Acute and developmental behavioral effects of flame retardants and related chemicals in zebrafish

Abstract

As polybrominated diphenyl ethers are phased out, numerous compounds are emerging as potential replacement flame retardants for use in consumer and electronic products. Little is known, however, about the neurobehavioral toxicity of these replacements. This study evaluated the neurobehavioral effects of acute or developmental exposure to t-butylphenyl diphenyl phosphate (BPDP), 2-ethylhexyl diphenyl phosphate (EHDP), isodecyl diphenyl phosphate (IDDP), isopropylated phenyl phosphate (IPP), tricresyl phosphate (TMPP; also abbreviated TCP), triphenyl phosphate (TPHP; also abbreviated TPP), tetrabromobisphenol A (TBBPA), tris (2-chloroethyl) phosphate (TCEP), tris (1,3-dichloroisopropyl) phosphate (TDCIPP; also abbreviated TDCPP), tri-o-cresyl phosphate (TOCP), and 2,2-,4,4′-tetrabromodiphenyl ether (BDE-47) in zebrafish (Danio rerio) larvae. Larvae (n ≈ 24 per dose per compound) were exposed to test compounds (0.4–120 µM) at sub-teratogenic concentrations either developmentally or acutely, and locomotor activity was assessed at 6 days post fertilization. When given developmentally, all chemicals except BPDP, IDDP and TBBPA produced behavioral effects. When given acutely, all chemicals produced behavioral effects, with TPHP, TBBPA, EHDP, IPP, and BPDP eliciting the most effects at the most concentrations. The results indicate that these replacement flame retardants may have developmental or pharmacological effects on the vertebrate nervous system.

Use of alternative assays to identify and prioritize organophosphorus flame retardants for potential developmental and neurotoxicity

“…A companion paper (Jarema et al 2015) presents information on the developmental neurotoxicity of these compounds in zebrafish. These assays are summarized in Table 2, along with additional information on the endpoints evaluated and key references for their use in toxicity screening.…”

“…In all cases, these decreases in spontaneous activity occurred in the absence of cytotoxicity during the 1 hour of exposure. In our companion paper, we evaluated neurobehavioral effects in zebrafish following acute and developmental exposure to these FRs (Jarema et al, 2015). Compared to the acute behavioral effects in zebrafish, in which all of the compounds were active, the MEAs detected fewer of these chemicals.…”

Identifying Chemical Groups for Biomonitoring

“…At the time of our 2012 review, NTP had announced planned testing of six chemicals in this group, based on a recommendation from the U.S. Consumer Product Safety Commission (NTP 2010). Recently published studies have added to concerns about non-halogenated aromatic phosphates (Behl et al 2015; Jarema et al 2015; McGee et al 2013; Morris et al 2014). …”

Multigenerational effects of tris(1,3-dichloro-2-propyl) phosphate on the free-living ciliate protozoa Tetrahymena thermophila exposed to environmentally relevant concentrations and after subsequent recovery

“…Previous studies demonstrated that acute exposure to relatively great concentrations of TDCIPP caused multiple toxicities (Jarema et al, 2015;Liu et al, 2016), but no information was available about multigenerational effects of environmentally relevant concentrations of TDCIPP. It has been recognized that exposure to chemicals can cause multigenerational effects through genomic and epigenetic effects.…”