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Objectives: To evaluate the extent to which lung cancer mortality risk estimates in relation to acrylonitrile (AN) exposure may have been confounded by smoking in the presence of misclassified smoking data., Methods: Subjects were 992 white men employed for three or more months between 1960 and 1996 at a chemical plant in Lima, Ohio. We used Monte Carlo-based sensitivity analysis to address possible confounding by smoking., Results: In Monte Carlo simulations that accounted for the relationship between smoking and AN exposure, mean relative risks for lung cancer mortality in relation to AN exposure decreased and we observed somewhat less evidence of an exposure-response relationship., Conclusions: Our simulations suggest that the relationship between AN exposure and lung cancer mortality was positively confounded by smoking in the original Lima cohort study.

As part of an historical cohort study to investigate the mortality experience of industrial workers exposed to chloroprene (CD) and other substances, including vinyl chloride monomer (VC), we analyzed mortality from all cancers combined, respiratory system (RSC) and liver cancer in relation to CD and VC exposures. Subjects were 12,430 workers ever employed at one of two U.S. sites (Louisville, KY (n=5507) and Pontchartrain, LA (n=1357)) or two European sites (Maydown, Northern Ireland (n=4849) and Grenoble, France (n=717)). Historical exposures for individual workers were estimated quantitatively for CD and VC. For sites L, M, P and G, respectively, average intensity of CD exposures (median value of exposed workers in ppm) were 5.23, 0.16, 0.028 and 0.149 and median cumulative exposures (ppm years) were 18.35, 0.084, 0.133 and 1.01. For sites L and M, respectively, average intensity of VC exposures (median value of exposed workers in ppm) was 1.54 and 0.03 and median cumulative exposures (ppm years) were 1.54 and 0.094. We performed relative risk (RR) regression modeling to investigate the dependence of the internal cohort rates for all cancers combined, RSC and liver cancer on combinations of the categorical CD or VC exposure measures with adjustment for potential confounding factors. We categorized exposure measures into approximate quartiles based on the distribution of deaths from all cancers combined. We also considered 5- and 15-year lagged exposure measures and adjusted some RR models for worker pay type (white/blue collar) as a rough surrogate for lifetime smoking history. All modeling was site-specific to account for exposure heterogeneity. We also computed exposure category-specific standardized mortality ratios (SMRs) to assess absolute mortality rates. With the exception of a one statistically significant association with duration of exposure to CD and all cancers combined in plant M, we observed no evidence of a positive association with all cancers, RSC or liver cancer and exposure to CD and/or VC using both the unlagged and lagged exposure measures: duration, average intensity or cumulative exposure to CD or VC; time since first CD or VC exposure; and duration of CD exposure or time since first CD exposure in presence or absence of VC exposure. We observed elevated and statistically significantly elevated RRs for some analysis subgroups, but these were due to inordinately low death rates in the baseline categories. With the possible exception of all cancer mortality in plant G, our additional adjustment of RRs for pay type revealed no evidence of positive confounding by smoking. We conclude that exposures to CD or VC at the levels encountered in the four study sites do not elevate mortality risks from all cancers, RSC or liver cancer. This conclusion is corroborated by our analysis of general mortality patterns among the CD cohort reported in our companion paper [G. Marsh, A. Youk, J. Buchanich, M. Cunningham, N. Esmen, T. Hall, M. Phillips, Mortality patterns among industrial workers exposed to chloroprene and other substances. I. General mortality patterns, Chem.-Biol. Interact., submitted for publication].

