Hexachlorobenzene as a possible major contributor to the dioxin activity of human milk

Abstract

A dioxinlike compound is a compound that binds to the aryl hydrocarbon (Ah) receptor, results in dioxinlike effects, and bioaccumulates. These are the three factors for including dioxinlike chemicals in the toxic equivalency factor (TEF) concept. Risk assessment of dioxinlike compounds is based on using these TEFs. Hexachlorobenzene (HCB) has all three features and should therefore be included in this TEF concept. Relative potency values express the potency of a specific compound in comparison to 2,3,7, 8-tetrachlorodibenzo-p-dioxin (TCDD), the most potent dioxinlike compound, with a relative potency value of 1. For the estimation of the total dioxin activity in an environmental biological sample, the TEF value of a compound is multiplied by the concentration in the specific matrix. This results in a certain amount of toxic equivalents (TEQs) for this compound. The summation of all TEQs in a certain mixture gives the total dioxin activity of this mixture. HCB binds to the Ah receptor about 10,000 times less than TCDD. HCB is also about 10,000 times less potent than TCDD based on in vitro cytochrome P4501A induction and porphyrin accumulation. Using a relative potency value of 0.0001, HCB could add 10-60% to the total TEQ in human milk samples in most countries. In a few countries such as Spain, Slovakia, and the Czech Republic, HCB levels in human milk expressed as TEQ could contribute up to a factor of six to the total TEQ in comparison to the contribution of polychlorinated dioxins, dibenzofurans, and biphenyls together, i.e., up to a daily intake of about 1 ng TEQ/kg for a breast-fed infant. The HCB levels in human milk in these countries are about the same as in India. Biochemical, immunological, and neurological alterations have been observed in infants fed breast milk in countries with relatively low TEQ levels in human milk. Based on the above information, it is clear that HCB should be classified as a dioxinlike compound, that more studies are needed to reduce the uncertainty in the estimation of a relative potency value for HCB, and that epidemiological studies should be undertaken in infants fed breast milk in countries with high HCB exposure levels. Furthermore, measurements of HCB levels in human and environmental samples in conjunction with other dioxinlike compounds is a prerequisite to estimate the total dioxin activity in these samples.