Workshop on the qualitative and quantitative comparability of human and animal developmental neurotoxicity, Work Group IV report: triggers for developmental neurotoxicity testing.
A Work Group was formed to evaluate the criteria considered important in determining when to require developmental neurotoxicity testing in animal studies (i.e., triggers for testing). The primary objective of the Work Group was to determine whether there is sufficient scientific evidence to support the triggers identified by the Environmental Protection Agency and determine whether there is sufficient evidence to use structure activity relationships (SAR) to trigger automatic testing of certain classes of chemicals. A weight of evidence (WOE) approach was recommended by the Work Group in order to assist in determining which agents should undergo developmental neurotoxicity testing and to what level of testing. Evaluation of biological effects, length and duration of exposure, and quality and quantity of data available on an agent should be used in the WOE approach. Agents that are teratogenic to the central nervous system (CNS) were considered of highest priority for developmental neurotoxicity testing, especially if there is the potential for a high degree of exposure. Neuropathic and neuroactive compounds, chemicals with hormone-like activity, and developmental toxicants (with effects other than structural abnormalities of the CNS) were also considered likely candidates for such testing. Although reluctant to recommend testing based solely on SAR or chemical class, the Work Group recognized the importance of considering SAR along with other toxicity data, pharmacokinetic data and potential human exposure in making final requirements or recommendations for further testing.(ABSTRACT TRUNCATED AT 250 WORDS)
Levine
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U.S. Environmental Protection Agency, Washington, DC.
Butcher
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D000818:Animals; D005260:Female; D006801:Humans; D009422:Nervous System Diseases / Q000139:chemically induced* / Q000196:embryology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012306:Risk; D013329:Structure-Activity Relationship; D014116:Toxicology / Q000379:methods*; D014481:United States; D014484:United States Environmental Protection Agency