Chemical testing strategies for predicting health hazards to children

The United States Environmental Protection Agency has proposed the developm ent of a Children's Health Test Program under the Toxic Substances Control Act. The Environmental Protection Agency's proposal for the children's heal th test battery has 12 different assays including general toxicity, genotox icity, carcinogenicity, neurotoxicity, and developmental and reproductive t oxicity. The current Environmental Protection Agency testing proposal is an "all or nothing" test battery. An alternative and preferable approach woul d be to use a science-based, tiered testing scheme. It is proposed that the Screening Information Dataset program, currently used by the Organization for Economic Go-operation and Development (OECD) for the Screening Informat ion Dataset-High Production Volume test battery, or equivalent, be consider ed for the first step. Step 1 would include acute and repeat dose toxicity testing, developmental toxicity testing (first species OECD 414 or OECD 422 ), reproductive toxicity screening (OECD 415 or 422), and genetic toxicity testing. For this step, the rat would be the initial and only species teste d unless the mouse was used for in vivo genetic toxicity. Step 2 of the pro posed children's health test battery would include developmental testing (s econd species OECD 414) or special mode of action studies performed for tho se chemicals that proved to be developmental toxicants in Step 1. Those che micals that tested positive as reproductive toxicants in Step 1 would be te sted in a two-generation reproduction study (OECD 416) or a special mode of action study. Steps 1 and 2 provide information on whether oncogenicity or developmental neurotoxicity testing is useful. Step 3 would include chroni c toxicity/oncogenicity testing for those chemicals that tested positive fo r genetic toxicity in Step 1, and positive for developmental concerns in St ep 2. In this step, chemicals would also be tested for developmental neurot oxicity if they showed evidence of neuropathy, behavioral effects, or neuro toxic potential in earlier studies. This stepwise approach would conserve r esources and answer scientific questions in a logical, orderly, timely, and cost-effective manner. (C) 2000 Elsevier Science Inc. All rights reserved.