Abstract
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.
Highlights
Developmental neurotoxicity (DNT) is probably the least tested health effect of chemicals: only about 150 substances have been subjected to the internationally agreed guideline studies
central nervous system (CNS) development is a complex process involving many different events, such as differentiation of progenitor cells, proliferation and cell migration, synaptogenesis, myelination, cell death, synthesis of neurotransmitters, and formation of receptors. These events occur within strictly controlled timeframes and, each event creates a different window of vulnerability to xenobiotic exposure (Rice and Barone, 2000; Rodier, 1994, 1995)
Once neurodevelopment is disturbed there is little potential for repair and it often leads to permanent consequences
Summary
Developmental neurotoxicity (DNT) is probably the least tested health effect of chemicals: only about 150 substances have been subjected to the internationally agreed guideline studies. The decision about whether a chemical should be recognized to have a possible trigger that would require DNT studies can, for example, be based on observations of neurological effects or induced structural abnormalities of the CNS.
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