Benzoic acid, 4-hydroxy-, C18-22-alkyl esters

Developmental toxicity / teratogenicity

Administrative data

Endpoint:

developmental toxicity

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Well documented study, conducted similar to 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

Guideline:

OECD Guideline 414 (Prenatal Developmental Toxicity Study)

Deviations:

yes

Remarks:

(only 12 animals were tested in the high dose group and body weights were recorded every 6 days only)

GLP compliance:

no

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Methyl 4-hydroxybenzoate

EC Number:

202-785-7

EC Name:

Methyl 4-hydroxybenzoate

Cas Number:

99-76-3

IUPAC Name:

methyl 4-hydroxybenzoate

Details on test material:

- Name of test material (as cited in study report): FDA 71-38
- Physical state: fine white crystalline material
- Analytical purity: no data

Test animals

Species:

rabbit

Strain:

other: Dutch-belted

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: virgin, adult females
- Housing: individually in mesh bottom cages
- Diet: ad libitum
- Water: tap water, ad libitum

ENVIRONMENTAL CONDITIONS
Temperature and humidity controlled (not further specified)

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Analytical verification of doses or concentrations:

not specified

Details on mating procedure:

- Impregnation procedure: artificial insemination
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 20E+6 motile sperm.

Duration of treatment / exposure:

Test item:
Day 6 through Day 18 of gestation

Positive control substance:
on Day 9 of gestation

Frequency of treatment:

Test groups: daily
Positive control group: single gaveage

Duration of test:

29 days

No. of animals per sex per dose:

- Vehicle control: 14 inseminated animals (11 pregnant animals)
- Positive control: 17 inseminated animals (10 pregnant animals)
- Test item 3.0 mg/kg bw/d Methylparaben: 20 inseminated animals (9 pregnant animals)
- Test item 14.0 mg/kg bw/d Methylparaben: 20 inseminated animals (9 pregnant animals)
- Test item 65.0 mg/kg bw/d Methylparaben: 14 inseminated animals (10 pregnant animals)
- Test item 300.0 mg/kg bw/d Methylparaben: 12 inseminated animals (9 pregnant animals)

Control animals:

yes, concurrent vehicle

Details on study design:

Positive control animals were treated with a single gavage of 6-Aminonicotinamide 2.5 mg/kg bw on test Day 9.

Examinations

Maternal examinations:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily

BODY WEIGHT: Yes
- Time schedule for examinations: on Days 0, 6, 12, 18 and 29 of gestation

FOOD CONSUMPTION AND COMPOUND INTAKE: Yes

POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation Day 29
- Organs examined: Caesarean section; the urogenital tract of each animal was examined in detail for normality.

Ovaries and uterine content:

The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Number of corpora lutea: Yes
- Number of implantations: Yes
- Number of early resorptions: Yes
- Number of dead foetuses: Yes

Fetal examinations:

- External examinations: Yes: [all per litter]
- Soft tissue examinations: Yes: [all per litter]
- Skeletal examinations: Yes: [all per litter]
The live fetuses of each litter were then placed in an incubator for 24 hours for the evaluation of the neonatal survival.

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)

1

Dose descriptor:

NOEL

Effect level:

>= 300 mg/kg bw/day (actual dose received)

Based on:

test mat.

Basis for effect level:

other: maternal toxicity

2

Dose descriptor:

NOEL

Effect level:

>= 300 mg/kg bw/day (actual dose received)

Based on:

test mat.

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

Effect levels (fetuses)

Dose descriptor:

NOEL

Effect level:

>= 300 mg/kg bw/day (actual dose received)

Based on:

test mat.

Basis for effect level:

other: teratogenicity

Fetal abnormalities

Abnormalities:

not specified

Overall developmental toxicity

Developmental effects observed:

not specified