Registration Dossier

Administrative data

Endpoint:
two-generation reproductive toxicity
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
other:
Justification for type of information:
REACH allows the assessment of the reproductive toxicity of a given chemical with the help of findings from studies with repeated administration. This is in line with the idea that the information requirements under REACH are regarded as the evaluation of endpoints which does not necessarily require data from specific studies. The test substance was tested in a 28 and 90-day repeated dose study (in rats) (Ciba Geigy Ltd., 1986 and 1987), in a prenatal OECD 414 study (Ciba Geigy Ltd., 1987). None of these studies showed any concern regarding reproductive toxicity of the test substance. Thus, a two-generation study is regarded as redundant. This waiving argument is in line with the guidance document R7a and is further justified as followed: Because of a high correlation, histopathology data and organ weights from repeated dose studies may be used to assess male fertility (Mangelsdorf, 2003). These parameters, taken from 90 day studies, were in fact shown to be more sensitive than fertility parameters measured during multi-generation studies. It could also be shown that exposure for 4 weeks suffices for an assessment of male fertility, although 90 day studies have been regarded as superior in the past because they cover a complete cycle of spermatogenesis (Mangelsdorf, 2003). If such a 28 day study shows neither relevantly elevated testis or ovary weights nor histopathological alterations in those organs, the weight of the evidence is that effects on reproduction are also not expected (BAuA Forschungsbericht Fb 984, 2003). A comparison of more than one hundred 90 day studies with two-generation studies that used the same test substance additionally showed that the NOAELs differed by less than the variation limit of studies, i.e. a factor of two (Janer, 2007). Therefore, the information gained from a two-generation study can be regarded as minimal if a 90 day study has been performed. Accordingly, there is no need for evaluation on a second species. References: - BAuA (2003). Extrapolation from results of animal studies to humans for the endpoint male fertility. Forschungsbericht Fb 984. - Janer G, Hakkert BC, Piersma, AH, Vermeire T, Slob W (2007). A retrospective analysis of the added value of the rat two-generation reproductive toxicity study versus the rat subchronic toxicity study. Reproductive Toxicol 24: 103-113 - Mangelsdorf I, Buschmann J, Orthen B (2003). Some aspects relating to the evaluation of the effects of chemicals on male fertility. Reg Toxicol Pharmacol 37: 356-369

Data source

Materials and methods

Results and discussion

Overall reproductive toxicity

Reproductive effects observed:
not specified

Applicant's summary and conclusion