Workshop on the qualitative and quantitative comparability of human and animal developmental neurotoxicity, Work Group II report: testing methods in developmental neurotoxicity for use in human risk assessment.
The Work Group addressed the design and content of a basic screening battery for detecting or flagging developmental neurotoxicity. It was agreed that a basic screening battery should be incorporated routinely into any developmental or reproductive toxicity study conducted for risk assessment purposes, and that a "triggered" stand-alone developmental neurotoxicity study, as exemplified by the current EPA proposal, should include greater in-depth evaluation of CNS function and pathology. Time constraints did not permit the group to address the design or content of such a stand-alone study. It was acknowledged unanimously that a basic screening battery may provide more information than simply the detection of neurotoxicity; however, it should not be expected to provide detailed dose-response information nor to identify the precise mechanism of agent action. The Work Group also agreed that a basic screening battery should include evaluation of multiple CNS functions, that observed alterations may be indicative of primary or secondary effects on the nervous system, that the test methods selected may differ based on what is known about the agent, and that the protocol for study conduct can be as important as the methods employed. In light of these assumptions, the Work Group recommended schedules for monitoring offspring development using measures of: 1) physical landmarks, 2) brain weights, 3) neuropathology, 4) functional observations, 5) motor activity, 6) reactivity, and 7) learning and memory. The species tested, sample sizes, treatment parameters, etc., would be determined by the type of developmental or reproductive toxicity study into which the basic screening battery was incorporated.(ABSTRACT TRUNCATED AT 250 WORDS)
Lilly Research Laboratories, Eli Lilly & Co., Greenfield, IN 46140.
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Buelke-Sam
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Mactutus
D000818:Animals; D005260:Female; D006801:Humans; D009422:Nervous System Diseases / Q000139:chemically induced* / Q000196:embryology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012306:Risk; D014116:Toxicology / Q000379:methods*; D014481:United States; D014484:United States Environmental Protection Agency