polychlorinated biphenyls, hexachlorobenzene, a nd 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 initiat ed during the fetal peri od, and exposure to endocrine disruptors, i.e., xenoestrogens , has been of concern. In this investigation we studied the concentra tions of the sum of 38 polychlorinated biphenyls (PCBs), p,p'-dichlorodipheny l-dichloroethylene, hexachlorobenzene (HCB), and chlordanes, in 61 cases wit h testicular cancer and 58 age-matched controls. Furthermore, case and control mo thers were also a sked 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 th e 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 = 1.921 (95% CI, 0.7-5.0). No consis tent 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 c oncern and is treated based on its hormone dependence. Agents that alter hormone ac tion 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 canc er. The present review is focused on agents that alter hormone action in the pr ostate 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 desig ned 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 meas ured concentrations in serum of several organochlorines by gas chromatography. We assessed point mutations in K-ras and p53 genes in tissue samples by polym erase chain reaction/single-strand conformation polymorphism and assess ed expression of p53 protein by

immunohistochemical methods. An elevat ed risk of colorectal cancer was associated with higher serum concentra tions of mono-ortho polychlorinated biphenyl (PCB) congeners 28 and 118. T he 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, hexachlor obenzene, and p,p'-DDE (4,4'- dichlorodiphenyltrichloroethene) showed n onsignificant increases in risk. Risk

associated with mono-ortho PC Bs 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 transvers ion-type mutations in both genes. These results generate the hypothesis that exposure to mono-or tho PCBs contributes to human colorectal cancer developm ent. The trend and magnitude of the association, as well as the observation of a molecular fingerprin t in tumors, raise the possibility that this finding may be causal.

Ichihara, T., N. Imai, et al. (2005). "Evidence of a thre shold dose for promotion of hepatocarcinogenesis by hexac hlorobenzene in a rat medi um-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. fo ci in the male22 F344/DuCrj (F344) rat liver was evaluat ed with 11 different dietary doses, ranging from 0.002 to 75 ppm, using a m edium-term liver bioassay system. No mortalities caused by HCB treatment were encountered, and no clin. changes were apparent. The nos. and areas of GS T-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 signific antly, increased. The present results indicate that HCB exerts a weak promot ion 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 organochlor ine pesticide residues and antioxidant enzyme activities in human breast tumors: is t here any association?" Breast

Cancer Research and Treatment 72 (2): 173-82. The levels of some organochlorine pes ticides (OCP)s (hexachlorobenzene, HCB, alpha-hexachlorocyclohexane, al pha-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 glut athione 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 peroxidati on (LP), glutathione S-transferase (GST) activity toward several substrates in cluding 1-chloro-2,4-dinitrobenzene (CDNB), 1,2-dichloro-4-nitrobenzene (DCNB), ethac rynic acid (EAA), 1,2-epoxy-3-(pnitrophenoxy)-propane (ENPP) were meas ured in tumor and surrounding tumor

free tissues of 24 female breast canc er patients and was evaluated whether there exist any associati on between the levels of OC Ps 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,GR d, GST CDNB, and GST DCNB were significantly higher in tumors than in cont rols. In tumors, signi ficant correlations were noted between: SOD and y-BHC; Se-GSH-Px and gamma-BHC; T-GSH-Pxand gamma-BHC; GSH-Px II and alpha-BHC, gamma-BHC; GSH and alphaBHC, gamma-BHC, HE; GRd and al pha-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 conc entrations of polychlorinated biphenyls, hexachlorobenzenes, and chlordanes in mother s 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 t hat environmental contamination with organochlorine pesticides may be related to risk of breast cancer. To investigate23 this association in a rural part of Au stralia, organochlorine contamination data from a breast milk organochlor ine study conducted in the st ate 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 av erage population of 2, 147,409 women. The Ovens-Murray region, which was t he region most contaminated with organochlorine pesticides, showed an elev ated SIR of 1.10 ( 95%CI, 1.03-1.17), although two other regions wit h lower organochlorine cont amination 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 cont amination and the age-standardized rate of breast cancer ac ross all regions. But a positive doseresponse relationship using an adjusted negative binomial model was detected for heptachlor epoxide. Our study may pr ovide limited support for the role of environmental contamination with organochl orine pesticides in the development

of breast cancer.

Kishima, M. O., L. F. Ba rbisan, et al. (2000). "Promo tion of hepatocarcinogenesis by hexachlorobenzene in energy- rest ricted 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 we re 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 ex ert any influence on the development of glutathione S-transferase placental fo rm (GST-P(+)) foci of hepatocytes. Simultaneous HCB exposure and energy restriction induced a significant increase in liver centrilobular hypert rophy and GST-P(+) foci development. Our findings suggest that energy restriction in creases liver response to low dose of HCB, unmasking the promoting pot ential 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 elec tronic 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 sele cted compds. The multivariate anal. allows us to propose a theor. model that correlates these descriptors with the carcinogenic activity in a series of c hem. compds. The protecting activity of antioxidants was analyzed by considering their competit ion 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 c oncentration of organochlorine pesticides with dietary intake and other lif estyle factors among urban Chinese women."

Environment International 33 (2): 157-63.24 Concerns about the carcinogenic and endocrine-disrupting characteristics of organochlorine pesticides (OCPs) hav e led to a global ban on OCP use. However, OCPs persist in the envir onment 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) is omers (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 in terview. 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 v egetable and fresh bean consumption was negatively associated with OCPs level. Ou r study suggests that dietary intake may be an important contribut or 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 canc er assocd. with environmental endocrine disruptors was evaluated in this case-control study. The adipose tissue concns. of polychlorinated biphenyls, hexachl orobenzene, p,p'-DDE, chlordanes, and polybrominated biphenyls in 76 cases wit h endometrial cancer and 39 controls with benign endometrial hyperplasia were an alyzed. 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 o ff value. However, for p,p'-DDE OR = 1.9, 95% CI= 0.8-4.8 was obtained. Addnl. estrogen repl acement 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 expo sure 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 Sw edish 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 exposure25 to 13 chemicals classified as "possibl e exposure", "prob able exposure" or "unexposed". Relative risks were obtai ned using Poisson models adjusted for age, period and geographical area. A sec ond analysis was performed, in which adjustment was additionally made for si multaneous exposure to other matrix chemicals and ionising radiations. R ESULTS: 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 asso ciated with excess TC among women.

Lu, Y. (2006). "Application of physiolog ically 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 hexachlorobenz ene and PCB 126: imp lication of sizedependent cellular growth ki netics." Arch Toxicol 82 (2): 103-16. The objectives of this study were twofold: (1) evaluating the carcinogenic potential of the mixture of two pe rsistent environmental pollutants, hexachlorobenzene (HCB) and 3,3',4,4',5-pent achlorobiphenyl (PCB 126), in an initiation-promotion bioassay involvin g 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 treatment s of initiator, two-thirds partial hepatectomy, and daily oral gavage of the mi xture 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 de velopment of initiated GST-P cells in the liver over time. In the model, t he initiated cells were partitioned into two subpopulations with the same division ra te 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, t he 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 experimen tal 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 C ontext Of Ito's Medium-Te rm Liver Foci Bioassay." Toxicologist 78 (1-S): 244-5. Hexachlorobenzene (HCB) is an important environmental contaminant. Due to its high lipophilicity and persistence in t he environment, human exposure to HCB has continued despite the curtailment of its usage. HCB is carcinogenic to26 laboratory animals with the liver as one of the primary tar get organs. We have incorporated the study of the re lationship between pharmacokinetics and pharmacodynamics into the Ito’s medium-t erm liver foci bioassay. Thus, we describe here the development of a PBPK m odel 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 (Scheufle r 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 fi ve 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 subc ompartments, one wit h a higher perfusion rate and lower partitioning and the other wit h a lower perfusion rate and higher partitioning. Uptake of HCB was diffu sion-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 inte stinal lumen. Reabsor ption of HCB from the intestine was incorporated in t he model. The resultant model adequately

described the available data sets. This model may be linked with a clonal growth model to quantitatively describe the relati onship 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 ap optosis 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 breas t cancer risk Canada." Cancer causes &

control : CCC 15 (4): 399-418.

Genes that metabolize the rate of cl earance 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 theref ore reasonable to ask if variants in the genes responsible for the metabolic activa tion of organochlorines are associated with different tissue burdens of organochlori nes and if these variants modify the risk of breast cancer in the population. We conducted a case-control study of

women who underwent an exci sion biopsy for suspected breast cancer in a Toronto hospital from 1995 to 1997. Patient s 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 GS TM1 had higher levels of breast organochlorines, and were at modestly in creased 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 s upport the hypothesis that organochlorines increase27 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 ma mmary tissue modulates biomarkers expression in ER?-positive breast ca rcinomas." 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. Organoc hlorine compds. (OCCs), such as pesticides and polychlorinated biphenyls (PCB s), are persistent lipophilic chems. identified as endocrine disruptors mainly with estrogenic effects. To test the hypothesis that the amt. and quality of or ganochlorine residues in adipose tissue adjacent to breast carcinoma affect the biol. behavior of the tumor, we studied biomarker expression in breast carci noma and OCCs body burden in patients from an urban area adjacent to Parana fl uvial 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 rec eptor (PR) and prolif erative activity (Ki-67) were measured in paraffin em bedded 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' dichlorodiphenyldichloroet hylene (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. br east carcinoma patients, there was a pos. correlation between PR expression (an estrogen induced protein) in the neoplastic cells and OCCs levels in adipo se tissue surrounding the tumor. More significant, all the ER?-pos. breast ca rcinomas from postmenopausal women exhibited high proliferation when organoc hlorine levels in the surrounding adipose tissue reached levels higher t han 2600 ppb. No assocns. were found between organochlorine body burden and any other marker of tumor aggressiveness such as node involvement ortumor size. Conclusion The present results support the hypothesis that or ganochlorine 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 com pds. and hormonal therapy could be expected to occur.

Muscat, J. E., J. A. Britton, et al. (2003). "Adipose concen trations 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 compou nds (OCs), such as pesticides and polychlorinated biphenyls (PCBs), and brea st cancer. The estrogenic effects of28 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 extrac tion 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 conc entration of pesticides and PCBs was correlated with baseline age and body mass index, but not wit h cancer stage. The highest tertile of total PCB conc entration 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 fo r 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 t heir highest levels. Self-reported home termiticide exposure, alcohol consumption (> or = 1 drink/day), and race were not associated with prognosis. The RR for cu rrent 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 ca ncer 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 studi es of hexachlorobenzene - Not yet available National Toxicology Program,.

NTP (2004). Hexachlorobenz ene. Report on carcinogens . Bethesda, MD, National Toxicology Program. 10: 134-135.

Oezden, S., T. Chen, et al. (2008). "Alterat ion 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 simula tion of hepatic preneoplastic foci development for four chlorobenz ene congeners in a medium-term bioassay." Toxicological Sciences 73 (2): 301-14. A combination of experimental and si mulation approaches was used to analyze clonal growth of glutathione-S-transferase pi (GST-P) enzyme-altered foci during liver carcinogenesis in an initiation-pro motion 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 perform ed 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 a fter initiation. A clonal growth stochastic model separating the init iated cell population into two distinct subtypes (referred to as A and B cells) was successfully used to describe the foci29 development data for the four chlorobenzenes . The B cells are initiated cells that display a selective growth advantage under c onditions that inhibit the growth of

initiated A cells or norma l 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 sensitiv ity analysis of model parameters. While TECB, PECB, and HCB all significantly increased fo ci volume, only HCB increased normal hepatocyte proliferation. Toget her, these results indicate that examining effects of chemicals on regenerative responses fo llowing partial hepatectomy may be a means for understanding t he carcinogenicity potent ial of chlorobenzene compounds.

Ou, Y. C., R. B. Conolly, et al. (2001). "A clonal growth model: time-course simulations of liver foci growth followi ng penta- or hexachlorobenzene treatment in a medium-term bioassay." Cancer Res 61 (5): 1879-89. A combination of experimental and simu lation approaches were used to analyze the clonal growth of preneoplastic, enzyme-altered foci during liver carcinogenesis in an initiation-promotion r egimen. 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 pentachlor obenzene (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'-deoxy uridine- 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 in ferred by a comparison of model outcomeswith 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 ca librated model for the DEN controls incorporated the hypothesis of two initia ted 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 adv antage under conditions that inhibit the growth of A cells and normal hepatocytes. The parameter values defined in the DEN controls were used to evaluate exper iments involving the administration of

PECB or HCB. Both PECB and HCB caused a significant increase in foci volume compared with the DEN c ontrols. HCB treatments resulted in increased proliferation of normal hepatocytes, whic h was not observed for PECB under the same treatment regimen. The best descr iption of the data resulted from the model incorporating the hy pothesis 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. This30 simulation work is an example of quantitat ive approaches that could be useful for the analysis of other init iation-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 Michal ovce district diagnosed between May 1997 and May 1999 were recruited through the On cology 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-chlor ophenyl)-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-fo r 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 associat ed 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 significan t, 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 persisten t, lipid-soluble chemicals in breast and abdominal adipose tissues: lessons learned from a breast cancer study." Cancer Epidemiology, Bi omarkers and Prevention 13 (3): 416-24. OBJECTIVES: We sought to determine di fferences between concentrations of persistent, lipid-soluble chemical contam inants in breast and abdominal adipose tissues and to explore whether concent rations measured in one tissue could predict concentrations in the other ti ssue. METHODS: We analyzed surgical specimens and measured concentrations of prevalent dioxins, furans, polychlorinated biphenyls, organochlorin e 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 reco nstruction, 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 adi pose tissues were correlated and that31 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 st udies that used different tissues. It may also facilitate future breast cancer st udies by allowing selection of controls among patients undergoing surgical proced ures other than breast surgery, minimizing concerns about overmatching. We also observed large differences in the lipid content of surgical specim ens. These differences underscore the need for lipid adjustment of concentrati ons 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 carci nogen, HCB induces the formation of liver tumors in female rats, whereas only a small percentage of males are responsive. Intercellular comm unication via gap junctions is decreased in carcinogenesis. Gap junctions are co mposed 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 effe cts result from gender differences in the constitutive expression of these Cxs. Rats were given HCB by gavage for five consecutive days. In the first experim ent, control and HCB-treated female rats were sampled on day 100. Intercellu lar communication was significantly decreased in HCB-treated females compar ed 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 fe males as compared to controls. Cx26 mRNA levels were 3-fold higher and Cx 32 mRNA levels were 8-fold lower in females compared with males. In a thir d experiment, ovariectomy abolished any

differences between male and female contro ls for both Cxs, while estradiol had a partial role in the regulation of Cx32. This suggests that the sexual dimorphism inhepatic Cx levels is determined by the ovarian hormones. However, the HCBinduced decrease in Cx32 and Cx26 m RNA 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 H epatocytes; 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 pat hway 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 ai m of this study was to

demonstrate the role of t he ILK pathway in the r egulation of adhering and gap junctions in liver cells. MH1C1 rat hepatocytes exposed to HCB for 7 days

showed increased levels of the inacti ve form of GSK3beta, i.e. phosphoGSK3beta, an important messenger of IL K 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 (k enpaullone 5 and 10 uM, SB- 415286 125 and 150 nM) markedly reduced GSK3beta acti vity and caused an approximately 50% decrease in E-cadherin mRNA levels, whereas Cx32 mRNA levels were unchanged. This suggests that in MH 1C1 cells, Cx32 expression is not modulated by GSK3beta, but depends on eit her 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 regulati on. Together, these data de monstrate that in rat hepatocytes E-cadherin is down-regulated by the ILK pathway via GSK3beta inhibition and up-regulated by Cx32 over expression. 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 in tegrin-linked kinase pathway in hexachlorobenzene-induced gender-specific ra t hepatocarcinogenesis." Toxicol Sci

88 (2): 346-57. Overexpression of the in tegrin-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 pathw ay. Hepatic ILK levels were markedly increased in HCB-treated female rats. Cy toplasmic/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 (G SK3beta), rendering it inac tive. 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 nucl ear translocation of beta-catenin, as demonstrated by both immunocytochemis try and flow cytometric analyses. Western blot analysis showed an 84% decr ease 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 downregula tion of intercellular communication33 does not occur as a result of either E-cadherin downregul ation or GSK3beta

inactivation.

Plante, I., D. G. Cyr, et al. (2007). "Sexual dimorphism in the regulation of liver connexin32 transcription in hexachlo robenzene-treated rats." Toxicol Sci 96 (1): 47-57. Hexachlorobenzene (HCB), an epigenetic carcinogen, causes female rats to be more susceptible to liver tumor formati on 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 prom oter 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 diffe red between males and females. The formation of this complex requires two binding sites to be intact in a fragment of the basal promoter (Fr 26). 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 ex pression 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 comp lex appears to be controlled by Akt and requires the integrity of a Myb site. Overa ll, results suggest that both the sexual dimorphism and the downregulation of Cx 32 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 se rum concentrations of highly prevalent organochlorine com pounds 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 wit h exocrine pancreatic cancer were

evaluated. The correlation between DDT and DDE was stronger in cases older than 60 yr than in younger cases, sugges ting that younger subjects incorporated the two compds. in a more independent manner than older ones. This indicated that, while in the elderly a larger propor tion of the p,p'-DDE body burden would

stem from metabolization of p,p'-DDT, the predomi nant source of DDE in younger cases would be backg round 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-hex achlorocyclohexane was also high

and was the same in men and in wom en, 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 an d 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 organochlor ine 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 det ermined. 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 se x, age, region of residence within the United States, and race/ethnicity. Condit ional logistic regression showed the organochlorine pesticide residue heptachl or 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 leve l 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-dich loro-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 epoxi de 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, o ccupation, and body mass index. Given the persistence of pesticides in the environm ent, these findings are still relevant today.

Raaschou-Nielsen, O., M. Pavuk, et al. (2005). "Adipose organochlorine concentrations and risk of breast cancer among postm enopausal 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 c ancer with mixed results. Our purpose

was to examine associations between or ganochlorines 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, C ancer, 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 conditio nal logistic regression. RESULTS: The results showed no higher risk of breast cancer among women with higher levels of any pesticides or polychlorinated bi phenyls; the RR associated with the upper quartile of 1,1-dichloro-2, 2-bis(p-chlo rophenyl)ethylene concentration was 0.7 [95% confidence interval (95% CI), 0.5-1. 2] contrasting the lo wer quartile, and for35 the sum of polychlorinated bi phenyls the similar risk wa s 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 hi gher 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 organochl orine 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). "H exachlorobenzene is a tumor co-carcinogen and induces alterations in insulin-growth fa ctors 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 relate d signaling proteins of the insulin growth factor family are involved in t he 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-nitros o 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 re ceptor substrate-1 (IRS-1) levels and on IRS-1 phosphorylation; (3) microsomal and cytosolic Protein Tyrosine Kinase (PTK) activities in ma mmary glands and NMU-induced tumors. Sprague Dawley rats were injected with 50 mg/kg body we ight of NMU at 50, 80, and 110 days old. HCB (100 mg/kg body weight) was admin istered 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 tumo r development. Para meters 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 phosphor ylation 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 signa ling 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 tyrosi ne 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 hepatic36 immunodetectable c-Myc, c-Fo s, 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-My c, 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 inhibito r of ODC activity, suggests that it is not regulated by polyamines. These resu lts may be relevant to the early

molecular events involved in HCB tumo r promoter activity in rat liver.

Raynal, N. J., M. Charbonneau, et al. (2005). "Sexual Dimo rphism 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 microarra y analysis, ii) the mRNA and protein levels of the liver gap junction subuni ts, connexin 26 and connexin 32 (Cxs), which are considered to be tumor suppre ssive, and iii) gap junctional intercellular communication (GJIC). M odulation of gene expressi on is the hallmark of epigenetic carcinogens such as HCB. DN A methylation exerts mechanistic control of gene expression. This study aimed to assess the effects of HCB on DNA methylation as a mechanism respons ible for the reducti on 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 in duced DNA hypermethylation of HpaII restriction site. Local DNA methylati on on the Cx32 prom oter was measured using methylation specific- PCR (MSP) of bisulfite-treated DNA (N=4). Results showed a 2.5-fold increase (p < 0.05) in t he methylation of the Cx32 promoter in HCB-treated female rat livers compared to controls. Moreover, results showed a marked sexual dimorphism in DNA methylat ion, with males having lower levels (p < 0.05) compared to control females, which correlated with the gender-difference in Cx32 mRNA levels. Overall, data s uggest that by inducing aberrations in global methylation, and more specifically in local hy permethylation of the Cx32 promoter, HCB acts as a tu mor promoter by modifyi ng 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). "O rganochlorines and risk of prostate cancer." Journal of Occupational and Environmental Medicine 45 (7): 692-702. This pilot study examined the relations hips of organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCB s) 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 regr ession 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. Adju sting for age, body mass index, and a history of prostatitis, oxychlor dane 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 s upports further investigation in this

area.

Strucinski, P., J. K. Ludwicki, et al . (2002). "Hexachlorobenzene (HCB) and total polychlorinated biphenyls (3PCBS) in hum an breast lipids and breast cancer risk in Polish women." Organohalogen Compounds 59 (Dioxin 2002): 365-368. The results of the current study suppor t 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 br east 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 persi stent organochlorine pollutants might be assocd. with chemother apy in women with breast cancer. All

women had measurable levels of hexac hlorobenzene, ?-HCH, p,p'-DDT, p,p'- DDE (dominant analyte), and total polychlo rinated 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 sl ightly 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, how ever, could result from the differences in mean age of donors in both groups, wher ein 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 hepatoc arcinogenicity 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 expl ored the possibility of applying a38 toxicogenomics approach by using compr ehensive 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., ac etaminophen, aspirin, phenylbutazone, rifampicin, ?-naphthyl isothiocyanate, and amiodarone as neg., prediction anal. of microarray (PAM) was performed. By tr aining and 10-fold cross validation, a classifier contg. 112 probe sets that gave an overall success rate of 95% was obtained. The validity of t he present discriminator wa s checked for 30 chems.

The PAM score showed characteristic time-dependent increases by treatment with several nongenotoxic hepatocarcinogen s, 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 pr otective increase, but the protective response is exhausted dur ing repeated administra tion. 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 categor y of nongenotoxic hepatocarcinogens causing

oxidative stress.

Verner, M. A., M. Charbonneau, et al. (2008). "Physiologica lly based pharmacokinetic modeling of persistent organic po llutants for lifetime exposure assessment: a new tool in breast cancer epidemiologic studies." Environmental Health Perspectives 116 (7): 886-

92. BACKGROUND: Despite exper imental evidence, most epidemiologic studies to date have not supported an association bet ween exposure to persistent organic pollutants (POP) and breast cancer incidence in humans. This may be attributable to difficulties in estimating bl ood/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 susceptib ility in breast cancer development. METHODS: We developed a physiologically based pharmacokinetic (PBPK) model that can account for any given ph ysiologic lifetime history. Using data on pregnancies, height, weight, and age, the model estimates the values of physiologic parameters (e.g., organ vo lume, composition, and blood flow) throughout a woman's entire life. We asse ssed the lifetime toxi cokinetic profile(LTP) for various exposure scenarios and physiologic factors (i.e., breastfeeding, growth, pregnancy, lactati on, and weight changes). RESULTS: Simulations for three POPs [hexachlor obenzene, polychlorinated biphenyl (PCB)- 153, PCB-180] using different lifetime physiol ogic profiles showed that the same blood concentration at 55 years of age can be reached despite totally different LTP. Aside from exposure levels, lact ation periods and weig ht 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 ar ound the time of diagnosis for lifetime exposure assessment, will enable res earchers conducting environmental epidemiology studies to reduce uncer tainty linked to past POP exposure estimation and to consider exposure duri ng time windows that are hypothesized to be mechanistically critical in carcinogenesis.

Waliszewski, S. M., M. T. Bermudez, et al . (2005). "Persistent or ganochlorine 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 or ganochlorine 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 lipophi lity, their residues bioconc. in lipid-rich tissues, according to the equil. pattern of inter nal 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 subject ed to surgery due to the diagnosis of breast abnormalities. The study pool c onstituted 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 studi ed 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 incr eased 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 am ong them and correlation of these pesticide levels with breast tumors. Calcd. relative risk (RR) va lues for the benign to control group and the malignant to control cases pres ented 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 pesti cide residue levels in women with benign breast abnormalities and higher relative ri sk related to op'DDT presence.

Waliszewski, S. M., M. V. Meza Hernandez, et al. (2003) . "Persistent organochlorine pesticide levels in women with breast c ancer 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 sample s of abdominal adipose tissue from women subjected to hernia surgery we re taken. The organochlorine pesticide40 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 c ancer group only 1.4 ± 1.3. The HCB levels were 0.043 mgkg-1 in the control group and 0.036 mg kg-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 mg kg-1 in the control group and 1.098 mg/kg in the breast cancer women's gr oup. 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 contro l 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 mino r birth rate. The statistica l test applied indicated no correlation between the two groups and those tests showed a possible correlation of higher exposition to or ganochlorine 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 import ance 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 polychlorodibenzodi oxins (PCDDs), polychlorodibenzofurans (PCDFs), polychlorobiphenyls (PCBs), or ganochlorinated pesticides (p,p'-DDE, p,p'-DDT, hexachlorobenzene), and polyb romodiphenyl 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 ar ea, whose lagoon is partly under direct industrial impact, had a contaminant load gr eater than that from the Rome area, primarily urban. For mothers from the V enice area, the correlation between fish and fishery product consumption and contam inant concentrations in milk was also explored, with however inconclusive results. The concentrations of PCDDs, PCDFs, dioxin-like PCBs, and organochlor inated 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: t he declining trend of the

aforesaid contaminants in milk is conf irmed to be in agreement with what was observed in other European countries. T he breast milk content of (137)Cs and (40)K radionuclides was also determi ned 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 measur ed 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 rec ent European studies. Exposure patterns differed between females and males: higher HCB concentrations were found in females than in males (geometric m ean 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, c onsumption of milk and cheese, and occupation related to i ndustry. The finding that women had three-fold higher levels of HCB than t he men deserves further investigation.

Barr, D. B., P. Weihe, et al. (2003). "P CBs and organochlorine pesticide concentrations in a Faroe Island 14-year old cohort: measurement using new methodology and

evaluation of correlations and patterns." Organoha logen Compounds 63 : 385-388. Polychlorinated biphenyls (PCB) and organochlorine pesticide patterns and

intercorrelations were measured in seru m samples of children. An accelerated solvent extn. and gel permeation chroma tog. were followed by isotope diln. GC/high resoln. MS. The most highly ch lorinated PCBs, esp. pentachloro and higher, were intercorrelated, but s howed poor correlations with the lower

chlorinated PCBs. PCBs of lower chlo rination were intercorrelated with each other. The commonly measured PCB 153 and 180 were correlated with oxychlordane, trans-nonachl or, p,p'-DDE, and mirex. Hexachlorobenzene and ?- hexachlorocyclohexane showed correlations with all of the most prevalent PCBs. A concn. gradient in the more highl y 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 t han 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 org anochlorine pesticides, such as dichlorodiphenyltrichloroethane (DDT) and its metabolites, hexachlorobenzene (HCB), alpha, beta and gamma-hexachlor ocycloexane (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 93042 ng g(-1) lipid wt, respectively. There was no significant difference between the concentrations of investigated pollut ants between the two cities and their countryside. No significant differences in OCPs and PCBs were found between primiparous and multiparous mothers. T here was no correlation between levels

of OCPs and PCBs in human milk and the age of mothers. There was a significant difference in the organochl orine levels, incl uding DDTs, between

mothers who have eaten fish once a w eek and those who consumed fish more than once (p>0.05). An analysis of the in fant exposure to OCPs and PCBs via breast milk indicated that the daily inta ke 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 treat ment." 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 (C YP)-dependent arachidonic acid (AA) metabolism, hepatic PGE production, and cytosolic phospholipase A2 (cPLA2) activity were investigated in an exper imental model of porphyria cutanea tarda induced by HCB. Female Wistar rats we re 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 generat ed, 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 e ffects of HCB on AA metabolism were previous to the onset of a marked por phyria and might contribute to different aspects of HCB-induced liver toxicity such as alterations of membrane fluidity and membrane-bound protein function. Obse rvations 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 or tho-polychlorinated biphenyl congeners, dichlorodiphenyldichloroethyl ene, hexachlorobenzene, and Mirex among male Lake Ontario sportfish consumers: t he 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. Us ing data collected as part of the New York State Angler Cohort Study, 203 males were considered with regard to history of Lake Ontario sportfish cons umption and sera levels of 57 orthosubstituted polychlorinated biphenyl (PCB) congeners, dichlorodiphenyldichloroet hylene, 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 severa l procedures. Recovery and lipidadjusted serum values for PCB congenerIUPAC 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 consum ption (P<0.001). A logistic regression model, using forward stepwise selecti on procedures (alpha in/out=0.002/0.004), was employed to account for high intercorrelations among organochlorine predictor variables. Mirex was the sole statis tically significant predictor variable of

"consumer/nonconsumer." A one-unit increas e in log Mirex was associated with

a 92.0% increase in the odds of hav ing 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 pr emise that long-term dietary consumption of Lake Ontario sportfish, even at comparatively low levels, contributes significantly to the body burden of or ganochlorine compounds in western New York anglers and sportsmen.

Bradman, A. S., J. M. Schw artz, et al. (2007). "Facto rs predicting organochlorine pesticide levels in pregnant Latina women livi ng 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 - dichlorodi phenyltrichloroethane (DDT), lindane (99% pure gamma-hexachlorocyclohexane (gam ma-HCH)), hexachlorobenzene (HCB) - occurs on a limited basis. We measured pa ra, 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 agricult ural 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 signi ficantly 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 and44 birthplace in an area of Mexico with recent use of OC pesticides were significant predictors of exposure. Time spent livi ng 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 lo wer than for each year lived outside the

United States. There was no difference bet ween 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 cu rrent intake of saturated fat or agricultural take-home exposure risk factor s. Lactation history and recent weight gain were negatively associated with seru m 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 Stat es, the results for HCB indicate the possibility of ongoing exposu re 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 organochlor ine 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 I nuit, 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. Ma ternal 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, dieldr in and toxaphene. Maternal PCB levels (as Aroclor 1260) averaged 4.42 (+/-9.03) microg/l in I nuit, which was 3.3 times higher than those found in Dene/Metis, and 3.4 times hi gher than levels in Caucasians. Mean DDE levels were 2.8 times higher in the Other non-Aboriginal group (Chinese, Filipino, East Indian and multiple ethnici ty) than in the Inuit group, at 3.99 microg/l and 1.42 microg/l, respectively. Co rd 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 fo r maternal/cord pairs ar e presented for selected45 organochlorines. Other results from this study, including ma ternal and cord metals data, will be presented elsewhere.

Carrizo, D., J. O. Grimalt, et al. (2006). "Physical-chem ical 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 correla ted 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 childr en at four years. No significant correlations with length of gestation we re 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 concentrati on increments in blood that surpassed the growth dilution effects, with the onl y 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 a ccumulation 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 prefer ential 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 concentra tion of toxic pollutants." International journal of obesity and related metabolic di sorders : journal of the International Association for the Study of Obesity. 26 (11): 1465-8. BACKGROUND: Body weight loss occu rring after a hypoenergetic diet or a gastroplasty could be followed by an increase in blood concentration of potentially toxic pollutants that can inte rfere with the hormonal system (endocrine disrupters). DESIGN: Thirty obese indivi duals 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 i ndicate 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. Pl omteux (2002). "Determination of organochlorine pesticide residues in the blood of healthy individuals." Clinical chemistry and l aboratory medicine :

CCLM / FESCC. 40 (4): 361-4.

Pesticide use is one of several factor s that have permitted maintenance of our supply of food in spite of continuing in crease 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 pr oduction, residues or derivatives may persist in food and the entire population ma y be exposed to t he trace amounts of the material. The human body burden a ssociated with long-term exposure may or may not be associated with illness. Persistent environmental contaminants such as pesticide residues have long been su spected 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 answe r this question, clinical toxicology laboratories should propose validated met hodologies 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 populat ion (104 men, 147 women) . Only 17.9% of the samples were free from detectable am ounts of pesticides and p,p'-DDE 1,1- dichloro-2,2-bis(p-chlorophenyl)ethyl ene was the most frequently detected residue (66.5%). Hexachlorobenzene was f ound 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 env ironmental exposures to contaminants through food. In this study, the author s 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 ot her) (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 e ssential fatty acids (e.g., median docosahexaenoic acid levels [microgram/l ] in Asian-Canadian females = 5.48, males = 4.38; in Euro-Canadian female s = 2.93, males = 2.27). Plasma organochlorine contaminant lip id weight concentrations varied by country of origin and by gender (e.g., median total pol ychlorinated biphenyls [microgram/kg] in Asian-Canadian females = 490.6, male s = 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 fi sh consumption variables were less

consistent than for the af orementioned predictor s. Given both t he health benefits and potential risks of fish consumption, policies that address diverse ethnocultural groups should support cont inued consumption of sport fish, but

from less-contaminated sour ces than are currently used.

Covaci, A., C. Hura, et al. (2008). "Organoc hlorine contaminants in hair of adolescents from Iassy, Romani a." Chemosphere 72 (1): 16-20. Human hair samples (n=42) from Iassy c ounty (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 wa s considered, significantly higher concentrations for most of the investigat ed 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 Greec e, Western Europe and China. In case of PCBs, the levels found in Ro manian samples were found to be in the same range compared to other previously published data.

De Felip, E., A. di Domenico, et al . (2004). "Polychlorobi phenyls 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 endoc rine homeostasis, this resulting in toxic effects in particular in the developing organism. However, the

role of these chemicals in determini ng 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 follicul ar fluid of polychlorobiphenyls (PCBs), 2,3,7,8-chlorosubstituted polychlo rinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs), 1,1, 1-trichloro-2,2-bis(4-ch lorophenyl)-ethane (p,p'-DDT) and its metabolites, and hexachlorobenzene (HCB) was investigated. With respect to PCBs, the sum of the thr ee most abundant congeners (PCBs 138, 153 and 180) was 1230 ng/g, lipid basis (0.37 ng/g, wet weight). Congener distribution profile overl apped 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 bel ow their determination limits. 1,1- dichloro-2,2-bis(4-chlorophenyl)-ethene (p ,p'-DDE) and HCB were detected in48 concentrations respectively in the order of 700 and 70 ng/g, lipid basis (approximately 0.2 and approximat ely 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 under stand the current cont amination status of organochlorine compounds (OCs) in human breast milk from three metropolitan cities in India (New Delh i, 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 DDT s and HCHs generally declined with time, implying the effect of various bans and re strictions 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 s hows that some infants are exposed to OCs to a greater extent, particularl y HCHs than the guideline standard.

Dewailly, E., G. Mulvad, et al. (1999). "Concentration of organochlorines in human brain, liver, and adipose tissue autopsy samp les from Greenland." Environmental Health Perspectives 107 (10): 823-828. BIOSIS COPYRIGHT: BIOL ABS. Organoc hlorines 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 organoc hlorine determination in liver, brain, omental fat, and subcutaneous abdominal fat samples collected from deceased

Greenlanders between 1992 and 1994. Elev en chlorinated pesticides and 14 polychlorinated biphenyl congeners were m easured in tissue lipid extracts by high-resolution gas chromatography wit h electron capture detection. Mean concentrations of polychlorinated bi phenyls, 2,2'-bis(4-chlorophenyl)-1,1- dichloroethylene, beta-hexachlorocyclohe xane, hexachlorobenzene, mirex, transnonachlor, and oxychlordane in adipose ti ssue samples from Greenlanders were 3-34-fold higher than those measured us ing the same analytical method in samples from Canadians in Quebec City, Quebec. Brain lipids contained lower concentrations of all organochlorines t han 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 great er concentration in liver lipids than in lipids from both adipose tissues (4-fol d; p < 0.05). Compar isons with available international data on adipose tissue levels reveal that the organochlorine body burden in the Inuit populat ion of Greenland is pres ently among the highest resulting from environmental exposure.49 Eggesbo, M., H. Stigum, et al. (2009). "Lev els 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, caus es 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 m ilk 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 m ilk 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 smok ers: b=-282, CI - 467 to -98; for never smokers: b=0.5, CI -149 to 150, p-va lue for interaction: 0.01.

Similar results were observed for head ci rcumference, crow n-heel length, and

SGA. CONCLUSIONS: We saw a m oderate association between HCB and markers of impaired fetal growth among past and current smokers. This finding may be non-causal and due to underlying genet ic 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. (2 003). "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 t he non-ortho-substituted congeners) and chlorinated pesticides [dichlorodiphenyltrich loroethane (DDT) and daughter products, hexachlorobenzene (HCB), mirex, aldr in, heptachlor, trans-nonachlor, oxychlordane] were assessed in the Astrakhan region, Russia. There were correlations between consumpt ion 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. co rrelated with breast milk concns. of the same pollutants. Educati on 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 Ar alsk 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 Kazakhst an. Aralsk was formerly located at the50 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, Ge rmany (4.25 microg/l; Median values). Regarding Hg, differences between child ren of Aralsk and Akchi were not significant and concentrations were lowe r than reference values from Germany.

DDE contamination of children from Ar alsk (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-Ca manas, et al. (2009). "Permeability and toxicological profile estimation of organochl orine 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 scr eening tool providing key information about the oral absorption, skin permeab ility (K(p)), brain-blood distribution coefficient (BB) and ecotoxicological parameters such as median lethal concentration (LC(50)) and bioconcentra tion 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-brai n 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). "Dietaryintake of hexachlorobenzene in Catalonia, Spain." Sci Total Environ 322 (1-3): 63-70. To assess the dietary intake of hexac hlorobenzene (HCB) by the population of Catalonia, Spain, a total-diet study wa s 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 obtai ned 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 f oods 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 adults51 (0.0024) and seniors (0.0019). All these va lues are considerably lower than the WHO tolerable daily intake (TDI), wh ich 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). "E xposure 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, swor dfish, 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 weigh t, respectively, whereas

the lowest HCB levels were found in cuttl efish, 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 report ed 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 we ight 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 gr oups, HCB intake from fish and seafood consumption was considerably lower than th e WHO tolerable daily intake (TDI), for non-cancer effects and for neoplastic effects in humans.

Fernandez, M. F., B. Olmos, et al. (2002). "Organochlor ine determination in human placentas from different regions." Organohalogen Compounds 58 (Dioxin 2002): 301-

303. This work studies the intrauterine exposu re of the fetus to some organochlorine compds. selected for their estrogen-mimi cking character, through the anal. of placenta samples from women in hospita ls in Granada, Almeria, Turku, and Copenhagen.

Focant, J. F., A. Sjodin, et al. (2004). "Measurement of sele cted polybrominated diphenyl ethers, polybrominated and polych lorinated biphenyls, and organochlorine pesticides in human serum and milk usi ng comprehensive tw o-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 s pectrometry (GCxGC-IDTOFMS) for the

simultaneous measurement of select ed polychlorinated biphenyls (PCBs), organochlorine pesticides (OCPs), and bromi nated flame retardants is presented.

In contrast to the reference met hods based on classical GC/MS, a single injection of the extract cont aining all compounds of interest results in accurate identification and quantification. Using GCxGC ensures the chromatographic52 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 r equired specificity. The us e of this new method with an automated sample preparation proc edure developed at the Centers for

Disease Control and Preventi on (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/micr oL 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% fo r OCPs measured in human serum. OCP, PBDE, and PCB levels measured us ing the two methods were highly correlated, and the deviations between t he 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." Environm ental Toxicology and Pharmacology 12 (2): 75-

81. Quantification of exposure to environm ental contaminants such as endocrine active chemicals (EACs) during critical periods of development, particularly in utero, remains largely unexplored. Ther efore, we tested t he hypothesis that EACs can be detected and quantified in sec ond trimester human amniotic fluid.

Amniotic fluid was obtained from women (n = 175) undergoing routine amniocentesis between 14 and 21 weeks gest ation. 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 phytoes trogens, 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 evaluat e 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 biomoni toring 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 materi als 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 PC B-biomonitoring, the organochlorine-compounds (DDE, HCB, beta-/gamma -HCH, PCDD/PCDF) and the polybrominated biphenyl ethers concer ning the investigations within the project "Sentinel Health Departments" in Baden-Wurttember g are represented. Additionally results from children fr om Kazakhstan (Aral-Sea area) and from53 teachers which are working in PCB pollute d 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, PC B 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 co mparison with the results of Kazakhstan (Aral-Sea area). The difficulty to pr oduce time series while the analyzing pollutants are more and more decreas ing, 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 us e of pesticides, have led to concerns about high levels of contami nation in humans, but little information is available to

assess whether these concerns are warrant ed. Samples of breas t 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 Dnipr odzerzhinsk, but the magnit udes 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-adjust ed serum concentrations of certain PCB congeners and chlorinated pesticides /metabolites among 323 pregnant primiparous women from U ppsala County (age 18-41 years) sampled 1996-1999. METHODS: Extensive personal intervie ws and questionnaires about personal characteristics were performed both dur ing and after pregnancy. Concentrations of organochlorine compounds in serum lipids in late pregnancy were analysed by gas chromatography. Associations betw een 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-nonachl or and p, p'-DDE increased with increased age and were highest in women sa mpled 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 ex posure levels, probably mainly during

childhood and adolescence. T he importance of early ex posures 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 significant ly with number of months women had been breast-fed during infancy. Short-term changes in bodily constitution may, however, also influence serum concentra tions, 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 durin g childhood and adolesc ence influence the body

burdens of the com pounds during pregnancy.

Greizerstein, H. B., C. Stinson, et al. (1999). "Comparison of PCB congeners and pesticide levels between serum and milk from lactating wom en." 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 m ean of 0.65 | 0.49 show ing no consistency among individuals prior to adjusting t he data for lipid content. The total PCB levels normalized for lipid content we re 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 hexachlorobenz ene." 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-i ndividual variations over time of serum levels of 2,2',4,4',5,5'-hexachlorobi phenyl (CB-153), 1,1-dichloro-2,2-bis(4- chlorophenyl)-ethene (p,p'-DDE) and hexach lorobenzene (HCB), considering the impact of a number of possible determi nants. METHODS: Blood samples were55 drawn for the same 39 subjects in 1991 and 2001. Interviews were made at both occasions. Lipid adjusted serum concentra tions of CB-153, p,p'-DDE and HCB

were determined in both sets of blood samples using gas chromatography-mass spectrometry. The fatty acid compositi on of the serum lipids was analyzed by means of gas-liquid chromatography. R ESULT: The CB-153 concentrations in serum had averagely decreased with 34% in between 1991 and 2001 (p<0.001). Of individual determinants only increasi ng BMI was associated with decreasing CB-153 levels (beta=-1.0, 95% CI -1.8 , -0.2, p=0.01), expl aining 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 t he variation. The average decrease of HCB was 53%, and was associated only with high fish consum ption in 1991, explaining 12% of the

variation. CONCLUSIONS: The results s upport a continuing decrease in human body burdens of PCBs, DDE and HCB dur ing the 1990s. The explanatory factors relative change of BMI and fish consumpt ion explained only a minor part of the

time-related variations in serum levels.

Hanaoka, T., Y. Takahashi, et al. (2002). "Residuals of beta-hexachlorocyclohexane, dichlorodiphenyltrichloroet hane, and hexachlorobenzene in serum, and relations with consumption of dietary com ponents 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'- dichlorodiphe nyltrichloroethane (p,p'-DDT) in 41 volunteers (14 men and 27 women) in a rural area of Northern Japan. These organochlorine levels were meas ured using gas-chromatography massspectrometry. By a self-administered dietary history questionnaire, the usual dietary intake was estimated. Their medi an 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. Level s 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 resu lts. No other statis tically 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 hum an 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 com position, 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 t ools have been developed. Here, we link quantitative structure-activity relationshi ps (QSARs) for response concentrations in water (LC50) to critical concentra tions 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 su ch 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 ve rsus polar narcotics and organochlorine versus organophosphor insecticides. LC 50 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 com pared to an independent validation data

set. About 60% of the variabi lity in lethal body burdens C50 is explained by the model. Explanations for differences betw een estimated and measured levels for 11 modes of action are discussed. In particu lar, relationships between the critical concentrations in organisms C50 and chemic al (Kow) or species (lipid content) characteristics are specified and tested. The analysis combines different models proposed before and provides a substant ial 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 anthropoge nic 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-tim e-of-flight mass spectrometry (GC-TOF MS) for screening anthropogenic organic c ontaminants in human breast adipose tissues has been investigated. Initially a target screening was performed for a list of 125 compounds which included persist ent halogen pollutant s [organochlorine (OC) pesticides, polychlorinated biphe nylss (PCBs), polybrominated diphenyl ethers (PBDEs)], polyaromatic hydrocarbon s (PAHs), alkylphenols, and a notable number of pesticides from the differ ent fungicide, herbicide and insecticide families. Searching for target pollutant s 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 (HPL C) or SPE cleanup. The fat-free LC fractions were then investigated by GC-T OF 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 in itially based on library fit using commercial nominal mass libraries. This was followed by co mparing the experimental accurate

masses of the most relevant ions with the theoretical exact masses with calculations made using the elemental co mposition calculator included in the57 software.The application of both tar get and nontarget approaches to around 40 real samples allowed the detection and conf irmation of several target pollutants including p,p'-DDE, hexachlorobe nzene (HCB), and some polychlorinated biphenyls (PCBs) and polyaromatic hy drocarbons (PAHs). Several nontarget compounds that could be considered anthropogenic pollutants were also

detected. These included 3,5-di-tert-butyl-4-hydro xy-toluene (BHT) and its metabolite 3,5-di-tert-butyl-4-hydroxy benzaldehyde (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 x enoestrogens, 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 c aulking (sealant) material found in masonry buildings has been well-document ed in several countries. A recent investigation of 24 buildings in the great er 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. ME THODS: This project compared serum PCB levels among male workers who inst alled and/or removed PCB-containing caulking material from buildings in t he greater Boston area with reference serum

PCB levels from 358 men from the sa me 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 we re 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 (l ess chlorinated) PCB congeners (#16, 26,28,33,74,66, and 60) was markedly hi gher than in other 5 workers and reference men. Only this worker was wo rking 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 sma ll numbers (6 construction workers who handled PCB caulking), the serum PCB le vels among the construction workers

exceed the referents. Com parison of the congener prof iles suggests that there

are substantial differences between t he 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 PC B exposure for construction workers.

Hue, O., J. Marcotte, et al. (2007). "Pla sma 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 organochl orines compounds, may have greater58 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 Parkin son'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 indivi duals 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 mo rbidly 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 c oncentration and BMI. Organochlorine concentrations, however, were correlat ed with age (BMI-adjus ted R(2)=0.46; p<0.001). At steady state body weight, to xic pollutant concentrations are not associated to obesity but st rongly correlate with age.

Jandacek, R. J., N. Anderson, et al. (2005). "Effects of yo-yo di et, caloric restriction, and

olestra on tissue distribution of hexachlorob enzene." Am J Physiol Gastrointest Liver Physiol 288 (2): G292-9. Chlorinated hydrocarbons ar e lipophilic, toxic, and persis tent in the environment and animal tissues. They enter the body in food and are stored in adipose tissue. Loss of body fat through caloric restricti on mobilizes stored lipophilic xenobiotics

and results in distribution to other tiss ues. We have studied the reversibility of this process in mice that followed a regi men of body weight cycling. Weight gain was followed by weight loss, a sec ond gain, and a second loss ("yo-yo diet regimen"). We measured the di stribution of orally gavaged [14C]hexachlorobenzene, which is sparingl y metabolized. We found that weight cycling has different effects in different organs. Continued weight loss resulted in

a threefold increase of 14C amount and conc entration 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 in crease 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 t he liver, which reflected an increase of fat in the liver. The regimen of wei ght 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 abs orption results in direct transport to the liver, where metabolism may take place before extrahepatic delivery. Lymphatic absorption can result in de livery of parent compound to nonhepatic tissues. Understanding the fate of an i ngested 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 vesse l 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 intere st along with a portal absorption marker, 3-O-methylglucose. Since lymph was diverted, the appearance in portal blood was solely the result of portal absorpti on. Absorption was quantified by the areas under the curve for the compound and marker . Portal absorption was a function of the octanol/water partition coeffici ents for four organochl orine compounds: hexachlorobenzene, pentachlor ophenol, DDT, and its met abolite 1,1,1-trichloro2,2-bischlorophenylethylene.

Jandacek, R. J. and P. Tso (2007). "Enter ohepatic circulation of organochlorine compounds: a site for nutritional intervention." J Nutr Biochem 18 (3): 163-7. Organochlorine compounds enterthe body primarily as components of the diet. Their removal from the body is via excret ion into the feces. There is evidence that many people are in a positive balance, with t he rate of intake of organochlorines exceeding that of thei r excretion. A desirable nutritional approach to this problem would both reduce dietary intake and increase fecal

excretion. Nonabsorbable di etary 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 in crease in excretion can be achieved by interference with the enterohepatic circul ation of organochlor ine compounds and

their metabolites. Data from animals and humans show that the presence of nonabsorbed lipid in the intestine can increase the rate of excretio n 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 t hat are present in food are lipophilic and carried by chylomicrons. We have studied the clearance of an organochlorine, hexachlorobenzene, from chylomicrons. Ch ylomicrons were obtained frommesenteric lymph of rats that were intraduodenally given 14Chexachlorobenzene and 3H-triolein. The la beled chylomicrons were injected intravenously into recipient rats, and t he clearance of isotopes was followed.60 Surprisingly, the hexachlorobenzene disapp eared from the plasma more rapidly than the triolein. This unexpected resu lt raises questions about the manner in

which hexachlorobenzene is delivered to ti ssues. 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 di phenyl ethers in human umbilical cord serum, maternal serum and milk from Wiel kopolska 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), hexachlorocycl ohexane isomers (HCHs), chlordanes and their metabolites, and 18 polychlorinated biphenyl (PCB) congeners were measured in maternal serum, umbilica l cord serum and human milk collected from 22 mothers living in the Wielkopolska region, Poland. Additionally, 11 polybrominated diphenyl ether (PBDE) congeners were meas ured in the human milk samples. p,p'-DDT and its major me tabolite, 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 se rum and milk were 343, 329 and 634ng/g lipid weight (lw). PCB cong eners 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, re spectively. Except for CBs 74, 101 and 105, which had a detection frequency of 77% , 23% and 82%, respectively, all investigated PCB congeners were meas ured in all human milk samples. The

median concentrations of sum PCBs in ma ternal 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 medi an of sum PBDEs in human milk was 2.0 ng/g lw (range 0.8 to 8. 4), with BDE 47 being alwa ys the most abundant PBDE congener and, together with BDE 153, being present in all samples. In general, results found in the investigat ed group are at the low end of the concentration range m easured in Europe.

Kang, J. H., H. Park, et al. (2008). "Distri bution of organochlorine pe sticides (OCPs) and polychlorinated biphenyls (PCBs) in hum an serum from urban areas in Korea." Chemosphere 73 (10): 1625-31. Concentrations of organochlorine pes ticides (OCPs) and polychlorinated biphenyls (PCBs) were determined in seru m samples from residents of a Korean urban area (Seoul). This study was per formed on 40 Koreans in the general population, aged 27-58, who had resided in urban areas for more than 10 years without occupational exposur e to organochlorine pollut ants. To our knowledge, this study was the first report on seru m 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 addi tion, 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. The61 dominant PCBs were PCB153, 138, 180, 187, and PCB118, wh ich contributed

60% to total PCBs. The median concentra tions 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 organoc hlorine compounds except beta-HCH were positively correlated with age, and hi gher 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 cont rolling the concentration of PCBs in the environment. Extensive monitoring progr ams 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). "Per sistent 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 Mini stry of Health, Belgium was set up to assess pollutant concentrations and related health effect biomarkers in humans living in two regions of Fl anders. The study was called the 'Flemish Environment and Health Study' (FLEHS). One of the goals was to measure present concentrations of persistent organochlor ine pollutants in a Flemish population and to compare values obtained from pooled and individual serum samples. Concentrations of selected organochlorin e pesticides, polychlorinated biphenyls (PCB) and polychlorinated dibenzo-p-dioxins (PCDD) and furans (PCDF) were measured by gas chromatography-mass spec trometry. TEQ values were also assessed by Chemical-Activated LUciferase gene eXpression (CALUX) bioassay. The study population consis ted of 200 women between 50 and 65 years living in two areas of Flanders, Be lgium. Because of the large volumes serum needed for all measurements, the c oncentrations of organochlorines were measured in 47 pooled serum samples or iginating from these women. The

concentrations of the indicator PCBs (359.8 ng/g fat) and organochlorine pesticides (hexachlorobenzene, p,p'-dichl orodiphenyldichloroethylene, p,p'- dichlorodiphenyl-trichloroethane, lindane and pentachl orophenol), were comparable to those found in other Eur opean 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 le vels than a comparabl e age group from Germany examined in 1996. The mean to tal 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 fa t. 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 pooli ng 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 pow er loss and no possibility of confounder adjustment, pooling is not the most effect ive way to study regional differences.

