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and guidelines have been published by different authorities, such as the Organization for Economic Cooperation and Development (OECD 1983, 1984, 1995, 1996, 2000a,b), the U.S. Environmental Protection Agency (EPA 1998a,b,c,d), and the U.S. Food and Drug Administration (FDA 1994,2000).

This appendix describes experimental animal and in vitro studies that are used to assess developmental toxicity and male and female reproductive toxicity from exposures to pesticides, industrial chemicals, and food ingredients. The testing of pharmaceutical agents is not described in detail here, but can be found in FDA (1994). A summary of the study types, protocols, endpoints and limitations is presented in Table D-1. A description of the manifestations of each type of toxicity and guidance on the interpretation of results from the studies also are presented.


Developmental toxicity is defined as adverse effects in the developing organism that can result from exposure before conception in either parent, exposure during gestation, or exposure during postnatal development from birth to sexual maturation. Adverse developmental effects can be detected at any point in the Life span of the organism. The major manifestations of developmental toxicity include death of the developing organism, structural abnormality, altered growth, and functional deficiency (EPA 1991).

Structural abnormalities in development include malformations and variations. A malformation is usually defined as a permanent structural change that can adversely affect survival, development, or function. The term variation indicates a divergence from the usual range of structural constitution that might not adversely affect survival or health. Because there is a continuum of responses from normal to severely abnormal, distinguishing between variations and malformations can be difficult.

Altered growth can result in an alteration in the size or weight of an organ or in body weight or size of exposed offspring. Changes in one indicator of altered growth might or might not be accompanied by other signs of altered growth. For example, changes in body weight

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