Ibuprofen

Toxicity to reproduction

Administrative data

Endpoint:

screening for reproductive / developmental toxicity

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

publication

Title:

Absorption, Distribution and Toxicity of Ibuprofen.

Author:

Adams S.S., Bough R.G., Vliffe E.E., Lessel B., Mills R.F.N.

Year:

1969

Bibliographic source:

Toxicol Appl Pharmacol 15: 310-330.

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

The thyroid and the ovaries were investigated for possible function impairment due exposure to the test substance. The gonadal function was checked by means of a reproductive study. Ten male and 20 female rats of proven fertility were maintained on a diet containing 0.035% test substance (ca 20 mg/kg bw) over a period of 60 days; control rats received the diet only. Thereafter, all rats received diet only and 2 treated females were cohabitated with one treated male for mating over a period of 14 days. The females were checked for pregnancy and litter size at birth.

GLP compliance:

no

Remarks:

pre-GLP study

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Ibuprofen

EC Number:

239-784-6

EC Name:

Ibuprofen

Cas Number:

15687-27-1

Molecular formula:

C13H18O2

IUPAC Name:

2-(4-isobutylphenyl)propanoic acid

Test material form:

solid

Specific details on test material used for the study:

- Name of test material (as cited in study report): Ibuprofen; i.e. 2-(4-isobutylphenyl)propionic acid)

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Boots
- Diet: ad libitum
- Water: ad libitum

Administration / exposure

Route of administration:

oral: feed

Vehicle:

unchanged (no vehicle)

Details on mating procedure:

- M/F ratio per cage: 1/2
- Length of cohabitation: 14 days

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

Exposure period: 74 days
Premating exposure period (males): 60 days
Premating exposure period (females): 60 days
Duration of test: 95 days (study terminated after parturition)

Frequency of treatment:

continuously in the diet

Doses / concentrations

Dose / conc.:

0.035 other: % in diet

Remarks:

Corresponsing to ca 20 mg/kg bw daily

No. of animals per sex per dose:

20 females and 10 males for the dose and control groups each

Control animals:

yes, plain diet

Positive control:

no

Examinations

Litter observations:

The females were checked for pregnancy and litter size at birth.

Reproductive indices:

The females were checked for pregnancy and litter size at birth.

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Mortality:

mortality observed, non-treatment-related

Description (incidence):

Two control females were killed in this period, one having a mammary abscess and the other an umbilical hernia.

Body weight and weight changes:

effects observed, treatment-related

Description (incidence and severity):

Treated female rats showed a small loss in weight, while the similarly treated males gained weight normally.

Reproductive function / performance (P0)

Description (incidence and severity):

Fifteen of the 20 females receiving the test substance and 16 of the 18 control females were pregnant after the 14-day mating period. All the males in the 2 groups mated successfully apart from 1 receiving the test substance; thus the failure of 2 of the 5 treated females to become pregnant may have been due to the infertility of this single male. Shortly before parturition 2 treated females had vaginal hemorrhage: One died with 10 fully formed fetuses in the uterus and extensive hemorrhage surrounding the placentae, gastric ulcers, and anemia.

The second was killed with lung congestion and had a large blood dot in one uterine horn but no dead or resorbed fetuses. The remaining treated females had uneventful pregnancies and gave birth to litters which an average contained 7.9 live young, compared with the control females which had litters of 7.3 live young.

Effect levels (P0)

Remarks on result:

not determinable because of methodological limitations

Remarks:

no NOAEL identified

Results: F1 generation

Effect levels (F1)

Key result

Remarks on result:

not measured/tested

Overall reproductive toxicity

Reproductive effects observed:

not specified