Registration Dossier

Administrative data

Description of key information

The repeated oral toxicity of 12-ketochenodeoxycholic acid has been evaluated basing on aread-across approach with ursodeoxycholic acid. The substance was tested in a 26-week study (1987). No Guideline or followed method is available in the source RTECS. 

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Study duration:
subacute
Species:
rat
Quality of whole database:
The study is cited by a well recognized database (RTECS); only results of the study are available and no other information is reported.

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Mode of Action Analysis / Human Relevance Framework

Additional information

On the basis of a read-across approach with ursodeoxycholic acid, the lowest toxic dose identified was 91 g/kg bw. The numerical dose data is a cumulative amount over the duration of the study.

Observed effects were: gastrointestinal hypermotility, diarrhea, hepatitis and diffuse hepatocellular necrosis, and changes in serum composition.


Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:
One read-across study available

Justification for selection of repeated dose toxicity inhalation - systemic effects endpoint:
Testing by the inhalation route is not considered appropriate, because exposure of humans via inhalation 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 repeated dose toxicity inhalation - local effects endpoint:
Testing by the inhalation route is not considered appropriate, because exposure of humans via inhalation 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 repeated dose toxicity dermal - systemic effects endpoint:
Testing by the dermal route is not considered as appropriate, 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).

Justification for selection of repeated dose toxicity dermal - local effects endpoint:
Testing by the dermal route is not considered as appropriate, 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).

Justification for classification or non-classification

The available study in RTECS reported effects at the total dose of 91 g/kg bw for ursodeoxycholic acid. The TDL0/day was calculated to be 500 mg/kg bw.

Since the negative effects were noted at a high dose and no other details are available on the study, basing on a read across approach, the classification of the substance for repeated dose toxicity is not judged needed.