Transthyretin-Binding Activity of Complex Mixtures Representing the Composition of Thyroid-Hormone Disrupting Contaminants in House Dust and Human Serum.

BACKGROUND

House dust contains many organic contaminants that can compete with the thyroid hormone (TH) thyroxine () for binding to transthyretin (TTR). How these contaminants work together at levels found in humans and how displacement from TTR relates to -TTR binding is unknown.

OBJECTIVES

Our aims were to determine the TTR-binding potency for contaminant mixtures as found in house dust, maternal serum, and infant serum; to study whether the TTR-binding potency of the mixtures follows the principle of concentration addition; and to extrapolate the TTR-binding potency to inhibition levels of -TTR binding in maternal and infant serum.

METHODS

Twenty-five contaminants were tested for their capacity to compete for TTR-binding with a fluorescent FITC- probe. Three mixtures were reconstituted proportionally to median concentrations for these chemicals in house dust, maternal serum, or infant serum from Nordic countries. Measured concentration-response curves were compared with concentration-response curves predicted by concentration addition. For each reconstituted serum mixture, its inhibitor-TTR dissociation constant () was used to estimate inhibition levels of -TTR binding in human blood.

RESULTS

The TTR-binding potency of the mixtures was well predicted by concentration addition. The inhibition in FITC- binding observed for the mixtures reflecting median concentrations in maternal and infant serum was extrapolated to 1.3% inhibition of -TTR binding in maternal and 1.5% in infant blood. For nontested mixtures reflecting high-end serum concentrations, these estimates were 6.2% and 4.9%, respectively.

DISCUSSION

The relatively low estimated inhibition levels at median exposure levels may explain why no relationship between exposure to TTR-binding compounds and circulating levels in humans has been reported, so far. We hypothesize, however, that 1.3% inhibition of -TTR binding may ultimately be decisive for reaching a status of maternal hypothyroidism or hypothyroxinemia associated with impaired neurodevelopment in children. https://doi.org/10.1289/EHP5911.