Assessing the potential impact on the thyroid axis of environmentally relevant food constituents/contaminants in humans

Occurrence and mode of action of potentially relevant goitrogens in human nutrition and their mode of action (MOA) are reviewed, with special focus on the anionic iodine uptake inhibitors perchlorate (PER), thiocyanate (SCN) and nitrate (NO3). Epidemiological studies suggest persistent halogenated organic contaminants and phthalates as well as certain antimicrobials to deserve increased attention. This also applies to natural goitrogens, including polyphenols and glucosinolates, food constituents with limited data density concerning human exposure. Glucosinolates present in animal feed are presumed to contribute to SCN transfer into milk and milk products. PER, SCN and NO3 are well-investigated environmental goitrogens in terms of MOA and relative potency. There is compelling evidence from biomarker monitoring that the exposure to the goitrogens SCN and NO3 via human nutrition exceeds that of PER by orders of magnitude. The day-to-day variation in dietary intake of these substances (and of iodide) is concluded to entail corresponding variations in thyroidal iodide uptake, not considered as adverse to health or toxicologically relevant. Such normal variability of nutritional goitrogen uptake provides an obvious explanation for the variability in radioactive iodine uptake (RAIU) measurements observed in healthy individuals. Based on available data, a 20 % change in the thyroidal uptake of iodide is derived as threshold value for a biologically meaningful change induced by perchlorate and other goitrogens with the same MOA. We propose this value to be used as the critical effect size or benchmark response in benchmark dose analysis of human RAIU data. The resulting BMDL20 is 0.0165 mg/kg bw/day or 16.5 mu g/kg bw/day. Applying a factor of 4, to allow for inter-human differences in toxicokinetics, leads to a TDI for perchlorate of 4 mu g/kg bw/day.