Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route
Endpoint conclusion:
no study available
Effect on fertility: via inhalation route
Endpoint conclusion:
no study available
Effect on fertility: via dermal route
Endpoint conclusion:
no study available

Effects on developmental toxicity

Description of key information
In Wistar rats no maternal and developmental toxicity was detected in a gavage study according to OECD Guideline 414 even at the high dose level of 1000 mg/kg bw/day (related to dry weight) which corresponds to the limit dose recommended in the Guideline. 
Effect on developmental toxicity: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
1 000 mg/kg bw/day
Species:
rat
Effect on developmental toxicity: via inhalation route
Endpoint conclusion:
no study available
Effect on developmental toxicity: via dermal route
Endpoint conclusion:
no study available
Additional information

In a dose-range-finding study (limited validity concerning maternal and developmental toxicity) 5 pregnant Wistar rats were gavaged with 0, 100, 300, 1000 mg/kg bw/day (related to dry mass) at day 6 -20 post coitum. No maternal toxicity was evident (all rats with live fetuses; no clinical signs; no effects on food consumption, mean body weight and body weight gain, no effects on corrected body weight gain or reproduction parameters). Necropsy at day 21 post coitum revealed no test item-related findings. No treatment-related effects were found on the fetal sex ratio, fetal body weights, and no abnormal findings during external examination. Therefore, dose levels of 100, 300 and 1000 mg/kg bw /day (related to dry mass) were considered appropriate for a main prenatal developmental toxicity study in the rat.

In the subsequent GLP study according to OECD guideline 414 (adopted 2001) groups of 22 pregnant Wistar rats were gavaged day 6 -20 post coitum (pc) with 0, 100, 300, or 1000 mg/kg bw/day (related to dry weight of the liquid test item; vehicle water; application volume 10 mL/kg bw); the study was terminated day 21 pc. Stability and homogeneity of the test substance has been shown. Non-pregnant rats were found only 2/22 in control and 1/22 in the low dose group. No clinical signs were detected. The mean food consumption was significantly reduced from day 6 to 9 post coitum in the high dose group, however, this transient reduction was considered to be test item-related but not adverse (no effect on body weight; reduction less than 10%). The mean body weight and body weight gain was similar in all groups and also no effects on corrected body weight gain was observed. No effects were seen on post-implantation loss and mean number of fetuses. Necropsy revealed no test item-related findings. Furthermore, no treatment-related effects were detected on the fetal sex ratio, fetal body weights, implantations, resorptions, dead fetuses, or abnormal fetuses. No test item related increase in external, visceral, or skeletal malformations or variations were found. Significantly higher incidence of incompletely ossified sternebra 5 was noted at the high dose level. Since this incidence was in the range of the historical control data it was considered to reflect the range of natural biological variability. In conclusion, the NOAEL for maternal and developmental toxicity is 1000 mg/kg bw/day (dry mass).

Justification for classification or non-classification