bluuebunny/crossref_metadata_2025 huggingface dataset:
An Evaluation of the Developmental Toxicity of 2,4-Pentanedione in the Fischer 344 Rat by Vapour Exposure
Authors: Tyl Rochelle W. , Ballantyne Bryan , Pritts Irvin M. , Garman Robert H. , Fisher Louan C. , France Kathryn A. , Mcneil Denise J.
Published: September 2013

The developmental toxicity of 2,4-Pentanedione (2,4-PD; CAS No. 123-54-6), a widely used industrial chemical, was investigated by vapour exposure, because of its widespread use, and potential for human exposure. Timed-pregnant Fischer 344 rats were exposed on gestational days (gd) 6 to 15 inclusive to analytically measured concentrations (as mean ± SD) of 53 ± 1.6, 202 ± 4.7 and 398 ± 5.7 ppm 2,4-PD vapour. At sacrifice (gd 21) foetuses were examined for external, visceral and skeletal variations and malformations. There was no maternal mortality, and body weight was reduced only at 398 ppm. Histological examination of maternal brains from the 398 ppm group showed no abnormalities. No treatment-related effects were seen on number of corpora lutea; total, nonviable or viable implants per litter; pre-or post-implantation losses; or foetal sex ratio. Reduced foetal body weight per litter was seen at 398 ppm (males and females and all foetuses) and 202 ppm (males and all foetuses). There was no concentration-related, or statistically significant, increase in the incidence of individual malformations, malformations by category (external, visceral or skeletal), or total malformations. Partial foetal atelectasis was increased at 398 ppm, and the increased incidence of 17 skeletal variants (out of 79 observed) indicated a consistent pattern of fototoxicity at 398 ppm. In summary, at 398 ppm there was maternal toxicity (reduced body weight) and foetotoxicity (reduced body weight and ossification) and at 202 ppm there was foetotoxicity (reduced body weight). Embryotoxicity or teratogenicity were not seen at any concentration. The no-observable-effects concentration was 53 ppm for both maternal and developmental toxicity.
A 90-Day Toxicity Study of the Effects of Petroleum Middle Distillates on the Skin of C3H Mice
Authors: Freeman James J. , Mckee Richard H. , Phillips Richard D. , Plutnick Robert T. , Scala Robert A. , Ackerman Larry J.
Published: September 2013

Petroleum middle distillates (PMDs) elicit skin tumors in mouse epidermal carcinogenesis studies. The response is characterized by a long latency with only a small percentage of animals developing tumors. Although the carcinogenic activity of certain other petroleum hydrocarbons largely depends upon the presence of polycyclic aromatic hydrocarbons (PAHs), many PMDs contain relatively low concentrations of PAHs. PMDs are also irritating to mouse skin, and chronic irritation may be involved in the development of skin tumors. This study was conducted to investigate the patterns of cutaneous irritation elicited by topical application of PMDs having compositional differences. The three PMDs selected for study were a steam cracked gas oil (SCGO), a lightly refined paraffinic oil (LRPO), and a jet fuel (JF). Male C3H/HeNCr1BR mice (25/group) were treated topically (37.5 μl 2x/week for 13 weeks) with 10%, 50% or 100% (undiluted) concentrations of each PMD. Catalytically cracked clarified oil (CCCO, 10%), a potent carcinogen to mouse skin, was also tested. The vehicle was a noncarcinogenic mineral oil with a viscosity of 90 SUS.

Cutaneous changes were evaluated by gross observations and light microscopy. Cutaneous irritation was the only significant toxic response in this study. Neither the vehicle nor any of the 10% PMD concentrations produced significant cutaneous irritation. The 10% CCCO and 50% PMD treatments all elicited slight to moderate proliferative and inflammatory changes in mouse skin. Ulcers were also observed microscopically in mice treated with 10% CCCO and 50% SCGO. The 100% SCGO treatment produced evidence of necrosis on Days 1–7 but not later in the study despite continued treatment. In contrast, the irritating effects of 100% LRPO were not evident until 2–3 weeks of study, and at study completion were characterized by moderately severe inflammatory and proliferative changes. The effects of 100% JF were qualitatively similar to 100% LRPO but less marked. Thus, the SCGO caused a different pattern of cutaneous responses than either LRPO or JF. The possible relationships of these cutaneous changes to epidermal carcinogenesis are being studied further.
Enhanced Arrhythmogenicity of Freon 113 by Hypoxia in the Perfused Rat Heart
Authors: Kawakami Tsuyoshi , Takano Takehito , Araki Ryuichiro
Published: September 2013

The interaction of Freon 113 (1,1,2-trichloro-1,2,2-trifluoro-ethane) and hypoxia on the heart conduction system was studied using electrocardiogram monitoring of isolated perfused rat hearts. Freon 113 (0.2 mM) alone elicited significant atrioventricular conduction delay (p > 0.05) and heart rate decrease (p > 0.01), which were significantly enhanced by hypoxia (75% oxygen decrease), for instance, resulting in 2:1 AV block. The data suggest that arrhythmogenicity of Freon 113 on the heart conduction system may be enhanced synergistically by hypoxia.
Dangerous and Cancer-Causing Properties of Products and Chemicals in the Oil Refining and Petrochemical Industry: Part V - Asbestos-Caused Cancers and Exposure of Workers in the Oil Refining Industry
Authors: Mehlman M.A.
Published: September 2013

