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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Endpoint:
one-generation reproductive toxicity
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
secondary literature

Data source

Reference
Reference Type:
publication
Title:
Toxicity study of methylprednisolone aceponate (ZK 91 588) (IV) -- fertility study in rats
Author:
Kageyama A et al
Year:
1991
Bibliographic source:
Yakuri To Chiryo 19 (8): 81-9 (1991)

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
A fertility study was carried out in rats and dose were given daily subcutaneous doses of 0, 0.004, 0.02 or 0.1 mg/kg bw/day. Treatment of the males commenced 60 days prior to mating. Treatment of females commenced 14 days prior to mating and continued up to day 7 of gestation. The dams were killed on day 21 of gestation and the foetuses examined.
GLP compliance:
not specified
Limit test:
no

Test material

Constituent 1
Reference substance name:
86401-95-8
Cas Number:
86401-95-8
IUPAC Name:
86401-95-8
Constituent 2
Reference substance name:
Methylprednisolone aceponate
IUPAC Name:
Methylprednisolone aceponate
Constituent 3
Reference substance name:
11β,17,21-Trihydroxy-6α-methylpregna-1,4-diene-3,20-dione, 21-acetate 17-propionate
IUPAC Name:
11β,17,21-Trihydroxy-6α-methylpregna-1,4-diene-3,20-dione, 21-acetate 17-propionate

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female

Administration / exposure

Route of administration:
subcutaneous
Duration of treatment / exposure:
Treatment of the males commenced 60 days prior to mating. Treatment of females commenced 14 days prior to mating and continued up to day 7 of gestation.
Frequency of treatment:
daily
Doses / concentrations
Remarks:
Doses / Concentrations:
0.004, 0.02 and 0.1 mg/kg body weight
Basis:
actual ingested
No. of animals per sex per dose:
22 rats per sex and dose

Examinations

Litter observations:
On day 21 of gestation, all dams were killed and their fetuses were examined for external, internal and skeletal abnormalities.

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Body weight and weight changes:
effects observed, treatment-related
Food consumption and compound intake (if feeding study):
effects observed, treatment-related

Reproductive function / performance (P0)

Reproductive performance:
no effects observed

Details on results (P0)

There was no effect on fertility. Parental body weight gain and food consumption were reduced at 0.02 mg/kg bw and above.

Effect levels (P0)

Dose descriptor:
NOEL
Effect level:
0.004 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
body weight and weight gain
food consumption and compound intake

Target system / organ toxicity (P0)

Critical effects observed:
not specified

Results: F1 generation

General toxicity (F1)

Mortality / viability:
mortality observed, treatment-related

Details on results (F1)

There were significant increases in the numbers of dead foetuses at 0.02 mg/kg bw and above.

Effect levels (F1)

Dose descriptor:
NOEL
Generation:
F1
Effect level:
0.004 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
mortality

Overall reproductive toxicity

Reproductive effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
The NOEL was 0.004 mg/kg bw/day.