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Administrative data

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route
Dose descriptor:
NOAEL
150 mg/kg bw/day
Additional information

Based on two oral studies in rats no treatment-related effects were recorded on fertility, offspring viability, growth or development . The oral doses across the two studies ranged from 16.7 to 250 mg/kg/day. In one study (Knox and Brooks) the dose of 150 mg/kg/day induced severe effects in females probably due to dystocia. However, this was not repeated at the same dose in the other study (Saillenfait et al) and only recorded for two females exposed at 200 mg/kg/day. Maternal weight gain and food consumption were significantly reduced at and above 200 mg/kg/day.

There was no significant increase in the incidence of resorptions, or malformations, at any dose in either of the two studies. In the

Saillenfait et al study fetal body weight was significantly reduced at and above 200 mg/kg/day but significant effects on skeletal development were only recorded at 250 mg/kg/day. Thus, DAP caused fetal toxicity at doses which also produced maternal effects (> 150 mg DAP/kg/day), but which did not affect fertility or induce significant embryo-lethality or teratogenicity.

Short description of key information:
The key information is based on the results of a guideline study performed under GLP in 2003 and a study published in 2008 (see the section of Developmental Toxicity). The study method used concerns a reproduction/developmental toxicity screening test [OECD TG 421] with parental exposure prior to mating until 1 to 4 days post partum. Endpoints related parameters examined include histopathological changes in the reproductive organs of parental animals as well as offspring viability, growth and development.

Effects on developmental toxicity

Description of key information
See section Effects on fertility.
Effect on developmental toxicity: via oral route
Dose descriptor:
NOAEL
150 mg/kg bw/day
Additional information

See section Effects on fertility.

Justification for classification or non-classification

The classification system for reproductive toxicity is subdivided in adverse effects on sexual function and fertility and adverse effects on development of the offspring. The key information provided here indicates that sexual function and fertility are not affected by oral DAP exposure at doses that induce parental and foetal toxicity. Although, there are indications that the gestation period might be delayed at lower dose levels, these proved not to be consistent or reproducible. Further, these were recorded at a dose that also induced histopathological changes in the liver. Developmental toxicity concerned mainly fetal body weight and only minimal differences in skeletal variations and malformations. Also these were only recorded at dose levels, which also affected maternal body weight

Classification was not considered, because only minor effects were recorded in skeletal examinations, and foetal weights were affected at dose levels that also affected maternal body weights.