In the oil refining and petrochemical industries exposure to cancer- causing asbestos particles, especially during equipment repair and maintenance, is very high. Up to 90% of workers in the oil refining industry had direct and/or indirect contact with asbestos, and more than half of this contact occurred without the use of any kind of precaution, thus these workers are in high risk of developing lung cancer and mesothlioma, both fatal diseases. The hazards include: inadequate health and safety training for both company personnel and workers, failure to inform about the dangers and diseases (cancers) resulting from exposure to asbestos; excessive use of large numbers of untrained and uninformed contract workers; lack of use of protective equipment; and archaeological approaches and responses to repairing asbestos breaks and replacement of asbestos in oil refining facilities. For a better understanding ofpractices and policies in the oil refining industry, refer to Rachel Scott's Muscle and Blood, in particular the chapter "Oil" (E.P. Dutton, New York, 1974), as well as to an editorial which appeared in the Oil and Gas Journal, April, 1968.
Polybrominated Biphenyl Exposure and Human Cancer: Report of a Case and Public Health Implications
Authors: Sherman Janette D.
Published: September 2013

This is a human case report of documented exposure to polybrominated biphenyls (PBBs), with serial PBB determinations, obtained over an 11 year period, and signs and symptoms characteristic of PBB exposure, culminating in cancer. No epidemiological studies of PBB and cancer are available, but structure- activity relationships and animal studies were predictive of malignancy. The patient did not have the risk factors of alcoholism or cigarette smoking.
Reanalysis of Epidemiological Data for Selenium Anti-Cancer Activity
Authors: Lange John H.
Published: September 2013

Investigations of the health effects of selenium have repeatedly noted an inverse relationship of selenium (both soil and human sera) and decreased prevalence of cancer. This has been found in cross sectional, case-control and ecological study designs. Reanalysis of age-adjusted death rates by cancer site revealed a significant inverse relationship for lung and all cancer with blood selenium. Methodological problems in this type of re search is discussed.
A Physiologically Based Pharmacokinetic Model for Chloropentafluorobenzene in Primates To Be Used in the Evaluation of Protective Equipment Against Toxic GASES
Authors: Crank William D. , Vinegar Allen
Published: September 2013

Chloropentaflurobenzene (CPFB) has been proposed as an innocuous simulant for the uptake of toxic gases. Exposure to CPFB in a training exercise could be inferred afterivards from a measurement of CPFB in expired breath. To understand the relationship between exposure and measurement, we have developed a physiologically-based pharmacokinetic (PB-PK) model for CPFB in primates. To test the model, inhalation exposures were conducted on anesthetized rhesus monkeys. CPFB concentration in expired breath was measured during and after exposure. Simulations of CPFB uptake and clearance agreed with experimental measurements in seven of eight monkeys. A human version of the model was used to simulate exposures consisting of a single breath or a few breaths. By showing a measurable CPFB concentration in expired breath after several hours of clearance, simulations with the human model indicated the suitability of CPFB as a simulant for toxic gases. (Slipported by U.S. Department of Defense contract #F33615-85-C-0532.)
Lipid Peroxidation of Ultrastructural Components of Rat Liver Induced By Metanil Yellow and Orange II: Comparison With Blend
Authors: Ramachandani Shanta , Das Mukul , Khanna Subhash K.
Published: September 2013

Metaizil yellow and Orange II are extertsively used in various industries and have not been included in the list of permitted food colours because of inadequate safety evaluation data. In this investigation the effect of Metanil yellow and Orange II on the lipid peroxidation in different subcellular fractions of liver was studied in order to understand the site of hepato-toxic potential and whether its blend has an additive, synergistic or antagonistic effect. Parenteral administration of Metanil yellow (80 mg/kg body weight) to rats for 3 days produced a highly significant (p < 0.001) increase in NADPH-dependent enzymatic lipid peroxidation in nuclear (62%), mitochondrial (104%) and microsomal (54%) fractions. The same dose of Orange II to rats showed a relatively less but significant effect in nuclear (62%), mitochondrial (59%) and microsomal (38%) membranes. The blend of Metanil yellow and Orange 11 (40 mg + 40 mg/kg body weight) given intraperitoneally for 3 days resulted in either synergistic or additive effect in nuclear (122%), mitochondrial (130%), and microsomal (62%) membranes. The pro-oxidant free or FeSO4/ ADP (1 mM/5 mM) or ascorbate (1 mM) dependent non-enzymatic lipid peroxidation in nuclear, mitochondrial and microsomal fractions was found to be enhanced by Metanil yellow to a greater extent as compared to Orange II, while the blend showed a synergistic or additive response. These results suggest that Metanil yellow and Orange II causes hepatic nuclear, mitochondrial and microsomal membrane damage and that the effect may be more severe with the use of blend.
The Effect of Aluminum On the Stromal Cells (in Vitro) On Bone Marrow in Rats
Authors: Zaman K. , Mukhtar M. , Siddique H. , Miszta H.
Published: September 2013

