Martha A. Waters

Polychlorinated Biphenyls and Neurodegenerative Disease Mortality in an Occupational Cohort

Background: Production of polychlorinated biphenyls (PCBs) ended in the United States in the 1970s, but PCBs persist in the environment and are detectable in the blood of approximately 80% of Americans over age 50. PCBs decrease dopamine levels in rats and monkeys. Loss of dopamine is the hallmark of Parkinson disease, a neurodegenerative disease. There are no epidemiologic studies of PCBs and neurodegenerative disease. Methods: We conducted a retrospective mortality study of 17,321 PCB-exposed workers to determine whether mortality from Parkinson disease, dementia, and amyotrophic lateral sclerosis was elevated compared with the U.S. population. All workers had a least 90 days employment in 1 of 3 electrical capacitor plants using PCBs from the 1940s to the 1970s. PCB serum levels from a sample of these workers in the 1970s were approximately 10 times the level of community controls. Results: We found no overall excess of Parkinson disease, amyotrophic lateral sclerosis, or dementia in the PCB-exposed cohort (standardized mortality ratios [SMRs]-1.40, 1.11, and 1.26, respectively, and number of deaths-14, 10, and 28 respectively). However, sex-specific analyses revealed that women had an excess of amyotrophic lateral sclerosis (SMR-2.26; 95% confidence interval [CI] = 1.08–4.15; 10 deaths). Furthermore, among highly exposed women (defined by a job-exposure matrix), we found an excess of Parkinson disease (SMR-2.95; 95% CI = 1.08–6.42; 6 deaths) and dementia (SMR-2.04; 95% CI = 1.12–3.43; 14 deaths). Conclusions: Our data are limited due to small numbers and reliance on mortality rather than incidence data, but are suggestive of an effect of PCBs on neurodegenerative disease for women. The literature does not offer an explanation for why women would be more affected than men by PCB exposure for these outcomes.

Mortality and Exposure Response among 14,458 Electrical Capacitor Manufacturing Workers Exposed to Polychlorinated Biphenyls (PCBs)

Background We expanded an existing cohort of workers (n = 2,588) considered highly exposed to polychlorinated biphenyls (PCBs) at two capacitor manufacturing plants to include all workers with at least 90 days of potential PCB exposure during 1939–1977 (n = 14,458). Causes of death of a priori interest included liver and rectal cancers, previously reported for the original cohort, and non-Hodgkin lymphoma (NHL), melanoma, and breast, brain, intestine, stomach, and prostate cancers, based on other studies. Methods We ascertained vital status of the workers through 1998, and cumulative PCB exposure was estimated using a new job exposure matrix. Analyses employed standardized mortality ratios (SMRs; U.S., state, and county referents) and Poisson regression modeling. Results Mortality from NHL, melanoma, and rectal, breast, and brain cancers were neither in excess nor associated with cumulative exposure. Mortality was not elevated for liver cancer [21 deaths; SMR 0.89; 95% confidence interval (CI), 0.55–1.36], but increased with cumulative exposure (trend p-value = 0.071). Among men, stomach cancer mortality was elevated (24 deaths; SMR 1.53; 95% CI, 0.98–2.28) and increased with cumulative exposure (trend p-value = 0.039). Among women, intestinal cancer mortality was elevated (67 deaths; SMR 1.31; 95% CI, 1.02–1.66), especially in higher cumulative exposure categories, but without a clear trend. Prostate cancer mortality, which was not elevated (34 deaths; SMR 1.04; 95% CI, 0.72–1.45), increased with cumulative exposure (trend p-value = 0.0001). Conclusions This study corroborates previous studies showing increased liver cancer mortality, but we cannot clearly associate rectal, stomach, and intestinal cancers with PCB exposure. This is the first PCB cohort showing a strong exposure–response relationship for prostate cancer mortality.

