Guidelines for Reproductive Studies

Food and Drug Administration (1966). Guidelines for Reproduction Studies for Safely Evaluation of Drugs for Human Use. Drug Review Branch, Division of Toxicological Evaluation, Bureau of Science, Food and Drug Administration, Washington, D.C. 

Bloom AD (1981) Guidelines for reproductive studies in exposed human populations. Guideline for studies of human populations exposed to mutagenic and reproductive hazards. Report of Panel II. White Plains. New York, March of Dimes Birth Defects Foundation, pp 37-110. 

US FDA (1966) Guidelines for reproduction studies for safety evaluation of drugs for human use. Rockville, Maryland, US Food and Drug Administration. 

Formal testing guidelines were established after thalidomide disaster. In 1966 guidelines were established by the FDA Guidelines for Reproduction Studies for Safety Evaluation... 

Drug Administration (FDA) established Guidelines for Reproductive Studies for Safety Evaluation of Drugs for Human Use (31). These... 

Effects manifesting during the ageing process are not included in any guideline for reproductive toxicity. For example, the reproductive span of females is limited from the time of sexual maturation to reproductive senescence. The time of sexual maturation may be assessed in the two-generation study, but reproductive senescence is not assessed. Consequently, effects on the reproductive span of females are not covered in the reproductive toxicity test guidelines. 

The ICFI has recently (1994) promulgated harmonized testing guidelines for reproductive toxicity in five study designs adopted by the European Union, Japan, and the United States in 1996 (Figure 4). 

In May 1980, Notification 698 from the MHLW specified the type of data required for the evaluation of safety in animals and Guidelines for Toxicity Studies were subsequently established in 1984. It is necessary to generate data on acute, sub-acute and chronic toxicity, effect on reproduction, dependence, antigenicity, mutagenicity, carcinogenicity and local irritation. 

Bloom, A. D., Ed. "Guidelines for Studies of Human Populations Exposed to Reproductive Hazards " March of Dimes Birth Defects Foundation New York, 1981, passim. 

Specific reproductive toxicity test guidelines have been published by OECD, US-EPA, and EU, see Table 4.18. In the following text, the principles of the various OECD tests are briefly described. Table 4.19 summarizes the various OECD test guideline studies for reproductive toxicity in more detail, including the parameters examined in each test, in order to provide a brief overview of the similarities and differences between the various reproductive toxicity smdies. 

In vitro studies will not, in the absence of more definitive data, provide a basis for a firm decision about the reproductive toxicity of a substance. Positive results from such smdies indicate that there may be some concern in relation to the potential for reproductive toxicity, but they can be overridden by clearly negative data from well-conducted test guideline smdies for reproductive toxicity. Negative data from in vitro smdies, if well conducted, may contribute to the weight of evidence. 

There were major differences in the protocol designs for rodent studies between Japanese and European studies. These were resolved by the ICH, which in 1993 published a guideline entitled Detection of Toxicity to Reproduction for Medicinal Products. ... 

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