Project Summary
Toxicological and epidemiologic studies have shown developmental neurotoxicity of polybrominated diphenyl
ethers (PBDEs), a group of flame retardants (FRs) widely used in the U.S. and elsewhere. With the phase-out
of PBDEs from the market since 2004, replacement FRs, including organophosphate flame retardants (OPFRs)
and novel brominated flame retardants (NBFRs), are increasingly added to consumer products to meet
flammability requirement. Tris(1,3-dichloro-2-propyl) phosphate (TDCPP) and Firemaster® 550 (FM 550) are
the most commonly used replacement FRs. TDCPP, also referred to as “chlorinated tris”, is an OPFR once
added to children’s sleepwear in the 1970s but later removed because of toxicity concerns.
Triphenylphosphate (TPP) and various TPP analogs are OPFR components in FM 550, while 2-ethylhexyl-
2,3,4,5-tetrabromobenzoate (TBB) and bis(2-ethylhexyl)-2,3,4,5-tetrabromophthalate (TBPH) are NBFR
components in FM 550. TDCPP, TPP and FM 550 have been reported to alter thyroid hormone levels, reduce
neuronal viability and replication, alter neuronal differentiation, cause abnormal embryogenesis and
development, affect neurobehavior, and change gene expression levels and DNA methylation in experimental
studies. Compared with experimental study evidence of OPFRs and NBFRs, there are significant gaps in our
understanding of their developmental neurotoxicity in humans. We propose to examine developmental
neurotoxicity of OPFRs and NBFRs using the Cincinnati-based Health Outcomes and Measures of the
Environment (HOME) Study, an existing birth cohort of 410 children from prenatal to 12 years of age, with
prenatal and postnatal exposure assessment, thyroid hormones, cognitive and behavioral tests, and
neuroimaging data. We hypothesize that prenatal and postnatal exposures to OPFRs and NBFRs are
associated with: 1) altered thyroid hormone levels in maternal, cord, and childhood serum samples; 2)
decreased child cognitive function; 3) poorer child neurobehavioral functioning; and 4) adverse impact on brain
structure, organization, and function identified by neuroimaging at age 12 years. The proposed research will be
the first to comprehensively study developmental neurotoxicity of both OPFRs and NBFRs in children.
Addressing neuroendocrinological, neurobehavioral, and neuroimaging aspects of brain development is highly
innovative for this investigation. The findings will be of critical value to scientific community and policy makers
evaluating potential impact of current-use replacement FRs on developing brain. The research is highly
relevant to the National Institutes of Health mission to identify potential chemical exposures that disrupt brain
development and provide critical data to inform prevention strategies.