T4 in serum, Decreased leads to Cognitive Function, Decreased

There are no inconsistencies in this KER, but there are some remaining uncertainties. It is widely accepted that changes in serum THs during development will result in alterations in behavior controlled by the hippocampus. This has been repeatedly demonstrated in animal models and in humans. A major uncertainty is the precise relationship between the degree, timing and duration of serum TH changes that leads to these behavioral deficits.

Inconsistencies may also exist for chemicals other than classical TPO inhibitors that may reduce serum TH and induce impairments in cognitive function, but through action on other endocrine systems, or via direct action on the brain in the absence of an intervening endocrine action.  

Except for a quantitative relationship between serum T4 and hearing loss in rodents (Crofton, 2004), there are no other reports of development of quantitative predictive models linking serum TH and adverse neurological outcomes. Insufficient data exist to develop a quantitative predictive model of adverse cognitive outcomes from serum TH concentrations. However, evidence from human studies suggests that decreases as low as 25% in serum T4 in pregnant women will yield small decrements in IQ in children (e.g., Haddow et al., 1995). Since publication of this seminal paper, several reports have appeared providing supportive if not direct confirmatory data on the association of reductions in maternal or early postnatal serum TH and adverse neurodevelopmental outcomes (e.g., Rovet and Willoughby, 2010, Wheeler et al., 2011, Willoughby et al., 2014, Wheeler et al., 2015; Pop et al., 1999, Pop et al., 2003, Kooistra et al., 2006, Henrichs et al., 2010, Korevaar et al., 2016). Based on these data, regulatory authorities have used 10 and/or 20% changes in serum T4 as a point of departure for hazard assessments in rodent studies (EPA, 2011).