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Toxicological information

Developmental toxicity / teratogenicity

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Administrative data

Endpoint:
developmental toxicity
Type of information:
experimental study
Adequacy of study:
key study
Study period:
October 1972
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Well performed and reported study. Relevant aspects (treatment, exminations etc.) are in line with the current guideline

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1972
Report date:
1972

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 414 (Prenatal Developmental Toxicity Study)
Deviations:
yes
Remarks:
body weights every 5 days recorded
GLP compliance:
no
Remarks:
performed before GLP guidelines
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Methyl 4-hydroxybenzoate
EC Number:
202-785-7
EC Name:
Methyl 4-hydroxybenzoate
Cas Number:
99-76-3
Molecular formula:
C8H8O3
IUPAC Name:
methyl 4-hydroxybenzoate
Constituent 2
Reference substance name:
Methyl paraben
IUPAC Name:
Methyl paraben
Details on test material:
Code:
FDA 71-38
Appearance:
fine white crystalline material

Test animals

Species:
rat
Strain:
Wistar
Details on test animals or test system and environmental conditions:
Husbandry:
Virgin adult female rats 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 15 of gestation, the females were dosed with different dosages of Methylparaben dissolved in water by oral intubation. Controls were treated with corn oil.
Dosage volume: 1 mL/kg body weight
Analytical verification of doses or concentrations:
not specified
Details on analytical verification of doses or concentrations:
No data
Details on mating procedure:
Virgin adult female rats were mated with young adult males, and observation of the vaginal sperm plug was considered Day 0 of gestation.
Duration of treatment / exposure:
Day 6 to Day 15 of gestation
Frequency of treatment:
Daily
Duration of test:
20 days
No. of animals per sex per dose:
Control: 24 mated animals (23 pregnant animals)
Aspirin: 24 mated animals (22 pregnant animals)
5.5 mg/kg bw/d Methylparaben: 24 mated animals (23 pregnant animals)
25.5 mg/kg bw/d Methylparaben: 24 mated animals (23 pregnant animals)
118.0 mg/kg bw/d Methylparaben: 24 mated animals (24 pregnant animals)
550.0 mg/kg bw/d Methylparaben: 24 mated animals (23 pregnant animals)
Control animals:
yes, sham-exposed
Details on study design:
Sham group was dosed with corn oil.

Examinations

Maternal examinations:
Body weight: on Days 0, 6, 11, 15 and 20 of gestation
Clinical signs/Mortality: daily
Food consumption
Ovaries and uterine content:
On Day 20 all dams were subjected to Caesarean section under surgical anesthesia, and the numbers of Corpora lutea, implantation sites, resorption sites and live and dead fetuses were recorded. The urogenital tract of each dam was examined in detail for anatomical normality.
Fetal examinations:
Body weights of the live pups were recorded. All fetuses were examined grossly for the presence of external congenital abnormalities. One-third of the fetuses of each litter underwent detailed visceral examinations employing 10x magnification. The remaining two-thirds were cleared in potassium hydroxide, stained with alizarin red 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 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
Key result
Dose descriptor:
NOAEL
Effect level:
550 mg/kg bw/day (nominal)
Based on:
test mat.
Remarks on result:
not determinable due to absence of adverse toxic effects
Remarks:
550 mg/ kg be per das was the highest dose tested
Key result
Dose descriptor:
NOAEL
Effect level:
550 mg/kg bw/day (nominal)
Based on:
test mat.
Basis for effect level:
other: developmental toxicity
Remarks on result:
not determinable due to absence of adverse toxic effects

Maternal abnormalities

Key result
Abnormalities:
no effects observed

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 significant skeletal findings or soft tissue abnormalities

Effect levels (fetuses)

Key result
Dose descriptor:
NOAEL
Effect level:
> 550 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Remarks on result:
not determinable due to absence of adverse toxic effects

Fetal abnormalities

Key result
Abnormalities:
no effects observed

Overall developmental toxicity

Developmental effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
The administration of Methylparaben up to 550 mg/kg bw/d to pregnant rats (on days 6 to 15 of gestation) did not have any significant effect on maternal or developmental parameters. Based on the result of this study the NO(A)EL for maternal and developmental effects can be set at 550 mg/kg bw/d.
Executive summary:

Methylparaben was administered to female pregnant rats from day 6 to day 15 of gestation. The test item was administered orally at dose levels of 5.5, 25.5, 118.0 and 550.0 mg/kg bw/d.

The administration up to 550 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 corn oil treated controls.

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