Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

Link to relevant study records
Reference
Endpoint:
fertility, other
Remarks:
based on test type (migrated information)
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: Data have been obtained by a secondary source (RTECS database) and it was not possible to assess the quality of the original source.
Reference:
Composition 0
Qualifier:
no guideline available
Principles of method if other than guideline:
not specified.
GLP compliance:
not specified
Test material information:
Composition 1
Species:
mouse
Strain:
not specified
Sex:
not specified
Route of administration:
oral: unspecified
Type of inhalation exposure (if applicable):
other: not applicable
Vehicle:
not specified
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
From day 7 to day 12 of pregnancy.
Dose descriptor:
other: TDLo
Generation:
F1
Effect level:
9 000 mg/kg bw (total dose)
Based on:
not specified
Sex:
not specified
Basis for effect level:
other: Effects on Embryo or Fetus. Fetotoxicity (except fetal death) in presence of maternal effects. The numerical dose data is a cumulative amount over the duration of the study.
Reproductive effects observed:
not specified
Conclusions:
The TDLo for fetotoxicity of ursodeoxycholic acid is 9 g/kg bw (total dose).
Executive summary:

After oral administration of ursodeoxycholic acid to pregnant mice from day 7 to day 12 of pregnancy, the TDLo for fetotoxicity is 9 g/kg bw (total dose), in presence of maternal effects.

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:
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.
Effect on fertility: via inhalation route
Endpoint conclusion:
no study available
Quality of whole database:
Exposure via inhalation route 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).
Effect on fertility: via dermal route
Endpoint conclusion:
no study available
Additional information

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 for the similar substance ursodeoxycholic acid.


Justification for selection of Effect on fertility via oral route:
Although the original report is not availbale, 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 study available
Quality of whole database:
Study not required by the tonnage level.
Effect on developmental toxicity: via inhalation route
Endpoint conclusion:
no study available
Quality of whole database:
Study not required by the tonnage level.
Effect on developmental toxicity: via dermal route
Endpoint conclusion:
no study available
Quality of whole database:
Study not required by the tonnage level.
Additional information

Developmental toxicity studies are not required by the substance tonnage level.

Toxicity to reproduction: other studies

Additional information

In conclusion, effects on reproduction related to methyl 3-α,7-α-diacetoxy-12-oxo-5-β-cholan-24-oate, basing on a read-across approach 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, methyl 3-α,7-α-diacetoxy-12-oxo-5-β-cholan-24-oate is not considered toxic to reproduction.