Uses of and Exposure to Trichloroethylene in U.S. Industry: A Systematic Literature Review

This article describes a systematic review of the industrial hygiene literature for uses of trichloroethylene (TCE) in industry for the exposure assessment of two population-based case control studies of brain cancer in the United States. Papers and reports that address uses of and exposures to TCE were identified from MEDLINE, TOXLINE, NIOSHTIC, the NIOSH Health Hazard Evaluation database (keywords: chlorinated solvents and trichloroethylene), and in other reviews. This search was complemented by reviewing the reference lists from the identified literature. The collected information was systematized by the Standard Industrial Classification (SIC) system, and measurement data reported in the literature were summarized in a database. TCE use was extensive from the early 1920s through the 1970s mainly as a degreasing agent in metal-fabricating operations. After the 1970s it became less popular because of environmental concerns. TCE historically has had a multitude of uses in many other industries, e.g., dry cleaning, textile, electronics, leather, and rubber. Also, many products like adhesives, drugs, paints, inks, and various industrial products have contained TCE. It was banned as a food additive and in cosmetics in 1977. The arithmetic mean (AM) of the measurements across all industries and decades was 38.2 ppm. The highest personal and area air levels were reported in vapor degreasing (AM of 44.6 ppm). Most TCE measurements were performed in the 1950s, 1970s, and 1980s. The data described here could be used by exposure assessors as is to identify the presence and approximate levels of exposure. Using the same information as a basis should increase the reliability of the assessments, making it easier to compare both the exposure assessment methods and the epidemiologic results across different studies.

Occupational Exposure to Pesticides and Risk of Adult Brain Tumors

The authors examined incident glioma and meningioma risk associated with occupational exposure to insecticides and herbicides in a hospital-based, case-control study of brain cancer. Cases were 462 glioma and 195 meningioma patients diagnosed between 1994 and 1998 in three US hospitals. Controls were 765 patients admitted to the same hospitals for nonmalignant conditions. Occupational histories were collected during personal interviews. Exposure to pesticides was estimated by use of a questionnaire, combined with pesticide measurement data abstracted from published sources. Using logistic regression models, the authors found no association between insecticide and herbicide exposures and risk for glioma and meningioma. There was no association between glioma and exposure to insecticides or herbicides, in men or women. Women who reported ever using herbicides had a significantly increased risk for meningioma compared with women who never used herbicides (odds ratio = 2.4, 95% confidence interval: 1.4, 4.3), and there were significant trends of increasing risk with increasing years of herbicide exposure (p = 0.01) and increasing cumulative exposure (p = 0.01). There was no association between meningioma and herbicide or insecticide exposure among men. These findings highlight the need to go beyond job title to elucidate potential carcinogenic exposures within different occupations.

Systematic Literature Review of Uses and Levels of Occupational Exposure to Tetrachloroethylene

Tetrachloroethylene has been one of the most widely used chlorinated solvents in the United States. This review provides a basis for tetrachloroethylene exposure assessment in population-based case-control studies. We performed literature searches in MEDLINE, TOXLINE, NIOSHTIC, and the NIOSH Health Hazard Evaluation databases using relevant search terms. We calculated weighted arithmetic means from the measurement data and compiled these into three summary tables by type of operation: (1) dry cleaning, (2) degreasing, and (3) other operations. We identified 258 relevant documents, of which 179 (69%) contained useful descriptive information. Within the dry cleaning industry, the overall arithmetic mean (AM) for personal tetrachloroethylene exposures was 59 ppm (range: 0–4636, n = 1395). Machine operators who transferred wet garments to a dryer had the highest levels (AM = 150 ppm [range: 0–1000, n = 441]) of the jobs in this industry. The AM for personal measurements associated with degreasing was 95 ppm (range: 0–1800, n = 206). In addition, we identified several other sources of substantial tetrachloroethylene exposure, including cleaning mining equipment, testing coal, cleaning animal coats in taxidermy, and cleaning and duplicating film. Exposure assessment in population-based, case-control studies is a complex process requiring substantial resources. Researchers conducting these types of studies will be able to use results of the measurements to quantify tetrachloroethylene exposure levels for various jobs.