We conducted an historical cohort study to investigate the mortality experience of industrial workers potentially exposed to chloroprene (CD) and other substances, including vinyl chloride (VC), with emphasis on cancer mortality, including respiratory system (RSC) and liver. In 1999, the International Agency for Research on Cancer (IARC) classified CD as a possible carcinogen (Group 2B); VC was classified in 1987 as a known human carcinogen (Group 1). Subjects were 12,430 workers ever employed at one of two U.S. industrial sites (Louisville, KY (n=5507) and Pontchartrain, LA (n=1357)) or two European sites (Maydown, Northern Ireland (n=4849) and Grenoble, France (n=717)), with earliest CD production dates ranging from 1942 (L) to 1969 (P). Two sites (L and M) synthesized CD with the acetylene process that produced VC exposures. We determined vital status through 2000 for 95% of subjects and cause of death for 95% of the deaths. Historical exposures for individual workers were estimated quantitatively for CD and VC. Workers ever exposed to CD ranged from 92.3% (M) to 100% (G); to VC from 5.5% (M) to 22.7% (L). We computed standardized mortality ratios (SMRs) (using national and regional standard populations) in relation to selected demographic, work history and exposure factors. We used worker pay type (white or blue collar) as a rough surrogate for lifetime smoking history. For the combined cohort, SMRs (95% CIs) for all causes combined, all cancers combined, RSC and liver cancer were, respectively, 0.72 (0.69-0.74), 0.73 (0.68-0.78), 0.75 (0.67-0.84) and 0.72 (0.43-1.13). Site-specific (L, M, P and G, respectively) SMRs were: for all cancers combined: 0.75 (0.69-0.80), 0.68 (0.56-0.80), 0.68 (0.47-0.95) and 0.59 (0.36-0.91); for RSC: 0.75 (0.66-0.85), 0.79 (0.58-1.05), 0.62 (0.32-1.09) and 0.85 (0.41-1.56); for liver cancer: 0.90 (0.53-1.44) (17 deaths), 0.24 (0.01-1.34) (1 death), 0.0 (0-2.39) (no deaths) and 0.56 (0.01-3.12) (1 death). Among all workers ever exposed to CD, SMRs were: for all cancers combined: 0.71 (0.66-0.76); for RSC: 0.75 (0.67-0.84); for liver cancer: 0.71 (0.42-1.14). We also observed no increased mortality risks among cohort subgroups defined by race, gender, worker pay type, worker service type (short/long term), time period, year of hire, age at hire, duration of employment, the time since first employment, and CD or VC exposure status (never/ever exposed). In summary, our study has many strengths and is the most definitive study of the human carcinogenic potential of exposure to CD conducted to date. We conclude that persons exposed to chloroprene or vinyl chloride at the levels encountered in the four study sites did not have elevated risks of mortality from any of the causes of death examined, including all cancers combined and lung and liver cancer, the cancer sites of a priori interest. This conclusion is corroborated by our detailed analyses of mortality in relation to qualitative and quantitative exposures to CD and VC at each of the four study sites, reported in our companion paper (Marsh et al., submitted for publication).

As part of an historical cohort study to investigate the mortality experience of industrial workers exposed to chloroprene (beta-CD) and other substances, all available industrial hygiene exposure monitoring data were collected and summarized. From discussions with on-site industrial hygiene personnel, it was apparent that these data were not collected for epidemiological purposes and, therefore, their use in characterization of exposures was problematic as the data mostly pertained to samples collected to investigate the performance of specific tasks. These data were, however, informative for validating the exposure modeling process used to estimate historical exposures. The data summarized below clearly indicate that exposures to beta-CD were lowered across the time period of this study. Typically, the exposures recorded were less than the occupational exposure limits of the periods in which the exposures were recorded. Additionally, exposure measurements recorded in the recent past do not represent the exposure actually experienced by the worker as a strict personal protective equipment use program has been in place for the facilities studied since the mid-1980s.

Objective: The objective of this study was to update the mortality experience of a cohort of workers with and without potential exposure to acrylamide (AMD) at three U.S. plants (n = 8508) and one plant in The Netherlands (n = 344)., Methods: We computed standardized mortality ratios (SMRs) using national and local rates and modeled internal cohort rates to assess site-specific cancer risks by demographic and work history factors and several exposure indicators for AMD., Results: For the 1925-2002 study period, we observed both deficit and excess overall mortality risks among the U.S. cohort for cancer sites implicated in experimental animal studies: brain and other central nervous system (SMR = 0.67, confidence interval [CI] = 0.40-1.05), thyroid gland (SMR = 1.38, CI = 0.28-4.02), testis and other male genital organs (SMR = 0.64, CI = 0.08-2.30); and for sites selected in earlier exploratory analyses of this cohort: respiratory system cancer (RSC) (SMR = 1.17, CI = 1.06-1.27), esophagus (SMR = 1.20, CI = 0.86-1.63), rectum (SMR = 1.25, CI = 0.84-1.78), pancreas (SMR = 0.94, CI = 0.70-1.22), and kidney (SMR = 1.01, CI = 0.66-1.46). Except for RSC, attributed earlier to muriatic acid exposure, none of the mortality excesses was statistically significant. In the Dutch cohort, we observed deficits in deaths for all sites of a priori interest. An updated analysis of our previous exploratory findings for pancreatic cancer in the U.S. cohort revealed much less evidence of a possible exposure-response relationship with AMD., Conclusion: AMD exposure at the levels present in our study sites was not associated with elevated cancer mortality risks.