Korrick, S. A., L. M. Al tshul, et al. (2000). "Measurement of PCBs, DDE, and

hexachlorobenzene in cord blood from inf ants 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), dich lorodiphenyl dichloroethene (pp'- DDE) and hexachlorobenzene (HCB)--in umbilical co rd blood. Cord blood provides the primary direct measure of prenatal ex posure to these contaminants, the key determinant of PCBs' neurodevelopmental toxi cities. The objective of this study was to characterize cord blood levels of PCBs, pp'-DDE, and HCB among 751

infants who were born betw een 1993 and 1998 to mothers residing adjacent to a

PCB- contaminated harbor in New Bedf ord, Massachusetts, and for whom the neurodevelopmental toxicities of these co mpounds are being studied. We refined standard analytic methods to optimize the s ensitivity and precis ion of trace-level PCB, p,p'-DDE, and HCB m easurements in blood. Using these methods, we

measured the concentrations of 51 indivi dual PCBs, their sum (sum(PCB)), p,p'- DDE, and HCB in cord serum. With corre ction for background contamination, the respective mean+/-SD cord serum conc entrations 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, in cluding groups at risk for high dietary PCB exposure. Of note, the contaminat ed 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 predomi nance of less-chlorinated congeners was generally consist ent with the characterist ics of the contaminated

site.

Kunisue, T., M. Muraoka, et al. (2006). "Contaminat ion status of persistent organochlorines in human breast milk from Japan: recent levels and temporal trend." Chemosphere 64 (9): 1601-8. Contamination levels of persist ent organochlorines (OCs) such as polychlorinated dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs), biphenyls (PCBs), dichlorodiphenyltrichloro ethane 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 higherthan the data obtained during 1998, indicating that the levels of these cont aminants in Japanese human

breast milk have not decreased sinc e 1998 and Japanese are continuously exposed to these chemicals, presumably via fish intake. In addition, OC levels in63 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 i ndicate that the mo thers 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 collect ed from Asian developing countries: Risk

assessment for infant s." Organohalogen Compounds 58 (Dioxin 2002): 285-288. The contamination level of polychlo rinated dibenzo-p-dioxin/dibenzofuran (PCDD/F), polychlorinated biphenyl, and organochlorine insecticides in human breast milk from dumping si tes 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 dum ping sites of municipal wastes and ref. sites have been exposed to these contaminants. T he 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 contam inants 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 refer ence values of polychlorinated biphenyls (PCBs) and hexachlorobenzene (HCB) in full-term neonates. PATIENTS AND METHODS: Cord blood samples were ta ken from 200 healthy, full-term neonates in 1998. Blood specimens were immediat ely centrifuged, and serum was stored in glass tubes at -20 degrees C up to analysis. Six PCB c ongeners (IUPAC No. 28, 52, 101, 138, 153, and 180) and HCB were determi ned with capillary gas chromatography with electron capture det ection. 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 evaluat ion because of unusually high PCB concentrations. Personal data of the remaining 199 newborns showed 106 male and 93 female neonates. Mean gestati onal 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 micr og/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 upt ake 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. Pol ychlorinated biphenyls (PCBs) and hexachlorobenzene (HCB) are ubiquitous carcinogenic and teratogenic compounds that are transplac entally transferred from mother to fetus during pregnancy. It was the aim of the present study to eval uate the possible influence of maternal age and duration of pregnan cy on the neonatal burden with these substances. Blood samples were tak en from 80 full-term German neonates within the first 12 h of life, before the fi rst oral feeding. The serum concentrations of s 0.96 mug/l, HCB concentration 0.61 mug/l. All det ectable 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 wit h maternal age (r = 0.249; p < 0.01), with 2.7-fold higher serum levels in offspr ing of 40-year-old as compared with 20- year-old women. It is conclud

Lackmann, G. M., J. Angerer, et al. (1999). "I nfluence 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 mater nal age and duration of pregnancy on the

neonatal burden with these substances. Bl ood 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 detec tion limit. PCB 153 showed the highest serum concentration (median 0.42 mi crog/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 signifi cantly with the gestational age of the newborns (r = 0.2639; p < 0. 01), with 50-140% higher se rum levels in children born at 42 weeks of gestation as compar ed 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 wit h these substances duri ng 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: pr eliminary 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 teratogeni c properties. They are chemically very stable and lipophilic and, therefore, a ccumulate in our food-chain. They are prenatally transmitted from mo ther 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 harmf ul 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 gla ss tubes at -20 degrees C until analysis. Three higher chlorinated PCB congener s (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-weig ht, age of the mothers, and smoking behaviour of the parents. In contrast, se rum 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 po llution 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 pol lution 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 persist ent 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 moni toring 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 in dividual samples of about 400 children per year. PCDD/PCDFs and so me relevant coplanar PCBs were determined in pooled samples from children in seven cycles from 1993 to 2003. Blood concentrations of the investigat ed compounds decreased in that time period by a factor of 2-4 with the except ion 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 a ssociated with about 30% higher median concentrations of DDE, HCB, PCBs and a 30% increase for mean PCDD/PCDF66 concentrations. Concerning demographi c 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 compar ed to girls for HCB, indicator PCBs and PCDD/PCDFs. The pattern of non-or tho and mono-ortho PC Bs 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 Hexa chlorobenzene Disposition By PCB126 Coexposure And Application Of PBPK M odeling 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 curtailm ent 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 fo ci bioassay. In both studies, fat had the highest concentra tions of HCB, followed by the other

tissues. The kinetics of tissue distributi on of HCB are dramat ically different between HCB alone group and the HCB+PCB 126 combination group, suggesting complex interaction mechanisms. Using PBPK modeling as a hypothesis-testing tool, we carried out computer simula tions 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 fa t, liver, erythrocytes, blood plasma, GI lumen, and rapidly and slowly pe rfused 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 PC B126. From our modeling exercises, we propos e 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 physiologic ally based pharmacokinetic model for hexachlorobenzene: incorporati on of pathophysiological states following partial hepatectomy and hexachlor obenzene 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 des cribe here an updated PBPK model for hexachlorobenzene (HCB) in male F344 rats with the incorporation of pathophysiological conditions. Two more feat ures contribute to the distinctness of this model from the earlier published ve rsions. This model took erythrocyte67 binding into account, and a particular e limination process of HCB, the plasma-togastrointestinal (GI) lumen passive diffu sion (i.e., exsorption), was incorporated. Our PBPK model was developed using data mined from multiple pharmacokinetic studies in the literatur e, and then modified to simulate HCB disposition under the conditions of our integrated pharmacokinetics/liver foci bioassay. This model included plasma, eryt hrocytes, liver, fat, rapidly and slowly perfused compartments, and GI lumen. To a ccount for the distinct characteristics of HCB absorption, the GI lumen was split into an upper and a lower part. HCB was eliminated through liver metabolis m and the exsorption process. The pathophysiological changes after partial hepat ectomy, such as alterations in the liver and body weights and fat volume, we re incorporated in our model. With adjustment of the transluminal diffu sion-related paramet ers, the model adequately described the data from the lit erature and our bioassay. Our PBPK model simulation suggests that HCB absorption and exsorption processes depend on exposure conditions; different ex posure conditions dictate different absorption and exsorption rates. This m odel forms a foundati on for our further exploration of the quantitative re lationship 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 C ontext Of Ito's Medium-Te rm Liver Foci Bioassay." Toxicologist 78 (1-S): 244-5. Hexachlorobenzene (HCB) is an important environmental contaminant. Due to its high lipophilicity and persistence in t he 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 tar get organs. We have incorporated the study of the re lationship between pharmacokinetics and pharmacodynamics into the Ito’s medium-t erm liver foci bioassay. Thus, we describe here the development of a PBPK m odel 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 (Scheufle r 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 fi ve 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 subc ompartments, one wit h a higher perfusion rate and lower partitioning and the other wit h a lower perfusion rate and higher partitioning. Uptake of HCB was diffu sion-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 inte stinal lumen. Reabsor ption of HCB from the intestine was incorporated in t he model. The resultant model adequately

described the available data sets. This model may be linked with a clonal growth model to quantitatively describe the relati onship 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 wast e 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 va riation 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 hexachlorobenz ene (HCB), polychlorinated biphenyls (PCB 28, 52, 101, 138, 153 and 180) and pol ychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) were analyzed in six composite plasma samples, while concentrations of di-, tri, and pentac hlorophenols, as well those of 1- hydroxypyrene were measured in the uri ne of these workers. The current mean PCDD/F concentration, 10.4 ng I-TEQ/kg lip id, 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 rec ently reported for various non-exposed populations. For the remaining analyzed subs tances in plasma and urine, there was not any significant increase in co mparison 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, laborator y and administration). The results of the present survey indicate that after 6 year s 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 work ers at a hazardous waste incinerator (HWI) in Catalonia, Spain, 8 years afte r regular operations in the facility. To compare these concentrations with t he baseline (1999) le vels and with those obtained in previous (2000 and 2005) surv eys. METHODS: The employees were divided into three groups according to t heir specific workplaces. Plasma analyses of hexachlorobenzene (HCB), polychlorinated biphenyls (PCBs 28, 52, 101, 138, 153 and 180) and polychlorinated dibenz o-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-trichl orophenol (TCP), pentachlorophenol (PCP) and 1- hydroxypyrene (1-HP) were carried ou t. 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 signifi cant increase for any of the compounds analyzed. In contrast, plasma levels of PCBs 28, 52 and 101 were significantly lower than the respective baseline conc entrations, 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 occupat ional 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 Cataloni a, Spain." J Food Prot 71 (10): 2148-52.

The concentrations of hexachlorobenzen e (HCB) were measured in samples of foodstuffs widely consumed by the populati on of Catalonia, Spain. Food samples were randomly acquired in 12 cities of Catalonia between March and June of 2006. HCB levels were determined by hi gh-resolution gas chromatography-highresolution mass spectrometry. The diet ary intake of HCB was subsequently estimated for the population of Cataloni a, 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, wit h mean levels of 0.481, 0.330, and 0.284 ng/g of fresh weig ht, 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 result s 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 we ight 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 noncancereffects 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 organi c contaminants in humans." Environmental Science and Technology 36 (15): 3318-25. A model of the absorption and desorp tion of persistent lipophilic organic pollutants in the human gastrointestinal trac t was formulated. The influence of the dietary intake of chemical, the chemic al concentration in human tissue, the physical-chemical properties of the c hemical, and the sorption properties of the feces on the predicted net mass transfer of chemical was explored and shown to be consistent with experimental observa tions. The model was parametrized and tested using a data set of approx imately 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 considerabl e individual and temporal variability in the sorption properti es of the feces. In a sample model application, good agreement was f ound between concentrations of70 octachlorodibenzo-p-dioxin in blood meas ured in different age groups of the background population and values predicted by the model.

Moser, G. A. and M. S. Mc Lachlan (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 partiti oning 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 fa ctor 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 di et and a vegetarian diet. The faeces/gas equilibrium partition coefficient K(FG) vari ed by over three orders of magnitude

between the different com pounds. A linear relationshi p between log K(FG) and log KOA, the octanol/air partition coe fficient, 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 vo lunteers who simply deleted fish and animal products from their normal di et, 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 lipid s that results in equilibr ation between the lumen

contents and the wall of the di gestive 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 wo men 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), polych lorinated biphenyls (PCBs), and hexachlorobenzene (HCB) are lipophilic com pounds that are ubiquitous in the environment and may cause adverse health effects in humans. METHODS: We examined the correlation between epidemio logical 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 fr om a case-control study on breast cancer risk. Usual diet, reproductive and m edical 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 capt ure 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 stronges t predictors for serum DDE levels were age, serum71 lipids, parity, and frui t and dairy consumption. Statisti cally significant predictors of PCB levels included age, serum lipids, par ity, and fish consumption. Serum HCB levels were related to age, serum lipid s, and fruit and red m eat consumption. CONCLUSIONS: Our findings are consistent with previous investigations that reported strong associati ons between organochlorine levels and age and serum lipids. The absence of other data showing an associat ion between fruit intake and organochlorine levels make the im portance of this finding unclear.

Nakai, K., T. Nakamura, et al. (2004). "Organochlorine pesticide residues in human breast milk and placenta in T ohoku, Japan." Organohalogen Compounds 66 (Dioxin 2004): 2537-2542. Several organochlorine pesticides were analyzed in human breast milk and placenta from 20 mothers to identify t he major pesticide compds. found in the cohort subjects. The concn. of organochlor ine pesticides in breast milk mainly depends on their accumulation in the mate rnal 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 ma ternal body burden. In addn., the concns. of some organochlorine pesticides such as hexachlorobenzene, oxy-chlordane, and trans-nonarchlor, in the placenta sa mples had significant neg. correlations with parity. This indicate s that the mothers elimi nate these pesticides during pregnancy and by breastfeeding them into t heir children. Considering that the concn. of pesticides in breast milk samples had no significant correlation with parity, monitoring of the placental pesti cide concn. may contribute to detg. the prenatal exposure of infants to organochlori ne pesticides. The contribution of fish consumption to the intake of pestici des was dependent on the kind of pesticide.

Nakashima, Y. and S. Ik egami (2000). "Hexachlorob enzene 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 envir onmental 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 concen tration ratio in fetuses was 3.4. In pregnant rats on the day before partu rition, the PECB concentrations in organs and fat tissue we re 3 to 4 times higher than those of HCB. After parturition, PECB rapidly disa ppeared 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 t he 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 dec reased gradually (T1/2 = 5.7 d) and PECB decreased rapidly (T1/2 = 2.8 d) during the 15 d afte r birth. These findings72 indicate that the PECB/HCB transferr ed to fetuses and suckling pups was the

same ratio found in the blood of their dams.

Nakashima, Y. and S. Ikegam i (2003). "High-fat diet enhances the accumulation of hexachlorobenzene (HCB) by pregnant rats dur ing 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 am ounts of HCB in the fat tissue and liver were greater in the high-fat diet gr oup than in the controls, no significant

differences in HCB concentration we re observed between the two groups. The high-fat diet group also showed more fe cal excretion of HCB . Therefore, HCB accumulation in rats fed a high-fat diet was enhanced more by continuous exposure to HCB than by adm inistration 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 disapp eared during lactat ion 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 wit h that in the control di et 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). "Or ganochlorine 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 organoc hlorines (OCs), such as DDTs, hexachlorocyclohexanes (HCHs), hexachl orobenzene (HCB), polychlorinated biphenyls (PCBs), and chlordane com pounds (CHLs) were determined in 34 human adipose tissues collected from Guiz hou Province, southern China, during 2002. DDT was the predominant c ontaminant 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 signi ficantly higher than those reported for developed countries. DDT levels in humans in Guizhou Province were73 comparable to those from Shanghai City, implying the presence of significant

sources of DDTs in in land and coastal areas in China. Age-dependent

accumulation of HCH concentration was f ound 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 s uggested 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). "Concentration s of environmental chemicals associated with neurodevelopmental effect s in U.S. populati on." Neurotoxicology 26 (4):

531-45. Humans are exposed to many environm ental 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 bi ological samples for many of these chemicals in a representative sampling of the U.S. population. Concen tration data of selected metals, persistent organic polluta nts, organophosphorus and carbamate insecticides, and cotinine are presented. For example, the 95th percentile

estimates for serum total PCBs (whole weight) in t he population aged 20 years and older is about 2.7 ng/g. The 95th percentile estimate s 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. populat ion. This reflects the effects of legislation, industry effort s, 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 le vels to be followed.

Noren, K., C. Weistrand, et al. (1999). "Distribut ion of PCB congeners, DDE, hexachlorobenzene, and methylsulfonyl met abolites of PCB and DDE among various fractions of human blood plasma." Archiv es of Environmental Contamination and Toxicology 37 (3): 408-414.

BIOSIS COPYRIGHT: BIOL ABS. The conc entrations of chlorinated biphenyls (CBs), 1,1-bis(4-chlorophenyl)-2,2-dic hloroethene (DDE), hexachlorobenzene (HCB), and the methylsulfonyl metabo lites of CBs (MeSO2-CBs) and DDE (MeSO2-DDE) were determined in human pl asma samples and in the fractions obtained by ultracentrifugation of plasma into very-low-density (VLDL), lowdensity (LDL), high-density (HDL) lipopr otein 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 wa s 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 the74 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 farm ers from Ghana." En vironmental Research

106 (1): 17-26. In the present study, the concentrati ons of persistent organochlorine (OC) pesticides such as dichlorodiphenyltri chloroethane and its metabolites (DDTs), hexachlorocyclohexane isomers (HCHs), hexachlorobenzene (HCB) and dieldrin in pooled samples of human breast milk(n=109), and seru m (n=115) from vegetable farmers in Ghana, dur ing 2005, were determined. Gas chromatography with mass spectrometry wa s used to quantify residue levels on a lipid basis of the OCs. The pattern of OCs in human flui d showed that DDTs was consistently the prevalent OC in m ilk and blood. The levels of DDTs, HCHs, and dieldrin in the breast milk samples we re 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 associati on between breast milk and serum residues. When daily intakes of DDTs and HCHs to infants through human breast milk were estimated, some indivi dual 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 um bilical cords from intra-pairs of twins at delivery." Reprod Toxicol 23 (3): 283-9. In this study, we examined the contam ination 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 s hows that the placental or fetal factor may influence the transfer or the accumulation of DDTs. The patterns of gene expressions of intra-pair of twin s 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. Moreov er, it showed the possibility that the pattern of gene expression in umbilical cord reflected the intra-uterine environment. However, the informati on from general pattern of the gene expression is limited. Theref ore, 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 timi ng." Archives of Disease in Childhood 91 (8): 642-

6. BACKGROUND: Exposure to organochl orine compounds (OCs) has been a subject of interest in recent years, giv en their potential neurotoxicity. Meconium is easily available and accumulates neurotox icants and/or metabolites from the 12th week of gestation. AIMS: To determi ne whether neurotoxicant s, specifically OCs, could be detected in serially collected meconium, and to compare the

results with those obtained in cord blood sa mples. METHODS: A sample of cord blood and three serial stool sample s were analysed in 10 newborns. Pentachlorobenzene (PeCB), hexachlo robenzene (HCB), polychlorinated biphenyls (PCBs), dichlorodiphenyl tric hloroethane (p,p'-DDT) and its metabolite dichlorodiphenyl dichloroethylene (p,p'-DDE), and hexachlorocyclohexane isomers (alpha-, beta-, gamma-, a nd delta-HCH) were analysed by gas chromatography. RESULTS: From seri al stool collection and analysis in newborns, there was an increase in the c oncentrations 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. Conc entrations 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 expos ure 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 in terpretation of neurotoxicants in meconium results is a complex process. Measurement in meconium of a wide range of neurotoxic substances should faci litate early identific ation of harmful exposures, and enable rehabilitation and in stigation of preventive measures.

Petrik, J., B. Drobna, et al. (2006). "Ser um PCBs and organochlorine pesticides in Slovakia: age, gender, and residence as determinants of organochlorine concentrations." Chemosphere 65 (3): 410-8. We measured organochlorine concentra tions of 15 polychlorinated biphenyl congeners and six organochlorin e 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 chromat ography with electron capture detection in 2002-2003. Elevated levels persist in subj ects from Michalovce district, site of former production facility, after almo st 20-years since the end of the PCB manufacturing. Sum of 15 PCB congener s 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. Relati vely 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. Cons istent differences between genders in both contaminated and backgro und areas are reported her e. Levels in males are about 20% higher in both districts. Levels of organochlor ine pesticides,76 particularly of DDT metabolite DDE and hexachlorobenzene are also elevated in the Michalovce district, reflecting intensiv e 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 re mains a source of relatively high environmental exposure for subjects in the Michalovce district.

Polder, A., G. W. Gabrielsen, et al. (2008). "Spatial and tem poral changes of chlorinated pesticides, PCBs, dioxins (PCDDs/PCDFs) and brominated flame retardants in human

breast milk from Norther n Russia." Science of the Total Environment 391 (1): 41-54. This study presents for the first ti me 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 Russi a in 2000-2002 (n=42), were compared to corresponding levels measured in 1993- 1996 (n=58). In addi tion brominated flame retardants (BFRs), consisting of polybrominated diphenylethers (PBDEs) (including BDE-209) and hexabromocycl ododecane (HBCD) were analysed in samples from 2000-2002 (n=37). The pr esent 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 mi crog/kg lw) and SigmaPCBs(16) (316 microg/kg lw) were highest in Murm ansk. The percentage of p,p'-DDT to SigmaDDTs and ratio DDE/DDT suggest possi ble ongoing use of DDT in Russia.

Levels of PBDE were low and domi nated by the congeners BDE-47 and BDE153. The deca brominated BDE-209 was detected in all analysed samples (median concentration 0.19 microg/k g 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). Fo r 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 duri ng the study period. The exposure of infants by PCDDs/PCDFs and dioxin-lik e PCBs is still exceeding the daily tolerable intake (TDI) in North West Ru ssia. However, the concentrations of

PCDDs/PCDFs and dioxin-like PCBs seem to decline very rapidly.

Polder, A., C. Thomsen, et al. (2008). "Levels and tempor al trends of chlorinated pesticides, polychlorinated biphenyls and br ominated flame retardants in individual human breast milk samples from Norther n and Southern Norway." Chemosphere 73 (1):

14-23. Human breast milk samples from prim ipara 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), polybromi nated diphenylethers (PBDEs) and hexabromocyclododecane (HBCD). CHBs, PBDEs and HBCD were only77 analysed in the Tromso samples. Su m-PCBs and sum-DDTs were the major organochlorines (OCs) (170 and 110 ng g(-1) lipid weight (lw), respectively).

Other OCs were found in le vels 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 wa s 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) PC Bs(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. No rstrom, 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 i ngested 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 unknow n. 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), dichlo rodiphenyltrichloroethane 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 b ears 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 cl asses. 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 ma le-specific metabolism of sigma-CHLORs. As fat depots became depleted, OC conc entrations in the remaining adipose tissue varied; sigma-DDTs and sigma-HCHs declined while those of sigmaCHLORs and sigma-PCBs generally increas ed. 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-CHLOR s (except males), sigma-ClBzs and sigma-PCBs remained constant for all cl asses of bears, ther efore there was no significant excretion or metabolism during the fast of the specific congeners in these compound classes typically f ound in polar bears. The ratio of plasma/adipose tissue and milk/adipose tissue OC concentrations was the same78 for before and after the fast indicating that OC concentrations in polar bears are probably at a steady state among various bo dy 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 increas ed in nursing cubs. Since developing young may be susceptible to the effects of environmental contaminants, the increased exposure of nursing cubs to OC s 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 conduc ted this study to evaluate blood levels of lead, mercury, and organochl orine 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 analyz ed each for lead, mercury, 14 polychlorinated biphenyl congen ers, 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 co rd 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), res pectively. We observed a statistically significant relationship between maternal age and cord blood concentrations of (a) lead, (b) mercury

Ribas, F., auml, et al. (2003). "Expos ure To Organochlorine Compounds Through Breastfeeding In A Population Exposed To Ai rborne Hexachlorobenz ene." Epidemiology

14 (5 Suppl): S40. Objective: Exposure to organochlori ne compounds occurs both in utero and through breastfeeding. Levels of hexachlor obenzene (HCB) in the cord serum of newborns from a population located in the vi cinity of an electrochemical factory in Spain are among the highest ev er 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, breas t milk and child's serum at 8 weeks of age. Results:Levels of organochlorine co mpounds 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 we re significantly correlated with the

concentrations in child's serum at 8 weeks of life. Those infants who were breastfed had higher concentrations of or ganochlorine 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 st atistically significant for all the

contaminants. Conclusions:Levels of HCB and p,p'DDE in colostrum in this population are among the hi ghest 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. Grim alt, et al. (2005). "Breastfeedi ng 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 hexachlorobenz ene (HCB) in the cord serum of newborns from a population located in the vi cinity of an electrochemical factory in Spain are among the highest ev er reported. We aimed to assess the degree of

breast milk contamination in this population and the subsequent exposure of children to these chemicals through breas tfeeding. 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 seru m at 13 months of age. Concentrations of OCs were detected and quantified in all colostrum and milk samples. The

concentrations in mature milk were lo wer 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 t he 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 concent rations in children's serum during the first year of life.

Ribas-Fito, N., M. Sala, et al. (2002). "A ssociation of hexachl orobenzene and other organochlorine compounds with anthropometri c measures at birth." Pediatr Res 52 (2):

163-7. The aim of the present study was to a ssess the association of prenatal exposure to hexachlorobenzene (HCB) and otherorganochlorine 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 organochlor ines measured in cord seru m, median levels of HCB were higher than for the other compounds (median of HCB = 1.13 ng/mL, median of dichlorodiphenyl dich loroethylene = 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 ve rsus 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 dichlorodipheny l dichloroethylene and polychlorinated biphenyls with length were not significant. The results did not vary when stratified for prematurity. These data suggest that HCB reduces in trauterine physical linear growth.

Ribas-Fito, N., J. Sunyer, et al. (2003). "[Changes in co ncentrations of organochloride compounds in women from Flix, Tarragona [Spain]]." Gac Sanit 17 (4): 309-11. The population of Flix (regi on of Ribera del Ebro, Tarra gona) is highly exposed to hexachlorobenzene (HCB) due to the closene ss of an electrochemical factory. Although the degree of HCB contaminati on 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 dichlorodipheny l dichloroethane (p,p'-DDE) and betahexachlorocyclohexane (beta-HCH) also decreased, although the difference was not statistically significant. In contra st, 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 contaminati on and infant intake." Ig iene 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 pollutant s in Greenlandic Inuit." Environmental Health Perspectives 116 (11): 1547-52. BACKGROUND: Persistent organic pollut ants (POPs) may influence epigenetic mechanisms; therefore, they could affect chromosomal stability and gene expression. DNA methylation, an epige netic mechanism, has been associated with cancer initiation and progression. Greenlandic Inuit have some of the highest reported POP levels worldwide. OB JECTIVE: Our aim in this study was to evaluate the relationship between plas ma POPs concentrations and global DNA methylation (percent 5-methylcytos ine) in DNA extracted from blood81 samples from 70 Greenlandic Inuit. Bl ood samples were collected under the Arctic Monitoring and Assessment Program and previously analyzed for a battery of POPs. METHODS: We used pyros equencing to estimate global DNA methylation via Alu and LINE-1 assays of bisulfite-treated DNA. We investigated correlations between plasma POP conc entrations and global DNA methylation

via correlation coefficients and linear r egression analyses. RESULTS: We found inverse correlations between percents methylcytosine and many of the POP concentrations measured. Linear regressi ons, adjusting for age and cigarette smoking, showed statistically significant in verse linear relationships mainly for the Alu assay for p,p'-DDT (1,1,1-trichlo ro-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 (bet a = -0.32), alphachlordane (beta = -0.75), mirex (beta = -0 .27), sum of polychlorinated biphenyls (beta = -0.56), and sum of all POPs (bet a = -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 envir onmental exposure to POPs and DNA methylation levels in a human populati on. Global methylation levels were inversely associated with blood plasma le vels for several POPs and merit further investigation.

Saghir, S. A., M. J. Bartels, et al. (2007). "Effect of org anic carbon content, clay type, and aging on the oral bioavailability of hex achlorobenzene in rats." Environ Toxicol

Chem 26 (11): 2420-9. Bioavailability of lipophilic chemicals is influenced by the physicochemical properties of soils/sediment such as par ticle size, pH, clay, and organic carbon content. The present study investigated t he effects of sediment composition and aging on the oral bioavailability of hex achlorobenzene (HCB) in rats. Formulated sediments were prepared using various ra tios of kaolinite and montmorillonite clay, sand, peat moss, and black car bon, 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 sign ificant (p = 0.049) reduction in the oral bioavailability of HCB from the sediment s compared to the corn oil standard and nonaged sediment indicating stronger interactions between HCB and sediment contents with aging. The mean reduction in or al bioavailability after one year of aging ranged from approximately 5 to 14% greater than t hat observed for nonaged sediments. The fecal elimination of the HCB-der ived 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 t he 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 ov erall toxicity evaluation of dioxins and hexachlorobenzene in human milk." Chemosphere 61 (9): 1215-20. A systematic method for analyzing di oxins (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. T he fractionation behavior of HCB on chromatography with silica gel, alumina, and activated carbon/silica gel, and the concentrated sulfuric acid decompositi on 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 ac tivated carbon/silica gel column. Moreover, HCB showed significant correla tion 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 semi quantitative food fre quency questionnaire was completed by participants. Nondiet ary determinants were investigated through a general questionnaire that addre ssed reproductive history, lifestyle, and social-demographic characteristics. Both women and their newborns had

detectable but low levels of OCs. T he 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 fa ctors. 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 relati onship (Pearson r=-0.25,P=0.052). Parity was the only nondietary factor that show ed 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, toget her explaining 28 % of the variance (P<001), in a multivariate model.83 Selden, A. I., Y. Floderus, et al. (1999). "P orphyrin status in aluminum foundry workers exposed to hexachlorobenzene and octach lorostyrene." Arch Environ Health 54 (4): 248-

53. The possible interference of hexac hlorobenzene and octachlorostyrene (i.e., thermal byproducts from hexachlor oethane 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 porphyri ns and porphyrin isomers. Workers exposed to hexachlorobenzene and octa chlorostyrene had a statistically significant increase in urinary total por phyrins, compared with controls (mean +/-

standard deviation: 13.63 +/- 11.13 micr omol/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 uroporphy rinogen decarboxylase activity was similar in both groups. There was a high correlation between levels of hexachlorobenzene and octachlorostyrene, respectively, in plas ma and urinary excretion of porphyrins; these findings, however, relied heavily on 1 subject for whom extreme values

were obtained. The results indicat ed that occupational exposure to hexachlorobenzene and octachlorostyr ene in aluminum degassing with hexachloroethane may affect porphyrin met abolism in a manner consistent with early secondary coproporphyrinuria-the firs t 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). "Comparis on hexachlorobenzene residues in placentas from Finland and Denmark (1997 -2001)." Organohalogen Compounds 66 (Dioxin 2004):

2791-2794. Statistical anal. of plac entas from Finland and Denm ark showed that their lipid contents have nearly normal distributi ons. The geometric means and the av. values are the same for the two cohorts, ho wever, 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, indica ting 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 ti mes of that in the Finnish cohort on both lipid base and wet wt. base. The differenc e 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). "C oncentrations of persistent organochlorine compounds in human milk and placenta are higher in Denmark than in Finland." Human Reproduction 23 (1): 201-10. BACKGROUND: A signific antly reduced male reproductive health status, including a higher prevalence of cr yptorchidism and hypospadias, has been documented in Danish men compar ed with Finnish men. Exposure to84 environmental pollutants with endocrine disr upting activities has been suggested as a possible contributing factor. In this study, we investigated whether there was a difference in milk and placental c oncentrations of persistent organohalogen compounds, between the two countries . METHODS: Organohalogens were analysed by high-resolution gas chro matography-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-cycl ohexane (beta-HCH), hex achlorobenzene (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 compar ed 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). "Pr enatal organochlorine pesticides in placentas from Finland: exposure of male in fants 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 bioaccumu lating toxicants using breast milk and placenta biomonitoring." Chemosphere 67 (9): S256-62. The exposure levels of placenta and pai red 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 cons tituents. Their concentrations are linearly correlated between milk and placent a in similar patterns for Danish and Finnish samples. Milk samples have hi gher levels of these pollutants than placenta on lipid base. However, the apparently not correlated compounds, such as alpha-HCH, pentachlor obenzene, pentachloroanisol e 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 se lected 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 vo lunteers were analyze d for presence of selected groups of chemical contaminants. The aim of this survey organized by85 WWF Poland (World Wildlife Fund) was highlighting the problem of man-made, persistent and bioaccumulative chemical s 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 contami nants: organochlorine compounds (pesticides and polychlor inated pesticides), phthalates and perfluorinated aliphatic substances. The total number of single chemicals found in the blood samples was 25, that repres ents 64% of the 39 chemicals looked for. The average number of compounds found in the samples was 21 (from 19 to 22). Among organochlorine co mpounds analyzed, the predom inant 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 sa mples the following congeners have been present: PCB-118, PCB-138, PCB-153, an d PCB-180 (concentrations ranging from 3,7 to 61 ng/g of fa t). The two predominant phtal ates 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 diiso butyl phthalate (DIBP) (concentration range from 10 to 63 ng/g of blood). Among fifteen perfluorinated aliphatic substances anal yzed, six have been present in each single sample (perfluorohex anesulfonic 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 anal ysis of potential impact of different factors on concentrations of particular contaminants in human blood. Results obtained in this survey confirm the ubiqu itous contamination by a cocktail of hazardous chemicals of every person tested. Humans being a part of the environment are being contaminated with t he same chemicals which are present in surrounding air, water, f ood, consumer articles, etc.

Sudaryanto, A., T. Kunisue, et al. (2005). "Specific accumu lation of organochlorines in human breast milk from Indonesia: Levels, dist ribution, accumulation kinetics and infant

health risk." Environmental Poll ution (Amsterdam, Netherlands) 139 (1): 107-117. This study detd. concns. of polychlori nated 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 hexachlorocyclohe xane 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 an d rural areas than urban localities, may be due to the differences in food habits and sources between the individuals

and locations. Data from Purwakarta si te 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 t han multiparas, suggesting th ese 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 accumu lation of organochlorines in human breast milk from Indonesia: levels, dist ribution, 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, wit h 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 locati ons. Data from Purwakarta site indicated continuing DDT exposure, whic h may confirm recent usage of DDT in Indonesia. A positive correlation was observed between concentration of OCs in human milk and age of mothers, primi paras women having higher OCs than multiparas, suggesting these parameters pl ay 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 mot hers living in Penang and Kedah, Malaysia." Archives of Environmental Contamination and Toxicology 49 (3): 429-37. This study determined the concentra tions 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 (CHL s), 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 di oxin equivalent concentra tions from 3.4 to 24 pgTEQs/g lipid wt. Levels of toxic equival ents (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 br east milk from Japan, impl ying that some of the87 residents in Malaysia may be exposed to spec ific pollution sources of dioxins and related compounds. No association was observed between OCs concentrations and maternal characteristics, which mi ght be related to a limited number of samples, narrow range of age of the donormothers, and/orother 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, suggesti ng 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 OC s 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 nor thern China." Environmental Research 99 (3):

285-93. Human milk specimens from 55 wo men in Shijiazhuang urban and Tangshan

rural areas in Hebei Province in nort hern China were collected and analyzed for persistent organic pollutants, such as p, p'-dichlorodiphenyldichloroethylene (p,p'- DDE), hexachlorobenzene (HCB), beta- hexachlorocyclohexa ne (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 primipar ous 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, respecti vely). In addition, we found the level of p,p'-DDE correlated positively with a di etary history of m eat consumption or consumption of internal organs of pigs and sheep (r=0.38 and r=0.52, respectively), but not with intake fr equencies 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 high er 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 milkand food is needed in China.

Thomas, G. O., M. Wilkinson, et al. (2006). "Organohalogen chemic als 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 18 3 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). C oncentration 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 lo wer concentrations of the more

chlorinated PCBs than males. Similar PBDE concentrations, and distributions, to those reported in the gener al population in Sweden in 2002 were found, despite differences in historical PBDE produc tion and usage. There is increasing88 regulation to control persistent and bioa ccumulative 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 pollu tants (POPs) leads to high levels in human milk and high doses of POPs for nur sing infants. This is currently not

considered in chemical risk assessment. A coupled model for bioaccumulation of organic chemicals in breas t-feeding mother and nursing infant was developed and tested for a series of organic com pounds. 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 ther eafter 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 Bu ryatia, Russia." Environ Pollut 146 (1): 225-32. Human breast milk samples collected during 2003/04 in Buryatia, a Russian autonomous republic, were analyzed in or der to assess human exposure to organohalogen compounds includ ing organochlorine pesticides, polychlorinated biphenyls (PCBs), and polybrominat ed diphenyl ethers (PBDEs). When compared with available worl dwide 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 exposur e to these organochlorines (OCs) in Buryatia. In contrast to OCs, PBDE conc entrations were low (0.46-1.7 ng/g lipid wt.). Out of 14 BDE congeners analyzed, BDE-28, BDE-47, BD E-100, BDE-153, BDE-197, and BDE-207 were de tected. 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). "Lev els of contamination for various pollutants present in Belgian human pl asma." Organohalogen Compounds 66 (Dioxin 2004): 2784-

2790.

The actual contamination's levels of various pollutants in human plasma from Belgium, including polychlorinated di benzodioxin/dibenzofurans (PCDD/Fs), polychlorinated biphenylsand organochlori ne pesticides (OCPs), as well as perfluorooctanesulfonate (PFOS) and re lated fluorochems. were assessed. Among the three fluorochems., PFOS wa s present at the highest concn.,89 followed by PFOA. Concerning dietary habi ts, PFOS concn. was significantly influenced by meat and milk consumption. On the contrary, PCB concns. were not significantly explained by any food c onsumption. 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 profile s 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). "Physiologica lly based pharmacokinetic modeling of persistent organic po llutants for lifetime exposure assessment: a new tool in breast cancer epidemiologic studies." Environmental Health Perspectives 116 (7): 886-

92. BACKGROUND: Despite exper imental evidence, most epidemiologic studies to date have not supported an association bet ween exposure to persistent organic pollutants (POP) and breast cancer incidence in humans. This may be attributable to difficulties in estimating bl ood/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 susceptib ility in breast cancer development. METHODS: We developed a physiologically based pharmacokinetic (PBPK) model that can account for any given ph ysiologic lifetime history. Using data on pregnancies, height, weight, and age, the model estimates the values of physiologic parameters (e.g., organ vo lume, composition, and blood flow) throughout a woman's entire life. We asse ssed the lifetime toxi cokinetic profile(LTP) for various exposure scenarios and physiologic factors (i.e., breastfeeding, growth, pregnancy, lactati on, and weight changes). RESULTS: Simulations for three POPs [hexachlor obenzene, polychlorinated biphenyl (PCB)- 153, PCB-180] using different lifetime physi ologic profiles s howed that the same blood concentration at 55 years of age can be reached despite totally different LTP. Aside from exposure levels, lact ation periods and weig ht 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 ar ound the time of diagnosis for lifetime exposure assessment, will enable res earchers conducting environmental epidemiology studies to reduce uncer tainty linked to past POP exposure estimation and to consider exposure duri ng time windows that are hypothesized to be mechanistically critical in carcinogenesis.

Verreault, J., R. J. Letcher, et al. (2009). " Dietary, age and trans-gen erational effects on the fate of organohalogen c ontaminants in captive sl edge 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 knowledge90 deficiencies in the life history of t he sampled animals. The present study investigated the influence of age, diet ary and trans-generational factors on the fate of major lipophilic chlorinated and brominated OHCs in adipose tissue of a potential surrogate captive s pecies for the polar bear (Ursus maritimus), the sledge dog (Canis familiaris) in West Gr eenland. Adult female sledge dogs (P) and their sexually-mature (F1) and/or pr e-weaning pups (F1-MLK) were divided into an exposed group (EXP) fed bl ubber from a Greenland minke whale (Balaenoptera acutorostrata) and a c ontrol group (CON) given commercially available pork fat. Large dietary treat ment-related differences in summed and individual congener/compound adipose tissue concentrations of polybrominated diphenyl ethers (PBDEs), hexachlorobenz ene (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 exist ed in PBDE, HCB, CHL and PCB concentrations, suggesting hi gher state of equili brium in adipose tissue concentrations from a very early st age of life. In contra st, the distribution pattern (proportions to the summed c oncentrations) 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 populati on." 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 Veracr uz, Mexico." Bulletin of Environmental Contamination and Toxicology 62 (4): 397-402. Biosis copyright: biol abs. rrm research article human patient pollution toxicology organochlorine pesticide resi dues environmental contami nant blood serum toxin clinical chemistry pesticides lindane pes ticide pp'ddt aldrin heptachlor op'ddt pp'dde pp'ddd alpha beta-endosulfan eps ilon-ddt veracruz mexico

Waliszewski, S. M., A. A. Aguirre, et al. (1999). "Comparison of or ganochlorine 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). "Comparis on of organochlorine pesticide levels between abdominal and br east adipose tissue." Bulletin of Environmental Contamination and Toxicology 71 (1): 156-62.91 Whitcomb, B. W., E. F. Sc histerman, et al. (2005). "R elative 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 fo cusing on organochlorine exposure and human health effects has relied upon serum fo r quantifying exposure despite adipose tissue being the purported "gold std.". The accuracy of exposure status is dependent upon serum being a valid and re liable proxy for adipose tissue regardless of compd. under study and serv ed as the impetus for study. Serum and omentum fat concns. for 62 polychlo rinated biphenyls (PCBs) and 7 organochlorine pesticides (OCPs) were det d. 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 ob sd. 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 co mpds. or when study samples include individuals with relatively low exposure s. These data support earlier findings and argue for concerted methodol. work ai med 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 pregnan t women from Germany." Journal of toxicology and env ironmental health. Part A. 71 (11-12): 703-9. Blood samples from 226 pregnant wo men aged between 19 and 41 yr, living in an industrialized area of Germany (Duisbur g birth cohort study), were collected between September 2000 and November 2002 and analyzed for their content of persistent organic pollutants (POPs). Level s 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-bas ed 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'- dichlorodiphenyltrichloroet hane (DDT), and 0.1-9.1 micr og/L (median: 0.54) 4,4'- dichlorodiphenyldichloroethene (DDE). Parameters influencing the POP levels in human blood were examined using multip le regression models. Levels and the levels scatter widths of most PCDD/F and PCB congeners and HCB increased significantly with age. Within the mu ltiple 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 lactation92 period for earlier born children decreased most POP blood levels, except for alpha- and gamma-HCH. Over the study per iod 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 We stern 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 studi ed in harp seals from eastern Canada. Possible effects on hepatic cytochr ome 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 pol ar compounds (lower chlorinated PCBs, toxaphenes, hexachlorocyclohexanes, and hexachlorobenzene) relative to more lipophilic compounds (higher chlorinated PCBs, dichlorodiphenyltrichloroethane [DDT], chlordane). In spite of substantia l contaminant mobilization from blubber in females and ingestion of contaminated mi lk 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 ac tivities were low, resulting in low

contaminant metabolism. This was confir med by similar contaminant patterns in milk and pups. A strong positive relation between CYP1A-like activities and body weight in the pups suggested not ye t 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 C YP450. The CYP450 enzyme activities were considered uns uitable indicators for contaminant mobilization and transfer in harp seals.

Yu, H. F., X. D. Zhao, et al. (2006). "Continuous su rveillance 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 a ccumulative levels and dynamic changes of organochlorine pesticides in human milk in Beijing from 1982 to 1998, and the effect of prohibition and restriction on t he 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 m ilk 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 concentration93 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 organochl orine pesticides 1983, the average

concentration of beta-BHC and total BHC fe ll 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). "B iomonitoring of polychlorinated biphenyls and organochlorine pesticides in human milk from mothers liv ing 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 hu man 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. chem s. 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 ques tionnaire. In total, 4314 samples were collected in the years 1999-2006 and analyzed for their content of these persistent org. pollutants (POPs). A cleardownward trend of median total PCB, DDT, ?-HCH and HCB values in all partici pants 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/k g 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 mo thers whereas an increasing no. of breastfed infants per mother led to a decrease. T he proportions of other

measured substances exceedi ng limits of quantific ation were as follows: dieldrin 68.6%, ?-HCH 1.3%, ?-HCH 60.1%, heptac hlor epoxide 41.5%, musk xylene 15.6%, musk ambrette 0.4%. We concl ude 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). "A ge at natural menopause and exposure to organochlorine pesticides in Hispanic wo men." J Toxicol Environ Health A 67 (18): 1407-

22. A cross-sectional study was conducted to evaluate the relationship between exposure to selected organochlorine pes ticides (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. In formation on age at menopause, reproductive history, demographic variabl es, 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 pesti cides below the detec tion limit. Women with serum p,p'-DDE leve ls greater than 23.6 ppb (h ighest quintile) had an adjusted mean age at menopause 1.7 yr ear lier than women with serump,p'-DDE levels less than 5.5 ppb (lowest quintile). However, no consistent dose-response effect was apparent across low, m edium, 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 wit h 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 ac tivity 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 transfe rase (UDPGT) in a time-dependent manner, without changes in T3 UDPGT. We propose that increased T4 to T395 conversion in the thyroid and in the gr eatly enlarged liver may account for the

maintenance of serum T3 concentration in hypothyroxinemic HCB-treated rats.

Alvarez, L., A. Randi, et al. (1999). "Eff ect of hexachlorobenzene on NADPH-generating lipogenic enzymes and L- glycerol-3-phos phate dehydrogenase in brown adipose

tissue." J Endocrinol Invest 22 (6): 436-45.

The effect of the in vivo administr ation 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 li pogenic 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, showi ng that the effect does not depend on the presence of thyroid hormones. These re sults 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 ti me 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 stimul atory effect of receptor-saturating doses of triiodothyr onine (T3) (50 microg/100 g body weight)

was observed on BAT ME and LG3PD acti vities in thyroidectomized rats, showing that the enzymes responded to th yroid hormone stimulation in a normal manner. The stimulatory effect of satu rating doses of T3 on ME and LG3PD was reduced by HCB. The results presented her ein 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 OC s in preschool children. METHODS: Children from a general population birth c ohort 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 dichlorodi phenyl trichloroeth ane (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 associat ed with PCB-118, while no relationship

was found between TSH and an y of the measured OCs. CONCLUSIONS: This study suggests that even at background leve ls of exposure, OC s may affect the thyroid system, particularly total T3 levels.96 Andrews, J. E. a. C., K. D. (1986). "Hexachlorobenzene-i nduced 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 gen etic instability, resulting from exposure to environmental toxicants, may increase an individual’s risk of developing breast cancer. It is important, therefore, to dete rmine the extent to which exposure to environmental pollu tants results in increased genetic instability. We have addressed this iss ue by examining both the levels of pollutants in breast milk, and DNA damage in breast-milk cells. Breast milk samples collected from twenty-one wom en living in the Springfield, MA and Albany, NY areas, were analyzed for levels of 101 polychlorinated biphenyl (PCB) congeners and 8 organochlor ine pesticides/metabolites (Hexachlorobenzene, oxychlordane, pp’ -DDE, op’-DDE, - Chlodane, transNonachlor, Mirex, and cis-Nonachlor). Ce lls in the milk were separated by centrifugation within one hour of milk collection, and DNA damage was assessed using the single cell gel electrophores is 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. Mot her’s age ranged from 21 to 40 years, and child’s age ranged from 3.5 to 67 weeks. PCBs and pes ticides were detected in all 21 milk samples. Among women who had not previ ously nursed a child (n = 15), there were significant positive correlations bet ween age of the wom an and 1) total PCB level, 2) Hexachlorobe nzene level, and 3) pp’-DDE level. None of these correlations were significant in women w ho had previously nursed a child (n = 6). All samples contained cells with detec table 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 Ce ll 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 ear lier clonal growth modeling studies on a series of chlorobenzenes, the probable exis tence of two cell types in glutathioneS-trasferase (GSTP) foci became apparen t. As suggested by other researchers, these two cell types are either susceptible or resistant to mitoi nhibitory 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 GS TP foci form, isolation of GSTP positive (GSTP+) cells from liver ac ross time allows capturing changing97 characteristics of an emerging malignant population. This study describes an attempt to isolate primary GSTP+ hepatocyt es using Ito’s bioassay protocol with diethylnitrosamine (DEN) as an initia ting agent and a 2/3 partial hepatectomy with concomitant dosing of hexachl orobenzene (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 si gnificant increase in liver weight was observed in rats coexposed to HCB and PC B 126. Either prim ary hepatocytes or liver sections were taken to analyze forma tion of GSTP+ foci . By treating cell suspension and/or culture with ethacrynic acid (EA) (Stenius et al., Carcinogenesis 15:1561-1566, 1994), GS TP+ hepatocytes were enriched by inducing toxicity to non-GSTP+ cells. In so doing, progressively more malignant cell populations can be subjected to ce ll cycle kinetic studies, genomic analyses, and clonal growth modeling to aid our in sight 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 lipophili c contaminants found in breast tissue

with a debated role in breast cancer development (BCD). HCB, a widespread organochlorine in the environment, is virtual ly present in 100% of North American women. Epidemiological studi es indicated that some br east cancer patients have higher HCB levels. We observed that long term exposure of human mammary epithelial cells to HCB increases the phos phorylation of c-er bB2 (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 epigenet ic 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 pa ssages of continuous exposure to HCB, an increase in proliferation was obs erved. These cells showed an increase in the phosphorylation of t he integrin-linked kinase (I LK), with a decrease in Akt/PKB levels. ECadherin, an important cell adhesion molecule, was also

decreased. Control cells sub-cultur ed on Matrigel® showed a distinctive branching pattern after 24h. However, HCB-exposed cells exhibited a rounded shape with minimal cellular contacts. Th is is suggestive of a decrease in

intercellular communication and cell adhes ion ; the latter is supported by the decrease in E-Cadherin expression in thes e cells. Moreover, a fter 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 co mmunication 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 contro ls E-cadherin expression. This work brings biological plausibility to the invo lvement of environmental contaminants in

BCD.98 Billi de Catabbi, S. C., C. P. Setton-Advr uj, et al. (2000). "Hex achlorobenzene-induced alterations on neutral and acidic sphingomye linases and serine pa lmitoyltransferase activities. A time course study in two strains of rats." Toxicology 149 (2-3): 89-100. Hexachlorobenzene (HCB) induces porphy ria both in humans and rodents, and hepatocarcinoma in rodents. In a previous work we observed that HCB produces a continuous decrease in hepatic sphingom yelin (SM) content in Wistar rats. A distinguishing characteristic of sp hingolipids breakdown products is their participation in anti-prolif erative and apoptotic proce sses and in the suppression of oncogenesis. As a first step to eluci date the role of SM decrease in the hepatotoxicity induced by HCB, the pres ent study evaluates the metabolic causes of the continuous decrease in hepat ic 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 diffe ring 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 allow ed a 2-day recovery period without HCB administration. Two phases in t he HCB-induced damages to sphingolipid

metabolism were observed. The first st age (7 days of trea tment), 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 Wist ar rats, hepatic SM levels decreased continuously throughout the experimen t, accompanied by increases in SPT, acidic sphingomyelinase (A-SMase) and neutral sphingomyelinase (N-SMase) activities (86, 28.5 and 78% increase, res pectively). 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) demonstrat es 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-i nduced alterations of SM metabolism do not correlate with HCB-induced accumulation of hepatic porphyrins; and (c) proposes a link between HCB-induced altera tions in phospholipid pattern and in SM metabolism. The increased SM hy drolysis produced as a consequence of SMases induction could be regarded as a cellu lar response to liver injury elicited by HCB, perhaps acting through the activati on of SM signal transduction pathway delaying the proliferative processes obser ved 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 co rd 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 organochl orines 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 cytok ine 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 (re ference group). Cord blood samples were collected for organochlorine and mercury analyses and also to isolate cord blood mononuclear cells (CBMCs) for t he in vitro assessment of cytokine production and expression of surface ma rkers 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-c hlorophenyl)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 cytoki nes 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 correlati on between tumor necrosis factor-alpha (TNF-alpha) secretion and plasma PCB, p,p'-DDE, and HCB concentrations (p < 0.05). Our data support a negat ive association between TNF-alpha secretion by CBMCs and prenatal organochlorine expo sure. If the relationship between organochlorine and TNF-alpha secr etion is causal, it would suggest a role for this important proinflammatory cytokine in mediating organochlorine-induced immunotoxicity in infants developm entally exposed to these compounds.

Bishop, J. B. (2002). Molecular Detecti on 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 d eath, 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 numer ical chromosome damage in sperm and early embryonic cells of rodents. T hese rodent sperm-FISH assays, which provide parallel models of similar sperm-FISH assays in humans, are being used for evaluating the aneugenic and clast ogenic 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 spe rm were obtained from NTP Reproductive Assessment by Continuous Breeding (R ACB) studies on hexachlorobenzene and100 tetrachloroazobenzeneare, and frozen samp les of mouse sperm were obtained from an RACB study of AZT/ddI and from micronucleus studies of benzene, diazoaminobenzene, anal ine and cyclophosphamide.

Blinova, V. G., D. A. Dobryn in, et al. (2003). "Prediction of chronic toxicity indexes of substituted benzenes using the John Stuart M ill (JSM) method for automatic generation of hypotheses." Nauchno-Tekhnicheskaya In formatsiya, 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 re sponsible for high, moderate and low toxicity to substituted benzene derivs. we re identified without chronic exptl.

studies on the lab. animals.

