Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

Link to relevant study records
Reference
Endpoint:
toxicity to reproduction
Remarks:
other: dominant lethal assay
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP Guidleline study
Qualifier:
according to
Guideline:
other: Rodent dominant lethal assay, antifertility and germ cell mutation (equivalent or similar to OECD 478)
Principles of method if other than guideline:
Rodent dominant lethal study: antifertility and germ cell cell mutation assay.
GLP compliance:
yes
Species:
mouse
Strain:
CD-1
Sex:
male/female
Route of administration:
inhalation
Vehicle:
unchanged (no vehicle)
Frequency of treatment:
6 hours /day for 5 days
Remarks:
Doses / Concentrations:
0, 1000, 10000, 50000 ppm
Basis:

No. of animals per sex per dose:
15 males / 30 Females
Control animals:
yes, concurrent no treatment
Reproductive function: sperm measures:
no effects observed
Key result
Dose descriptor:
NOEL
Effect level:
50 000 ppm
Based on:
test mat.
Sex:
male
Basis for effect level:
other: No effects on reproductive performance of male mice
Dose descriptor:
other:
Remarks on result:
not measured/tested
Key result
Reproductive effects observed:
no
Lowest effective dose / conc.:
50 000 ppm
Conclusions:
HFC 134a did not affect male fertility or cause mutagenic effects through sperm
Executive summary:

In a dominant lethal assay, CD1 male mice were exposed to up to 50000 ppm HFC 134a for 5 days. After the last exposure, each male was housed with 2 virgin females for 4 consecutive nights. Further matings with new females were conducted at weekly intervals for a total of 8 times. The study indicated that HFC 134a did not affect male fertility or cause mutagenic effects through sperm.

Effect on fertility: via oral route
Endpoint conclusion:
no study available
Effect on fertility: via inhalation route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEC
172 000 mg/m³
Study duration:
subacute
Species:
mouse
Effect on fertility: via dermal route
Endpoint conclusion:
no study available
Additional information

In a dominant lethal assay on a structurally related substance (1,1,1,2-tetrafluoroethane), CD1 male mice were exposed to up to 50000 ppm for 5 days. The study indicated that the substance did not affect male fertility or cause mutagenic effects through sperm.

 

In a fertility study on a structurally related substance (1,1,1,2-tetrafluoroethane), rats were exposed to up to 50 000 ppm throughout gametogenesis, mating, pregnancy and lactation. There were no adverse effects on the fertility and reproductive performance of treated animals or on the development, maturation or reproductive performance of up to two successive generations.

 

In a 13-week inhalation toxicity study, rats were exposed to up to 137000 mg/m3 (40000ppm) 6-hr/day, 5 days/wk . Histopathological examination of control and high exposure level group rat reproductive organs did not reveal any evidence for effects on the reproductive organs.

Overall the available studies show no evidence of any adverse effect on reproduction.

Short description of key information:

The substance gave rise to no adverse effects on fertility in a dominant lethal assay and in a fertility study. In addition it gave rise to no adverse effects on reproductive organs in a 13-week inhalation toxicity study.  

Effects on developmental toxicity

Description of key information

The substance showed no maternal toxicity nor developmental effects in rat and rabbit developmental toxicity studies.

Link to relevant study records
Reference
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
Qualifier:
according to
Guideline:
OECD Guideline 414 (Prenatal Developmental Toxicity Study)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Details on test animals 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.
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.
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
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.
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.
Key result
Dose descriptor:
NOEC
Effect level:
> 40 000 ppm (analytical)
Based on:
test mat.
Basis for effect level:
other: other:
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.
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
Abnormalities:
not specified
Key result
Developmental effects observed:
no
Lowest effective dose / conc.:
40 000 ppm

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

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.

Effect on developmental toxicity: via oral route
Endpoint conclusion:
no study available
Effect on developmental toxicity: via inhalation route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEC
137 600 mg/m³
Study duration:
subacute
Species:
rat
Effect on developmental toxicity: via dermal route
Endpoint conclusion:
no study available
Additional information

Developmental toxicity studies were conducted in Sprague Dawley rats (gestation days 7-16) and New Zealand rabbits (gestation days 6-18) using daily 6-hr exposures at up to 137600mg/m3 (40000 ppm). There were no effects on either the adults or the offspring. The level of 137600 mg/m3 was chosen as it is 50% of the lower flamability level.

Justification for classification or non-classification

No adverse effects have been observed in a selection of reliable fertility, repeat dose and developmental toxicity studies. It is therefore considered that classification is not required.