Teresa M. Schnorr

NTP-CERHR expert panel report on the reproductive and developmental toxicity of bisphenol A.

Robert E. Chapin, Jane Adams, Kim Boekelheide, L. Earl Gray Jr, Simon W. Hayward, Peter S.J. Lees, Barry S. McIntyre, Kenneth M. Portier, Teresa M. Schnorr, Sherry G. Selevan, John G. Vandenbergh, and Susan R. Woskie Pfizer, Inc., Groton, CT University of Massachusetts, Boston, MA Brown University, Providence, RI U.S. Environmental Protection Agency, Research Triangle Park, NC Vanderbilt University Medical Center, Nashville, TN Johns Hopkins University, Baltimore, MD Schering Plough Research Institute, Summit, NJ American Cancer Society, Atlanta, GA National Institute for Occupational Safety and Health, Cincinnati, OH U.S. Public Health Service (Ret), Silver Spring, MD North Carolina State University, Raleigh, NC University of Massachusetts, Lowell, MA

Video Display Terminals and the Risk of Spontaneous Abortion

BACKGROUND The relation between spontaneous abortion and the use of video display terminals (VDTs) is of great public health concern. Previous investigators of this issue have reported inconsistent findings. METHODS To determine whether electromagnetic fields emitted by VDTs are associated with an increased risk of spontaneous abortion, a cohort of female telephone operators who used VDTs at work was compared with a cohort of operators who did not use VDTs. To obtain reliable estimates of exposure, we determined the number of hours of VDT use per week from company records and measured electromagnetic fields at VDT workstations and, for purposes of comparison, at workstations without VDTs. Operators who used VDTs had higher abdominal exposure to very-low-frequency (15 kHz) electromagnetic fields (workstations without VDTs did not emit very-low-frequency energy). Abdominal exposure to extremely-low-frequency fields (45 to 60 Hz) was similar for both operators who used VDTs and those who did not. Among 2430 women interviewed, there were 882 pregnancies that met our criteria for inclusion in the study. RESULTS We found no excess risk of spontaneous abortion among women who used VDTs during the first trimester of pregnancy (odds ratio = 0.93; 95 percent confidence interval, 0.63 to 1.38), and no dose-response relation was apparent when we examined the womens hours of VDT use per week (odds ratio for 1 to 25 hours per week = 1.04; 95 percent confidence interval, 0.61 to 1.79; odds ratio for greater than 25 hours per week = 1.00; 95 percent confidence interval, 0.61 to 1.64). There continued to be no risk associated with the use of VDTs when we accounted for multiple pregnancies, conducted separate analyses of early abortion, late abortion, and all fetal losses, or limited our analyses to spontaneous abortions for which a physician was consulted. CONCLUSIONS The use of VDTs and exposure to the accompanying electromagnetic fields were not associated with an increased risk of spontaneous abortion in this study.

A dose-response analysis and quantitative assessment of lung cancer risk and occupational cadmium exposure.

We performed a quantitative assessment of the risk of lung cancer from exposure to cadmium based on a retrospective cohort mortality study of cadmium-exposed workers. The study population consisted of white male workers who were employed for at least 6 months at a cadmium smelter between January 1, 1940, and December 31, 1969, and who were first employed at the facility on or after January 1, 1926. The study findings were analyzed using a modified life-table analysis to estimate standardized mortality ratios (SMRs), and various functional forms (i.e., exponential, power, additive relative rate, and linear) of Poisson and Cox proportional hazards models to examine the dose-response relationship. Estimates of working lifetime risk (45 years) were developed using an approach that corrects for competing causes of death. An excess in mortality from lung cancer was observed for the entire cohort (SMR = 149, 95% confidence interval (CI) = 95, 222). Mortality from lung cancer was greatest among non-Hispanic workers (SMR = 211, 95% CI = 131, 323), among workers in the highest cadmium exposure group (SMR = 272, 95% CI = 123, 513), and among workers with 20 or more years since the first exposure (SMR = 161, 95% CI = 100, 248). A statistically significant dose-response relationship was evident in nearly all of the regression models evaluated. Based on our analyses, the lifetime excess lung cancer risk at the current Occupational Safety and Health Administration standard for cadmium fumes of 100 micrograms/m3 is approximately 50 to 111 lung cancer deaths per 1000 workers exposed to cadmium for 45 years.

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.

Cancer risks among workers exposed to metalworking fluids: A systematic review

Metalworking fluids (MWFs) are commonly used in a variety of industrial machining and grinding operations. The National Institute for Occupational Safety and Health (NIOSH) estimates that more that one million workers are exposed to MWFs. NIOSH conducted a comprehensive and systematic review of the epidemiologic studies that examined the association between MWF exposure and cancer. Substantial evidence was found for an increased risk of cancer at several sites (larynx, rectum, pancreas, skin, scrotum, and bladder) associated with at least some MWFs used prior to the mid-1970s. This paper provides the evidence pertaining to cancer at these sites. Cancer at those sites found to have more limited or less consistent evidence for an association with MWF (stomach, esophagus, lung, prostate, brain, colon, and hematopoietic system) will not be discussed in this paper but are discussed in the recent NIOSH Criteria for a Recommended Standard-Occupational Exposure to MWFs. Because the changes in MWF composition that have occurred over the last several decades may not be sufficient to eliminate the cancer risks associated with MWF exposure, reductions in airborne MWF exposures are recommended.

