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Toxicological information

Developmental toxicity / teratogenicity

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Administrative data

Endpoint:
developmental toxicity
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
May 1973
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Well performed and reported study. Relevant aspects (treatment, examinations etc.) are in line with the current guideline.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1973
Report Date:
1973

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 414 (Prenatal Developmental Toxicity Study)
Deviations:
yes
Remarks:
only 12 animals in high dose group, body weight every 6 days recorded
GLP compliance:
no
Remarks:
performed before GLP guidelines
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
Code:
FDA 71-38
Appearance:
fine white crystalline material

Test animals

Species:
rabbit
Strain:
other: Dutch-belted
Details on test animals and environmental conditions:
Husbandry:
Virgin, adult female rabbits were individually housed in mesh bottom cages in temperature and humidity-controlled quarters with free access to food and fresh tap water.

.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on exposure:
Beginning on Day 6 and continuing daily through Day 18 the females were dosed with 3, 14, 65 or 300 mg Methylparaben/kg bw or 2.5 mg 6-Aminonicotinamide/kg bw (positive control on Day 9). The negative controls were treated with the vehicle (water) at a level equivalent to the group receiving the highest dose level.
Analytical verification of doses or concentrations:
not specified
Details on analytical verification of doses or concentrations:
No data
Details on mating procedure:
On Day 0, each doe was given an injection of 0.4 mL human chorionic gonadotropin (400 IU) via the marginal ear vein. 3 hours later, each doe was inseminated artificially with 0.3 mL of diluted semen from a proven donor buck using approximately 20 x 10(exp 6) motile sperm.
Duration of treatment / exposure:
Methylparaben:
Day 6 to Day 18 of gestation

6-Aminonicotinamide:
on Day 9 of gestation
Frequency of treatment:
Daily
Duration of test:
29 days
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
3.0 mg/kg bw/d
Basis:
actual ingested
Remarks:
Doses / Concentrations:
14.0 mg/kg bw/d
Basis:
actual ingested
Remarks:
Doses / Concentrations:
65.0 mg/kg bw/d
Basis:
actual ingested
Remarks:
Doses / Concentrations:
300.0 mg/kg bw/d
Basis:
actual ingested
No. of animals per sex per dose:
Control: 14 mated animals (11 pregnant animals)
6-Aminonicotinamide: 17 mated animals (10 pregnant animals)
3.0 mg/kg bw/d Methylparaben: 20 mated animals (9 pregnant animals)
14.0 mg/kg bw/d Methylparaben: 20 mated animals (9 pregnant animals)
65.0 mg/kg bw/d Methylparaben: 14 mated animals (10 pregnant animals)
300.0 mg/kg bw/d Methylparaben: 12 mated animals (9 pregnant animals)
Control animals:
yes, concurrent vehicle
Details on study design:
None

Examinations

Maternal examinations:
Body weight: on Days 0, 6, 12, 18 and 29 of gestation
Clinical signs/mortality: daily
Food consumption
Ovaries and uterine content:
On Day 29 of gestation all does were subjected to Caesarean section under surgical anethesia and the numbers of Corpora lutea, implantation sites, resorption sites and dead fetuses were recorded. The urogenital tract of each animal was examined in detail for normality.
Fetal examinations:
Body weights of the live pups were recorded. All fetuses underwent a detailed gross examination for the presence of external congenital abnormalities. The live fetuses of each litter were then placed in an incubator for 24 hours for the evaluation of the neonatal survival. All surviving pups were sacrificed and examined for visceral abnormalities (by dissection). All fetuses were cleared in potassium hydroxide, stained with Alizarin S dye and examined for skeletal defects.
Statistics:
None
Indices:
No data
Historical control data:
No data

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:
Maternal toxic effects:no effects

Details on maternal toxic effects:
- All pregnant animals (except of 1 female in the control group) survived until scheduled necropsy and no clinical signs were noted
- Body weights were not affected by treatment
- The relevant reproduction parameters (no. of Corpora lutea, implantation sites/dam, resorptions etc.) were not affected by treatment with the test item

Effect levels (maternal animals)

open allclose all
Dose descriptor:
NOEL
Effect level:
300 mg/kg bw/day (actual dose received)
Basis for effect level:
other: maternal toxicity
Dose descriptor:
NOEL
Effect level:
300 mg/kg bw/day (actual dose received)
Basis for effect level:
other: developmental toxicity

Results (fetuses)

Details on embryotoxic / teratogenic effects:
Embryotoxic / teratogenic effects:no effects

Details on embryotoxic / teratogenic effects:
- Sex ratio and fetal body weight were not affected by treatment
- No dose related skeletal findings or soft tissue abnormalities

Fetal abnormalities

Abnormalities:
not specified

Overall developmental toxicity

Developmental effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
The administration of Methylparaben up to 300 mg/kg bw/d to pregnant rabbits (on days 6 to 18 of gestation) did not have any effect on maternal or developmental parameters. Based on the result of this study the NOEL for maternal and developmental effects can be set at 300 mg/kg bw/d.
Executive summary:

Methylparaben was administered to female pregnant rabbits from day 6 to day 18 of gestation. The test item was administered orally at dose levels of 3, 14, 65 and 300 mg/kg bw/d.

The administration up to 300 mg Methylparaben/kg bw/d had no clearly discernable effect on nidation or maternal or fetal survival. The number of abnormalities seen in either soft or skeletal tissues of the test groups did not differ from the number occuring spontaneously in the vehicle treated controls.