Registration Dossier

Administrative data

Endpoint:
toxicity to reproduction
Data waiving:
other justification
Justification for data waiving:
other:
Justification for type of information:
The following information is taken into account for any hazard / risk assessment:
Information from the repeated dose oral study in rats does not suggest any effects on male or female sex organs even at systemic toxic dose levels. In the 28-day repeated dose study organ weights of testes, epididymes and ovaries were comparable to controls and no histopathological chages were observed in these organs up to the highest dose tested. Additional information on fertility is therefore not regarded as priority at this point in time. According to the review Mangelsdorf and Buschmann (2002) who compared information obtained in repeated dose studies on male fertility with those obtained in fertility studies, a 28 -day repeated dose study in which weights of testes and histopathology is determined is already sufficient to detect effects on male fertility. They also conclude that if at the highest dose levels, which produce significant toxicity in other organ systems, no effects on any of these parameters have been found, it can be concluded with a high level of confidence, that a compound is not a male reproductive
toxicant. Further testing on this endpoint should be considered to be of low priority.

References:
Mangesldorf I, Buschman J, Federal Institute of Occupational safety and Health, Extrapolation from Results of Animal studies to humans for the endpoint male fertility, Dortmund, Berlin, Dresden 2002).
Aulmann W., Regul Toxicol Pharmacol.2012 Jul;63(2):286-90. Epub 2012 Mar 28.

Data source

Materials and methods

Results and discussion

Overall reproductive toxicity

Reproductive effects observed:
not specified

Applicant's summary and conclusion