Workshop on the qualitative and quantitative comparability of human and animal developmental neurotoxicity, Work Group III report: weight of evidence and quantitative evaluation of developmental neurotoxicity data.
Work Group III discussed the qualitative and quantitative evaluation of developmental neurotoxicity data for risk assessment purposes. The Work Group concurred with the assumption that developmental neurotoxicity may result from as little as a single exposure, dependent on dose and gestational time of exposure. Maternal toxicity, during the pregnancy and/or lactational period, may confound interpretation of effects observed in the offspring, but the majority of the group agreed that if significant effects were observed in a developmental neurotoxicity study, these effects should be presumed relevant to potential risk in humans. Others in the group indicated that these effects should be designated developmental toxicity but not necessarily developmental neurotoxicity. Concurrent toxicity (in the same organism, at the same dose, etc.) was also discussed, with the same concern as with maternal toxicity, i.e., are the results observed from developmental neurotoxicity per se or from other toxicity impacting on and confounding the neurotoxicity test results. A majority of the group regarded any effect observed in a neurotoxicity test as consistent with developmental neurotoxicity. The minority reserved this designation only for neurotoxic results observed at the lowest adverse effect level and in the absence of other developmental toxicity. Discussion on weighting tests in the battery focussed on apical tests which require the most integrated functions with the caveat for confounding effects from other toxicities. Developmental neurotoxicity data were viewed as potentially useful in establishing a reference dose. The interpretation of statistically significant findings was discussed with caveats for Type I errors, consistency, biological plausibility of findings, and the concern that current draft guidelines and test rules require adult toxicity with the risk of confounding.(ABSTRACT TRUNCATED AT 250 WORDS)
Bushy Run Research Center/Union Carbide Corporation, Export, PA 15632.
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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; D014481:United States; D014484:United States Environmental Protection Agency