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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.

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.

Objective: We sought to determine if workers exposed to dioxins in pentachlorophenol (PCP) manufacturing were at increased risk of death from specific causes., Methods: We examined death rates among 773 workers exposed to chlorinated dioxins during PCP manufacturing from 1937 to 1980 using serum dioxin evaluations to estimate exposures to five dioxins., Results: Deaths from all causes combined, all cancers combined, lung cancer, diabetes, and ischemic heart disease were near expected levels. There were eight deaths from non-Hodgkin lymphoma (standardized mortality ratios = 2.4, 95% CI = 1.0 to 4.8). We observed no trend of increasing risk for any cause of death with increasing dioxin exposure. However, the highest rates of non-Hodgkin lymphoma were found in the highest exposure group (standardized mortality ratios = 4.5, 95% CI = 1.2 to 11.5)., Conclusions: Other than possibly an increased risk of non-Hodgkin lymphoma, we find no other cause of death related to the mixture of the dioxin contaminants found in PCP.

This study examined serum levels of 2,3,7,8-substituted chlorinated dioxins and furans, and 15 PCBs for 346 New Zealand employees who worked at a site that manufactured 2,4,5-trichlorophenol (TCP) and 2,4,5-trichlorophenoxy acetic acid (2,4,5-T). Participants with potential TCP or 2,4,5-T exposures had mean lipid-adjusted 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD) levels of 9.9 ng kg(-1) lipid compared to 4.9 ng kg(-1) for workers with no exposure at the site. Among exposed workers, we found evidence of differences in 2,3,7,8-TCDD levels by department and duties. Workers involved in an accidental release had the highest mean 2,3,7,8-TCDD levels, 37.9 ng kg(-1), followed by workers in the trichlorophenol plant, 23.4 ng kg(-1). Workers with potential intermittent exposures to 2,3,7,8-TCDD in construction, maintenance, mechanics, and transport had 2,3,7,8-TCDD levels above New Zealand background levels of 3.9 ng kg(-1), indicating workplace exposures. Among participants with work history indicating no 2,3,7,8-TCDD exposures, we observed some individuals with 2,3,7,8-TCDD levels above background levels. However, in most cases, these workers reported workplace exposures not recorded on their work histories or held other jobs with the potential for 2,3,7,8-TCDD exposures outside the plant. All other dioxin, furan, and PCB levels were similar among the exposed and unexposed workers.

Objective: We examined the overall mortality rates of 1599 workers employed between 1969 and 1988 at a New Zealand site, which manufactured trichlorophenol., Methods: We developed exposure estimates for 2,3,7,8-tetrachlorodibenzo-p-dioxin from a serum dioxin evaluation and used standardized mortality ratios (SMR) and proportional hazards models to evaluate risk from exposure., Results: Among exposed workers, deaths from total cancers (SMR = 1.1, 95% confidence intervals [CI]: 0.9-1.4), non-Hodgkin lymphoma (SMR = 1.6, 95% CI: 03-4.7), and ischemic heart disease (SMR = 1.1, 95% CI: 0.9-1.5) were slightly greater than expected, whereas deaths from lung cancer (SMR = 0.8, 95% CI: 0.4-1.5) were less than expected. We observed no significant trends with exposure levels., Conclusions: Although this study is small, we found no increasing trend of cancer or disease risk with increasing 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure with the possible exception of all cancers combined.

The authors examined 1,615 workers exposed to dioxins in trichlorophenol production in Midland, Michigan, to determine if there were increased mortality rates from exposure. Historical dioxin levels were estimated by a serum survey of workers. Vital status was followed from 1942 to 2003, and cause-specific death rates and trends with exposure were evaluated. All cancers combined (standardized mortality ratio (SMR) = 1.0, 95% confidence interval (CI): 0.8, 1.1), lung cancers (SMR = 0.7, 95% CI: 0.5, 0.9), and nonmalignant respiratory disease (SMR = 0.8, 95% CI: 0.6, 1.0) were at or below expected levels. Observed deaths for leukemia (SMR = 1.9, 95% CI: 1.0, 3.2), non-Hodgkin lymphoma (SMR = 1.3, 95% CI: 0.6, 2.5), diabetes (SMR = 1.1, 95% CI: 0.6, 1.8), and ischemic heart disease (SMR = 1.1, 95% CI: 0.9, 1.2) were slightly greater than expected. No trend was observed with exposure for these causes of death. However, for 4 deaths of soft tissue sarcoma (SMR = 4.1, 95% CI: 1.1, 10.5), the mortality rates increased with exposure. The small number of deaths and the uncertainty in both diagnosis and nosology coding make interpretation of this finding tenuous. With the exception of soft tissue sarcoma, the authors found little evidence of increased disease risk from exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin.