Bloksma, N. (2004). "Effect s 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). "E xploring 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 functi on in a sample of 66 sportsmen selected from among participant s 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 hy potheses. Blood samples were analyzed for compounds based on a priori identified lit erature-cited evidence of thyroid disruption. These incl uded hexachlorobenzene and polychlorinated biphenyl congeners 19, 28, 47, 118, 153, 169, 180, 183, and 187. Time of sample collection, serum triglycerides, choleste rol, 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 pot ential 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" model s, alpha=0.15) using the cr iterion of maximum partial correlation at each step. Several procedures were considered to address

contaminant data below the limit of det ection in the reduced models with no change in selected predictors. Hexa chlorobenzene (beta=-0.113) and age (beta=0.007) were selected as predictor s 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 statistica lly significant with a type I error of 0.05 and a power of 0.80. These fi ndings 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 Ce ll-Cell Interactions By Epigenetic Hepatocarci nogens." Toxicol Sci 84 (1-S): 336-7. Mechanisms of epigenetic carcinogenesis involve disruption of cell or tissue homeostasis, such as cell-cell intera ctions mediated by various types of junctions. Gap junctions are formed by c hannels that allow direct communication between cells (GJIC), while adher ing junctions maintain tissue integrity by linking cells together. Gap and adhering junctions are physically and functionally

interrelated membrane structures. Connexi ns and cadherins are key proteins in gap and adhering junctions, respectively. Wh ile 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 hexachl orobenzene (HCB), an important environmental contaminant, t hat 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 pat hway 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 vitr o studies, using specific inhibitors and overexpression systems confir med not only the role of ILK pathway in cell-cell interactions, but also t he functional interrelationships between connexins and cadherins. Down-regulati on of proteins forming gap and adhering junctions allow initiated cells to e scape control from neighboring cells, thus promoting their clonal ex pansion. The importance of such mechanisms in carcinogenesis is illustrated by the fact that human tumors of various origins

show low levels of immunoreactive c onnexins and cadherins. Moreover, studies suggest that lost of cell-cell interact ion proteins is an early event in the carcinogenesis process. Overall, dat a support the cont ention 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). "A bnormal kinetic behavior of uroporphyrinogen decarboxylase obtained fr om rats with hexachlorobenzene-induced porphyria." J

Biochem Mol Toxicol 19 (1): 19-24. Uroporphyrinogen decarboxylase is an esse ntial enzyme in all organisms and functions in the heme biosyn thetic pathway, catalyzing the decarboxylation of the four acetate groups of uroporphyrinogen to form coproporphyrinogen. This work examines whether the four sequential decar boxylations occur at the same active site, and explores whether hexachl orobenzene-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 const ant velocity was obtained with all the mixtures, indicating that uropor phyrinogen and pentacarboxy-porphyrinogen react at the same active site, i.e. the fi rst and fourth decarboxyl ations occur at the same site. In contrast, in exper iments with enzyme from rats with hexachlorobenzene-induced porphyria, the to tal 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 differ ent sites, but with cross-inhibition. This suggests that t he 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 uroporphyri nogen 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 pur ified liver enzyme of both normal and hexachlorobenzene porphyric rat. The st udy 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 r each the Vmax at any of the substrate concentrations assay ed (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, particula rly Cu2+ and Pb2+, and against thermal inactivation. Zn2+ did not affect enzymat ic 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 enzymat ic activity in the range of concentrations assayed. beta-Mercaptoethanol had dive rse effects, as regards both the concentration assayed and the enzymatic sample used. Assays with cystine

showed a dual behaviour of both norma l and porphyric enzymatic activity. Western blots for both preparations rev ealed a single band (65 kDa) with a similar intensity.This study show that hexachlorobenzene treatment modifies the physicochemical properties of liver Ur oD leading to a sharp decrease of its activity, without affecting its antigenic reactivity probably as a consequence of changes at the conformational level pr omoted by the bindi ng of its reported

inhibitor.

Chipman, J. K. (2004). "B iomarkers For Nongenotoxic Ca rcinogens." Toxicologist 78 (1- S): 318. Nongenotoxic carcinogens are thought to act via disturbance of the balance between cell death and cell pro liferation, leading to clonal expansion of preneoplastic cells. The precise mechanisms t hat 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 proliferat ive advantage are important in recognising103 this activity in rodent studies. This may be helpful in the interpretation of rodent carcinogenicity that may occur in the abs ence of genotoxicity, and to be able to extrapolate to human risk assessment. T he dose response relationships and species differences in response are cr itical 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 junc tion intercellular communication and the status of DNA methylation have s hown particular promise as relevant biomarkers in conjunction with functional studies as above. For example, the rodent non-genotoxic hepat ocarcinogens Wy-14, 643, 2, 3, 7, 8- tetrachlorodibenzo- p-dioxin, methapyr ilene and hexachlorobenzene and the rat kidney carcinogens chloroform and p-dich lorobenzene all disrupt gap junction plaques containing connexin 32 in the ta rget 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. Transcr iptomic analyses are leading to the

identification of furt her novel potential biomarkers associated with species- and tissue- specific nongenotoxic carcinogenesis such as the induction of hepatic fibrinogen / angiopoietin-related prot ein by monoethylhexylphthalate.

Cochon, A. C., N. Gonzalez, et al. (2002) . "Effects of the porphyrinogenic compounds hexachlorobenzene and 3,5- di ethoxycarbonyl-1,4-dihydr ocollidine 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 st udy was to extend the investigations on the effects of porphyrinogen ic compounds on polyamine metabolism. This was achieved by studying putrescine, spermidine and spermine levels in a model of acute porphyria, i.e. 3,5- diethoxycar bonyl-1,4-dihydrocollidine (DDC)-induced porphyria, and in a model of non-acute porphyria, i.e. hexachlorobenzene (HCB)- induced porphyria. HCB administration to fe male Wistar rats fo r 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 cont rast to HCB, DDC treat ment 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 orni thine 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 pat hway. 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 c ontributing to alter the cytoskeleton.104 Cochon, A. C., L. C. San Martin de Vial e, et al. (1999). "Effe cts 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 env ironmental pollutants, induces uroporphyria and phospholipid altera tions in rat liver. Harderian glands produce a secretion that is rich in lipids and accumulate large amounts of protoporphyrin. The aim of the pr esent study was to determine if

hexachlorobenzene administration to ra ts 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 (W istar 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 s phingomyelin/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 c ontent 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 ar e strain-dependent and porphyria-independent." Comp Biochem Physiol C Toxicol Pharmacol 130 (2): 199-207. Hexachlorobenzene (HCB) alters phospho lipid 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 phos pholipid composition in order to investigate if there is any relati onship between HCB-induced porphyrin metabolism disruption and phospholipid al terations. For this purpose, a timecourse study of HCB effects on brain phos pholipids was performed in two strains of rats differing in their susceptibilit y to acquire hepatic porphyria: Chbb THOM (low); and Wistar (high). This paper show s for the first time that rat brain phospholipids are affected by HCB exposu re. Comparative studies show that HCB-induced disturbances in brain phospho lipid patterns are time and straindependent. Thus, whereas major phos pholipids, phosphat idylcholine and phosphatidylethanolamine were more altered in Wistar rats, minor phospholipids, phosphatidylinositol and phosphatidylseri ne were more affe cted in Chbb THOM rats. HCB intoxication led to a sphi ngomyelin/phosphatidylcholine molar ratio lower than the normal, in both strains. As was expected, brain porphyrin content was not altered by HCB intoxication in ei ther strain. It can be concluded that HCB is able to alter brain phospholipid metabo lism in a strain-dependent fashion, and

in the absence of alterations in brain heme metabolism. In addition, HCB-induced105 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 ch lorinated pesticides in adult Native Americans." Environ Health Perspect 115 (10): 1442-7. BACKGROUND: Recent research sugges ts that diabetes, a condition whose incidence is increasing, is associated with exposure to polych lorinated biphenyls (PCBs) and chlorinated pesticides. OBJECT IVES: We investigated the potential association between diabetes and serum levels of PCBs, dichlorodiphenyldichloroet hylene (DDE), hexachlorob enzene (HCB), and mirex in a cross-sectional study of an adult Na tive-American (Mohawk) population. METHODS: Through a standardized questio nnaire 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 gluc ose, triglycerides, and cholesterol. Participants who had fasting-glucose val ues > 125 mg/dL and/or who were taking

antidiabetic medication were defined as persons with diabetes. We conducted logistic regression to assess the potent ial 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 categoriz ed in tertiles, and the lowest tertile was used as the reference category. R ESULTS: The prevalence of diabetes was 20.2%. The odds ratio (OR) of having di abetes for participants in the highest tertile of total PCB concentration compar ed 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 a fter controlling for potential confounders, whereas a negative association was observed for mirex.

Cote, S., P. Ayotte, et al. (2006). "Plasma organochlor ine concentrations and bone

ultrasound measurements: a cr oss-sectional study in peri-and postmenopausal Inuit

women from Greenland." Envi ronmental health : a global access science source [electronic resource]. 5 : 33. BACKGROUND: Inuit women are highly exposed through their traditional

seafood based diet to or ganochlorine compounds, some of them displaying endocrine disrupting properties. We hypothes ized 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 paramet ers (QUS) at the right ca lcaneum of 153 peri- and postmenopausal Inuit women (49-64 year old) from Nuuk, Greenland, and106 investigated the relation between thes e parameters and plasma organochlorine concentrations. We used high-resoluti on 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 validat ed questionnaire to document dietary and lifestyle habits as well as reproducti ve and medical histories. RESULTS: Concentrations of PCB 153, a surrogate of exposure to most organochlorines present in plasma samples, were inve rsely correlated to QUS parameters in univariate analyses (p < 0.001). Howeve r, PCB 153 concentrations were not
associated with QUS values in multivar iate analyses that comprised potential confounding factors such as age, body we ight, 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 organochlori nes exposure is related to osteoporosis in Greenlandic Inuit women, but the hypot hesis that exposure to dioxin-like compounds might be linked to decr eased 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: po ssible 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 det ermine 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 w hether porphyria parameters ca n be useful as biomarkers of HCB persistence in rats. Hepatic ur oporphyrinogen decarboxylase activity, its inhibitor formation, porphyrin content and co mposition 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 c ourse of urinary porphyrin excretion was studied for 7 weeks either by continuous treatment fo r 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 t han that observed in animals analysed immediately

at the end of each treatment. Rats treat ed with HCB for 1 week showed a modest decrease in uroporphyrinogen decarboxylas e and low inhibitor formation, and exhibited a greater enzyme inhibition, inhibitor formation, hepatic porphyrin accumulation, and an altered pattern of por phyrin composition in the absence of the exogenous drug. Independen t of the treatment, urinar y 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 wit hdrawal 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 in107 heme biosynthesis can be considered effe ctive markers of HCB persistence in

rats or of irreversible HCB-induced dam age. Taking into account the delayed and enhanced metabolic effects of HCB, it is advisable that porphyria parameters should be evaluated not only immediately a fter exposure, but also some time afterwards, especially in susceptible and occupationally-e xposed populations.

De Coster, S., G. Koppen, et al. (2008). "P ollutant effects on genot oxic 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 incine ration, a high density of traffic and housing or intensive use of pesticides, c ould contribute to the high incidence of

cancer observed in Flanders. METHOD S: Subjects were 1583 residents aged

50-65 from 9 areas with diffe rent types of pollution. Cadmium, lead, p,p'-DDE, hexachlorobenzene, PCBs and dioxin-like activi ty (Calux test) were measured in blood, and cadmium, t,t'-muconic acid and 1-hydroxypyrene in urine. Effect biomarkers were prostate specific antigen, carcinoembr yonic antigen and p53 protein serum levels, number of mi cronuclei per 1000 binucleated peripheral blood cells, DNA damage (comet assay) in peripheral blood cells and 8-hydroxydeoxyguanosine in urine. Confounding fa ctors were taken into account. RESULTS: Overall significant diffe rences between areas were found for carcinoembryonic antigen, micronucle i, 8-hydroxy-deoxyguanosine and DNA damage. Compared to a rural area with mainly fruit production, effect biomarkers were often significantly elevated around wa ste 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 we re almost three times higher close to industrial installations than 5 kilometres up wind of the main industrial installations (p < 0.0001). Positive exposure-effect relati onships 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-hydr oxypyrene). 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 abov e the p90 and higher serum values of carcinoembryonic antigen. Significant a ssociations 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 biomarke rs 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. Fe rnstrom, 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 hypotheti cal 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 th e organochlorine pesticides 1,1- dichloro-2,2- bis(p-chlorophenyl)ethylene (DDE) and hexachlorobenzene (HCB) in cultured human lympho cytes." Chemosphere 71 (7): 1335-9. The possible genotoxic potential of 1,1-di chloro-2,2-bis(p-chlorophenyl)ethylene (DDE), which is a metabolite of dich lorobiphenyltrichloroetane (DDT), and hexachlorobenzene (HCB), which are or ganochlorine pesticides have been evaluated in vitro by using human lym phocytes as test system. Genetic damage was determined by scoring the frequency of micronuclei (MN) in primary lymphocyte cultures obtained from differ ent 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 concentrati on 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-Ca manas, et al. (2009). "Permeability and toxicological profile estimation of organochl orine 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 scr eening tool providing key information about the oral absorption, skin permeab ility (K(p)), brain-blood distribution coefficient (BB) and ecotoxicological parameters such as median lethal concentration (LC(50)) and bioconcentra tion 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-brai n 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 persi stent environmental pollutant with (auto)immune effects in humans and rats. The Brown Norway (BN) rat is very susceptible to HCB-induced immunopatho logy, 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 fo r 21 days. CsA treatment started 2 days prior to HCB exposure and rats we re 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 an d lung still occurred but infiltrations of eosinophilic granulocytes into the lung we re prevented. Restimulation of spleen cells with the T-cell mitogen ConA and the macrophage activator LPS clearly

showed that CsA inhibited T-cell acti vation, 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 e ffects." 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 immunopatho logy 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 fo r all adverse effects induced by HCB. Macrophages are probably also import ant and the relationship between macrophages and T cells was further inve stigated. To eliminate macrophages clodronate-liposomes were used. Furthermo re, a kinetic study was performed to obtain insight in the early phase of the HCB-induced immune response. Also, experiments were performed to detect s pecific memory T cells. Therefore, an adoptive transfer study was performed. Ou r results indicate that macrophages

are indeed involved in HCB-induced skin lesi ons, lung eosinophilia, and elevation of IgM against ssDNA. Kinetics showed t hat both skin and lung lesions appeared early after exposure. Moreover, i mmune effects could not be adaptively transferred. Thus, both macrophages and T cells are involved in HCB-induced immune effects but HCB exposure does not l ead to specific T cell sensitization. Presumably, HCB exposure induces ma crophage activation, thereby generating adjuvant signals that polyclonally stimulat e 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 To xicity." 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 syst em, 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 infl ammatory 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 le vels 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 t he 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 i nduction 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 evidenc e that HCB induced a systemic inflammatory response, accompanied by oxidative stress and an acute phase response. In conclusion, this study conf irms 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 advers e effects are hepatic porphyria, neurotoxicity, and adverse effects on t he reproductive and immune system. To obtain more insight into HCB-induced me chanisms 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 RG U-34A GeneChip microarray. Most significant (p < 0.001) changes, compar ed 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 thym us 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 in111 drug metabolism, porphyria, and the repr oductive system. In line with previous histopathological findings we re increased transcript levels of markers for granulocytes and macrophages. New findings include the upregulation of genes encoding proinflammatory cytokines, antio xidants, acute phas e proteins, mast cell markers, complements, chemok ines, and cell adhesion molecules. Generally, gene expression data provide ev idence that HCB induces a systemic inflammatory response, accompanied by oxidative stress and an acute phase response. In conclusion, this st udy confirms previously observed (immuno)toxicological effects of HC B but also reveals several new and mechanistically relevant gene products. T hus, transcriptome profiles can be used as markers for several of the proce sses that occur after HCB exposure.

Ezendam, J., I. Vissers, et al. (2 003). "Immunomodulatory effects of tetrachlorobenzoquinone, a reactive met abolite of hexachlorobenzene." Chem Res

Toxicol 16 (6): 688-94. Hexachlorobenzene (HCB) is an envir onmental 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 ar e stimulated after oral exposure to HCB.

HCB as a rather inert chemical is not lik ely to bind covalently to macromolecules. The oxidative metabolite of HCB, tetrac hlorobenzoquinone (TCBQ), which is in a redox equilibrium with tetrachloroh ydroquinone (TCHQ), can bind to macromolecules, hence may form hapten-carrier complexes in vivo. We have assessed in the reporter antigen-poplit eal 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 e ffects by activating macrophages. Seven days later, cell number and TNP specif ic 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 ELISPO T. Both oxidative metabolites were able to induce the formation of germinal centers as assessed by immunohistochemistry and an IgG1 respons e 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 com pound specific memory response.

Ezendam, J., J. G. Vos, et al. (2005). "Research articles mechanisms of

hexachlorobenzene-induced adverse immune e ffects in brown norway rats." J

Immunotoxicol 1 (3): 167-75. Hexachlorobenzene (HCB) is an environmen tal 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 inflammatory112 skin and lung lesions, enlarged spleen and lymph nodes (LN) and elevated humoral responses. This review descri bes recent experiments that were performed to elucidate the mechani sms underlying these adverse immune

effects. The metabolites tetrachlor ohydroquinone and tetr achlorobenzoquinone are capable of generating neoantigen-specif ic T-cells in the mouse reporter antigen popliteal lymph node assay with 2,4,6-trinitr ophenyl-Ficoll. Additional experiments in BN rats have shown that T-cells are involved in the development of HCB-induced skin lesions, the incr ease 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 cyt okines 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 anti bodies are less pronounced after macrophage eliminati on. 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, synthet ic, and environmental chemicals for binding to the androgen receptor." Chemical Research in Toxicology

16 (10): 1338-58.

A number of environmental and industr ial chemicals are reported to possess androgenic or antiandrogenic activities. These androgenic endocrine disrupting chemicals may disrupt the endocrine syst em 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 bi nding 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 environm ental chemicals that encompass a broad range of structural classes, includi ng steroids, diethylstilbestrol and related chemicals, antiestrogens, flutamide derivatives, bisphenol A derivatives, alkylphenols, parabens, alkyloxyphenols, pht halates, siloxanes, phytoestrogens, DDTs, PCBs, pesticides, organophosphate in secticides, and other chemicals.

Some of these chemicals are environm entally persistent and/or commercially important, but their AR bind ing affinities have not been previously reported. To the best of our knowledge, t hese results represent the largest and most diverse data set publicly available for chemical binding to the AR. Through a careful structure-activity relationship (SAR) exam ination of the data set in conjunction with knowledge of the recently reported lig and-AR crystal stru ctures, we are able to define the general structural require ments for chemical binding to AR. Hydrophobic interactions are important fo r AR binding. The interaction between113 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 prev iously reported results for estrogen receptor binding.

Fernandez-Tome, M. C., S. C. Billi de Cata bbi, et al. (2000). "Heme metabolism and lipid peroxidation in rat kidney hex achlorobenzene- induced porphyria: A compartmentalized study of biochemical pat hogenic mechanisms." Kidney Blood Press

Res 23 (1): 20-6. In the present study, the effect s of hexachlorobenzene (HCB) on lipid peroxidation and heme metabolism in the di fferent constitutive suborgans of the kidney were determined. For th is purpose, conjugated diene and malondialdehyde levels, as lipid per oxidation parameters, and porphyrin accumulation, uroporphyrinogen decarboxyla se activity, and its inhibitor formation, as measures of heme metabo lism, were determined in renal cortex, medulla, and papilla. Adult Wistar rats were treated with HCB duri ng 1, 2, 3, or 4 weeks. A significant increase in cortic al conjugated dienes was observed from

the 1st week of treatment. The malondial dehyde 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 wee ks 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, respecti vely. The results demonstrate a direct

correlation between the oxidat ive 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 Intera cts With Postnatal Genistein To Induce Changes In Reproductive Development Of Fe male Sprague Dawley Rats." Toxicologist

78 (1-S): 220. Estimates of safe exposure levels ar e based primarily on the results of animal studies employing single test chemical s, 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 ac tive 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 da ily intake (TDI) as determined by the US-EPA on gestations days 9-16. The mi xture used contained organochlorines (TCDD, PCBs, methoxychlor, DDT, DDE, dieldrin, endosulfan, hexachlorobenzene, hexachlorocyclohe xane, mirex and heptachlor) and the metals lead and cadmium. Following de livery half the pups of each treatment group were injected subcutaneously with 10 ug genistein/g BW/day on postnatal114 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 wei ghts or reproductive endocrine outcome

measures. Treatment with t he mixture had no effect on sexual maturation in

either sex whereas the mi xture/genistein combination induced a significant delay in vaginal opening but had no effect on preputial separation. These data suggest that developmental exposure to environm ental toxicants representative of contemporary human tissue residues is unlik ely to induce additive or synergistic effects on the reproductive tract. Ho wever, our data suggest that exposure complex mixtures of toxicants can inte ract 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 ingesti on of hexachlorobenzene (HCB), a fungicide added to wheat seedlings. Thes e 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 childr en 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 durati on of 2.2 years. Many patients had dermatologic, neurologic, and orthopedic symptoms and signs. The observed clinical findings include sca rring 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%), cogwhee ling (41.9%), enlarged thyr oid (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 el evated. 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-expos ed patients compared to 0.07 ppm in unexposed controls. Offspring of mot hers 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 increasi ng 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. Usi ng mice expressing the low affinity form of the AH receptor (AHRd), we in vestigated whether the enhancement of uroporphyria by HCB involves an obligator y increase in CYP1A2 as measured by specific enzyme assays and immunoblotting . We compared the ability of HCB, in

combination with iron dextr an and the porphyrin precur sor, 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 a ffinity AHRd. In C57BL/6 mice, HCBenhanced uroporphyria was associated with a doubling of CYP1A2. HCB treatment produced uroporphyri a 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 accumu lated in 129 Hfe(-/-) mice. In conclusion, some minimal basal expre ssion 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 prom oting 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-transfe rase 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 diethylnitrosami ne (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 herbi cide 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 centrilo bular hypertrophy, DEN-initiated HCBfed animals showed severe liver centr ilobular hypertrophy and significant GSTP+ foci development. These findings i ndicate that the medium-term assay adopted in this study does not reveal anyliver 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 a ssure that the activity measured originates from xenobiotic compounds onl y. Serum samples representing high, medium and lower accumulation of persi stent organic pollutants (POPs) were extracted using solid-phase extracti on (SPE) followed by normal-phase highperformance liquid chromatography (NP-HP LC) 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 ce lls, stably transfected with an estrogen receptor (ER) luciferase reporter vector (estrogen response element chemically activated luciferase expression, ERE-CALU X), were exposed to the reconstituted

SPE-HPLC extracts for dete rmination 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-HP LC extracts from serum spiked with

the PCBs. Similar effects on ER transacti vation were observed for the direct in

vitro and the ex vivo anal ysis experiments. The ER transactivation responses determined for actual serum samples were in the linear range of the doseresponse curve. 17beta-Estradiol titrat ions showed that the xenoestrogenic

effects were mediated via ER. Mor eover, our SPE-HPLC-ERE-CALUX assay was demonstrated to elicit high interlabor atory correlation. In the present study the combination of SPE-HPLC purificati on 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/antagonist ic 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 wit h the reduction of fasting insu lin levels in men but not in

women." Metabolism: clinical and experimen tal.|Metabolism 51 (4): 482-6. Environmental pollutants can act as endoc rine modulators. In this study, we examined whether weight loss-induced changes in plasma organochlorine compounds (OC) were associated with thos e 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 bip henyl (PCB) mixture (Aroclor 1260), 1 PCB congener (PCB 153), and 3 pesticides (2,2'-bis(4- chlorophenyl)-1,1-dichloroethylene (p ,p'-DDE), beta-hexa chlorocyclohexane (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 treat ment, 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 le vels, the greater the reduction in fasting insulin was in response to weight loss in men (-.49 < r < -.59, P <.05), but not in117 women (-.22 < r <.01, not significant [N S]). 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 significant ly correlated after correction for fat mass loss (-.46 < partial r < -.51, P val ues ranging from.05 to.07). These results suggest that weight loss-induc ed increase in plasma pollutant levels tends to be independently associated with t he reduction of fasting insu lin 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 t heir effect." Toxicology and Applied Pharmacology 197 (3): 236-237.

Jarrell, J., A. Gocmen, et al . (1998). "Evaluation of repr oductive outcomes in women inadvertently exposed to hexachlorobenzene in southeastern Turkey in the 1950s " Reprod Toxicol

12 (4): 469-76

in southeastern Turkey during the per iod of 1955-57, women were accidentally exposed to the fungicide hexachlorobenzen e (HCB) after eating contaminated seed grain and developed porphy ria 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 undertak en to evaluate the effects of HCB on women with a known high dose exposure. A retrospective controlled cohort comparison study of three groups was c onducted. 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 approx imately 40 years (n=42/group). Blood samples were taken for analysis of seru m HCB, estradiol, follicle-stimulating hormone (FSH) and inhibin. Frequency of HCB detection was greatest in Group 3, while number of cases with HCB val ues exceeding 1 ng/mL was significantly greater in Groups 1 and 2. There were no differences in the other biochemical measures. Interviews were completed fo r each patient regarding reproductive history (number of pregnancies, live bi rths, spontaneous abortions, still births and sex of live babies). Multiple comparisons of the three groups, based on Fisher's test found the groups were inhom ogeneous. When serum HCB was analyzed using correlated response logistic regr ession, there was a strong relationship between serum HCB levels and risk for spon taneous abortion but not sex ratio of children. The following findings were m ade. HCB is detectable and ubiquitous in serum samples from women in the c ountry of Turkey with identified and unidentified exposure event s. Spontaneous abortion risk is not restricted to women with identifiable exposure to HCB but to a surrogate ma rker of exposure118 (serum HCB sample). The risk of s pontaneous abortion with HCB exposure requires further investigation.

Kirkland, D., M. Aardema, et al. (2005). "Evaluation of the ab ility 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, G enetic Toxicology and Environmental Mutagenesis 588 (1): 70. On the title page, the URL of the webs ite 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 ab ility 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 lymphom a assay (MLA)+in vitro micronucleus (MN) or chromosomal aberrations (CA) test --has been evaluated for its ability to discriminate rodent carcinogens and non-ca rcinogens, 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 categoris e the performance of these assays using the response categories we established. T he sensitivity of the three-test battery was high. Of the 553 carcinogens for which there were valid genotoxicity data, 93% of the rodent carcinoge ns evaluated in at least one assay gave positive

results in at least one of the three test s. Combinations of two and three test systems had greater sensitivit y than individual tests resu lting in sensitivities of around 90% or more, depending on test combination. Only 19 carcinogens (out of 206 tested in all three tests, consi dering CA and MN as alternatives) gave consistently negative results in a full th ree-test battery. Mo st were either carcinogenic via a non-genotoxic mechanism (liver enzyme inducers, peroxisome proliferators, hormonal carcinogens) c onsidered not necessarily relevant for humans, or were extremely weak (pre sumed) genotoxic carcinogens (e.g. Nnitrosodiphenylamine). Two carcinogens (5-chloro-o-toluidine, 1,1,2,2- tetrachloroethane) may have a genotoxic el ement to their carcinogenicity and may have been expected to produce positiv e results somewhere in the battery.

We identified 183 chemicals t hat were non-carcinogenic a fter testing in both male and female rats and mice. There were genot oxicity 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-carc inogens 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 mechani sm by which genotoxicity may be induced (whether it is relevant for t he whole animal or human) and using weight119 of evidence approaches to assess t he carcinogenic risk from a positive genotoxicity signal. It also highlights deficie ncies in the current prediction from and understanding of such in vitro results fo r 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 devel opment 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 t he in vitro MN test, particularly in combination with other assays, because the published database for this assay is relatively small at this time. The specific ity values for the in vitro MN assay may improve if data from a la rger proportion of the know n non-carcinogens becomes available, and a larger published database of results with the MN assay is urgently needed if this test is to be appr eciated for regulatory use. However, specificity levels of <50% will still be unacceptable. Despite these issues, by adopting a relative predictivity (RP) measur e (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 likel y to be a rodent carcinogen than a noncarcinogen. Likewise, negative results in all three tests indicate the chemical is greater than two times more likel y 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 ca rcinogenic potential from batteries of positive or negative results.

Kishima, M. O., L. F. Ba rbisan, et al. (2000). "Promo tion of hepatocarcinogenesis by hexachlorobenzene in energy- rest ricted 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 we re 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 ex ert any influence on the development of glutathione S-transferase placental fo rm (GST-P(+)) foci of hepatocytes. Simultaneous HCB exposure and energy restriction induced a significant increase in liver centrilobular hypert rophy and GST-P(+) foci development. Our findings suggest that energy restriction in creases liver response to low dose of HCB, unmasking the promoting pot ential 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 hexac hlorobenzene-induced porphyria." Biochem

Pharmacol 39 (5): 817-825.

Koppen, G., A. Covaci, et al. (2002). "P ersistent organochlori ne 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 Mini stry of Health, Belgium was set up to assess pollutant concentrations and related health effect biomarkers in humans living in two regions of Fl anders. The study was called the 'Flemish Environment and Health Study' (FLEHS). One of the goals was to measure present concentrations of persistent organochlor ine pollutants in a Flemish population and to compare values obtained from pooled and individual serum samples. Concentrations of selected organochlorin e pesticides, polychlorinated biphenyls (PCB) and polychlorinated dibenzo-p-dioxins (PCDD) and furans (PCDF) were measured by gas chromatography-mass spec trometry. TEQ values were also assessed by Chemical-Activated LUciferase gene eXpression (CALUX) bioassay. The study population cons isted of 200 women between 50 and 65 years living in two areas of Flanders, Be lgium. Because of the large volumes serum needed for all measurements, the c oncentrations of organochlorines were measured in 47 pooled serum samples or iginating from these women. The

concentrations of the indicator PCBs (359.8 ng/g fat) and organochlorine pesticides (hexachlorobenzene, p,p'-dichl orodiphenyldichloroethylene, p,p'- dichlorodiphenyl-trichloroethane, lindane and pentachl orophenol), were comparable to those found in other Eur opean 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 le vels than a comparabl e age group from Germany examined in 1996. The mean to tal 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 fa t. 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 pooli ng of serum samples offers the possibility to measure exposure in the whole study population on a more cost-effective way. However, because of statistical pow er loss and no possibility of confounder adjustment, pooling is not the most effect ive way to study regional differences.

Kumar, V., C. Majumdar, et al. (2008). "Effects of endocri ne disrupting chemicals from leather industry effluents on male reproduc tive system." J Steroid Biochem Mol Biol

111 (3-5): 208-16. The leather tanning industry is characteri zed by the production of different kinds of effluents, generated in each step of l eather processing. These effluents have various chemical compounds which may c ause toxicity and endocrine disruption and are thus known as endocrine disrupti ng chemicals (EDC). This study was

aimed to examine the andr ogenic potential of leather industry effluents collected from northern region of India. Hershber ger assay data showed a significant increase (p<0.05) in the weight and st ructure 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 nam ely, cytochrome P450scc, 3beta-hydroxysteroid dehy drogenase, 17beta-hydroxysteroid dehydorgenase in castrated and intact ra ts. This was further supported by121 increased enzymatic activities measured in vitro spectrophotometrically. Serum hormone profile demonstrated a dose depe ndent 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 wate r 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 t hat the effluents from leather industry have potential EDC demonstr ating androgenic activities.

Langer, P., A. Kocan, et al. (2008). "Increased thyroid volume, prevalence of thyroid antibodies and impaired fasting glucose in young adults from or ganochlorine cocktail polluted area: outcome of transgener ational 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 th yroid 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 wit h 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 hi gher than that in all young subjects from BCGR. At the same time, also t he 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 exposur e to high OCs levels of their mothers during their prenatal and perinatal life. Thus, the data may be compatible with present views on transgenerational trans mission 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 biologic al 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 454122 adults was examined within t he 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 environ mentally 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 determi ned in serum by high resolution gas chromatography using microelectron capt ure detector and microcapillary column. Thyroid volume (ThV) was measured by r eal time sonography using the ellipsoid method with the aid of sonographic in strument Sonoline SI-400 (Siemens, Germany). The level of TSH was estimat ed by supersensitive immunoradiometric method using commercial kits by Imm unotech (Marseille, France). Pearsons correlation coefficients after logarithmic transformation of values and Spearmans

correlation coefficients were used for statis tical evaluation. RESULTS: Significant positive association (p<0.01) was f ound between DDE and PCB, DDE and HCB, while that between PCB and HCB was not signi ficant. Similar positive association (p<0.01) was also found between each individual organochlor ine and their sum. Significant negative association (p<0 .01) was found between ThV and TSH. When using categorical PCB values ei ther >2000 (N=208) or >3000 (N=127) ng/g lipid, significant positive associati on (p<0.05 and p<0.01, respectively) was found between the sum of all organochlor ines (PCB+DDE+HCB) and ThV, while that between PCB and ThV (p<0.01) wa s found only at the PCB levels >3000 ng/g lipid. When using Spearmans correlati on 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 asso ciations were found, this study, like several others, could not exactly define t he participation level of individual POPs in their common toxic effects, but po ssibly contributed to the recognition and elucidation of some problem s 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 elec tronic parameters that characterize the action of carcinogens, i.e descriptors such as electron affinity, ?(HOMO-LUMO), dipole moments, electrostatic attracti on, formation heat (H f) and permeability of the cellular membrane (c Log P) for se lected compds. The multivariate anal. allows us to propose a theor. model that correlates these descriptors with the carcinogenic activity in a series of c hem. compds. The protecting activity of antioxidants was analyzed by considering their competit ion 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 ti me-course study, the effects of HCB on plasma GC, its adrenal synthesis and stimul ation, 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 kinet ic 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 meas ured with or without ACTH. Results show that plasma CORT in intoxicated ani mals dropped significantly after 2 and 4 weeks of treatment (23% and 58%, respec tively), and then remained constant until the 8th week. HCB also promoted a reduction in the number of hepatic GR (50-55%) without modifying affinity. Afte r 8 weeks, when porphyria was well established (40-50-fold increase in ur inary 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 gluc ose 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-hybr id yeast assay to quantify the effects of xenobiotics on thyroid horm one-mediated gene expression." Environmental Toxicology and Chemistry 27 (1): 159-67. Over the last few years, increasing ev idence has become available that some chemicals may have thyroid hormone- disr upting potencies. The effects exerted via thyroid hormone receptors (TR) have not been studied thoroughly. The present study investigates chemical thyr oid 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-hy brid 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 ac tions were studied in the absence and presence of 5 x 10(-6) mo l/L T(3), which induced maximal beta-galactosidase activity. The compounds tested included t he specific TR-antagonist amiodarone, as well as a series of phenols, phthal ate, organochlorine pesticides (OCPs), polyhalogenated aromatic hydrocarbons (PHA Hs) 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-is opropylphenol are specific agonists. Interestingly, some compounds showed potentiated ant agonistic effects when tested in combination with T(3), which suggests that TR-mediated transcription may be disrupted in vivo. The 20% relative inhi bitory 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 hum an thyroid system. Altogether the results124 of the present study show that the newly developed, yeast two-hybrid assay can

be used as a valuable tool for identif ication and quantific ation of compounds active in disturbing thyroid hormone homeost asis at the level of TR. The results are further evidence of thyroid-related e ffects of environmentally relevant PHAHs.

Li, Y. F., N. Shi, et al. (2006). "[To xicity and oxidative stress on rats by hexachlorobenzene]." Zhonghua Lao Dong We i 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 peroxidas e (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, hippocam pus, 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 hippocam pus 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 t he hippocampus of rats in the high dosage group. (4) In cerebral cortex and hippocam pus 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 phos phatase of both dosage groups was also decreased, but the contents of both seru m albumin and total cholesterol were significantly higher than those of t he 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 mechani sm of neurotoxicity and hepatotoxicity.

Liu, G. H., K. D. Yang, et al. (2005). "[Effects of residues of organochlorine pesticides on reproductive endocrine in human]." We i 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 increas e of blood burden of organochlorine pesticides, levels of the hormones such as follicle stimulating hormone (FSH), estradiol (E2) and progesterone (P) in t he maternal blood and FSH, luteinizing hormone (LH) and E2 in the umbilical cord blood increased in dose-effect manner, respectively. However, the horm ones, for example, LH in the women

blood and P in the cords blood decreased re spectively with the rising pesticides'

levels and an obvious dose-effect relati onship was found. (2) The expressional125 abundances of alpha-estrogen receptor (a lpha-ER), beta-endo rphin (beta-EP) and gonadotropin releasing hormone (GnRH) in the placentae and alpha-ER and beta-EP in the cord tissues went up res pectively in dose-effect manner following the rising pesticides' burdens. (3) The ti mes of the previous adverse pregnancy

outcomes increased with the increase of the residues' burdens and there were significant differences between the cont rol and various residue groups, but the times in the high-residue was smaller t han that in the mid -residue group (P < 0.01). The average weights of the newbor n in various residue groups were heavier comparing to the control. Ther e was no significant difference between the high residue group and the control. However, significances existed among the low, intermediate, and c ontrol group (P < 0.05). Mor eover, the rank from high to low was the low-residue, mid-resi due and high residue group. CONCLUSION: The residues of organochlorine pestici des (DDT and BHC and their metabolites) possess reproductive and developmental to xicities, 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. Mazze tti, et al. (2007). "Melatonin fo rmation in pineal gland from rats with hexachlorobenzene experim ental 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 rhythm icity 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 determi ne the contents of tryptophan and its metabolites in pineal gland of normal and hexachlorobenzene-treated rats in

order to find alterations potentially related to porphy ria cutanea tarda. Results

show that in animals with this ex perimental porphyria some tryptophan metabolite levels (serotonin and 5-hydroxyi ndoleacetic acid) increase only during the light period, whereas tryptophan c ontent remained equal to the controls. Hydroxyindole-O-methyltransfe rase activity also increases by light in pineal gland

from hexachlorobenzene-treated rats. On t he 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, neoplas tic 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 tran scription 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 incr eases the activity of malic enzyme (ME). In this report, we sh ow 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 liver126 enzymes, such as glyceraldehyde- 3-phosphate dehydrogenase, phosphoenol pyruvate carboxykinase, and mito chondrial alpha-glyce rol-3-phosphate dehydrogenase, are not affected by HCB. T he induction of ME mRNA levels is accompanied by an increase in ME prom oter activity, as demonstrated by transient transfection experiments perfo rmed in rat hepatoma H35 cells. In an attempt to identify the cis-regulatory el ements responsible for the HCB effect, different promoter deletions and mutati ons were used. The results obtained localize the responsive region between positions -315 and -177. This region does

not contain either consensus xenobiot ic response or activating protein-1 elements, the two main mediators of di oxin compounds described to date. In contrast, a thyroid hormone response elem ent (TRE) is located between - 281 to

-261. Deletions and mutations of the TRE element do not respond to HCB, demonstrating that this element mediat es the response of this dioxin-type compound. As ME gene expression is regul ated mainly by thyroid hormones, we next investigated the role of T3 recept or (T3R) in the ME gene transcriptional induction mediated by HCB. Using Scatchar d 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). "[Pe culiar remaining of some PCB congeners in the patients with Yusho for more t han 30 years]." Fukuoka Igaku Zasshi 94 (5): 136-43. Concentrations of polychlori nated biphenyl (PCB) congeners, hexachlorobenzene (HCB) and dichloro dich lorophenyl ethylen (DDE) in the blood of Yusho patients (n = 28) were statistically compared with those in the blood of Fukuoka residents (n = 151). T he 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 Fu kuoka 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 pecul iar accumulative properties in Yusho patients. The concentration of PCB # 118 had been markedly decreased after the ingestion of PCBs and would be metaboliz ed to hydroxylated PCB, which might cause estrogen disturbance in the Yusho patients.127 Matsuoka, M., H. Ishibashi, et al. (2005). "The potential c ontribution 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 bioa ssays that assess estrogenic activity. In the present study, we investigate the levels of dietary phytoestrogens, organochlorine pesticides and the estrogenic acti vity of various diets for an exptl. fish and discuss the potential contributi on of these substances to estrogenic activity, in comparison with those used in previous studies. After hydrolysis with ?-glucuronidase, genistein and daidzein we re detected in all of the diets, and there were no significant differences in the contents of thes e substances among present and previous investigations. In addn., organochlorine pesticides, such as hexachlorobenzene (HCB), ?-benzene hexach loride (?-BHC), ?-BHC, transnonachlor, and/or endrin, were detected in mo st fish diets. All of these diets exhibited higher levels of activation of ? estrogen receptors than with ? estrogen receptors in an in vitro yeast-based bi oassay. 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, i ndicating the necessity for more careful selection of the feeding diet and measur ement of estrogenic substances when performing routine screening assays for endocrine-disrupting chems.

Mazzetti, M. B., M. C. Tair a, et al. (2004). "Hexachlorobenzene impairs glucose metabolism in a rat model of porphyria cut anea tarda: a mechanistic approach." Arch

Toxicol 78 (1): 25-33. Hexachlobenzene (HCB), one of the most persistent environmental pollutants, induces porphyria cutanea tarda (PCT). T he aim of this work was to analyze the effect of HCB on some aspects of glucos e metabolism, particularly those related to its neosynthesis in vivo. For th is purpose, a time-course study on gluconeogenic enzymes, pyruvate car boxylase (PC), phosphoenolpyruvate carboxykinase (PEPCK), glucose-6-phos phatase (G-6-Pase) and on pyruvate kinase (PK), a glycolytic enzyme, was ca rried 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 eval uated. 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 considerabl e 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 stor age 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 pr ogressed (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 promot ed a time-dependent increase in urinary128 chemiluminiscence (fourfold) and hepatic malondialdehide (MDA) content (fivefold), while the liver tryptophan le vel was only raised at the longest

intoxication times. These results would suggest that HCB treatment does not cause a primary alteration in the mechani sm of pancreatic insulin secretion and that the changes induced by the fungici de 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 leve ls 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 produc ed by the fungicide. Tryptophan adds its effect to this decrease in the higherphases of HCB intoxication, where its levels overcome the control values possi bly owing to the drastic decline of UROD. This derangement of carbohydrates leads porphyric hepatocytes to have lower levels of free glucose. These resu lts 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 pr oportion of blood samples from the general population, have been found to alte r thyroid hormone levels in animals and humans. However, studies of these relationships in adult men are limited

and results across studies have been inc onsistent. 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 cons idered. However, when results were additionally adjusted for p, p(')-DDE, inverse associations with T(3) were significant for PCB 138, PCB 153, su m of PCBs and three different PCB groupings, and HCB, while the positive as sociations between p,p(')-DDE and T(3) also remained. In conclusion, se rum 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-chlo rophenyl)ethane; HCB, hexachl orobenzene; MDL, method detection limit; NHANES, national health and nutrition examination survey: p,p(')- DDE, 1,1-dichloro-2,2-bis(p-chlor ophenyl)ethylene; PC B, polychlorinated biphenyl; T(3), triiodothyroni ne; 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 Us ing Population Based Met hods on Gene Expression Data." Chetty, M [Editor] 7 (S). Discovering toxicity biomarkers is import ant in drug discovery to safely evaluate possible toxic effects of a substance in early phases. We tried evolutionary

classification methods for selecti ng the important classifier genes in hexachlorobenzene toxicity using micr oarray data. Using modified genetic algorithms for selection of minimum number of features for classification of gene expression data, we discover ed 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% accu racy 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 hexach lorobenzene (HCB) in the rat was investigated by seeking to determi ne 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 histopat hologic changes in skin and lung were assessed after exposure. After 3 weeks of exposure, urinary metabolites of the mercapturic acid and oxidative biotransfo rmation pathways were identified using high-performance liquid chromatography (HPLC) and liquid chromatographymass spectrometry (LC-MS). Oral exposure of th e rats to 450 mg/kg HCB resulted in an increase in relative spl een 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- an d 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 wa s true for the urinar y levels of the oxidative metabolite pentac hlorophenol (PCP). Thus, results indicate that metabolites of the mercaptur ic acid pathway are not involved in the induction of splenomegaly and skin and lung pathology caus ed by HCB exposure in BN rats130 and that the main urinary metabolite of HCB in these BN rats is PCP. Since PCP itself, as well as other cytochrome P 450-derived metabolites from HCB, are not likely to be involved in the inducti on of splenomegaly and skin and lung pathology, it is suggested that eitherthe 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 environm ental pollutant hexachlorobenzene causes eosinophilic and gr anulomatous inflammation and in vitro airways hyperreactivity in the Br own Norway rat." Arch Toxicol 76 (4): 236-47.

Based on observations that the persistent environmental pollutant hexachlorobenzene (HCB) induces inflamma tory 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 f eatures of human Churg-Strauss syndrome (CSS), we hav e 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 ra ts 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 arecoli ne and serotonin. In addition, lungs were lavaged to count and differentiate la vage cells, and skin, lungs, heart, kidneys, and lymph nodes were processed for hist opathological inve stigation. 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 featur e of CSS, in the lungs and skin of BN/SsNOlaHsd rats. Thus, it is concluded that the persistent environment al 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. Bloksm a, 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 athy mic 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 re constitution. 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 le sion development and body weight gains were assessed during exposure and spleen and liver weights as well as131 histopathologic changes in skin, lung, and spleen were assessed after exposure. Oral HCB exposure of athymic and euthymic ra ts 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 wei ghts 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-deplet ed 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 sp lenic changes by HCB and therefore it is suggested that HCB acts diffe rently from many allergenic and autoimmunogenic low molecular weight co mpounds that trigger pathology via thymus-dependent mechanisms. A role fo r mononuclear phagocytes and, in BN rats, eosinophilic granulocytes, in t he HCB-induced pathology is suggested since these cells were prominently pres ent in the HCB-induced lesions.

Michielsen, C. P., A. Leusink-Muis, et al. (2001). "Hex achlorobenzene-induced eosinophilic and granulomatous lung inflammation is associated with in vivo airways hyperresponsiveness in the Brown Norw ay rat." Toxicol Appl Pharmacol 172 (1): 11-20. We investigated whether the eosinophil ic 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 methac holine. 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 increasi ng 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 formati on and perivascular and peribronchiolar infiltration of eosinophils, as well as in creased responsiveness to methacholine. Oral exposure to HCB for 7 days caus ed 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 thr eefold 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 in creased numbers of eosinophilic granulocytes in the lung interstitium , particularly around the bronchi and

bronchioli. No correlation was observ ed between serum IgE levels and AHR. Data suggest that HCB induces AHR by stimulating eosinophilic lung132 inflammation and that the preexistent microgranulomas may predispose to development of the HCB-i nduced lung pathology.

Mueller, P., I. Wolff, et al. (2002). "Screening toward genotoxic effects of halogenated hydrocarbons." Naunyn-Schmiedeber g's Archives of Pharmacology 365 (Supplement 1):

R137.

Nakano, K., M. Ishizuka, et al. (2009). "Absol ute requirement for iron in the development of chemically induced uroporphyria in mi ce treated with 3-methylcholanthrene and 5-

aminolevulinate." BioMetals: an International Journal on t he 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 uroporphy ria. The role of iron in the development of porphyria has not been el ucidated. We exami ned 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 ir on. They were treated with 3-methylcholanthrene (MC), an archet ypal inducer of CYP1A, and 5- aminolevulinate (ALA), precursors of porphyrin and heme. We found that uroporphyrin (URO) levels and uroporphyrin ogen 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 (MR OD) activities, the CYP1A2-mediated reaction, were markedly induced in t he livers of both ND and IDD mice treated with MC and ALA. UROX activity, suppos edly 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. Ik egami (2000). "Hexachlorob enzene 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 envir onmental 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 nm ol/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 concen tration ratio in fetuses was 3.4. In pregnant rats on the day before partu rition, the PECB concentrations in organs and fat tissue we re 3 to 4 times higher than those of HCB. After parturition, PECB rapidly disa ppeared from the body of nursing rats133 during the lactation period, especially when compared with HCB. On day 2 after birth, HCB and PECB concentrations in the stomach content s of suckling pups were highest, and the PECB concentration was 3.5 times higher than that of

HCB. HCB in the stomach contents dec reased gradually (T1/2 = 5.7 d) and PECB decreased rapidly (T1/2 = 2.8 d) during the 15 d a fter birth. These findings

indicate that the PECB/HCB transferr ed 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 ur inary porphyrin excretion in neonates born to mothers exposed to ai rborne hexachlorobenzene." Environ Health Perspect 110 (2): 205-9.

The existence of a link betw een hexachlorobenzene (HCB) and porphyria cutanea tarda has been known for a long ti me. However, the epidemiologic data on effects on health caused by prenatal exposure have not provided convincing evidence that HCB alters porphyrin met abolism. Our objectives were to analyze urinary porphyrin excretion and HCB in ma ternal serum and fetal cord blood in neonates born in a village (Flix) near a chlorinated solvent factory, to detect possible adverse effects in urinary por phyrin excretion caused by prenatal exposure, and to assess t heir 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 Mo ra 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 mot hers. We obtained 68 urine specimens of singleton neonates on t he third day after birth to test for urinary porphyrin excretion. We obtai ned 52 fetal cord blood and 56 maternal serum samples for HCB analysis. Total ur inary 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 porphyri n concentration was 37.87 micromol/mol creatinine. Coproporphyrin I and coproporphyrin III we re the major porphyrins excreted. We found no positive relationshi p between urinary por phyrin excretion and HCB levels. However, we observ ed an association between maternal smoking and coproporphyrin excretion. Al though 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 concentrati ons, 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 measured134before 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. a fter the program, whereas concns. of most detected organochlorines were si gnificantly increased. Changes in organochlorine concns. were neg. assocd. with changes in serum T3 concn. (significantly for p,p'-DDT, HCB, Aroc lor 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 decr ease in serum T3 concn. and RMR. Further studies are needed to verify whetherthese findings are causally related.

Pelletier, G., S. Masson, et al. (2009). "C ontribution of methylmercury, polychlorinated biphenyls and organochlorine pesticides to the toxicity of a contaminant mixture based on Canadian Arctic population blo od profiles." Toxicology Letters 184 (3): 176-85. Human populations are simultaneously exposed to a variety of anthropogenic contaminants. However, despite extensive literature on animal ex posure to single compounds, data on the toxicity of comple x mixtures are scarce. The Northern Contaminant Mixture (NCM) was formula ted to contain the 27 most abundant

contaminants in the same relative proportions found in the blood of Canadian Arctic populations. Sprague-Dawley rat dam s were dosed from the first day of gestation until weaning with methylmerc ury (MeHg), polychlorinated biphenyls (PCBs) or organochlorines pesticides (O Cs) 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 Th yroid Stimulating Hormone (TSH) levels, thyroid gland morphology, brain taurine content and cerebellum and hippocampus protein expression patterns re sulting from such exposures were monitored. Pups' increased mortality ra te and impaired growth observed in the NCM treatment group were attributed to MeHg, while decreased circulating thyroxine levels and pertur bations of thyroid gland morphology were mostly attributable to PCBs. Interestingly, despite comparable reduction in serum thyroxine levels, PCBs and PTU exposur es produced markedly different effects on pup's growth, serum TSH level and brain taurine content. Analysis of cerebellum and hippocampus protein expr ession patterns corroborated previous cerebellum gene expression data, as c ontaminant co-exposure in the NCM significantly masked the effects of individual components on protein twodimensional electrophoresis patterns. I dentification by MALD I-TOF/TOF MS of differentially expressed proteins invo lved 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; Mu ftu, 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 symptom s resulted from accidental ingestion of hexachlorobenzene (HCB)-treated seed gr ain in Turkey 25 years ago and involved about 4,000 persons with a 10% mort ality. Twenty-five years later, 161 patients, 63 women and 98 men, with histories of HCB exposure as children or young adults were studied. Many pat ients had persistent abnormal porphyrin metabolism and prominent neur ological, dermatologic, and orthopedic symptoms and signs. Thyromegaly was seen in 60% of the women and 27% of the men. The children born to porphyric mother s 25 years ago all died of pembe yara secondary to maternal milk and transplacent al 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). "Tur kish 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 Parkin son's disease." Neurotoxicology 29 (4): 584-90. This study aimed to investigate the asso ciation of Parkinson's disease (PD) with dietary exposure to polychlorinated bipheny ls (PCBs) and methylmercury (MeHg) in a community with increased exposure levels . A total of 79 clinically verified idiopathic PD cases and 154 controls matc hed 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 lifet ime 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 vari ables. Increased ORs for dietary intakes of whale meat and blubber during adult life were stat istically significant. The ORs for occupational exposure to solvents, pesticides and metals also suggested an

increased risk for PD. Current serum c oncentrations of summation operator PCB and related contaminants suggested slight ly increased ORs, although only betahexachlorocyclohexane (beta-HCH) was stat istically significant. Increased intake

of whale meat and blubber in adult life was significantly associated with PD, thus suggesting a positive associ ation between previous ex posure to marine food contaminants and development of PD.

Pieters, R., J. G. Vos, et al. (2005). "Immunotox ic 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 carci nogen, HCB induces the formation of liver tumors in female rats, whereas only a small percentage of males are responsive. Intercellular comm unication via gap junctions is decreased in carcinogenesis. Gap junctions are co mposed 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 effe cts result from gender differences in the constitutive expression of these Cxs. Rats were given HCB by gavage for five consecutive days. In the first experim ent, control and HCB-treated female rats were sampled on day 100. Intercellu lar communication was significantly decreased in HCB-treated females compar ed 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 fe males as compared to controls. Cx26 mRNA levels were 3-fold higher and Cx 32 mRNA levels were 8-fold lower in females compared with males. In a thir d experiment, ovariectomy abolished any

differences between male and female contro ls for both Cxs, while estradiol had a partial role in the regulation of Cx32. This suggests that the sexual dimorphism inhepatic Cx levels is determined by the ovarian hormones. However, the HCBinduced decrease in Cx32 and Cx26 m RNA levels was maintained in ovariectomized rats, suggesting that t he 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 hepat ic 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 concomit ant with the activati on of the integrinlinked kinase (ILK) pathway, leading to t he activation and nuclear translocation of Akt and the inactivation of glycogen synthase kinase-3beta (GSK3beta). Ecadherin, an adhering junction protein, is al so 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 display ed significantly lower Cx32 mRNA levels and Akt was also activated and translocated into the nucleus. Using a137 constitutively active Akt expression ve ctor, 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-activ e form of Akt, we showed that Cx32 protein levels were reduced in transfect ed cells as compared with cell transfected with the wild-type inactive Akt vector, s uggesting that the nuclear form of Akt is responsible for the downregul ation of Cx32. Overall, these data indicate that Cx32 is downregulated by t he ILK pathway activation in rat hepatocytes and that

this is mediated via the activati on 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 ep igenetic 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 si gnificant decrease in gap junctional intercellular communication (GJIC). The la tter 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 Assa y. No significant differences between groups were observed for the two co mplexes formed with Fr53; for Fr110 a significant 3-fold decrease in the int ensity of the complex formed was observed between HCB-treated and control females, while no changes were observed in proteins isolated from male livers. Furt hermore, a female-specific 5-fold decrease in binding was observed with Fr26. Supershift exper iments 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 result s from a decrease in the binding of transcription factors which stim ulate the expression of Cx32.