The aim of this study was to describe the effects of aluminum on the stromal cells of rat bone marrow using a combination of in vivo exposure and in vitro culture of bone marrow. The toxic effects of aluminum are manifested by a decrease in the erythrocyte count and hemoglobin level in the peripheral blood. Aluminum stimulated an increase in the number offibroblasts while the macrophage count dropped. The number of adipocytes remained unaffected. An increase in mean corpuscular hemoglobin (MCH) was also found in the peripheral blood of experimental animals.
Indication of Dna Strand Breaks in Human White Blood Cells after In Vitro Exposure to Toluene Diisocyanate (TDI)
Authors: Marczynski Boleslavv , Czuppon Adam B. , Marek Wolfgang , Baur Xaver
Published: September 2013

Toluene diisocyanate (TDI), used expecially for the production of polyurethanes, is known to induce chromosome aberrations, base-pair substitution, and frameshift mutation after metabolic activation. Following treatment of human blood by TDI, the isolated DNA was analyzed by anion-exchange chromatography (FPLC) before and after denaturation. In addition, DNA from white blood cells was analyzed by alkaline and neutral filter-elution and pulsed-field gel electrophoresis (PFGE). The results show that TDI induced single-and double-strand breaks in the DNA of white blood cells in vitro. The elution rate, calculated after alkaline filter elution, was significantly increased after TDI treatment. An average size of the TDI-induced DNA fragments was estimated by PFGE to be smaller than 250 kb. Denaturation and renaturation of TDI-treated DNA indicated that DNA could be cross-linked by TDI. Purified DNA treated with TDI in buffer alone does not induce DNA fragments as shown by FPLC. These findings indicate that DNA damages are induced by TDI after the biotransformation of TDI. The results show that TDI exposure induces DNA damage of white blood cells in vitro.
Liver Carcinogenesis is Not a Predicted Outcome of Chemically Induced Hepatocyte Proliferation
Authors: Melnick Ronald L. , Huff James
Published: September 2013

Cell proliferation has long been recognized as a basic component of multistage carcinogenesis. Based largely on the finding that certain nongenoloxic chemical carcinogens induce cell proliferation in the same organ that develops tumors after long-term exposure, some suggest that the increased rates of cell division account for the carcinogenicity of these chemicals. This paper examines relationships between chemically induced liver toxicity, cell proliferation, and liver carcinogenesis; major factors include consistency, transient vs. sustained dose-response correspondence, and scientific plausibility. For a presumed mechanism to be valid, a sustained proliferative response is critical, largely because transient increases in hepatocyte proliferation are not sufficient to induce cancer or promote liver tumor development.

A consistent association between liver toxicity and carcinogenicity has not been established. Our evaluation of studies on purported relationships between chemically induced cell proliferation and liver carcinogenesis shows: 1) that inconsistencies in sex and species specificity exist, 2) that a large percentage of proliferative responses are transient, 3) that inconsistencies in response to various hepatic peroxisome proliferators are common, and 4) that dose-response and duration relationships have not been sufficiently examined.

Studies of proliferative responses of putative preneoplastic cells in the liver indicate that these cells divide faster than normal hepatocytes and also have higher death rates. Chemicals that induce cell proliferation in preneoplastic foci do not always provide a persistent increase in replication rates, even with continuous exposure. A selective growth advantage to preneoplastic cells in the liver may be provided either by an enhancement of the replication rates of these cells compared to the surrounding normal hepatocytes, by inhibition of cell loss, or by inhibition of the growth rate of normal cells.

More work is needed to understand how chenvcal carcinogens and noncarcinogens affect cell division and cell loss of normal hepatocytes and of preneoplastic cells; measurements of hepatocyte proliferation alone are not sufficient to elucidate mechanisms of liver tumor development or to predict liver carcinogenesis. Because of our limited knowledge of the complex molecular changes occurring during liver cancer, it would be inappropriate and far too premature to amend scientific risk assessment procedures for nongenotoxic chemical carcinogens based on oversimplified or incompletely tested speculations.
Suppressed Natural Killer Cell Activity in Patients with Silicone Breast Implants: Reversal upon Explantation
Authors: Campbell Andrew , Brautbar Nachman , Vojdani Aristo
Published: September 2013

We have previously shown that natural killer (NK) cell activity is significantly suppressed in patients with silicone breast implants. These patients were symptomatic and the suppression of natural killer cell activity was associated with additional significant immunological abnormalities (Vojdani et al, 1992a). Our studies have recently been confirmed by Smith et al. (1994), who described natural killer cell activity suppression following exposure to silicone gel, and reversal upon removal of the gel.

This study has been designed to evaluate natural killer cell activities in symptomatic women with silicone breast implants and again after explantation of the implants. Each patient served as her own control. Our findings show a marked significant increase in previously suppressed natural killer cell activity in 50% of the patients. In the other 50%, no change or suppressed NK activity was observed. These findings are compatible with recent studies in experimental animals, which show that administration of silicone reduces natural killer cell activity, and that this is reversible upon removal of the silicone.

