Fertility studies reproductive/developmental toxicity testing

Common Study Protocols. The dog is the most commonly used nonrodent species in safety assessment testing (i.e., acute, subchronic, and chronic studies). The exception to this is its use in developmental toxicity and reproductive studies. For developmental toxicity studies, the dog does not appear to be as sensitive an indicator of teratogens as other nonrodent species such as the monkey (Earl et al., 1973) or the ferret (Gulamhusein et al., 1980), and, for reproductive studies, the dog is not the species of choice because fertility testing is difficult to conduct (due to prolonged anestrus and the unpredictability of the onset of proestrus) and there is no reliable procedure for induction of estrus or ovulation. 

The combined repeated dose toxicity study with the reproduction/developmental toxicity screening test (OECD TG 422, US-EPA OPPTS 870.3650) comprises a basic repeated dose toxicity study and a fertility/developmental toxicity screening test and, therefore, can be used to provide initial information on possible effects on a limited number of reproductive performance parameters. The test does not provide complete information on all aspects of reproduction, has a relatively short period of exposure, and does not provide evidence for dehnite claims of no reproductive effects, while positive results are useful for initial hazard assessment. Furthermore, results regarding repeated dose toxicity are influenced by the pregnant state of the female animals (see also Sections 4.7.3.1 and 4.7.5.2.2). 

OECD TG 421 and TG 422 Reproduction/ Developmental Toxicity Screening Test (with or without the Combined Repeat Dose Toxicity Study) From 2 weeks prior to mating until at least day 4 postnatally 3 dose levels plus control n = 8-10 pregnant females Fertility Pregnancy length and birth Fetal and pup growth and survival until day 3 + short-term test - limited exposure period - limited number of end-points - limited sensitivity due to number of animals... 

If peri-postnatal tests, developmental neurotoxicity smdies, or specific male or female fertility studies are available they can be used to identify a substance as being toxic to reproduction. Data from such studies alone cannot be used to identify a substance as being of no concern in relation to reproduction. 

Bisphenol A causes adverse reproductive and developmental effects in animal studies. But, is the weight of evidence sufficient to consider bisphenol A of high or moderate concern for reproductive and/or developmental toxicity In 2003, the European Union concluded that bisphenol A may adversely affect fertility (reproductive toxic) and that low dose studies indicate bisphenol A may be a development toxicant. Since the EU risk assessment of bisphenol A, a significant body of experimental data has been published evaluating the toxicity potential of bisphenol A at low doses. There is considerable debate on which studies are relevant for evaluating low dose effects of bisphenol A. Issues in the debate include the type of animal studied (the Charles River-Sprague Dawley rat, for example, is the least sensitive test animal to estrogenic chemicals), the... 

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