Registration Dossier

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:
OECD Guideline 414 (Prenatal Developmental Toxicity Study)
GLP compliance:
no
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
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 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 / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
2000, 10000 ppm
Basis:
nominal conc.
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

Applicant's summary and conclusion