Since NK cells are important in the control of tumor cell growth, we propose here that patients with reduced NK cell activity are at a higher risk of developing cancer, a concept recently described in experimental animals (Potter et al., 1994; Salhon et al, 1994).
Modulative Effects of Metabolic Effectors on Benzo(A)Pyrene-Induced Cytotoxicity and Mutagenicity in Mammalian Cells
Authors: Hsie Abraham W. , Recio Leslie
Published: September 2013

Conjugation and detoxification of mixed function oxidase (MFO)-mediated benzo(a)pyrene [B(a)P] metabolites with glucuronic acid and glutathione (GSH) are major pathways of B(a)P elimination and ultimately excretion in vivo. We have studied the effects of uridine diphosphate α-D-glucuronic acid (UDPGA) and GSH, a cofactor for the synthesis of glucuronide and GSH conjugates, respectively, on B(a)P-induced cytotoxicity and mutagenicity in mammalian cells. The S9-mix used in the Chinese hamster ovary cell/hypoxanthine-guanine phosphoribosyltransferase (CHO/HPRT) mutational assay was supplemented with either UDPGA, GSH, or GSH plus purified GSH-S-transferases (GSHTs), to study modulation of glucuronide and GSH detoxification mechanisms on B(a)P-induced cytotoxic and mutagenic effects. We found that the addition of UDPGA to S9-mix reduces cytotoxicity induced by either B(a)P or B(a)P 6-OH but not by B(a)P 7,8-diol [B(a)P-diol]. The reduction of B(a)P and B(a)P 6-OH-induced cytotoxicity by glucuronide conjugation is likely due to elimination of cytotoxic phenols and quinones. The addition of GSH to the S9-mix resulted in a reduction of B(a)P- and B(a)P-diol-induced cytotoxicity. GSH plus GSHT reduced B(a)P-induced cytotoxicity and mutagenicity. GSH inhibited the mutagenicity at low concentrations of B(a)P-diol. GSH plus GSHTs inhibited the cytotoxicity and mutagenicity of B(a)P-diol at concentrations not affected by GSH alone. These studies demonstrate that mechanisms of detoxification can affect the biological activity of B(a)P and B(a)P-diol as profoundly as bioactivation by the MFO system. Future research should address studies of mutagenicity modulation by metabolic effectors at both the molecular (DNA sequence) and cellular (quantitative mutagenesis) level.
Reproductive and Neurobehavioral Effects of Cochineal Administered To Mice in the Diet
Authors: Tanaka Toyohito
Published: September 2013

Mice were given the natural color additive cochineal in their food to provide dietary levels of 0 (control), 0.5, 1.0, and 2.0%, from five weeks of age in the Fo generation to nine weeks of age in the F1 generation, and selected reproductive and behavioral parameters were measured. Cochineal had few adverse effects on litter size, weight, or sex ratio. The average body weight of offspring during the lactation period was significantly decreased in higher-dosed groups of each sex. With regard to the neurobehavioral parameters, surface righting at postnatal day (PND) four was significantly affected in male offspring during the lactation period. Several parameters of movement activity in females were significantly different from controls at eight weeks of age in the F0 generation and at three weeks of age in the F1 generation. Multiple water T-maze performance of females was affected in treatment groups in the second trial at seven weeks of age in the F1 generation. The dose levels of cochineal in this study produced some adverse effects in reproductive and neurobehavioral parameters in mice.
Toxicological Investigations in the Semiconductor Industry
Authors: Schmidt Reiner , Scheufler Horst , Bauer Siegfried , Wolff Lona , Pelzing Matthias , Herzschuh Rainer
Published: September 2013

The prenatal toxic effects of contaminated vacuum pump oil (Sample A) and solid waste products (Samples B and C) originating from aluminum plasma etching processes in semiconductor manufacturing were investigated. Three strains of pregnant mice with different degrees of sensitivity during organogenesis (days 6-15 of gestation) were treated daily with 1000 mg/kg b. w. (Sample A), 500 or 750 mg/kg b.w. (Sample B), and 250, 500, or 750 mg/kg b.w. (Sample C). On day 18 of pregnancy, the animals were killed and examined for gross changes, number and weight of live fetuses, as well as the number of postimplantation losses and malformations. Analytical data showed that the investigated wastes contained various halogenated hydrocarbons and inorganic compounds.

Sample A revealed no signs of prenatal toxic action. In contrast, administration of Samples B and C caused strong prenatal toxic effects. The number of live fetuses declined in a dose-related manner, and evidence of intrauterine growth retardation was noted in fetuses that survived to day 18. The number of fetuses with malformations (only cleft palates) rose significantly in accordance with the doses and sensitivity of the strains (> 95% of the fetuses of the most sensitive strain after 750 mg/kg; 85% after 500 mg/kg).
Toxicity and Carcinogenicity of T-Butyl a Lcohol in Rats and Mice Following Chronic Exposure in Drinking Water
Authors: Cirvello Joseph D. , Radovsky Ann , Heath James E. , Farnell Daniel R. , Lindamood Charles
Published: September 2013

t-Butyl alcohol (TBA) was administered in drinking water to F344/N rats and B6C3F1 mice for two years using 60 animals/dose/sex/species. Male rats received doses of 0, 1.25, 2.5, or 5 mg/ml and females received 0, 2.5, 5, or 10 mg/ml, resulting in average daily doses of approximately 85, 195, or 420 mg TBA/kg body weight for males and 175, 330, or 650 mg/kg for females. Ten rats per group were evaluated after 15 months. Male and female mice received doses of 0, 5, 10, or 20 mg/ml, resulting in average daily doses of approximately 535, 1,035, or 2,065 mg TBA/kg body weight for males and 510, 1,015, or 2,105 mg/kg for females. Survival was significantly reduced in male rats receiving 5 mg/ml, female rats receiving 10 mg/ml, and male mice receiving 20 mg/ml. Long-term exposure to TBA produced increased incidences of renal tubule adenoma and carcinoma in male rats; transitional epithelial hyperplasia of the kidney in male and female rats; follicular cell adenoma of the thyroid in female mice; and follicular cell hyperplasia of the thyroid and inflammation and hyperplasia of the urinary bladder in male and female mice. In addition, a slight increase in follicular cell adenoma or carcinoma of the thyroid (combined) in male mice may have been related to the administration of TBA.
Environmental Personal Injury Litigation as One Source of Response Effects: Findings From the National Exposure Registry
Authors: Allred Sarah L. , Burg Je Anne R.
Published: September 2013