Plante, I., D. G. Cyr, et al . (2003). "Overexpression of the in tegrin-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 H epatocytes; 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 pat hway 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 ai m of this study was to

demonstrate the role of t he ILK pathway in the r egulation of adhering and gap junctions in liver cells. MH1C1 rat hepatocytes exposed to HCB for 7 days

showed increased levels of the inacti ve form of GSK3beta, i.e. phosphoGSK3beta, an important messenger of IL K 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 (k enpaullone 5 and 10 uM, SB- 415286 125 and 150 nM) markedly reduced GSK3beta acti vity 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 ei ther another messenger of the ILK pathway, such as Akt, or another pathway . Stable transfections of MH1C1 cells with Cx32 expression vector to increase Cx32 expressi on levels resulted in a

marked increased Ecadherin mRNA levels thereby suggesting a link between Cx32 and E-cadherin regulati on. Together, these data de monstrate that in rat hepatocytes E-cadherin is down-regulated by the ILK pathway via GSK3beta inhibition and up-regulated by Cx32 over expression. 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 in tegrin-linked kinase pathway in hexachlorobenzene-induced gender-specific ra t hepatocarcinogenesis." Toxicol Sci

88 (2): 346-57. Overexpression of the in tegrin-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 pathw ay. Hepatic ILK levels were markedly increased in HCB-treated female rats. Cy toplasmic/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 (G SK3beta), rendering it inac tive. 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 nucl ear translocation of beta-catenin, as demonstrated by both immunocytochemis try and flow cytometric analyses. Western blot analysis showed an 84% decr ease 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 downregula tion of intercellular communication139 does not occur as a result of either E-cadherin downregul ation or GSK3beta

inactivation.

Porpora, M. G., E. M edda, et al. (2009). "Endomet riosis 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 industr ialized countries, it af fects approximately 10% of women of reproductive age. Its et iology is unclear, but a multifactorial origin is considered to be most plaus ible. Environmental organochlorinated persistent pollutants, in particular diox ins 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-lik e PCBs (NDL-PCBs) and dioxin-like PCBs (DL-PCBs), 1,1-dichloro-2,2,-bi s(4-chlorophenyl)-ethene (p,p'-DDE), and hexachlorobenzene (HCB) were determined by ion-trap mass spectrometry. DRCALUX bioassay was employed to asse ss the 2,3,7,8-te trachlorodibenzo-pdioxin toxicity equivalent (TEQ) c oncentrations 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% c onfidence interval (CI), 1.61-8.91], NDL-PCB-138 (OR = 3.78; 95% CI, 1.60-8.94), NDL-PCB-153 (O R = 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 PC B 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 contam inant hexachlorobenzene." Environ Health Perspect 111 (4): 461-6. Hexachlorobenzene (HCB) is a persistent environmental cont aminant that has the potential to interfere with steroid ho rmone regulation. The prostate requires precise control by androgens to regulate it s growth and function. To determine if HCB impacts androgen action in the pros tate, 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 pr omoter 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 c ontent and c-Myc, c-Fo s 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 activa tion 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) prot ein. 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 recept or signal transduction pathway. HCB is a weak agonist of the Ah R, and the evidence that HCB toxicity is mediated via the AhR complex is lim ited and inconclusive . In the present study, female Wistar rats were admin istered 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 assa yed 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 phosphorylatio n 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 t ogether, our data demonstrates that HCB may induce EGFR transactivati on 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 re ceptor 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) cont ent of liver microsomes and plasma141 membrane, and on EGFR-tyrosine kinase activi ty in the microsomal fraction were investigated. In addition, we studied t he 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 co rrelated 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 hi ghest 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 ra ts treated with HCB had higher levels of EGFR than untreated rats; treated rats also had less EGFR present in hepatocyte plasma membrane fractions t han did untreated rats. HCB altered the phosphotyrosine content and protein phosphory lation of some microsomal and cytosolic proteins in a biphasic dose-re sponse relationship. At the low dose, phosphorylation and phosphotyros ine content of several microsomal proteins were increased; however, these effects were diminished or reversed at the higher doses. Our results suggest that ch ronic 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 protei n tyrosine phosphorylation. The level of sensitivity

encountered in our studies is extraordinar y, 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 struct ural 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 pr edisposes rats to the development of porphyria and accelerates xenobiotic-tr iggered 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 s poradic porphyria cutanea tarda induced by

hexachlorobenzene in female Wistar ra ts (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-fo ld the urinary excretion of deltaaminolevulinate, porphobilinogen, and porphyrins, respectively. Ethanol exacerbated the precursor excretions elicited by hexachlorobenzene. Hepatic porphyrin levels increased by hexachlor obenzene 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 uropor phyrinogen activity; in the ethanol + hexachlorobenzene group, this decrease o ccurred before the one caused by

hexachlorobenzene alone. Ethanol ex acerbated the effects of142 hexachlorobenzene, among others, on t he rate-limiting enzyme deltaaminolevulinate synthetase. The plasma ac tivities of enzymes that are markers of hepatic damage were similar in all drug- treated groups. These results indicate that 1) ethanol exacerbates the bioc hemical 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 predispositi on, and 4) hepatic damage showed no correlation with the devel opment 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. Novi c, 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 endocri ne 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 Co mmission for the scientific evidence of their endocrine disruption activity. The subs tances belong to different categories defined in the EU Commission report: (i) liter ature evidence for certainly active as endocrine disrupters, (ii) fo r potentially active, (iii) for less probable active - lacking evidence, and (iv) for certaint y 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 net work is applied for the classification of compds. regarding thei r literature evidence for the endocrine disruption activity. The devel oped classification model is proposed as a tool for a preliminary assessment of potential endocrine disrupter s, 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 expe rimental models." Journal of toxicology

and environmental health. Part A. 69 (1-2): 53-76. Long-range transport of persistent or ganic compounds by air and ocean currents from industrialized areas resulted in high le vels of these pollutants in food webs

in the Svalbard area. With the aim to test if organochl orine (OC) exposure in freeliving polar bears from Svalbard affe cted their plasma steroid hormone concentrations, it was found that polych lorinated biphenyls (PCBs) were associated with increased pr ogesterone levels in females. The sum of pesticides (sigma pesticides) and sigma PCBs cont ributed 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 to143 study the effects of selected OCs (i.e ., PCB 153 and PCB 126) on animal health as a consequence of effects on endocri ne-regulated functions such as reproduction and immunity in a goat m odel 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 ut ero and in the suckling period influenced reproductive functions and bot h PCB 153 and PCB 126 exerted immunomodulatory effects on the offspri ng, 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 devel opment and optimization of a cell-based androgen reporter assay using the Chinese ham ster ovarian cell line (CHO K1) in the 96-well format. The recent reports on increasing exposure of humans and wild-life to environmental endocrine disrupti ng 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 vi rus-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 lucifera se 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 testoste rone 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, proges terone, dexamethasone and cortisol showed weak activity at high concentrations. RT-PCR and western blot confirmed proper transcription and translati on as well as stable expression of the AR gene in the cells. About 60 different chemicals (mostly pesticides or their metabolites, and common industrial chem icals) were screened with the cell line for their ability to stimulate luciferase acti vity or inhibit that evoked by 0.1 nmol/l R1881, used as a positive androgenic c ontrol. About 10 hi ghly potent antiandrogenic chemicals were identified. The most potent anti-androgenic compounds identified in our assa y 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 signifi cant agonistic activity. In conclusion,

we demonstrate that the bioassay based on this cell line provides a reliable test for detecting androgenic and anti-androgen ic 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 co mpound 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 hexac hlorobenzene 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 re cords and cancer registry data. Serum

levels of hexachlorobenzene were ve ry high in males who worked in the electrochemical factory (geometri c 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, preval ence of self-reported common chronic conditions, and porphyria cutanea tarda, th yroid pathology, Parkinson's disease, cancer, and reproductive outcomes were within the ranges observed in other studies. Employment in the plant, howev er, 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 descr ibed. The results suggest that exposure

to hexachlorobenzene did not affect the general health status of the this population, but it was associ ated with specific health ef fects of the most highly exposed subjects.

Schell, L. M. (2002). Mohaw k culture, behavior, toxica nt exposure and health. Crisp

Data Base National Institutes of Health . New York.

Considerable concern exists overpossible effects on human physical and psychological development of endocrine disrupting environmental contaminants such as polychlorinated biphenyls (PCB s). Native American communities are particularly at risk owing to subsistenc e systems and a cultural ethos involving greater contact with the physical envir onment. The proposed study follows-up 220 Mohawk adolescents aged 17-21 years, w ho participated in a previous study when they were 10-16 years old. All adolescents are mem bers 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 interrelati onship between Mohawk cu ltural identity, traditional Mohawk customs, behaviors rela ted to toxicant exposure and current

toxicant burden. Serum level of PCBs will be assessed by congener specific analysis. The study will determine 1) t he relationship of congeners and their hydroxylated metabolites to thyroid function (thyroid hormone levels and antithyroid antibodies), and 2) psychosocia l 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 old145 psychosocial outcomes. Variation in susceptibility to PCB effects will be determined by examining the effects of concurrent toxicant exposure (hexachlorobenzene, Mirex, dichlorodi phenyldichloroethene, lead), diet, and indicators of PCB metabolism, on the fo cal measures of adult functioning. The proposed study will clarify the causal pathw ays between culturally identifying behavior, PCB exposure and body burden, thyroid functioning, cognitive functioning, social behavior and school functi oning while identifying activities that are important to maintain cultural identify and unrel ated to exposure.

Schell, L. M. (2003). Mohaw k culture, behavior, toxica nt exposure and health. Crisp

Data Base National Institutes of Health . New York.

Considerable concern exists overpossible effects on human physical and psychological development of endocrine disrupting environmental contaminants such as polychlorinated biphenyls (PCB s). Native American communities are particularly at risk owing to subsistenc e systems and a cultural ethos involving greater contact with the physical envir onment. The proposed study follows-up 220 Mohawk adolescents aged 17-21 years, w ho participated in a previous study when they were 10-16 years old. All adolescents are mem bers 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 interrelati onship between Mohawk cu ltural identity, traditional Mohawk customs, behaviors rela ted to toxicant exposure and current

toxicant burden. Serum level of PCBs will be assessed by congener specific analysis. The study will determine 1) t he relationship of congeners and their hydroxylated metabolites to thyroid function (thyroid hormone levels and antithyroid antibodies), and 2) psychosocia l 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, dichlorodi phenyldichloroethene, lead), diet, and indicators of PCB metabolism, on the fo cal measures of adult functioning. The proposed study will clarify the causal pathw ays between culturally identifying behavior, PCB exposure and body burden, thyroid functioning, cognitive functioning, social behavior and school functi oning while identifying activities that are important to maintain cultural identify and unrel ated to exposure.

Schulte, A., J. Althoff, et al. (2002). "Two immunotoxicity ring studies according to OECD TG 407-comparison of data on cyclos porin 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 immuno toxicological potential of

unknown substances. These studies followed OECD TG 407 and included a

number of additional exam inations. CSA was selected as model for its immunosuppressive and HCB as model for its immunostimulating effects.146 Reproducibility of data was defined by signi ficant findings in at least 50% of participating laboratories. In-life clinical observations, values for WBC parameters, and changes of lymphoid organ weights sugges ted immune effects. Elevated IgM titers indicated increased antibody formation in HCB-exposed rats. Cellularity of T-cell com partments in thymus (medu lla), spleen (PALS), and lymph nodes (paracortical zone of me senteric and popliteal LN) were dose dependently decreased in CSA-treated rats. The numbers of follicular germinal

centers were reduced in LN. HCB induc ed cellular prolifer ation 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, statisti cal inference was limited to low numbers of partici pating laboratories. In spleen, both substances decreased lymphoblast prolifer ation 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 subpopulati ons were identified in spleen for both substances. In order to predict imm unomodulatory effects of CSA or HCB, histomorphologic examinati on of lymphoid tissues resulted in the most reliable and sensitive data to distinguish immunosuppression and -stimulation.

Sekihashi, K., A. Yamamoto, et al. (2002). "Com parative investigation of multiple organs

of mice and rats in the come t assay." Mutation research. 517 (1-2): 53-75. Mice and/or rats are usually used to det ect chemical carcinogenicity and it has

been known that ther e 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 sensitivit y at one equitoxic le vel but not at one equidose. Therefore, groups of four mice or rats were treated once intraperitoneally or orally with a c hemical at highest dose without death and

distinct toxic manifestati on. When the death was not obser ved at 2000 mg/kg of a chemical, 2000 mg/kg was used for the come t 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 pos itive 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-carcinogen s in both species were positive in one organ (urinary bladder for 2,4-dime thoxyaniline 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 cytogenet ic 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 diffe rences in genotoxicity at one equitoxic level are not consistent with species di fference in carcinogenicity and that the use of both species is appropriate to indi cate a carcinogenic potential in the comet assay with multiple organs, when chem icals being positive in at least one organ are judged to be comet assay-positive.

Sonne, C., R. Dietz, et al. (2005). "Do organohalogen contami nants contribute to histopathology in liver from East Gr eenland polar bears (Ursus maritimus)?" Environmental Health Perspectives 113 (11): 1569-74. In East Greenland polar bears (Urs us maritimus), anthropogenic organohalogen compounds (OHCs) (e.g., polychlorinated biphenyls, dichlorodiphenyltrichloroethane, and polyb rominated diphenyl ethers) contributed

to renal lesions and are believed to r educe 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 gr anulomas), mild bile duct proliferation accompanied by fibrosis, and fat accumula tion 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. win ter). 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 t hat these findings were caused by aging and long-term exposure to OHCs. Theref ore, 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 ev aluated in relation to OHC concentrations in a mammalian wildlife species, and the in formation 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 organohal ogen cocktail." Envi ronmental Research 106 (1): 72-80. We assessed the relationship between exposure to organohalogen polluted minke whale (Balaenoptera acutorostr ata) blubber and liver morphology and function in a generational c ontrolled study of 28 Greenland sledge dogs (Canis familiaris). The prevalence of portal fibr osis, mild bile duct hyperplasia, and vascular leukocyte infiltrations was signi ficantly higher in the exposed group (all Chi-square: p<0.05). In case of gr anulomas, 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 significa ntly highest in the control group (both148 ANOVA: p<0.05). We therefore sugges t 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). "P CBs, 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 polychlorinat ed 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 kill er cell (NK) activity, antiphospholipid antibodies, antinuclear ant ibody, prolactin, progester one, thyroid-stimulating hormone (TSH) and free T4 were examined in 45 patients with a history of three or more (3-11) consecutive first-tr imester 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 sa mples for PCBs, HCB and DDE between patients and controls. Hypothyroidism, hy perprolactinemia, luteal phase defects, NK cell activity and the presence of autoant ibodies were also not associated with levels of any of the compounds in t he patients. CONCLUSION: PCBs, HCB and

DDE are not associated with miscarri age and immunoendocrine abnormalities in patients with a history of recurrent miscarriage.

Sunyer, J., C. Herrero, et al. (2002). "Serum organochl orines 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 specie s of laboratory mammals, but the human evidence is contradictory. In a st udy among adults of a population highly exposed to HCB (Flix, Catalonia, S pain), the prevalence of PCT was not increased. We aimed at analysing the associ ation of individual urinary porphyrins

with the serum concentrations of HCB and other organochlorine compounds in this highly exposed populat ion. METHODS: A cross-sectional study on total porphyrins was carried out in 1994 on 604 in habitants of the general population of Flix, older than 14 years. Of them, 241 subjects (c omprising 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 organochl orine compounds, were determined by gas chromatography coupled to electron capture detection. RESULTS: Coproporphyrin I (CPI) and copr oporphyrin 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 ex plained by age, alcohol, smoking, or other organochlorine compounds. No association was found between149 uroporphyrin I and III excretion, nor heptaporphyrin excretion, and HCB. CPIII increased with smoking (p < 0.05). CO NCLUSION: HCB exposure in this highly exposed population did not increase ur inary 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 porphy ria that resembles human porphyria cutanea tarda (PCT) in several animal s pecies. It has been demonstrated that high glucose ingestion prevents porphyria development, and high-fat/high-protein diets enhance HCB porphyrinog enic ability. On the cont rary, 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 we re 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 dec reased about 40% due to fungicide

intoxication. The effect of HCB on thes e two activities accounted for the higher glycogen content observed in treated ani mals; (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 mi ght contribute to the biochemical porphyria picture and would a ccount for the effect of glucose above mentioned.

Wade, M. G., S. Paren t, et al. (2002). "Thyroid toxicity due to subchronic exposure to a complex mixture of 16 organochlorines, l ead, 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 contaminat e 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 comm on human exposure. While many of the mechanisms of thyroid toxicity of these substances are potentially complementary, little is known of the degr ee of interaction of common persistent contaminants on responses of the HPT axis . To investigate the potential effects of a complex, environmentally relevant mi xture on the HPT axis, sexually mature male rats were administered a mixture of 16 common organochlorines (dichlorodiphenoxytrichlor oethane [DDT], p,p'-dichlor odiphenoxydichloroethylene [p,p'-DDE], hexachlorobenzene [HCB], tetrachlorodibenzo-p-dioxin [TCDD], polychlorinated biphenyls [PCBs], me thoxychlor, endosulfan, heptachlor, hexachlorocyclohexane, dieldrin, aldr in, mirex, and several chlorinated benzenes, and metal contaminants [lead, c admium]). The doses of the mixture

that were administered were related to minimum risk levels or tolerable daily150 intakes of these substances, as deriv ed by risk assessment with the 1x, 10x, 100x, and 1000x groups receiv ing 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 tr eatments by gavage, endpoints related to circulating thyroid hormone (serum thyr oxine [T(4)], trii odothyronine [T(3)], thyroid stimulating hormone [TSH], and se rum 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 trans ferase [UGT] and out er-ring deiodinase [ORD]) were assessed. All examined endpoints were significantly altered by the mixture albeit with great variability betw een endpoints in the sensitivity. While most endpoints examined did not show si gnificant changes at mixture doses below 1000x, 2 endpoints, TSH and hepatic out er 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 dos e until, at the highest dose, this parameter was signific antly 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 ot her endpoints. These results demonstrate that low doses of ubiquitous envir onmental contaminants can alter HPT physiology in sexually mature males.

Weiss, B. (2006). "Endocrine disruptors as a fa ctor in mental reta rdation." Davidson, PW [Editor]; Myers, GJ [Editor]; Weiss, B [Editor]. Inte rnational Review of Research in

Mental Retardation : 195-223.

Woods, A. S., S. C. Moyer, et al. (2003). "Interaction of chlorisondamine with the neuronal nicotinic acetylcholi ne receptor." J Proteome Res 2 (2): 207-12. An epitope was found on the alpha2-nicotini c isoform of the neuronal nicotinic acetylcholine receptor that would likely form salt bridges with quaternary ammonium compounds and a cation-pi inte raction with the pi-cloud of an aromatic ring. Chlorisondamine, a nicotini c antagonist, exerts a long-lasting, if not permanent, blockade of the ion channel gated by acetylcholine. Blocking of the ion channel prevents nicotine from exer ting its rewarding effect on the CNS. Chlorisondamine contains two qu aternary ammonium groups and a tetrachloroisoindoline ring. We propose t hat 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, wher eas the tetrachlorobenzene portion of

the tetrachloroisoindoline ri ng 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 or ganic molecules (chlorisondamine and hexachlorobenzene) was undertaken us ing matrix assisted laser desorption/ionization mass spectrometry.151 

### CODE 6 (young populations) References

Akita, M., M. Kato, et al. (2002). "Teratogenic effe cts 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 contami nants extd. from whale bacon products on gestation day 11.5 rat embryos cultured fo r 48 h in the in vitro whole embryos culture system were evaluated. Hi gh and low contaminated groups had no significant change on heart rate, embryoni c blood circulation and total no. of somites. Crown-rump length of embr yos 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 w eak anomalies of cacogenesis to telencephalon or mandibla and hematoma of cranioface or fore limbs with 50% incidence, suggesting that the organohalogen contami nants from whale products show the teratogenicity to rat em bryos during organogenesis in a dosedependent manner. The teratogenic effect oc curred at environmentally relevant concns. of these compds.

Alvarez, L., A. Randi, et al. (2000). "Repr oductive effects of hexachlorobenzene in female rats." J Appl Toxicol 20 (1): 81-7. Hexachlorobenzene (HCB) is a polyhal ogenated aromatic hydrocarbon widely

distributed in the environment. In anima l testing, HCB has been shown to be a reproductive toxin. Previous investigat ions of the effects of HCB on ovarian function have yielded equivocal result s. Thus, the effects of chronic administration of HCB (1 g kg(-1) body w t.) on the ovary and pituitary hormone levels, hepatic and uterine oestradiol receptors, ovaria n histopathological changes and oestrus cycle characteristi cs were investigated in spontaneously cycling rats. Our data demonstrate that HCB treatment, under the conditions of the present study, reduced ci rculating levels of oestr adiol and prolactin without

differences in serum concentrations of progesterone. Follicle- stimulating

hormone serum levels were elevated. He xachlorobenzene treatme nt resulted in irregularity of cycles, characterized main ly as prolonged periods of oestrus with a

reduced number of ova recovered. In addi tion, HCB administration resulted in significantly decreased uterine nuc lear oestrogen receptor levels. Histopathological examinat ion revealed degenerative changes of the ovarian follicles and germinal epithelium and incr eased numbers of atresic follicles.

Anas, M. K., C. Guillemette, et al. (2005). "In utero and lactational exposure to an environmentally relevant organochlorine mixtur e disrupts reproductive development and function in male rats." Biology of Reproduction 73 (3): 414-26. We hypothesized that in utero and lactationa l exposure of male rats to a mixture of more than 15 organochlorines, resemblin g that found in blub ber from northern152 Quebec seals, alters reproductive develop ment and function. Female rats were gavaged with either corn oil (controls) or the organochlorine mixt ure 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 mi xture 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 statistica l 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 tota l thyroxine levels did not differ because of organochlorine treatment. T herefore, in utero and lactational exposure to an environmentally relevant organochlori ne mixture adversely affects the reproductive system of male rats, perhaps via antiandrogenic effects during testis development, suggesting a possible repr oductive 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). "Organochl orines 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. al ters reproductive functi on. Four groups of prepubertal female pigs were fed increasi ng doses of OC through puberty, breeding, gestation and lactation. Offspring body length decreased with increasing OCs; birth wts., ano-genital distanc e and testosterone levels of male piglets were reduced in treated groups. At puberty, s perm 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 testic ular function are compromised by maternal exposure to OCs. In vi tro studies reveal that the same OCs reduce sperm function and embryonic competence, lik ely through some other mechanism.

Barnett, J. B., L. Barfield , et al. (1987). "The effect of in utero exposure to hexachlorobenzene on the developing immune res ponse 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, humor al, and innate immunity in swine." Toxicological Sciences 77 (1): 41-50.

Few studies have characterized the immunot oxic potential of complex mixtures of organochlorines (OCs) that bear envir onmental relevance. We monitored immune parameters in male piglets exposed in utero and through lactation to an OC mixture which was designed to approximat e that found in the traditional diet of Arctic aboriginal popul ations. Prepubertal sows were administered orally either corn oil (control group) or the OC mixture in increasi ng doses (low, medium, and high). The sows were inseminated wit h the semen from an untreated boar and OC treatment was continued throughout ge station and lactation (21 days). Blood

was collected from the sows at delivery and monthly fr om 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-ol d piglets. At 6 months, the lymphoproliferative res ponse 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 com pared 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 hyopneu moniae. Our results indicate that developmental exposure to an environment ally 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 cr itical windows of human reproduction and development." Environmental Research 109 (1): 93-100. Investigators often employ a single cro ss-sectional measure of in utero exposure when evaluating associations between organochlorine (OCs) pesticides/metabolites and adverse r eproductive 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 unsuccessf ul 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 fr om 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=1 0), 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 the154 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, respec tively) 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), respecti vely), 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), respective ly). These data, though limited by sample size and the possibility of laborat ory measurement error, suggest that OC concentrations may change over crit ical windows. This underscores the importance of timing biospec imen collection to critical windows for development in the assessment of reproductive and/or developmental effects.

Bourque, A. C., A. Singh, et al. (1995). "Ultrastructural c hanges in ovarian follicles of monkeys administered hexachlorobenzene." Amer ican Journal of Veterinary Research

56 (12): 1673-1677.

Bowers, W. J., J. S. Nakai, et al. (2004) . "Early developmental neurotoxicity of a PCB/organochlorine mi xture 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 polych lorinated 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 Gr eat Lakes/St. Lawrence basin. Pregnant Sprague-Dawley rats were dosed orally wit h 0.013, 0.13, 1.3, or 13 mg/kg of the chemical mixture or 15 mg/kg of Aroc lor 1254 from gestation day (GD) 1 to postnatal day (PND) 23. The highest mi xture dose decreased maternal gestation and lactation body weight, and produced high mortality rates (80% overall) and reductions in offspring weig ht that persisted to adult hood. Aroclor 1254 produced smaller but persistent decreases in offs pring weight without affecting maternal weight or offspring mort ality. Aroclor 1254 and 13 mg /kg of the mi xture produced comparable decreases in maternal and offspring serum T4 levels and comparable alterations to ma ternal thyroid morphology. Aroclor 1254 delayed the righting reflex and ear opening, accele rated eye opening, and reduced grip strength at PNDs 10-14. T he 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 e ffects on early neurodevelopment. This PCB/organochlorine pesticide mi xture affects mortality, growth, thyroid function,

and neurobehavioral devel opment in rodents.155 Buck, G. M., J. E. Vena, et al. ( 2002). "PCB congeners and pesticides and female fecundity, New York State Angler Pros pective Pregnancy Study." Environmental Toxicology and Pharmacology 12 (2): 83-92. Consumption of PCB-c ontaminated sport fish from Lake Ontario has been reported to be associated with dimini shed 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 di aries 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 ch romatography and electron capture for 66 PCB congeners and seven pesticides. Laboratory values were recovery, background and fat corrected prior to natur al log transformation. Using stepwise discriminant analysis, congeners IUPAC #205 and #206 and hexaclorobenzene were significantly and positively asso ciated with increasing TTP when women were categorized as becoming pregnant in the first or first thr ee 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 func tion and embryo development in the porcine model." Biology of Reproduction 67 (1): 80-7.

We evaluated the effects of an environmenta lly relevant mixture of more than 15 organochlorines on the develop ment of pig oocytes and sperm during in vitro fertilization (IVF). Oocytes were cocultur ed with sperm in IVF medium containing increasing concentrations of an organochlori ne mixture, similar to that found in women of highly exposed populations. Ex posure to the or ganochlorine 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 blas tocyst 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 mixtur e 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 imm ediately reduced in a dose-dependent manner by the organochlorines , followed by diminished vi ability 2 h later. From these results, it appears that reduced s perm 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 developmen t, and supports recent concerns that such pollutants harm reproductive heal th in humans and other species.156 Carreno, J., A. Rivas, et al. (2007). "E xposure of young men to organochlorine pesticides in Southern Spai n." Environmental Research 103 (1): 55-61. It has been hypothesized that endocrine disruptors and espec ially synthetic estrogenic environmental contaminants (xenoes trogens) are etiologic factors in the global decrease of sperm count s and other problem s of the male reproductive tract, including cryptorchidi sm, hypospadias, and testicular cancer. This possibility has prompted research into the current and historical incidence of these diseases. The largest area of int ensive greenhouse agriculture in Europe is

near the Mediterranean coast of Southern Spain, where th is 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, met hoxychlor, endosulfans, and DDT and its

metabolites were identified. Detectable conc entrations of p,p'-DDE were found in 96% of serum samples. Among the rema ining DDTs, o,p'-DDD was the most prevalent, detected in 65% of serum samples. Detectable concentrations of

endosulfan I or II or their me tabolites endosulfan-diol, or -sulfate were found in all samples; endosulfan-diol was the most frequently detect ed metabolite (92%) followed by sulfate. Results indicate that men of reprodu ctive age in Southern Spain have been and are exposed to organoc hlorine pesticides. Because many of these chemicals have estrogenic and ant i-androgenic activity, further research is warranted to interpret the male r eproductive health consequences of this

exposure.

Carrizo, D., J. O. Grimalt, et al. (2008). "Pentachlorobenz ene, 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 ess entially result from metabolism of these chlorinated hydrocarbons. In contrast , examination of a rural population of children where the same compounds were pres ent at relatively low levels points to other inputs besides transformation of PeCB and HCB being responsible for

the measured PCP concentrati ons. In both populations, t he results showed that a major proportion of the organochlorine co mpounds present in these children's serum at 4 years of age was incor porated during the lactation period.

Chevrier, J., B. Eskenazi, et al. (2008). "Effects of exposure to polychlorinated biphenyls and organochlorine pesticides on thyroid f unction during pregnancy. " Am J Epidemiol

168 (3): 298-310. In this study, the authors' objec tive was to determine whether serum concentrations of polychlorinated bipheny ls (PCBs), hexachlorobenzene, p,p'- dichlorodiphenyl trichlor oethane (DDT), o,p'-DDT, and p,p'-dichlorodiphenyl dichloroethylene (DDE) are associated with thyroid function during pregnancy. These compounds, as well as thyroid-stim ulating hormone, total thyroxine, and free thyroxine, were measured in seru m samples collected between October157 1999 and October 2000 from 33 4 pregnant women living in the Salinas Valley, California. Data were analyzed by multivar iate linear regression . After adjustment for covariates, seven of the 19 PCB congeners detected in more than 75% of participants and the sum of those c ongeners were negatively associated with free thyroxine concentrations. PCBs 44, 52, and 183 remained significant after

the exclusion of two outliers. Hexachlo robenzene concentrations were negatively associated with both free thyroxin e and total thyroxine. PCB and

hexachlorobenzene concentrations were st rongly correlated, which hampered the authors' ability to identify their independ ent associations with thyroid function. None of the exposures under study were associated with thyroid-stimulating hormone. Results suggest that exposure to PCBs an d/or hexachlorobenzene at background levels may affect thyroid function during pregnancy. These findings are of particular significance, since thyroi d 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 c ontaminants detected in Canadian Arctic human populations." Jour nal of toxicology and envi ronmental health. Part A.

71 (2): 93-108. As part of the program to investigate mi xture effects of envir onmental pollutants, this study describes clinical, biochemica l, and histopathological effects in rats perinatally exposed to a mixture of persistent organochlor ine pollutants and methylmercury that simulates the blood cont aminant 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 mixt ure of organochlorine pollutants (referred to as mixture hereafter) from gestational day (GD) 1 to postnatal day (PND) 23. Positive and vehi cle controls were given Aroclor 1254 (Aroclor hereafter, 15 mg/k g bw) and corn oil (vehicl e), 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 fo r analysis. Gestati onal and lactational exposure of rats to mixture up to 5 mg /kg bw produced adverse effects in the offspring, including growth suppressi on, decreased spleen and thymic weights,

increased serum cholesterol and liver micr osomal enzyme activities, lower liver retinoid levels, and histological changes in the liver, thyroid, and spleen. Histological changes in the liver consist ed of hepatic inflammation, vacuolation, and hypertrophy, while alterations in t he thyroid were characterized by hypertrophy and hyperplasia of follicles. The hepatic and thyroidal effects were mild even at the highest dose. The sp leen showed a dose-dependent atrophy in the lymphoid nodules and peria rteriolar lymphatic shea th regions. Aroclor produced effects similar to those seen in the highest mixture group. In summary, this study demonstrates that exposure to the reconstituted mixt ure at 5 mg/kg bw produced growth suppression, changes in organ weights, and biochemical and histopathological changes in liver, thyr oid, 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 t hat 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. Copel and, et al. (1976). "The effect s of pentachloronitrobenzene, hexachlorobenzene, and relat ed compounds on fetal development." Toxicology and Applied Pharmacology 35 : 239-256.

Dallaire, R., E. Dewailly, et al. (2008). "Effects of prenat al 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 st udies have revealed that prenatal exposure to polychlorinated biphenyls (PCBs) and other organochlorine compounds (OCs) affect neurodevelopmen t during infancy. One of the mechanisms by which PCBs might interfer e with neurodevelopment is a deficit in thyroid hormone (TH) concentrations. OBJECTIVES: We investigated the potential impact of transplacental expo sure to PCBs and hexachlorobenzene (HCB) on TH concentrations in neonates from two remote coastal populations exposed to OCs through the consum ption of seafood products. METHODS: Blood samples were collected at birth from the umbilical cord of neonates from Nunavik (n=410) and the Lower North Shor e of the St. Lawrence River (n=260) (Quebec, Canada) for thyroid parameters [thyroid-stimulating hormone (TSH), free T4 (fT4), total T3 (tT3), and th yroxine-binding glob uline (TBG)] and contaminants analyses. RESULTS: In multiv ariate models, umbilical cord plasma concentrations of PCB 153, the predominant PCB congener, were not associated with TH and TSH levels in both populat ions. 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 c ohort. CONCLUSION: OCs levels were not

associated to a reduction in THs in neonates from our two popula tions. 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 pestic ides in human breast milk and cryptorchidism." Environmental Health Perspectives 114 (7): 1133-8.

INTRODUCTION: Prenatal ex posure to some pesticide s can adversely affect male reproductive health in animals . We investigated a possible human association between maternal exposur e 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 indi vidual pools between 1 and 3 months159 postpartum and analyzed for 27 organochlorine pesticides. RESULTS: Eight organochlorine pesticides were measurabl e in all samples (medians; nanograms per gram lipid) for cases/controls: 1,1-di chloro-2,2-bis(4-chlorophenyl) ethylene (p,p -DDE) : 97.3/83.8; beta-hexachlor ocyclohexane (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) et hane (p,p -DDT) : 4.6/4.0; dieldrin: 4.1/3.1 ; cis-hept achloroepoxide (cis-HE) : 2.5/2.2. Five compounds [octachlorostyrene (OCS); pentachl orobenzene, 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, pentachl oroanisole (PCA), gamma-HCH, 1,1- dichloro-2-(2-chlorophenyl) -2,2(4-chl orophenyl) ethane, tr ans-chlordane, alphaHCH, and o,p -DDE, both concentrations and detection rates were low (26.5- 71.5%). Heptachlor, HCH (lc delta, eps ilon), aldrin, beta-endosulfan and transheptachloroepoxide were detected at neglig ible concentrations and low detection rates and were not analyzed further. Se venteen 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-) ox ychlordane, 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 cryp torchid and healthy boys for individual chemicals. However, combined statisti cal analysis of the eight most abundant persistent pesticides showed that pesticide leve ls 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 ex posure suggests that testicular descent in the fetus may be adversely affected.

den Tonkelaar, E. M., H. G. Ve rschuuren, et al. (1978). "Hex achlorobenzene toxicity in pigs." Toxicology and Applied Pharmacology 43 : 137-145.

Denham, M., L. M. Schell, et al. (2005). "R elationship of lead, mercury, mirex, dichlorodiphenyldichloroethylene, hexachlor obenzene, 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 neur ologic and endocrine effects. These effects have prompted concern about al terations in human reproductive development. Few studies have examined the effects of these toxicants on

human sexual maturation at levels co mmonly 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, dich lorodiphenyldichloroet hylene (p,p'-DDE), hexachlorobenzene (HCB), polychlorinated biphenyls (PCBs), mirex, lead, and mercury. METHODS: This study was c onducted with residents of the Akwesasne160 Mohawk Nation, a sovereign territory t hat spans the St Law rence River and the

boundaries of New York State and On tario 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 mi rex levels exceeding the US Food and Drug Administration recommended tole rance limits for human consumption have been found in local animal specie s. 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 par ticipants' exposure status . Attainment of menses (menarche) was assessed as present or abs ent at the time of the interview. Congener-specific PCB analysis was available, and a ll 16 PCB congeners detected in >50% of the sample were in cluded 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, PC Bs, mirex, lead, and mercury) were entered into the logistic regression model . Age, socioeconomic status (SES), and BMI were tested as potential cofounders an d 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 leve ls were well below the Centers for

Disease Control and Preventi on action limit of 10 micr og/dL, and PCB levels were consistent with a cumulative, cont inuing exposure patte rn. 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 r egression analysis that corrected for age, SES, and other pollu tants (p,p'-DDE, HCB, mirex, and mercury) indicated that, at their respective geomet ric 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 number s 52, 70, 101 [+90], and 187) was associated with a significantly greater probability of having reached menarche (beta = 2.13). Predicted probabilities at diffe rent levels of lead and PC Bs 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 menar che; at the 75th per centile of E-PCB levels, 86% of 12-year-old Mohawk girls were predicted to have reached

menarche. No association was observ ed between mirex, p,p'-DDE, or HCB and menarcheal status. Although BMI was not a significant predictor, we tested BMI161 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 st atus. 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 m enarcheal status. CONCLUSIONS: The analysis of multichemical expos ure among Akwesasne Mohawk Nation adolescent girls suggests that the attain ment of menarche may be sensitive to relatively low levels of lead and ce rtain PCB congeners. This study is distinguished by the ability to test many toxicants simultaneously and thus to

exclude effects from unmeasured but c oexisting exposures. By testing several PCB congener groupings, we were able to determine that specifically a group of potentially estrogenic PCB congeners affe cted 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 te sted suggest that results should be interpreted cautiously. Additional inve stigation 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). "Lev els 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, caus es 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 m ilk 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 m ilk 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 smok ers: b=-282, CI - 467 to -98; for never smokers: b=0.5, CI -149 to 150, p-va lue for interaction: 0.01.

Similar results were observed for head ci rcumference, crow n-heel length, and

SGA. CONCLUSIONS: We saw a m oderate association between HCB and markers of impaired fetal growth among past and current smokers. This finding may be non-causal and due to underlying genet ic 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: levels162 of contamination, influenc ing factors, and infant risk assessment." Environmental

Research 108 (1): 86-93. The concentrations of dichlorodipheny trichloroethane and its metabolites (DDTs), hexachlorobenzene (HCB), hexachlorocycl ohexane 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) wa s used to identify and quantify residue levels on a lipid basis of organochlor ine 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-chlorina ted 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, suggesti ng the influence of such factors on OC burdens in lactating mother s. 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 hi gher than these guidelines.

Fenster, L., B. Eskenazi, et al. (2006). "Asso ciation 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, organochlorin e compounds were widely used as

insecticides in the United States. Therea fter, their use was severely restricted after recognition of their persistence in t he environment, their toxicity in animals, and their potential for endocrine disruption. Although substantial evidence exists for the fetal toxicity of organochlori nes in animals, information on human reproductive effects is conflicting. We investigated whether infants' length of gestation, birth weight, and crown-heel le ngth were associated with maternal serum levels of 11 different organochlorine pesticides: p,p - dichlorodiphenyltrichloroethane (p,p -DDT ), p,p -dichlorodiphe nyldichloroethylene (p,p -DDE), o,p -dichlorodiphenyltrichlo roethane (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 a ssociations 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 ges tational duration associated with any of the other organoc hlorine 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 dur ing 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 circ ulating 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. ME THODS: Birth weight was obtained for 197 singleton infants drawn from the ge neral population born in two cities in

Ukraine in 1993 to 1994. Concentrations of seven organochlorine pesticides (p,p'-DDT, p,p'-DDE, beta-hexachloro cyclohexane, hexachlorobenzene, transnonachlor, oxychlordane, heptachlor epo xide) 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. RE SULTS: The greatest differences wereseen 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 adjustm ent for gestational age. Adjustment for potential confounders made the pattern di sappear. Other chemicals showed no convincing evidence of effects. CONCL USIONS: Prenatal exposure to the chemicals studied, at concentrations curr ently 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. Ph illilps, et al. (1977). "Effe ct of hexachlorobenzene on reproduction in the rat." Archives of Environmental Contam ination and Toxicology 5 (2):

207-216.

Hansen, L. G., R. M. Teske , et al. (1979). "Hexachlorobe nzene and feline reproduction: effectsof ground pork contaminated by dietar y 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, a nd 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 initiat ed during the fetal peri od, and exposure to164 endocrine disruptors, i.e., xenoestrogens , has been of concern. In this investigation we studied the concentra tions of the sum of 38 polychlorinated biphenyls (PCBs), p,p'-dichlorodipheny l-dichloroethylene, hexachlorobenzene (HCB), and chlordanes, in 61 cases with testicular cancer and 58 age-matched controls. Furthermore, case and control mo thers were also a sked 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 th e 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 consis tent 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 Rhes us monkeys." Toxi cology 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 conc entrations of polychlorinated biphenyls, hexachlorobenzenes, and chlordanes in mother s 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, hexachlor obenzene and beta-benzene hexachloride."

Science of the Total Environment 368 (2-3): 557-64. The effects of organochlorines on hum an reproduction have been recently under scrutiny. Some negative effects on anima l reproduction have b een reported. In this study we aimed to evaluate the e ffect of maternal contamination with a certain group of organochlorin es, which are cyclodienes, HCB (hexachlorobenzene) and beta-BHC (bet a-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 prematur ity were taken from health files. Our study did not show any significant negative effect on outcomes such as birth weight, small for gestation age, prev ious miscarriage or still birth, head

circumference or sex ratio. An inc onsistent increase across oxychlordane exposure levels for prematurity was f ound. 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 sm all numbers and may be explained by loss of contaminants through the aborted fetu s. These results suggest that the165 declining contamination levels of thes e chemicals do not impose a threat to human reproduction.

Khera, K. S. (1974). "Ter atogenicity 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 refer ence values of polychlorinated biphenyls (PCBs) and hexachlorobenzene (HCB) in full-term neonates. PATIENTS AND METHODS: Cord blood samples were ta ken from 200 healthy, full-term neonates in 1998. Blood specimens were immediat ely centrifuged, and serum was stored in glass tubes at -20 degrees C up to analysis. Six PCB c ongeners (IUPAC No. 28, 52, 101, 138, 153, and 180) and HCB were determi ned with capillary gas chromatography with electron capture det ection. 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 evaluat ion because of unusually high PCB concentrations. Personal data of the remaining 199 newborns showed 106 male and 93 female neonates. Mean gestati onal 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 micr og/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 upt ake 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: pr eliminary 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 teratogeni c properties. They are chemically very stable and lipophilic and, therefore, a ccumulate in our food-chain. They are prenatally transmitted from mo ther 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 harmf ul 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 immediately166 centrifuged, and serum was stored in gla ss tubes at -20 degrees C until analysis. Three higher chlorinated PCB congener s (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-weig ht, age of the mothers, and smoking behaviour of the parents. In contrast, se rum 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 micr og/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 po llution 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 pol lution 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 Southe rn Spain. OCs were extracted from placenta by solid-liquid technique and purified by preparative liquid chromatography. Gas chromatography/ele ctron-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, endos ulphan-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 mater nal body mass index was significantly associated with higher endos ulphan concentrations in placenta, and greater maternal weight gain was significant ly 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 th is exposure to enhance preventive

measures.

Madeddu, A. and S. Sciacca (2008). "[Biologi cal 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 A ugusta and showed a strong association between the consumption of local fish and the increased risk of children born malformed among women of t he same city, the authors, in collaboration with the judicial authorities, have in itiated a study on the tracki ng 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 r egion not exposed to the same risk of contamination, thereby reinforcing the i dea that some substances from industrial

source found in the environment and in t he body of the mothers of Augusta have been able to contribute to the higher in cidence of congenital malformations and abortions in the examined region, and leading a company petrochemicals to recognize the families of born ma lformed an economic compensation.

Nakashima, Y. and S. Ik egami (2000). "Hexachlorob enzene 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 envir onmental 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 nm ol/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 concen tration ratio in fetuses was 3.4. In pregnant rats on the day before partu rition, the PECB concentrations in organs and fat tissue we re 3 to 4 times higher than those of HCB. After parturition, PECB rapidly disa ppeared 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 t he 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 dec reased gradually (T1/2 = 5.7 d) and PECB decreased rapidly (T1/2 = 2.8 d) during the 15 d a fter birth. These findings

indicate that the PECB/HCB transferr ed 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 relations hip 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 persist ent organic pollutants (POP s) contamination are logical candidates in the investigation of the, as yet, unex plained association between allergic disease and progressive industrialisation. POPs have been detected in human cord blood, placent al 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 st udy was to determine if POPs were168 detectable in maternal blood, cord bl ood, placental tissues, adipose tissue and breast milk samples from randomly select ed Western Australian women (n = 31), where allergic disease is epidemic. Gas chromatography was used to detect polychlorinated biphenyl compounds [PCB s] (as Aroclor 1232, 1254, 1260) and organochlorine (OC) pesticides, including p,p'-DDT, p,p'-DDE, hexachlorobenzene (HCB), lindane, heptachl or epoxide, dieldrin and chlordane. Secondly, we assessed the relationship bet ween POP levels detected in vivo and maternal and neonatal responses (cytokine and lymphoproliferatio n) to allergens and mitogens. RESULTS: Low level POP c ontamination 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 r eported over 20 years ago. There were no consistent relationships between POP leve ls 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 provi des the first evidence (in Australia) since the early 1990's that adipose OC levels have continued to fall. The negligible levels in this randomly select ed group are significantly lower than those previously recorded, suggesting that POP c ontamination (at biologically relevant levels) is not likely to be a major contri buting factor in the increasing rates of allergy in Western Australia. Howeve r, the relationship between Th1 immune

function and OC contamination is consis tent 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 uri nary porphyrin excretion in neonates born to mothers exposed to ai rborne hexachlorobenzene." Environ Health Perspect 110 (2): 205-9.

The existence of a link betw een hexachlorobenzene (HCB) and porphyria cutanea tarda has been known for a long ti me. However, the epidemiologic data on effects on health caused by prenatal exposure have not provided convincing evidence that HCB alters porphyrin metabo lism. Our objectives were to analyze urinary porphyrin excretion and HCB in ma ternal 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 t heir 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 Mo ra 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 mot hers. We obtained 68169 urine specimens of singleton neonates on t he third day after birth to test for urinary porphyrin excretion. We obtai ned 52 fetal cord blood and 56 maternal serum samples for HCB analysis. Total ur inary 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 porphyri n concentration was 37.87 micromol/mol creatinine. Coproporphyrin I and coproporphyrin III we re the major porphyrins excreted. We found no positive relationshi p between urinary por phyrin excretion and HCB levels. However, we observ ed an association between maternal smoking and coproporphyrin excretion. Al though 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). "C ontribution of methylmercury, polychlorinated biphenyls and organochlorine pesticides to the toxicity of a contaminant mixture based on Canadian Arctic population blo od profiles." Toxicology Letters 184 (3): 176-85. Human populations are simultaneously exposed to a variety of anthropogenic contaminants. However, despite extensive literature on animal ex posure to single compounds, data on the toxicity of comp lex mixtures are sca rce. The Northern Contaminant Mixture (NCM) was formula ted to contain the 27 most abundant

contaminants in the same relative proportions found in the blood of Canadian Arctic populations. Sprague-Dawley rat dam s were dosed from the first day of gestation until weaning with methylmerc ury (MeHg), polychlorinated biphenyls (PCBs) or organochlorines pesticides (O Cs) 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 Th yroid Stimulating Hormone (TSH) levels, thyroid gland morphology, brain taurine content and cerebellum and hippocampus protein expression patterns re sulting from such exposures were monitored. Pups' increased mortality ra te and impaired growth observed in the NCM treatment group were attributed to MeHg, while decreased circulating thyroxine levels and pertur bations of thyroid gland morphology were mostly attributable to PCBs. Interestingly, despite comparable reduction in serum thyroxine levels, PCBs and PTU exposur es produced markedly different effects on pup's growth, serum TSH level and brain taurine content. Analysis of cerebellum and hippocampus protein expr ession patterns corroborated previous cerebellum gene expression data, as c ontaminant co-exposure in the NCM significantly masked the effects of individual components on protein twodimensional electrophoresis patterns. I dentification by MALD I-TOF/TOF MS of differentially expressed proteins invo lved 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, hexachl orobenzene, and beta-hexachl orocyclohexane and risk of cryptorchidism in offspring." Environ Res 105 (3): 364-9. Prenatal exposure to environmental endocri ne disrupters has been postulated to cause adverse effects on male reproductive health. Exposure to organochlorine pesticides with anti-an drogenic and estrogenic potency has been shown to

interfere with the sex-horm one-dependent process of testic ular descent in animal

models. We examined the relation betwe en serum levels of the pesticides heptachlor epoxide (HCE), hex achlorobenzene (HCB), and betahexachlorocyclohexane (beta-HCCH) in pr egnant women, and t he occurrence of cryptorchidism in their sons. These th ree pesticides were previously suggested as risk factors for cryptorchidism. In a nested case-control design, we compared

serum levels between mothers of case s (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 suppor t for an association of cryptorchidism with exposure to low levels of HCE or HCB. For beta-HCCH the findings were somewhat suggestive of an associ ation but were inconclusive.

Ribas-Fito, N., M. Sala, et al. (2003). "O rganochlorine compounds and concentrations of thyroid stimulating hormone in newborns." Occupational and Environmental Medicine

60 (4): 301-3.

AIMS: To assess the association betw een prenatal exposure to organochlorine compounds and thyroid status in newborns from an area with high levels of hexachlorobenzene (HCB). METHODS: A tota l 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. Level s 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 withi n the range of normal reference values (<25 mU/l). Dichlorodiphenyl dichlo roethylene (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 associ ated with TSH. CONCLUSIONS: Although this community is highly exposed to HCB, no association was found between this organochlorine and TSH concen trations 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 an imal models, but little information is171 available in humans. OBJECTIVES: Our go al was to study the association of prenatal exposure to HCB with the soci al 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 Calif ornia Preschool Social Competence Scale and the Attention-Deficit Hyperacti vity Disorder (ADHD) were scored by each 4-year-old child's teacher. Organoc hlorine compounds were measured in cord serum. Children's diet and parent al sociodemographic information were obtained through questionnaire. RESULTS: Ch ildren 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 consi dered 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 expe rimental models." Journal of toxicology

and environmental health. Part A. 69 (1-2): 53-76. Long-range transport of persistent organi c compounds by air and ocean currents from industrialized areas resulted in high le vels of these pollutants in food webs

in the Svalbard area. With t he aim to test if organochlor ine (OC) exposure in freeliving polar bears from Svalbard affe cted their plasma steroid hormone concentrations, it was found that polych lorinated biphenyls (PCBs) were associated with increased pr ogesterone levels in females. The sum of pesticides (sigma pesticides) and sigma PCBs cont ributed 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 endocri ne-regulated functions such as reproduction and immunity in a goat m odel 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 ut ero and in the suckling period influenced reproductive functions and bot h PCB 153 and PCB 126 exerted immunomodulatory effects on the offspri ng, whereas acute exposure of adult mice had minor effects on male reproductive function.

Rush, G. F., J. H. Smith, et al. (1983). "P erinatal hexachlorobenzene toxicity in the

mink." Environmental Research 31 : 116-124.

Salmon, M. L., S. G. M adanagopal, et al. (2002). "Effe cts 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 of172 embryonic cells to HCB exposure has been evaluated for several different cytotoxic responses, incl uding 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 Ala ska Arctic natives. Assays were then performed to determine the subsequent e ffects 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 s hort-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 mo dulations 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 Akwesas ne Mohawk youth: a preliminary study." Environmental Toxicology and Pharmacology 18 (2): 91-99. The effects of endocrine disrupting env ironmental 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 Mohaw k 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 hav e contaminated the local ecol. This study examines the relationship betw een measures of thyroid function and endocrine disrupting environmental toxicant s. Both with and without statistical adjustment for other toxicant s, 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 nonlin ear relationships is warranted. Despite

the linear assocns. with TS H and free and total thyroxine, PCBs were not related

to the increased occurrence of these ho rmones outside the clin. normal range for the testing lab.

Schell, L. M., M. V. Gallo, et al. (2008). "R elationship 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 doc umented 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 f unction. 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 t he local environment. We used multiple regression analysis to examine the effe ct of PCB groupings, p,p'-DDE, HCB, lead, and mercury on thyroid hormones after adjusting for sociodemographic covariates and controlling for all other to xicants. RESULTS: Exposure to PCBs affects the thyroid hormone profile in adolescents. T he group of persistent PCBs was positively associated with TSH but in versely related to FT(4). Nonpersistent PCBs were significantly and negatively re lated to FT(4) only. HCB was negatively associated with T(4), and l ead was positively associat ed with T(3) . Breast-fed adolescents had higher levels of persi stent PCBs and p,p'-DDE but not of nonpersistent PCBs or any other toxica nt when compared with non-breast-fed adolescents. Though having lower levels of persistent PCBs and p,p'-DDE, nonbreast-fed adolescents exhibited signifi cant relationships between persistent PCBs and TSH and FT(4), but breast-fed adolescents did not. It appears that

PCBs from breast milk obscure the re lationship between prenatal PCB exposure and thyroid function by adding random va riation in PCB levels. CONCLUSION: Our results demonstrate a reduction in thyr oid function in adolescents in relation

to their current serum levels of PCBs. These observations are consistent with the hypothesis that pre-natal exposure to PC Bs alters thyroid function in a longlasting manner but does not exclude the possibility that post natal exposure is

influential also.

Sims, D. E., A. Singh, et al . (1991). "Alteration of primat e ovary surface epithelium by exposure to hexachlorobenzene: a quantitat ive study." histology and Histopathology 6 : 525-529.

Singh, A., D. Friesen, et al . (1990). "Hexachlorobenzene toxici ty in the monkey ovary. I. ultrastructure induced by low (0.1 mg/k g) dose exposure." Electron microscopy 12 : 282-

283.

