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Key value for chemical safety assessment

Effects on fertility

Additional information

In a guideline study (OECD 422) the test substance was administered by daily oral gavage to male and female Wistar rats at dose levels of 0, 10, 25 or 50 mg/kg body weight/day. The males were exposed for 2 weeks prior to mating, during mating, and up to termination (for 28 days). The females were exposed for 2 weeks prior to mating, during mating, duringpost-coitum,and at least 3 days of lactation (for 38 to 56 days).

There were no changes for reproduction, breeding data and pup development that were considered to be an effect of treatment.The definitive reproduction, breeding and developmental NOAEL was established as being 50 mg/kg body weight/day for the test material.

In another study the reproductive capacities of male Sprague Dawley rats after exposure to test substance were analysed. Therefore hormone studies and an analysis of sperm and testes morphology were performed. For both studies 10 mg/kg bw of test substance were applied. For hormone studies: intraperitoneal injection of test substance were performed, for analysis of sperm and testes morphology subcutaneous implanted mini pump provided the test substance.

The test substance had no effect on the concentration of plasma cholesterol and testicular interstitial fluid progesterone, 17 alpha-hydroxyprogesterone and androstenedione. In addition the analysis of sperm and testes morphology showed no changes.

Short description of key information:

Based on the the fact that no changes in reproduction, breeding and pup development were seen in this OECD 422 study (repeated substance application via oral gavage (28 to 56 days), study conducted under GLP standards) the NOAEL was reported to be 50 mg/kg body weight/day in rats.

Effects on developmental toxicity

Additional information

Within the above mentioned combined repeated dose toxicity study with reproduction /developmental toxicity screening study (OECD 422) effects on pre- and perinatal pup development of the submission substance were investigated. Under the above described conditions (test substance administration via daily oral gavage to male and female Wistar rats, dose levels of 0, 10, 25 or 50 mg/kg body weight/day; males 28 days; females 38 to 56 days) there were no effects seen in pup development (effects examined e.g. body weight, external abnormalities, viability).Therefore a developmental NOAEL of 50 mg/kg body weight/day (i.e. highest dose tested) was reported.

Justification for classification or non-classification

Based on the negative findings in the combined repeated dose toxicity study with reproduction / developmental screening test and no effects on male fertility as seen in the non standard test in rats (hormone analysis and sperm and testis morphology) the submission substance has not to be classified for toxicity to reproduction according to Regulation (EC) No. 1272/2008 and Council Directive 67/548/EEC.

Additional information