The potential for error in survey responses obtained from people involved with environmental personal injury litigation was examined in a registry of persons exposed to the chemical trichloroethylene. Two subgroups were selected and compared: environmental personal injury plaintiffs and nonlitigants residing in the same community. Self-reported information on demographic characteristics revealed no statistically significant differences. Although plaintiffs reported higher rates of symptoms and health problems, only 2 of the 20 comparisons on health were statistically significant. The overall similarity between the two groups suggests that environmental personal injury plaintiffs may be no more likely than nonlitigants to provide inaccurate information in health surveys.
Developmental Toxicity of Orange B Given to Rats in Drinking Water
Authors: Collins T.F.X. , Black T.N. , Ruggles D.I.
Published: September 2013

Orange B, a pyrazolone dye used to color frankfurter and sausage casings, was given in distilled drinking water to pregnant Osborne-Mendel rats throughout gestation. Assessed on the basis of fluid consumption, the dose levels of 0, 0.05, 0.1, 0.2, and 0.4% corresponded to daily Orange B consumption of 0, 67.5, 129.6, 266.6, and 532.3 mg/kg body weight, respectively. On gestation day 20, the females were euthanized and cesarean sections were performed. Throughout gestation, the treated animals consumed less fluid than did the controls, but the decreases were not dose-related. Feed consumption and maternal weight gain were not affected. No dose-related changes were seen in maternal clinical findings, implantations, fetal viability, or fetal size (weight and length). No compound-related effects were seen in sternebral development. Ossification of the interparietal bones was reduced at some dose levels, but the decreases were considered random because of absence of dose response. No dose-related effect was seen in the incidence of skeletal variations in fetuses or in the number of litters containing fetuses with skeletal variations. Skeletal development, as measured by the average number of ossified vertebrae, was similar in all groups. Soft-tissue development was not affected by dose levels of 0.05 to 0.2%. In animals treated with 0.4% Orange B, significant increases were seen in the incidence of hydroureters (severe and moderate), in the average numbers of fetuses with at least one and at least two soft-tissue variations per litter, and in the percentage of litters containing fetuses with at least two soft-tissue variations.
Acute and Subacute Toxicity Tests of Madder Root, Natural Colorant Extracted From Madder (Rubia Tinctorium), in (C57Bij6 x c3H)F1 Mice
Authors: Ino Natsuko , Tanaka Takuji , Okumura Ataru , Morishita Yukio , Makita Hiroki , Kato Yoshiaki , Nakamura Mikio , Mori Hideki
Published: September 2013

As part of the safety assessment of madder root (MR), a food colorant extracted from madder (Rubia tinctorium), toxicity tests were undertaken using (C57BL/6 x C3H)F1 mice of both sexes. An acute toxicity test was performed by 14-day administration of MR dissolved in distilled water by gavage at doses of 0, 500, 2000, 3500, and 5000 mg/kg body weight to groups of each sex. One male mouse dosed at 5000 mg/kg body weight was dead before the end of the study, indicating that the maximum tolerated dose of MR was between 3500 and 5000 mg/kg body weight. A subacute toxicity test of MR was performed using 62 mice of each sex, mixing their diets with MR at concentrations of 0, 0.3, 0.6, 1.25, 2.5, and 5% for 90 days. All mice tolerated these doses of MR well. The body weight gains of either sex were not affected by the treatment. None of the mice treated with MR showed clinical signs of toxicity. Histopathological examinations showed retention cysts of the kidneys and epidermal vaginal cysts in a few of the treated or control mice. No hyperplastic, preneoplastic, and neoplastic lesions and no pathological findings of toxicity were found. These results suggest that dietary exposure of MR at these doses has no acute or subacute toxic effects on mice.
Comparative Short-Term Health Responses To Sulfur Dioxide Exposure and Other Common Stresses in a Panel of Asthmatics
Authors: Gong Henry , Lachenbruch Peter A. , Harber Philip , Linn William S.
Published: September 2013

We studied 14 unmedicated sulfur dioxide (S02)-sensitive asthmatics to test the hypothesis that SO2 exacerbates asthma more than other everyday respiratory stressors. In Phase I, subjects underwent controlled exposures to 0.0, 0.5, and 1.0 ppm SO2 with light, medium, and heavy exercise (average ventilation 30, 36, and 43 l/min, respectively). Lung function, symptoms of asthma, and psychophysical (stamina) changes were measured. Function, symptom, and stamina responses correlated modestly. Increasing SO2 had stronger unfavorable effects than increasing exercise. In Phase II, subjects performed eight different physical tasks in SO2-free ambient air while symptoms and stamina were measured. Fast stair-climbing evoked symptoms similar to the effects of 0.5 ppm SO2/light exercise, while stamina reduction was comparable to 0.5 ppm SO2/heavy exercise. In Phase III, subjects recorded time-activity patterns, symptoms, and stamina during randomly selected intervals on a typical weekday and weekend day. Most reported activities were sedentary. Infrequent, strenuous Phase III exercise increased symptoms more than did 0.5 ppm SO2/light exercise, but with less effect on stamina. We conclude that for typical mild asthmatics, ten-minute SO2 exposures at concentrations >0.5 ppm andventilation >30 l/min can cause short-term asthma manifestations more intense than those usually experienced from everyday stresses without SO2 exposure.
An Approach for Incorporating Tissue Composition Data Into Physiologically Based Pharmacokinetic Models
Authors: Pelekis Michael , Poulin Patrick , Krishnan Kannan
Published: September 2013

