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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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable, well documented study report.

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
Unnamed
Year:
1987
Report Date:
1983
Reference Type:
publication
Title:
Teratology Screen in rats with tripropyleneglycol diacrylate with cover letter
Author:
EPA
Year:
1994
Bibliographic source:
TSCATS/OTS0572415
Report Date:
1983
Reference Type:
publication
Title:
Initial Submission: Letter from Rhone-Poulenc Inc to USEPA regarding teratology screen studies of various compounds in rats with attachments and cover letter
Author:
EPA
Year:
1992
Bibliographic source:
TSCATS/OTS0571218
Report Date:
1983
Reference Type:
publication
Title:
Teratology Screen in rats with tripropyleneglycol diacrylate with cover letter
Author:
EPA
Year:
1994
Bibliographic source:
TSCATS/OTS0572416
Report Date:
1982

Materials and methods

Principles of method if other than guideline:
The test substance was administered by gavage to 22 pregnant rats from day 6 to day 15 of gestation to evaluate the embryo/fetal toxicity and teratogenic effects.
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): C-258
- Physical state: liquid
- Analytical purity: assumed to be 100%, no data on purity
- Lot/batch No.: 3-81
- Storage condition of test material: room temperature

Test animals

Species:
rat
Strain:
Sprague-Dawley
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Breeding Laboratories
- Age at study initiation: 5 weeks upon receipt, ca. 14 weeks at start of mating period
- Weight at study initiation: females ca. 233 g on day 0
- Housing: individually, 1 male with 2 feamles during mating
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 9 weeks


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 24.5 °C )76°F (1.0 S.D.)
- Humidity (%): 57% (4.8 S.D.)
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on exposure:
PREPARATION OF DOSING SOLUTIONS: The dosing solution was prepared fresh weekly by mixing a specified amount of the test material with the
vehicle.

Analytical verification of doses or concentrations:
not specified
Details on mating procedure:
- Impregnation procedure: cohoused
- If cohoused:
- M/F ratio per cage: 1 male / 2 females
- Length of cohabitation: maximum of 3 weeks
- After 10 days of unsuccessful pairing replacement of first male by another male with proven fertility.
- Further matings after two unsuccessful attempts: no data
- Verification of same strain and source of both sexes: yes
- Proof of pregnancy: vaginal plug or sperm in vaginal smear referred to as day 0 of pregnancy
Duration of treatment / exposure:
days 6 through 15 of gestation
Frequency of treatment:
once daily
Duration of test:
animals were sacrificed on day 20 of gestation
Doses / concentrations
Remarks:
Doses / Concentrations:
250 mg/kg bw
Basis:
nominal conc.
No. of animals per sex per dose:
22 female animals
Control animals:
yes, concurrent vehicle
Details on study design:
- Dose selection rationale: the dose was selected according to a screening study (TSCATS/OTS0546549, 1982), in which 6 females per group were treated with 50, 250, and 500mg/kg of the test substance following the same experimental setup as the main experiment. 1 rats died at the highest dose of 500 mg/kg bw. This animal exhibited distended lung with pale areas and dilated pelvis. Two further animals in the high dose group exhibited dilated pelvis and one of these animals had white areas and ulcerated areas on the stomach and the stomach contained white or yellow-white material. Since obviously excessive toxicity occured at 500mg/kg b.w., 250mg/kg b.w. was used in the main study.

Examinations

Maternal examinations:
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: once daily


DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: once daily


BODY WEIGHT: Yes
- Time schedule for examinations: day 0, 6, 9, 12, 15 and 20 of gestation


POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day # 20
- Organs examined: uterus and ovaries of each dam
Ovaries and uterine content:
The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Gravid uterus weight: Yes
- Number of corpora lutea: Yes
- Number of implantations: Yes
- Number of early resorptions: Yes
- Number of late resorptions: Yes
Fetal examinations:
- External examinations: Yes: [all per litter]
- Soft tissue examinations: Yes: [1/3 per litter ]
- Skeletal examinations: Yes: [2/3 per litter ]
- Head examinations: No data
Statistics:
various statistical methods used: National Cancer Institue Package, Box's test for homogeneity of variances, one-way classification analysis of variance
(ANOVA), Dunnett's T-test, one degree of freedom Chi-square test with Yates continuity correction, Fisher's Exact test. All pairwise comparisons were
evaluated at the 5.0% probability (one-tailed) level.
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:yes

Details on maternal toxic effects:
no increase of clinical observations compared to controls was observed, 1/22 animals died, no significant differences in body weight were noted
compared to controls, food and water consumption was comparable to controls.

Effect levels (maternal animals)

Dose descriptor:
LOAEL
Effect level:
250 mg/kg bw/day
Basis for effect level:
other: maternal toxicity

Results (fetuses)

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

Details on embryotoxic / teratogenic effects:
no statistically significant effects compared to controls were observed

Effect levels (fetuses)

open allclose all
Dose descriptor:
NOAEL
Effect level:
250 mg/kg bw/day
Basis for effect level:
other: embryotoxicity
Dose descriptor:
NOAEL
Effect level:
250 mg/kg bw/day
Basis for effect level:
other: teratogenicity

Fetal abnormalities

Abnormalities:
no effects observed

Overall developmental toxicity

Developmental effects observed:
no

Applicant's summary and conclusion