Workshop on the qualitative and quantitative comparability of human and animal developmental neurotoxicity, Work Group I report: comparability of measures of developmental neurotoxicity in humans and laboratory animals.
Assessment measures used in developmental neurotoxicology are reviewed for their comparability in humans and laboratory animals, and their ability to detect comparable adverse effects across species. Compounds used for these comparisons include: substances of abuse, anticonvulsant drugs, ethanol, methylmercury, lead, PCBs, and ionizing radiation. At the level of functional category (sensory, motivational, cognitive and motor function, and social behavior), close agreement was found across species for all neurotoxic agents reviewed, particularly at high exposure levels. This was true even though the specific end points used to assess these functions often varied substantially across species. In addition, it was found that: 1) the U.S. EPA Developmental Neurotoxicology Test Battery presented at the Workshop would have identified the hazard to humans of exposure to the above compounds, although it may have underestimated human risk in some cases; 2) assessment of developmental neurotoxicity should involve evaluation of all categories of function; 3) for most compounds reviewed, the neurotoxic effects of prenatal exposure cannot be attributed to maternal toxicity, and exposure at or just below the threshold for such toxicity is an appropriate upper level for developmental neurotoxicity testing; 4) maternal exposure during the postnatal period poses a number of serious methodological problems; and 5) animal studies would better parallel human studies if more emphasis was placed on evaluation during development.
Stanton
M E
ME
Neurotoxicology Division, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711.
Spear
L P
LP
D000818:Animals; D000927:Anticonvulsants / Q000009:adverse effects / Q000633:toxicity; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000209:etiology; D006801:Humans; D007231:Infant, Newborn; D007854:Lead / Q000009:adverse effects / Q000633:toxicity; D008767:Methylmercury Compounds / Q000633:toxicity; D009357:Neonatal Abstinence Syndrome; D009422:Nervous System Diseases / Q000139:chemically induced / Q000196:embryology / Q000209:etiology*; D011078:Polychlorinated Biphenyls / Q000009:adverse effects / Q000633:toxicity; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011839:Radiation, Ionizing; D014481:United States; D014484:United States Environmental Protection Agency
D000927:Anticonvulsants; D008767:Methylmercury Compounds; D007854:Lead; D011078:Polychlorinated Biphenyls