The objective of this study was to develop an approach for incorporating tissue composition data into physiologically based pharmacokinetic (PBPK) models in order to facilitate "built-in" calculation of tissue:air partition coefficients (PCs) of volatile organic chemicals. The approach involved characterizing tissue compartments within PBPK models as a mixture of neutral lipids, phospholipids, and water (instead of using the conventional description of them as "empty" boxes). This approach enabled automated calculation of the tissue solubility of chemicals from n-octanol and water solubility data, since these data approximate those of solubility in tissue lipids and water. Tissue solubility was divided by the saturable vapor concentration at 37°C to estimate the tissue:air PCs within PBPK models, according to the method of Poulin and Krishnan (1995c). The highest and lowest lipid and water levels for human muscle, liver, and adipose tissues were obtained from the literature and incorporated within the tissue composition-based PBPK model to calculate the tissue:air PCs of dichloromethane (DCM) and simulate the pharmacokinetics of DCM in humans. The PC values predicted for human tissues were comparable to those estimated using rat tissues in cases where the relative levels of lipids and water were comparable in both species. These results suggest that the default assumption of using rat tissue:air PCs in human PBPK models may be acceptable for certain tissues (liver, adipose tissues), but questionable for others (e.g., muscle). The PBPK modeling exercise indicated that the interindividual differences in tissue dose arising from variations of tissue:air PCs may not be
Neutral Endopeptidase (NEP) and Its Role in Pathological Pulmonary Change With Inhalation Exposure To JP-8 Jet Fuel
Authors: Pfaff John K. , Tollinger Brian J. , Lantz R. Clark , Chen Huizhong , Hays Allison M. , Witten Mark L.
Published: September 2013

Through a simulated flightline exposure protocol, Fischer 344 rats (F344) were subjected to an aerosol/vapor mix of the military jet fuel, JP-8. Previous studies with this model of lung injury have revealed significant increases in pulmonary resistance, increased alveolar clearance of 99mTcDTPA, and a decrease in bronchoalveolar lavage fluid (BALF) concentration of the neuropeptide substance P (SP). Exposures to JP-8 were nose-only and for one hour daily. Six groups of Fischer 344 rats were exposed for 7, 28, or 56 days at two JP-8 concentrations (low dose = 469-520 mg/m3/hr, high dose = 814-1263 mg/m3/hr). Exposed groups were matched with longitudinal controls. In response to JP-8 inhalation, exposure animals demonstrated a dose-dependent as well as duration-determined reduction in BALF SP concentration. Both JP-8 concentrations caused significant pathological changes in lower pulmonary structures.

We designed this study to elucidate the cause of SP deficits following JP-8 inhalation through correlation with neutral endopeptidase (NEP) concentration taken from paired samples. NEP activity is significantly increased after 28 days of high-dose exposure (HD28) when compared with longitudinal controls and low-dose exposures (7D, 28D, and 56D). A significant inverse relationship between SP and NEP activity is demonstrated through Spearman rank-order correlation (rs = -0.42, n = 52, p < 0.05), suggesting inactivation of SP as the cause of its deficit. Pulmonary airway changes strongly implicate airway epithelium as a primary site of injury. Tachykinin degradation from the peptidase, NEP, plays a role in the process of airway cell injury. This research demonstrates the possible use of NEP and SP lung concentrations as biomarkers of chronic hydrocarbon exposure.
The Great Lakes: a Historical Overview
Authors: Hicks Heraline E.
Published: September 2013

The Great Lakes are collectively the largest inland body of freshwater on this planet. For more than two hundred years, the Great Lakes basin has been used as a resource for industry, agriculture, shipping, and recreation. The physical characteristics of the basin and the long retention time of chemicals in the lakes combine to make this huge freshwater resource a repository for chemical by-products of these activities. Many of the more than one thousand chemicals detected in the waters, sediment, or biota of the Great Lakes have known toxic effects.

This overview will identify the 11 most persistent toxic chemicals known as "critical" Great Lakes pollutants. It also will describe some of the adverse health effects that have been observed in fish and other wildlife because of exposure to these pollutants. Finally. it will discuss some of the early human health studies that 1) have demonstrated a correlation between increased body burdens and fish consumption, and 2) suggest an association between consumption of contaminated Great Lakes fish and adverse human health effects.
Fish Consumption and Other Characteristics of Reproductive-Aged Michigan Anglers—a Potential Population for Studying the Effects of Consumption of Great Lakes Fish On Reproductive Health
Authors: Courval Jeanne M. , Dehoog Jane V. , Holzman Claudia B. , Tay Eugene M. , Fischer Lawrence , Humphrey Harold E.B. , Paneth Nigel S. , Sweeney Anne M.
Published: September 2013

