3α,7α-dihydroxy-12-oxo-5β-cholan-24-oic acid

Endpoint summary

Description of key information

The experimental oral LD50 in rats is 4600 mg/kg bw. 

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

4 600 mg/kg bw

Quality of whole database:

It was not possible to assess the quality of the literature study because it was not possible to consult the original study report, but the LD50 value was reported by a validated toxicological database (RTECS) and the rationale for the read-across support the applicatio of the value obtained for ursodeoxycholic acid to 12-ketochenodeoxycholic acid. The results of the QSAR study carried out with ACD/Tox Suite reports a lower LD50 value, indicating a possible moderate acute toxicity risk, but the QSAR result was considered not sufficient to classify 12-ketochenodeoxycholic acid into class IV of acute oral toxicity according to GHS.

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

An experimental oral LD50 in rats value is available from literature for the similar substance ursodeoxycholic acid. The applicability of this study to 12-ketochenodeoxycholic acid is supported by the attached rationale for the read-across. The value (LD50: 4600 mg/kg bw) does not agree to predicted oral LD50 value in rats, calculated by ACD/Tox Suite (LD50: 1500 mg/kg bw), but this value has a reliability index of 0.63 and, according to this prediction, the probability that the LD50 for 12-ketochenodeoxycholic acid were equal or lower than 5000 mg/kg bw is 93%, and the probability that this value were equal or higher than 300 mg/kg bw is of 95%. Therefore, on a weight of evidence approach, the LD50 of 4600 mg/kg bw deriving from the read-across with ursodeoxychollic acid can be considered sufficiently reliable. No values are available for inhalation and dermal routes, and no experimental values have been produced, because not necessary, considering that exposure by these routes is unlikely and not significant. A subcutaneous LD50 in rabbits is available in literature for the similar substance ursodeoxycholic acid and, according to this value (LD50: > 2000 mg/kg bw), it can be supposed that acute dermal toxicity will be low.

Justification for selection of acute toxicity – oral endpoint
Although it was not possibile to assess the quality of the information reported in the experimental study, the oral LD50 value reported for rats is consistent with the rationale for the read-across, although the predicted value of the QSAR study carried out with ACD/Tox Suite indicate a moderate oral acute toxicity (LD50 of 1500 mg/kg bw).

Justification for selection of acute toxicity – inhalation endpoint
No experimental data was deemed necessary for inhalation route, because 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).

Justification for selection of acute toxicity – dermal endpoint
No experimental data was deemed necessary for dermal route, because skin contact 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). Moreover, according to data related to a similar substance (Ursodeoxycholic acid), no dermal toxicity is expected on the basis of the subcutaneous acute toxicity value in rabbits (LD50 > 2000 mg/kg bw).

Justification for classification or non-classification

In conclusion, basing on the available toxicological information, no classification for acute toxicity by oral, inhalation and dermal routes is deemed necessary for 12-ketochenodeoxycholic acid, according to Regulation (EC) N.1272/2008.