Recent developments in regulatory requirements for developmental toxicology

A number of legislative and regulatory changes have occurred over the past 5 years to prompt the re-evaluation of the regulatory requirements for deve lopmental toxicity testing and use of the data for risk assessment. In part icular, passage of the 1996 Food Quality Protection Act (FQPA) in the Unite d States required the USEPA to evaluate children's health risks in a more r igorous fashion, and to apply an additional 10-fold safety factor if data w ere inadequate or children appeared to be more sensitive than adults. A rev iew of the testing protocols required by USEPA led to extension of the dosi ng period to term in the prenatal developmental toxicity study and the addi tion of endpoints to the 2-generation reproduction study protocol as indica tors of possible neurologic, reproductive, or immune alterations. Revised t esting guidelines for pesticides and toxic substances were published by USE PA in 1998, including a developmental neurotoxicity testing protocol. Furth er review for FQPA implementation resulted in the proposal for a core set o f required toxicology studies, including routine developmental neurotoxicit y, adult neurotoxicity. and adult immunotoxicity studies. In addition, deve lopment of new testing guidelines in several areas was recommended. these g uidelines to be used in conjunction with Or as follow-up when indicated Fro m standard testing: developmental immunotoxicity, carcinogenesis, specializ ed neurotoxicity studies, endocrine disrupter studies, pharmacokinetics, an d direct dosing of neonates. The impact of these efforts on the policies fo r toxicity testing of pesticides are discussed, and these issues are curren tly being reviewed on a broader scale, in particular, by evaluating the ade quacy of the methods used for reference values (e.g. chronic RfD, RfC). Thr ee major areas of focus for this review include life stages evaluated, endp oints assessed, and the duration of exposure used in various studies. A maj or focus of these efforts is to ensure that children's health risks are bei ng adequately addressed in the risk assessment process. (C) 2001 Elsevier S cience Ireland Ltd. All rights reserved.