Avima M. Ruder

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.

Indoor particles and symptoms among office workers: results from a double-blind cross-over study

Background. We studied the effects of removing small airborne particles in an office building without unusual contaminant sources or occupant complaints. Methods. We conducted a double-blind crossover study of enhanced particle filtration in an office building in the Midwest United States in 1993. We replaced standard particle filters, in separate ventilation systems on two floors, with highly efficient filters on alternate floors weekly over 4 weeks. Repeated-measures models were used to analyze data from weekly worker questionnaires and multiple environmental measurements. Results. Bioaerosol concentrations were low. Enhanced filtration reduced concentrations of the smallest airborne particles by 94%. This reduction was not associated with reduced symptoms among the 396 respondents, but three performance-related mental states improved; for example, the confusion scale decreased (−3.7%; 95% confidence limits (CL) = −6.5, −0.9). Most environmental dissatisfaction variables also improved;eg, “stuffy” air, −5.3% (95% CL = −10.3, −0.4). Cooler temperatures within the recommended comfort range were associated with remarkably large improvement in most outcomes; for example, chest tightness decreased −23.4% (95% CL = −38.1, −8.7) for every 1°C decrease. Conclusions. Benefits of enhanced filtration require assessment in buildings with higher particulate contaminant levels in studies controlling for temperature effects. Benefits from lower indoor temperatures need confirmation.

Associations between Polymorphisms in DNA Repair Genes and Glioblastoma

A pooled analysis was conducted to examine the association between select variants in DNA repair genes and glioblastoma multiforme, the most common and deadliest form of adult brain tumors. Genetic data for ∼1,000 glioblastoma multiforme cases and 2,000 controls were combined from four centers in the United States that have conducted case-control studies on adult glioblastoma multiforme, including the National Cancer Institute, the National Institute for Occupational Safety and Health, the University of Texas M. D. Anderson Cancer Center, and the University of California at San Francisco. Twelve DNA repair single-nucleotide polymorphisms were selected for investigation in the pilot collaborative project. The C allele of the PARP1 rs1136410 variant was associated with a 20% reduction in risk for glioblastoma multiforme (odds ratioCT or CC, 0.80; 95% confidence interval, 0.67-0.95). A 44% increase in risk for glioblastoma multiforme was found for individuals homozygous for the G allele of the PRKDC rs7003908 variant (odds ratioGG, 1.44; 95% confidence interval, 1.13-1.84); there was a statistically significant trend (P = 0.009) with increasing number of G alleles. A significant, protective effect was found when three single-nucleotide polymorphisms (ERCC2 rs13181, ERCC1 rs3212986, and GLTSCR1 rs1035938) located near each other on chromosome 19 were modeled as a haplotype. The most common haplotype (AGC) was associated with a 23% reduction in risk (P = 0.03) compared with all other haplotypes combined. Few studies have reported on the associations between variants in DNA repair genes and brain tumors, and few specifically have examined their impact on glioblastoma multiforme. Our results suggest that common variation in DNA repair genes may be associated with risk for glioblastoma multiforme. (Cancer Epidemiol Biomarkers Prev 2009;18(4):1118–26)

Mortality in dry-cleaning workers: an update.

BACKGROUND A cohort of 1,708 dry-cleaning workers identified from union records was exposed to perchloroethylene (PCE), a known animal carcinogen and probable human carcinogen, for at least 1 year before 1960. Many workers also had exposure to Stoddard solvent, a petroleum-based dry-cleaning solvent. METHODS Vital status was updated through 1996 and life table analyses conducted. RESULTS The cohort had excess cancer mortality (271 deaths, standardized mortality ratio [SMR] 1.25, 95% confidence interval [CI] 1.11-1.41). Elevated SMRs for tongue, bladder, esophagus, intestine, lung, and cervical cancer, pneumonia, and diseases of the stomach and duodenum were statistically significant. CONCLUSION The current study confirms findings of prior updates and other studies that dry-cleaning workers have excess cancer mortality at several sites. Although important lifestyle and socioeconomic risk factors exist for both cervical and esophageal cancer mortality, excesses of these sites in the PCE only subcohort and among workers with longer duration of PCE exposure suggest an association with PCE exposure.

Research Recommendations for Selected IARC-Classified Agents

Objectives There are some common occupational agents and exposure circumstances for which evidence of carcinogenicity is substantial but not yet conclusive for humans. Our objectives were to identify research gaps and needs for 20 agents prioritized for review based on evidence of widespread human exposures and potential carcinogenicity in animals or humans. Data sources For each chemical agent (or category of agents), a systematic review was conducted of new data published since the most recent pertinent International Agency for Research on Cancer (IARC) Monograph meeting on that agent. Data extraction Reviewers were charged with identifying data gaps and general and specific approaches to address them, focusing on research that would be important in resolving classification uncertainties. An expert meeting brought reviewers together to discuss each agent and the identified data gaps and approaches. Data synthesis Several overarching issues were identified that pertained to multiple agents; these included the importance of recognizing that carcinogenic agents can act through multiple toxicity pathways and mechanisms, including epigenetic mechanisms, oxidative stress, and immuno- and hormonal modulation. Conclusions Studies in occupational populations provide important opportunities to understand the mechanisms through which exogenous agents cause cancer and intervene to prevent human exposure and/or prevent or detect cancer among those already exposed. Scientific developments are likely to increase the challenges and complexities of carcinogen testing and evaluation in the future, and epidemiologic studies will be particularly critical to inform carcinogen classification and risk assessment processes.

