Abstract  With a common study protocol, case-referent studies within cohorts were performed in Denmark, Norway, Sweden, and Finland to study reproductive hazards of women doing dry-cleaning work. Due to national differences not all of the studies could follow exactly the same procedures in data collection, but they were all based on the linkage of cohorts of dry-cleaning and laundry workers to national registers of births and reproductive failures. Summary measures from each study were combined without the data being pooled. The most significant finding was an increased risk of spontaneous abortion among the most exposed women in the Finnish data. This finding was only supported by the results of the other studies to a minor degree, and the combined odds ratio had confidence limits which included unity.

Abstract  The major initial metabolites of the chlorinated ethylenes in hepatocyte suspensions isolated from phenobarbital treated rats were as follows (rates of metabolite production in nmol/10(6) cells/min are given in brackets): vinylidene chloride, dichloroacetic acid (0.015); cis-1,2-dichloroethylene, 2,2-dichloroethanol (0.24); trans-1,2-dichloroethylene, dichloroacetic acid (0.005); trichloroethylene, chloral hydrate (2.7); tetrachloroethylene, trichloroacetic acid (0.08). Comparison of the metabolism of the chlorinated ethylenes by isolated hepatocyte suspensions and hepatic microsomes indicates that the initial products of the three dichlorinated ethylenes from cytochrome P-450 in hepatic microsomes are rapidly and extensively metabolized in the hepatocyte, where the Phase II enzymes are present. In contrast, the initial metabolites of trichloroethylene and of tetrachloroethylene in the two systems are identical. The abilities of the chlorinated ethylenes to induce unscheduled DNA synthesis was assessed in isolated hepatocytes using a method which does not require the blocking of semi-conservative DNA synthesis. Vinylidene chloride, cis-1,2-dichloroethylene and trichloroethylene induced unscheduled DNA synthesis, while trans-1,2-dichloroethylene and tetrachloroethylene did not.

Abstract  Continuous exposure of Mongolian gerbils to perchloroethylene (PCE) (120 ppm) for 12 months in an inhalation chamber caused no changes in body or brain weights. The protein content, the concentration of lipid phosphorus or cholesterol were unaltered in the cerebral cortex and hippocampus. Howeve, a small change in the fatty acid pattern of phospholipid was observed. In the phosphatidylethanolamine of cerebral cortex and hippocampus a decrease was found among the long-chain, linolenic acid-derived, fatty acids. The ratio 22:4 (N-6)/22:5 (N-3) was increased, indicating a shift towards the corresponding linoleic acid-derived 22-carbon fatty acids. The observed changes among poly-unsaturated fatty acids are similar to those appearing after peroxidation and either protein or essential fatty acid malnutrition. However, an attractive explanation for the changes is that they represent a response to the fluidizing properties of PCE.

Abstract  The neurobehavioral effects of 10 known toxicants were examined as part of a multidisciplinary screening battery. The toxicants included carbaryl (CAR), triadimefon (TDM), heptachlor (HEP), chlordane (CDN), diethylhexyl phthalate (DEHP), carbon tetrachloride (CCl4), phenol, trichloroethylene (TCE), tetrachloroethylene (PER or perchlorethylene), and dichloromethane (DCM or methylene chloride). A functional observational battery and motor activity measurements were conducted before exposure, at specified times after an acute exposure, and during and after 14-d exposure. Severity scoring analysis was used to generate profiles of effect. The pesticides, CAR, TDM, HEP, and CDN, displayed the most acute neurotoxicity and were active at lower proportions of their respective acute LD50 values than were the solvents or the industrial chemicals. Although CAR and TDM showed little or no neurobehavioral effects with repeated dosing, cumulative neurotoxicity and lethality were evident with HEP and CDN. Phenol produced acute convulsive effects, and the most prominent finding with repeated exposure was lethality. DEHP displayed no neurobehavioral toxicity. The organic solvents, TCE, PER, CCl4, and DCM, produced various degrees of general nervous system depression following acute administration of high dose levels. Repeated dosing produced little or no effect with TCE or PER, marked physiological changes with CCl4, and cumulative toxicity and lethality with DCM. Some results of these studies were unexpected and should provide impetus for further research. Overall, these findings illustrate the utility of these screening methods.