There has been considerable interest in the benefits and risks of eating Great Lakes fish, particularly with regard to reproductive health. We report the results of a survey conducted from 1993-1995 among Michigan anglers. The survey was designed to identify a reproductive-aged cohort of persons who consume high or low levels of Great Lakes fish in order to study the impact of polyhalogenated biphenyl (PHB) compounds and other toxins on human reproduction outcomes. Using fishing license data obtained from the Michigan Department of Natural Resources, we identified anglers of early reproductive age (18-34 years) in ten Michigan counties. The screening survey ascertained demographic, behavioral, fish consumption, and reproductive history information on anglers and their partners. Over 4,000 angler households were contacted. One thousand nine hundred fifty questionnaires were returned from 1,168 households. The median age of respondents was 30 years; 58% were male and 64% reported being married. Slightly more than one-half the respondents had attended or graduated from college, and less than 10% had not completed high school. In the past year, most respondents (46%) reported having eaten sport-caught fish 1-12 times, while 20% reported having eaten no sport-caught fish; 20% had consumed 13-24 meals. More sport-caught fish was consumed in the spring and summer than in the fall and winter, and males reported eating more fish than females. About 43% of our respondents reported that they intend to have one or more children in the next five years. Of these respondents, 287 couples had no identified impairments to reproduction and therefore would be eligible to participate in the future reproductive study.
Harmonizing Human Health Studies in the Great Lakes
Authors: Hicks Heraline E. , Spengler Robert F.
Published: September 2013

Epidemiological studies of exposed human populations can provide valuable evidence of human health effects. Information has been sparse on human health effects associated with consumption of contaminated Great Lakes fish. As part of its Great Lakes Human Health Effects Research Program, the Agency for Toxic Substances and Disease Registry (ATSDR) has funded ten projects. Of these studies, eight are epidemiologic investigations of human exposure and potential health effects from consumption of contaminated fish.

To strengthen and to enhance the findings and comparability across the health studies, ATSDR has initiated several activities. These activities include harmonizing questionnaires, analytical protocols, human health end points, and contaminants tested. Also included is the establishment of a quality assurance and quality control (QA/QC) program and tissue bank. These activities will allow ATSDR to enhance exposure assessment in the Great Lakes basin.

In addition, these research activities allow ATSDR to evaluate and to interpret data across all the projects, including a basin-wide health risk analysis on exposure, levels of contaminants or body burden, and the potential for human health effects from exposure to Great Lakes contaminants.
Reference Range Data for Assessing Exposure To Selected Environmental Toxicants
Authors: Needham L.L. , Patterson D.G. , Burse V.W. , Paschal D.C. , Turner W.E. , Hill R.H.
Published: September 2013

We analyzed blood and urine specimens from 32 charter boat captains, anglers, and spouses from both groups, who reportedly ate fish from Lakes Michigan, Huron, or Erie, for selected environmental toxicants. The toxicants measured in serum were polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), coplanar polychlorinated biphenyls, other polychlorinated biphenyls (PCBs), and persistent pesticides. Nonpersistent pesticides and elements were measured in urine; and elements were measured in blood. Internal dose levels of these toxicants will be compared to reference range data that we have compiled. These reference range data will be used to ascertain the exposure status of individuals or groups within this study.
Canadian Health Databases Relevant To Great Lakes Basin Research
Authors: Johnson Kenneth C.
Published: September 2013

Several population-based health databases exist in Canada which provide valuable systematic information for facilitating epidemiological evaluation of human health in the Great Lakes Basin. They include the long-established Canadian Mortality Database, a national birth defects registry, a provincial hospitalization database, and provincial and national cancer registry systems. The most recent addition is the National Enhanced Cancer Surveillance System which currently is being implemented to allow for detailed evaluation of air and water quality concerns in relation to a range of cancer types. The system includes statistical evaluation of geographical cancer incidence patterns; development of a national environmental quality database; and systematic collection of individual risk factor information for a large number of newly diagnosed cancer cases and a population control group. A brief description of each database and examples of relevant research using each of these databases is presented.
Prevalence of Pathogenic Acanthamoeba (Protozoa: Amoebidae) in the Atmosphere of the City of San Luis Potosi, Mexico
Authors: Rodriguez-Zaragoza Salvador , Magana-Becerra Alejandro
Published: September 2013

Several species of pathogenic Acanthamoeba cause infections to humans, but amoebic keratitis is more frequently found than any other due to the increasing number of contact lens wearers in the world. Cysts and trophozoites of these amebas are airborne and may pollute water from the air. We investigated the proportion of pathogenic Acanthamoeba from the atmosphere of the city of San Luis Potosi. Samples were taken by the impinger method, every month during one year. We isolated 23 strains of Acanthamoeba, 61% of them were non-pathogenic, 31% were non-pathogenic with invasive capacity and 8% were pathogenic to mice. Almost 40% of these strains represent danger of infections to humans. The isolations were more abundant during the dry season in the south (urban) and west (suburban) stations, which means that the sanitary conditions around stands may enhance the proportion of pathogenic strains in the surroundings.
Reproductive and Neurobehavioral Effects of Chlorpropham Administered to Mice in the Diet
Authors: Tanaka Toyohito
Published: September 2013

