1,1-dichloroethylene

Developmental toxicity / teratogenicity

Administrative data

Endpoint:

developmental toxicity

Type of information:

experimental study

Adequacy of study:

key study

Study period:

No data

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Well described and conducted study with very little deviations from the OECD guidelines

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1979

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 414 (Prenatal Developmental Toxicity Study)

Deviations:

yes

Remarks:

low frequency of body weight measurement, only one third of the litters examined for soft-tissues examination

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

1,1-dichloroethylene

EC Number:

200-864-0

EC Name:

1,1-dichloroethylene

Cas Number:

75-35-4

Molecular formula:

C2H2Cl2

IUPAC Name:

1,1-dichloroethene

Details on test material:

- Name of test material (as cited in study report): vinylidene chloride
- Substance type: production grade
- Physical state: liquid
- Analytical purity: 99.5 %
- Impurities (identity and concentrations): monomethylether of hydroquinone (MEHQ) / residual concentration : 1-5 mg/L
- Source: The Dow Chemical Company, Midland, Mich.

Test animals

Species:

rat

Strain:

Sprague-Dawley

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Spartan Research Animals, Inc., Haslett, Mich.
- Weight at study initiation: 250 g
- Housing: housed individually in wire-bottom cages
- Diet: commercial laboratory animal chow (Ralston Purina Co., St. Louis, Mo.) ad libitum
- Water: tap water ad libitum

Administration / exposure

Route of administration:

oral: drinking water

Vehicle:

water

Details on exposure:

- Rate of preparation of diet (frequency): daily
- Concentration in vehicle: 200 mg/L

Analytical verification of doses or concentrations:

no

Details on analytical verification of doses or concentrations:

No data

Details on mating procedure:

The day on which sperm were found in the vaginal smear of rats was considered as day 0 of pregnancy.

Duration of treatment / exposure:

10 days : from day 6 to day 15 of gestation

Frequency of treatment:

ad libitum

Duration of test:

Until day 21 of gestation

No. of animals per sex per dose:

24 rats for control
26 rats for 200 mg/L group

Control animals:

yes, concurrent vehicle

Details on study design:

No data

Examinations

Maternal examinations:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily
- Cage side observations not included.

Time schedule for body weight examinations: days 6, 10, 16 and 21 of gestation
Water consumption for each animal determined every 3 days or less and exposure calculated as g vinylidene chloride/kg body weight/day

POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day 21
- Organs examined: weight of maternal liver

Ovaries and uterine content:

The uteri of nonpregnant animals were stained with a 10 % solution of sodium sulfide and examined for evidence of early resorption sites (Kopf et al., 1964)
The number and position of live, dead, and resorbed fetuses were noted

Fetal examinations:

After being weighed, measured (crown-rump length), and the sexes noted, all fetuses were examined for external alterations and cleft palate. One-third of the fetuses from each litter, selected at random, was examined immediately for evidence of soft-tissue alterations by dissection under a stereomicroscope (Staples, 1974). The head of each rat fetus which was examined for soft-tissue alterations was placed in Bouin's solution and subsequently examined by the razor section technique of Wilson (1965). All fetuses were cleared with KOH, stained with alizarin red-S (Dawson, 1926), and examined for skeletal alterations.

Statistics:

The incidence of pregnancy was analyzed by the Fisher exact probability test (Siegel, 1956).
The Wilcoxon test as modified by Haseman and Hoel (1974) was used to evaluate the incidence of fetal alterations.
Fetal body weights and body measurements, maternal body and liver weights, and food and water consumption data were analyzed by a one-way analysis of variance (Steel and Torrie, 1960). The level of significance reported was p< 0.05.

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:
No test dams died. No change in food and water consumption was noted. No alteration of liver weight.
The incidence of pregnancy was not significantly altered by exposure to 1,1-dichloroethene.

Effect levels (maternal animals)

Dose descriptor:

NOAEL

Effect level:

40 mg/kg bw/day

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:
Statistically significant increase in the average number of corpora lutea per dam (mean ± SD : 12 ± 2 vs. 14 ± 3 for control vs. 1,1-dichloroethene group, respectively)
The mean fetal crown-rump length was significantly greater than that of the controls (Mean of the litter means ± SD : 46.6 ± 2.4 vs. 47.8 ± 1.3 mm for control vs. vinylidene chloride group, respectively)
No significant effect on the average number of implantations, live fetuses, resorptions, sex ratio or body weight
Neither skeletal alteration nor major malformations was significantly different from the controls

Effect levels (fetuses)

Remarks on result:

other: not specified

Remarks:

not specified

Fetal abnormalities

Abnormalities:

not specified

Overall developmental toxicity

Developmental effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

No evidence of toxicity to the dams or their offspring
NOAEL = 200 mg/L = 40 mg/kg bw/day

Executive summary:

The teratogenic effect of 1,1-dichloroethene was assessed on Sprague-Dawley pregnant rats given 200 mg/L of 1,1-dichloroethene in drinking-water (equivalent to 40 mg/kg/day) from day 6 to day 15 of gestation. No evidence of toxicity to the dams or their offspring was observed.