Mortality among 24,865 workers exposed to polychlorinated biphenyls (PCBs) in three electrical capacitor manufacturing plants: A ten-year update

The objective of this analysis was to evaluate mortality among a cohort of 24,865 capacitor-manufacturing workers exposed to polychlorinated biphenyls (PCBs) at plants in Indiana, Massachusetts, and New York and followed for mortality through 2008. Cumulative PCB exposure was estimated using plant-specific job-exposure matrices. External comparisons to US and state-specific populations used standardized mortality ratios, adjusted for gender, race, age and calendar year. Among long-term workers employed 3 months or longer, within-cohort comparisons used standardized rate ratios and multivariable Poisson regression modeling. Through 2008, more than one million person-years at risk and 8749 deaths were accrued. Among long-term employees, all-cause and all-cancer mortality were not elevated; of the a priori outcomes assessed only melanoma mortality was elevated. Mortality was elevated for some outcomes of a priori interest among subgroups of long-term workers: all cancer, intestinal cancer and amyotrophic lateral sclerosis (women); melanoma (men); melanoma and brain and nervous system cancer (Indiana plant); and melanoma and multiple myeloma (New York plant). Standardized rates of stomach and uterine cancer and multiple myeloma mortality increased with estimated cumulative PCB exposure. Poisson regression modeling showed significant associations with estimated cumulative PCB exposure for prostate and stomach cancer mortality. For other outcomes of a priori interest--rectal, liver, ovarian, breast, and thyroid cancer, non-Hodgkin lymphoma, Alzheimer disease, and Parkinson disease--neither elevated mortality nor positive associations with PCB exposure were observed. Associations between estimated cumulative PCB exposure and stomach, uterine, and prostate cancer and myeloma mortality confirmed our previous positive findings.

NAT2 slow acetylation and bladder cancer in workers exposed to benzidine

This study expands a previous study of NAT2 polymorphisms and bladder cancer in male subjects occupationally exposed only to benzidine. The combined analysis of 68 cases and 107 controls from a cohort of production workers in China exposed to benzidine included 30 new cases and 67 controls not previously studied. NAT2 enzymatic activity phenotype was characterized by measuring urinary caffeine metabolite ratios. PCR‐based methods identified genotypes for NAT2, NAT1 and GSTM1. NAT2 phenotype and genotype data were consistent. A protective association was observed for the slow NAT2 genotype (bladder cancer OR = 0.3; 95% CI = 0.1 = 1.0) after adjustment for cumulative benzidine exposure and lifetime smoking. Individuals carrying NAT1wt/*10 and NAT1*10/*10 showed higher relative risks of bladder cancer (OR = 2.8, 95% CI = 0.8–10.1 and OR = 2.2, 95% CI = 0.6–8.3, respectively). No association was found between GSTM1 null and bladder cancer. A metaanalysis risk estimate of case‐control studies of NAT2 acetylation and bladder cancer in Asian populations without occupational arylamine exposures showed an increased risk for slow acetylators. The lower limit of the confidence interval (OR = 1.4; 95% CI = 1.0–2.0) approximated the upper confidence interval for the estimate obtained in our analysis. These results support the earlier finding of a protective association between slow acetylation and bladder cancer in benzidine‐exposed workers, in contrast to its established link as a risk factor for bladder cancer in people exposed to 2‐naphthylamine and 4‐aminobiphenyl. Study findings suggest the existence of key differences in the metabolism of mono‐ and diarylamines. Published 2005 Wiley‐Liss, Inc.

Increased frequency of chromosome translocations in airline pilots with long-term flying experience

Background: Chromosome translocations are an established biomarker of cumulative exposure to external ionising radiation. Airline pilots are exposed to cosmic ionising radiation, but few flight crew studies have examined translocations in relation to flight experience. Methods: We determined the frequency of translocations in the peripheral blood lymphocytes of 83 airline pilots and 50 comparison subjects (mean age 47 and 46 years, respectively). Translocations were scored in an average of 1039 cell equivalents (CE) per subject using fluorescence in situ hybridisation (FISH) whole chromosome painting and expressed per 100 CE. Negative binomial regression models were used to assess the relationship between translocation frequency and exposure status and flight years, adjusting for age, diagnostic x ray procedures, and military flying. Results: There was no significant difference in the adjusted mean translocation frequency of pilots and comparison subjects (0.37 (SE 0.04) vs 0.38 (SE 0.06) translocations/100 CE, respectively). However, among pilots, the adjusted translocation frequency was significantly associated with flight years (p = 0.01) with rate ratios of 1.06 (95% CI 1.01 to 1.11) and 1.81 (95% CI 1.16 to 2.82) for a 1- and 10-year incremental increase in flight years, respectively. The adjusted rate ratio for pilots in the highest compared to the lowest quartile of flight years was 2.59 (95% CI 1.26 to 5.33). Conclusions: Our data suggests that pilots with long-term flying experience may be exposed to biologically significant doses of ionising radiation. Epidemiological studies with longer follow-up of larger cohorts of pilots with a wide range of radiation exposure levels are needed to clarify the relationship between cosmic radiation exposure and cancer risk.