Chlorpropham was given in the diet to provide levels of 0(control), 0.15, 0.30, and 0.60%, from 5 weeks of age of the F0 generation to 9 weeks of age of the F1 generation in mice, and selected reproductive and neurobehavioral parameters were measured. There were no adverse effects of chlorpropham on either litter size or litter weight and sex ratio at birth. The average body weight of offspring was significantly affected in the low-dose group of each sex and in the high-dose group of females, and was increased in the middle-dose group of males during the lactation period. In neurobehavioral parameters, surface righting at postnatal day (PND) 7 was significantly affected in male offspring in a dose-related manner. Swimming head angle at PND 4 was significantly restrained in male offspring in a dose-related manner, and olfactory orientation at PND 14 was significantly depressed in female offspring in a dose-related manner. The dose levels of chlorpropham in the present study produced some adverse effects in reproductive and neurobehavioral parameters in mice.
Cellular Bioavailability of Natural Hormones and Environmental Contaminants as a Function of Serum and Cytosolic Binding Factors
Authors: Crain D. Andrew , Noriega Nigel , Vonier Peter M. , Arnold Steven F. , McLachlan John A. , Guillette Louis J.
Published: September 2013

Environmental contaminants have been reported to function as hormone mimics in various wildlife species. To investigate a potential mechanism for the interaction of contaminants with the endocrine system, we evaluated the cellular bioavailability of numerous chemicals. Hormone binding proteins from oviductal cytosol of the American alligator (Alligator mississippiensis) and yellow-bellied turtle (Trachemys scripta ) were used in competitive binding assays with [3H] 17β-estradiol. Most of the environmental contaminants, and the potent, synthetic estrogen diethylstilbestrol (DES), did not interact with the cytosolic binding proteins. Among the compounds tested, o,p'-DDT and toxaphene exhibited the greatest affinity for the binding proteins. The functional consequence of the apparent lack of interaction of most contaminants with binding proteins was studied in a strain of yeast containing the human estrogen receptor (YES assay). The activation of YES with estradiol was reduced 30% in the presence of a physiological concentration (0.01 mg/mL) of human sex hormone binding globulin (SHBG), a hormone binding protein found in the blood. In contrast, the activity of DES was not inhibited by 0.01 mg/mL SHBG. Interestingly, ethinyl estradiol, a major component of contraceptives, did not appear to appreciably interact with SHBG in the YES system. Together, these data suggest that cytosolic and circulating binding proteins bind many environmental contaminants with much less affinity than native steroids. Therefore, such contaminants may be more hormonally active than previously hypothesized.
Selective Vulnerability of Dopaminergic Systems To Industrial Chemicals: Risk Assessment of Related Neuroendocrine Changes
Authors: Mutti Antonio , Smargiassi Audrey
Published: September 2013

Increased serum prolactin (PRL) is a common finding among subjects exposed to styrene, perchloroethylene, lead (Pb), and manganese (Mn) at levels below the current threshold limit values. On a group basis, abnormally high basal PRL shows a dose-related distribution among workers exposed to styrene, Pb, and Mn. On the basis of dose-response relationships, the benchmark doses (BMD) for styrene metabolites in urine, lead in blood (Pb-B), and Mn in urine (Mn-U), are 4 mg/g creatinine, 112 μg/L, and 0.3 μg/L, respectively. Noteworthy, the BMD for Mn-U and Pb-B is well below the upper reference limit. A shift in the distribution but not in the prevalence of abnormally high values of serum PRL was observed among perchloroethylene-exposed dry cleaners, which makes interpretation in terms of risk difficult. The measurement of PRL thus provides opportunities for early identification of excess exposure to neurotoxic chemicals affecting dopaminergic control of pituitary secretion. For styrene, Pb, and Mn the BMD provides an objective and statistically determined threshold, which seems to be in good agreement with the estimated no-observed-adverse-effect-level (NOAEL). The NOAEL, however, is based on traditional approaches that require the application of uncertainty factors, e.g., a default factor of 10 when extrapolating the NOAEL from the lowest-observed- adverse-effect-level (LOAEL). Due to its sensitivity to a number of potential confounders, caution must be exercised when using PRL as a screening test at the individual level. Also, age and sex dependent variations in susceptibility may hamper extrapolations from the occupational settings to the general population.
La passation de questionnaire – Chronique d’un solliciteur de l’espace public
Authors: Daniel François-Joseph
Published: September 2013

Filling Out Questionnaires - Chronicle of a Public Space Solicitor: In a composite public space where people are increasingly exposed to solicitations of all kinds, distributing and collection questionnaire survey data can be problematic. If the culture of solicitation is widely accepted by most, refusal mechanisms are equally culturally established. The aim of this paper is to profile the solicitation work of surveyors through the ethnographic description of a questionnaire interviewer's work. This article relies in particular on the need to understand the interaction framework that both unites the interviewee and the interviewer, and determines the efficiency with which the questionnaire is administered. The ability to cope with this framework – the set of tangible and intangible elements that structure and limit, but also permit the completion of the interview – constitutes an important skill of the interviewer in action.
XI Conference of the International Society for Quality-of-Life Studies (ISQOLS) “Discovering New Frontiers in Quality of Life Research” (1-4 November 2012, Venice, Italy)
Authors: Maggino Filomena
Published: September 2013

This report on the recent eleventh conference of the International Society for Quality of Life Studies (ISQOLS), which took place in Venice, traces the development of methods and movements involved in measuring quality of life, including the new BES project, established at the Italian National Institute of Statistics, and the initiative “How is Life”, led by OECD.