Updated Italian cohort data continues to confirm lack of mesothelioma risk in pooled cohort of international cosmetic talc miners and millers.

OBJECTIVES: To assess potential mesothelioma risk following inhalation of cosmetic talc, we updated previous iterations of a pooled cohort analysis, post-study statistical power analysis, and confidence interval function analysis for a pooled cohort of international cosmetic talc miners/millers given new Italian cohort data. METHODS: Five cohorts of cosmetic talc miners/millers were pooled. Expected numbers of mesotheliomas for each cohort were reported by the original authors. We based our post-study statistical power analysis on an a priori one-sided significance level of 0.05, and exact Poisson and approximate distribution probabilities. To evaluate the confidence interval function for the observed pooled mesothelioma standardized mortality ratios (SMRs), we calculated the probability for the upper 100(1-2α)% confidence limit that equals various SMRs of interest. RESULTS: The pooled cohorts generated a total observation time of 135,524.38 person-years. Overall, 4.14 mesotheliomas were expected (mid-value estimate), though only one case of mesothelioma has been confirmed in the pooled cohort to date. We calculated 71% and 87% post-study power to detect a 2.5-fold or greater and a 3.0-fold or greater increase in mesothelioma, respectively. Our complimentary confidence interval function analysis demonstrated that the probability that the true mesothelioma SMR for the pooled cohort was at or above 2.0 or at or above 3.0 was 0.00235 and 0.00005, respectively. CONCLUSIONS: Based on the updated results of our various analyses, the current epidemiological evidence from cosmetic talc miner/miller cohort studies continues to not support the hypothesis that the inhalation of cosmetic talc is associated with an increased risk of mesothelioma.

Ethylene Oxide: Cancer Evidence Integration and Dose-Response Implications.

The International Agency for Research on Cancer (IARC) and the United States Environmental Protection Agency (USEPA) classified ethylene oxide (EtO) as a known human carcinogen. Critically, both noted that the epidemiological evidence based on lymphoid and breast cancers was "limited," but that the evidence in animal studies was "sufficient" and "extensive" (respectively) and that EtO is genotoxic. The USEPA derived one of the highest published inhalation unit risk (IUR) values (3 × 10-3 per [µg/m3 EtO]), based on results from 2 epidemiological studies. We performed focused reviews of the epidemiological and toxicological evidence on the carcinogenicity of EtO and considered the USEPA's reliance on a genotoxic mode of action to establish EtO's carcinogenicity and to determine likely dose-response patterns. Higher quality epidemiological studies demonstrated no increased risk of breast cancers or lymphohematopoietic malignancies (LHM). Similarly, toxicological studies and studies of early effect biomarkers in animals and humans provided no strong indication that EtO causes LHM or mammary cancers. Ultimately, animal data are inadequate to define the actual dose-response shape or predict tumor response at very low doses with any confidence. We conclude that the IARC and USEPA classification of EtO as a known human carcinogen overstates the underlying evidence and that the IUR derived by USEPA grossly overestimates risk.

Ethylene oxide and risk of lympho-hematopoietic cancer and breast cancer: a systematic literature review and meta-analysis.

PURPOSE: To conduct a systematic literature review and meta-analysis of studies of lympho-hematopoietic cancers (LHC) and breast cancer risk among persons occupationally exposed to ethylene oxide (EO). METHODS: We performed a literature search for articles available in PubMed and Web of Science databases to identify literature and subsequently systematically searched the reference lists of identified studies, published review papers and meta-analyses, as well as relevant government or regulatory documents. We qualitatively reviewed 30 studies and conducted meta-analyses on 13 studies. Pooled risk estimates were calculated using random effects models, stratifying by occupational group, cancer type and decade of publication. RESULTS: The overall meta-relative risks (meta-RRs) for LHC and breast cancer, respectively, were 1.48 (95% CI 1.07-2.05) and 0.97 (95% CI 0.80-1.18). The meta-RR's for LHC among EO production and EO sterilization workers were 1.46 (95% CI 0.85-2.50) and 1.07 (95% CI 0.87-1.30), respectively. We observed higher risks of LHC in the earlier published studies, compared to the later studies, and the meta-RR's for the 1980s, 1990s, 2000s, and the 2010s, respectively, were 3.87 (95% CI 1.87-8.01), 1.38 (95% CI 0.85-2.25), 1.05 (95% CI 0.84-1.31), and 1.19 (95% CI 0.80-1.77). CONCLUSIONS: The most informative epidemiology studies, which were published in the 2000s and 2010s, do not support the conclusion that exposure to EO is associated with an increased risk of LHC or breast cancer.

Asbestos fiber length and its relation to disease risk.

Differences in chemical and crystalline composition, fiber dimension, aerodynamic characteristics and biodurability are among the critical factors that define the toxicological and pathological consequences of asbestos exposure. Specifically, fiber dimension can impact whether the fiber is respired, whether and how deeply it is deposited in the lung, and how efficiently and rapidly it may be cleared. This paper provides a current, comprehensive evaluation of the weight of evidence regarding the relationship between asbestos fiber length and disease potency (for malignant and nonmalignant endpoints). In vitro studies, animal exposure studies and epidemiology data were reviewed. We found that the data reported over the last several decades consistently support the conclusions that exposure to fibers longer than 10 µm and perhaps 20 µm are required to significantly increase the risk of developing asbestos-related disease in humans and that there is very little, if any, risk associated with exposure to fibers shorter than 5 µm. Fiber length as a predictor of potency has been evaluated by several federal agencies in the U.S. and could significantly influence future regulatory decisions for elongated mineral particles (EMPs) and high-aspect ratio nanoparticles (HARNs).

Biomarkers of Exposure to Polycyclic Aromatic Hydrocarbons and Cognitive Function among Elderly in the United States (National Health and Nutrition Examination Survey: 2001-2002).

Recent studies report a link between common environmental exposures, such as particulate matter air pollution and tobacco smoke, and decline in cognitive function. The purpose of this study was to assess the association between exposure to polycyclic aromatic hydrocarbons (PAHs), a selected group of chemicals present in particulate matter and tobacco smoke, and measures of cognitive performance among elderly in the general population. This cross-sectional analysis involved data from 454 individuals aged 60 years and older from the 2001-2002 National Health and Nutrition Examination Survey. The association between PAH exposures (as measured by urinary biomarkers) and cognitive function (digit symbol substitution test (DSST)) was assessed using multiple linear regression analyses. After adjusting for age, socio-economic status and diabetes we observed a negative association between urinary 1-hydroxypyrene, the gold standard of PAH exposure biomarkers, and DSST score. A one percent increase in urinary 1-hydroxypyrene resulted in approximately a 1.8 percent poorer performance on the digit symbol substitution test. Our findings are consistent with previous publications and further suggest that PAHs, at least in part may be responsible for the adverse cognitive effects linked to tobacco smoke and particulate matter air pollution.