Abstract  Hazardous air pollutants are plausible candidate exposures for autism spectrum disorders. They have been explored in recent studies for their role in the development of these disorders.

We used a prevalent case-control design to screen perinatal exposure to 35 hazardous air pollutants for further investigation in autism etiology. We included 383 children with autism spectrum disorders and, as controls, 2,829 children with speech and language impairment. All participants were identified from the records-based surveillance of 8-year-old children conducted by the Autism and Developmental Disabilities Monitoring Network in North Carolina (for children born in 1994 and 1996) and West Virginia (born in 1992 and 1994). Exposures to ambient concentrations of metal, particulate, and volatile organic air pollutants in the census tract of the child's birth residence were assigned from the 1996 National Air Toxics Assessment annual-average model. We estimated odds ratios (ORs) for autism spectrum disorders and corresponding 95% confidence intervals (CIs), comparing across the 20th and 80th percentiles of log-transformed hazardous air pollutant concentration among the selected controls, using semi-Bayes logistic models and adjusting for sampling variables (surveillance year and state), a priori demographic confounders from the birth certificate and census, and covarying air pollutants.

We estimated many near-null ORs, including those for metals, established human neurodevelopmental toxicants, and several pollutants that were elevated in a similar study in California. Hazardous air pollutants with more precise and elevated OR estimates included methylene chloride, 1.4 (95% CI = 0.7-2.5), quinoline, 1.4 (1.0-2.2), and styrene, 1.8 (1.0-3.1).

Our screening design was limited by exposure misclassification of air pollutants and the use of an alternate developmental disorder as the control group, both of which may have biased results toward the null. Despite these limitations, methylene chloride, quinoline, and styrene emerged (based on this analysis and prior epidemiologic evidence) as candidates that warrant further investigation for a possible role in autism etiology.

Abstract  To evaluate the risk of cancer and other diseases among workers engaged in aircraft manufacturing and potentially exposed to compounds containing chromate, trichloroethylene (TCE), perchloroethylene (PCE), and mixed solvents.

A retrospective cohort mortality study was conducted of workers employed for at least 1 year at a large aircraft manufacturing facility in California on or after 1 January 1960. The mortality experience of these workers was determined by examination of national, state, and company records to the end of 1996. Standardised mortality ratios (SMRs) were evaluated comparing the observed numbers of deaths among workers with those expected in the general population adjusting for age, sex, race, and calendar year. The SMRs for 40 cause of death categories were computed for the total cohort and for subgroups defined by sex, race, position in the factory, work duration, year of first employment, latency, and broad occupational groups. Factory job titles were classified as to likely use of chemicals, and internal Poisson regression analyses were used to compute mortality risk ratios for categories of years of exposure to chromate, TCE, PCE, and mixed solvents, with unexposed factory workers serving as referents.

The study cohort comprised 77,965 workers who accrued nearly 1.9 million person-years of follow up (mean 24.2 years). Mortality follow up, estimated as 99% complete, showed that 20,236 workers had died by 31 December 1996, with cause of death obtained for 98%. Workers experienced low overall mortality (all causes of death SMR 0.83) and low cancer mortality (SMR 0.90). No significant increases in risk were found for any of the 40 specific cause of death categories, whereas for several causes the numbers of deaths were significantly below expectation. Analyses by occupational group and specific job titles showed no remarkable mortality patterns. Factory workers estimated to have been routinely exposed to chromate were not at increased risk of total cancer (SMR 0.93) or of lung cancer (SMR 1.02). Workers routinely exposed to TCE, PCE, or a mixture of solvents also were not at increased risk of total cancer (SMRs 0.86, 1.07, and 0.89, respectively), and the numbers of deaths for specific cancer sites were close to expected values. Slight to moderately increased rates of non-Hodgkin's lymphoma were found among workers exposed to TCE or PCE, but none was significant. A significant increase in testicular cancer was found among those with exposure to mixed solvents, but the excess was based on only six deaths and could not be linked to any particular solvent or job activity. Internal cohort analyses showed no significant trends of increased risk for any cancer with increasing years of exposure to chromate or solvents.

