Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

Description of key information

The effects 1, 2, 3, 6-tretrahydrophthalic anhydride (THPA) on fertility, pregnancy and early lactation of the offspring have been investigated in a reproduction/developmental toxicity screening study conducted according to OECD test methods. Groups of rats were dosed by oral gavage at levels of 100, 250 and 600 mg/kg/day. Males were treated for 2 weeks prior to pairing and during pairing of all females until the day before necropsy, for a total of 6 weeks. Females were treated for 2 weeks prior to pairing, during pairing and throughout the gestation and lactation periods and for 4 days post partum. No significant changes and no treatment-related effects were detected in males and females during the in vivo phase. No significant differences in oestrus cycles, pre-coital interval and copulation plugs were observed and reproductive parameters (copulatory index and fertility index) did not show relevant intergroup differences in both sexes. No differences in the number of implantations or pre-birth loss data were noted. A prolonged gestation period, statistically significantly different from controls was noted with a dose-related trend. No toxicologically significant differences were noted in litter weight, mean pup weight and sex ratio. Total litter size was slightly reduced in animals dosed at 600 mg/kg/day. On the basis of the results obtained, the lower dose of 250 mg/kg/day was considered to be the No Observed Adverse Effect Level (NOAEL).

Effect on fertility: via oral route
Endpoint conclusion:
adverse effect observed
Dose descriptor:
NOAEL
250 mg/kg bw/day
Study duration:
subacute
Species:
rat

Effects on developmental toxicity

Description of key information

The effects 1, 2, 3, 6-tretrahydrophthalic anhydride (THPA) on fertility, pregnancy and early lactation of the offspring have been investigated in a reproduction/developmental toxicity screening study conducted according to OECD test methods. Groups of rats were dosed by oral gavage at levels of 100, 250 and 600 mg/kg/day. Males were treated for 2 weeks prior to pairing and during pairing of all females until the day before necropsy, for a total of 6 weeks. Females were treated for 2 weeks prior to pairing, during pairing and throughout the gestation and lactation periods and for 4 days post partum. No significant changes and no treatment-related effects were detected in males and females during the in vivo phase. No toxicologically significant differences were noted in litter weight, mean pup weight and sex ratio. Total litter size was slightly reduced in animals dosed at 600 mg/kg/day. On the basis of the results obtained, the lower dose of 250 mg/kg/day was considered to be the No Observed Adverse Effect Level (NOAEL).

Effect on developmental toxicity: via oral route
Endpoint conclusion:
adverse effect observed
Dose descriptor:
NOAEL
250 mg/kg bw/day
Study duration:
subacute
Species:
rat

Justification for classification or non-classification

Classification is not justified based on the available information from a screening study for reproduction/developmental toxicity