Cohort study of workers at a New Zealand agrochemical plant to assess the effect of dioxin exposure on mortality.

OBJECTIVES: To describe how the exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) influenced mortality in a cohort of workers who were exposed more recently, and at lower levels, than other cohorts of trichlorophenol process workers. DESIGN: A cohort study. SETTING: An agrochemical plant in New Zealand PARTICIPANTS: 1,599 men and women working between 1 January 1969 and 1 November 1988 at a plant producing the herbicide 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) with TCDD as a contaminant. Cumulative TCDD exposure was estimated for each individual in the study by a toxicokinetic model. PRIMARY OUTCOME MEASURES: Calculation of cause-specific standardised mortality ratios (SMRs) and 95% confidence intervals (95% CI's) compared those never and ever exposed to TCDD. Dose-response trends were assessed firstly through SMRs stratified in quartiles of cumulative TCCD exposure, and secondly with a proportional hazards model. RESULTS: The model intercept of 5.1 ppt of TCDD was consistent with background TCDD concentrations in New Zealand among older members of the population. Exposed workers had non-significant increases in all-cancer deaths (SMR=1.08, 95% CI 0.86 to 1.34), non-Hodgkin lymphoma (SMR=1.57, 95% CI: 0.32 to 4.59), soft tissue sarcoma (one death) (SMR=2.38, 95% CI: 0.06 to 13.26), diabetes (SMR=1.27, 95% CI: 0.55 to 2.50) and ischaemic heart disease (SMR=1.21, 95% CI: 0.96 to 1.50). Lung cancer deaths (SMR=0.95, 95% CI: 0.56 to 1.53) were fewer than expected. Neither the stratified SMR nor the proportional hazard analysis showed a dose-response relationship. CONCLUSION: There was no evidence of an increase in risk for 'all cancers', any specific cancer and no systematic trend in cancer risk with TCDD exposure. This argues against the carcinogenicity of TCDD at lower levels of exposure.

Lymphatic and hematopoietic cancers among benzene-exposed workers.

OBJECTIVE: High benzene exposure is related to acute nonlymphocytic leukemia. Recently, myelodysplastic syndrome has been observed at low benzene exposure levels. METHODS: We updated a mortality study of workers with benzene exposure examining acute nonlymphocytic leukemia and myelodysplastic syndrome. We calculated standardized mortality ratios with 95% confidence intervals and examined latency and trends for cumulative exposure levels. RESULTS: All leukemias (standardized mortality ratio = 1.21; 95% confidence interval = 0.74 to 1.97) and acute non-lymphocytic leukemia (standardized mortality ratio = 1.04; 95% confidence interval = 0.34 to 2.44) were at expected levels. We observed one death from myelodysplastic syndrome (standardized mortality ratio = 6.48; 95% confidence interval = 0.17 to 38.15). We observed no trend for cumulative exposure levels. CONCLUSIONS: Our results for all leukemias are consistent with a small increase in risk observed in the lower-exposed subgroups of the Pliofilm study; however, our results are also consistent with no increased risk especially for acute nonlymphocytic leukemia.

Brain Cancer in Workers Employed at a Laboratory Research Facility.

BACKGROUND: An earlier study of research facility workers found more brain cancer deaths than expected, but no workplace exposures were implicated. METHODS: Adding four additional years of vital-status follow-up, we reassessed the risk of death from brain cancer in the same workforce, including 5,284 workers employed between 1963, when the facility opened, and 2007. We compared the work histories of the brain cancer decedents in relationship to when they died and their ages at death. RESULTS: As in most other studies of laboratory and research workers, we found low rates of total mortality, total cancers, accidents, suicides, and chronic conditions such as heart disease and diabetes. We found no new brain cancer deaths in the four years of additional follow-up. Our best estimate of the brain cancer standardized mortality ratio (SMR) was 1.32 (95% confidence interval [95% CI] 0.66-2.37), but the SMR might have been as high as 1.69. Deaths from benign brain tumors and other non-malignant diseases of the nervous system were at or below expected levels. CONCLUSION: With the addition of four more years of follow-up and in the absence of any new brain cancers, the updated estimate of the risk of brain cancer death is smaller than in the original study. There was no consistent pattern among the work histories of decedents that indicated a common causative exposure.

Cancer mortality of workers exposed to styrene in the U.S. Reinforced plastics and composite industry.

BACKGROUND: Epidemiologic studies have reported increased risk of lymphohematopoietic cancers, lung cancer, and pancreatic cancer after exposure to styrene, although findings across studies are not consistent. METHODS: We update a large study of reinforced plastic industry workers with relatively high exposures to styrene, examining cancer risks associated with exposure levels. The study includes 15,826 workers who were exposed between 1948 and 1977 with vital-status follow-up from 1948 to 2008. We examine mortality rates associated with cumulative exposure, duration of exposure, peak exposures, average exposure, and time since first exposure to styrene. Exposure estimates were truncated starting in 1977, the period with the lowest exposures, leaving 27% of the study group with incomplete work histories. RESULTS: The standardized mortality ratios were 0.84 (95% confidence interval = 0.69-1.02) for all lymphatic and hematopoietic cancers combined, 0.72 (0.50-1.00) for non-Hodgkin lymphoma, and 0.84 (0.60-1.14) for leukemia. There was no trend with either cumulative exposure to styrene or number of peaks. Pancreatic cancer deaths were at expected levels (0.96 [0.73-1.22]). There were more lung cancer deaths than expected (1.34 [1.23-1.46]), although with a marked inverse trend with cumulative exposure. CONCLUSION: We found no coherent evidence that styrene exposure increases risk from cancers of the lymphatic and hematopoietic tissue, pancreas, or lung.