The results from this large scale cohort study of workers followed up for over 3 decades provide no clear evidence that occupational exposures at the aircraft manufacturing factory resulted in increases in the risk of death from cancer or other diseases. Our findings support previous studies of aircraft workers in which cancer risks were generally at or below expected levels.

Abstract  Although many studies have examined the associations between occupational exposures and kidney cancer, the evidence is not consistent. To examine the risk of occupational exposures on kidney cancer, we carried out a follow-up study on the economically active Swedish population, based on the latest update of the Swedish Family-Cancer Database. We calculated standardized incidence ratios (SIR) and 95% confidence intervals (CIs) for different occupational groups, adjusted for age, period, and socioeconomic status. The reference group was all the economically active population. An increased risk of renal parenchymal cancer was observed for miners and quarry workers, drivers, sales agents, transport workers, and public safety and protection workers among men, and launderers and dry cleaners among women. Significantly increased SIRs of renal pelvical cancer were also observed for the food manufacture workers among men, and journalists and shoe and leather industry workers among women. Male forestry workers, smelters, and metal foundry workers had increased risk for unspecified kidney cancer. Although smoking may explain some of these results, exposure to gasoline, diesel, their exposure products, some metal and chemicals in shoe and leather works, and dry-cleaning products may be associated with kidney cancer.

Abstract  In a large case-control study (n = 1,926) of spontaneous abortion (SAB), exposure to solvents was ascertained by a telephone interview that asked about occupational use of 18 specific solvents or products, as well as an open-ended "other" solvent category. The adjusted odds ratio for use of any solvent was 1.1 (0.8, 1.5). Solvents for which at least a doubled crude risk of SAB was found included perchlorethylene (OR = 4.7, 95% CI = 1.1, 21.1), trichloroethylene (OR = 3.1, CI = 0.9, 10.4), and paint thinners (OR = 2.3, CI = 1.0, 5.1). Comparing exposure greater than 10 hours per week versus less did not show consistent dose-response effects. By solvent class, an association was seen with aliphatic solvents (adjusted OR = 1.8, 95% CI = 1.1, 3.0), but there was no dose-response effect by hours of use. Household use of solvent-containing products was generally not strongly associated with SAB, nor did it appear to confound the association seen with occupational use. From this and other studies, occupational exposure to at least some solvents appears associated with SAB. The associations of solvent exposure and fetal growth among liveborn offspring of controls was also examined

Abstract  We performed three types of studies to evaluate the genotoxicity of the chlorinated organic solvent perchloroethylene (PERC or tetrachloroethylene) and its volatile metabolites, trichloroacetyl chloride (TCAC) and trichloroacetic acid (TCA), as well as the volatile metabolites of trichloroethylene, i. e. dichloroacetyl chloride (DCAC), dichloroacetic acid (DCA), and 2,2,2-trichloroethanol (TCE). In the first set of studies, which involved the evaluation of these chemicals in the Microscreen prophage-induction assay, only DCA (³S9) was genotoxic, producing 6.6–7.2 plaque-forming units/mM. This places DCA among the weakest of the >100 chemicals that have been identified previously as inducers of prophage in this assay. In the second set of studies, which involved the evaluation of these chemicals in the vapor state in Salmonella TA100 using a Tedlar® bag vaporization technique, DCA (³/–S9), DCAC (–S9), and TCAC (³/–S9) were mutagenic, producing 3–5x increases in revertants/plate relative to the background. S9 enhanced the mutagenic potency of DCA but had no effect on the mutagenic potency of TCAC. The potencies ranged from 0.7 to 3.9 rev/p. p. m., resulting in a potency ranking of DCA > DCAC {approx} TCAC. The lowest effective concentrations were 50–300 p. p. m., which are similar to those for ethylene oxide and epichlorohydrin in this assay. In the third set of studies, the mutation spectra of DCA, DCAC, and TCAC were determined at the base-substitution allele hisG46 of Salmonella TA100. DCA and DCAC induced primarily G · C {uparrow} A · T transitions, whereas TCAC induced primarily G · C {uparrow} T · A transversions, which was also the predominant mutation among the background revertants. The DCAC and DCA mutation spectra might be explained by a mutational mechanism in which the compounds are metabolized to etheno adducts on cytosine, causing the DNA polymerase to misincorporate. This report is the first demonstration of the mutagenicity of DCA and of the mutation spectrum of any of these chlorinated organics. In conjunction with previous studies, these results support consideration of a genotoxic mechanism for the carcinogenicity of PERC and trichloroethylene because of the mutagenicity of their metabolites, including DCA.