We examined the serum lipid adjusted levels of 2,3,7,8-substituted chlorinated dioxins and furans, and four coplanar PCBs for 98 workers. We found workers who worked only in the trichlorophenol units had mean lipid adjusted 2,3,7,8-TCDD levels of 36.8 ppt significantly higher (p<0.05) than 6.0 ppt in the reference group. Workers who worked only in the pentachlorophenol units had mean lipid adjusted levels for 123478-HxCDD of 14.8 ppt, 123678-HxCDD of 156.4 ppt,123789-HxCDD of 23.7 ppt, 1234678-HpCDD of 234.6 ppt, and OCDD of 2,778.2 ppt significantly higher (p<0.05) than the reference group levels for the same congeners of 7.5, 71.8, 8.0, 67.5, and 483.2 ppt, respectively. While we did find 12378-PeCDD levels higher than the reference group in trichlorophenol and pentachlorophenol workers, the differences are small, and could be attributed to normal variation. All furan levels among the trichlorophenol or pentachlorophenol only workers were not significantly different than the reference group. Workers with both trichlorophenol and pentachlorophenol exposures had mean dioxin levels consistent with complex chlorophenol exposures. Tradesmen who worked throughout the plant had congener profiles consistent with both trichlorophenol and pentachlorophenol exposures. PCB 169, 23478-PeCDF, 123478-HxCDF, and 123678-HxCDF levels were also significantly greater (p<0.05) in these tradesmen than in the reference group. We found distinct patterns of dioxin congeners many years after exposure among workers with different chlorophenol exposures. We were effectively able to distinguish past trichlorophenol exposures from pentachlorophenol exposures based on differing serum dioxin profiles among workers.

We evaluated serum concentrations of five selected dioxin, furan, and polychlorinated biphenyls (PCB) congeners among 412 workers at a Midland, Michigan plant that manufactured trichlorophenol and pentachlorophenol (PCP) and formulated chlorophenol-based products. We examined occupational indicators of exposure to these chlorophenols taking into account intrinsic factors such as age and body fat and potential environmental sources of exposure from consumption of local game and fish and other occupations. All five congeners were significantly associated with age and body fat. 2378-TCDD serum concentrations were associated with trichlorophenol operations, total years employed at the plant, as well as working as a hazardous waste worker. 123678-H(6)CDD serum concentrations were related to occupational PCP exposure, chloracne, recent weight loss, eating local game, and working as a hazardous waste worker. Serum concentrations of PCB126 were related to smoking (inversely), and eating local fish or local game. Other factors such as diet and jobs outside of the chlorophenol plant exposures had only a very minor impact on dioxin and furan concentrations in these 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.

Several studies have found that current levels of 2,3,7,8 tetrachlorodibenzo-p-dioxin in serum lipids are related to age with older persons generally having higher levels. To account for this age pattern, reference ranges based on national samples have been established in order to allow determination of background levels for regional studies. In several studies, body mass index (BMI), has also been associated with current 2,3,7,8 tetrachlorodibenzo-p-dioxin levels with increasing body mass index related to increasing levels. We measured lipid-adjusted serum levels for all 2,3,7,8-substituted dioxins and furans in 62 chemical manufacturing workers with chlorophenol exposures and 36 workers without chlorophenol exposures employed at the same location. We then assessed the impact of age and BMI on the serum levels of all these compounds in the presence of other potential confounders. We found that both factors are important independent determinants of serum levels of 2,3,7,8-substituted dioxins and furans. Specifically, age and BMI are both important factors for assessing background levels of 2,3,7,8 tetrachlorodibenzo-p-dioxin, 1,2,3,7,8 pentachlorodibenzo-p-dioxin and the calculated total toxic equivalency. BMI, but not age, is important for assessing background levels of higher chlorinated dioxins and some hexachlorofurans. We conclude that age and BMI are both important considerations when comparing a potentially exposed group to a referent group, or to national norms. Further, age and BMI may also be important in epidemiology studies where back-extrapolation from current dioxin levels is used to assess historical chlorophenol exposure.

Using gas chromatography/mass spectrometry, we measured lipid-adjusted serum levels for all 2,3,7,8-substituted dioxins and furans, and four coplanar polychlorinated biphenyls in 62 workers with chlorophenol exposure and 36 workers without chlorophenol exposures working at the same plant during the same time. We oversampled among workers diagnosed with chloracne. Mean dioxin background levels from 36 nonchlorophenol workers were estimated as 6.0 parts-per-trillion (ppt) for 2,3,7,8 tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD) and 67.5 ppt for 1,2,3,4,6,7,8 heptachlorodibenzo-p-dioxin (Hepta-CDD). We found different dioxin and furan profiles for trichlorophenol and pentachlorophenol (PCP) workers. Among trichlorophenol workers with chloracne, we found 2,3,7,8-TCDD (mean=30.5 ppt) above background levels and among PCP workers with chloracne, we found high levels of Hepta-CDD (mean=312.5 ppt) and other higher chlorinated dioxins and furans. Cumulative exposure estimates for dioxins for both 2,3,7,8-TCDD and the higher chlorinated dioxins created in the early 1980s for our epidemiology studies were highly correlated with serum dioxin levels when age and body mass index were taken into account. While workers previously diagnosed with chloracne had high serum dioxin levels, some workers without diagnosed chloracne also had high levels. Among tradesworkers with plant-wide responsibilities, we observed serum dioxins and PCB levels higher than background indicating workplace exposures. We estimate that the mean level of 2,3,7,8-TCDD present in the serum of workers on the date workplace exposure terminated was 267 ppt (ranging from 8 to 1184 ppt) assuming a 9-year half-life, 582 ppt (ranging from 10 to 2,641 ppt) assuming a 7-year half-life, and 1928 ppt (ranging from 22 to 17,847) when a toxicokinetic model is used. We conclude that our findings are consistent with other studies reporting high serum dioxin levels among chlorophenol workers after occupational exposures.