Fertility and general reproductive performance

Reproduction studies (fertility and general reproductive performance, embryo-toxicity and peri/postnatal toxicity) ... 

Segment I fertility and general reproductive performance study. This is an overall screening study. 

IRDC. 1984. Study of fertility and general reproductive performance in rats (IR-83-145). International Research and Development Corporation Mattawan, MI. 

Studies of the compound citral indicated that the developmental toxicity no-observed-adverse-effect level (NOAEL) in rats was approximately 60 mg/kg (Delgado et al. 1993). In rats exposed to citral vapor, no adverse effects on fetuses were observed up to or above levels that were toxic to the mothers (Gaworski et al. 1992). Studies of the compound P-myrcene indicated that the NOAEL for fertility and general reproductive performance was 300 mg/kg daily (Paumgartten et al. 1998), whereas that for developmental toxicity was 250 mg/kg (Delgado et al. 1993) and that for the compound citral was below 60 mg/kg (Delgado et al. 1993). 

Typical toxicity tests do not allow for evaluation of reproductive toxicity, which can be defined as effects on the ability to reproduce, or on the survivability of embryos, fetuses, or infants. Therefore, specific tests were developed to specifically address this important area of potential toxicity. The testing guidelines include separate tests to evaluate the development of the fetus, fertility of the adults, and general reproductive performance (table 5.4). Each test requires a year or more to complete, and the tests are generally quite expensive. 

The analysis of effects on reproductive performance (including fertility) and development by human recombinant proteins is a complex issue. In general, non-human primates are often the most relevant species. The studies have generally been complicated by abortions however, there has been no evidence of a teratogenic effect (Trown et al, 1986 Terrel and Green, 1993). Particular consideration should be given to development of mechanistic-based studies to avoid the need for non-human primate studies for the next generation of IFN therapies. 

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