Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LOAEL
1 500 mg/kg bw/day
Species:
mouse
Quality of whole database:
Basing on a read-across approach on a similar substance (ursodeoxycholic acid), no effects on fertility have been reported by repeated dose toxicity studies and the lack of toxicity on fertility is confirmed by the developmental studies and by the high doses at which negative effects have been generally observed. The results of the QSAR study, therefore, have been considered not reliable in a weight of evidence approach. In conclusion, the provided information is considered sufficient to assess the toxicity on fertility of the substance.
Effect on fertility: via inhalation route
Endpoint conclusion:
no study available
Quality of whole database:
Exposure of humans via inhalation is unlikely and not significant. The substance is solid with very low vapor pressure and it is only used at industrial sites by trained workers, under operative conditions not forming aerosols and dusts and under specific risk control measures (as described in the Exposure Scenarios).
Effect on fertility: via dermal route
Endpoint conclusion:
no study available
Additional information

Basing on a read-across approach on the similar substance ursodeoxycholic acid, no effects on fertility have been reported by repeated dose toxicity studies and the lack of toxicity on fertility is confirmed by the developmental studies and by the high doses at which negative effects have been generally observed. The results of the QSAR study, therefore, have been considered not reliable in a weight of evidence approach.


Justification for selection of Effect on fertility via oral route:
Although the original report is not available, the toxicological database reporting the information is well recognized.

Justification for selection of Effect on fertility via dermal route:
Exposure of humans via dermal route is unlikely and not significant. The substance is only used at industrial sites by trained workers, wearing suitable protective gloves and clothes, under specific risk control measures (as described in the Exposure Scenarios).

Effects on developmental toxicity

Effect on developmental toxicity: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
1 000 mg/kg bw/day
Species:
rat
Quality of whole database:
Basing on a read across approach on a similar substance (ursodeoxycholic acid), the developmental effects of the substance have been observed only at high doses, with the exception of the effects on the offspring of rabbits, but condisering that this is the only species in which negative effects have been observed at 65 mg/kg bw/day and that the extent of the effects has not been reported, the TDLo value can be considered not relevant for the overall assessment. In conclusion, the provided information is considered sufficient to assess the developmental toxicity of the substance.
Effect on developmental toxicity: via inhalation route
Endpoint conclusion:
no study available
Quality of whole database:
Exposure of humans via inhalation is unlikely and not significant. The substance is solid with very low vapor pressure and it is only used at industrial sites by trained workers, under operative conditions not forming aerosols and dusts and under specific risk control measures (as described in the Exposure Scenarios).
Effect on developmental toxicity: via dermal route
Endpoint conclusion:
no study available
Quality of whole database:
Exposure of humans via dermal route is unlikely and not significant. The substance is only used at industrial sites by trained workers, wearing suitable protective gloves and clothes, under specific risk control measures (as described in the Exposure Scenarios).
Additional information

Basing on a read across approach on the similar substance ursodeoxycholic acid, the developmental effects of the substance have been observed only at high doses, with the exception of the effects on the offspring of rabbits, but considering that this is the only species in which negative effects have been observed at 65 mg/kg bw/day and that the extent of the effects has not been reported, the TDLo value can be considered not relevant for the overall assessment.


Justification for selection of Effect on developmental toxicity: via oral route:
The selected study provides the up-to-date and more completed information on developmental toxicity of the susbtance.

Toxicity to reproduction: other studies

Additional information

In conclusion, basing on a read-across approach, effects on fertility and development have been observed only at very high doses and, according to the study of Stìtinová V et al. (2003), the NOAELs for maternal toxicity and developmental toxicity can be established at 1000 mg/kg bw/day.

Justification for classification or non-classification

Basing on the overall data and according to Regulation 1272/2008/EC, 12-ketochenodeoxycholic acid is not considered toxic to reproduction.