Elizabeth Ward

Questionable Relation of Aryl Hydrocarbon Hydroxylase to Lung-Cancer Risk

To test whether the genetically determined trait, aryl hydrocarbon hydroxylase inducibility, affects susceptibility to lung cancer, we measured this trait in cultured lymphocytes from a normal population, patients with lung cancer and progeny of such patients. We found very low aryl hydrocarbon hydroxylase activity (19 per cent of normal) in about half the patients with lung cancer. Only part of this activity can be accounted for by reduced cell growth and by reduced protein synthesis. In an indirect assessment of inducibility, both 57 progeny and 27 matched controls had a mean inducibility of 2.95 and a similar distribution into low, intermediate and high groups (chi-square = 0.3 P = 0.9). No differences in basal or induced activity were observed. Thus, if patients with lung cancer possess altered aryl hydrocarbon hydroxylase inducibility or activity these characteristics are not transmitted to their progeny.

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 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.

Genotoxicity in workers exposed to methyl bromide

To address the genotoxicity of in vivo methyl bromide (CAS 74-83-9) exposure in humans, we collected blood and oropharyngeal cells as part of a cross-sectional morbidity study of methyl bromide-exposed fumigation workers and their referents. Micronuclei were measured in lymphocytes and oropharyngeal cells, and hypoxanthine-guanine phosphoribosyl transferase gene (hprt) mutations were measured in lymphocytes. A total of 32 workers and 28 referents provided specimens. Among current non-smokers, mean hprt variant frequencies (Vfs) were found to be elevated among workers compared to referents (geometric mean: workers=4.49x10(-6), referents=2.96x10-(6); two-sided p=0.22); this difference was more pronounced among workers with 4 h or more of recent methyl bromide exposure compared to referents (geometric mean: workers=6.56x10(-6), referents=2.96x10(-6); two-sided p=0.06). Mean oropharyngeal cell micronuclei were higher among workers compared to referents (mean: workers=2.00, referents=1.31; two-sided p=0.08); the results were similar when workers with 4 h or more of recent methyl bromide exposure were compared to referents (mean: workers=2.07, referents=1.31; two-sided p=0.13). No consistent differences between workers and referents were observed for frequencies of kinetochore-negative lymphocyte micronuclei, or kinetochore-positive lymphocyte micronuclei. The study was limited by a sample size sufficient only for detecting relatively large differences, absence of a reliable method to measure the intensity of workplace methyl bromide exposures, and relatively infrequent methyl bromide exposure (e.g., the median length of exposure to methyl bromide during the 2 weeks preceding the survey was 4 h). In conclusion, our findings provide some evidence that methyl bromide exposure may be associated with genotoxic effects in lymphocytes and oropharyngeal cells. Further study on the genotoxicity of methyl bromide exposure in humans is warranted.

Ethylene oxide and breast cancer incidence in a cohort study of 7576 women (United States)

Background: Ethylene oxide (ETO) is a sterilant gas considered to be a human carcinogen, due primarily to excess hematopoietic cancer in exposed cohorts. ETO causes mammary tumors in mice, and has been associated with breast cancer incidence in one small epidemiologic study. Methods: We have studied breast cancer incidence in a cohort of 7576 women employed for at least one year and exposed for an average 10.7 years while working in commercial sterilization facilities. Breast cancer incidence (n = 319) was ascertained via interview, death certificates, cancer registries, and medical records. Interviews were obtained for 68% of the cohort. Results: The standardized incidence ratio (SIR) for incident breast cancer in the whole cohort using external referent rates (SEER) was 0.87 (0.77–0.97). The SIR for those in the top quintile of cumulative exposure, with a 15 year lag, was 1.27 (0.94–1.69), with a positive trend of increasing SIR with increasing exposure (p = 0.002). SIRs are under-estimated because breast cancer incidence in the whole cohort was under-ascertained, due to incomplete response and lack of complete coverage by state cancer registries. In internal nested case–control analyses of those with interviews (complete cancer ascertainment), controlling for reproductive risk factors, a positive exposure–response was found with the log of cumulative exposure with a 15-year lag (p = 0.0005). The odds ratio by quintile of cumulative exposure were 1.00 (0 exposure due to 15 year lag), 1.06, 0.99, 1.24, 1.42, and 1.87. Conclusions: Our data suggest that ETO is associated with breast cancer, but a causal interpretation is weakened due to some inconsistencies in exposure–response trends and possible biases due to non-response and incomplete cancer ascertainment.

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.