Occupational Exposure to Polychlorinated Biphenyls and Risk of Breast Cancer

Background Despite the endocrine system activity exhibited by polychlorinated biphenyls (PCBs), recent studies have shown little association between PCB exposure and breast cancer mortality. Objectives To further evaluate the relation between PCB exposure and breast cancer risk, we studied incidence, a more sensitive end point than mortality, in an occupational cohort. Methods We followed 5,752 women employed for at least 1 year in one of three capacitor manufacturing facilities, identifying cases from questionnaires, cancer registries, and death certificates through 1998. We collected lifestyle and reproductive information via questionnaire from participants or next of kin and used semiquantitative job-exposure matrices for inhalation and dermal exposures combined. We generated standardized incidence ratios (SIRs) and standardized rate ratios and used Cox proportional hazards regression models to evaluate potential confounders and effect modifiers. Results Overall, the breast cancer SIR was 0.81 (95% confidence interval, 0.72–0.92; n = 257), and regression modeling showed little effect of employment duration or cumulative exposure. However, for the 362 women of questionnaire-identified races other than white, we observed positive, statistically significant associations with employment duration and cumulative exposure; only smoking, birth cohort, and self- or proxy questionnaire completion had statistically significant explanatory power when added to models with exposure metrics. Conclusions We found no overall elevation in breast cancer risk after occupational exposure to PCBs. However, the exposure-related risk elevations seen among nonwhite workers, although of limited interpretability given the small number of cases, warrant further investigation, because the usual reproductive risk factors accounted for little of the increased risk.

Maternal Occupational Exposure to Polycyclic Aromatic Hydrocarbons: Effects on Gastroschisis among Offspring in the National Birth Defects Prevention Study

Background: Exposure to polycyclic aromatic hydrocarbons (PAHs) occurs in many occupational settings. There is evidence in animal models that maternal exposure to PAHs during pregnancy is associated with gastroschisis in offspring; however, to our knowledge, no human studies examining this association have been conducted. Objective: Our goal was to conduct a case–control study assessing the association between estimated maternal occupational exposure to PAHs and gastroschisis in offspring. Methods: Data from gastroschisis cases and control infants were obtained from the population-based National Birth Defects Prevention Study for the period 1997–2002. Exposure to PAHs was assigned by industrial hygienist consensus, based on self-reported maternal occupational histories from 1 month before conception through the third month of pregnancy. Logistic regression was used to determine the association between estimated occupational PAH exposure and gastroschisis among children whose mothers were employed for at least 1 month during the month before conception through the third month of pregnancy. Results: The prevalence of estimated occupational PAH exposure was 9.0% in case mothers (27 of 299) and 3.6% in control mothers (107 of 2,993). Logistic regression analyses indicated a significant association between occupational PAHs and gastroschisis among mothers ≥ 20 years of age [odds ratio (OR) = 2.53; 95% confidence interval (CI): 1.27, 5.04] after adjusting for maternal body mass index, education, gestational diabetes, and smoking. This association was not seen in mothers < 20 years (OR = 1.14; 95% CI: 0.55, 2.33), which is notable because although young maternal age is the strongest known risk factor for gastroschisis, most cases are born to mothers ≥ 20 years. Conclusion: Our findings indicate an association between occupational exposure to PAHs among mothers who are ≥ 20 years and gastroschisis. These results contribute to a body of evidence that PAHs may be teratogenic.