Abstract  Seventeen chemicals (solvents, insecticides and intermediates in the production of textiles and resins) were tested in a short-term in vitro system with human lymphocytes to determine their toxic action. The parameters studied were the tritiated thymidine uptake and cell viability in cultures grown with or without a rat liver metabolizing system (S-9 mix). Data obtained showed that 1,3-dichlorobenzene, 1,2-dichlorobenzene, hexane, 1,2-diiodoethane, 1,4-dichlorobenzene, tetrachloroethylene, 2,3-dibromopropanol, chloromethyl methyl ether, 1,2- and 1,3-dibromopropane, in order, exerted the more toxic effects; ethyl acetate, cyclohexane, cyclohexanone and benzene showed lower toxic activity. The chemicals lost their toxic power in the presence of the metabolizing system with the exception of 1,2- and 1,3-dichlorobenzene which maintained in some degree their toxicity even in the presence of the S-9 mix. Only chloromethyl methyl ether elicited unscheduled DNA synthesis acting as DNA damaging agent.

Abstract  14C-Perchloroethylene is covalently bound to DNA, RNA and proteins of rat and mouse organs in vivo after ip injection. Covalent Binding Index values are typical of weak-moderate and weak initiators, for mouse and rat liver, respectively. The greater amounts of labelings detected in mouse liver and in rat kidney macromolecules are consistent with the known toxic and carcinogenic actions of this compound. In vitro binding of perchloroethylene to nucleic acids and proteins proceeds through the involvement of the P-450-dependent mixed function oxidase system from liver microsomes. Kidney, lung and stomach microsomal fractions are uneffective. Cytosolic enzymes from all assayed organs are much more efficient than liver microsomes in bioactivating the compound. GSH addition to liver microsomal system greatly enhances binding extent. This observation suggests that GSH plays a role in the binding of perchloroethylene metabolites as for symmetrically substituted haloethanes.

Abstract  Dichloroacetic acid (DCA) and trichloroacetic acid (TCA) are found in drinking water and are metabolites of trichloroethylene. They are carcinogenic and promote liver tumors in B6C3F1 mice. Hypomethylation of DNA is a proposed nongenotoxic mechanism involved in carcinogenesis and tumor promotion. We determined the effect of DCA and TCA on the level of DNA methylation in mouse liver and tumors. Female B6C3F1 mice 15 days of age were administered 25 mg/kg N-methyl-N-nitrosourea and at 6 weeks started to receive 25 mmol/liter of either DCA or TCA in their drinking water until euthanized 44 weeks later. Other animals not administered MNU were euthanized after 11 days of exposure to either DCA or TCA. DNA was isolated from liver and tumors, and after hydrolysis 5-methylcytosine (5MeC) and the four bases were separated and quantitated by HPLC. In animals exposed to either DCA or TCA for 11 days but not 44 weeks, the level of 5MeC in DNA was decreased in the liver. 5MeC was also decreased in liver tumors from animals exposed to either chloroacetic acid. The level of 5MeC in TCA-promoted carcinomas appeared to be less than in adenomas. Termination of exposure to DCA, but not to TCA, resulted in an increase in the level of 5MeC in adenomas to the level found in noninvolved liver. Thus, hypomethylated DNA was found in DCA and TCA promoted liver tumors and the difference in the response of DNA methylation to termination of exposure appeared to support the hypothesis of different mechanisms for their carcinogenic activity.

