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Administrative data

Description of key information

The repeated oral toxicity of the simila substance ursodeoxycholic acid has been evaluated 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

Link to relevant study records
Reference
Endpoint:
sub-chronic toxicity: oral
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: Although the study is cited by a well recognized database (RTECS), only results of the study are available, and no other information is reported.
Reference:
Composition 0
Qualifier:
no guideline available
Principles of method if other than guideline:
Rats were orally administered with ursodeoxycholic acid for a period of 26 weeks.
GLP compliance:
not specified
Test material information:
Composition 1
Species:
rat
Route of administration:
oral: unspecified
Vehicle:
not specified
Analytical verification of doses or concentrations:
not specified
Clinical signs:
not specified
Mortality:
not specified
Body weight and weight changes:
not specified
Food consumption and compound intake (if feeding study):
not specified
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
effects observed, treatment-related
Description (incidence and severity):
Changes in serum composition
Clinical biochemistry findings:
not specified
Urinalysis findings:
not specified
Behaviour (functional findings):
not specified
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
not specified
Histopathological findings: non-neoplastic:
effects observed, treatment-related
Description (incidence and severity):
hepatitis, diffuse hepatocellular necrosis
Histopathological findings: neoplastic:
not specified
Details on results:
TDLo: 91 g/kg bw
The numerical dose data is a cumulative amount over the duration of the study.
Dose descriptor:
dose level: TDL0
Effect level:
91 000 mg/kg bw (total dose)
Based on:
test mat.
Sex:
not specified
Dose descriptor:
dose level: TDL0
Effect level:
500 mg/kg bw/day (nominal)
Based on:
not specified
Sex:
not specified
Critical effects observed:
not specified
Conclusions:
The lowest toxic dose identified was 91 mg/kg bw/day.
Executive summary:

The repeated oral toxicity of ursodeoxycholic acid has been evaluated in a 26-week study of 1987. The lowest toxic dose identified was 91 mg/kg bw/day. Observed effects were: gastrointestinal hypermotility, diarrhea, hepatitis and diffuse hepatocellular necrosis, and changes in serum composition.

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

Link to relevant study records
Reference
Endpoint:
repeated dose toxicity: inhalation
Data waiving:
exposure considerations
Justification for data waiving:
other:
Critical effects observed:
not specified
Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: inhalation - local effects

Link to relevant study records
Reference
Endpoint:
repeated dose toxicity: inhalation
Data waiving:
exposure considerations
Justification for data waiving:
other:
Critical effects observed:
not specified
Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - systemic effects

Link to relevant study records
Reference
Endpoint:
repeated dose toxicity: dermal
Data waiving:
exposure considerations
Justification for data waiving:
other:
Critical effects observed:
not specified
Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - local effects

Link to relevant study records
Reference
Endpoint:
repeated dose toxicity: dermal
Data waiving:
exposure considerations
Justification for data waiving:
other:
Critical effects observed:
not specified
Endpoint conclusion
Endpoint conclusion:
no study available

Mode of Action Analysis / Human Relevance Framework

Additional information

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 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 is unlikely and not significant. The substance is solid with very low vapour 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 vapour 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. The TDLo/day was calculated to be 500 mg/kg bw.

Since the negative effects were noted at an high dose and no other details are available on the study, the classification of the substance for repeated dose toxicity is not judged necessary.