Mechanistic Insights into TCDD Toxicity

The test compound analyzed in this study was 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) (LGC Standards, Wesel, Germany), a persistent organic pollutant and endocrine disruptor compound, and the corresponding highest concentration tested was 25 nM. The rationale for the selection of the test compound was to include a well-known xenobiotic of high relevance for human and environmental health. Therefore, we included TCDD and its concentration from a previous study for in vitro exposures to the human hepatic cell line HepaRG. Concentration selection was based on the translation of external intakes into internal doses in hepatic cells. The external intake estimates from plasma monitored levels or environmental, accidental, and occupational conditions of TCDD were associated with target tissue (liver cells) dosimetry using a generic physiologically based biokinetic model. The highest serum levels observed correspond to an intake of up to 15 ng/kg_bw/d which corresponded to an internal dose in the liver cells of up to 25 nM TCDD [20 (link)].