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Developmental neurotoxicity – challenges in the 21st century and in vitro opportunities

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Lena Smirnova1, Helena T. Hogberg1, Marcel Leist2, and Thomas Hartung1,2
Centers for Alternatives to Animal Testing (CAAT) at
1 Johns Hopkins Bloomberg School of Public Health, USA, and
2 University of Konstanz, Germany

Summary


In recent years neurodevelopmental problems in children have increased at a rate that suggests lifestyle factors and chemical exposures as likely contributors. When environmental chemicals contribute to neurodevelopmental disorders developmental neurotoxicity (DNT) becomes an enormous concern. But how can it be tackled? Current animal test-based guidelines are prohibitively expensive, at $1.4 million per substance, while their predictivity for human health effects may be limited, and mechanistic data that would help species extrapolation are not available. A broader screening for substances of concern requires a reliable testing strategy, applicable to larger numbers of substances, and sufficiently predictive to warrant further testing. This review discusses the evidence for possible contributions of environmental chemicals to DNT, limitations of the current test paradigm, emerging concepts and technologies pertinent to in vitro DNT testing and assay evaluation, as well as the prospect of a paradigm shift based on 21st century technologies.

 

Keywords: environmental exposure, developmental neurotoxicity, species extrapolation, predictivity

 

 

ALTEX 31(2), 129–156


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