Singleton, H., R. F. Mervis, et al. (2002). "Developmental Exposure to Hexachlorobenzene (Hcb) in the Rat Result s in Ectopic and Dysmorphic Cerebellar Purkinje Cells [Abstract]." Society for N euroscience Abstract Viewer and Itinerary

Planner 2002 : Abstract No. Hexachlorobenzene (HCB) is a dioxin-l ike organochlorine co mpound that binds to the aryl hydrocarbon re ceptor (Ah). HCB may impair thyroid metabolism. HCB is widespread in the environment and accumu lates in biological systems. It is transplacentally transferred from mot her 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 st arting two weeks bef ore pregnancy until the pups were weaned. Controls received co rn oil. Pups were sacrificed when 22 days-old and cerebella were stained usi ng the Golgi-Cox method. There were seven male subjects per group. Using coded slides, from each subject seven174 randomly selected Purkinje cells (PCs) were evaluated for soma size and areal

extent of their dendritic arbor. There we re no differences between groups for PCs that had correctly migrated and were located in the Purkinje cell layer. However, there were also a sign ificant number of neurons with Purkinje cell-like characteristics that had improperly migrat ed into the molecular cell layer. These highly dysmorphic PCs had dendritic areas 90% smaller, and somas 75% smaller, than normal. Since thyroid func tion influences critical aspects of cerebellar development, the abnormal mi gration of PCs and their dysmorphic development may reflect the neurotoxic impact of HCB exposure on thyroid

function.

Smink, A., N. Ribas-Fito, et al. (2 008). "Exposure to hex achlorobenzene 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 we ight and body mass index (BMI) in a general population with no local pollution so urces. METHODS: Starting from mid 1997, all mothers presenting for antenatal exposure in Menorca were recruited. Subsequently, 482 children were enrolle d. HCB was measured in cord blood. Weight and height were measured at bi rth 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 (bet a= 0.80 (0.34)) th an children with HCB levels lower than 0.46 ng/mL. No statistically significant associations were found in height. Children in the higher exposur e 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 organochlor ine compounds." Environmental Health Perspectives 116 (10): 1407-10. BACKGROUND: Hexachlorobenzene (HCB ) and other organochlorines induce porphyria cutanea tarda (PCT) in animal st udies. Evidence in humans, however, is contradictory. In neonates and adults from a population historically highly exposed to HCB (Flix, Catalonia, Spai n), no relation with PCT or with porphyrin

excretion was found. OBJECTIVES: We aimed to analyze the association between urinary porphyrin excreti on 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 t he 68 children with porphyrins we measured in cord blood, 52 children 4 years of age provi ded blood to measure organochlorine compounds, hair for methyl mercury, and urine for porphyrin excretion pattern. RESULTS: Quantitat ive porphyrin excretion was within the175 normal values. However, total porphy rins, 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-chloropheny l)ethane (p,p'-DDT), and polychlorinated biphenyl congener 153 (P CB-153). We found no association with methylmercury. When we fitted multip le pollutant models, p,p'-DDE had the strongest association. We found these associ ations 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 to xic effect of the organochlorines, especially for p,p'-DDE, on the hepatic hem e-synthesis pathway that differs from the major effects seen in PCT.

Takser, L., D. Mergler, et al. (2005). "Thy roid hormones in pregnancy in relation to environmental exposure to organochlorin e compounds and mercury." Environmental Health Perspectives 113 (8): 1039-45. Polychlorinated biphenyls (PCBs), chlo rinated pesticides, and mercury are global

environmental contaminants that can di srupt the endocrine system in animals and humans. However, there is little ev idence that they can interfere with endocrine status in pregnant women and neonates at low le vels of exposure. The aim of this study was to examine thyr oid hormone levels during pregnancy and in

cord blood in relation to blood conc entrations of organochlorine compounds (OCs) and Hg in healthy women recr uited during pregnancy. We found a significant negative correlation between mate rnal total triiodothyronine levels and three non-coplanar congeners (PCB-138, PCB-153, and PC B-180), three pesticides (p,p -DDE, cis-nanochlor, and hexachlorobenzene), and inorganic Hg independently, without any ot her changes in thyroid status. No significant relationships were observed between OCs and cord serum thyroid hormones. Cord serum free thyroxin was negativ ely 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). "O besity: Childhood BMI Rises with Prenatal Exposure to

Hexachlorobenzene." Environmen tal 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 chil dhood. The study was the first pros pective look at prenatal exposure of HCB in a general population, sa ys corresponding aut hor 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 Pollutant s, which was signed in 2001. The compound was widely used, starting in 1933, to kill f ungi on crop seeds and in some manufacturing176 processes. Its commercial use in the Unite d 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 re lative 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 e xpectant 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 bi rth and at age 6.5 years. Analysis showed that each doubling in cord bl ood HCB levels was asso ciated 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 overw eight was a statistically si gnificant 1.7 times higher per doubling in cord blood HCB level, and the rela tive 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 corr elation 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 ha logenated compounds or endocrine disruptors,” says Wilfried Karmaus, a prof essor of epidemiology at the Un iversity of South Carolina. In his study of Michigan wome n who ate large quantities of home-caught fish, maternal

levels of DDE did correlate with BMI and we ight in the women’s adult children aged 20 to 50. That study, which relied on historic an alyses of blood samples in which HCB had not been measured, will be publis hed 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 both ers 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 developmen t or the metabolism of fat, but we don’t

know which substance and which mechanism.” Smink cautions that the new study does not s uggest that HCB, or indeed any other organochlorine, is the sole explanation fo r 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 th ink that the proportion of the ongoing obesity epidemic is minimal when it comes to HCB e xposure. However, it is important to reduce prenatal exposure to toxicants like HCB to pr event 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 lo cal pollution sources are located and avoid eating food which has been grown there,” Smink says. “Pregnancy is a really important time for deve lopment,” 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 fe tus you can't decide not to live under these

conditions.”

Torres-Arreola, L., G. Berkowit z, et al. (2003). "Preterm bi rth in relation to maternal organochlorine serum leve ls." Ann Epidemiol 13 (3): 158-62.

PURPOSE: To evaluate the associations of serum levels of p,pacute;-DDE and two other persistent organochlorine pesti cides, 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 lar ge 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 increas ed risk of preterm birth among women in the highest tertile of beta-HCH (adjus ted odds ratio 1.85, 95% CI = 0.94-3.66, p value for test of trend p = 0.08) compar ed 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 c ountries 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 asso ciation between body mass index (BMI) standard deviation score (SDS) and prenatal exposure to hexachlorobenzene, dichlorodiphenyldichloroethylene ( DDE), dioxin-like compounds, and polychlorinated biphenyls (PCBs). METHOD S: In this prospective birth cohort study, we assessed a random sample of mo ther-infant pairs (n = 138) living in Flanders, Belgium, with follow-up until t he children were 3 years of age. We measured body mass index as standard devia tion 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 modi fication by maternal smoking and the child's age. At 1 year, children of sm oking 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 c oncentrations between the 90th and 10th percentiles = 0.13). On t he 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 al l 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 findings178 and to assess possible mechanisms by which these pollutants could alter energy

metabolism.

Villeneuve, D. C., L. G. Panopio, et al. (1974). "Plac ental transfer of hexachlorobenzene

in the rabbit." Environmental Physiology and Biochemistry 4 : 112-115.



### CODE 7 (compilations) References

Agency for Toxic Substances and Disease Regi stry (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 ca re providers; public health statement; health effects; chemical and physical in formation; production, import, use and disposal; potential for human exposure; analytical methods; regulations and advisories; glossary. Health hazards incl ude: immunotoxic effects; embryotoxic effects; porphyria cutanea tarda (skin lesions, arthritis, liver to xicity, 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 fo r Hexachlorobenzene (update)." Agency for Toxic Substances and Disease Registry U.S. Public Health Service 350

.

Bishop, J. B. (2002). Molecular Detecti on 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 d eath, 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 numer ical chromosome damage in sperm and early embryonic cells of rodents. T hese rodent sperm-FISH assays, which provide parallel models of similar sperm-FISH assays in humans, are being used for evaluating the aneugenic and clas togenic 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 spe rm were obtained from NTP Reproductive Assessment by Continuous Breeding (R ACB) studies on hexachlorobenzene and tetrachloroazobenzeneare, and frozen samp les of mouse sperm were obtained179 from an RACB study of AZT/ddI and from micronucleus studies of benzene, diazoaminobenzene, anal ine 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 imm une effects. Oral exposure causes inflammatory skin and lung lesions, enl arged spleen and lymph nodes (LN), and elevated humoral responses. This review describes recent expts. that were performed to elucidate the mechani sms underlying these adverse immune

effects. The metabolites tetrachlor ohydroquinone and tetr achlorobenzoquinone are capable of generating neoantigen-specif ic T-cells in the mouse reporter antigen popliteal lymph node a ssay with 2,4,6-trinitrophenyl- Ficoll. Addnl. expts.

in BN rats have shown that T-cells ar e involved in the development of HCBinduced skin lesions, the increase in aur icular LN wt., lung eosinophilia, and humoral responses. However, splenomegal y and macrophage infiltration in the spleen and lung occur independent of T-cell s. Remarkably, HCB does not induce T-cell sensitization in BN rats, suggesting that T-cells are activated nonspecifically, for example by macrophage s. Transcriptome profiles obtained after subchronic HCB exposure to BN rats reveal that HCB induces a systemic inflammatory response in which seve ral innate immune cells, such as macrophages, and pro-inflammatory cytoki nes are involved. Addnl. expts. have shown that macrophages are implicated in HCB-induced skin lesions, in particular in the aggravation of skin effe cts. Also, HCB-induced lung eosinophilia and elevation of anti-ssDNA IgM ant ibodies 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 Toxa phene." 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 pr oduce adverse health effects following a lifetime exposure, based on health consi derations. 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 mi ce; hexachlorobenzene, 0.03 ppb, rats; 1, 1, 2, 2-tetrachloroethane, 0.1 ppb, mi ce; and toxaphene, 0. 03 ppb, mice. PHGs based on non-cancer endpoints are: Barium, 2000 ppb, absence of180 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, unc ertainty factors, and water consumption

intake. These PHGs were finalized S eptember 2003 after extensive periods for scientific peer review and public input.

Huijbregts, M. A., L. J. Rombouts, et al. (2005). "Hum an-toxicological effect and damage factors of carcinogenic and noncarci nogenic chemicals fo r life cycle impact assessment." Integr Environ Assess Manag 1 (3): 181-244. Chemical fate, effect, and damage shoul d be accounted for in the analysis of human health impacts by toxi c 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 factor s are expressed as disabi lity-adjusted life years (DALYs). Human effect factors contai n a disease-specific and a substancespecific component. The disease-specif ic component depends on the probability

of disease occurrence and the distribut ion of sensitivities in the human population. The substance-specific compone nt, equal to the inverse of the ED50, represents the toxic poten cy of a substance. The new method has been applied to calculate combined human damage and e ffect 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 carc inogenic effects and a factor of 125 for noncarcinogenic effects. The interspecie s conversion factor , the (non)cancer effect conversion factor, and the average noncancer damage fa ctor 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 envir onmental levels of polychlorinated biphenyls and certain organochlor ine pesticides--hexachlorobenzene, dichlorodiphenyl trichlor oethane and its primary metabo lite, dichlorodiphenyl dichloroethene--are generally on the dec line, early-life exposures to these prevalent contaminants continue. The re view will describe cu rrent understanding of the potential neurodevelopmental c onsequences of low-level exposures to

these contaminants. RECENT FINDINGS: Animal models suggest that early-life exposures to polychlorinated biphenyls, dichlorodiphenyl

trichloroethane/dichlorodi phenyl dichloroethene or hexachlorobenzene are associated with decreased cognitive or behav ioral function in later development. Despite almost 30 years of research, however, results of human studies are inconsistent regarding the nature of t he observed effects and their persistence over time. Overall, epidemiologic studi es support modest associations of primarily prenatal polychl orinated biphenyl exposures with differences in181 neuromotor development, decrements in cognition and behavioral deficits, particularly regarding attent ion and impulse control. There are limited published human data regarding potentia l neurodevelopmental toxi cities of early-life exposures to dichlorodiphenyl trichlor oethane/dichlorodipheny l dichloroethene and hexachlorobenzene. SUMMARY: Exposu res to polychlorinated biphenyls, dichlorodiphenyl trichloroethane/di chlorodiphenyl dichloroethene and hexachlorobenzene are likely detrimental to neurodevelopment. Effective control of exposure is complicated by vari able exposure sources and variable contaminant levels in food, particularly fi sh, 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). "Neuroc hemical targets and behavioral effects of organohalogen compounds: an updat e." Crit Rev Toxicol 36 (3): 253-89. Organohalogen compounds (OHCs) have been used and still are used extensively as pesticides, flame retar dants, hydraulic fluids, and in other industrial applications. These compounds are stable, most of ten lipophilic, and may therefore easily biomagnify. Today t hese 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 t he polychlorinated biphenyls (PCBs) and the pesticide dichlorodiphenyl trichl oroethane (DDT) were detected in the

environment. In the 1970s it was discove red that PCBs and some chlorinated pesticides, such as lindane, have neurot oxic potentials after both acute and chronic exposure. Although the use of PCBs, DDT, and other halogenated pesticides has been reduced, and environment al levels of these compounds are slowly diminishing, otherhalogenated compounds with pot ential of toxic effects are being found in the environment. T hese include the brominated flame retardants, chlorinated paraffins (PCA s), and perfluorinated compounds, whose levels are increasing. It is now es tablished that several OHCs have neurobehavioral effects, indicating adverse effects on the central nervous system (CNS). For instance, several repo rts 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 t he 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 ex posure: widespread toxicant produces pervasive effects." Environ Health Perspect 112 (7): A416.

Reed, L., V. Buchner, et al. (2007). "Env ironmental toxicology and health effects

associated with hexachlorobenzene exposure." Rev Environ Health 22 (3): 213-43.182 The synthetic industrial chemical hexac hlorobenzene (HCB) is a white crystalline solid compound. The substance is a bi oaccumulative, persistent, and toxic pollutant. Historically HCB was commonl y used as a pesticide and fungicide. Although HCB production and use has ceas ed in many countries, the compound is still generated inadvertently, as a bypr oduct and/or impurity in the manufacture of various chlorinated compounds, and released into the environment. Hexachlorobenzene is ubiqu itous in air, water, soil, and biological matrices, as well as in major environmental compartmen ts. Exposure to this substance is a public health concern because of its asso ciation with a wide range of adverse health effects. The International Agency for Research on Cancer and the United

States Environmental Protection A gency classify HCB as a probable human carcinogen. Although globally the consumpt ion of HCB-contaminated food is the principal source of environm ental exposure, exposure c an 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 syst emic impairment (thyroid, liver, bone, skin), as well as damage to the kidneys and blood cells and the immune, endocrine, developmental, and nervous system s. In this review, we discuss the sources of HCB and the pot ential for human exposure, as well as systemic, carcinogenic, and teratogenic health effects.

Sjostrom, M., A. Kolm an, et al. (2008). "Est imation of human blood LC50 values for use in modeling of in vitro-in vivo data of t he ACuteTox project." Toxicology in Vitro 22 (5):

1405-11. The main aim of the ACuteTox projec t, under EU 6th Framework programme, is to investigate whether animal toxicity te sts 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 in vitro-invivo modeling, by using statistical correlation between invitr o IC50 molar values (the 50% inhibitory concentration for the endpoints measured) and human blood molar concentrations LC50 (50% lethal conc entrations). The LC50 values were

calculated from time-related sub-let hal and lethal blood concentrations determined from human acute poisoni ng cases. The 3T3 standard NRU assay (3T3 NRU) was chosen, among the various basal cytotoxicity assays, applied in the ACuteTox project, to dem onstrate the applicability of the IC50/LC50 values for invitro-invivo modeling. Linearregression 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 ev aluation 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 addi tional organ-specific and biokinetic tests

are needed in order to im prove the predictability.183 Tanabe, K. and T. Matsumoto (2002). "Predi ction of carcinogenicity of chlorinecontaining organic compounds by neural networ k." Journal of Computer Chemistry, Japan 1 (1): 23-28. A neural network was applied to the predict ion of the carcinogenicity of 41 kinds of org. chlorine- contg. compds. Se ven kinds of structural and quantum-chem. descriptors: mol. wt., log P. Gibbs free energy, ionization potential, LUMO energy, HOMO-LUMO energy gap, and C onnolly vol. were detd. These descriptors were entered into the input la yer of a three-layered neural network, and carcinogenicity data from the NTP dat abase were entered into the output layer as teaching data. The network wa s 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. I dentification of chems. that have the potential to cause injury to the immune syst em 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 em ployed in rodents in which the first tier is a general screen fo r (immuno)toxicity including enhanced histopathol. of lymphoid organs and the sec ond tier consists of more specific immune function studies including host re sistance tests or mechanistic studies. Studies with the potent i mmunotoxicants TCDD, TBTO, HCB, azathioprine, and cyclosporin A are discussed, which prov ide data correlating histopathol. with immune function changes. This is followed by a discussion of the outcomes of enhanced histopathol. investigation in t he 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 conclu sions 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. pathologist s 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 an d home preparation.

AU - ABOU-ARAB A AK.

BIOSIS COPYRIGHT: BIOL ABS. Monitori ng of pesticide residues in Egyptian tomatoes and its products was studied. The average contents of HCB, lindane, dieldrin, heptachlor epoxide and DDT derivatives were det ected at levels 0.009, 0.003, 0.006, 0.008 and 0.083 mg/kg, respecti vely. On the other hand, the levels of dimethoate, profenofos and piri miphos-methyl were 0.461, 0.206 and 0.114 mg/kg, respectively. In ketchup and paste samples, most organochlorine and184 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 substanc es to the Great Lakes: IADN results to

1996." /u0103

. The primary objective of th is document is to report bienn ial loadings estimates for the atmospheric deposition of toxic subst ances to the Great Lakes for 1995-96. Three deposition processes ar e considered: Wet deposition by precipitation, dry particle deposition by sedi mentation, and net diffusive gas exchange that combines the effects of absorption from ai r to water with volati lization from water to air. The estimates presented are based on measurements taken largely at the Integrated Atmospheric Depos ition Network master stat ions, of which there is one per lake. Toxic substances measur ed include dieldrin, DDT, polychlorinated biphenyls, polycyclic aromatic hydrocar bons, lead, arsenic, hexachlorobenzene, and chlordane. Discussion of the findings considers three fundamental issues: The magnitude of the loadings, the m anner in which each loading component contributes to the total, and the variat ion or trends in the loadings across the Great Lakes Basin and over many years.

(2000). "C-56 Monitoring Data from the Michi gan State Office of Toxic Materials Control with Cover Letter Dated 010981." EPA/OTS; Doc #40-8149021

.

(2000). "Contaminants in water and precipitat ion from the Canadia n 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 substanc es 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, polychlori nated biphenyls, and polycyclic aromatic hydrocarbons. Ambient concentrations are also compared to water quality objectives.

(2000). "Determination of leve l of quantification for meas uring 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. En vironment Canada has included hexachlorobenzene (HCB) and polychlori nated dibenzo-p-dioxins & dibenzofurans (PCDD/PCDF) in its list of toxic substances that are persistent, bioaccumulative, and anthropogenic. Virtual elim ination of substances in this list

from the environment is t he main objective of the dept.'s Toxic Substance Management Policy. The level of quantificati on (LoQ) prescribed in this report will

be used as a baseline to assist in establis hing a virtual elimin ation target for HCB and PCDD/PCDF. The LoQ is defined as the lowest concentration of a target185 compound that can be quantifi ed confidently. The report summarizes the study design & experiments for determining t he 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 rep licate analyses are presented suggesting
an estimated LoQ for each toxic substance.

(2000). "Final Report on the To xic Substances Survey of Lakes Michigan, Superior, and Tributary Streams." EPA/OTS; Doc #40-8390045

.

(2000). "Letter to Usepa Concerning the Enclos ed Document for the Initial List of 100 Chemicals Grouped in 4 Sets of 25 for Evaluat ion in Atsdr/Epa Toxicological Profiles with Attachment." EPA/OTS; Doc #110-871004

.

(2002). "Toxicological Profile for Hexachlorobenzene (Sep tember 2002)."

See also PB97-121065.

Abou-Arab, A. A. K., M. S. Kawther, et al. (1999). "Q uantity estimation of some contaminants in commonly used medicinal plants in the Egyp tian market." Food Chemistry 67 (4): 357-363.

BIOSIS COPYRIGHT: BIOL ABS. Pestici de residues, heavy metal contents and

aflatoxins were estimated in five medi cinal plants frequently used by both infants and adults (peppermint, chamomile, anise, caraway and tilio). Samples were

collected from different sources in t he 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. Chlorpyr ifos, parathion, diazinon and endosulfan

were not detectable in mo st of the samples under in vestigation. The results

indicated that some of the collect ed samples contained some types of organophosphorus and orgnochlor ine pesticide residues, wit hin the limits of The Egyptian Organization for Standardization and Quality Control (EOS) maximum limits for pesticide residues on medi cinal 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 s howed that the most frequently isolated fungi were penicillium sp., A. niger and Fusa rium sp. Nevertheless, the finding of natural mycotoxin contaminati on was negative in all samples.

Adeyeye, A. and O. Osibanjo (1999). "Resi dues of organochlorine pesticides in fruits, vegetables and tubers from Nigerian market s." 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, v egetables 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 DDT186 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 organophosphat e pesticide residues in fruits, vegetables and

sediments. The concentrated solvent extract was sealed in a polymeric membrane tube, dialysed in cyclohexane an d the solvent repl aced with hexane. The organophosphates were analysed on a s pecific thermionic detector without further clean-up. For the organochlori ne 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 detec tion 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 m ug/kg when the final volume was

made to 0.5 mL. At the detection lim its the method produced a very high

coefficient of variation for both or ganochlorine and organophosph ate 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 climat ology pollution air pollution organic compounds environment persistent organic pollutants pollutant pcbs aldrin chlordane pcdds pcdf s ddt dieldrin endrin heptachlor hexabromobiphenyl hexachlorobenzene mirex toxaphene

Angulo, R., I. Costabeber, et al. (1999). "Or ganochlorinated residue in milk processed with L. acidophilus." Acta Alimentaria 36 : 51-53.
BIOSIS COPYRIGHT: BIOL ABS. Current ly the nourishment and the health are intimately related, therefore appears a new fermented or added milk generation of live microorganisms that produce benef icial 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 effe cts 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 obtai n added milk of live microorganisms that produce effects mo re sound and healthy with respect to environmental pollutants as orga nochlorine 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 environm ent. Three categories of indicators are presented: Indicators of health effe cts, which relate human exposure to

environmental contaminants to measurable effects on health or health risk; indicators of exposure, either contami nant 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 ket one that functions as both a denaturant and solvent in cosmetic products. One method of produc tion is acetone condensation, followed by catalytic hydrogenation. MIBK may cont ain the following impurities: dimethyl heptane, methyl isobutyl carbinol, mesi tyloxide, acetic acid, 4-methyl-2- hydroxypentane, and methyl n-butyl ke tone. According to the Chemical Manufacturers Association, MIBK produc ers 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 200 0 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 lis ted for use as a denaturant of alcohol

is 4.0%. MIBK is also listed in the Na tional Formulary as an alcohol denaturant that is used as an excipient for drugs. The metabolites, 4-hydroxy-4-methyl-2- pentanone (MIBK oxidation produ ct) and 4-methyl-2-pentanol (4-MPOL) (MIBK reduction product) were detected in bl ood samples from guinea pigs injected intraperitoneally with MIBK. Values fo r 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, ar e expected either to be conjugated with sulfate or gl ucuronic 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 det ected 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 exposu re. 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 we re the principal MIBK metabolites in mice dosed intraperitoneally with MI BK. The percutaneous absorption of MIBK was demonstrated in 'a study involvin g guinea pigs. A maximum percutaneous uptake rate of 1.1 umol/min/cm2 was obser ved at 10 to 45 min after the initiation of exposure. Both gross and microsc opic evidence of lung damage have been reported in acute inhalation toxicity studi es in which mice and guinea pigs were exposed to MIBK. Increased pulmonary ar terial pressure was noted in acute188 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 ra ts. 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 tw o rabbits for 10 h either by flooding the test site or placement of a cott on pad impregnated with t he 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 valu es for MIBK have been reported: 1.14 ml/kg (rats), 0.59 f 0.23 g/kg (mi ce), and 0.919 ml/kg (guinea pigs). Intraperitoneal injection of MIBK was a ssociated with pulmonary vascular effects in cats. Increased pulmonary arterial pres sure, but not bronchoconstriction, was induced in cats dosed intravenously with MIBK. In short-term exposure experiments, male and female Fische r-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 conc entration. Increases in liver and kidney weight were also observed at these c oncentrations. 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 conti nuously (inhalation) to 100 or 200 ppm MIBK over a period of 2 weeks. Incr eased kidney weight and microscopic evidence of toxic nephrosis of the proxim al tubules were reported only for rats, and this finding was noted at both concent rations of exposure. Increased liver weight (rats) was also noted after ex posure 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 da ys per week (6 h/day) for 4 weeks. No

"clear-cut" test substance-related abnorma lities were noted at gross necropsy. No evidence of gross pathologic effects wa s 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 st udy, seven applications of undiluted MIBK (3 ml/kg each, 5 to 12 h) were made to the shaved ski n of two rabbits over a period of 15 to 21 days. Local skin changes consisted of polymorphonuclear infiltration in the upper dermis. No system ic 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 concent rations ranging from 50 to 1000 ppm 5 days per week (6 h/day) for 90 days. In creased liver weight was noted following exposure to 1000 ppm; however, hepatic le sions 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 not189 observed at gross or microscopic exami nation. Increased liver and kidney weight

was observed in male Wistar albino rats exposed to 410 mg/m3 MIBK for 90 days. At microscopic examination, hya line 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 durati on), gross examination revealed no

differences in tissues examined betw een test dogs and monkeys and controls. Liver function test results (dogs only) also indicated no differences between test and control dogs. Nephrotoxicity and increa sed 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 dai ly 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 drinki ng water) for 120 days. In a subchronic dermal toxicity study, MIBK (in sunflower o il) 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 fo llicles 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. Ho wever, preexposure of rats to MIBK

caused a dose-related increase in DCB-ind uced GLDH activity. In this study, the mitochondrial enzyme, GLDH was assessed in serum as, a quantitative sign of hepatic necrosis. In other studies (oral dosi ng), the hepatotoxicity of chloroform in Sprague-Dawley rats was enhanced after the administration of MIBK or its major metabolites, 4-MPOL and 4-hydroxymethy l isobutyl ketone (minimally effective dose of each = 5 mmol/kg), and the hepatot oxicity 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, re duced mitotic activity of these cells, and an increase in the number of hepatocyt es with pathology. Neither histologic evidence of liver damage nor lipid deposit ion 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 hepatot oxicity of 1,2- dichlorobenzene, chloroform, hexachlorobenzene, and carbon tetrachloride. Neuropathological changes in the most distal portions of t he tibial and ulnar nerves were observed in young adult rats ex-posed (inhalati on) to 1500 ppm MIBK for up to 5 months. The neuropathological changes observed ma y have been related to the presence of 3% methyl n-butyl ketone in the comme rcial grade of MIBK that was tested. No differences in the performance of sc hedule-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 subst ance-related changes were not ed. In a 7-day study in190 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 ma ximum motor-fiber conduction velocity

in the tail nerve. MIBK did not induce peripheral neuropathy in groups of Sprague-Dawley albino rats injected intraper itoneally 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 emulsi on) 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; neurotoxic ity 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 y ear. Tissue samples from the brainstem, nerves, and muscles were examined at necr opsy. The test substance (98% pure) contained 0.9% methyl n-butyl ket one and trace amounts of 4-methyl-2- hydroxypentane. In another study, MIBK c ontaining 0.9% methyl n-butyl ketone was injected subcutaneously (150 mg) into ca ts 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 fr om 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 reacti ons ranging from slight to moderate skin irritation in rabbits and slight ski n irritation in guinea pigs. Repeated applications (seven) of undiluted MIBK overa 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 puti da) was 275 mg/L in a 16-h study. MIBK was not mutagenic in the Ames test (Salm onella typhimurium strains) or in the mitotic gene conversion assay (Saccharom yces cerevisiae strain) with or without metabolic activation. Mammalian mutagenici ty test results (with or without metabolic activation) for MIBK in the follo wing assays were also negative: mouse lymphoma, unscheduled DNA synthesis, mi cronucleus, cell transformation, and chromosome damage. MIBK is among t he chemicals that have been approved by the NTP for testing in a toxicology/c arcinogenesis study. MIBK did not induce any treatment-related increases in embryo toxicity or fetal malformations in pregnant Fischer 344 rats or CD-1 mice t hat inhaled MIBK at concentrations of 300, 1000, or 3000 ppm. There was evidenc e of treatment-related maternal toxicity only at the highest concentrati on tested. In another study, MIBK was applied to the skin (lower 2/3 of tail) of an unspecified number of male white rats191 daily (4 h/day) at doses of 300 or 600 mg/kg for four months. Changes in the

testes included a reduction in the numberof spermatocytes, spermatids, and spermatozoa. Blood and breath sample s 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 bl ood 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 fo llowing exposure to several volatile organic solvents during spray painting: brai n, liver, lung, vitreous fluid, kidney,

and blood. The threshold for MIBK-induc ed irritation of the lungs of human subjects was 0.03 to 0.1 mg/L after 1 mi n of respiration. Ocular irritation was noted in 12 volunteers exposed to 200 ppm MIBK (inhalation) for 15 min. Nasal, ocular, and throat irrita tion were experienced by no more than four of six volunteers subjected to six 20-min exposures (inhalatio n) 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 sym ptoms reported by three of the eight volunteer s ex-posed to MIBK at concentrations up to 48.8 ppm during light physical exercise for 2 h. Ocul ar 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 mi n and 80 ppm for the remainder of the day. Slightly enlarged livers and nonspecif ic 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 s ubjects tested. In another st udy, the potential narcotic impact of MIBK on CNS function was eval uated 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 r eport, 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 indi cated 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 re cent 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 ingredien t, based on published data indicating that MnBK (methyl n-butyl ketone, a known neurot oxin) is present as an impurity in MIBK at concentrations-as high as 3.0%. Ac-cording to the Chemical Manufacturers Association, MIBK pr oducers indicated in 1999 that MnBK is

either not found in MIBK or is found in tr ace amounts (typically 0.01% to 0.06% and al-ways less than 0.1 %). After consi dering the new impurities data, data192 indicating that the only repor ted 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 fl uid would not be likely under normal use conditions, the Panel agreed that MIBK c ould be used safely as a solvent in nail polish removers in a controlled applicat ion system. However, given the known

neurotoxic effects of Mn BK, the Panel stressed t he importance of continued

efforts to limit the concentration of this impurity in MIBK. Furthermore, the Panel stressed the importance of avoiding i nhalation exposure to MIBK, based on evidence of lung, kidney, or liver da mage 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 th is 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 es tablished regulations, the Panel assumes that cosmetic product fo rmulators 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 agr eed 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 Ex pert 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 environ ment. Owing to the large number of chemicals in use and the paucit y 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 eval uate the performance of three multimedia environmental fate models (spatially- and n on-spatially-explic it) at a European

scale. The assessment was conducted for f our polycyclic aromat ic 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 exerci se as predicted concentrations were typically within a factor of 3 of the median observed concentrations. Furthermore, there was good correspondence between predict ions and observations in regions

that had elevated median observed concentr ations for both sp atially-explicit models. On the other hand, all three m odels consistently underestimated median

observed concentrations in sediment and soil by 1-3 orde rs of magnitude.193 Although regions with elevated medi an observed concentrations in these environmental media were broadly identifi ed by the spatially-explicit models, the magnitude of the discrepancy betw een predicted and median observed

concentrations is of concern in the c ontext of chemical risk assessment. These

results were discussed in terms of fa ctors influencing model performance such as the steady-state assumption, ina ccuracies 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-sol uble compounds-hexachlor obenzene 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- effe ct levels and allowable daily intakes from reproduction data encom passes exposure of the dam to the test xenobiotic prior to pregnancy, during gestation and duri ng lactation. The fetus/infant can be exposed to the xenobiotic as well as t he dam's metabolic products of the test xenobiotic during gestation and la ctation. 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 it s 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 approxim ately 2 weeks after weaning their

first litter to a second untreated male. Die tary 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 premat ing period. There were no apparent toxicological effects regarding the dam nor were any of the reproduction parameters (feed consum ption, dam weight, litter si ze, pup weight, external anomalies and day 4 viability index) signific antly different from control values. Following impregnation, the body weight of the dam increased appreciably during gestation, but its feed consumption increas ed only slightly. During lactation, the dam's feed consumption increased mark edly while its body weight increased slightly. Consequently, when dams received t he xenobiotic in their diet they consumed slightly less xenobiotic per uni t of body weight during gestation when compared to the gavaged dams, whereas the situation was dramatically reversed during lactation. While the greater cons umption of xenobiot ic 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 generati ons, there was no evidence of any differences between the two litters when each sampling date was assessed separately, except for the day 4-HCB re sults 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 additi on, the amount of HCB, PCBs and

fat in the neonates' stomachs decreas ed during lactation, as the pups age increased (P</=0.035). These prelimi nary 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 cu rrent knowledge about transformation rates and products of pesticides in the at mosphere is reviewed. Reactive species

and their concentrations in the atmos phere are presented. Reactions of pesticides with these species (including photo lysis) in the gas and the particulate phase are evaluated from available ex perimental data. The potential of estimation methods is discussed. Experimental techniques for laboratory and

outdoor measurements are reviewed. Fi nally, an estimation is made of uncertainties in atmospheric lifetimes due to chemical or physical reactions. It is

concluded that the most im portant transformation of pesticides in the atmosphere is due to reaction with OH radicals. Veryfew experimental dat a for pesticides are available though. The levels of uncertainty in OH radical concentrations are acceptable, however, for a proper estimati on of atmospheric removal rates due to

reactions with OH radicals of thos e pesticides for which experimental transformation rates (of hom ologues) 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 pollutant s in the atmosphere and es tablish the long-range atmospheric transport of organic pollu tants to remote marine areas.

Hexachlorobenzene and hexac hlorocyclohexane isomer s are present in the remote marine atmosphere. Polychlorobiphe nyls, total DDT, dieldrin, chlordane, and two phthalate ester plasticizers were also found in the samples. The concentrations of pollutants in the atmo sphere remote from continental sources are good measures of the minimum concent rations of air pollutants on Earth.

Atuma, S. S. and M. Aune (1999). "Method for the dete rmination 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 re search article human pcb congeners determination toxin polychlorinated bi phenyl blood serum chlorinated pesticides pesticide organochlorine compounds xenobi otic toxin determination technique toxicology methodology blood and lym phatics validity toxicology method reproducibility development sweden europe195 Bainy, A. C., B. R. Woodin, et al. (1999). "Elevated levels of multiple cytochrome P450 forms in tilapia from Billings Reservoi r-Sao Paulo, Brazil." Aquatic Toxicology 44 (4):

289-305. BIOSIS COPYRIGHT: BIOL ABS. Cytochro me P4501A (CYP1A) levels in tissues of fish inhabiting polluted areas have been used extensively in biomonitoring studies in Europe and North America. Ho wever, little informa tion 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 CYP3 A-like proteins, as well as rates of alkoxy-resorufin-O-dealkylases (ARODs ) with methoxy-, et hoxy-, pentoxy- and benzyloxyresorufin substrates, were anal yzed in liver and kidney microsomes from tilapia (Oreochromis n iloticus) from a reference site (Estacao de Piscicultura de Pindamonhangaba, Sao Paulo) and a polluted site (Billings Reservoir, Sao Paulo, Brazil). Levels of total micros omal 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 at mospheric 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. Atmos pheric fate of pesticides and their possible effects in ecosystems bey ond the immediate surrounding of the application site are not actively cons idered in currently used regulatory risk

assessment schemes. Concern with re spect to atmospheric transport and subsequent deposition of pesticides in non-ta rget areas is however growing. In

this article the results of discussions on the possibilities of implementing atmospheric fate in regulatory risk assessm ent are presented. It is concluded that implementing atmospheric fate in r egulatory 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 reco mmended that the risk assessment scheme should follow a tiered approach. Thefirst ti er should be entered only if the existing regulatory risk assessment procedure, in cluding a local PEC:PNEC calculation, has been passed and involves a test for the pesticide's total atmospheric emission potential, i. e. its potentia l for becoming airborne during and after application. The second tier, which is only entered if the tota l emission potential is higher than a certain trigger value, should consist of a PEC:PNEC calculation of regional off-site areas (10-50 km) (t ier 2A). If the pesticide's atmospheric transport potential is expected to exce ed 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-re gulated pollutants in North Sea produced water discharges." Environ Toxicol Chem : 1.196 Produced water collected from the Un ited 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 us ing gas chromatography coupled to mass spectrometry (GC-MS) in a numberof 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 occurr ence in produced wate r 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, decachlorobi phenyl and octachlorodibenzofuran.

Balasanmugam, K., S. K. Visw anadham, 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 ioni zation" leads to ions characteristic of the analyte, owing to ion-molecule r eactions between the "reagent" ion and the neutral analyte in the laser-generated plum e. Polycyclic aromatic hydrocarbons show formation of an ion corresponding to (M + O - H)(-) in their negative-ion laser mass spectra when mixed with co mpounds such as sym-trinitrobenzene, sodium nitrate and sodium peroxide. NO(-)(2), O(-), and O(-)(2) serve as "reagent" ions in these compounds. Formati on 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. Sw eetman, et al. (2005). "Hex achlorobenzene 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 source s in maintaining ambient levels,

and its ultimate sinks in the environm ent. Global production exceeded 100,000 tonnes and primary emissions to atmosphere probably peaked in the 1970s.

There has been a consistent downward tr end 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 lo cation, but the aver age half-life from all the studies is approximat ely 9 years. Estimates are made of the contemporary burden in the environment; these r ange between 10,000 and 26,000 tonnes and197 are dominated by the loadings in treat ed and background soils, sediments and

oceans. Estimates of the trends of HCB em issions 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 woul d have made it a significant source of HCB to the env ironment. Whilst the amount of HCB being emitted from contemporary soil is much lower, only a sma ll 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 Ne w Zealand populati on." Chemosphere 54 (10): 1431-

43. Concentrations of polychlorinated dibenz o-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), polychlorinated biphenyls (PCBs), and organochlorine pesticides were measured in the seru m of a sample of the New Zealand population aged 15 years and older. This was the first study to obtain representative measures of PCDDs, P CDFs 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 ar ea of residence, ethnicity, age, and sex. Of the 80 possible strata, sufficient serum fo r chemical analysis was available for 60, to which 1,834 individual samples c ontributed. 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 st rata. 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 bet ween the sexes, or between people of Maori (the indigenous peopl e of New Zealand) and non-Maori ethnicity.

Concentrations of PCDDs and PCDFs t ended to increase in a North-South direction, possibly reflecting greater le vels of industrialization and population concentration, and concentrati ons of the pesticide produc ts were highest in the South, possibly reflecting historical use patterns. Results were consistent with a recent study of concentrations of thes e compounds in the milk of first-time

mothers.

Behrooz, R. D., A. Esmaili-Sari, et al. (2009). "Organochlorine pesticide and polychlorinated biphenyl in feat hers of resident and migratory bi rds 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-hexac hlorocyclohexane (HCH) isomers, together with polychlorinated biphenyl (P CB) 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 s outhwest of Iran (Khuzestan, coast of the198 Persian Gulf) and kept in museum colle ctions. 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 t hat trophic level, feeding strategy, and taxonomic group are influencing factors for the OC concentrations in bird

feathers. An estimate of the risk associ ated suggests that levels of OCPs and

PCBs were lower or close to the thres hold 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 env ironmental health. Part A. 65 (2): 165-82. The consumption of fish and sea ma mmals can be an impor tant source of exposure to organochlorine compounds (O Cs) and heavy metals in populations relying on seafood for subsistence. Expos ure to these substances, especially during the prenatal period, has been shown to induce immunotoxic effects in mammals. Immunological status was asse ssed 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 ne wborns 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 func tional responses of the main cellular subsets T, B, and NK (nat ural killer) cells. Concentrations of polychlorinated biphenyls (PCBs) and mercury were res pectively three- and twofold higher, significantly greater, in the subsistence fishing group than in the reference group. Compared to the reference group, t he subsistence fishing group showed significant decreases in the proportion of the naive helper T-cell subset CD4+CD45RA, T-cell prolif eration following an in vitr o 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 merc ury and PCBs, while T-cell clonal expansion was negatively associated wit h PCBs and p,p'-DDE. Mercury was inversely correlated to plasma IgM. Data sh ow that subtle functional alterations of the developing human immune system may resu lt from in utero exposure to OCs and mercury. Epidemiological studies ar e 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 t he Risk Society." J Environ Manage 90 (4): 1655-62. Key concepts of Risk Society as elabor ated by Ulrich Beck and others (Beck, U., 1992 (trans. Mark Ritter). T he Risk Society. Sage Publications, London. Beck, U., 1995, Ecological Politics in the Age of Ri sk. Polity Press, Cambridge. Beck, U.,199 1999, World Risk Society. Polity Press, Cambridge. Giddens, A., 1994, Beyond Left and Right. Polity Press, Oxford. Be ck, U., Giddens, A. and Lash, S., 1994, Reflexive Modernisation: Politics, Tradi tion and Aesthetics in the Modern Social Order. Stanford University Press, Stanfor d. Beck, U., Bonss, W. and Lau, C., 2003, Theory, Culture & So ciety 2003, Sage, London, 20 (2), pp. 1-33.) are illuminated though a case study of managed environmental risk, namely the hexachlorobenzene (HCB) controversy at Bo tany, a southeast suburb of Sydney. We observe the way multiple stakeholde r decision-making plays out a number of Risk Society themes, including the em ergence of 'unbounded risk' and of highly 'individualised' and 'reflexive' risk communities. Across several decades, the events of the HCB story support Risk Soci ety predictions of legitimacy problems faced by corporations as they harness technoscientific support for innovation in their products and industrial processes wit hout due recognition of social and environmental risk. Tensions involving identity, trust and access to expert knowledge advance our understanding of de mocratic 'sub-political' decisionmaking and ways of distribut ing environmental risk.

Benn, S. and R. Jones (2009). "The role of symbolic capital in stakeholder disputes: decision-making concerning intrac table 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 co llaborative fashion with government,

environmentalists and the local comm unity. The study describes the new processes and structures specifically designed to address the decision-making and the issues of stakeholder percepti on and identity construction which have influenced the outcomes. Decision-making in such disputes is often theorized from the perspective of t he emergence of highly indivi dualized and reflexive risk communities and changing modes and expectat ions 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 sym bolic capital rather than an active collaboration to solve the ongoing issue of the waste. As well, issues of access to expert knowledge highlight the relati onship between conditions of uncertainty, technoscientific expertise and identity. The events of the st udy highlight the challenges faced by contemporary tec hnoscientific corporations such as chemicals companies as they must deliv er 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 dist inctions made in t he literature between modernity and late or reflexive modernity.

Bennett, D. H., W. E. Kastenberg, et al. (1999). "General formu lation of characteristics time for persistent chemicals in multimedi a environment." Environmental Science and Technology 33 (3): 502-509.200 BIOSIS COPYRIGHT: BIOL ABS. A si mple yet representative method for determining the characteristic time a persistent organic pollutant remains in a multimedia environment is presented. The c haracteristic 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 pr oportion of mass in each environmental medium. We explore the premise that us ing a steady-state distribution of the mass in the environment provides a means to calculate a representative estimate

of the characteristic time while maintain ing a simple formulation. Calculating the steady-state mass distribution incorporates the effect of advective transport and nonequilibrium effects resulti ng from the source terms. Using several chemicals, we calculate and compare the characterist ic time in a repr esentative multimedia environment for dynamic, steady-s tate, 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) duri ng summer 2001. After six weeks, concentrations of polychlorinated bipheny ls (PCBs), hexachlorobenzene (HCB), p,p'-DDE, and trace metals were measur ed in the transplanted mussels. It was investigated whether total dissolved wa ter and sediment pollutant levels or bioaccumulation factors (BAFs) and bi ota-sediment accumulation factors (BSAFs) were predictive for mussel tiss ue 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 leve ls 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 Eur ope 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 tiss ue concentration and water or sediment concentration were weak or nonsignifi cant. Then the measured environmental factors (dissolved calcium, pH, oxygen, organic carbon and clay content in the sediment) were taken into account applyi ng multiple regression analysis, and no

increase in the described va riation of pollutant accumulation was observed. TheBAF and BSAF for all pollutants varied up to 1000-fold even after TOCnormalization. Clear negative relations hips were found between BAFs/ BSAFs and environmental levels. However, even at constant environmental

concentrations a 10- to 100-fold variat ion 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 enantiomer s to trace pesticide emissions: This novel approach provides clue s to sources of pesticides found in the atmosphere." Environmental Science & Technology 33 (9): 206-209.201 Biosis copyright: biol abs. rrm using enant iomers to trace pesticide emissions: this novel approach provides clues to sources of pesticides found in the atmosphereyjournal article pollution to xicology pesticides un environmental program environmental cont amination ddt pollutant atmospheric emissions enantiomers pesticide chlordane heptachlor aldrin dieldrin endrin toxaphene

mirex hexachlorobenzene environment al 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. polym orpha) 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 contami nated 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 m easured before the fl ood. 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 di scharge or release of contaminated

sediments from numerous dams located in the watershed. Concen trations of total dioxin-like PCBs reached dangerous leve ls 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 PO P pollution by AChE and EROD

activities in Zebra mussels from the Italian Great Lakes." Chemosphere 61 (8): 1074-82. The increase of ethoxyresorufin dealky lation (EROD) and the inhibition of acetylcholinesterase (AChE) as biomarkers have been commonly used in vertebrates for the persist ent organic pollutants (POPs) biomonitoring of aquatic environments, but very few studies have been performed for invertebrates.

Previous researches demonstrated the in terference due to some chemicals on

EROD and AChE activities of the fres hwater bivalve Zebra mussel (Dreissena polymorpha) in laboratory and field studies, showing its possible use for the screening of POP effects. We investigated the contami nation of the Italian subalpine great lakes (Maggior e, Lugano, Como, Iseo, Ga rda) 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 in hibitors 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 c ontrols. The planar compounds pollution, able to activate the EROD activity, seem s higher in some sampling stations of202 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 interesti ng opposite effect of AhR-binding compounds and trace metals. Finally, the possible use of Zebra mussel specimens maintained at laboratory condi tions as controls against the selection of the less polluted sampling site is discussed.

Binelli, A., C. Riva, et al. (2007). "Biomarkers in Zebr a mussel for monitoring and quality assessment of Lake Maggiore (Italy)." Biomarkers 12 (4): 349-68. Three different biomarkers (acetylchol inesterase (AChE), ethoxy resorufin-Odeethylase (EROD) and DNA strand breaks) were m easured in Zebra mussel (Dreissena polymorpha) specimens collect ed 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 s patial variation of exposure to manmade contaminants. Mussels maintained at fixed laboratory conditions were used as controls to eliminate potential in terference due to environmental factors. Biomarker data were also supported by t he analysis of several chemicals (six dichlorodiphenyltrichloroethane (DDTs), 23 polychlorinated biphenyls (PCBs), 14 polybrominated diphenyl ethers (PBDEs), 11 polycyclic aromat ic hydrocarbons (PAHs) and hexachlorobenzene (HCB)) measur ed in the mussel soft tissues by gas chromatographic analyses. We found a negative correlation between temperature and AChE activity, wh ile any measured environmental or physiological factor seemed to influence EROD activity and DNA strand breaks. A positive relationship was found between ER OD activity and all of the measured chemicals, except for PAHs, which co rrelated with the amount of DNA strand breaks. Significant differences were noted for all biomarkers, both among sampling stations and between control and ex perimental data, even if the general level of variability was low. The biomarke rs 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 wa s compared with resu lts obtained in a previous study carried out over the same sampling period in 2003. Results indicated a strong influence of temper ature on AChE activity and probable

interference of substrate inhibition of ER OD activity, pointing out the need to take care in the interpretation of data com parisons. The results obtained with two

different metrics used for the measure of DNA strand breaks is also discussed, as well as the relationship betwe en EROD activity data and potential genotoxicity.

Bishop, C. A., N. A. Mahony, et al. (1999). "Reproductive success and biochemical effects in tree swallows (Tachycineta bi color) exposed to chlorinated hydrocarbon

contaminants in wetlands of the Great Lak es and St. Lawrence River Basin, USA and

Canada." Environmental To xicology and Chemistry 18 (2): 263-271. BIOSIS COPYRIGHT: BIOL ABS. Repr oduction and biochemical indicators (vitamin A, ethoxyresor ufin-O-deethylase (EROD), highly carboxylated porphyrins) of contaminant effects, and concentrations of organochlorine203 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 diet s, insects were collected, by ligature, from nestlings at four of these sites. Diet samples were analyzed for retinol and alpha- and beta-carotene. Marked diffe rences were found in chlorinated hydrocarbon residues in eggs and nestli ngs among sites; however, we did not find any significant differences in hat ching or fledging success. The maximum polychlorinated biphenyl (PCB) concentrati on 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 me asurements of interspecies variability." Environmental Science and Technology 33 (11): 1805-1813.

BIOSIS COPYRIGHT: BIOL ABS. The a ccumulation 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 bec ause 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 em ployed to analyze the data, and it was

established whether the accumulation of a given compound was due primarily to equilibrium partitioning, kinetically lim ited gaseous deposition, or particle-bound deposition. The interspecies variability in uptake was then examined, and it was found that for those compounds which had ac cumulated primarily via kinetically limited gaseous deposition and particle-bou nd 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 contaminat ed harbor sediments." Environ Sci Technol

37 (18): 4213-20. Aqueous concentrations of polychlori nated biphenyls (PCBs), polyaromatic hydrocarbons (PAHs), pentachlorobenzen e, and hexachlorobenzene (HCB) were determined by exposing low-density polye thylene (LDPE) strips to the pore waters and the overlying water in two c ontaminated harbors. LDPE strips were also exposed in the laboratory to sedi ment slurries and to stagnant sediments collected at the same locations. Surprisi ngly short equilibration time scales (1-60 days for log K(ow) < 7) were observed fo r the exposures to sediment slurries. This was a result of a profound decreas e in transport resistance, due to the presence of particles in the aqueous boundar y 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 equilibr ium amounts in the strips and LDPEwater partition coefficients. Sediment-wat er partition coefficients for PAHs were204 higher than for PCBs and chlorobenz enes by approximately 1 order of magnitude. A one-dimensional diffusion m odel was used to describe contaminant uptake by LDPE strips from stagnant sedi ments. 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 wa ters and water columns indicated that a fair degree of equilibrium existed for PCBs and that one sediment was a potential source of PAHs. Concentrati ons 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 At lantic transect." Mar Pollut Bull 54 (6): 814-9.

Borga, K., H. Hop, et al. (2007). "Selective bioaccumulati on 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 sele cted 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 show ed efficient eliminat ion of chlordanes, whereas the opposite was found for little auk. Kittiwake showed higher accumulation of persistent CP and metabol ites than auks, whereas accumulation

of less recalcitrant CPs was low.

Borrell, A. and A. Aguilar (2007). "Organochlorine concent rations declined during 1987-

2002 in western Mediterranean bottlenose dol phins, a coastal top predator." Chemosphere 66 (2): 347-52. We collected blubber samples from bottlenose dolphins st randed on Spain's Mediterranean coasts over a 25-year period (1978-2002). Samples were analyzed to determine time trends in le vels of: HCB (hexachlorobenzene), PCB (polychlorinated biphenyls) and tDDT (dichlorodiphenyltrichloroethane and its metabolites). Overall, levels were high rela tive to other areas. This reflects both the ubiquity of organochlorine polluti on 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 t he pollutant loads in the environment are gradually being reduced; either by degradati on or by migration of the compounds to other regions. A comparison with dol phin species that have an oceanic205 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 me rcury and selenium were measured in eggs of thick-billed murres, norther n 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 fulm ars, and beta-HCH in the murres and fulmars. Mercury increased si gnificantly in eggs of murres and fulmars, whereas mercury in the kittiwakes did not change significantly over the study period. Statistical analyses included stable-nitrogen is otope 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 c ontinue 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 st udies have been devoted to the sources and emissions of Persistent Organic Poll utants (POPs) at regional and global scales. While significant improvement s in knowledge have been achieved for some pesticides, the quantitative understand ing of the emission processes and emission patterns for "non-pesticide" POPs are still considered limited. The key issues remaining for the non-pesticide PO Ps are in part determined by their general source classification. For i ndustrial chemicals, such as the polychlorinated biphenyls (PCBs), there is considerable uncertainty with respect to the relative importance of atmos pheric 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 combusti on and industrial processes (PCDD/Fs), there is still a large uncertainty with re spect to the relative contribution of emissions from unregulated sources such as backyard barrel burning that requires further consideration and c haracterisation. For hexachlorobenzene (HCB), the relative importance of pr imary 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 pr erequisite for any a ttempt to understand and predict the distribution and fate of t hese chemicals on a regional and global scale as well as to efficiently mi nimise 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 c hemicals 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 emergi ng management theory, and they analyse the case study from several disciplin es. Disputes such as that over HCB destablilise the political/administrative/te chnoscientific regime that is the modern state. Citizens engage in 's ub-political' processes which require recognition of

what Ulrich Beck and others have termed 'indi vidualisation'. This sees decisionforming and decision-making functions pus h outwards into community-driven structures. There we find new styles of public participation, resolution of asymmetries between knowledge and ex pertise, 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 lym phocytes of different rat strains in immunotoxicity." Toxicol Pathol 27 (2): 171-9. In order to study the intestinal muco sal 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 or ganized lymphocytes were examined microscopically. In addition, the single lymphocytes in the epithelium (IEL) and lamina propria (LPL) were analyzed by fl ow cytometry. Next, the use of flow cytometry analysis was ex plored to detect changes in the IEL T-lymphocyte population in subacute oral studies with the immunom odulating agents azathioprine and hexachlorobenzene. Un treated 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 demon strated that hexachlorobenzene increased the number of intraepithelia l 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 intest ines 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 chlorina ted 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. Indivi dual chlorinated biphenyls (CBs) and chlorinated pesticides (p,p'-DDT and metabolites, HCHs and HCB) were determined in blubber samples of 40 har bour 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 i mmature specimens were similar (14.9 mug/g lipi The North Sea and Baltic Sea popul ations were identified as distinctly separate on the basis of levels and com positions of these contaminants. The ecological risk associated with dioxin-lik e 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 treat ment removes negative effects of environmental pollu tants on reproduction in an Arct ic seabird." Proc Biol Sci

273 (1605): 3117-22.