Abstract  The clastogenicity of tetrachloroethylene (tetra) was detected by means of the micronucleus assay using hepatocytes and relticulocytes from ddY male mice, to understand its effects in upon hepatocellular carcinomas in mice. The frequency of micronucleated hepatocytes of mice that received a single injection of tetra after partial hepatectomy increased to levels that were significantly higher than those of controls treated with solvent. However, the micronucleus assay using peripheral blood reticulocytes from ddY male mice, revealed that tetra did not induce to a statistically significant increase in micronucleus frequency. These results suggested that tetra metabolites have a clastogenic effect in vivo upon mouse liver but not upon bone marrow cells.

Abstract  Perchloroethylene (PERC) is used widely as an industrial dry cleaning solvent and metal degreaser. PERC is an animal carcinogen that produces increased incidence of renal adenomas, adenocarcinomas, mononuclear cell leukemia, and hepatocellular tumors. Oxidative DNA damage and lipid peroxidation were assessed in 38 women with (dry cleaners) or without (launderers) occupational exposure to PERC. PERC exposure was assessed by collecting breathing zone samples on two consecutive days of a typical work week. PERC levels were measured in blood drawn on the morning of the second day of breathing zone sample collection in dry cleaners and before a typical workday in launderers. Blood PERC levels were two orders of magnitude higher in dry cleaners compared to launderers. A significant correlation was noted between time weighted average (TWA) PERC and blood PERC in dry cleaners (r=0.7355, P<0.002). 8-Hydroxydeoxyguanosine (8-OHdG), ng/mg deoxyguanosine (dG) in leukocyte nuclear DNA was used as an index of steady-state oxidative DNA damage. Urinary 8-OHdG, microg/g creatinine was used as an index of oxidative DNA damage repair. Urinary 8-epi-prostaglandin F(2alpha) (8-epi-PGF), ng/g creatinine was used as an index of lipid peroxidation. The mean+/-S.D. leukocyte 8-OHdG in launderers was 16.0+/-7.3 and was significantly greater than the 8.1+/-3.6 value for dry cleaners. Urinary 8-OHdG and 8-epi-PGF were not significantly different between dry cleaners and launderers. Unadjusted Pearson correlation analysis of log transformed PERC exposure indices and biomarkers of oxidative stress indicated a significant association in launderers between blood PERC and day 1 urinary 8-OHdG (r=0.4661, P<0.044). No significant associations between exposure indices and biomarkers were evident in linear models adjusted for age, body mass index, race, smoking (urinary cotinine, mg/g creatinine) and blood levels of the antioxidants Vitamin E and beta-carotene. The mean+/-S.D. leukocyte 8-OHdG value in control white women was 17.8+/-7.4 and was significantly greater than the 11.8+/-5.9 in control black women. No significant differences by race were evident for the other biomarkers. Smoking status was not significantly associated with any of the oxidative damage indices. Results indicate a reduction in oxidative DNA damage in PERC exposed dry cleaners relative to launderers, but PERC could not clearly be defined as the source of the effect.

