Reproduction toxicity tests

This chapter briefly describes the current standard study designs and then focuses on current issues in developmental and reproductive toxicity testing. 

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. 

Test Guidelines Adopted for Reproductive Toxicity Testing Title... 

Overview of In Vivo Reproductive Toxicity Test Guideline Studies... 

In the OECD Draft Guidance Document on Reproductive Toxicity Testing and Assessment (OECD 2004d), the term endocrine disruption is defined as above. 

OECD. 2004d. Draft guidance document on reproductive toxicity testing and assessment. OECD Series on Testing and Assessment No. 43. Environment Directorate, Joint Meeting of the Chemicals Committee and the Working Party on Chemicals, Pesticides and Biotechnology. November 10, 2004 (1st version). Paris OECD. 

Reproductive toxicity tests are not required to support Phase I clinical studies in men. Detailed histological evaluations of the male reproductive organs should be performed in the repeated-dose toxicity studies. Male fertility studies in the rodent, however, would be expected to support Phase III studies. 

The FDA allows women to enter carefully controlled and monitored trials in which adequate contraceptive measures and pregnancy testing are performed without requiring results from animal reproductive toxicity tests. In Japan and Europe, because of the high level of concern regarding imintentional exposure of the developing embryo or foetus, an assessment of fertility in a rodent, and embryo/foetal development in a rodent or non-rodent are required if women of childbearing potential are to be included in a Phase I trial. The FDA would expect such results to support Phase II and Phase III studies. 

Less complex test systems, including nonmammalian and in vitro cultures, are recommended only for pre-screening or secondary studies to elucidate mechanisms. A useful statement for use with lACUC committees comes from this section, as follows In short, there are no alternative test systems to whole animals currently available for reproduction toxicity testing with the aims set out in the introduction. ... 

Barrow PC (2009) Reproductive toxicity testing for pharmaceuticals under ICH. Reprod Toxicol 28 172-179... 

Nonclinical Reproductive Toxicity Testing Requirements for Drugs, Pesticides, and industriai Chemicais in india and China... 

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