Recent studies have shown that t he detrimental effects of anthropogenic pollutants may be worse if organisms are ex posed to natural stress. In this study, we examined whether negative effects of organochlorines (OCs) could beinfluenced 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 t he study population (hexachl orobenzene, oxychlordane, p,p'-dichlorodiphenyldic hloroethylene and polychlo rinated biphenyl), were measured. The relationships between OC s and fitness components (i.e. nesting

success and return rate between br eeding seasons) were then compared between the birds receiving anti-paras ite treatment and the controls. Among untreated males, higher blood residues of OCs were associated with lowered nesting success, while in males receivi ng anti-parasite treat ment, there was no

detrimental effect of OCs on fitness. Retu rn rate was not affected by treatment or OCs. Our findings suggest that parasites may be an important fa ctor 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 be tween ecological variables and four organochlorine pollutants in an artic glaucous gull (Lar us hyperboreus) population."

Environ Pollut 136 (1): 175-85. The Arctic has become a sink for organoc hlorine contaminants (OCs) from lower latitudes, and relatively high levels hav e been found in different biota. Recent studies of the glaucous gull, Larus hyper boreus, a top predator in the arctic food web, have documented that high blood resi dues of various OCs are related to lower reproductive performance and reduc ed adult survival. Here we provide additional evidence that OCs are having ecol ogical 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 shown208 that gulls with high levels of PCBs in t heir 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 oxych lordane (P<0.05) were positive and significantly related to ti me 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 fl ight 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 adul ts 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 impor tance 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). "Deliberat ive public participation and hex achlorobenzene 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. Specifical ly, 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 commi ttee in combination with the corporate sponsor was unable to agree on a mutua lly acceptable technological pathway. This stalemate might have been attributable in part to the time spent on the task of review. A diligent participation work ing 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. Montenegr o-Guillen, et al. (1999). "Chl orinated 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 Decem ber 1995 in the main coastal lagoons on the Pacific side of Nicaragua, where mo st of the country's agriculture and pesticide use has been taking place for decades. Results for a wide range of organochlorine pesticides in lagoon sedime nts 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 Estero s 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). "Devel opment of a bioassay fo r thyroid disruption in patients exposed to endocrine di srupting chemicals." Organohalogen Compounds

56 (Dioxin 2002): 103-105. The authors present a new bioassay that in vestigates the inhibitory effects of chems. on the activity of 5'-deiodinase type II en zyme. 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). "Eff ects of aging and sedi ment composition on hexachlorobenzene desorption resistance compared to oral bioavailability in rats." Chemosphere 72 (3): 432-41.

Studies were conducted to assess the ef fects of black carbon, clay type and aging (1-1.5yr) on desorption and bioavai lability of hexachlorobenzene (HCB) in spiked artificial sediments. Tenax (a super sorbent)-mediated desorption was

used to examine the effects of thes e parameters on the physicochemical availability of HCB. The T enax-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. Tw o sediments with higher black carbon content exhibited much greater aging e ffects (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 feca l 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 de fined by the desorption of HCB from sediments, provides a reasonable predict ion of the oral bi oavailability of

sediment-bound HCB to rats. These result s showed that montmorillonite clay, black carbon and aging reduced physicochem ical 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 t he transference of hexachlorobenzene from a green alga (Chlorella kessleri) to an estuary crab (Chasm agnathus granulatus), and to analyze the toxic effects that the xeno biotic has on the latter. The effect of hexachlorobenzene uptake was evaluat ed measuring oxidative stress, Uroporphyrinogen decarboxylase activity and morphometric parameter alteration, and also performing a histological analysis of crab hepatopancreas. Results

demonstrated that hexachlorobenzene enters t he alga, is accumulated in it, and then transferred into the crab, ca using a decrease in Uroporphyrinogen decarboxylase activity in both organi sms. The high malondialdehyde levels detected in crab hepatopancreas after the toxic treatment suggested the

existence of hexachlorobenzen e-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 mor phometric parameter, reduced 20% with respect to the control. The histolog ical 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-desorpt ion behaviors of hydrophobic organic compounds in sediments of Lake C harles, Louisiana, USA." Environmental Toxicology and Chemistry 18 (8): 1610-1616.

BIOSIS COPYRIGHT: BIOL ABS. Neut ral organic contaminants commonly reside on the solid portion of soils and sedi ments. The extent of desorption from these solids determines the fate, reactivi ty, and toxicity. Numerous researchers have observed that, after an initial expos ure 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 desorpti on of chlorobenzenes, hexachl ld reasonably be interpreted using a single irreversible isotherm. Consequences of these results interms of sediment qualit y criteria (SQC) are also discussed. Finally, an index of fractional irrevers ible adsorption is proposed and tested.

Chen, X., A. Christopher, et al. (2002). "C rystal structure of the F87W/Y96F/V247L mutant of cytochrome P-450cam with 1,3, 5-trichlorobenzene bound and further protein engineering for the oxidati on of pentachlorobenzene and hexachlorobenzene." J Biol

Chem 277 (40): 37519-26. We reported previously that the F87W/Y96F/V247L mut ant of cytochrome P450cam (CYP101) from Pseudomonas putida catalyzed the rapid oxidation of lightly chlorinated benzenes , but pentachlorobenzene oxi dation 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 substrat e was bound to crystallographically independent CYP101 molecules in at leas t three different orientations, which were distinguished by the angle be tween the benzene ring and the porphyrin,

and one orientation contained an Fe-Cl interaction. In a nother orientation, the substrate was almost parallel to the hem e, with a C-H bond closest to the iron.211 The enzyme/substrate contacts sugges ted that the L244A mutation should promote the binding of pentachlorobenzene and hexachlorobenzene by creating space to accommodate the extra ch lorines. 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 ti mes faster than the F87W/Y96F/V247L parent mutant. The rate of hexachlor obenzene oxidation was increased 200-fold, to 2.0 min(-1). Both substrates are oxidized to pentachlorophenol, which is degraded by micro-organisms. In princi ple, the F87W/Y96F/L244A/V247L mutant could have applications in the bioremedi ation of polychlorinated benzenes.

Choi, J. W., M. Matsuda, et al. (2001). "Accumulati on profiles of persistent organochlorines in waterbirds from an estuar y in Korea." Arch Environ Contam Toxicol

41 (3): 353-63. Persistent organochlorine pollutants (P OPs), such as polychlorinated dibenzo-pdioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), polychlorinated biphenyls (PCBs), and organochlori ne (OC) pesticides such as DDTs (dichlorodiphenyltrichloroethane), HCHs ( hexachlorocyclohexane isomers), CHLs (chlordane compounds) and HCB (hexac hlorobenzene), were measured in subcutaneous fat of resident and migrat ory birds collected from the Nakdong River estuary (NRE) in Korea. Black-ta iled gull, a resident bird from the NRE, contained greater concentrati ons 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 highe r 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 co mmon 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 du e to intake of locally contaminated fish near the NRE. Elevated OC pesticide leve ls in migratory birds indicated that these birds have been exposed to DDTs and HCHs during their migration in

Southeast Asian countries where chlorinat ed pesticides are still used. 2,3,7,8- Tetrachloro dibenzo-p-dioxin equivalents (T EQs) 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 begi nning 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 demonstrat e the potential for HCH gas deposition to coastal212 Antarctic seas, while the water-air fugacity ratios for HCB imply that volatilization

does not account for the observed decr ease 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 superoxid e 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 ar omatic compounds ( PACs), a group of chemical contaminants commonly found in the sediments of urban marine areas, alters the ability of peritoneal ma crophages (Mphis) from English sole (Pleuronectes vetulus) to produce cytot oxic reactive oxygen intermediates (ROIs). Initially, assay conditions including co ncentration of Mphis, type of in vitro stimulant, tissue culture media, and inc ubation 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 ly mphatic sinus. Peritoneal Mphis were harvested on days 1, 3, 7, and 14 post-inje ction. Elicited per itoneal Mphis from English sole

Colume, A., S. Cardenas, et al. (1999). "Semiautomatic met hod for the screening and determination of 23 organochlorine pesticide s in horticultural samples by gas chromatography with electron-capture det ection." Journal of Chromatography a 849 (1):

235-243. BIOSIS COPYRIGHT: BIOL ABS. A rapi d, simple, efficient device for the extraction-preconcentration of 23 organochl orine 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 laye r 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 sear ch, 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 te chnique called retention time locking

was used to match GC-AED and GC wit h mass spectrometry (MS) retention times to those of the database. Samp les 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 prec ision of retention time matching and the accuracy of the database search. Analytical re tention times matched database retention times within 0.32 min. Using elemental cr iteria, the database s earch identified the correct compound for 41 of 44 pesticide st andards. For blind spikes of fruit and vegetable extracts, the database sugges ted 22 of 26 spiked pesticides as

matche s. Nineteen were ident ified by GC/MS. The combi nation 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 fr om sediments." Chemosphere 39 (11): 1971-1982. BIOSIS COPYRIGHT: BIOL ABS. Experim ents were carried out concerning competition effects in slow desorption. Excess lab-added 1,2,4-trichlorobenzene (TCB) decreased the slowly desorbing amo unts of aged in situ polychlorinated biphenyls (PCBs) and chlorobenzenes in sediment from Lake Ketelmeer (KM), The Netherlands, after 14 d of TCB-sedim ent contact time (f actor of 1.2-2.7). Another experiment showed that the presence of large quantit ies 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 sorp tion 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). "Occ urrence of organochlorin e pesticides (OCPs) and their enantiomeric signatures, and conc entrations 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, emeral d rockcod and Adelie penguin from the Ross Sea, Antarctica. HCB and DDTs were pr evalent 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 wa s evaluated. Enantioselective gas chromatography was used for the evaluati on of enantiomeric fractions (EFs) for alpha-HCH and oxychlordane. An increase of 14% in the (+)alpha-HCH enantiomer was found from krill through peng uin, suggesting the enantioselective biotransformation increased proportionatel y with trophic level. Polybrominated diphenyl ethers (PBDEs) were measured an d 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 det ection 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 thy nnus) 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 thei r age, thus they occupy different trophic levels during their lifespan. He xachlorobenzene (HCB), p,p'-DDE and polychlorinated biphenyls (PCBs) are well-known persistent organic pollutants (POPs) in the Mediterranean basin. The re lationship between stable isotopes of nitrogen (N) and the POP residue levels in tissues has recently increased knowledge on the link between the tr ophic levels and the contaminant accumulation. Trophic levels were estima ted 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 show ed 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 signi ficantly. 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). "O rganochlorine 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 efflu ent in marine waters. In order to evaluate the suitability of mu mmichog as a sentinel species and to support the interpretation of biological effects data, tissue concentrations of polychlorinated dibenzo-p-dioxins and di benzofurans, (PCDDs), chlorophenolic compounds (CPs), polychlorinated biphenyls (PCBs), and chlorinated pestic -pdioxin toxic equivalent concentrations were slightly above the threshold for ethoxy resorufin O-deethylase inducti on. 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 pl ant and that PCDD/Fs and CPs typical of the BKM were transpor ted 40 km downstream from the mill. Patterns and levels of persistent contam inants differed between sites within the Estuary, indicating that the fish di d 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 or ganic 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 inte rface is one of the most important215 processes determining the environmental fate and human exposure of these compounds. The main processes contribut ing to air-soil exchange of SVOC are dry deposition (both by vapour adsorption and in associ ation with particles), wet deposition (by precipitation scavenging of vapour- and particle-sorbed chemicals)

and volatilisation from the soil. Thes e processes are reviewed and evalua

Crane, M. and M. Babut (2007) . "Environmental quality standar ds 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 effo rt by the European Commission to develop consistent, Europe-wide environmental quality standards (EQS) that are scientifically based and protective of Eu rope's surface waters. This commentary describes progress to date in deriving EQ S 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 ar e included, and biot a EQS are proposed for methyl-mercury, hexachlorobenzene and hexachlorobutadiene. Important remaining questions include whether t he 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-cu tting issues about the cessation of discharges of naturally occurring or ubi quitous 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 onocrotalu s) nesting at lake Mikri Prespa, North

Western Greece." Bulletin of Envir onmental Contaminat ion and Toxicology 62 (4): 383-

389. Biosis copyright: biol abs. rrm resear ch 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-wes tern lake mikri prespa greece

Crouch Edmund, A. C. and C. Green Laura "Comment on "Per sistent organic pollutants

in 9/11 world trade center rescue workers: re duction following detoxification" by James Dahlgren, Marie Cecchini, Harpreet Ta khar, and Olaf Paepke [Chemosphere 69/8 (2007) 1320-1325]." Chemosphere 69 (8): 1330-2; discussion 1333-6.

Custer, T. W., C. M. Cu ster, et al. (1999). "Or ganochlorine contaminants and reproductive success of double-crested corm orants from Green Bay, Wisconsin, USA." Environmental Toxicology and Chemistry 18 (6): 1209-1217. In 1994 and 1995, nesting success of double- crested cormorant s (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 (incl uding total polychlorinated biphenyls (PCBs) and DDE), hepatic microsomal ethoxyresorufin-O- dealkylase (EROD) activity in embryos, and eggshell thi ckness. 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 wit h 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 logi stic regression of hatching success versus DDE, dieldrin, and PCB concentrations in sibli ng eggs identified DDE and not dieldrin or PCBs as a significant risk factor. A logistic regression of hatching success versus DDE and eggshell thickness imp licated 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 concent rations in double-crested cormorant eggs in Green Bay are still having an effe ct on reproduction in this species.

Czaja, K., J. K. Ludwicki, et al. (1999). "E ffect of changes in excretion of persistent organochlorine compounds with human breast milkon related exposure of breast-fed

infants." Archives of Environm ental Contaminat ion 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-d ichloro-2,2-bis(4-chlorophenyl)ethane) (p,p'-DDD), (1,1-dichloro-2,2-bis(4-ch lorophenyl)ethylene) (p,p'-DDE), and polychlorinated biphenyls (PCBs) with human milk during lactation. The shortest lactation studied took 16 weeks, and t he 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 bl ood." Human Reproduction 17 (8): 1973-9. BACKGROUND: Various studies have been per formed 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 al ternative approach, as we selected one group of men with very poor semen qual ity and another group with normal semen quality and determined the bl ood organochlorine contents in order to determine

whether a difference in these levels could be established. Organochlorine compounds, including polychlorinated bi phenyls (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 volunt eers. 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 significant ly decreased sperm count in relation

to an elevated PCB metabolite level wit hin the subgroup of men with normal semen quality is important. This is the first time that a correlation between exposure to environmental pollutant s with endocrine-disrupting capacity and human sperm quality has been observed.

Daly, G. L., Y. D. Lei, et al. (2007). "Pes ticides in western Canadian mountain air and

soil." Environ Sci Technol 41 (17): 6020-5. The distribution of organochlorine pestici des (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 B anff National Park is east of the divide. XAD-based passive air samp lers, yielding annually av eraged 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 in cludes agricultural regions in British Columbia and Washington State. Endosulfan, dieldr in, and a-hexachlorocyclohexane were the most prevalent OCPs in air and soil; hexachlorobenzene was only abundant in air; chlorothalonil, dacthal, and pentachlor onitrobenzene were also consistently present. OCP air concentrations were similar across the three transects, suggesting efficient atmospheric mixi ng on a local and regional scale. Soil

concentrations and soil/air concentration ra tios of many OCPs were significantly higher west of the Continent al 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 wit hin, the soils. Higher deposition, due to more precipitation falling at lower tem peratures, likely occurs west of the divide and at higher elevations. Higher ret ention, due to higher soil organic matter content, is believed to occur in soils below the tree line. Highest pesticide concentrations are thus found intemperate m ountain 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 autoa ntibodies." Environmental Health Perspectives 109 (2): 173-178. Pentachlorophenol (PCP), hexachloro cyclohexane-[alpha], -beta, and -[gamma] (HCH-[alpha], -beta, and -[gamma]) , polychlorinated biphenyls (PCBs), and hexachlorobenzene (HCB) are widely distribut ed 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 lympho cyte subpopulations, in vitro lymphocyte response) or humoral (plasma cytokine levels, imm unoglobulin autoantibodies) immunologic218 dysfunctions. We studied 146 patient s who had been occupationally exposed primarily to PCBs for more than 6 mont hs. Lymphocyte subpopulations, in vitro responses to mitogens and allogeneic st imulator cells, plasma neopterin, cytokines, soluble cytokine receptors, soluble adhesion molecules, anti-Ig autoantibodies, and liver transaminases we re determined. Blood levels of the different compounds were strongly corre lated 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 i mmune parameters. An exception was the statistically signi ficant negative association of HCB with interferon-[gamma] (IFN-[gamma]), indicati ng that HCB has a significant impact on Th1 lymphocytes. Patients with HCB bl ood levels above the mean of 1,109 ng/L more often had undetect able IFN-[gamma] blood levels than patients below

the mean. Patients with increased PC B 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 hi gher IFN-[gamma] plasma levels, providing some evidence for a cumulati ve 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 PC P, which showed a strong dose-dependent relationship with immunologic impairm ents. Our data suggest that long-term exposure of patients to HCB su ppresses IFN-[gamma] production.

Datta, S., K. Ohyama, et al. (1999). "Evi dence for organochlorin e contamination in

tissues of salmonids in Lake Tahoe." Ecotoxicology and Environmental Safety 42 (1):

94-101.
BIOSIS COPYRIGHT: BIOL ABS. To ev aluate the extent of organochlorine pollution in the Sierra Nevada ecosystem, residues of certain organochlorines in

lake trout and Kokanee fish from Lake T ahoe, an alpine lake located between the Sierra Nevada Mountain Range and the Ca rson Range of California and Nevada, were analyzed. Multiresidue analysis in fish muscle revealed wet weight concentrations of total polychlorinated bi phenyls (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 mixt ure (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 conf irmed using gas chromatography/mass spectrometry (GC-MS). The results of to tal PCB analysis indicated that residues

found in f219 de Catabbi, S. B., R. W. de Calmanovici, et al. (1999) . "Porphyria-induced hepatic porphyrinogen carboxy-lyase inhibitor and its in teraction with the active site(s) of the enzyme." Biochem Mol Biol Int 47 (6): 945-56. Porphyrinogen carboxy-lyase is an en zyme that sequentially decarboxylates uroporphyrinogen III (8-COOH) to yield c oproporphyrinogen III (4-COOH). In mammals this enzyme activity is im paired by hexachlorobenzene treatment, through generation of an enzyme inhibito r. The interaction of porphyrinogen carboxy-lyase inhibitor, extracted from the liver of hexac hlorobenzene-treated rats, with substrate decarboxylation sites on the enzyme, was studied using four different carboxylated substrat es belonging to the isomeric III series of naturallyformed porphyrinogens containing 8-,7-,6- and 5- COOH. Similar inhibitor effects were elicited against all the substrat es assayed, with the exception of pentacarboxyporphyrinogen III in which decar boxylation was not inhibited to same extent. Enzyme protection assays in the presence of the different substrates, indicated that each porphyri nogen 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 dism utase 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-Benz oyl-L-Arginine ethyl ester interact with the inhibitor, noticeably reducing its abilit y to inhibit porphyrinogen carboxy-lyase. Albumin, histidine, serine, cysteine and im idazol, 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 ar ginine residues, blocking the access of substrates to histidine and altering t he adequate orientation for decarboxylation by masking the positively charged acti ve site necessary for porphyrinogen binding to the enzyme. In addition an indi rect effect of the inhibitor mediated through free radicals could be discarded.

De Felip, E. and A. M. Ingelido (2004). "Lev els 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 s ubstances (PTS) occurs daily, mainly through diet. As a consequence of cont inuous exposure, and because of their biological persistence, PTS are virtually pr esent in all individuals, stored in their fatty tissues. The exposure of the Italian general populati on to PTS is a fact of relevance from a public health perspective, because of the number of toxic effects associated to these compounds, po ssibly 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 Sto ckholm on persistent organic pollutants (POP), a group of highly toxic PTS, has entered into force last May. This will oblige parties to develop national implem entation plans, thus creating a new220 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 Zeehavenk anaal 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 bioa ssay, using concentrations realistic for the field situation. In step two, yolks of oystercatcher eggs were extracted and the embryotoxic potency of th is extract was studied in the same bioassay, using doses of 1, 10 and 100% of the contam inant load in one average egg. The

extract contained hexachlorobenzene and PC Bs. However, presence of other compounds could not be excluded, since these were not analysed.

Hexachlorobenzene induced a no nsignificant decrease in lymphocyte density in the bursa of Fabricius. The egg extrac t 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. Raffael li, et al. (2008). "Cytot oxic effects induced by hexachlorobenzene in Squilla mantis (L.) (C rustacea, Stomatopoda). " Environ Toxicol

23 (1): 9-14.

Contamination of marine environments by hexachlorobenzene (HCB) represents a serious concern for potential consequenc es on ecosystem and human health. Despite this, information on cytotoxic e ffects on marine organism s is still largely lacking. In this study, we investigat ed 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 leve l, feeding behavior, and commercial exploitation for human cons umption. Time course ex periments revealed that low concentrations of HCB (i.e. 50 nM) det ermine an exponentially decrease of Na(+)/K(+)-ATPase activity and a signific ant modification of cellular membrane fluidity. Significant negative relationsh ips between Na(+)/K(+)-ATPase activity and membrane fluidity were observed, s uggesting that changes in the structure and packing of cellular membranes induced by HCB may be the primary factor affecting the activity of essential b ilayer-associated enzymes. Overall these findings suggest that even small concentra tions of HCB may determine important changes on cell metabolism with potential ca scade effects on recruitment of this commercial species.

Dewailly, E., P. Ayotte, et al . (2000). "Susceptibility to in fections and immune status in Inuit infants exposed to organochlor ines." Environ Health Perspect 108 (3): 205-11.221 We investigated whether organochlori ne exposure is associated with the

incidence of infectious diseases in I nuit infants from Nunavik (Arctic Quebec, Canada). We compiled the num ber of infectious disease episodes during the first year of life for 98 brea st-fed and 73 bottle-fed inf ants. Concentrations of organochlorines were measured in early breast milk samples and used as surrogates to prenatal exposure leve ls. Immune system parameters were determined in venous blood samples coll ected from infants at 3, 7, and 12 months of age. Otitis medi a was the most frequent di sease, with 80. 0% of

breast-fed and 81.3% of bottle-fed inf ants 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 infant s 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 increas ed with prenatal exposure to p,p'-DDE (RR, 1.52; CI, 1.05-2.22) and hexach lorobenzene (RR, 1.49; CI, 1.10-2.03). Furthermore, the

RR of recurrent otitis m edia ( [Greater/equal to] 3 episodes) increased with prenatal exposure to these compounds. No c linically relevant differences were

noted between breast-fed and bottle-fed in fants 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-des tructive pollution exposure assessment in the European hedgehog (Erinaceus europaeus): IV. Hair versus soil analysis in exposure and risk assessment of or ganochlorine compounds." Environ Pollut 145 (3):

861-8. Few ecotoxicological studies on mamma ls use non-destruct ive methodologies, despite the growing ethical concern ov er the use of destructive sampling methods. In the present study we assessed exposure of hedgehogs (Erinaceuseuropaeus) to polychlorinated biphenyls (PCBs), dichloro-diphenyltrichloroethanes (DDTs), hexac hlorocyclohexanes (HCHs) and hexachlorobenzene (HCB), by investigati ng 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 hai r from the different study areas. Furthermore, the individual variation of c ontamination 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. Ou r results show that concentrations of organochlorine compounds in soils alone are not predictive of the risk of these pollutants to hedgehogs and that tissue analyse s 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 conc entrations of a number of metals and organic compounds in blood and urine of 28 workers employed at a new hazardous waste incinerator (HWI), befor e operation of th e plant. METHODS: Plasma analyses of hexachlorobenzene (H CB), polychlorinated biphenyls (PCB 28, 52, 101, 138, 153 and 180), benzene, toluene, ethylbenzene, m-xylene, and polychlorinated dibenzo-p-dioxins and di benzofurans (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 measur ed. 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 undertheir 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. P CDD/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 t he concentrations of PCBs were of the same order of magnitude as those re cently 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 lowe r than those considered as potential

reference values. Metal concentrations in blood and urine were also of the same order of magnitude than previously repor ted 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. Syrgianni s, 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-la titude temperate glacier in Alberta, western Canada (52ˆ N, 117ˆ W). In contra st 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 concentrati ons occurring about 1960 and again in 1989. Meltwater from glaciers may contri bute 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 Envi ronmental Contami nation and Toxicology 37 (1): 110-

114.
BIOSIS COPYRIGHT: BIOL ABS. Live r tissue from male and female adult American white pelicans (Pelecanus eryt hrorhyncos) were individually analyzed for organochlorine compounds and trac e elements. Levels of most organochlorines, specifically SIGM ADDT, 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 al so 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 contami nation 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. Unhat ched eggs and plasma samples from prefledged bald eagles (Haliaeetus leucocep halus) from a recovering population

in the Canadian Great Lak es Basin were contami nated with organochlorine compounds at levels comparable to thos e 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 nestli ngs from Lake Superior compared to those from Lake Erie (0.0012 and 0.0006 mg/kg we t weight, respectively). Migration routes and over-winter locations of avian pr ey 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 eval uating 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 pr ocessed. 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 we ll. Long-range transport of pollutants between 2002 and 2005 was evaluated using the Potential Source Contribution Function hybrid receptor model. Indica ted potential source areas of PCBs224 coincide with many well-known ur ban 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 e ffort 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 hav e driven industries and companies to change their process configurations and thei r chemical releases to reduce the release of higher ranking chemicals. But, chemicals that are higher ranked due to mass release may not be particularly toxi c 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 Re lease Inventory were used as inputs to a Level III fugacity model to esti mate fate, transport, and steady state

concentrations of chemicals in the envir onment. The resulting concentrations in the air and water, for each chemical, were determined using the fugacity model and were then compared with toxicity data, t he 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 system s reported in the literature. MH -

ECOLOGY

Elliott, J. E., C. J. Henny, et al. (1999). "C hlorinated hydrocarbons in livers of American mink (Mustela vison) and river otter (Lutra canadensis) from the Columbia and Fraser River basins, 1990-1992." Environment al Monitoring and Assessment 57 (3): 229-252. BIOSIS COPYRIGHT: BIOL ABS. We investigated chlorinated hydrocarbon contaminants in aquatic mustelid specie s 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 bi phenyls (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 samp le taken near Portland had a mean concentration of 1500 mug/kg, within a r ange of concentrations associated with reproductive effects in captive mink. C oncentrations of 2,3,7,8-TCDD and TCDF were generally below detection limits, exc ept for one otter collected near a pulp mill at Castlegar225 Environmental Protection Agency. Great Lak es National Program Office. Environment Canada (2005). Greak Lakes Binational Toxics Strategy Assessment of Level 1 Substances, Summary, Govt Reports A nnouncements & Index (GRA&I), Issue 20,

2006 : 68. Prepared in cooperation with Environment Canada, Toronto (Ontario).

The Great Lakes Binational To xics Strategy (GLBTS) was signed by the United States and Canada (the Parties) in 1997 to adv ance 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 Lak es National Program Office. Environment Canada (2006). Great Lakes Binational To xics Strategy: Canada -- United States Strategy for the Virtual Elmination of Persis tent Toxic Substances in the Great Lakes, Govt Reports Announcements & I ndex (GRA&I), Issue 20, 2006 : 26. Prepared in cooperation with Environment Canada, Toronto (Ontario).

The Great Lakes Binational To xics Strategy (GLBTS) was signed by the United States and Canada (the Parties) in 1997 to adv ance the goals of Article II(a) of the Great Lakes Water Quality Agreement (G LWQA). 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 Europ ean Parliament and of the Council of 28 Jan. 2003 concerning the ex port 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 haz ardous chemicals subject to the prior informed consent (PIC) procedure of the Rotterdam Convention, certain other

hazardous chemicals banned or re stricted within the EU or a Member State, and all chemicals when exported insofar as their classifica tion, packaging and labelling is concerned (how ever, 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 authorit ies; participation of the EU in the Convention; chemicals subject to export notification, PIC notification and PIC procedure; information and other require ments associated with the export and import of dangerous chemicals; technical as sistance; monitoring and reporting. In annexes: lists of chemicals subject to t he export notification procedure, qualifying for PIC notification and subject to the PI C procedure; notificat ion requirements of banned or severely restricted chemicals; ex port notifications; list of chemicals subject to export ban (cosmetic soaps containing mercury, and the following persistent organic pollutants: aldrin, chlo rdane, 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 hexachlor obenzene 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 scavengi ng by precipitation and dilution by prevailing southwesterly winds blown from the atmosphere of the South China Sea. In contrast, trace pr ecipitation and prevailing nor theasterly winds during the dry season (October to March) resu lted in higher gaseous PCB and HCB

concentrations. Instantaneous air-wate r 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 hom ologues and HCB in this study are from water to air (net volatilization). The hi ghest 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 ambi ent 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 report ed to be greatly impacted by PCBs.

Farrar, N. J., K. Prevedouros, et al. (2006). "Continental sca le passive air sampling of persistent organic pollutants usi ng 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 invest igate short-term spatial variability of persistent organic pollutants (POPs). Device s were sealed in airtight containers to eliminate the possibility of contam ination during transit and couriered to recipients with deployment instructions. Exposure times of 7days permitted the use of back trajectory analysis to furt her understand the factors responsible for influencing the large-scale spatial dist ribution of PCBs, PBDEs, PCNs, PAHs, lindane and HCB. Following sampler harves t, devices were sealed and returned for analysis. Comparison of sequestered le vels showed that PAHs exhibited the greatest spatial variability (b y a factor of 30) with higher levels often associated with greater population densit y. In contrast, HCB values were much more uniform, reflecting its well mixed distribut ion 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 t he environmental and physiological processes determining the a ccumulation of organochlorine compounds in European mountain lake fish through multivar iate analysis (PCA and PLS)." Sci Total

Environ 404 (1): 148-61. The presence of organochlorine co mpounds (OCs)-namely hexachlorobenzene (HCB), hexachlorocyclohexanes (HCH), polychlorobiphenyls (PCBs #28, 52, 101, 118, 138, 153 and 180), dichlor odiphenyltrichloroethane (DDT) and dichlorodiphenyldichloroet hane (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 tem perature) and physiological parameters (lipid content, age, weight and size) was assessed. Principal components analysis (PCA) and partial least squares (PLS) models we re 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 co mpounds. Some differences were found

between the muscle and liver in the effe cts of the percent age of lipids on the accumulation of organochlorine co mpounds and the behaviour of HCB. Moreover, PCBs tended to accumulate more in liver rather than in muscle. PCA scores clearly differentiated samples accord ing to the lake of origin. PLS models confirmed that temperature and altitude we re 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 organochl orine pesticides (OCPs) hexachlorobenzene (HCB) and dichlorodi phenyltrichloroethane (DDT) and its related metabolites (p,p'-DDT, p,p'-DDE, and p,p'-DDD) were quantified in edible tissues from seven marine species (E uropean hake, red mullet, blue whiting, Atlantic mackerel, blue and red shrimp, European flying squid, and Mediterranean mussel) from t he Gulf of Naples in the southern Tyrrhenian Sea (Italy). PCBs 118, 138, and 153 were t he dominant congeners in all the species

examined. The concentrations of all PC Bs (from not detectable to 15,427 ng g(- 1) fat weight) exceeded thos e of all the DDTs (from no t 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 concentrati ons were below the maximum residue limits established for fish and aquatic pr oducts by the Decreto Ministerale 13 May 2005 in all the samples analyzed; therefor e 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 Un ion 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). "A ccumulation patterns of organochlorines in juveniles of Arctocephalus australis found st randed along the coast of Southern Brazil."

Environ Pollut 146 (1): 262-7. The present study was conducted to eluc idate 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 concentra tions occurred in the following order:

PCBs>DDTs>CHLs>HCHs>HCB. OC concentra tions 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 positiv e association with lipid content (except for HCB). However, the poor nutritional status of these animals, possibly following a starvation period, is likely to have allo wed 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- stimulat ed insulin release from RINm5F cells." Toxicol Appl Pharmacol 159 (3): 194-203. Polychlorinated biphenyls (PCBs) are environmental contam inants that induce release of insulin in rat insulinoma cells, RI Nm5F (Fischer et al., Life Sci. (1996) 59, 2041-2049). In the present study the mechanisms of this effect were investigated using noncytot oxic concentrations (10 micr og/ml) of a PCB mixture, Aroclor-1254, and the pure PCB congeners 2,2',4,4'-tetrachlorobiphenyl and 2,2',4,4',5, 5'- hexachlorobi phenyl. Treatment of RINm5F cells with each of these agents resulted in a rapid increase in intr acellular free calcium. The presence of extracellular calcium was required fo r PCB-induced insulin release because

removal of calcium from the medium attenuated the effect. In addition, pretreatment of RINm5F cells with t he 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 rele ase 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- induc ed insulin release. Furthermore, the results suggest that insulin release by PC Bs is independent of the activation of

MAPKs.

Fisher, B. E. (1999). "Most unw anted." 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 envir onment, 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 wi ldlife. While the effects of POPs on human health are unclear, many researchers believe th at long-term exposure229 contributes to increasing rates of bi rth defects, fertility problems, greater susceptibility to disease, diminished in telligence, 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, heptac hlor, hexachlorobenzene, mirex, and toxaphene. Of the remaining three POPs, polychlorinated biphenyls are industrial products (used in electrical transfo rmers), and dioxins and furans are unintentional by- products of industrial processes.

Fitzgerald, E. F., S. A. Hwang, et al. (2001). "The asso ciation between local fish consumption and DDE, mirex, and HCB concent rations 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 ext ent to which the consumption of local fish contaminated with p,p' -dichlorodiphenyl dichloroethylene (p,p'-DDE), mirex, and hexachlorobenzene (HCB) has impac ted the concentrations of these compounds in the milk of nursing M ohawk women residing along the St. Lawrence River. From 1986 to 1992, 97 M ohawk 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 fr om 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 great est 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 ma y 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 o ff 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 polychlorinat ed dibenzo-p-dioxins, dibenzofurans (PCDD) and their precursors chlorinated benzenes and phenols. The

contamination of the select ed products with these organ ic xenobiotics proved to be very variable. Remains of firewor ks contained octachlorinated dioxins and furans up to 142 ng I-TEQ/kg as well as hexachlorobenzene in the range of 0.05230 t high temperatures during the deflagrati on of black powder charges could not suppress the formationof PCDD/F from appropriate precursors.

Fomin, A., A. Paschke, et al. (1999). "A ssessment of the genotox icity of mine-dump material using the Tradescantia-stam en hair (Trad-SHM) and the Tradescantiamicronucleus (Trad-MCN) bi oassays." 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 cu rrent standard German leaching test methods (S4 eluate) as well as leachat es obtained using a new eluation method (pHstat4) were tested and compared. Conc entration of heavy metals in the p ed

increased mutation rates when solutions co ntaining more than 32% eluate were used. The low pH of the pHstat4 eluate was not responsible for the genotoxicity observed using both bioassays, as indicat ed by the lack of si gnificant mutation

rates in the nitric acid controls. Th is 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. Youngl ai, 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 environm ental toxicants and potential interaction with postnatal genistein, gross enlargement of thoracic mammary glands was observed in female offspring at 200 days of age. Theref ore, the objective of this study was to analyze the effect of in ut ero exposure to a mixtur e of toxicants on mammary gland morphology. Time-mated Sprague-Dawle y 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 post natal exposure to phytoestrogens in soy formulas poses breas t cancer benefit or risk, and potential

interactions with environmental toxicants ar e unknown. Therefore, half the female pups from each treatment group receiv ed either subcutaneous vehicle or genistein (10 microg/g body weight [bw]/d ay) on postnatal days 2-8. Following necropsy at 200 days of age, a pathol ogist, blinded to treatment groups, examined mammary gland hist opathology. Only mild histological changes were found in mammary glands of rats expos ed to the mixture in utero while pronounced ductal hyperplasia, lactational changes, and fibrosis were observed in mammary glands from the genistein gr oup and were more prominent in the mixture + genistein group. Mammary gl ands of the control group were histologically normal. Collectively, our re sults reveal that postnatal exposure to pharmacological levels of genistein induc es profound morphological changes in the mammary glands of adult female rats, and that high levels of phytoestrogens possess the potential to modulate the toxico logical effects of toxicant mixtures.231 Gagne, F., M. Pardos, et al. (1999). "Toxicity evaluation of organic sediment extracts resolved by size exclusion chromatogr aphy using rainbow trout hepatocytes." Chemosphere 39 (9): 1545-1570.

BIOSIS COPYRIGHT: BIOL ABS. T he (geno)toxicity of sediment

dichloromethane extracts and fracti ons obtained by size exclusion chromatography were evaluated to investigate effects based on size fractionation. In this study, three sedi ments 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)fractionat ed sediment extracts. The liver cells were exposed to c mental sulfur (S8) a ccounted for 14-41% of extractable sulfur and were found to elute in the post-colu mn volume (PCV) fraction despite its molecular weight of 256 amu. Heavy meta ls 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 extr acts, sublethal effects were present principally by the HMW and LMW fractions suggesting that some chemicals were also associated with high molecular wei ght 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 t he 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." Bu ll Environ Contam Toxicol

68 (2): 230-6.

Gan, P., Y. Fan, et al. (2001). "[Experiment of biodegrad ation 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 diffe rent sites after incubating about 2 months. During the growth of the mix ed microorganisims on chlorobenzenes, the accumulating consumption of oxygen, the microbial population curve and the

concentration of released Cl- were invest igated. The result showed that the mixed microorganisms were able to ut ilize 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 activi ty of the living cells. The order in

which the chlorobenzenes we re readily degraded was 1,4- dichlorobenzenez[356.7 micrograms/(L .d)] > 1,2,4- tr ichlorobenzene[110.4 micrograms/(L.d)] > hexachlorobenzene[ap proximately 6 micr ograms/(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 reacti on 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 io ns 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 el ement of HCB. After identification of the final dechlorination products, we can conc lude that the reaction of HCB with CaO at 300-400 degrees C is through a dechlorin ation/polymerization pathway, which is induced by electron transfer. An over all reaction formula for HCB reaction with CaO was proposed and was energet ically quite favorable. The results are helpful for the further comprehension of t he reaction mechanism for thermal

dechlorination of PCDD/Fs in CaO rich matrices.

Gerhard, I., B. Monga, et al. (1999). "Chlorinated hydr ocarbons in infertile women."

Environmental Research 80 (4): 299-310.

BIOSIS COPYRIGHT: BIOL ABS. This st udy was conducted to investigate the hypothesis that chlorinated hy drocarbons (CHC) may affect fertility in women. In 489 infertile women, CHC levels were measured in whole blood. Different anamnestic and clinical parameters were obt ained or investigated in order to detect possible associations to CHC concen trations. CHC levels were correlated to the women's age, body mass index, and nationality. Especia lly 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 gener al population." Osteoporos Int 11 (12): 1036-42. Persistent organochlorines (POCs), such as polychlorinated biphenyls (PCBs) and DDT, are present at relatively hi gh concentrations in food and show estrogenic, anti-estrogenic or anti-androgenic activity in biological test systems. Because bone mineral density (BMD) in me n 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 y ears) from the general Swedish population. Ten PCB congeners, five DDT isomers, hexachlorobenzene, three hexachlorocyclohexane isomers, tr ans- nonachlor and oxychlordane were analyzed by gas chromatography. Quant itative bone measurements were performed by dual-energy X-ray absorptiome try 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 ho rmonal 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 Sw eden 1991-1997: spatial and temporal trends."

Sci Total Environ 246 (2-3): 195-206. Results from the Swedish control progr amme 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 report ed during the 1970s-1990s also has occurred in meat-producing animals duri ng 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 exposu re of the animals. The organochlorine concentrations were higher in bovines than in swine, and declined faster in swine than in bovines. Moreover, the concentra tions of CB 153 and p,p'-DDE were similar in bovines, but in swine the av erage concentrations of the two compounds differed two-fold. Apart fr om possible species differences in metabolism of organochlorines, this may be due to differe nces 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 duri ng the summer period. Finally, a sexdependent difference in concentrations wa s indicated in swine, but not in bovines. Our study shows that a lot of in formation 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 le vels of selected persistent organic pollutants, namely polychlo rinated biphenyls (PCBs), dichlorodiphenyltrichloroetane and it s degradation products (DDTs) and hexachlorobenzene (HCB), in Mediterranean sediments, including data published from 1971 to 2005, has been conducted in or der to assess their main drivers and pressures in the environment. The app lication of mapping tools (GIS) and234 statistical instruments enabled the a ssessment of geographical and temporal trends. Chemical contamination mainly or iginates 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 leve ls of contaminatio n for the region. A decreasing temporal trend in concentra tions 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 iden tified 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 Oc tober 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, so me 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 di ssolved phases) and from not detected (ND) to 170 ng l(-1) for t he 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 or ganochlorine compounds and atrazine (mean 82 ng l(-1)) among the polar pesti cides. 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 ma tter associated to runoff and sediment resuspension. Whereas for more water soluble contaminants, such as the agrochemicals, their seasonal use had a hig her incidence in contaminant fluxes. Bulk chemical parameters such as SPM , DOC, POC, %OC, %ON and C/N ratio provided additional information on the or ganic matter sources. This provides a better understanding of the temporal variability of the contaminant

concentrations.

Gouin, T., D. Mackay, et al. (2004). "E vidence for the "grasshopper" effect and fractionation during long-range atmospheric tr ansport of organic contaminants." Environ

Pollut 128 (1-2): 139-48. Although there is indisputable evidenc e that long-range atmospheric transport (LRAT) of organic contami nants occurs on a global scale, uncertainties remain

about the detailed mechanism and extent of this phenomenon as well as the physical-chemical properties which facilit ate LRAT. In this study, we discuss how235 mass balance models and monitoring dat a can contribute to a fuller understanding of the mechani sm 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 emissi on-deposition event) and "global fractionation" (the differing behavior of chemicals as they are transported). It is shown that simple ma ss 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 avail able evidence supports the notion that many persistent organic pollutants exper ience varying degrees of "hopping" during their environmental journey and as a consequence become fractionated

with distance from source.

Grace, D. (2009). "Errant corporations, di ffuse 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 vari ous aspects of the HCB legacy at the Orica plant at Botany. Whet her explicitly or implicit ly, they are concerned with questions of ethics; with the just distri bution 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 t heir significance for corporate ethics.

Gregoraszczuk, E. L., K. Milczarek, et al. (2008). "Steroid secret ion following exposure

of ovarian follicular cells to three differ ent 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 Atlant ic cod liver, and two mixtures extracted from burbot liver, 'Mjosa mix' and 'Losna mi x'. The POP mixtures were chemically

characterized. Co-culture of theca and granulosa cells, were exposed for 48h with different doses of 'Marine mix', 'Mjo sa mix' or 'Losna mix'. As an end point cell viability was determinated by LDH te st, steroid analysis by EIA and caspase3 by colorimetric substrate. Chemic al characterization of the mixtures

demonstrated that the 'Mari ne mix' contained high levels of DDTs and PCBs. In the 'Mjosa mix', the dominant pollu tants 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 'Mar ine 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 t heir 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 proc esses 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 sect or in Poland." Environ Sci Pollut Res Int

14 (5): 326-32.

BACKGROUND: The aim of t he project was to measure the actual emissions of PCDD/F, PCBs and HCB from 20 selected me tallurgical installations in Poland, in order to update the nationa l inventory of dioxin em ission from metallurgical industry for developing a strategy for dioxins and furans emission abatement from the subject facilit ies (UNEP 2005). METHODS: Sampling methodology used in this work was developed at the Cracow University of Technology because of the complexity of simultaneous sampli ng and determining PCDFs, PCDDs, PCB

and HCB. For the determination a GC-MS /MS system was used. RESULTS AND

DISCUSSION: Results from the work indi cate that the highest dioxins and PCB

concentrations were recorded for iron ore si ntering plants at 1.10-1.32 ng total1 TEQ/Nm3 followed by aluminium scrap me lting 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 alumin ium plants the HCB concentrations were in the range of only 10.1-22.7 ng/ Nm3. CONCLUSIONS: The above investigations indicate that secondar y aluminium production is the most significant dioxins source, if calculated as emission factor values. However, iron ore sintering plants are operating at mu ch higher production capacity, causing this process to become the major source of dioxins, PCB and HCB pollution to the atmosphere in Poland. RE COMMENDATIONS AND PERSPECTIVES: Based on the performed tests and the envir onmental reviews of selected plants

several recommendations were formulated for the reduction of generation or of emission of these pollutants from iron ore sintering plant s, electric arc furnace steel production processes, hot-blast furnace operations, secondary aluminium smelting and primary zinc pr oduction 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 ecosyst em of the Lagoon of Venice were studied, in order to provide a general pi cture of conditions in the lagoon in terms of contamination by persistent organic po llutants (POPs). We present here novel data on atmospheric deposition, water, sedi ment and clam samples collected in the lagoon during the period Januar y 2001-December 2004. Atmospheric deposition was sampled monthly at six site s located both close and far from large industrial and urban sources. Water sample s were collected monthly from fifteen237 stations, and twenty-five samples of sediments and clams (Tapes philippinarum)

were collected in four areas where cl ams are farmed and harvested inside the lagoon. All samples were analys ed for PCDD/Fs, PCBs and HCB by HRGC/HRMS in the same laboratory. All samples examined (atmospheric deposition and water) substantially confi rmed the spatial pattern reported in previously published data on sediment s and atmospheric deposition: the zone surrounding the Porto Marghera petroc hemical plant always had the highest levels of POPs (i.e., PCDD/Fs: atmos phere 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: atmos phere 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 encount ered 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 ar e 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 relati onship to sex steroid concentrations and phallus size in juvenile American alligators. " Archives of Envir onmental 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 steroidog enesis. Embryonic exposure to environmental contaminants in the eggs has been hypothesized to be the causal agent for these changes. However, posthatch ling exposure can also contribute to , dieldrin, endrin, mirex, oxychlordane, SIGMADDTs, and SIGMAPCBs compared to juveniles from the other lakes. Fu rther, we observed no correlations between

serum contaminant concentrations and se x steroid concentrations (estradiol17beta and testosterone). However, serum te stosterone was significantly lower in males from Lake Apopka and Orange Lak e compared to Lake Woodruff NWR. We did not observe relationships between p hallus 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 compou nds." Analytical Communications 36 (6): 235-242.

BIOSIS COPYRIGHT: BIOL ABS. The so lvation 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 of238 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 hepatoc arcinogenicity of hexachlorobenzene, pentachl orobenzene, 1,2,4,5-tetr achlorobenzene, 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 chlorobenz ene isomers, a thor ough 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-dichlorobenz ene (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 forma tion of GSTP1-1 positive foci and that DCB does not. The num bers and area of foci were greatest following HCB promotion, and TeCB and PeCB were approximately equal in their promoting ability. Levels of hepatic C YP1A2, 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 chlorobenz ene isomers may indi cate promotional ability, and that this property mi ght 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." Envi ronmental Toxicology and Pharmacology

19 (2): 231-238. The T-Screen represents an in vi tro bioassay based on thyroid hormone dependent cell proliferation of a rat pituitary tumor ce ll line (GH3) in serum-free medium. It can be used to study interfer ence of compds. with thyroid hormone at the cellular level, thus bridging the gap between limitations of assays using either isolated mols. (enzymes, trans port proteins) or complex in vivo expts. with all the complex feedback mechanisms present. Co mpds. are tested both in the absence and presence of thyroid hormone (EC50 conc n. of T3) to test for both agonistic and antagonistic potency. Thyroid horm ones (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: Tr iac; 3,3',5,5'-tetraiodothyroacetic acid: Tetrac) induced cell growth, with the rank or der 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 horm one 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 ac tive potencies of pure chems. or

environmental mixts.

Hall, A. J., C. D. Duck, et al. (1999). "Organochlorine contaminants in Caspian and

harbour seal blubber." Envir onmental Pollution (Series A) . Ecological and Biological

106 (2): 203-212. BIOSIS COPYRIGHT: BIOL ABS. Organochl orine contaminants (pesticides and individual polychlorinated biphenyl congeners, PCBs) were measured in Caspian (Phoca caspica) seal blubber and compar ed 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. Ex posure to certain pesticides and organochlorines has been shown to be risk fa ctors. Epstein-Barr virus (EBV) is a human herpesvirus that has been associated with some subgroups of NHL, such as Burkitt lymphoma and lymphomas relat ed to severe immunosuppression. In this study, we measured lipid adjusted blood concentrations of 36 congeners of polychlorinated biphenyls (PCBs), p,p'-d ichlorodiphenyl-dichloroethylene (p,p'- DDE), hexachlorobenzene (HCB), four diffe rent 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. Ti ters of antibodies to the Epstein-Barr early antigen (EA) were correlated to concentrations of organochlorines. We found a significant difference in lipid adjusted blood conc entrations 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% c onfidence interval (CI) =0.94-3.8. This risk was further increased in those with a level above the

median value of "sum of PC Bs" (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 these240 chemicals. Also for the "sum of imm unotoxic 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 neurologic al impairment?" Environ Res 88 (3): 141-4. The concentration of certain persist ent organic pollutants was determined in a family including both parents and one son with neurological impairment suggested to be Attention Deficit-Hyperac tivity 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, a nd 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, compar ed 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 t he age of 17, the mother wa s exposed to DDT in her home environment. We discuss the potential of fetal and breas t-feeding exposure of the son. Neurodevelopm ental impairment has been re ported for dioxins and PCBs, but DDT seems to have been less investigated in this respect.

Hauser, B. and P. Popp (1999). "M embrane extraction combined with thermodesorption/gas chromatography and mass selective detection for the analysis of volatile organic compounds in water." J ournal 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 anal ysis by using it in conjunction with

membrane extraction. A flow of nitr ogen passes through a silicone hollow fiber immersed in the water sample and extrac ted volatile organic compounds are enriched in a sorption tube m ounted on top of the extrac tion cell. The sorption tube is then placed in the thermodesorpt ion 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, brom obenzene, ethylbenzene, 1,1,2,2- tetrachloroethane, and 1,2/1,4-dichlor obenzene. The method was found to be suitable for compounds with boiling point s up to 220ˆC as memory effects increased considerably from dich loro- to hexachlorobenzene. Highly contaminated groundwater samples were analyzed. Quantitative results corresponded well with those achieved with conventional

Hellstrom, A., H. Kylin, et al. (2004). "Dis tribution of some organochlorine compounds in pine needles from Central and No rthern Europe." Environ Pollut 128 (1-2): 29-48. Levels of selected organoc hlorine compounds in pine needles were measured in two sampling series. The first seri es collected in 1989 covered Southern241 Germany to Northern Scandinavia, and the second collected in 1990 covered

Czechoslovakia to Estonia. The levels of alpha-hexachlorocyclohexane (alphaHCH) and hexachlorobenzene (HCB) were re latively uniform throughout Europe, while the levels of gamma-hexachlor ocyclohexane (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 concentra tions. 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. Br adbury (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, A ugust 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 en vironmental monitoring environmental contamination chlordane pesticide pollu tant tissue residue toxicity reference

values ddt dieldrin endrin hexac hlorobenzene mercury heavy metal pcbs polychlorinated biphenyls freshwater ecol ogy risk assessment water quality great lakes north america mh - congresses

Henschler, R., K. E. Appel , et al. (2001). "Proliferati on and differentiation of murine haemopoietic progenitor cells in stroma-free cu lture in the presence of metabolites of chlorinated pesticides." Toxicol In Vitro 15 (1): 31-7.

We have studied the influence of metabolit es of chlorinated pesticides (lindane, pentachlorophenol, hexachlorobenz ene) 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), tetr achloro-p-benzoquinone (Cl(4p)BQ), but not their positional isom ers, 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 cultur ed under conditions which lead to selfrenewal than under conditions which lead to granulocyte-macrophage

differentiation. Under the latter co nditions, Cl(4)pHQ and Cl(4p)BQ even stimulated growth at intermediate conc entration 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 t he granulocytic lineage was increased at high concentration levels of each test compound. However, stimulat ory effects on the macrophage lineage were observed at inte rmediate concentration levels of Cl(4)pHQ, Cl(4p)BQ and 2,4,6- Cl(3)P, and differentiation into erythrocytes was242 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 me chanisms could lead to myeloplastic

disorders.

