title: Adequacy of required regulatory hazard testing for the detection of potential hormonal activity of crop protection chemicals.
abstract: The capacity of some synthetic chemicals, the so-called "endocrine-disrupting chemical," to alter hormonal activity, as well as the adequacy of the testing of chemicals to evaluate this capacity, has been called into question. Among the chemicals indicted have been certain crop protection agents or pesticides. Crop protection chemicals rank among the most closely regulated and thoroughly tested chemicals in use in both the human health and environmental hazard areas. However, it has been proposed that in vitro and in vivo screening tests be used to identify potential endocrine-active chemicals and to supplement or replace required regulatory bioassays. In vitro tests, such as receptor binding, examine a single chemical event, do not measure toxicity, post-receptor-mediated biological response, or the absorption, distribution, metabolism, and elimination of a chemical. Therefore, data derived solely from such a limited testing technique should not be used as a basis for selection of chemicals for making regulatory decisions. In vivo screening tests, such as the uterotrophic assay, which promise to provide a rapid answer to a targeted question, do not capture the complexity of the biological response. As in the case with in vitro tests, results from a single in vivo test, such as a change in uterine weight, should not be used as a basis for regulatory decision making. Further, it has been suggested that such a screening battery should be put into place for ecotoxicity testing. Yet it is well recognized that endocrine-active chemicals that affect fish and wildlife in their natural habitat have been shown to cause similar adverse effects in laboratory test animals. Therefore, these screening tests do not add value to the current regulatory test battery. Evidence is presented that demonstrates that the regulatory safety assessment paradigm has a low likelihood of missing potential endocrine-active chemicals and has served society well.
authors.affiliation: Department of Toxicology, Novartis Crop Protection, Inc., Greensboro, NC 27419-8300, USA.
authors.forename: J T
authors.initials: JT
authors.lastname: Stevens
authors.forename: W
authors.initials: W
authors.lastname: Gfeller
authors.forename: L
authors.initials: L
authors.lastname: Machemer
authors.forename: K H
authors.initials: KH
authors.lastname: Leist
mesh_terms: D000818:Animals; D004285:Dogs; D004703:Endocrine System / Q000187:drug effects; D005333:Fetus / Q000187:drug effects; D017408:Guidelines as Topic; D006801:Humans; D051379:Mice; D010575:Pesticides / Q000633:toxicity*; D011817:Rabbits; D051381:Rats; D012098:Reproduction / Q000187:drug effects
chemical_list: D010575:Pesticides