1,1-difluoroethylene

Developmental toxicity / teratogenicity

Administrative data

Endpoint:

developmental toxicity

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Non-GLP and non-guideline study, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1978

Report date:

1978

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 414 (Prenatal Developmental Toxicity Study)

GLP compliance:

no

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

1,1-difluoroethylene

EC Number:

200-867-7

EC Name:

1,1-difluoroethylene

Cas Number:

75-38-7

Molecular formula:

C2H2F2

IUPAC Name:

1,1-difluoroethene

Details on test material:

Two large green compressed gas cylinders labeled:
Isotron 1132a - difluoroethylene
Vinylidene Fluoride Monomer
were received from Pennwalt Corporation by Litton Biokinetics, Inc. (LBI) on October 11 and designated as LBI No. 1875.

Test animals

Species:

rat

Strain:

other: CRL:COBS CD (SD) BR

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Breeding Laboraties, Inc., Portage, Michigan
- Age at study initiation: 82 days
- Fasting period before study: no
- Housing: individually in wire cages
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 12 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.1-21.6
- Humidity (%): no data
- Photoperiod (hrs dark / hrs light): 12 / 12

Administration / exposure

Route of administration:

inhalation: gas

Type of inhalation exposure (if applicable):

whole body

Vehicle:

unchanged (no vehicle)

Details on exposure:

The test material was metered from compressed gas cylinders into a diluting stream of filtered, conditioned air. The exposures were conducted in dynamic 1.5 cubic meter stainless steel and glass chambers operated under negative pressure.

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

The chamber airborne concentrations were monitored periodically throughout the exposure using a Scott Model 216 Hydrocarbon Analyzer. The instrument had been previously calibrated with known concentrations of Isotron 1132a using methane as an internal standard.

Details on mating procedure:

- Impregnation procedure: cohoused
- If cohoused:
- M/F ratio per cage: 1/1
- Length of cohabitation: until a copulatory plug was present
- Verification of same strain and source of both sexes: yes
- Proof of pregnancy: vaginal plug, referred to as day 0 of pregnancy

Duration of treatment / exposure:

6 hours

Frequency of treatment:

10 days (days 6-15 of gestation)

Duration of test:

20 days

Doses / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
2000, 10000 ppm
Basis:
nominal conc.

Doses / concentrations 2

Remarks:

Doses / Concentrations:
2034.1 (+/- 213), 10114.7 (+/- 1363.4) ppm
Basis:
analytical conc.

No. of animals per sex per dose:

20

Control animals:

yes, concurrent no treatment

Details on study design:

Mated female rats were assigned sequentially to treatment groups and identified by cage cards.

Examinations

Maternal examinations:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Daily for changes in general appearance, bahaviour and condition.

DETAILED CLINICAL OBSERVATIONS: No

BODY WEIGHT: Yes
- Time schedule for examinations: Days 0, 6, 15 and 20

FOOD CONSUMPTION: Yes
- Time schedule: During the periods 0-6, 6-15 and 15-20 of gestation.

WATER CONSUMPTION: No

POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day 20
- Organs examined: Visceral and thoracic organs

Ovaries and uterine content:

The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Gravid uterus weight: no data
- Number of corpora lutea and their placement in the uterine horns: Yes
- Number of implantations: Yes
- Resorption sites: Yes
- Live and dead foetuses: Yes

Fetal examinations:

- External examinations: Yes: all per litter
- Soft tissue of the head, thoracic and visceral organs examinations: Yes: 1/3 per litter
- Skeletal examinations: Yes: 2/3 per litter

Statistics:

Statistical analysis of the data was performed using the litter as a basic sampling unit. This concept has been widely supported with regard to teratology. Dunnett's t-test was used to determine statistical significance (p<0.05) with regard to difference between means with near-normal distribution (body weights and food consumption of dams, mean pup weight based on litter averages). Ratios, i.e., sex ratio and pregnancy ratio, were analyzed with a 2x2 contingency table with Yates' correction. With regard to discontinuous parameters as measured by the number of abnormal fetuses within a litter, Wilcoxon Rank Sum was used.

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:

Maternal toxic effects:no effects

Effect levels (maternal animals)

Dose descriptor:

NOAEL

Effect level:

>= 10 000 ppm

Basis for effect level:

other: maternal toxicity

Results (fetuses)

Details on embryotoxic / teratogenic effects:

Embryotoxic / teratogenic effects:no effects

Effect levels (fetuses)

Dose descriptor:

NOAEL

Effect level:

>= 10 000 ppm

Basis for effect level:

other: teratogenicity

Fetal abnormalities

Abnormalities:

not specified

Overall developmental toxicity

Developmental effects observed:

not specified