Immunologic findings among lead-exposed workers

A comprehensive panel of immune parameters was evaluated among 145 lead-exposed workers with a median blood lead level (BLL) of 39 micrograms/dL (range: 15-55 micrograms/dL) and 84 unexposed workers. After adjusting for covariates, we found no major differences in the percentage of CD3+ cells, CD4+ T cells, CD8+ T cells, B cells, or NK cells between lead-exposed and unexposed workers, although the association between lead exposure and the number of CD4+ T cells was modified by age. We also found no differences between exposed and unexposed workers in serum immunoglobulin levels, salivary IgA, C3 complement levels, or lymphoproliferative responses. However, among exposed workers, the percentage and number of B cells were positively associated with current BLL, serum IgG was negatively associated with cumulative lead exposure, and the percentage and number of CD4+/CD45RA+ cells were positively associated with cumulative lead exposure. We found no evidence of a marked immunotoxic effect of lead at the exposure levels studied, although some subtle differences in immunologic parameters were noted.

Increased bladder cancer risk among workers exposed to o-toluidine and aniline: a reanalysis

Introduction In 1991, the US National Institute for Occupational Safety and Health (NIOSH) reported an increased bladder cancer risk in a cohort of 1749 workers potentially exposed to o-toluidine and aniline at a chemical manufacturing plant. As additional information showed that workers in certain departments had been misclassified regarding o-toluidine exposure, we therefore conducted a reanalysis of the data using updated exposure categories. Methods We updated exposure categories based on information ascertained during a plant walkthrough, documents on file at the plant, interviews with current and former employees, and answers provided by company and union officials to specific questions. Bladder cancer incidence was determined through 31 December 1988 and mortality through 31 December 1994. Results Thirteen cases of bladder cancer were observed versus 3.57 expected (New York State rates excluding New York City) (standardised incidence ratio (SIR) 3.64, 95% CI 1.94 to 6.23). Among workers classified as definitely exposed, increasing risks were observed for longer duration of employment (for ≥10 years, standardised rate ratio (SRR) 6.07, 95% CI 0.77 to 48.17) and time since first employment in the exposed departments (for ≥20 years, SRR 3.39, 95% CI 0.40 to 29.03). One bladder cancer death was observed among those definitely exposed. Conclusions These findings are comparable to the results reported earlier by NIOSH, and confirm that workers in this plant have an increased risk of bladder cancer.

Gliomas and farm pesticide exposure in men: the upper midwest health study.

Abstract The National Institute for Occupational Safety and Health evaluated farm pesticide exposure and glioma risk in a study that included 457 glioma cases and 648 population-based controls, all adult men (18–80 yr old) and nonmetropolitan residents of Iowa, Michigan, Minnesota, and Wisconsin. Multiple logistic regressions were used to control for farm residence, age, age group, education, and exposure to other pesticides. No associations were found between glioma and 12 specific pesticides. We estimated adjusted odds ratios (ORs) and 95% confidence intervals (Cls) and found reduced glioma risk for insecticides (OR = 0.53, Cl = 0.37–0.77), fumigants (OR = 0.57, Cl = 0.34–0.95), and organochlorines (OR = 0.66, Cl = 0.47–0.94). In analyses excluding proxy respondents (47% of cases) most Cls included 1.0. No positive association of farm pesticide exposure and glioma was found. Other farm exposures may explain the excess brain cancer risk seen in previous studies.

Underlying and multiple cause mortality in a cohort of workers exposed to aromatic amines.

BACKGROUND The National Institute for Occupational Safety and Health (NIOSH) has previously conducted studies of bladder cancer incidence and mortality at a synthetic dye plant that manufactured beta-naphthylamine from 1940 through 1979. This report extends the period of mortality follow-up 13 years and analyzes both underlying and nonunderlying causes of death. METHODS The vital status of each cohort member, as of December 31, 1992, was determined by using the National Death Index and information from the Internal Revenue Service and the U.S. Postal Service. The NIOSH life table analysis system (LTAS) was used to generate person-year-at-risk and the expected numbers of death for 92 categories of death, using several referent rates (U.S. underlying, Georgia underlying, U.S. multiple cause). RESULTS There were three bladder cancer deaths listed as underlying cause, yielding a standardized mortality ratio (SMR) based on U.S. rates of 2.4 (95% confidence interval (CI) = 0.5, 7.0) and a total of eight bladder cancers listed anywhere on the death certificates (SMR based on multiple cause referent rates = 5.6; 95% CI = 2.4, 11.1). Mortality from esophageal cancer, which had been significantly elevated in the previous study, was no longer significantly elevated (SMR = 2.0; 95% CI = 0.8, 4.1). Mortality from all causes was significantly higher than expected (SMR = 1.5; 95% CI = 1.3, 1.6). CONCLUSIONS The elevated bladder cancer risk in this cohort was detected by the multiple cause, but not the underlying cause, analysis. Elevated mortality from other causes of death, especially among short-term workers, may be related to regional and lifestyle factors.