Hillier Oam, N., J. Gennissen, et al. (2009) . "Our battle with hexa chlorobenzene: citizen perspectives on toxic waste in Botany." J Environ Manage 90 (4): 1605-12. The perspectives of residents are br ought together in this assembly of statements concerning t he management of hexachlor obenzene waste in Botany, a southeastern suburb of Sydney. The paper indicates how residents have responded as participants in public partici pation 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 t he State Government spons ored Commission of Inquiry,

indicate the deficit of resources fa ced 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 s perm whales stranded in the s outhern 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 aromat ic 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 bl ubber) 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 C 57BL/10ScSn mice with iron greatly

sensitizes them to the inducti on of hepatic porphyria caused by hexachlorobenzene (HCB). HCB will also ca use 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. inject ions of dextran sulfate (control), iron (Imferon) or combined iron and HCB. 6 week s after treatment plasma ALT levels and hepatic free iron, porphyrin, lipid per oxides and 8- hydroxyguanosine (8- OHdG) levels were analyzed. Hepatic por phyrin level was significantly (p < 0.001) increased following combined iron/HC B treatment as compared to control243 mice. The level of lipid peroxides increas ed 9-fold (p = 0.001) and 35-fold (p < 0.001) after iron and iron/HCB treatment re spectively, whereas the level of 8- OHdG was increased 2.5-fold (p = 0.002) an d 7.5-fold (p < 0.001) after iron and iron/HCB treatment respectively as co mpared 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 event s of hepatic carcinogenesis in experimental porphyria.

Horvath, M. E., S. P. Faux, et al. (2001). "Vitamin E protects against ironhexachlorobenzene induced porphyria and forma tion 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-O HdG) was studied in the livers of C57BL/10ScSn mice following hexach lorobenzene (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 contro l group. Mice treated additionally with vitamin E had significant (P<0.001) lower levels as compared with the HCB-iron group. Sim ilarly, 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 vi tamin E (P<0.02). The data support the hypothesis that the mechanism of hepat ic 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 possessi ng oestrogenic activity (x enooestrogens). They are persistent and accumulate in fatty tissue. Aim of our study is to address the question, whether a selection of such co mpounds 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 undescen ded testes, were examined by highresolution gas chromatography and mass spec trometry for DDT and metabolites, polychlorinated biphenyls (PCB), to xaphenes, hexachlorocyclohexane (HCH), chlorinated cyclodienes and chlorinat ed benzenes. We were able to find

accumulation of all substances in ever y patient. Statistical analysis revealed a highly significant difference between pat ients from the control group and those from the undescended testes gr oup 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 case s, prenatal exposure to exogenous oestrogens is an attractive and plausible hy pothesis. In order to confirm this, some questions will have to be answered in further studies: effect of exposure to244 xenooestrogens during a spec ific period of development, probable role of other substances with proven or suspected ho rmonal activity, potential synergism of such compounds and differences in individual susceptibility.

Houtman, C. J., C. P. Sw art, et al. (2002). "DR- and ER-CALUX assays as tools to direct toxicity identification and eval uation of endocrine disr upting chemicals." Organohalogen Compounds 58 (Dioxin 2002): 349-352. The authors present the development of a toxicity identification and evaluation (TIE) method for diox in-like and estrogenic compds. of sediments, directed by responses generated in dioxin responsive (DR)- and estrogen responsive (ER)- CALUX (Chem. Activated Lucifer ase Gene Expression) assays.

Howe, T. S., S. Billings, et al. (2004). "S ources 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 hexac hlorobenzene (HCB) were measured in spruce needles at 36 sites in eastern Al aska 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 concent ration ratios of isomeric PAHs indicates the relative importanc e of combustion and petrogenic sources. The relative combustion contribution is largest in coastal samples and smallest near Fairbanks. In contrast, the concentrati on 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 Dol ah, et al. (1999). "Predicting st ress in benthic communities of

southeastern U.S. estuaries in relation to chemical contaminat ion of sediments." Environmental Toxicology and Chemistry 18 (11): 2557-2567.

BIOSIS COPYRIGHT: BIOL ABS. Matc hing 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 ex posure. 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 quotient s > 1.0, which is the beginning of the range associated with a hi gh 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 organi c chemicals in earthworms, including a compartment for the gut contents. A M onte 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 equili brium partitioning (EP), independent of the uncertainties in all of the model param eters. 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 par ticularly useful when the organism's food source is specifically cont aminated and EP c annot be applied.

James, P. (2009). "The supervi sion of environmental risk: t he case of HCB waste or Botany/Randwick?" J Environ Manage 90 (4): 1576-82. The governance activities of capital and t he state include attempts to control the timing and spacing of social activities such as the production of environmental risks and settlement of different social gr oups. The supervisory activities that have shaped the environmental and social history of the Bo tany/Randwick area are identified here, to ex amine how the HCB waste risk developed in that community. The analysis shows that multiple environmental risks and an ethnically diverse, working class comm unity have been brought together in space to create environmental injustic e. Analysing the governance of one

environmental risk like hexachlorobenz ene (HCB) waste may not increase understanding about communities facing mu ltiple environmental risks or the supervisory processes that lead to the unfair accumulation of risks for particular places or social groups. Lessons fr om the environmental justice movement suggest that reframing problem s like HCB waste management at Botany/Randwick as distributive justic e 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 distribut ion of planar and non-planar chlorobiphenyls, 4,4'-DDE and hexachlo robenzene in sheep and lambs." Chemosphere

38 (11): 2607-12. The bioconcentration and distribution pa ttern 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 thei r offspring continuously exposed during the two months lactation period. Analyse s were performed by high resolution gas chromatography. The levels of individual organochlorines va ried significantly between tissues; the tissue/blood ratio (on a fat basis) varied by two orders of246 magnitude for individual congeners. T he 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 li pophilic organochlorines in ovine

dentine." Arch Oral Biol 46 (12): 1111-6. The bioconcentration of lipophilic organochl orines 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 hexachlorobi phenyls IUPAC Nos. 155 and 169) and organochlorine pesticides 1,1-bis(4-chlor ophenyl)-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 wit h sulfuric acid and hexane. The concentration of organochlorines in dent ine 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 ti ssue 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 bioconcent ration 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 in teractions, play a part in the different bioconcentrations of individual organochlor ine 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 ch lordane and estimates of gas exchange for Lake On tario." 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 temperat ure range of 5-35 degrees C. The HLC variation versus temperature (K) was de scribed by logH=m/T+b. Parameters of this equation were (with standard deviation s) 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'-D DE: m=-2043+/-240, b=8.37+/-0.82. The HLCs (Pa m3 mol(-1)) at 25 degr ees C (298.15 K) were: TC=29; CC=27; TN=32; p,p'-DDE=33 and HCB=35. These HL Cs values were used to calculate fugacity ratios from paired air and water data from Lake Ontario, July 1998. The resulting fugacity ratios predict that vo latilization 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 adv erse 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 ther efore wished to eval uate the impact of

the HCB environmental event on the sex rati o of the progeny of the survivors. We undertook an assessment of 1) the effects of HCB expo sure on the proportion of male births of individual subjects who had survived, 2) variables that significantly predicted the proportion of males among th ese 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 co mpared to control populations. However, subjects reporting exposure at th e 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 th ese women also significantly predicted the percent males per subj ect. The available national data demonstrated a significant reduction in t he 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 s ubjects over their reproductive lifespan. The HCB episode does not explain t he pattern of the national trend from a population perspective.

Jensen-Lee, C. (2009). "When unequals are treated equal ly: 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/dem ocratisation. The paper argues that the standard operat ing 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 form al equality dating back to Aristotle, it is argued that treating unequals equally results in the circumvention of deliberative democratic ideals by perpetuating ent renched structural inequalities while nonetheless giving the superficial appearance of fair play.

Jones, K. C. and P. De Voogt (1999). "Persistent organic pollu tants (POPs): State of the science." Environmental Pollution (S eries A). Ecological and Biological 100 (1-3): 209-

221.
BIOSIS COPYRIGHT: BIOL ABS. T he environmental chemistry and ecotoxicology of persistent organic pollut ants (POPs) are fascinating areas of scientific research. Our objective in th is paper is to provide a brief, focussed248 overview of what constitutes a POP, hi ghlight the harmful effects they may have on biota, make some comments on t heir 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 Na tional 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 tar get control. The objective s of the control are to monitor consumer exposure to health hazards and to enforce national and European Community regulations. T he Danish Veterinary and Food Administration is responsible for estab lishing methods, data manipulation, and evaluation, but actual analyses are perfo rmed at 4 regional laboratories. In addition to a description of the Danish National Pestic ide Monitoring Program on food, the effects of lowering the repor ting limits are discussed. Pesticides

included are those in current use as well as chlorinated pesticides like lindane, DDT, and HCB, occurring in food now prim arily as a result of environmental contamination. Commodi ties analyzed are fruits, vegetables, cereals, bran, fish, and animal products such as meat, butte r,cheese, fat, and eggs . In fruits and vegetables, residues were detected in 10% of 2515 samples, with higher incidences of detection for foreign commodi ties. Violation rate was 0.6%. In food of animal origin, low levels of organochl orine pesticides were detected in most fish samples and in more than half of t he 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). "Immunot oxicology and veterinary medicine." Acta

Veterinaria Brno 68 (1): 57-79.

BIOSIS COPYRIGHT: BIOL ABS. Imm unotoxicology investigates unwanted adverse effects of xenobiotics (pestici des, heavy metals from emissions, new DNA-recombinant products, immune re sponse modulators, monoclonal antibodies, drugs and others) on the immune system of man and animals. Immunotoxicology in veterinary medici ne 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 s upported by a complex set of tests

rather than limited number of them. The extent of f unctional and non-functional immunity tests should be determined on the basis of knowledge about the

mechanism of the toxic effects of xenobiot ics in animals. This knowledge can be supplied by biochemistry, toxico logy, pharmacology and histopathology (histochemistry and immunohistochemis try). The up-to- date knowledge about immunosuppressive effects of pesticides and their po249 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. Met hods were developed for preparing liquid/liquid and glass wool column satu rators for generating chemical stock solutions for conducting aquatic bioa ssays. Exposures have been conducted using several species of fish, invert ebrate, and mollusks in static and flowthrough conditions using these methods . Stock solutions for 82 organic chemicals were prepared using these sa turation units. The primary purpose of stock generation was to provide a conti nuous and consistent amount of toxicant laden so mparison purposes to water solubilit y values available in the literature. Literature solubility values from a dat abase by Yalkowsky et al. (1) provided information on temperatures and data qua lity 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 wa ter concentrations were generally lower (R=0.98) but were in close agreement with

Kannan, K., M. Kawano, et al. (1999). "E xtractable 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 chlo rinated organics. In this study, the

concentrations and distribution of ex tractable organohalogens (EOX = EOCI + EOBr + EOI) were measured in sedimen t, 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 fac ility. The concentrations of the orga th its elevated proportions relative to the conc entrations of EOBr or EOI in biota suggest that wastes from the chloralkal i processes are a potential source of chlorinated organics present in the environm ent. The relative proportion of known (such as, polychlorinated biphenyls (P CBs), dibenzo-p-dioxins/dibenzofurans (PCDDss), polychlorinated naphthalenes (P CNs), and organochlorine pesticides) to unknown organochlorines in sediment, blue crab, fishes, bi rds, 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 fa ctors such as breast-feeding, parity, and smoking contribute to the variati on of organochlorine compounds (OC: dichlorodiphenyldichloroethene, hexachlorobenzene, betahexachlorocyclohexane, and the sum of pol ychlorinated 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 c onditions were gathered by questionnaires administered to the parents and intervie ws with the mother. Height and weight were determined during the medical examinat ion. Exclusion of incomplete data250 and nonbiologic children of t he mothers yielded a sample of 337 children. We applied regression analysis with indicato r 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 det erminants analyzed,

more of the variance of t he OC concentration is acc ounted for by breast-feeding than by any other variable. Exclusiv e breast-feeding beyond 12 wk was associated with a doubling of OC whol e blood concentration compared with bottle-fed children (dichlorodiphenyldichl oroethene, 0.28 microg/L versus 0.55 microg/L; beta-hexachlor ocyclohexane, 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 micr og/L). These findings indicate that breast-feeding can lead to an extended dur ation of increased OC exposure in

childhood.

Karmaus, W., J. Kuehr, et al. (2001). "Inf ections and atopic disorders in childhood and organochlorine exposure." Arch Environ Health 56 (6): 485-92. The authors investigated whether organochl orine exposure is associated with prevalence of otitis media, pneumoni a, pertussis, asthma, and increased immunoglobulin E levels in children. Or ganochlorine concentrations and histories of infection and atopic manifestation were available for 343 children, and immunoglobulin E levels were availa ble for 340 children. The authors applied logistic and linear regressions and c ontrolled for confounder s. In general, the prevalence of infections in children wa s not related to organochlorine exposure. However, for the combined effect of dichlorodiphenyld ichloroethene with polychlorinated biphenyls or hexachlor obenzene, 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 abov e 200 kU/l (odds ratio = 2.28; 95% confidence interval = 1.20, 4.31). Th is is the first study in which dichlorodiphenyldichloroethene has been identified as a subs tantial risk factor for

asthma and for increased i mmunoglobulin E blood levels.

Khim, J., K. Kannan, et al. (1999). "Characte rization and distribution of trace organic

contaminants in sediment from Masan Ba y, Korea. 1. Instrumental analysis." Environmental Science and Technology 33 (23): 4199-4205.

BIOSIS COPYRIGHT: BIOL ABS. Masan Ba y, 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 an d 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) c ongeners, and 16 polycyclic aromatic251 hydrocabons (PAHs) to characterize t heir spatial distribution and contamination

status. Concentrations of NP in sedi ment ranged from 113 to 3890 ng/g on a dry weight basis (dry wt), whereas concent rations 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 t he 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, concent rations 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 great er near the sites of industrial and shipping activities. Concentrations of tar get analytes were not related to TOC. Although the mean concentra tions of PCBs and PAHs in sediments were less than the suggested sediment quality guidelines (S QG), their concentrations in

some locations were close to or abov e 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." En vironmental 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 exper ienced environmental deterioration since 1994, when it was formed by construction of a sea dike. This study used instrumental analysis and in vitro bioassa ys to characterize organic contaminants

in sediment collected from 11 stati ons on Lake Shihwa. Alkylphenol (AP)

concentrations in Lake Shihwa sedim ent ranged from 20.2 to 1,820 ng/g nonylphenol and from 4.69 to 50.5 ng/g oc tylphenol, on a dry weight basis. Max ignificant dioxinlike activity was associ ated with fractions c ontaining classic aryl hydrocarbon receptor agonist s, such as PCBs, but t he mid-polarity fractions containing PAHs and most polar fractions yielded significant dioxinlike activity. Overall, most of the in vitro bioassa y responses appear to have been caused by

unidentified and/or undetectable com pounds 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 assum ed to be the most important and common prey of polar bears (Ursus maritimus). Ho wever, 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 obser ved feeding on harp seal (Phoca groenlandica) carcasses. Sample s of both harp and ringed seals were obtained and organochlorine (OC) occurrenc e 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 spec imens in late moult. The industrial252 chemicals, polychlorinated biphenyls (PCBs) and hexachlorobenzene (HCB), and the OC pesticides bis-2,2,(chloropheny l)- 1,1,1-trichloroethanes (DDTs), hexachlorocyclohexanes (HCHs), and chlo rdanes (CHLORs) were analysed in blubber. The concentrations of sigma PC B (sum of concentrations of 16 PCB congeners) and sigma DDT (sum of concentra tions 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 concentr ations of 11,133 and 6847 ng g-1 lipid weight, respectively. The mean concent rations of the CHLORs, oxychlordane and trans-nonachlor, were 1311 and 3743 ng g-1 lipid weight, respectively, while

the mean concentrations of HCB and HC H 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 coul d accumulate significantly higher PCB concentrations. We suggest that polar bears feeding along the ice- edge east of Svalbard in May and June preferentially pr ey on harp seals instead of ringed seals, and that this may partly explain t he variation in PCB concentrations among polar bears from the Norwegian Arctic. An hypothesis is that the harp seal may function as a transport ve ctor of OCs into the high Arctic environment.

Klopman, G. and S. K. Chakrava rti (2003). "Structure-activit y 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 31 3 chemicals were used as inputs to train the expert system. The trai ning data set covers inactive, weak as well as very powerful ER binders and represents a variety of chemical compounds. Substructural features a ssociated with ER binding activity (biophores) and features that prevent receptor binding (biophobes) were identified. Although a singl e phenolic hydroxyl group wa s found to be the most important biophore responsible for the estrogenic activity of most of the chemicals, MultiCASE also identified otherbiophores and structur al 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 eac h biophore were constructed as part of the expert system and can be used to predict the activi ty 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 pollut ants." Science of the Total Environment

233 (1-3): 131-140.

BIOSIS COPYRIGHT: BIOL ABS. Concerns about possible combination effects of environmental chemicals with estrogenic ac tivity have motivated the search for253 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 pharmaco logy. In the present communication, we draw attention to conceptual framew orks relevant for a sound analysis of the effects of mixtures of oestrogenic com pounds. 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 wastewat er treatment plant effluent using instream invertebrates and the Ceriodaphnia dubia chronic toxicity

test." Water Research 33 (1): 266-278. BIOSIS COPYRIGHT: BIOL ABS. The purpos e 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 to xicity tests was used to detect a possible cause-effect relations hip between the plant discharge and the receiving water quality. In addition to biological and chem ical quality of the river upstream and downstream from the WWT P outfall, we assessed Hydropsychid life cycle as a field bio-indicator. Laborat ory experiments were carried out using the 7-day Ceriodaphni a dubia chronic toxicity test. Field and laboratory studies were performed simultaneously almost every month from March 1995 to February 1996. Throughout the year, we obs erved a biological degradation at downstream site compared to upstream si te 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 ofchemical pollution of ecosystems in the kafirnigan and kyzylsu river valleys on t he frequency of chromosome aberrations in house miceyresearch article mus mu sculus 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). "Pesti cides and other chemical residues in Swiss total diet samples." Mitteilungen aus Lebens mitteluntersuchung und Hygiene = Travaux

de chimie alimentai re et d'hygiene. 90 (1): 78-107.

BIOSIS COPYRIGHT: BIOL ABS. Foodstuffs contribute to the total exposure of man to pesticides and other c ontaminants. 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 r epresentative for daily nutrition were analyzed with a multi residue method capable of detecti ng more than 300 contaminants. 66 different pesticides and pesticide me tabolites, 8 plasticizers and 6 PCBcongeners were found and quant itatively determined. For most pesticides and organochlorine contaminants the estimated daily intake was found to be much less than 1% of the corresponding AD I values. Among the investigated plasticizers, the results obtained for phthal ates are of particular interest. The254 highest value being 10 % of the ADI was found for bis-n-butyl-phthalate. This finding indicates that more a ttention should be drawn to this class of substances in fut ure. Interesting is the fact that t he intake of fungicides from fruits is more important than from salad. This observation is in c ontrast to the opinion that

salad in wintertime is the main source.

Kurpios, M. and A. Nowosielski (1999). "Chl orinated 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 mu scular 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 chlo rinated 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 he xachlorobenzene (HCB) are ubiquitous compounds that have tumor- promoting properties if applied together with tobacco-specific carcinogens. It was t he purpose of the present study to investigate whether parental smoking by itself will incr ease the prenatal uptake of such organochloric compounds. With the informed consent of the parents, blood samples were taken from 80 full- term neonat es before the first oral feeding. Six PCB congeners (PCB 28, 52, 101, 138, 153, and 180) and HCB were analyzed with capillary gas chromatography. Info rmation 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), passi ve smoking mothers (n = 33), and nonsmoking families (n = 35). Neonates bor n to active smoking mothers had the highest PCB and HCB concentrations comp ared 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 concent rations 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). "Cyt ochrome P450 CYP1A1 enzyme activity and DNA adducts in placenta of women envir onmentally exposed to organochlorines."

Environmental Research 80 (4): 369-382.255 BIOSIS COPYRIGHT: BIOL ABS. Organoc hlorine 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 effect s in newborns from women exposed to organochlorines through the consumption of species from marine food chains, natal organochlorine expos ure was determined by measuring these compounds in umbilical cord plasma. The amount of bulky polycyclic aromatic hydrocarbon (PAH)-related DNA adducts was significant ly greater in the Lower-North-Shore group than in the reference group. Placent al 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 bot h biomarkers, smoking was found to be an important confound

Lamoureux, E. M. and B. J. Brownawell (2004). "Influence of soot on hydrophobic organic contaminant desorpti on and assimilation efficien cy." 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 ex periments in an effort to assess and compare the importance of soot in controlling HOC desorption and depositfeeder assimilation efficiency. Th ree contaminants, naphthalene (NAP), benzo[a]pyrene (BaP), and hexachlor obenzene (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 Nere is succinea assimilation efficiency experiments on the BaP- and HCB-contaminated sorbates were conducted. Both NAP and BaP desorption rates for s oot and soot-amended sediments were reduced by at least a factor of tw o relative to unamended sediment. Hexachlorobenzene desorption rates were similar for both the soot-amended and

the unamended sediments. Re sults of N. succinea assimilation efficiency experiments indicate a trend similar to the desorption experiments: higher

assimilation of BaP from unamended relati ve to soot-amended sediment and little

difference in assimilation between treatm ents for HCB. However, soot was more effective in reducing BaP desorption than a ssimilation efficiency, which would be consistent with the hypothes is that the gut fluid di ssolution by deposit feeders may partially decouple biological availabi lity from chemical availability.

Lee, M. H. and P. D. Ryu ( 1999). "Sanitation and tissue residue problems in high quality pork." Asian-Australasian J ournal of Animal Sciences 12 (2): 233-243.

BIOSIS COPYRIGHT: BIOL ABS. Food sa fety 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 effect s of ingesting natural and human-made xenobiotics. Use of drugs in animal pr oduction for the treatment and control of256 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 resi dues 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 veterinar y 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 f unction of particle size." Environmental Health Perspectives 107 (9): 721-726.

BIOSIS COPYRIGHT: BIOL ABS. House dus t is a repository for environmental pollutants that may accumulate indoors fr om both internal and external sources over long periods of time. Dust and track ed-in soil accumulate most efficiently in carpets, and the pollutants associ ated with dust and soil may present an exposure risk to infants and toddlers, who spend significant porti ons of their time in contact with or in close proximit y to the floor and who engage in frequent mouthing activities. The availability of ca rpet dust for e ameter, and each fraction was analyzed for 28 pesticides and 10 polyc yclic 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 pyrethroid s 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 bioaccu mulation and toxic effects of hexachlorobenzene using the polyurethane f oam 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 hydr ocarbon 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 receiv ing industrial wastewaters containing HCB and other pollutants, using the st andardized polyurethane foam units (PFU) method. Field samples were taken from ei ght stations estab lished along the Fuhe River in January and August 2006. The conc entration 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 comm unities. This study demonstrated the257 applicability of the PF U method in monitoring the effects of HCB on the level of

microbial communities.

Liu, W., P. Li, et al. (2 005). "Short-term toxic effect s 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 solubl e protein level of broadbean (Vicia faba) seedlings were researched at different soil concentrations of chlorobenzene (CB), 1,2,4-trichlor obenzene (TCB) and hexachlorobenzene (HCB). The results showed that root grow th 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 ther e was a delay in returning to the control level. The tota l soluble protein content in seedlings

increased with TCB concentration and durati on 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 exposur e to 5 d of TCB stress to clear tap water for 3 d, SOD activity at 50 micr og x g(-1) TCB recovered towards control level (P>0.05) while a significant incr ease in SOD activity was observed at 100 and 200 microg x g(-1) TCB compared to cont rol (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 seedl ings was not observed after a 3 d

exposure.

Liu, W., Y. S. Yang, et al . (2004). "Root growth inhibiti on and induction of DNA damage in soybean (Glycine max) by chlorobenzene s in contaminated soil." Chemosphere

57 (2): 101-6. The cytotoxic and genotoxic effect s of 1,2,4-trichlorobenzene (TCB), chlorobenzene (CB), and hexachlorobenzen e (HCB) on root growth and DNA strand breakage damage of soy bean nuclei in the test soil were studied using the comet assay. Results indicated that the r oot growth was signifi cantly 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 s ensitive to the TCB than the root growth. There was a significant dose-re sponse 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 bi omarker of soybean exposed to TCB contamination. Significant cytotoxic th reshold concentration of the TCB exposure on the root growth inhibiti on 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). "Season al 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 pr oduction and application of organochlorine pesticides (OCPs) although, data on thei r nationwide distribution and seasonal variations in the atmosphere is still s parse. Passive air samplers (PAS) were

therefore utilized to obtain seasonal dat a from 37 Chinese cities and three background sites in 2005. Concentrations and spatial and season al distribution of dichlorodiphenyltrichloroethanes (DDTs), chlordanes (CHLs), hexachlorobenzene (HCB), and endosulfans (Endo) are presented in this paper, and their potential sources are discussed ba sed on the dataset. It is estimated that ca. 95% of DDTs present in the atmo sphere of Chinese cities was still from technical DDT, while only ca. approximat ely 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 curr ent sources of technical DDT. The DDT

concentrations in several Chinese cities seem to match well with the reported

DDT concentrations in human breast m ilk. A low TC/CC ratio was observed across China in the winter to spring, wh ich 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 fr om combustion sources. Samples with higher endosulfan concentrations occu rred in the cotton production areas, indicating its major use in killing cotton pests.

Lloyd-Smith, M. (2009). "Inf ormation, power and environmental justice in Botany: the role of community informati on systems." J Environ Manage 90 (4): 1628-35.

In the environmental conflict that su rrounds the sighting of hazardous waste facilities there is usually a volatile mi x of disparities in power, expertise and information access as well as differing views on risk, which are all played out amidst commercial arrangements and environ mental 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) bas ed on participatory models can help address the outstanding issues of capacity, information access, power inequities and environmental justice. CISs are an e ffective response to the five crucial elements of a toxic dispute, that is, t he dialogue, capacity building, information access, evaluation of hazards and risk, and expertise. This paper will review the role of community accessible information sys tems in the dispute in Botany over the management and destruction of Orica Australia's sto ckpile of the persistent organic pollutant, hexachlorobenzene (HCB). It will focus on the role of CIS in responding to the challenges for expert in formation delivery, and in addressing the disparity of informational power within the toxic dispute.259 Lloyd-Smith, M. E. and L. Bell (2003). "Tox ic disputes and the rise of environmental justice in Australia." In t J Occup Environ Health 9 (1): 14-23. The paper examines the rise of environment al justice issues in Australia, evident in two toxic disputes; the first, in a Pe rth outer suburb in We stern Australia where

residents faced both a hazardous waste dump and the nation's biggest chemical fire; and the second, in the Sydney s uburb 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 loca l 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 communi cation of risk. The informational inequity and resource disparit ies 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 wom en." Eur J Cancer Prev 11 (2): 129-35.

Information on the associati on 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 r egulation. 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 fa ctors, there was no evidence of a relationship betw een beta-HCH, HCB and PCBs and breast cancer risk (OR for beta-HCH tertile 3 vers us 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). "Sorpt ion 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 we re investigated. In experiments, environmentally relevant concentra tions of pentachlorophenol (PCP), hexachlorobenzene (HCB), and dichlorobipheny l (DPCB) were applied to living (both growing and nongrowing) bacteria as well as to dead bacteria. For PCP (an ionizing chemical), bacterial growth dec reased, and bacterial death increased, as the PCP concentration increased. In sorpti on 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 noni onizing chemical) did not af fect bacterial growth or260 death at all HCB concentrations investi gated. 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). "E vidence of the impact of ENSO events on temporal trends of hexachlorobenzene air c oncentrations over the Great Lakes." Sci

Total Environ 313 (1-3): 177-84. This study presents an evidence for associ ation of the air concentrations of HCB measured in the Great Lakes region wit h 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 st rong correlations with the Multivariate ENSO index (MEI) during winter (Dec ember-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. Departu res of HCB air concentrations for each winter during 1992-1999 from t hat averaged over all winters of 1992-1999, i.e. the anomaly, also show the same tempor al 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 agric ulture, from industrial sources in North

America and in the rest of the world hav e decreased substantially compared to those in the 1970s and could not by t hemselves account for observed HCB air

concentrations around the Great Lakes si nce the 1990s. Interannual fluctuations

of HCB concentrations are caused most lik ely 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 c oncentrations 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). "Phytoto xicity of chlorinated benzenes to Typha angustifolia and Phragmites communis." Environ Toxicol 24 (1): 43-8. Healthy growth of plants is a prer equisite 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 la ck of phytotoxicity data impedes their application in field sites. This study inve stigated 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 s pecies-dependent, with Typha demonstrating significantly higher tolerance than Phragm ites. The concentration of 1,3,5-TCB261 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 chlorinat ed benzenes in sediments on Typha increased with decreasing chlorine atom s. 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 it s higher availability and easiness to be taken up by plants. The conclusion wa s supported by both growth rate calculations and plant height measurement s. (c) 2008 Wiley Periodicals, Inc. Environ Toxicol, 2009.

Macleod, M. and D. Mackay (1999). "An asse ssment of the environmental fate and exposure of benzene and the chlor obenzenes in Canada." Chemosphere 38 (8): 1777-

1796. BIOSIS COPYRIGHT: BIOL ABS. Systemat ic modelling of the fate of benzene and the chlorobenzenes is presented whic h follows a four-stage process of chemical classification, quantifyi ng discharge rates and environmental concentrations, evaluative assessment of fate and regional mass balance modelling has been carried out for the sout hern Ontario region. The EQC model was applied to determine t he 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 st eady 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 pres ented. Results sugges t 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 Gr eenland 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 lo wer than concentrations typically found in sediments at lower la titudes. The observed temporal trends (direct and indirect dating) show a dec reasing total PCB concentration. Even though local contamination sources exist, the POP deposition in the studied area is most likely a result from long-r ange transport. The hypothesis about "cold condensation" suggests a latitudinal frac tionation to occur between different volatile compounds during the transport towa rd the pole. In this study a time delay in the deposition for the low-chlori nated PCBs (tri- and tetrachlorinated), compared to their emission histories and compared to higher chlorinated PCBs, was indicated. Although very low tetr a-BDE #47 concentrations are observed in262 this study, there are indications for an increasing concentration in recent sediment layers that may reflect incr easing environmental concentrations at lower latitudes. The investigated pesticides are still in use at lower latitudes,

however neither chlordane nor HxCBz s how any distinct temporal trend of increasing or decreasing concentrati on 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 phototransformati on in the presence of TiO2 and humic substances leads to a disappear ance of these compounds. The reaction rate is dependent on the semiconductor ox ide 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 dibe nzofurans (PCDD/Fs), polychlorinated biphenyls (PCBs), polychlorinated naphthalenes (PCNs), polybrominated diphenylethers (PBDEs), polychlo rinated diphenylethers (PCDEs), hexachlorobenzene, and polycycl ic aromatic hydrocarbons through fish and seafood consumption by children of Catal onia, Spain, was assessed. In 2005, samples of the 14 most consumed marine species in Catalonia were randomly acquired in various cities of the c ountry. 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 re spective tolerable daily intake of those pollutants for which it has been alr eady established (metals, PCDD/Fs plus dioxin-like PCBs, HCB, and PAHs). In rela tion 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 Laur entian Great Lakes." Environ Pollut 129 (1): 131-44.

Data from recent sediment and surf ace water surveys have been collated and mapped to illustrate the spatial distribut ion of contaminants across the entire

Great Lakes basin. Information from histor ical surveys, together with data from surface water monitoring programs in thr ee 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 contam ination while Lake Ontario had the highest. Contaminants such as gamma-HCH (lindane) and263 dieldrin were ubiquitous in surface wa ters across the entire basin, which was indicative of atmospheric sources. The distribution of other compounds including hexachlorobenzene, octachlorostyrene and mire x indicated the presence of local

sources within the watersheds of the c onnecting channels. Surficial sediment

contamination was found to have decreas ed markedly since the late 1960s and 1970s. Similarly, surface water contami nation decreased ov er 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 contaminant s, 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. Bioav ailable concentrations of hydrophobic organic substances in aqueous te sts often decrease as a result of (bio)sorption, volatilization, or degra dation. In the present study, partitioning driven administering (PDA) is introduced as an approach to maintain constant exposure levels of hydrophobic organics in aqueous test s. The working principle of PDA is to control dissolved concentrations by partitioning from a dom inating solid phase. For this purpose, test compounds are loaded on an octadecyl ocess was demonstrated, and PDA was successfully ap plied 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 multicompar tment systems is discussed.

McGeer, J. C., K. V. Brix, et al. (2003). "Inverse relati onship between bioconcentration factor and exposure concentra tion for metals: implicati ons for hazard assessment of metals in the aquatic environment." Environ Toxicol Chem 22 (5): 1017-37. The bioconcentration factor (BCF) and bioac cumulation factor (BAF) are used as

the criteria for bioaccumulation in t he context of identifying and classifying

substances that are hazardous to the aquatic environment. The BCF/BAF criteria, while developed as surrogates fo r chronic toxicity and/or biomagnification of anthropogenic organic substances, are ap plied to all substances including

metals. This work examines the theoretic al 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 inorgani c 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 criter ia, as currently applied, are inappropriate for the hazard identification and classification of metals. Furthermore, using BCF and BAF data leads to conclusions that are264 inconsistent with the toxico logical data, as values ar e highest (indicating hazard) at low exposure concentrations and are lo west (indicating no hazard) at high exposure concentrations, where impac ts are likely. Bioconcentration and bioaccumulation factors do not distingui sh between essential mineral nutrient, normal background metal bioaccumulation, the adaptive capabilities of animals to vary uptake and elimination within the spectrum of ex posure 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). "Fra mework for the interpretati on 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 bet ween the vegetation and the gas phase, kinetically limited gaseous deposition, or wet and dry particle-bound deposition. Each of these processes depends on differe nt atmospheric concentrations, plant properties, and environmental variables. He nce, in interpreting measurements of SOCs in plants, it is imperative that t he major process respons ible for t nt (KOA) of the chemical. The mathematical analysis leads to two interpretive tools, both log-logplots, one of the quotient of t he vegetation and gas-phase concentrations vs KOA and one of the quotient of t he vegetation and particle-bound concentrations vs the quotient of the particle-bound and gaseous concentrations. Each of these plots contains three di stinct and easily reco gnizable segments, and each segment corresponds to one of th e three deposition processes. When the experi

McNellis, R. P., J. D. Fallo n, et al. (2001). "Water-Qualit y 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 dist ribution of organoc hlorine 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 we re: cis-chlordane, o,p'-DDD; p,p-DDE; p,p-DDT; hexachlorobenzene; transnonachl or; 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 in265 streambed sediment that ex ceed guidelines for classi fication of sites with high probabilities of adverse effe cts to aquatic organisms. Total DDT was the only OC within an urban land use that exceeded guid elines for piscivorous wildlife.

Meijer, S. N., W. A. Ockenden, et al. (2003). "Spatial and te mporal 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 gat hered for 1994-1996. Comparisons of the masses of chemicals sequestered by t he SPMDs during these different time intervals are used to investigate s patial and temporal trends. Results are

discussed in the context of source s, 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 s equestered amounts of the homologue groups (expressed as a ratio to penta-PCB) s how a clear latitudinal trend, with the relative contribution of the lighter c ongeners increasing with in creasing latitude, providing evidence of latitudinal fracti onation. Absolute amounts of HCB increase with latitude, suggesting this compound is undergoing cold condensation. Sequestered amounts of PC Bs 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 di scuss the interpretation of these observations and conclude they impl y that the underlying trends of current ambient levels of PCBs in European ba ckground air are still largely controlled by primary emissions, rather than recycli ng/secondary emissions from the major environmental repositories such as soils or water bodies.

Meijer, S. N., W. A. Ock enden, et al. (2003). "Global di stribution and budget of PCBs and HCB in background surface soils: imp lications 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 PC B concentrations (26 and 97,000 pg/g dw) were found in samples from Greenland an d mainland Europe (France, Germany, Poland), respectively. Background soil PCB concentrations were strongly influenced by proximity to source regi on 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 in266 the global data set, with the correlation coefficients being greater for HCB and the lighter PCBs than for heavier hom ologues. OM-rich soils in the NH consistently contained the highest burdens; such soils are a key global compartment for these compounds. Evi dence for global fractionation of PCBs

was found in the subset of soils from lati tudes north of the global source region but was not discerned with the global dat a set The full data set was used to

estimate the burden for i ndividual 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 formulati ons of the fungicide, pentachloronitrobenzene on early life stage dev elopment of the Japanese medaka (Oryzias latipes)." Chemosphere 71 (10): 1957-62. Quintozene is a fungicide c ontaining 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 go lf courses, FFII were tested for toxicity to early life stages of the Japanes e 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 concent ration of 71 microgl(-1). Eggs and fry showed developmental abnormalities, in cluding ocular malformations and retarded development of the brain, not ochord, 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 abnorma lities were 750 and 100 microgl(-1), respectively. In medaka exposed to the FFII formulation, si milar patterns of mortalities, reduced hatching success and developmental abnormalit ies were observed, but at higher

test concentrations that were consist ent with the proportion of quintozene in the formulation. For medaka exposed to the formulation, the LOECs for abnormalities of the eye and all other dev elopmental abnorma lities were 10,000 and 1,000microgl(-1), respectively. Overall, these data indicate that studies

should be conducted to assess the risk of ex posure 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 res ponses 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 transloca tor (Arnt) proteins. The archetypal Ah receptor ligand, 2,3,7,8- tetrachlorodibenzo(p)dioxin, activated Ah receptor267 and induced lacZ reporter activity at conc entrations of >/=0.3 nM. Mixtures of halogenated and nonhalogenated Ah re ceptor ligands produced additive signaling responses in this yeast bioassa y. These results were consistent with the existence of a common binding site and mechanism of ligand-mediated Ah receptor activation. Although yeast hav e no natural counterpart to the Ah receptor pathway, expression of hum an Ah receptor and Arnt under the appropriate conditions provides a func tional model system for studying Ah receptor activation and signal transduction.

Miniero, R., G. Ceretti, et al. (2006). "Per sistent and toxic substances in the Venice lagoon biota: an approach for quantitative dat a analysis for risk management." Ann Ist Super Sanita 42 (4): 453-60. An approach based on hypothesis testi ng 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), hexachlorob enzene (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 identif ied. The central district is under the impact of the Porto Marghera industrial settlement and the city of Venice,

whereas the southern and northern district s 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-s odium alloy." Chemosphere 55 (11): 1439-46.Dechlorination of hexachlorobenzene (HCB) was achieved by a liquid potassiumsodium (K-Na)-alloy. HCB in a cyclohexa ne/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 po wer of cyclohexane. Decreasing orders of chlorobenzenes i dentified after a 15-min reaction, by
amount were 1,2,3,4->1,2,3,5->1,2,4,5- for tetrachlorobenz enes, 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 form ed 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-tetrachl orobiphenyl, 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 sa mple obtained from a reaction mixture after 30 min contained only 14 PCBs in tr ace amounts, indicating that the PCBs

formed were also further dechlorinat ed by K-Na alloy. Non-chlorinated compounds--such as methylbenzene, dimeth ylbenzene, dimer of tetrahydrofuran, and dicyclohexyl (dimer of cyclohexane)--wer e also identified in the samples. A268 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 w hen subjected to intensive mechanical treatments. A reference trial using calcium hydride- hexachlorobenzene is first presented. No residual traces of the organohalide com pound were found in the reacted powders or in the gaseous phase sampled from t he headspace of the milling reactor. The solid products of the reaction were restricted to CaHCl and CaCl2 salts and graphite. Similar combusti on-like phenomena were observ ed when contaminated mud samples were added to initial r eactants. 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 thermochem icalbreakdown of the hazardous compounds. A transformation yield great er than 99.6% was obtained with a decrease of the toxic equi valent concentration from 2492 to 0.788 mug/kg. Unlike

conventional incineration me thods, the mechanically in duced burst processes run under a strictly confined envir onment and controlled conditions.

Monirith, I., H. Nakata, et al. (1999). "Per sistent organochlorine residues in marine and

freshwater fish in Cambodi a." Marine Pollution Bulletin 38 (7): 604-612.

BIOSIS COPYRIGHT: BIOL ABS. Concent rations of persistent organochlorines (OCs) such as PCBs (polychlorinated biphenyls), DDT compounds (DDTs), HCH (hexachlorocyclohexanes) isomers (HCHs ), chlordane com pounds (CHLs) and HCB (hexachlorobenzene) were determi ned in 27 species of marine and

freshwater fish collected from Cambodi a. 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 sout hwest Atlantic and Antarctic oceans." Mar

Pollut Bull 50 (7): 778-82.

Moser, G. A. and M. S. McLachlan (1999). "A non-absorbabl e dietary fat substitute enhances elimination of persi stent lipophilic contaminant s in humans." Chemosphere

39 (9): 1513-1521.

BIOSIS COPYRIGHT: BIOL ABS. For i ndividuals contaminated with persistent lipophilic pollutants, there is an urgent need for a therapy to enhance269 contaminant elimination from the body and hence reduce long term exposure. This study investigated the possibilit y of enhancing the excretion of native chemical via the faeces by augmenting the lipophilic properties of the faeces with the non-absorbable lipid substitute ol estra. The faecal excretion of polychlorinated dibenzo-p-dioxins and di benzofurans (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 com pound from the body. It is concluded that regular consumption of olestra may provide a therapeutic approach for reducing the body burden of persistent li pophilic contaminants.

Mu, H., C. Wesen, et al. (1999). "Response factors of or ganochlorine compounds in the electrolytic conductivity detecto r." 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 res ponse factors (RFs) of chlorinated fatty acids and compared them with those of ot her chlorinated compounds. We also

studied the effect of reacto r temperature and total gas flow-rate on the RFs. The ELCD RFs of different organochlorine co mpounds 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). "P CDDs, PCDFs, PCBs and HCB in marine and
estuarine sediments from Queens land, Australia." Chemosphere 39 (10): 1707-1721.

BIOSIS COPYRIGHT: BIOL ABS. Concentrati ons of 2,3,7,8-chlorine substituted PCDDs, PCDFs, selected PCB congener s and HCB were determined in sediment samples collected from site s along the east coast of Queensland in

northern Australia. PCDDs were detect able 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 chlori nated PCDDs exists along the Queensland

coast.

Muir, D., B. Braune, et al. (1999). "Spat ial and temporal trends and effects of

contaminants in the Canadian Arctic marine ec osystem: 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 te mporal trends of persist ent organic pollutants and heavy metals in the Canadian Arctic ma rine 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 per sistent organochlorines (OCs) (PCBs, DDT- and chlordane-related compounds, hexachlorocyclohexanes, t seals have only been studied recently at one locati on. Contaminant measurements in bearded seal, harbour seal, bowhead whale and killer whale tissues from the270 Canadian Arctic are very lim ited 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 vari ability 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 cha nge 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 ci s-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, Ts ubame, Jouzo and Yahiko) during the period from September 1999 to November2001. 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 collect ed at urban sites of the Niigata Plain

was almost the same in their concentra tion 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 concentrati ons from 2000 to 2001. The lower POPs concentrations in winter and the higher PO Ps 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, li near 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 equat ion. The results suggest that HCB level is influenced by not only the emi ssion 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 c ontamination in the surrounding areas.

Nakatsu, N., T. Nakamura, et al. (2007). "Evaluation of action mechanisms of toxic chemicals using JFCR39, a panel of human c ancer 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 In stitute. The JFCR39 system can be used to predict the molecular targets orevaluate the action mechanisms of the test compounds by comparing their cell growth inhibition profiles (i.e., fingerprints) with those of the standard anticancer dr ugs 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, agricultu ral chemicals, drugs, and synthetic intermediates. Fingerprints of 130 chem icals were determined and stored in the271 database. Sixty-nine of 130 c hemicals ( approximately 60%) satisfied our criteria for the further analysis and were classified by cluster analysis of the fingerprints

of these chemicals and several standard ant icancer drugs into the following three clusters: 1) anticancer drugs, 2) c hemicals that shared similar action mechanisms (for example, ouabain and digo xin), and 3) chemicals whose action

mechanisms were unknown. These result s suggested that chemicals belonging to a cluster (i.e., a cluster of toxic chem icals, a cluster of anticancer drugs, etc.)

shared similar action mechanism. In su mmary, 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 to xaphene, PCBs, PCDDs, chlordane, and several other persistant organic compound s. 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) differe nt from those of t he 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 fe male 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 us ing 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 pr edicted to measured concentrations in eggs was 1.0 +/- 0.27 among chemicals, y ears, and colonies for this exposure

scenario. This result was in excell ent agreement with field assessments of herring gull diet composition in Lake On tario of 80-82% fish. The ability to perform accurate a priorisimu lations for the range of te st conditions employed in the validation constituted a rigorous te st of the soundness of the model's272 structure and parameterization. With s pecies-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 mole cular 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 tre nds in pollutant levels and shell thickness in eggs of merlin in Norway, in relation to its mi gration 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 leve ls 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 t hat the Fennoscandian merlin population declined from the 1950' he egg. Pestici de levels were generally decreasing during the period covered by the study, and a parallel improvement in shell thickness was observed. Ringing recoveri es indicated that different wintering areas were used by merlins from nor thern and southern Norway. This was a possible contributing factor for the obser ved regional variation in pollutant

concentrations.

O'Hara, T. M., M. M. Krahn, et al. (1999). "Organochlorine c ontaminant levels in Eskimo

harvested bowhead whales of ar ctic 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 s ubsistence 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, hexachlor obenzene and lipid levels decreased and other OC levels did not change signif icantly with increasing length. Most organochlorine contaminants have low conc entrations in tissues of the bowhead whale compared to concentrations in ti ssues of other cetaceans, especially Odontocetes. Based on allowable daily inta kes (ADI) levels established by the

Canadian Northern Contami nants Program (Ottawa, On tario, Canada) "safe"273 levels of blubber to consume were ca lculated. Chlordane levels in bowhead

whale blubber results in the most restrictive consum ption amount (50 g blubber/day). We expect no adverse e ffects related to these organochlorine

contaminants to occur in bowhead whales or in consumers of their tissues. However, investigation of low level chr onic exposure effects and a more rigorous assessment of histopathology, biomarke rs, 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). "I nadvertent 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 or der to provide some indications of the extent and significanc e of childhood exposure to xenoestrogens, including pesticides, epoxy resins, and polycarbonates . After more than four decades of pesticide use, little is known about thei r adverse effects on health. There is a need to address the potential risks associat ed with the current contamination of water, soils, and foods in many agricul tural areas. In south endrin, endosulfan, o,p'-DDE, and o,p'-DDD, am ong others. Of the 113 sa mples studied, 43 were positive for one or more pesticides, some of which have estrogenic activity. The

number of new substances that mimi c the action of endogenous estrogens is increasing rapidly. These endocrine-disrupting chemical s 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). "H alogenated environmental contaminants in perch (Perca fluviatilis) from Latvian co astal areas." Sci Total Environ 239 (1-3): 19-30.

The environmental contami nation 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 concentrati ons 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 concentrati ons of total PCB were similar at all study locations [0.7-1.4 ppm on a lipid we ight (l.w.) basis], although a site close to the City of Riga indicat ed the presence of a local PCB contamination source.

The contamination source was identified ma inly by a higher relative content of lower chlorinated PCB congeners in the samp les. 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. T he brominated flam e retardant compound 2,2',4,4'-tetrabromdiphenyl et her was present in the ran ge 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-chlor ophenyl) 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 in274 an area of the former Soviet Un ion, the Gulf of Riga, is similar to that observed in other parts of t he Baltic area.

Oskam, I. C., E. Ropstad, et al. (2003). "Organochlorines affect the major androgenic hormone, testosterone, in male polar bears (U rsus maritimus) at Svalbard." Journal of toxicology and environm ental health. Part A. 66 (22): 2119-39. Normal sexual development and s ubsequent reproductive function are dependent on appropriate testosterone produc tion and action. The regulation of steroid hormones, including androgens, can be influenced by both biological and environmental factors, including environm ental chemicals. Concentrations of organochlorines are consider ably 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) fr om the Svalbard ar ea. In this study,

testosterone concentration variations we re described for male polar bears during different seasons and for all age groups. To study possible relationships between plasma testosterone concentrations and bi ological factors, such as age, axial girth, and extractable plasma fat, and organochlorine contaminants including hexachlorocyclohexanes, hexachlorobenzen e, chlordanes, p,p'-DDE, and 16 individual polychlorinated biphenyl (PCB) c ongeners, identical statistical analyses were performed on the total population and a subsample of reproductively active adults. Of the biological factors, axia l 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 contributio ns to the variation of the plasma

testosterone concentration. The conti nuous 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). "E stimation of vapor pressures, solubilities and Henry's law constants of selected persi stent organic pollutants as functions of temperature." Chemosphere 39 (5): 811-832.

BIOSIS COPYRIGHT: BIOL ABS. An inter nally consistent set of temperature dependent physical-chemical pr operty data was derived for 73 persistent organic pollutants, including polychlorinated biphenyls, diphenylethers, dibenzo-pdioxins, and dibenzofurans, organochlorinat ed pesticides and polycyclic aromatic hydrocarbons. Measured dat a reported in the liter ature were expanded by different estimation and regression methods. Temperat ure 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 i nput 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). "Conc entrations of selected trace metals (Cu, Pb, Zn), organochlorines (PCB s, HCB) and total PAHs in mangrove oysters

from the Pacific Coast of Mexi co: an overview." Mar Pollut Bull 44 (11): 1303-8.

Payne, J. P. and A. Kortenkamp (1999). "Com bination effects of a mixture of four weakly oestrogenic environmental pollut ants." Annual Congre ss 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 combinati on effects of a mixtur e of four weakly oestrogenic environmental pollutantsym eeting abstract mcf-7 cell line proliferation o,p'-ddt environmental pollutant mit ogenic effects toxicity p,p'-dde

hexachlorobenzene beta-hexachloro cyclohexane toxicology estrogen

Pereira, W. E. and T. J. Leiker (1999) . "Distribution and transport of selected anthropogenic lipophili c organic compounds associat ed 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 th is scale, distribution and transport of selected hydrophobic halogen ated organic compounds associated with suspended sediment fr om the lower Mississippi River and its principal tributaries were determined during two sp ring and two summer cruises. Lipophilic organic compounds identified on t he suspended sediment included hexachlorobenzene, pentac hlorobenzene, pentachl oroanisole, dacthal, chlordane (cis- and trans-), nonachlor (tr ans-), 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 pr oposed for inclusion in the system of toxicity equivalency factors (TEFs) curr ently used for dioxin- like compounds. In this paper, we explore the practical implic ations of the propos ition to the Agency for Toxic Substances and Disease Regi stry (ATSDR) programs by comparing respective health guidance values for 2,3, 7,8-tetrachlorodibenzo-p-dioxin (TCDD) and HCB (expressed as total toxicity equi valents [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-lik e 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). "Complyi ng with future water regulations : With regulatory activity picking up momentum into 2000, utilities mu st anticipate and strategically plan for compliance." Journal of the Am erican Water Works Association 91 (3): 46-58.276 BIOSIS COPYRIGHT: BIOL ABS. To co mply with future regulations, water utilities will need to anticipate and stra tegically plan for upcoming regulatory requirements. Existing regulations set by the US Environmental Protection Agency under the Safe Drinking Water Ac t have been previously reviewed. This article reviews current regulatory trends that water utilities should consider in strategic planning so that they can comp ly 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 chemic al 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: Incide nt cases of exocrine pancreatic cancer were prospectively identified, and interviewed face-to-face during hospital admission (n=135). Serum concentrati ons of OCs were analyzed by highresolution gas chromatography with electr on-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-manua l 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 le ss variability in the other OCs.

CONCLUSIONS: Concentrations of most OCs were higher in the less affluent occupational social classes. In pancreat ic 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 cont ribution of different social processes and environmental chemical exposures to the etiology of pancreatic and other

cancers.

Postupalsky, S., K. D. Hughes , et al. (1999). "Organochlori ne 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 betwe en female age and egg contaminant concentrations. Organochlorine contami nant (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. Simila rly, eggshell thickness did not vary significantly with female age or year. Among PCB congeners, neither the degree nor the positioning of chlorine substituti on on the biphenyl ring, nor the degree of hydrophobicity, had any significant infl uence on contaminant bioaccumulation as birds aged. Eggs from females sampl ed in more than one year indicated

considerable annual variation in OC leve ls, presumably reflecting differences in
recent exposur

Provini, A. and S. Galassi (1999). "Polychlo rinated biphenyls and chlorinated pesticides in bird eggs from Calabria (Southern Italy )." Ecotoxicology and Environmental Safety

43 (1): 91-97. BIOSIS COPYRIGHT: BIOL ABS. Polychlo rinated biphenyl (PCB) and chlorinaed pesticide levels in eggs of two terrestr ial (kestrel and sparrowhawk) and two aquatic (heron and mallard) birds were determined in inhabited areas and woodlands of Calabria. The eggs of the tw o terrestrial raptors were more polluted than those of the aquatic birds. Among the raptors, the kestre l 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, organochl orines and metal levels in green mussel, Perna viridis L. from the coas tal waters of the Philippines." Fisheries

science : FS. 65 (3): 441-447.