Update of the NIOSH life table analysis system: A person-years analysis program for the windows computing environment†

BACKGROUND Person-years analysis is a fundamental tool of occupational epidemiology. A life table analysis system (LTAS), previously developed by the National Institute for Occupational Safety and Health, was limited by its platform and analysis and reporting capabilities. We describe the updating of LTAS for the Windows operating system (LTAS.NET) with improved properties. SOFTWARE DEVELOPMENT PROCESS A group of epidemiologists, programmers, and statisticians developed software, platform, and computing requirements. Statistical methods include the use of (indirectly) standardized mortality ratios, (directly) standardized rate ratios, confidence intervals, and P values based on the normal approximation and exact Poisson methods, and a trend estimator for linear exposure-response associations. SOFTWARE FEATURES We show examples using LTAS.NET to stratify and analyze multiple fixed and time-dependent variables. Data import, stratification, and reporting options are highly flexible. Users may export stratified data for Poisson regression modeling. CONCLUSIONS LTAS.NET incorporates improvements that will facilitate more complex person-years analysis of occupational cohort data.

Potential Health Effects of Occupational Chlorinated Solvent Exposure

Abstract:  Based on toxicology, metabolism, animal studies, and human studies, occupational exposure to chlorinated aliphatic solvents (methanes, ethanes, and ethenes) has been associated with numerous adverse health effects, including central nervous system, reproductive, liver, and kidney toxicity, and carcinogenicity. However, many of these solvents remain in active, large‐volume use. This article reviews the recent occupational epidemiology literature on the most widely used solvents, methylene chloride, chloroform, trichloroethylene, and tetrachloroethylene, and discusses other chlorinated aliphatics. The impact of studies to date has been lessened because of small study size, inability to control for confounding factors, particularly smoking and mixed occupational exposures, and the lack of evidence for a solid pathway from occupational exposure to biological evidence of exposure, to precursors of health effects, and to health effects. International differences in exposure limits may provide a “natural experiment” in the coming years if countries that have lowered exposure limits subsequently experience decreased adverse health effects among exposed workers. Such decreases could provide some evidence that higher levels of adverse health effects were associated with higher levels of solvent exposure. The definitive studies, which should be prospective biomarker studies incorporating body burden of solvents as well as markers of effect, remain to be done.

Proportionate mortality among unionized roofers and waterproofers

BACKGROUND The United Union of Roofers, Waterproofers, and Allied Workers (UURWAW) is one of the 15 building and construction trades departments in the AFL-CIO. The U.S. roofing industry, including both roofing and waterproofing applications, both unionized and nonunionized, comprises about 25,000 firms, employing approximately 300,000 people, about 200,000 of whom are involved in the application of roofs. The specific toxins to which roofers may be exposed at the job site include, among others, bitumens (asphalt and/or coal tar pitch) as well as asbestos and fiberglass from roof removal operations. Excess deaths from occupational injuries are also of concern. METHODS This study evaluated causes of mortality among 11,144 members of the UURWAW. Age-adjusted proportionate mortality ratios (PMRs) were computed with 95% confidence intervals (CI) using U.S. age-, gender-, and race-specific proportional mortality rates for the years of the study, 1950-1996. RESULTS Statistically significant increased PMRs were found for all injuries (PMR = 142, CI = 134-150), especially falls (PMR = 464, CI = 419-513) and other injuries (PMR = 121, CI = 107-137), cancers of the lung (PMR = 139, CI = 131-148), bladder (PMR = 138, CI = 111-170), esophagus (PMR = 134, CI = 107-166), larynx (PMR = 145, CI = 106-193), and cancers of other and unspecified sites (PMR = 130, CI = 112-149), pneumoconioses and other nonmalignant respiratory diseases (PMR = 115, CI = 103-128), and homicides (PMR = 153, CI = 135-172). The occupational exposures which may have contributed to the excess risks of malignant and nonmalignant respiratory diseases include, among others, asphalt fumes, coal tar pitch volatiles and asbestos; however, cigarette smoking must also be considered a contributing factor. CONCLUSIONS The present study underscores the need to control airborne exposures to hazardous substances and especially to examine fall prevention efforts within the roofing industry. Am. J. Ind. Med. 37:478-492, 2000. Published 2000 Wiley-Liss, Inc.

Background levels of polychlorinated biphenyls in the U.S. population.

BACKGROUND Polychlorinated biphenyl (PCB) exposures are encountered by the general public by eating contaminated food or living near a previously operating PCB factory or hazardous waste site. PCBs affect the immune, reproductive, nervous, and endocrine systems and are carcinogens. PCBs were banned in the United States in 1977. For public health, it is important to be able to estimate individual risk, especially for vulnerable populations, to monitor the decline in risk over time and to alert the public health community if spikes occur in PCB exposures, by measuring serum PCB levels. The historical decline in PCB exposures cannot be documented within a repeatedly tested general population, since there is no such population. Therefore, our aim was to model serum PCB levels in the US general population over time using published data. METHODS Models were developed based on 45 publications providing 16,914 background PCB levels in sera collected 1963-2003. Multiple linear regression and exponential decay were used to model the summary PCB levels. RESULTS Background levels of higher-chlorinated PCBs (five or more chlorines) in sera increased before 1979 and decreased after 1979; a quadratic model was the best fit. However, the exponential decay model explained better the low PCB serum levels still seen in the general population. For lower-chlorinated serum PCBs, no increase or decrease was shown (1.7ppb for all years). CONCLUSIONS Limitations for both models were lack of repeated measures, non-randomly selected study participants, selected years, concentration on geographic areas centered on PCB waste sites, lack of adjustment for BMI or for laboratory methods. Despite the limitations, this analysis shows that background PCB levels in the general population are still of concern. Future work should focus on uncertainties governing how to interpret the levels with respect to possible long term health effects.