Methyl 3-α,7-α-diacetoxy-12-oxo-5-β-cholan-24-oate

Endpoint summary

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.

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

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

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.