有机磷阻燃剂(OPFRs)在环境中含量丰富且持久,但毒性信息有限。它们与有机磷酸酯农药的结构相似性引起了人们对发育神经毒性(DNT)的极大关注。然而,目前的体内检测不适合提供缺乏数据的OPFRs数量的DNT信息。在过去的十年里,开发了一种体外电池来增强DNT评估,由评估神经发育和功能中的细胞过程的测定法组成。在这项研究中,小模式生物的行为数据也包括在内.为了评估这些检测是否提供了足够的机械覆盖率,以优先考虑进一步测试和/或识别危害的化学品,利用综合化学环境(ICE)和文献中的其他信息,开发了一种综合测试和评估方法(IATA)。确定了人体生物监测和暴露数据,并应用了基于生理的毒物动力学模型,以根据最大血浆浓度将体外毒性数据与人体暴露相关联。评估了8个OPFR,包括芳香族OPFR(磷酸三苯酯(TPHP),异丙基苯基磷酸酯(IPP),2-乙基己基二苯基磷酸酯(EHDP),磷酸三甲苯酯(TMPP),磷酸异癸基二苯基酯(IDDP),叔丁基苯基二苯基磷酸酯(BPDP)和卤代FR((三(1,3-二氯-2-丙基)磷酸酯(TDCIPP),三(2-氯乙基)磷酸酯(TCEP))。两种代表性溴化阻燃剂(BFR)(2,2'4,4'-四溴二苯醚(BDE-47)和3,3',选择具有已知DNT潜力的5,5'-四溴双酚A(TBBPA)作为毒性基准。来自DNT电池的数据表明,芳族OPFR在与BFR相似的浓度下具有活性,因此应进一步评估。然而,这些分析提供了有限的信息的机制的化合物。通过整合来自ICE和文献的信息,内分泌干扰被认为是一种潜在机制.这项IATA案例研究表明,人类暴露于某些OPFRs可能导致血浆浓度与发挥体外活性的血浆浓度相似,表明对人类健康的潜在关注。
Organophosphorus flame retardants (OPFRs) are abundant and persistent in the environment but have limited toxicity information. Their similarity in structure to organophosphate pesticides presents great concern for developmental neurotoxicity (DNT). However, current in vivo testing is not suitable to provide DNT information on the amount of OPFRs that lack data. Over the past decade, an in vitro battery was developed to enhance DNT assessment, consisting of assays that evaluate cellular processes in neurodevelopment and function. In this study, behavioral data of small model organisms were also included. To assess if these assays provide sufficient mechanistic coverage to prioritize chemicals for further testing and/or identify hazards, an integrated approach to testing and assessment (IATA) was developed with additional information from the Integrated Chemical Environment (ICE) and the literature. Human biomonitoring and exposure data were identified and physiologically-based toxicokinetic models were applied to relate in vitro toxicity data to human exposure based on maximum plasma concentration. Eight OPFRs were evaluated, including aromatic OPFRs (triphenyl phosphate (TPHP), isopropylated phenyl phosphate (IPP), 2-ethylhexyl diphenyl phosphate (EHDP), tricresyl phosphate (TMPP), isodecyl diphenyl phosphate (IDDP), tert-butylphenyl diphenyl phosphate (BPDP)) and halogenated FRs ((Tris(1,3-dichloro-2-propyl) phosphate (TDCIPP), tris(2-chloroethyl) phosphate (TCEP)). Two representative brominated flame retardants (BFRs) (2,2\'4,4\'-tetrabromodiphenyl ether (BDE-47) and 3,3\',5,5\'-tetrabromobisphenol A (TBBPA)) with known DNT potential were selected for toxicity benchmarking. Data from the DNT battery indicate that the aromatic OPFRs have activity at similar concentrations as the BFRs and should therefore be evaluated further. However, these assays provide limited information on the mechanism of the compounds. By integrating information from ICE and the literature, endocrine disruption was identified as a potential mechanism. This IATA case study indicates that human exposure to some OPFRs could lead to a plasma concentration similar to those exerting in vitro activities, indicating potential concern for human health.