1,1,1-trifluoroethane

Developmental toxicity / teratogenicity

Administrative data

Endpoint:

developmental toxicity

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP OECD Guideline study

Data source

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

1993

Report date:

1993

Reference 2

Reference Type:

publication

Title:

Acute, Subchronic and Developmental Toxicity and Genotoxicity of 1,1,1-trifluoroethane (HFC-143a)

Author:

Brock, WJ, Trochimowicz, HJ, Farr, CH, Millischer, R-J, & Rusch, GM

Year:

1996

Bibliographic source:

Fundamental and Applied Toxicology, 31, 200-209 (1996).

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 414 (Prenatal Developmental Toxicity Study)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

1,1,1-trifluoroethane

EC Number:

206-996-5

EC Name:

1,1,1-trifluoroethane

Cas Number:

420-46-2

Molecular formula:

C2H3F3

IUPAC Name:

1,1,1-trifluoroethane

Details on test material:

Named either H-19440 or HFC-143a

Test animals

Species:

rat

Strain:

Sprague-Dawley

Details on test animals or test system and environmental conditions:

162 nulliparous females, 64 days old were received from Charles River Breeding Lab., Kingston, NY. Males of the same strain were used for breeding. Rats were individually housed in wire mesh cages in temperature (21-25 deg.C) and humidity (40-60%) controlled rooms with a 12 hr light-dark cycle. They were given Purina Rodent Chow #5002 and tap water ad libitum except during exposures.

Administration / exposure

Route of administration:

inhalation: gas

Type of inhalation exposure (if applicable):

whole body

Vehicle:

unchanged (no vehicle)

Details on exposure:

exposures were conducted daily on days 7-16 of gestation for 6 hrs/day.

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

Samples of the chamber air were withdrawn hourly and analyzed by gas chromatography. Nominal concentrations were within 90 to 110% of analytical controls.

Details on mating procedure:

Females were individually caged with males from an in-house colony. Copulation was determined (Day 1) by the presence of a copulation plug.

Duration of treatment / exposure:

Exposures were conducted daily from Day 7 through day 16 of gestation.

Frequency of treatment:

daily

Duration of test:

From day of copulation plug until day 21.

Doses / concentrations

Remarks:

Doses / Concentrations:
0 (control), 2000, 10000, and 40000 ppm
Basis:
analytical conc.

No. of animals per sex per dose:

25

Control animals:

yes, sham-exposed

Examinations

Maternal examinations:

Animals were observed on arrival, twice during quarantine, daily in the morning from Day 1- 22 and in the afternoon on days 7-16. Body weights were measured on days 1, 7, 9, 11, 13, 15, 17 and 22G. Food consumption was measured on the same days as well as on days 3 and 5.

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: [ half per litter ]
- Skeletal examinations: Yes: [ half per litter ]
- Head examinations: Yes: [ #? per litter ]

Statistics:

Statistical evaluations will be at p

Indices:

At termination viscera will be examined grossly, uterine weight measured, corpora lutea counted for each ovary with the number of viable fetuses recorded. The number of implantations will be determined using ammonium sulfate staining and the number of early resorptions calculated. Fetuses will be examined for soft tissue abnormalities or skeletal abnormalities

Historical control data:

Historical control data are available if needed to clarify uncertainties.

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:

Maternal toxic effects:no effects

Details on maternal toxic effects:
HFC-143a was administered by inhalation to groups of 25 female rats on days 7 -16 of gestation at exposure levels of 0, 2000, 10000, and 40000 ppm. There was no evidence of maternal or developmental toxicity at any level tested. The NOEC was greater than 40,000 ppm for the dam and conceptus.

Effect levels (maternal animals)

Key result

Dose descriptor:

NOEC

Effect level:

> 40 000 ppm (analytical)

Based on:

test mat.

Basis for effect level:

other: other:

Results (fetuses)

Details on embryotoxic / teratogenic effects:

Embryotoxic / teratogenic effects:no effects

Details on embryotoxic / teratogenic effects:
HFC-143a was administered by inhalation to groups of 25 female rats on days 7 -16 of gestation at exposure levels of 0, 2000, 10000, and 40000 ppm. There was no evidence of maternal or developmental toxicity at any level tested. The NOEC was greater than 40,000 ppm for the dam and conceptus.

Effect levels (fetuses)

Key result

Dose descriptor:

NOEC

Effect level:

> 40 000 ppm

Based on:

test mat.

Sex:

not specified

Remarks on result:

not determinable due to absence of adverse toxic effects

Fetal abnormalities

Abnormalities:

not specified

Overall developmental toxicity

Key result

Developmental effects observed:

no

Lowest effective dose / conc.:

40 000 ppm

Any other information on results incl. tables

HFC-143a was administered by inhalation to groups of 25 female rats on days 7 -16 of gestation at exposure levels of 0, 2000, 10000, and 40000 ppm. There was no evidence of maternal or developmental toxicity at any level tested. Treatment-related findings were not observed in litter size, embryo-fetal loss and litter and fetal weight. Effects on the incidence of malformation were not observed at any exposure level. A significant increase in the incidence of fetal visceral variations in the litters of all the exposed groups in comparison to the control group was seen. The actual incidences were 1.6, 10.5, 8.7, and 10.0 % for the 0, 2000, 10000, and 40000 ppm groups, respectively. Retarded renal papillary development was the primary and most frequently recorded observation. The higher values observed in the 1,1,1-trifluoroethane-exposed litters are not considered to be biologically significant for three reasons. First, in the study, the control value was abnormally low relative to historical control values for retarded renal papillary development which averaged 10.5% and ranged from 6.8 to 16.2 % for 5 other studies conducted within the same period (1991-1992). Second, the increases did not show concentration-dependent response. Third, there was a lack of other developmental effects in the study. The NOAEC for maternal and developmental toxicity in rats was 40,000 ppm

Applicant's summary and conclusion

Conclusions:

HFC-143a was administered by inhalation to groups of 25 female rats on days 7 -16 of gestation at exposure levels of 0, 2000, 10000, and 40000 ppm. There was no evidence of maternal or developmental toxicity at any level tested. The NOEC was greater than 40,000 ppm for the dam and conceptus.

Executive summary:

HFC-143a was administered by inhalation to groups of 25 female rats on days 7 -16 of gestation at exposure levels of 0, 2000, 10000, and 40000 ppm. There was no evidence of maternal or developmental toxicity at any level tested. The NOEC was greater than 40,000 ppm for the dam and conceptus.