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Thyroid toxicants and neurodevelopment: Molecular initiating event may be an important consideration
Citation:
Gilbert, M., S. Thomas, K. OShaughnessy, I. Hassan, C. Riutta, J. Ford, A. Smith, W. Oshiro, AND C. Wood. Thyroid toxicants and neurodevelopment: Molecular initiating event may be an important consideration. SOT Annual Meeting, Baltimore, MD, March 11 - 15, 2019.
Impact/Purpose:
Abstract for SOT Annual Meeting
Description:
Developmental neurotoxicity is a primary concern for thyroid disrupting chemicals (TDCs). Many environmental TDCs include antimicrobials, pesticides, flame retardants, and perfluorinated compounds. These TDCs reduce circulating levels of thyroid hormones (THs) by distinct and/or overlapping mechanisms, many of which are not well characterized. It is unclear if these chemicals also reduce THs in the brain and cause neurodevelopment defects. This study investigated the potential neurotoxicological effects of one of the antimicrobials known to be a TDC, triclosan, which is purported to alter liver clearance and/or interfere with serum binding proteins. Pregnant rats were dosed with a single high dose of triclosan (300mg/kg/day) by gavage or vehicle control once daily from gestational day 6 (GD6) to postnatal day 21 (PN21). Results show that triclosan did not induce changes in litter size or pup body weight. No effects were seen on liver weight or body:liver weight ratios in dams or pups but liver metabolism genes were increased in expression. Serum total and free T4 were reduced in the dam (GD20 and PN21) and pup (PN0, PN2, PN6, PN14) to varying degrees; however, thyroid stimulating hormone (TSH) was unchanged. In the neonatal brain, no gene expression changes associated with TH dysfunction were detected, and there was no evidence of a TH-dependent phenotype (heterotopia). Neither were behavioral tests of learning and memory (trace fear conditioning) or sensory motor function (prepulse inhibition) impaired in adult offspring. These data suggest that despite reductions in serum T4 in dams and offspring, according to these metrics, the developing brain does not appear to be adversely affected by triclosan. Future studies describing the quantitative relationship between THs in the serum and brain and more sensitive measures of neurodevelopmental impairment are needed to more fully characterize the risk of these chemicals and others with similar mode(s) of action. This work does not reflect EPA policy.