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.

Tenth revision U.S. mortality rates for use with the NIOSH Life Table Analysis System.

Objective: The objective of this study was to update rate files for the NIOSH Life Table Analysis System for Personal Computers (PC LTAS) reflecting the newly adopted tenth revision changes to the International Classification of Diseases. Methods: PC LTAS allows researchers to conduct comparative mortality and morbidity analyses for the purpose of identifying disease-exposure associations using person-time-at-risk for age, race, sex, and calendar time-specific reference rates from 1940. Previously available through 1998, files for the United States and individual states were updated through 2004 using uncensored population data. Tenth revision causes were added if compatible with earlier NIOSH death categories, based on revisions 5 through 9. A few new cause categories were added. Results: The resulting NIOSH categories are described for two new U.S. rate files: 1960 through 2004 and 1940 through 2004. Conclusion: The new U.S. rate files are available online or on request.

Mortality among Navajo uranium miners.

OBJECTIVES To update mortality risks for Navajo uranium miners, a retrospective cohort mortality study was conducted of 757 Navajos from the cohort of Colorado Plateau uranium miners. METHODS Vital status was followed from 1960 to 1990. Standardized mortality ratios were estimated, with combined New Mexico and Arizona non-White mortality rates used for comparison. Cox regression models were used to evaluate exposure-response relationships. RESULTS Elevated standardized mortality ratios were found for lung cancer (3.3), tuberculosis (2.6), and pneumoconioses and other respiratory diseases (2.6). Lowered ratios were found for heart disease (0.6), circulatory disease (0.4), and liver cirrhosis (0.5). The estimated relative risk for a 5-year duration of exposure vs none was 3.7 for lung cancer, 2.1 for pneumoconioses and other respiratory diseases, and 2.0 for tuberculosis. The relative risk for lung cancer was 6.9 for the midrange of cumulative exposure to radon progeny compared with the least exposed. CONCLUSIONS Findings were consistent with those from previous studies. Twenty-three years after their last exposure to radon progeny, these light-smoking Navajo miners continue to face excess mortality risks from lung cancer and pneumoconioses and other respiratory diseases.

Prioritization of NTP reproductive toxicants for field studies

Population studies that evaluate human reproductive impairment are time consuming, expensive, logistically difficult, and with limited resources must be prioritized to effectively prevent the adverse health effects in humans. Interactions among health scientists, unions, and industry can serve to identify populations exposed to potential hazards and develop strategies to evaluate and apply appropriate controls. This report describes a systematic method for prioritizing chemicals that may need human reproductive health field studies. Rodent reproductive toxicants identified from the National Toxicology Program (NTP) Reproductive Assessment by Continuous Breeding (RACB) protocol were prioritized on the basis of potency of toxic effect and population at risk. This model for prioritization links NTP findings with data from the National Occupational Exposure Survey (NOES) and the Hazardous Substance Data Base (HSDB) or the High Production Volume Chemical Database (HPVC) to prioritize chemicals for their potential impact on worker populations. The chemicals with the highest priority for field study were: dibutyl phthalate, boric acid, tricresyl phosphate, and N, N-dimethylformamide.

Prevalence of respiratory symptoms among female flight attendants and teachers

Background: Potential health effects of the indoor environment in office buildings and aircraft have generated considerable concern in recent years. Aims: To analyse the prevalence of self reported respiratory symptoms and illnesses in flight attendants (FAs) and schoolteachers. Methods: Data were collected as part of a study of reproductive health among female FAs. The prevalences of work related eye, nose, and throat symptoms, wheezing, physician diagnosed asthma, chest illness, and cold or flu were calculated and stratified by smoking status in 1824 FAs and 331 schoolteachers. Results: FAs and teachers were significantly more likely to report work related eye (12.4% and 7.4 %, respectively), nose (15.7% and 8.1%), and throat symptoms (7.5% and 5.7%) than were other working women (2.9% eye, 2.7% nose, and 1.3% throat symptoms). FAs were significantly more likely than teachers and referent working women to report chest illness during the prior three years (32.9%, 19.3%, 7.2%, respectively). Both study groups were more likely to report five or more episodes of cold or flu in the past year than were other working women (10.2% of FAs, 8.2% of teachers, 2.3% of referents), and both groups were more likely to report wheezing than other working women (22.8% of FAs, 28.4% of teachers, 16.4% of referents). FAs were significantly less likely than teachers and other working women to report ever having been diagnosed with asthma (8.2%, 13.3%, 11.8%, respectively). Conclusions: Overall, FAs and schoolteachers report a higher prevalence of work related upper respiratory symptoms, chest illness, and cold or flu than the general working population.