"Test guideline

Qualifier: equivalent or similar to guideline

Guideline: OECD Guideline 414 (prenatal Developmental Toxicity Study)

GLP compliance: no

Limit test: no

Test material information

Reference substance name: 1,1-difuloroethylene

EC number: 200-867-7

EC name: 1,1-difluoroethylene

Cas. number: 75-38-7

Molecular formula: C2H2F2

IUPAC Name: 1,1-difluoroethylene

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 (CD) BR

Source: Charles River Breeding Laboratories, 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 (0C): 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

Nominal concentrations: 2000, 10000 ppm

Analytical concentrations: 2034.1 (+/- 213), 10114.7 (+/- 1363.4) ppm

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, behavior and condition

Detailed Clinical Observations: No

Body Weight: Yes on Days 0, 6, 15 and 20

Food Consumption: Yes, 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:

Grand 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. The 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 use

P0 Female CRL:COBS CD (SD) BR Rats