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Bisphenol A shapes children's brain and behavior: towards an integrated neurotoxicity assessment including human data.

ABSTRACT: Concerns about the effects of bisphenol A (BPA) on human brain and behavior are not novel; however, Grohs and colleagues have contributed groundbreaking data on this topic in a recent issue of Environmental Health. For the first time, associations were reported between prenatal BPA exposure and differences in children's brain microstructure, which appeared to mediate the association between this exposure and children's behavioral symptoms. Findings in numerous previous mother-child cohorts have pointed in a similar worrying direction, linking higher BPA exposure during pregnancy to more behavioral problems throughout childhood as assessed by neuropsychological questionnaires. Notwithstanding, this body of work has not been adequately considered in risk assessment. From a toxicological perspective, results are now available from the CLARITY-BPA consortium, designed to reconcile academic and regulatory toxicology findings. In fact, the brain has consistently emerged as one of the most sensitive organs disrupted by BPA, even at doses below those considered safe by regulatory agencies such as the European Food Safety Authority (EFSA). In this Commentary, we contextualize the results of Grohs et al. within the setting of previous epidemiologic and CLARITY-BPA data and express our disquiet about the "all-or-nothing" criterion adopted to select human data in a recent EFSA report on the appraisal methodology for their upcoming BPA risk assessment. We discuss the most relevant human studies, identify emerging patterns, and highlight the need for adequate assessment and interpretation of the increasing epidemiologic literature in this field in order to support decision-making. With the aim of avoiding a myopic or biased selection of a few studies in traditional risk assessment procedures, we propose a future reevaluation of BPA focused on neurotoxicity and based on a systematic and comprehensive integration of available mechanistic, animal, and human data. Taken together, the experimental and epidemiologic evidence converge in the same direction: BPA is a probable developmental neurotoxicant at low doses. Accordingly, the precautionary principle should be followed, progressively implementing stringent preventive policies worldwide, including the banning of BPA in food contact materials and thermal receipts, with a focus on the utilization of safer substitutes.

SUBMITTER: Mustieles V

PROVIDER: S-EPMC7285610 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Bisphenol A shapes children's brain and behavior: towards an integrated neurotoxicity assessment including human data.

Mustieles Vicente V Fernández Mariana F MF

Environmental health : a global access science source 20200609 1

Concerns about the effects of bisphenol A (BPA) on human brain and behavior are not novel; however, Grohs and colleagues have contributed groundbreaking data on this topic in a recent issue of Environmental Health. For the first time, associations were reported between prenatal BPA exposure and differences in children's brain microstructure, which appeared to mediate the association between this exposure and children's behavioral symptoms. Findings in numerous previous mother-child cohorts have ...[more]

PMID: 32517692

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Project description: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.

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Bisphenol A shapes children's brain and behavior: towards an integrated neurotoxicity assessment including human data.

Publications

Bisphenol A shapes children's brain and behavior: towards an integrated neurotoxicity assessment including human data.

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