Objectives: To assess the possible relationship between formaldehyde exposure and mortality risk from pharyngeal cancer (PC), in particular nasopharyngeal cancer (NPC)., Methods: Subjects were 7328 workers employed at a plastics-producing plant (1941-1984). Vital status for 98% of the cohort and cause of death for 95% of 2872 deaths were determined. Reconstructed exposures to formaldehyde, particulates and pigment were used to compute several exposure measures. Standardized mortality ratios (SMRs) were computed for several demographic, work history and formaldehyde exposure variables. In a nested case-control study, seven cases of NPC and 15 cases of other PC were matched on race, sex, age and year of birth to four controls from the cohort. Among interviewed subjects, lifetime smoking history was determined using respondents or proxies for all but one control subject., Results: Statistically significant 2.23-fold and fivefold excesses for PC and NPC, respectively, were observed. Fivefold range NPC excesses were observed for both short ( < 1 year) and long-term workers and were concentrated among workers hired during 1947-1956. Only three NPC cases were exposed to formaldehyde for longer than one year, and each had low average intensity of formaldehyde exposure (0.03-0.60 ppm). Only a few exposure measures revealed some evidence of an association with all PC or NPC. For all PC combined, adjustment for smoking and year-of-hire in the case-control study generally corroborated findings from the cohort study., Conclusions: Overall, the pattern of findings suggests that the large, persistent nasopharyngeal and other PC excesses observed among the Wallingford workforce are not associated with formaldehyde exposure, and may reflect the influence of nonoccupational risk factors or occupational risk factors associated with employment outside the Wallingford plant.

Objectives: The present study provides additional analyses of data obtained earlier on lung cancer risk among workers with acrylonitrile exposure., Methods: The original authors provided the data. For total mortality and the cancer sites of a priori interest (lung, stomach, brain, breast, prostate, and the lymphatic and hematopoietic systems), standardized mortality ratios (SMR) and 95% confidence intervals (95% CI) were computed, the total United States and surrounding counties being used as standard populations. Regional rate-based SMR values were also computed between lung cancer and cumulative acrylonitrile exposure., Results: Except for lung cancer, the external comparisons corroborated the earlier internal comparisons (no increased cancer mortality risk). For lung cancer, the external comparisons revealed death deficits for the unexposed workers (SMR 0.68, 95% CI 0.5-0.9) and all categories of acrylonitrile-exposed workers. The SMR obtained using external rates and the most exposed group (SMR 0.92. 95% CI 0.6-1.4) differed from the corresponding relative risk (RR) of the internal rates (RR 1.5, 95% CI 0.9-2.4)., Conclusions: The analysis of the present study provides little evidence that acrylonitrile exposure increases the mortality risk of cancers of a priori interest, including lung cancer. The lung cancer findings of the external comparison differed from the earlier findings of the internal comparisons. Selection bias (as the healthy worker effect) was probably not responsible. Additional follow-up and analyses, especially of the unexposed workers with low lung cancer rates, may help elucidate the internal and external comparison differences. Results from both comparisons should be presented when the relative risks differ markedly, as both have advantages and disadvantages.

Objectives: To examine the association between exposure to acrylonitrile (AN) and cancer mortality by performing an independent and extended historical cohort study of workers from a chemical plant in Lima, Ohio included in a recent NCI-NIOSH study., Methods: Subjects were 992 white males who were employed for three or more months between 1960 and 1996. We identified 110 deaths and cause of death for 108. Worker exposures were estimated quantitatively for AN and qualitatively for nitrogen products. Statistical analyses included U.S. and local county-based SMRs and internal relative risk regression of internal cohort rates., Results: No statistically significant excess mortality risks were observed among the total cohort for the cancer sites implicated in previous studies: stomach, lung, breast, prostate, brain, and hematopoietic system. We observed a statistically significant bladder cancer excess based on four deaths (SMR=7.01, 95% CI=1.91-17.96) among workers not exposed to AN. Among 518 AN-exposed workers, we observed a not statistically significant excess of lung cancer based on external (SMR=1.32, 95% CI=.60-2.51) and internal (RR=1.98, 95% CI=.60-6.90) comparisons. Although the trends were not statistically significant, exposure-response analyses of internal cohort rates showed monotonically increasing lung cancer rate ratios with increasing AN exposure, with RRs exceeding 2.0 in the highest exposure categories., Conclusions: With the possible exception of lung cancer, this study provides little evidence that exposure to AN at levels experienced by Lima plant workers is associated with an increased risk of death from any cause including the implicated cancer sites., (Copyright 1999 Wiley-Liss, Inc.)