Critical aspects in reproductive and developmental toxicity testing of environmental chemicals.
The process of toxicity testing of environmental chemicals is ruled by a framework of guidelines (OECD, OPPTS, etc.). The present paper will describe the process from the biological tests for environmental chemicals up to potential labelling and will focus on some critical aspects in this cascade of events. It is also the aim of this paper to give an overview of the existing documents and draft documents relevant for this field and available in the internet. Based on the current situation, the following points are discussed as critical issues: life stage considerations and their implications on testing, usefulness of investigations in juvenile animals, requirements for ADME studies, design and endpoints in fertility studies, use and usefulness of developmental milestones, performance of special studies versus one-study-design, considerations on transplacental carcinogenicity and early aging, significance of maternal/parental toxicity, application of triggers to justify studies, inclusion of new endpoints into test guidelines, and test strategies applied. Based on this, the usefulness of risk considerations in the current EU classification system for toxicity to reproduction as well as potency considerations will be discussed and suggestions will be made to improve the basic requirements for chemical testing which have remained relatively unchanged over the past 20 years.
Buschmann
Jochen
J
Fraunhofer Institute of Toxicology and Experimental Medicine, Nikolai-Fuchs-Str. 1, 30625 Hannover, Germany. buschmann@item.fraunhofer.de
D000818:Animals; D047108:Embryonic Development / Q000187:drug effects; D005062:European Union; D047109:Fetal Development / Q000187:drug effects; D017408:Guidelines as Topic; D015386:Hazardous Substances / Q000633:toxicity; D006801:Humans; D012098:Reproduction / Q000187:drug effects; D018570:Risk Assessment / Q000379:methods; D018675:Toxicity Tests / Q000592:standards*
D015386:Hazardous Substances