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

Abstract

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.

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

“…Full details of the exposure modelling were the subject of an earlier report. 11 The work history records and serum data were used to estimate TCDD dose rates for each job exposure group, and because of the 7-year half-life of TCDD, this informed earlier exposure levels. There were two basic assumptions in the exposure reconstruction model: firstly that exposure for an individual job within a job exposure group could be modelled as a constant, consistent and average exposure rate in nanograms per year.…”

Hepatocellular carcinoma and the risk of occupational exposure

“…Many studies have indicated that the carcinogenic capacity of TCDD may be due to the interaction between TCDD and the aryl hydrocarbon receptor (AhR). This receptor is implicated in several xenobiotic metabolisms but there is evidence that AhR is able to control other genes, some of which have a pro-oncogenic capacity [182][183][184] . The TCDD is an important AhR agonist and is therefore able to induce and enhance HCC development and diffusion [184] .…”

Non-infective occupational risk factors for hepatocellular carcinoma: A review

“…Oral administration of PCB 126 resulted in a notably higher incidence of HCA and CLC (32,226). The most important epidemiological studies of TCDD carcinogenicity were cohort studies of herbicide producers and users in the US, the Netherlands and Germany, and of the residents of a contaminated area at Seveso, Italy (218,230–233). All found an increased risk for lung cancer, soft tissue sarcoma and non-Hodgkin lymphoma, primarily in the more heavily exposed sub-groups (135,218).…”

“…TCDD is well known to upregulate the genes encoding the enzymes involved in xenobiotic metabolism, such as CYP1A1 (238). However, increasing data indicates that AhR controls the expression of a variety of genes not associated with xenobiotic metabolism (239,233). In human lymphocytes, TCDD, a potent AhR agonist, markedly increased the frequency of SCEs (234).…”