Academic journal article Environmental Health Perspectives

Workgroup Report: Incorporating in Vitro Alternative Methods for Developmental Neurotoxicity into International Hazard and Risk Assessment Strategies

Academic journal article Environmental Health Perspectives

Workgroup Report: Incorporating in Vitro Alternative Methods for Developmental Neurotoxicity into International Hazard and Risk Assessment Strategies

Article excerpt

This is the report of the first workshop on Incorporating In Vitro Alternative Methods for Developmental Neurotoxicity (DNT) Testing into International Hazard and Risk Assessment Strategies, held in Ispra, Italy, on 19-21 April 2005. The workshop was hosted by the European Centre for the Validation of Alternative Methods (ECVAM) and jointly organized by ECVAM, the European Chemical Industry Council, and the Johns Hopkins University Center for Alternatives to Animal Testing. The primary aim of the workshop was to identify and catalog potential methods that could be used to assess how data from in vitro alternative methods could help to predict and identify DNT hazards. Working groups focused on two different aspects: a) details on the science available in the field of DNT, including discussions on the models available to capture the critical DNT mechanisms and processes, and b) policy and strategy aspects to assess the integration of alternative methods in a regulatory framework. This report summarizes these discussions and details the recommendations and priorities for future work. Key words: high-throughput screening, in vitro developmental neurotoxicity models, regulatory use, validation. Environ Health Perspect 115:924-931 (2007). doi:10.1289/ehp.9427 available via [Online 6 February 2007]


Chemicals present in the environment have a potential impact on neurodevelopment and children's health. In recent years, much attention has been given to model development and risk assessment procedures for reproductive toxicity, but the specific area of developmental neurotoxicity (DNT) has been relatively neglected in testing and risk assessment studies. Although epidemiologic and animal studies on developmental neurotoxicants have been carried out (Evangelista de Duffard and Duffard 1996), most chemicals in use have been tested scarcely or not at all for DNT. To properly assess the risk of chemicals for human health, data on DNT are necessary and this need is recognized by all stakeholders.

In 1998, the U.S. Environmental Protection Agency (U.S. EPA 1998) published the Health Effects Test Guidelines OPPTS 8706300 on DNT (U.S. EPA 712-C-98-239), and the Organisation for Economic Co-operation and Development (OECD) is currently finalizing a new draft Test Guideline (TG) for DNT (OECD 2006). To support and promote these efforts, this workshop focused on two immediate needs for DNT testing: first, the identification of in vitro and nonmammalian alternative methods that may recapitulate critical aspects of the development of the human nervous system; and second, how results from such alternative methods could be integrated into current in vivo testing strategies and the existing regulatory framework. Our hope is that this approach will decrease the number of chemicals reliant on DNT data solely from in vivo mammalian DNT tests and, consequently, refine, reduce--and maybe partly replace--the need for animal testing. Furthermore, we hope this workshop report will provide the basis for discussion in the expert communities on DNT testing and that such a discussion will identify the best steps forward.

Definition of DNT

Chemicals may adversely affect the nervous system in various ways (Ray 1999). They may perturb commitment of neural stem cells, proliferation of neuronal progenitor cells, cell migration, synaptogenesis, cell death, formation of transmitters and receptors, trimming of connections, myelinization, and development of the blood-brain barrier (BBB). Impairment of the nervous system can lead to a variety of health effects such as altered behavior, mental retardation, and other neurodevelopmental disabilities and diseases (Li et al. 2005; Olney 2002; Rodier 1995).

For the purpose of this report, DNT is defined as the adverse effects of substances (regulated foreign compounds or xenobiotics) on the nervous system associated with exposure during development. …

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