BIOSIS COPYRIGHT: BIOL ABS. Cont amination by butyltins (BTs), organochlorine compounds (OCs) and heavy metals was examined in green mussels collected along the coastal ar eas of the Philippi nes in 1994 and 1997. Significant BTs concentrations rev ealed widespread contamination along nearshore marine waters. Relatively high BTs concentrations were observed in samples collected from areas with high boat ing activities, suggestive that the source of TBT (tributyltin) is coming fr om 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 Ba y. 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 meta l toxicants and pose no risk for human health. To our knowledge, this is the first comprehensive r

Rae, I. and P. Brown (2009). "M anaging the intractable: co mmunicative structures for management of hexachlorobenzene and other scheduled wastes." J Environ Manage

90 (4): 1583-92. This paper explores issues of gov ernance and decision-making structures associated with the problem of hexachlorobenzene (HCB ) waste at Botany in New South Wales. From a government persp ective, the problem is 'downstream' of a well-known national controversy over whether Australia should have a hightemperature incinerator (HTI) to 'dis pose' of such scheduled wastes. The 1992278 decision not to proceed with HTI follow ed an extensive process of public consultation, which, against the expect ations of industry and government, saw the emergence of Australia-wide communi ty opposition. Alte rnative national management plans were formulated for t he treatment of several types of organochlorine waste, with t he scheme of these plans first approved in 1993 by

the Australian and New Zealand Envi ronment and Conservation Council (ANZECC). The HCB Management Plan is one of three such plans (the others being for PCBs and organochlorine pesticide s). With this, AN ZECC established the Scheduled Waste Management Group comp rising government officials, and the National Advisory Body (NAB) made up of stakeholders. O fficially the NAB had oversight of the HCB pr oblem until 2002 when it was disbanded. As a result of the HTI experience, new community c onsultation protocols were introduced in

association with the alternative m anagement plans. For HCBs, which are confined almost entirely to Orica's Botany site in southeastern Sydney, this led to

the establishment of t he Community Participation and Review Committee (CPRC), a representative body with re view and advisory functions. This paper draws conclusions from this history about government processes of decision making, the role of individual and instit utional 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 envir onmental initiatives. Social Studies of Science 27, 819-863.] we identify swings towards, t hen away from institutionalised trust. Across two decades, government and industry have placed faith in centrally controlled mechanisms for public parti cipation, hoping to garner trust and legitimate privileged technological so lutions. On the 'backswings', these processes have seen public trust dissi pate in the face of government misunderstanding of the opportunities fo r effective bureaucratic interventions.

Ribes, A., J. O. Grimalt, et al. (2002) . "Temperature and organic matter dependence of the distribution of organochlor ine compounds in mountain so ils from the subtropical Atlantic (Teide, Tenerife Is land)." Environ Sci Technol 36 (9): 1879-85. Surface soil samples from Teide m ountain (Canary Islands) have been analyzed for polychlorobiphenyls (PCBs), DDTs, hexachlorocyclohexanes (HCHs), hexachlorobenzene (HCB), and pentachlorobenzen e. The samples were situated

between 10 and 3400 m above sea level being distributed below, at, and above the permanent inversion layer system characte ristic of the subtropical Atlantic. All OC concentrations were, in general, lo w when compared with the data from urban, agricultural, or w oodland soils reported elsewh ere. 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 carb on (TOC), showing high coefficients in the log(OC) versus log(TOC) correla tions. The slopes of the curve fitted straight lines were, in turn, highly corre lated to the log-transformed octanol-air coefficients of the compounds. This overall OC distribution points to steady-state

conditions for the concentrations of thes e compounds in these mountain soils, in279 equilibrium with TOC. The equilibrium conditions ar e 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 reciproc al of average annual atmospheric temperatures also showing a temperat ure dependence for their distribution in the high mountain system. The calculated ps eudo-enthalpies for this dependence, 120-160 kJ x mol(-1), exhibit higher va lues than those of octanol-air phase change calculated from laboratory experimen ts 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 hy drocarbon contaminants in Hong Kong surficial s ediments." Chemosphere 39 (6): 913-923. BIOSIS COPYRIGHT: BIOL ABS. Twenty su rficial sediments were sampled from nearshore Hong Kong waters during 1997-1998, and analyzed for a range of chlorinated pesticides and polychlorinat ed 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 concentra tions in Victoria Harbour. arl River Delta, and to a lesser extent dev elopments 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 sedim entary 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 increasi ng boiling point (bp) of the aromatic contaminants, but removal efficiencies still approached 100% well below the bp. Decontamination

rates were therefore modelled accordi ng to a pollutant evaporation-diffusion transport model. For the calcerous and sedi mentary soils, this model reasonably correlated removal of roughly the first 2/ 3 of the naphthalene, but gave only fair predictions for hexachlor obenzene and 4-chlorobiphenyl. It was necessary to heat the clay soil above the aromati cs bp to achieve high decontamination efficiencies. Weight loss data imply that fo r temperatures from near ambient to as much as 150 degrees C, interactions of eac h 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, al though the higher temperatures needed280 to remove aromatics from the clay may re flect a more prominent role for surface desorption than evaporation. Th is would be consistent with our estimates that the clay can accommodate all of the initial pollutant loadings within a single surface monolayer, whereas the calcerou s and sedimentary soils cannot.

Riva, C., A. Binelli, et al. (2008). "Evaluatio n of several priority pollutants in zebra mussels (Dreissena polymorpha) in the lar gest 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 HCH s) 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 hav e pointed out high DDT levels in D. polymorpha specimens from Lake Maggi ore (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 t hose found in a previous monitoring campaign carried out in 1996. Future moni toring 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 Un ited Nations Environment Programme (UNEP) is currently coordinating negot iations to develop a binding global agreement by late in the year 2000 to pr ohibit, restrict, or reduce the production, use, or release of certain persistent or ganic pollutants (POPs). POPs are a small subset of organic chemicals whose char acteristics of persistence in the environment, accumulation in biological organisms, and toxicity make them priority pollutants and environmental ri sks to humans and ecosystems. Und of persistence, bioaccumulation, toxici ty, and long-range transport in a policy context. The theoretical, empirical, and multimedia modeling approaches used reveal that guidance for setting POPs scr eening criteria can be developed using a combination of science and policy i nput. These approaches suggest that criteria adopted under regiona l POPs agreements in North America and Europe

are reasonable and tend to isolate a limit ed number of clearly hazardous POPs from the majority of organic chemica

Rodas-Ortiz, J. P., V. Ceja-Moreno, et al . (2008). "Vitellogenin in duction and increased plasma 17beta-estradiol concentrations in ma le 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 matu re male nile tilapia (Oreochromis281 niloticus) from three lakes (Rio, En medio and Limon) in Chiapas, Mexico. Vitellogenesis induction was found in t ilapias from Rio and Limon, moderately high E(2) levels in Rio and Limon tilapias, compared with controls (cultured tilapias). Significant correlations betw een benzo(a)pyrene (BaP) metabolites and hexachlorobenzene (HCB) with Vt g and E(2) were found. The results of this study indicate that endocrine disruption ex ists 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 co llected using bulk samplers inside the Lagoon of Venice. Seventy-seven atmo spheric deposition samples were collected monthly over a 12-month per iod (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, PC Bs, HCB and PAHs. Differences in mean daily fluxes of all organic pollutant s between industrial, urban and lagoonal stations were clear, atmospheric depositi ons at industrial sites being higher than target values for dioxin deposition reco mmended by the EU stra tegy 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 hypothetic al centre-point of the ma in sources of atmospheric

emissions from Porto Ma rghera. The calculated l oadings, compared with the previous estimates, show that annual lo adings 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 fr om the atmosphere is of the same order of magnitude of t hat 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 chemic al and ecological factors in trophic transfer of organic chemicals in aquat ic food webs." Environmental Toxicology and Chemistry 18 (6): 1250-1257. BIOSIS COPYRIGHT: BIOL ABS. Trophi c 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 Ko w > 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 biom agnification. 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) contam inant 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 m odel 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 sensitiv ity 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 fo r 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 t he analysis of 44 chemicals in eggs and maternal tissues of 6 fish species and s napping 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 app roximately 20-fold. The majority of observed lipid normalized egg/maternal ti ssue concentration ratios for indivi

Russo, J. and L. Lagadic (2000). "Effects of parasitism and pesticide exposure on characteristics and functions of hemocyte popul ations in the freshw ater 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 t he freshwater snail Lymnaea palustris. Animals were eit her infected by a trematode parasite (Metaleptocephalus sp.), or exposed to environmental contaminants, namely atrazine and hexachlorobenzene (HCB). Three populations of circulating hemocytes, morphologically and cytoc hemically distinct (round cells, hyalinocytes, granulocytes), were ident ified in both control and parasitized or pesticide-exposed snails. After 6 h of ex posure, 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. Hya linocytes 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 ex posure 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 we re obtained in atrazine-treated snail hemocytes, with unchanged phagocytosis and decreased phorbol 12- myristate 13-acetate-stimulated producti on of reactive oxygen in termediates. No increase in phagocytosis, or in the production of reactive oxygen intermediates, was observed in hemocytes from parasitized sn ails. Infection with the immunologically compatible trematode parasit e Metaleptocephalus sp. and exposure to atrazine generated similar reactions from circul ating 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 organoc hlorine compound widespread in the environment, highly lipophilic, that accumulate s 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 deliv ery 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). "Asso ciation between serum concentrations of hexachlorobenzene and polychlor obiphenyls 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 envir onmental occurrence, that accumulates in the biological system. It affe cts the porphyrine metabolism, thyroid hormones, and

the liver function in animals. Al though HCB is one of the most common organochlorine compound in humans, little inve stigation on its health effects has been done. Polychlorobiphenyls (PCBs) ar e also widespread toxic environmental contaminants. The aim of the present study was to investigate the association of

serum HCB and PCB concentrations wit h thyroid hormone status and liver enzymes in human. METHODS: Thyroid stimulating hormone (TSH), total and free thyroxine (T4), aspartate aminotrans ferase (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 associat ion with GGT (a relative increase of284 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 st udies 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 se rum of inhabitants living near an electrochemical factory." Occupat ional 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 li ving near an electrochemical factory with a high airborne concentra tion of hexachlorobenzene (HCB). Methods-Serum samples from 608 people (328 selected from a random sample) were collected in 1994. Information on lifestyles, occupati on, and medical condition was obtained by questionnaire. Results-HCB and pol ychlorinated biphenyls (PCBs) were detected in all samples (means 36.7 ng/ml and 4.3 ng/ml respectively), followed by dichlorodiphenyl di chloroethane (DDE) and bet a-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). Concent rations of HCB were the highest ever reported. Occupation in the factory was t he main determinant of the variation in concentrations of HCB (regression coeffici ents 1.52 (SEM 0.14) in ln (HCB) for workers in the product

Scharenberg, W. and B. Struwe-J uhl (2006). "White-tailed eagles (Haliaeetus albicilla) in Schleswig-Holstein no longer endangered by organochlori nes." Bull Environ Contam

Toxicol 77 (6): 888-95.

Schell, L. M. (2000). "Mohawk Cu lture, Behavior, Toxicant Exposure and Health." Crisp

Data Base National Institutes of Health

. Considerable concern exists overpossible effects on human physical and psycholo gical development of endocrine disrupting environmental contaminants such as pol ychlorinated biphenyls (PCB s). Native American communities are particularly at r isk owing to subsist ence systems and a cultur al ethos involving greater contact with the physical envir onment. 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 ar e members of the Mohawk Nation at Akwesasne which i s located on the St. Lawrence River, adjacent to hazardous waste sites wher e PCB s have contaminated the local ecology. The investigation examines the interrelat ionship between Mohawk cultural identity, traditional Mohawk cu stoms, behaviors related to toxicant exposure and current toxicant burden. Se rum level of PCBs wi ll be assessed by congener specific analysis. The study wil l determine 1) the re lationship of285 congeners and their hydroxylat ed metabolites to thyr oid function ( thyroid hormone levels and anti-thyroid antibodi es), and 2) psychosocial outcome s including school behavior and performance, hyperactivity, and adaptation to th e community. Data gathered for the past st udy 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 ol d psychosocial outcomes. Variation in susceptibilit y to PCB effects will be det ermined by examining the effects of concurrent toxic ant exposur e (hexachlorobenzene, Mirex, dichlorodiphenyldichloroethene, lead), d iet, and indicators of PCB metabolism,

on the focal measures of adult functioni n g. The proposed study will clarify the causal pathways between culturally id enti fying behavior, PCB exposure and body burden, thyroid functioning, cogniti ve fun ctioning, social behavior and school functioning while identifying activiti es 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 isofla vones and lignans) and organochlorine compounds (such as pesticides and pol ychlorinated 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 additi on, residues of organochlorine compounds

can be detected in the tissue of a la rge 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 hy potheses. Uterine fibroids are benign tumors whose growth is highly depende nt 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 im portant female heal th outcomes. We propose to conduct a population-based case-c ontrol study to determine whether biomarkers of exposure to phytoes trogens 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 Instit utes 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-per son interview to assess medical, reproductive, menstrual, contraceptive, and other characteristics. For the proposed study, we will enroll from TU LEP a subset of 175 premenopausal women with new, ultrasound-confirmed uterine fibroids (cases) and 175 premenopausal controls, frequency matc hed on age and race. From each of286 these women we will obtain a serum sa mple (for organochlorine analyses), an overnight urine sample (for phy toestrogen analyses), and food frequency questionnaires. In addition, in a sub-samp le 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, di eldrin, HCB, and beta-BHC) and total lipids using standard methods. Urine samp les will be analyzed for excretion of isoflavones (daidzein, genistein, equol , and O-desmethylangolensin) and lignans (enterodiol and enterolact one) and urinary creatinine. Phytoestrogen excretion and organochlorine residues in cases and controls will be compared using

multivariate unconditional lo gistic regression models.

Schymura, M. J. (1999). "Cor e--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 out reach 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 PC B exposures, body burdens, and health effects among Native Americans residi ng 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 par ticipants 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 asse ss 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 additi on, it will serve as a liaison with the Laboratory Services Core, with responsibil ity for indoor air, dust and tap water monitoring for PCBs and blood sampling for 68 PCB congeners, p,p'-DDE, mirex, hexachlorobenzene, thyroxine, triiodothyroni ne, thyrotropin, testosterone, and beta-estradiol from all study participants. This Core Unit will assess in vivo cytochrome P-4501 A2 activity in sele cted Mohawk adults through a caffeine breath test, a safe and non- invasive procedu re that measures the rate at which

labelled carbon dioxide is exhaled as an indi rect monitor. Outreach will consist of transmitting the results to study partici pants, assisting the Mohawk community in developing health education and promoting programs, and evaluat ing mortality, morbidity, and risk factors patterns at Ak wesasne 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 furnis h all students and projects in the program with statistical support. Using it s familiarity with exposure assessment, Geographic Information Systems, epidem iologic and statistical methods, and public health, this Core unit will assess t he exposure status of adult mohawk participants to PCBs for all relevant s ources, and determine the relationship of exposure to body burdens, cytochrome p- 450 activity, and alteractions in287 endocrine hormones. Economy of effort will be achieved by having these functions performed by one central uni t. This coordinated approach was recommended by the Mohawk community, a nd has been endorsed by our Expert Advisory Panel to minimize duplication and disruption.

Schymura, M. J. (2000). "Cor e--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 out reach 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 PC B exposures, body burdens, and health effects among Native Americans residi ng 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 par ticipants 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 asse ss 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 additi on, it will serve as a liaison with the Laboratory Services Core, with responsibil ity for indoor air, dust and tap water monitoring for PCBs and blood sampling for 68 PCB congeners, p,p'-DDE, mirex, hexachlorobenzene, thyroxine, triiodothyroni ne, thyrotropin, testosterone, and beta-estradiol from all study participants. This Core Unit will assess in vivo cytochrome P-4501 A2 activity in sele cted Mohawk adults through a caffeine breath test, a safe and non- invasive procedu re that measures the rate at which

labelled carbon dioxide is exhaled as an indi rect monitor. Outreach will consist of transmitting the results to study partici pants, assisting the Mohawk community in developing health education and promoting programs, and evaluat ing mortality, morbidity, and risk factors patterns at Ak wesasne 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 furnis h all students and projects in the program with statistical support. Using it s familiarity with exposure assessment, Geographic Information Systems, epidem iologic and statistical methods, and public health, this Core unit will assess t he exposure status of adult mohawk participants to PCBs for all relevant s ources, 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 uni t. This coordinated approach was recommended by the Mohawk community, a nd 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 worker s removing old elastic sealants." Int Arch Occup Environ Health 82 (1): 99-106.288 OBJECTIVES: To estimate the inte rnal PCB level in Swedish workers specialised in PCB abatement in buildings and to m easure possible effects of PCB on thyroid function and aspects of the immune system. METHODS: Thirty six of 40 eligible workers (90%) remo ving old elastic sealants containing PCB and 33 control construction workers provided blood samples for determination of 19 PCB congeners and some ot her organochlorine compounds (hexachlorobenzene and p,p'-DDE), thyr oid function hormones and a set of cytokines. The PCB exposed group was re investigated after 10 months for a

trend assessment. RESULTS: The sum of 19 PCB congeners in blood plasma from the occupationa lly PCB-exposed group was twic e 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 t he groups while the lipid-adjusted

hexachlorobenzene levels were of the same magnitude. No statistically significant increase in overall PCB leve ls was observed in the abatement workers at follow-up and some congeners even dec lined. 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 inter nal PCB load than unexposed colleague construction workers, tentatively secondar y to historical exposure. A system of protective measures seemed to be effici ent since no further increase was noted after a longish period of additional expos ure. 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). "B ioaccumulation profiles of polychlorinated biphenyl congeners and organochl orine pesticides in Ganges River dolphins." Environmental Toxicology and Chemistry 18 (7): 1511-1520.

BIOSIS COPYRIGHT: BIOL ABS. Isom er-specific concentrations of polychlorinated biphenyls (PCBs) includi ng non-, mono-, and di-ortho-substituted congeners, DDT and its metabolites, hexac hlorocyclohexane (HCH) isomers, chlordane compounds, and hexachlorobenz ene (HCB) were determined in river dolphin blubber and prey fishes co llected 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 organoch lorine pesticides suggested that there is less metabolism due to cytochrome P450 enzymes in Ganges river dolphins than in marine or terres trial mammals. The mean 2,3,7,8- tetrachlorodibenzo-p-dioxin equivalents (TEQ s) 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. Arauj o, et al. (1999). "Organochlor ine compounds in subtropical and tropical marine organisms: A meta-anal ysis." 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 determi nations 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 concentra tion of 23 ng g-1 (dry weight), and a mean of 2.89 analytes per sample; t he corresponding mean tissue burden is 4608 ng g-1 (dry wei

Sochova, I., J. Hofman, et al. (2007). "E ffects of seven organic pollutants on soil

nematode Caenorhabditis el egans." Environ Int 33 (6): 798-804. Caenorhabditis elegans is a free-living so il nematode that is commonly used as a model for toxicity tests. T he 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 an d hexachlorobenzene). The exposure

to all chemicals was carried out in th ree test media (soil, agar, and aquatic medium), and adult mortality was ev aluated after 24 and 48 h. Toxaphene was

the most toxic substance wit h LC(50) (48 h) of 379 mg/k g in the soil and 0.2 mg/L in the aquatic medium. Quinoline was the mo st 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. Lo nger than 24-h test duration was found necessary for getting more correct data on toxicity. In comparison with other studies, C. elegans was le ss sensitive than other soil invertebrates. Different response might be attributed to differ ent exposure routes and shorter test duration. Equilibrium partitioning theory wa s used to calculate K(oc) from results of soil and aquatic tests but this approac h was found not working. Our results suggest that the tests wit h nematode C. elegans shoul d be included to the battery of tests for risk a ssessment 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 oxi dative 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 signific ant 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 activi ty in brain were290 found during all the exposure day s. In brain, HCB also significantly elevated the contents of reactive oxygen species (R OS), thiobarbituric acid- reactive substances (TBARS, as an indicator of lipid peroxidation products), glutathione disulfide (GSSG), and activities of ni tric oxide synthase (NOS), glutathione peroxidase (GPx), and glutathione reductase (GR), and inhibited activities of acetylcholinesterase (AchE) and glutathi one S-transferase (GST). The results clearly demonstrated that envir onmentally 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 co mpounds and pesticide intermediates." Chemosphere 38 (4): 693-698.

BIOSIS COPYRIGHT: BIOL ABS. The acut e toxicities of 19 substituted benzene compounds and intermediates of pesticides to Photobacterium phosphoreum in beta -CD aqueous solution (5 g) were st udied and compared with those in water through luminescent bacteria toxicity test, and 15 min-EC50 values were obtained. The presence of bet a -CD significantly reduce biotoxicities of the lowpolarity compounds, while for the higher-p olarity compounds, such effect was slight. The differences of biotoxic ities were correlated with Log10Kow (octanol/water partition coe fficients). A significant linearrelationship 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). "M odeling the effect of snow and ice on the global environmental fate and long-range trans port 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 envi ronmental fate and longrange transport (LRT) of semivolatile organic compounds (SOCs). Investigated compounds include HCB, PCB28, PCB 180, PBDE47, PBDE 209, 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 sout h is more pronounced than in scenario 1 ("southward shift"). The presence of s now 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. Ma rcotrigiano (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 pol ychlorinated biphenyls including coplanar congeners, DDT compounds and HCB were measured in different tissues (muscle, liver and eggs) of two Medi terranean shark species: namely Centrophorus granulosus and Squalus bl ainvillei. 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 muscl e. 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 TE Qs values were nonand mono-ortho congeners than di-ortho ones in muscle, liver and eggs of both species. Among the non- ort ho, PCB 126 was the major contributing individual to the total TEQs in both species.

Storelli, M. M., R. G. Stu ffler, et al. (2003). "Polycyclic aromatic hydrocarbons, polychlorinated biphenyls, chlorinated pesti cides (DDTs), hexachlorocyclohexane, and

hexachlorobenzene residues in smoked seafood." J Food Prot 66 (6): 1095-9.

Smoked seafoods were screened for t he presence of polycyclic aromatic hydrocarbons (PAHs), polychlorina ted biphenyls (PCBs), and other organochlorine compounds. Total PAH c oncentrations 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)py rene 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 samp les analyzed, and benzo(a)anthracene was found in all samples and at particularl y 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 co mpounds in the Gulf of

Bothnia: sediment and bent hic species." Chemosphere 40 (9-11): 1205-11. Surface sediment, amphipods (Monoporei a affinis), isopods (Saduria entomon) and fourhorn sculpins (Oncocottus quadricor nis) were collected at two coastal292 stations in the Gulf of Bothnia, one in the Bothni an 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 gr oups 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 co mpounds 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 sugg ested as an indicator that integrates single media half-lives and phas e partitioning. However, the application of this indicator is hindered by the fact that ther e are different definit ions 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 t he environment as a function of time in a dynamic multim edia model. These measures include the equivalence width, which corresponds to t he residence time at steady state, the

mean value of the functi on of mass vs time ("mean time"), and the clearance time. The temporal remote state is defi ned 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 st ate reflects the long-term removal rate of a chemical and is used as a persistenc e benchmark. Correlations of the three measures of Pov to the persistence benchmark are analyzed. The maximum equivalence width, which is obtained with rel ease to one of the media air, water, or soil, is a good approximatio n 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). "S patial 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 s howed that alpha-HCH and HCB were293 homogeneously distributed in the circ umpolar 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 LF L in Yukon (YK), which is unique among the sites by virtue of its high altit ude and low latitude, resulting in higher precipitation rates and summer temperat ures. Strong temper ature dependence of alpha- and gamma-HCH at this location sugg ests that secondary emissions, i.e., re-evaporation from surfaces, were more impo rtant at this site than others. It is hypothesized that a higher prec ipitation rate at LFL fa cilitated the transfer of alpha-HCH from the atmosphere to surf ace 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 poten tial of HCB from air to seawater,

whereas seawater/air exch ange direction of alpha-HCH varies in the circumpolar

environment.

Sunyer, J., M. Torrent, et al. (2005). "Prenatal dichloro diphenyldichloroethylene (DDE) and asthma in children." Environ Health Perspect 113 (12): 1787-90.

Prevalence of asthma increases with in creasing dichlorodiph enyldichloroethylene (DDE) levels. However, the effect of early-life exposur e, the fundamental window of exposure, is unknown. We assessed the association between prenatal DDE and other organochlorine com pounds, and atopy and asthma during infancy. All women presenting for antenatal care in M enorca (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%) child ren. Asthma was defined on the basis of wheezing at 4 years of age, persist ent 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). Wheezi ng at 4 years of age increased with DDE concentration, particularly at the hi ghest quartile [9% in the lowest quartile (< 0.57 ng/mL) vs. 19% in the highest quart ile (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 o ccurred with the same strength among nonatopic subjects and among those with persistent wheezing or diagnosed

asthma. DDE was not associated with at opy alone. Prenatal exposure to DDE residues may contribute to development of asthma.294 Takahashi, M., T. Negishi, et al. (2009). "A lterations in gene expr ession of glutamate receptors and exocytosis-related factors by a hydroxylated-polych lorinated 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 di sturbing endogenous

hormonal activities at least in vitro. Ho rmonal activities of hydroxylated PCBs raise a possibility of their interferi ng with normal brain development which is strictly regulated by endogenous hormones . We investigated whether and how prenatal exposure to a congener of hydrox ylated 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 expr ession by oligo DNA microarrays and subsequent validations by quantitative RT-P CR 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 hydr oxylated PCBs with thyroid hormonedisrupting potencies leads to abnormal br ain 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 peri od 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 we t wt in B. exustus) and B. exustus the highest bioconcentration factors. Co mparing 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). "Infl uence of long contact times on sediment sorption kinetics of spiked chlo rinated compounds." Environ Toxicol Chem

24 (9): 2154-9.295 The desorption kinetics of hex achlorobenzene (HCB) and 2,4,4'- trichlororbiphenyl (PCB 28) spiked to a fi eld 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 kinet ics. Purge-induced desor ption experiments lasted from 300 to more than 4,000 h. Fast-, sl ow-, and very-slow-desorbing fractions could be distinguished. The desorption pa tterns changed with contact time from mainly fast- and slow-desorbing fractions toward the domination of slow- and very-slow-desorbing fractions. The desorpt ion 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'-tetrac hlorobiphenyl applied to the sediment purged for more than 4,000 h showed that ve ry 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 c aused not only by long contact times but, perhaps, also by the accessibility of spec ific 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 wh ales strand periodically along the U.S. coast, and these strandings offer an opportuni ty for the collection of tissues for biomonitoring of contaminant exposure in cetaceans, as well as for specimen archiving. Concentrations of organochl orine (OC) contaminants (e.g., PCB congeners, pesticides, DDTs) were measured in tissue samples from pilot

whales that stranded in 1986 and 1990 al ong 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 brai n, 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 popul ation highly exposed to airborne hexachlorobenzene (HCB) were selected to st udy the elimination kinetics of this chemical in humans. The volunteers pr ovided blood, 24-hr urine, and feces samples for analysis of HCB and metabo lites. 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 repor ted. All analyzed feces samples contained unchanged HCB (range, 11-3,025 ng/g dry weight; mean +/- SD, 395 +/- 629). The HCB concen tration in feces strongly correlated296 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 nonabs orbed foodborne HCB. The equilibrium is also compatible with a nonbiliary passive trans fer of the chemical to the intestinal

lumen. Two HCB main metabolit es, 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 [E nviron Health Perspect 105:78-83 (1997)]. The comparison between feces and urine showed that whereas daily urinary

elimination of metabolites ma y 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 estimat ed HCB adipose depots. Features of HCB kinetics that we present in this study, i. e., nonsaturated intesti nal elimination of

HCB and excretion in feces and urine of inert glutathione derivatives, may explain, in part, the absence of porphyri a 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 exam ined 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 si milar compounds searching system (SCSS) on a toxicogenomics database. The datasets of 55 compounds

administered to rats in the Toxic ogenomics Project (TGP) database in Japan were used in this study. Using the fo ld-change ranking method developed by Lamb et al. [Lamb, J. , Crawford, E.D., Peck, D., Mode ll, J.W., Blat, I.C., Wrobel, M.J., Lerner, J., Brunet, J.P., Subramanian, A., Ro ss, 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 sm all 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 t he database. In-house generated data for clofibrate, phenobarbital, and a proprieta ry compound were tested to evaluate the performance of the SCSS method. Pheno barbital and clofibrate, which were

included in the TGP databas e, scored highest by the SCSS method. Other high scoring compounds had effects similar to either phenobarbital (a cytochrome P450s inducer) or clofibrate (a peroxisome proliferat or). Some of high scoring compounds identified using the proprietary compound-administered rats have been known to cause similar toxicologica l changes in different species. Our results suggest that the SCSS method could be used in drug discovery and297 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 adver se effects of new compounds.

Tricklebank, K. A., M. J. Kingsford, et al. (2002). "Organochlorine pesticides and hexachlorobenzene along the central coast of New South Wale s: 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 damself ish 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. Al pha 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 distribut ion in organochlorines between urban and reference locations shown using non-paramet ric 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 to tal concentrations of organochlorine residues in fish. Significant, but w eak associations were found between organochlorine residues and size, gonad so matic and liver somatic indices.

Tsuji, L. J., B. C. Wain man, 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 organochl orine 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 contaminat ion, especially for PCBs. Few data exist with respect to human body burden of or ganochlorines (OCs) in residents of communities located in close proximity to these radar line sites. We compared plasma OC concentration (unadjusted for to tal 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 Kasheche wan First Nation without such a radar installation, and Hamilton, a city in s outhern Ontario, Canada). This type of analysis is important as it allows for an initial investigation of contaminant data without imputing any values. The two-stat e log-linear model (employing both nondetectable and detectable concentrati on frequencies and applicable to PCB congeners 28 and 105 and cis-nonachlor) and the four-state log-linear model (using quartile concentration frequencie s 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 subject298 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 differentia l distribution amo ng the concentration quartiles. In general, people from Hamilton had higher frequencies of nondetections and of concentrations in the fi rst 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 Kashec hewan 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 m odel, but significantly lower than expected in the 1st quartile for beta-HCH. The le vels 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 mamma ls). Moreover, the levels of total p,p'-DDT were greater for Fort Al bany and Kashechewan women compared to these same aboriginal groups.

Tuomisto, J. and L. Hagmar (1999). "Environm ental health in the east Baltic region: Pesticides and persistent organic com pounds." Scandinavian Journal of Work

Environment and Health 25 (Suppl 3): 65-72. BIOSIS COPYRIGHT: BIOL ABS. Expos ure to, and the potential effects of, pesticides and persistent organic pollutant s in the East Baltic region are reviewed. Exposure of the average popul ation to chlorinated compounds seems lower than in most of western Europe, and current pesticide use is very low. However, due to infrastr ucture failures and poor management controls, industrial hot spots and inadequate storage sites exist that cause high risks to small population fractions. The low ex posure of the general popul ation is indi pesticide residues and persistent organic compound s in the Baltic countries and northwestern Russiais low, but local sites of concern exist.

Umino, Y., S. Tsuji, et al . (2002). "[Determination and surv ey of hexachlorobenzene in food red nos. 104 (phloxine) and 105 (rose bengal e) 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) co rresponded to 0.0052% of the ratio for the Tolerable Daily Intake (8.5 micr ograms for 50 kg body weight) of HCB developed by the IPCS.

UnivofCincinnati (2000). "Mor tality Study of Montague, Mich igan 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 bipheny ls and some pesticides in perch (Perca fluviatilis) from in land waters of Latvia." Chemosphere 38 (9): 2053-2064.

BIOSIS COPYRIGHT: BIOL ABS. Pol ychlorinated biphenyls (PCBs), DDTrelated substances, hexachlor ocyclohexane (HCH) isomers and hexachlorobenzene (HCB) were analysed in perch (Perca fluviatilis) from Latvian lakes and rivers. DDE is present in the hi ghest concentrations in all samples; 62- 170 ng/g lipid weight in perch from rura l areas and 460 ng/g in perch from the Riga area. Individual dominating PCB c ongeners 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 su bstances is in the same range as in background areas in Sweden. Riga, the major urban ar ea in Latvia, is shown to be more polluted with PCBs than other areas in Latvia.

Valters, K., A. Olsson, et al. (1999). "Contamination so urces in Latvia: Levels of organochlorines in perch (Perca fluviatili s) from Rivers Daugava and Lielupe." Ambio

28 (4): 335-340.

BIOSIS COPYRIGHT: BIOL ABS. This st udy was aimed to search for potential sources of polychlorinated bi phenyls (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-chlor ophenyl) sulfone (BCPS) and two hexachloro-cyclohexane (HCH) isomers were quantified in perch (Perca fluviatilis) from the rivers Daugav a 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 Ba ltic 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 micr opollutants 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 met hod was applied as a tool to estimate bioavailability in soil. The accumulati on of organic micropollutants was measured in two earthworm species (Eisenia andr ei and Aporrectodea caliginosa) and in 30-microm poly(dimethylsi loxane) (PDMS)-coated solid -phase micro extraction (SPME) fibers after exposure to two fiel d-contaminated soils. Within 10 days, steady state in earthworms was reached, and within 20 days in the SPME fibers. Steady-state concentrations in both earth worm 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 cont aminants in pore water, derived from SPME measurements, were used to calc ulate concentrations in earthworms.

Measured concentrations in earthworms we re close to estimated concentrations

from the SPME fiber meas urements. Freely dissolved concentrations of contaminants in pore water, derived fr om SPME measurements, were used to calculate bioconcentration factors (BCF) in earthworms. A plot of log BCFs300 against the octanol-water partition coeffi cient (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. Grim alt, et al. (2004). "Atmospheric semivolatile organochlorine compounds in European high-mo untain areas (central Pyrenees and high Tatras)."

Environ Sci Technol 38 (13): 3525-32. Atmospheric samples from two Eur opean high-mountain areas showed similar composition of semivolatile organoc hlorine compounds (SOC), such as polychlorobiphenyls (PCBs), DDTs, endosul fans, 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 domin ant SOC. This compound is only found in the gas phase exhibiting uniform concent rations irrespective of season and air mass origin. SOC of present use, lik e HCHs and endosulfans, were found in higher concentrations in the warm peri ods, 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 precurso r 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 tropos phere (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), re spectively) than overall average.

Van Jaarsveld, J. A. and W. A. Van Pul (1999). "Modelling of at mospheric transport and deposition of pesticides." Wate r, Air, and Soil Pollution 115 (1-4): 167-182.

BIOSIS COPYRIGHT: BIOL ABS. M odelling of atmospheric transport and deposition of pesticides is presented and di scussed. Modelling on regional scale builds on the existing knowledge gained in ot her air pollution fields. An overview of current modelling studies on trans port 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 spatia l distribution of the concentrations and depositions. However, large uncertainti es are present in this type of modelling and are for the great er part induced by the uncertainty in the emissions and subsequently in the exchange pr ocess 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 im plications 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. T he 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 Aborigin al 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, toxa phene, 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. Thedeveloping foetus and breastVan Pul, W. A., T. F. Bidleman, et al. (1999). "Atmospheric transport and deposition of pesticides: An assessment of current k nowledge." 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 Fa te of pesticides in the atmosphere; implications for risk as sessment, held in Driebergen, the Netherlands, 22-24 April, 1998. In general there is a short age of measurement dat a to evaluate the deposition and reemission processes. It wa s concluded that the mechanisms of transport and dispersion of pesticides c an be described similarly to those for other air pollution components and thes e mechanisms are rather well-known. Large uncertainties are present in t he exchange processes at the interface between air and soil/water/vegetation. In a ll process descriptions the uncertainty in the physicochemical properti es play an important role. Particularly those in the vapour pressure, Henry's law constant and its temperature dependency. More ac curate data on physicochemical properti es 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 inte rleukin-4 is not." Scand J Immunol 52 (5): 519-24. Exposure of Wistar rats to the immunotoxic compounds hexachlorobenzene (HCB), bis(tri-n-butyltin)ox ide, and benzo(a)pyrene was pr eviously 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 unequ ivocal 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 in versely related to IL-10 levels. Secondly, BN rats were infe cted with Trichinella spiralis, an infection previously found to induce IL-4 producti on. 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 ra ts both the mRNA expression and the production of IL-10 were decr eased. 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 infe cted 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, wher eas IL-4 is not.

VelsicolChemCorp (2000). "1,2,3,4,7,7-Hexac hloronorbornadiene Response to the 13th Interagency Testing Committee Report(48 Fr55681) with Cover Letter Dated 101183." EPA/OTS; Doc #40-8483021

.

Verbruggen, E. M., H. J. C. Klamer, et al. (1999). "G radient elution reversed-phase high-performance liquid chromatography for frac tionation 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 hydrophobici ty values (log Kow) of components in complex samples. In this study, the sl ope (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 el uent (phi) were first obtained by isocratic runs for a set of micropollutants with diverse struct ures, 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 e ffect of thioctamide --the commercial form of alpha lipoic acid amide--on the por phyrinogenic action of hexachlorobenzene (HCB). For this purpose, porphyria wa s induced in rats by chronic HCB treatment, with or without si multaneous 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 syn thase 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 HCB303 effects by means of its free radical sca venging ability, and by having a direct effect on uroporphyrinogen-decarboxylase activity.

Vives, I., J. O. Grimal t, et al. (2005). "Age dependence of the accumulation of organochlorine pollutants in br own trout (Salmo trutta) fr om a remote high mountain lake (Redo, Pyrenees)." Environ Pollut 133 (2): 343-50. Polychlorobiphenyls (PCBs), hexachlorocyclohexanes (HCHs), hexachlorobenzene (HCB) and DDT were exam ined 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 env ironments. Results indicate that fish age is the main fact or of variability among specimens in this population that is subjected to atmo spheric 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 lipophilicit y) are better correlated with fish age than low molecular weight compounds. A transforma tion from 4,4'-DDT to 4,4'-DDE occurs in fish after ingestion; this results in amplifi ed 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 observ ed among younger fish (age, 1 year). Due to this effect, the relative OC co mposition does not reflect the main OC pollutants in the lake waters.

Vorkamp, K., F. F. Rige t, et al. (2008). "Levels and trends of persistent organic pollutants in ringed seals (Phoca hispida) fr om Central West Greenl and, with particular focus on polybrominated diphenyl ethers (PBDEs)." Environ Int 34 (4): 499-508. Polybrominated dipheny l 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 bet ween 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 si milar time trend study on ringed seal blubber [Riget F, Vorkamp K, Dietz R, Rastogi SC. Temporal trend studies on polybrominated dipheny l ethers (PBDEs) and polychlorinated biphenyls (PCBs) in ringed seals from East Greenland. J Environ Monit 2006; 8: 1000-5]. A clear East>West difference wa s 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 c oncentrations, typically exceeding SigmaPBDE by two orders of magni tude. The concentrations of HCH and304 toxaphene were in an intermediat e 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 es tablished under for example the Arctic Monitoring and Assessment Programme was confirmed, but apparently, more

data are needed for chlordane-related co mpounds 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 pr oportions of PCBs and DDTs and lower proportions of chlordanes and HCHs were found in seals from East Greenland

than in those from West Greenland. Ba sed 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 ma y be caused by different exposure

situations related to contaminant em issions 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). "Organoc hlorine pesticides and polychlorinated biphenyls in household com posts and earthworms (Eisenia foetida)." Environmental Toxicology and Chemistry 18 (6): 1157-1163.

BIOSIS COPYRIGHT: BIOL ABS. Thr ee indoor, household composts and the earthworms living in them were analyzed for their congener-specific content of polychlorinated biphenyls (PCBs) and or ganochlorine pesticides, including DDTs, chlordanes, dieldrin, and penta- and hexac hlorobenzene. 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 cont rol 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 circ ulate 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 is omers, beta-HCH mean concentration was305 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 constit uent (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 dec reased. HCB decreased 3.7 times from 0.033 to 0.009 mg kg(-1) on a fat bas is; 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 substituti on with pyrethroids used in agriculture and by the Mexican Ministry of He alth in sanitary programmes.

Waliszewski, S. M., R. Villalobos-Pietrini, et al. (2003). "Per sistent 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 pr ogrammes 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 fr om the previous study, it was noted that DDT levels decreased significantly in 2001 as a re sult of the substitution of the organochlorine insecticides with pyrethroid s 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." Envi ronmental Toxicology and Chemistry 18 (6):

1323-1328.
BIOSIS COPYRIGHT: BIOL ABS. The C anadian 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 the306 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 t he 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 developmen t. 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 Chi na: 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 mainla nd part of the PRD differed in socioeconomic development history and chem ical management policies. Polyurethane foam (PUF)-passive air sampling (PAS) was deployed at 21 regional air qualitymonitoring stations across the PRD in summer and winter, respectively. Dichlorodiphenyl-trichloroethane ( DDT), chlordane and hexach lorobenzene (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 winte r; 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) rati os (0.27) found in the mainland in

winter. HCB concentrations were relati vely uniform across the PRD, and long range transport of HCB from inland/Nort h China to the PRD in winter was suggested.

Wania, F. (1999). "On the orig in of elevated levels of persistent chemicals in the

environment." Environmental Science and Po llution 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 degr adation. However, contrary to this,

circumstances have been described when cont amination 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 c an be made that underst anding, quantifying and predicting these causes could prov ide a general conceptual framework for studying the fate of chemicals in the environment.

Waters, M. D., H. F. Stack, et al. (1999). "Genetic toxicol ogy data in the evaluation of potential human environmental ca rcinogens." Mutation Research. 437 (1): 21-49.307 BIOSIS COPYRIGHT: BIOL ABS. In 1969, th e International Agency for Research on Cancer (IARC) initiated the M onographs 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 t hat 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. Reco mmendations are made for assessing

chemicals based on the str ength of evidence from sh ort-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 t heir limitations are. The effects of uncertainty and variation in the chemical properties, discharges, and landscape parameters on model outcome have been exam ined by other researchers. Here, the role of landscape properties in c ontrolling region-to-region differences in chemical fate is examined. Specific ally, regions of Canada and the ChemCAN model are used to explore the regi on-to-region difference in fate for benzo[a]pyrene, hexachlorobenzene, tetrachloroethylene, alphahexachlorocyclohexane, 2,2',5,5'-tetr achlorobiphenyl (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 t he methods for obtaining the landscape parameters used here are giv en. 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 t hat 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 c oncluded that the quality of results obtained from regional environmen tal 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, sol ubility, 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 (d ichlorophenoxyacetic acid (2,4-D), trichlorophenoxyacetic acid (2,4,5-T), atrazine, picloram, 4-chlorobenzeneamine, pentachlorophenol (PCP), hexachlorobenze ne (HCB), 1,1-bi s-4-chlorophenyl2,2,2-trichloroethane (DDT), tric hloroethene, benzene, phenol, linear308 alkylbenzenesulfonate (LAS)). The different inherent toxicity of the pollutants is strongly modified by interactions with t he 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 param eters of the soils that determine the degree of sorption

Woodburn, K. B., T. A. Marino, et al. (2008). "Determinati on of the dietary absorption efficiency of hexachlorobenzene with the c hannel 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 ex posure 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 dy namics. No detectable metabolism of HCB by catfish was found. A two-box ki netic model effectively modeled the uptake and clearance of (14)C-HCB in ca tfish, with a calculated assimilation efficiency of the chemical into the whol e catfish of 67% (growth corrected). The growth-corrected pseudo first-order eliminat ion 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). "C ytological and biochemical alterations in Carassius auratus hepatocytes from exposur e to sediment containing dioxins and related compounds." Archives of Envir onmental Contamination and Toxicology 37 (3):

358-363. BIOSIS COPYRIGHT: BIOL ABS. Cytolo gical and biochemical alterations of crucial carp (Carassius auratus) hepato cytes were characterized after exposure

to sediments from a lake contami nated 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 c hanges 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 activi ties were strongly induced in liver. A trend from rough endoplasmic reticulum (RER) to SER was observed. Our results suggest that the dioxin-lik e 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. Organi c compounds and inorganic elements

were determined in leachates from 11 landf ill sites in Japan. With regard to the inorganic elements, the c oncentration of boron was found to be fairly high. More than 100 organic compounds were detect ed and several impor tant compounds such as organic phosphates, 1,4-dioxane, phthalates, and bisphenol A were present at high concentrations. Waste pl astics are a possible origin for these compounds. The ratio of characteriz ed 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 surf actants--Tween 60, 61 or 65-- as the sole carbon source to sustain methanogene sis and dechlorination, as well as the effect of long-term exposure of enriched cultures to these surfactants, was investigated through the development of th ree sediment-derived cultures. Over a one-year period, the carbon source in thes e cultures was gradu ally 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 partia lly degraded and conver ted to methane. Transition from glucose to Tween surfact ants 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. Th is 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 contam inants 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 este rs) on methanogenesis and the microbial

reductive dechlorination of hexachlor obenzene (HCB) was examined using three anaerobic, HCB-dechlorinati ng mixed cultures, one glucose fed and two lactate fed, that were derived from contaminat ed 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 activi ty. Tween-61 and -65 exhibited the lowest

inhibition of HCB dechlorination at initia l surfactant concentrations of 200 and 1,000 mg. On the other hand, the Tween su rfactants, especia lly Tween-81 and - 85, enhanced the rates of both methanogen esis and HCB dechlorination when the low metabolic activity lactate-f ed culture was used. The observed rate enhancements may be attributed to bacterial cell membrane modification by310 Yuan, S., M. Tian, et al. (2006). "Electrokinetic move ment of hexachlorobenzene in clayed soils enhanced by Tween 80 and beta-cyclodextrin." J Hazard Mater 137 (2):

1218-25. This study describes the compar ative behavior of hexachlorobenzene (HCB) contaminated clayed soils in an electrok inetic (EK) system enhanced by Tween 80 and beta-cyclodextrin (beta- CD). The pH of the soils was controlled by Na2CO3/NaHCO3 buffer. Negligible HC B 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. Al though 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 fo r the result. The mechanism of the movement of HCB was proposed as t he enhanced desorption of HCB from soil, the dissolving of HCB in the soil pore fl uid and the movement of HCB with the

electroosmotic flow. Obvious movement of HCB was also observed in the EK treatment of real HCB-contaminated clay ed soil enhanced by beta-CD. It is an alternative approach to use facilitati ng agents such as beta-CD to enhance the

EK movement of HCB in t he contaminated clayed soils.

Yuan, S. Y., C. J. Su, et al. (1999). "Microbial dechlorination of hexachlorobenzene in anaerobic sewage slu dge." Chemosphere 38 (5): 1015-1023.

BIOSIS COPYRIGHT: BIOL ABS. From th is study of the dechlorination of hexachlorobenzene (HCB) in municipal sewage sludge by an anaerobic mixed culture, we determined the dechlorinati on 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 occurduring agitation. Biotransformation occurred along a pathway of HCBpentachlorobenzene (QCB)-1,2,3,4-tethl orobenzene (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 obser ved within a substrate concentration range of 2-50 me, but slowed do wn significantly at concentrations of 50 mg/L or higher. High-to-low dechl orination mtes under three reducing conditions were identified as methanogeni c conditions (0.30 mg/L/day) > sulfatereducing conditions (0.12 mg/L/day) > deni tryfying conditions (0.08 mg/L/day).

Zakikhani, M., M. S. Dortch, et al. (2004) . Risk Characterization for Future Training

Scenarios at the Massachusetts Militar y Reservation (MMR), Govt Reports Announcements & Index (G RA&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 pot ential human and ecological health risks associated with emission of pyrotechni c compounds during future training

exercises at the Massachusetts Militar y Reservation. Air dispersion modeling311 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 asse ssments. The Army Risk Assessment Modeling System (ARAMS) was used to conduct the human health risk assessment, which evaluated a site visito r or trespasser exposed to air and soil using air concentrations and deposition rate s from the air dis persion modeling.

ARAMS was also used to evaluate the time for deposited compounds to reach groundwater and the peak concentration upon contact with the wa ter table. Of the 24 compounds evaluated, only Cr(VI), with an incremental c ancer risk of 2.4 x 10(exp -6), posed a potent ial 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 so il screening toxicity benchmarks for the ecological risk assessment for the purpose of retaining or eliminating chemicals

from the assessment. Toluene an d hexachlorobenzene were the only compounds that exceeded the soil toxicity benchmarks. However, because of the slight exceedence and its nonbio-accu mulating properties, toluene is not considered to be a chemical of potent ial concern. Alt hough hexachlorobenzene exceeded the toxicity benchmark, uncerta inties and conservative assumptions

associated with the model ed 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 Re servation (MMR), Final Results, Govt Reports Announcements & Index (GRA&I), Issue 06, 2006 : 84. Final rept. The original document contains color image s. Prepared in cooperation with U.S. Army

Center for Health Promotion and Pr eventive Medicine, Aberdeen Proving Ground, MD. This study was conducted to evaluate pot ential human and ecological health risks associated with emission of pyrotechni c compounds during future training

exercises at the Massachusetts Militar y 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 asse ssments. The Army Risk Assessment Modeling System (ARAMS) was used to conduct the human health risk assessment, which evaluated a site visito r or trespasser exposed to air and soil using air concentrations and deposition rate s from the air dis persion modeling.

ARAMS was also used to evaluate the time for deposited compounds to reach groundwater and the peak concentration upon contact with the wa ter table. Of the 24 compounds evaluated, only Cr(VI), with an incremental c ancer risk of 2.4 x 10(exp -6), posed a potent ial 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 so il screening toxicity benchmarks for the ecological risk assessment for the purpose of retaining or eliminating chemicals312 from the assessment. Toluene an d hexachlorobenzene were the only compounds that exceeded the soil toxicity benchmarks. However, because of the slight exceedence and its nonbio-accu mulating properties, toluene is not considered to be a chemical of potent ial concern. Alt hough hexachlorobenzene exceeded the toxicity benchmark, uncerta inties and conservative assumptions

associated with the model ed 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 ER OD induction and histology in nile tilapia

Oreochromis niloticus." Mar Environ Res 50 (1-5): 385-91. The effect of environmental pollutants present in sediment s obtained from Bahia de Chetumal, a bay on the border between Mexico and Belize, was studied in nile tilapia (Oreochromis niloticus) intraperitoneally inje cted with sediment

extracts from six different sites of the Bay. Sediment samples used for the study contained a variety of organic chemical s such as organochlorine pesticides, polychlorinated biphenyls (PCBs) and polynuclear aromatic hydrocarbons (PAHs). Total cytochrome P- 450 and EROD ac tivity were measured in fish liver. Haematological and histol ogical analyses were also carried out. Hepatic P-450

content in treated fish incr eased from 43 to 240%, and EROD activity from 85 to 160% compared to controls. Extracts fr om two sampling sites inhibited EROD activity. There were positive significant correlations between P- 450 content and

the levels of PCBs 44 and 128. EROD ac tivity correlated to HCB, op'-DDE, pp'- DDE, pp'-DDD, mirex and PCB 18 concent rations. Blood examination showed cell degeneration and binucleated leukocyt es with abnormal chromatin. Extract treatment also resulted in foci of hyper plasia on the basement of gill lamellae, hypertrophy and oedema in gills and liver necrosis. Control fish showed no

abnormalities. The results dem onstrate that sediments fr om Bahia of Chetumal have the potential to cause histopatholog ical, haematological and biochemical

alterations in fish. The administration of s ediment 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 frac tions." Environ Pollut 152 (1): 245-52. Temporal changes in the distri bution of exogenous HCB and DDT among different soil organic matter fractions we re 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 frac tions 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 increas ed 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). "Tem poral change in the distribution patterns of hexachlorobenzene and dichlorodiphenyltri chloroethane among various soil organic

matter fractions." Environ Pollut 150 (2): 234-42. Residence time-dependent distributi on patterns of hexachlorobenzene (HCB) and dichlorodiphenyltrichlo roethane (DDT) among different soil organic matter

fractions of three Chinese soils were in vestigated. 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 dec reased, while those in the lipid and IR

fractions increased. One- and two-com partment first order, and one- and twoparameter pore-diffusion kinet ic 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 ac hieved 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 t he 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 fungi cide, to female breast c ancer risk. The current study, with a total of 304 breast cancercases and 186 controls recruited in Connecticut between 1994 and 1997, exami ned 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-N ew Haven Hospital (New Haven, CT) and histologically diagnosed either as breast cancer or benign breast disease. Information on major known or suspect ed 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 cont rols (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 ev er breast feeding, an odds ratio (OR) of 0.5 [95% confidence interval (CI), 0.2-1.4] wa s observed when the highest quartile was compared with the lowest quartile. Ho wever, no association was observed among parous women who reported never breast feeding (OR = 0.7; 95% CI, 0.3-1.7 for the fourth quar tile). For nulliparous women, the adjusted OR was 2.1314 (95% CI, 0.5-8.8) for the third tert ile 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). "Simul taneous analysis of organophosphorus and organochlori ne pesticides in animal fat by gas chromatography with pulsed flame photometric and micro-elec tron capture detectors." Journal of Separation Science 25 (8): 527-537. A method using simultaneous pulsed fl ame photometric (PFPD) and microelectron capture detection (?ECD) in gas chromatog. (GC) was developed and

validated for the anal. of 23 organophosphorus (OP) an d 17 organochlorine (OC) pesticides in animal fat. The method enta iled the extn. of animal tissue (mixed with twice the sample wt. of sodium sulfat e) with 7 mL Et acet ate 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 chroma tog. column (4.5 mL/min flow rate of 70/30 Et acetate/cyclopent ane). 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 inje ctor 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 pesti cides 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 fo r methamidophos, acephate, and omethoate

which are more difficult in GC anal. due to their more polar nat ure. Fenthion and phorate also gave more variable recoveri es, presumably due to their degrdn. to

sulfones and sulfoxides. In fortification recovery expts. at several different concns. over multiple days, reproducib ilities of 10-20% relative std. deviation were achieved, and limits of quant itation were typically 10-20 ng/g.