Elimination rates of dioxin congeners in former chlorophenol workers from Midland, Michigan.

BACKGROUND: Exposure reconstructions and risk assessments for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and other dioxins rely on estimates of elimination rates. Limited data are available on elimination rates for congeners other than TCDD. OBJECTIVES: We estimated apparent elimination rates using a simple first-order one-compartment model for selected dioxin congeners based on repeated blood sampling in a previously studied population. METHODS: Blood samples collected from 56 former chlorophenol workers in 2004-2005 and again in 2010 were analyzed for dioxin congeners. We calculated the apparent elimination half-life in each individual for each dioxin congener and examined factors potentially influencing elimination rates and the impact of estimated ongoing background exposures on rate estimates. RESULTS: Mean concentrations of all dioxin congeners in the sampled participants declined between sampling times. Median apparent half-lives of elimination based on changes in estimated mass in the body were generally consistent with previous estimates and ranged from 6.8 years (1,2,3,7,8,9-hexachlorodibenzo-p-dioxin) to 11.6 years (pentachlorodibenzo-p-dioxin), with a composite half-life of 9.3 years for TCDD toxic equivalents. None of the factors examined, including age, smoking status, body mass index or change in body mass index, initial measured concentration, or chloracne diagnosis, was consistently associated with the estimated elimination rates in this population. Inclusion of plausible estimates of ongoing background exposures decreased apparent half-lives by approximately 10%. Available concentration-dependent toxicokinetic models for TCDD underpredicted observed elimination rates for concentrations < 100 ppt. CONCLUSIONS: The estimated elimination rates from this relatively large serial sampling study can inform occupational and environmental exposure and serum evaluations for dioxin compounds.

TCDD exposure estimation for workers at a New Zealand 2,4,5-T manufacturing facility based on serum sampling data.

Employment in the manufacture of the herbicide 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) is associated with potential exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and elevated serum lipid TCDD concentrations can be measured in workers for decades after terminated occupational exposure. As part of an epidemiological study of 1599 workers employed at a facility in New Plymouth, New Zealand that manufactured 2,4,5-T, serum TCDD concentrations measured in blood samples from 346 workers were used with work history records and a simple pharmacokinetic model in a linear regression to estimate dose rates associated with specific job exposure groups at the facility. The model was used to estimate serum TCDD concentration profiles over time for each individual in the full study group and accounted for 30% of the observed variance in TCDD concentrations in the serum donor subgroup. The model underestimated measured concentrations substantially for eleven individuals in the study group; examination of questionnaire data revealed a variety of activities apart from routine employment at the facility that may have contributed to the measured serum TCDD concentrations. Estimated serum TCDD concentrations were below 300 p.p.t. for all individuals in the cohort over the entire study time period, lower than estimates for other 2,4,5-T worker populations. This finding is consistent with occupational medicine records, which indicated that no cases of chloracne were ever diagnosed among workers employed on the site. The modeled exposures will be used in an evaluation of mortality patterns of workers at this facility.

Serum concentrations of chlorinated dibenzo-p-dioxins and dibenzofurans among former Michigan trichlorophenol and pentachlorophenol workers.

This study examines serum levels of 2,3,7,8-substituted chlorinated dioxins and furans, and PCBs for 375 Michigan workers with potential chlorophenol exposure, 37 Worker Referents, and 71 Community Referents. The chlorophenol workers were last exposed to trichlorophenol and/or pentachlorophenol 26-62 years ago. Employees working only in the trichlorophenol units had mean lipid-adjusted 2378-tetrachlorodibenzo-p-dioxin (TCDD) levels of 15.9 ppt compared with 6.5 ppt in the Worker Referents. Employees working only in the pentachlorophenol units had mean lipid-adjusted levels for 123478-H6CDD of 16.1 ppt, 123678-H6CDD of 150.6 ppt, 123789-H6CDD of 20.2 ppt, 1234678-H7CDD of 192.6 ppt, and OCDD of 2,594.0 ppt compared with the Worker Referent levels for the same congeners of 7.5, 74.7, 8.6, 68.7, and 509.1 ppt, respectively. All furan and PCB levels among workers in the trichlorophenol and/or pentachlorophenol departments were similar to the Worker Referents. The Tradesmen who worked throughout the plant had dioxin congener profiles consistent with both trichlorophenol and pentachlorophenol exposures. PCB levels and levels of 23478-P5CDF, 123478-H6CDF, and 123678-H6CDF were also greater in these Tradesmen than in the Worker Referents. The Worker Referent group had higher levels of dioxins and furans than the Community Referents indicating the potential for exposure outside the chlorophenol departments at the site. Distinct patterns of dioxin congeners were found many years after exposure among workers with different chlorophenol exposures. Furthermore, past trichlorophenol exposures were readily distinguishable from past pentachlorophenol exposures based on serum dioxin evaluations among workers. These data can be used to better assess dioxin exposures in future health studies.

Communication of epidemiology study results by industry: the Dow Chemical Company approach.

Communicating epidemiology study results to subjects, affected workers, and community members is an important part of compliance and alignment with our company's policies, industry's Responsible Care Principles, and the doctrines of Good Epidemiology Practices. It is the responsibility of the investigators to interpret their research appropriately for each audience, and to assure that all who have a need or right to know get information in a form meaningful to them. We discuss study communication with examples from a recent evaluation of communication efforts within Dow and our experience with occupational and community studies on dioxin. We also discuss how we currently structure worker and community communication based on this experience. Since each Dow protocol must include a communication plan, when we agree to undertake a study, we are also agreeing to communicate study results. Depending upon the nature and type of the study, there may also be some prestudy communication. We encourage all investigators to share the results of their studies more broadly than just scientific publication and plan for the study communication before the study is initiated.