Abstract  BACKGROUND: This multicentre population-based case-control study was conducted to estimate the urothelial cancer risk for occupational exposure to aromatic amines, polycyclic aromatic hydrocarbons (PAH), and chlorinated hydrocarbons besides other suspected risk factors. METHODS: In a population-based multicentre study, 1035 incident urothelial cancer cases and 4298 controls matched for region, sex, and age were interviewed between 1991 and 1995 for their occupational history and lifestyle habits. Exposure to the agents under study was self-assessed as well as expert-rated with two job-exposure matrices and a job task-exposure matrix. Conditional logistic regression was used to calculate smoking adjusted odds ratios (OR) and to control for study centre and age. RESULTS: Urothelial cancer risk following exposure to aromatic amines was only slightly elevated. Among males, substantial exposures to PAH as well as to chlorinated solvents and their corresponding occupational settings were associated with significantly elevated risks after adjustment for smoking (PAH exposure, assessed with a job-exposure matrix: OR = 1.6, 95% CI: 1.1-2.3, exposure to chlorinated solvents, assessed with a job task-exposure matrix: OR = 1.8, 95% CI: 1.2-2.6). Metal degreasing showed an elevated urothelial cancer risk among males (OR = 2.3, 95% CI: 1.4-3.8). In females also, exposure to chlorinated solvents indicated a urothelial cancer risk. Because of small numbers the risk evaluation for females should be treated with caution. CONCLUSIONS: Occupational exposure to aromatic amines could not be shown to be as strong a risk factor for urothelial carcinomas as in the past. A possible explanation for this finding is the reduction in exposure over the last 50 years. Our results strengthen the evidence that PAH may have a carcinogenic potential for the urothelium. Furthermore, our results indicate a urothelial cancer risk for the use of chlorinated solvents

Abstract  A death certificate case-control study of primary liver cancer and occupation was conducted to determine if the high risk of liver cancer in Mexican-Americans can be explained by farmworker exposures to pesticides. The association of liver cancer with the petroleum and chemical industry and with other potentially high-risk occupations was also examined. For the years 1969 to 1980, 1,742 deaths from primary liver cancer were identified for Texas males. Controls were randomly selected from other causes of deaths among males excluding all neoplasms, liver and gallbladder diseases, infectious hepatitis, and alcoholism, and were frequency matched to cases by age, race, ethnicity, and year of death. Risk for farmworkers based on age, race, and ethnicity-adjusted odds ratios (ORs) was not excessive (OR = 1.4, 95% confidence limits [C.L.] 0.8-2.2) but was larger than the risk for farmers (OR = 1.0, 95% C.L. 0.8-1.2). Excess risk in the petroleum and chemical manufacturing industries was confined to oil refinery workers (OR = 2.0, 95% C.L. 1.1-3.5). Other occupations with twofold risk or greater were plumbers and pipefitters (OR = 2.0, 95% C.L. 1.0-3.8), butchers and meat cutters (OR = 2.6, 95% C.L. 1.1-6.6), textile workers (OR = 3.1, 95% C.L. 1.2-7.8), cooks (OR = 2.2, 95% C.L. 1.1-4.5), and longshoremen (OR = 2.2, 95% C.L. 0.6-7.4).

Abstract  There is considerable potential for worker exposure to tetrachloroethylene, both by skin contact and by inhalation, during its use in dry cleaning and degreasing operations. This paper reviews accounts of both accidental overexposures of workers and controlled exposures of human subjects by these two routes of exposure. Several reported cases of accidental overexposure to anesthetic doses of the chemical reveal that recovery was generally complete but prolonged, and accompanied by many days of measurable levels of the chemical in the patient's alveolar breath. Chronic overexposures of workmen have lessened since the general acceptance by the Western world of the recommended TLV of 100 ppm for 8 hr of daily exposure. Controlled inhalation studies with volunteer subjects at this level of exposure revealed no effects upon health but did indicate a slight decrement in performance on a coordination test. Additional behavioral and neurological tests revealed no interactive effects when alcohol or diazepam, two depressant drugs, were added singly to tetrachloroethylene exposures. Individual susceptibility to the vapor of this chemical, as evidenced by subjective complaints, was noted in approximately one of ten subjects. The authors conclude that the TLV concentration of 100 ppm in the workplace has a negligible margin of safety regarding unimpaired performance during repeated exposures which could be especially hazardous if the worker is physically active or is in a situation where skin absorption presents an added burden.

