Testing methods for developmental neurotoxicity of environmental chemicals

Human brain development is slow and delicate, involving many unique, though interrelated, cellular events. The fetus and child are often more suscepti ble to chemical toxins that alter the structure and/or function of the brai n, although susceptibility varies for individual neurotoxicants. Early expo sure to neurotoxins has been implicated in neurological diseases and mental retardation. Pesticide exposures pose a particular concern since many are designed to be neurotoxic to pests and can also affect humans. Acknowledgin g the potential for vulnerability of the developing brain, EPA recently beg an to "call in" data on developmental neurotoxicity (DNT) from manufacturer s of pesticides already registered and considered to be neurotoxic-around 1 40 pesticides. Chemicals are to be tested following the DNT testing guideli ne (OPPTS 870.6300). This paper assesses whether tests performed according to this guideline can effectively identify developmental neurotoxicants. We found the testing guideline deficient in several respects, including: It i s not always triggered appropriately within the current tiered system for t esting; It does not expose developing animals during all critical periods o f vulnerability; It does not assess effects that may become evident later i n life; It does not include methodology for consideration of pharmacokineti c variables; Methodology for assessment of neurobehavioral, neuropathologic al, and morphometry is highly variable; Testing of neurochemical changes is limited and not always required. We propose modifications to the EPA testi ng guideline that would improve its adequacy for assessing and predicting r isks to infants and children. This paper emphasizes that deficiencies in th e testing methodology for developmental neurotoxicants represent a signific ant gap and increase the uncertainty in the establishment of safe levels of exposure to developing individuals, (C) 2000 Academic Press.