Dioxin relative effect potencies calculated from human thyroid data

We have recently published a paper1 on derivation of relative effect potencies (REPs) of a group of potent endocrine-active chemicals, the dioxin-like compounds (DLCs). The toxic equivalency factors (TEFs), assigned on the basis of the REPs, are an important component in the risk assessment of DLCs human exposures. At present, this concept is based mainly on in vivo animal experiments using oral dosage. Consequently, the current human TEFs derived from mammalian experiments are applicable only for exposure situations in which oral ingestion occurs. Nevertheless, these “intake” TEFs are commonly—but incorrectly—used by regulatory authorities to calculate “systemic” toxic equivalents (TEQs) based on human blood and tissue concentrations, which are used as biomarkers for either exposure or effect. We sought to determine REPs for systemic human concentrations of dioxin-like mixture components using thyroid volume or serum-free thyroxine (FT4) concentration as the outcomes of interest. We used a benchmark concentration and a regression-based approach to compare the strength of association between each DLC and the thyroid end points in 320 adults residing in an organochlorine-polluted area of eastern Slovakia. We found that REPs calculated from thyroid volume and FT4 were similar. The regression coefficient (β)-derived REP data from thyroid volume and FT4 level were correlated with the World Health Organization (WHO) TEF values (Spearman r = 0.69, P = 0.01 and r = 0.62, P = 0.03, respectively). The calculated REPs were mostly within the minimum and maximum values for in vivo REPs derived by other investigators (Haws et al. 2006). We concluded that our REPs calculated from thyroid end points realistically reflect human exposure scenarios because they are based on chronic, low-dose human exposures and on biomarkers reflecting body burden. Compared with previous results, our REPs suggest higher sensitivity to the effects of DLCs.