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Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route
Endpoint conclusion:
adverse effect observed
Dose descriptor:
NOAEL
200 mg/kg bw/day
Study duration:
subacute
Species:
rat
Effect on fertility: via inhalation route
Endpoint conclusion:
no study available
Effect on fertility: via dermal route
Endpoint conclusion:
no study available
Additional information

A combined repeat dose and reproductive/developmental toxicity screenng test was reported for a structurally related compound (MIHW, Japan, 1998). For read-across justification see the Annex of the CSR. This study was identified to be well conducted and reported. As for the reproductive ability of parent animals, no effects were detected in males but on estrous cycle examination, continuous diestrous was observed in three females of the 600 mg/kg group and the mean estrous cycle of this group showed extension compared with the control group. There were no effects of the test substance on the copulation or fertility indices. Pathological examination hardly showed abnormalities in the reproductive organs of animals. With regard to the effects on neonates, viability on day 4 of lactation was decreased in the 600 mg/kg group, and male and female pups of the 600 mg/kg group showed lower body weights on day 4 of lactation. There are no significant differences in the delivery index and live birth index. Also, no external and visceral abnormalities related to the test substance were detected in any of the offspring. On the basis of these findings, the NOEL for reproductive toxicity to parental rats was considered to be 600 mg/kg/day for males, and 200 mg/kg for females. Moreover, the NOEL of the test substance to F1 offspring was established to be 200 mg/kg/day.


Short description of key information:
In a combined repeat dose and reproductive/developmental toxicity screenng test with a structurally related compound no adverse findings were reported for male animals. In females, the mean estrous cycle of of high dose asnimals showed extension compared with the control group. The NOAELs are therefore 600 mg/kg and 200 mg/kg for males and females, respectively.

Justification for selection of Effect on fertility via oral route:
Guideline study

Effects on developmental toxicity

Description of key information
In a Developmental toxicity study according to OECD guideline 414 and in compliance with GLP, no developmental toxicity was observed in the 100, 300 and 1000 mg/kg groups.
Effect on developmental toxicity: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
1 000 mg/kg bw/day
Study duration:
subacute
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

A prenatal developmental toxicity study was performed with the test article following GLP principles and OECD testing guideline 414. Mated female Wistar Han rats were assigned to four dose groups, each containing twenty-two animals. The test item was administered once daily by gavage from Day 6 to 19 post-coitum at doses of 100, 300 and 1000 mg/kg (Groups 2, 3 and 4 respectively). The rats of the control group (Group 1) received the vehicle, propylene glycol, alone. Accuracy, homogeneity and stability of formulations were demonstrated by analyses. At 1000 mg/kg, there was one premature death where a relationship to treatment could not be excluded since similar weight loss and lower food consumption were also noted for surviving females. For surviving females, maternal toxicity consisted of reduced body weights, body weight gains, body weight corrected for uterine weight and food consumption. No maternal toxicity was observed in the 100 and 300 mg/kg groups. No developmental toxicity was observed in the 100, 300 and 1000 mg/kg groups. In conclusion, based on the results in this prenatal developmental toxicity study the maternal No Observed Adverse Effect Level (NOAEL) for the test article was established at 300 mg/kg and the developmental NOAEL was at least 1000 mg/kg.


Justification for selection of Effect on developmental toxicity: via oral route:
GLP compliant guideline study

Justification for classification or non-classification