Methylprednisolone

Developmental toxicity / teratogenicity

Administrative data

Endpoint:

developmental 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) (VI) -- perinatal and postnatal study in rats

Author:

Kageyama A et al

Year:

1991

Bibliographic source:

Yakuri To Chiryo 19 (8): 107-20 (1991)

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

In a peri/post-natal study, female rats were given daily subcutaneous doses of 0, 0.04, 0.2 or 1 mg/kg bw/day from day 17 of gestation up to day 21 post partum.

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

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

Administration / exposure

Route of administration:

subcutaneous

Duration of treatment / exposure:

From day 17 of gestation to day 21 after delivery

Frequency of treatment:

daily

No. of animals per sex per dose:

24 female rats per dose

Examinations

Fetal examinations:

All dams (F0) were allowed to deliver spontaneously and their offsprings (F1) were examined for growth and functional development.

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:

Details on maternal toxic effects:
Suppression of body weight gain and food consumption and prolongation of gestation period were observed in dams of 1.0 mg/kg body weight group.

Effect levels (maternal animals)

Dose descriptor:

NOEL

Effect level:

0.2 mg/kg bw/day (actual dose received)

Based on:

test mat.

Basis for effect level:

other: maternal toxicity

Results (fetuses)

Details on embryotoxic / teratogenic effects:

Details on embryotoxic / teratogenic effects:
A decrease in body weight and increase in abnormal number of lumbar vertebrae were observed in offspring of 1.0 mg/kg body weight group.
No abnormality in the functional development, behavior and reproductive performance of offsprings were observed even at the highest dosage of 1.0 mg/kg body weight.

Effect levels (fetuses)

Dose descriptor:

NOEL

Effect level:

0.2 mg/kg bw/day (actual dose received)

Based on:

test mat.

Basis for effect level:

other: fetotoxicity

Fetal abnormalities

Abnormalities:

not specified

Overall developmental toxicity

Developmental effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

From the above results, the no-effect dose of the test substance was estimated to be 0.2 mg/kg body weight for general toxicity in dams (F0), 0.2 mg/kg body weight for reproductive toxicity in dams (F0) and 0.2 mg/kg body weight for developmental toxicity in F1 offsprings.