Abstract  A 6-week-old breast-fed infant had obstructive jaundice and hepatomegaly. When a dry-cleaning solvent, tetrachloroethylene, was detected in the mother's milk and blood, breast-feeding was discontinued. Rapid clinical and biochemical improvement followed. The child grew normally and had normal liver function during 2 years of follow-up.

Abstract  6 alpha-chloroepoxides have been tested for in vitro activity in a variety of systems. The epoxides were cis- and trans-1-chloropropene oxide, cis- and trans-1,3-dichloropropene oxide, trichloroethylene oxide and tetrachloroethylene oxide. The epoxides were assayed for mutagenicity in the absence of metabolic activation in S. typhimurium TA1535 and E. coli WP2 uvrA and for preferential inhibition of growth of DNA-repair-deficient E. coli. All 6 epoxides possessed DNA-modifying activity as evidenced by their ability to preferentially inhibit DNA polymerase-deficient E. coli. All of the test chemicals except trichloroethylene oxide were mutagenic for S. typhimurium and all except trichloroethylene oxide and tetrachloroethylene oxide were mutagenic for E. coli Wp2 uvrA. Cis- and trans-1,3-dichloropropene oxide were the most potent mutagens and DNA modifiers. For all cases, the cis isomers were more active than the corresponding trans isomers. alpha-Chloroepoxides are considered likely to be the active intermediates of the carcinogenic parent halo-olefins. These mutagenicity studies are considered relevant in assessing the carcinogenicity of the parent hydrocarbons.

Abstract  Fischer 344 rats and B6C3F1 mice of both sexes were exposed to 400 ppm perchloroethylene (PER) by inhalation, 6 hr/day for 14, 21, or 28 days or to 200 ppm for 28 days. Increased numbers of peroxisomes were seen under the electron microscope and increased peroxisomal cyanide-insensitive palmitoyl CoA oxidation was measured (3.6-fold increase in males and 2.1-fold increase in females) in the livers of mice exposed to PER. Hepatic catalase was not increased. Peroxisome proliferation was not observed in rat liver or in the kidneys of either species. Trichloroacetic acid (TCA), a known carcinogen and hepatic peroxisome proliferating agent, was found to be a major metabolite of PER. Blood levels of this metabolite measured in mice and rats during and for 48 hr after a single 6-hr exposure to 400 ppm PER showed that peak blood levels in mice were 13 times higher than those seen in rats. Comparison of areas under the curves over the time course of the experiment showed that mice were exposed to 6.7 times more TCA than rats. The difference in metabolism of PER to TCA in mice and rats leads to the species difference in hepatic peroxisome proliferation which is believed to be the basis of the species difference in hepatocarcinogenicity. Peroxisome proliferation does not appear to play a role in the apparent carcinogenicity of PER in the rat kidney.

Abstract  Lifetime occupational histories as well as information on known and suspected breast cancer risk factors were collected by means of a self-administered questionnaire from 1018 women with incident breast cancer ascertained from the British Columbia Cancer Registry, and from 1020 population controls. A matched case-control study design was used. Conditional logistic regression for matched sets data and the likelihood ratio were used in a two-step procedure and were performed separately for pre-menopausal women, post-menopausal women, and for all cases combined. Excess risk was noted for several white-collar occupations. Significantly increased risk was observed: (1) among pre-menopausal women: in electronic data-processing operators; barbers and hairdressers; in sales and material processing occupations; and in the food, clothing, chemical and transportation industries; (2) among post-menopausal women: in schoolteaching; in medicine, health, and nursing occupations; in laundry and dry-cleaning occupations; and in the aircraft and automotive, including gasoline service station, industries. Several significant associations were also seen in the combined group of pre- and post-menopausal women, particularly in crop farmers and in the fruit and vegetable, publishing and printing, and motor vehicle repair industries. The results of this study suggest excess breast cancer risk in a number of occupations and industries, notably those that entail exposure to solvents and pesticides.