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Toxicological information

Repeated dose toxicity: inhalation

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Administrative data

Endpoint:
sub-chronic toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP study conducted following OECD protocol

Data source

Referenceopen allclose all

Reference Type:
study report
Title:
Unnamed
Year:
1993
Report Date:
1993
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:
OECD Guideline 413 (Subchronic Inhalation Toxicity: 90-Day Study)
Deviations:
yes
Remarks:
an additional 10 rats/sex/level were included as a post exposure observation group
GLP compliance:
yes (incl. certificate)

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
Rats of 22 days of age were obtained from Charles River, Kingston, NY. They were quarantined for approx. 2 wks. The animal room was maintained at 23 +/- 2 deg C and 55 +/- 15% rel. humidity. Individual housing in wire mesh ss cages,

Administration / exposure

Route of administration:
inhalation: gas
Type of inhalation exposure:
whole body
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
Groups of 20 M and 20 F rats were exposed, 6-hr/d, 5d/wk for a total of 64 (M) or 65 (F) exposures. Ten/sex/group were sacrificed at the end of he exposure perion and 10/sex/group were held for an additional 4 wks and then sacrificed.
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
Gas samples (~0.1 ml) were analyzed with a Hewlett Packard 5880A GC with an FID. Samples were chromatographed on a 10 ft. by 1/8 inch ss column packed with 5% KRYTOX 60/80 Carbo Pack B. Samples were collected at approx. 30 min. intervals. Exposure levels were determined by comparing the detector response to a standard curve of the responses obtained with standard gas mixtures.
Duration of treatment / exposure:
6-hr/day
Frequency of treatment:
5 days/wk for 13 weeks
Doses / concentrations
Remarks:
Doses / Concentrations:
0 (control), 2020, 10141, and 40072 ppm
Basis:
analytical conc.
No. of animals per sex per dose:
20
Control animals:
yes, sham-exposed
Details on study design:
Exposure levels were determined based on two previous 4-week studies that were conducted at exposure levels of 0, 2000, 10,000 and 39000 ppm. In the first study, exposures were conducted by the nose only route and effects were noted that were attributed to heat stress. In the second study, exposures were conducted by the whole body route and there were no apparent treatment related effects.
Positive control:
none

Examinations

Observations and examinations performed and frequency:
Rats were observed during the exposures, twice daily for health status on exposure days and once daily during non-exposure days. Body weights were measured and detailed clinical observations were conducted once per week. At the conclusion of the exposure period, a group of 10 rats/sex/level were observed for an additional 4 weeks. Food consumption was measured weekly. An ophthalmological exam was conducted prior to the first exposure and prior to the sacrifice at 13 weeks. Clinical laboratory, urinalysis and hematology evaluations were conducted at 45 and 90 days on 10 rats/sex/level. Rats were fasted for approx. 16 hrs prior to blood collection.
Sacrifice and pathology:
All animals were given a gross necropsy examination, organ weights were measured on the spleen, heart, lungs, liver, kidneys, adrenals, testes, ovaries and brain, and tissues were collected from over 40 organs and fixed including reproductive organs. These were examined from the rats in the control and high exposure level from the rats sacrificed at 90 days. If any abnormalities were noted, those tissues would have been examined from the rats in the post exposure period and from the other exposure groups.
Other examinations:
Peroxisome proliferation measurements were conducted on 5 rats/sex/level.
Statistics:
Body wts., body wt. gains, organ wts., clinical laboratory and biochemical measurements were analyzed by a one-way analysis of varience. Additionally, the F-test, Dunnet's test, Bonferroni correction, Cochran-Armitage test, Bartlett's test Kruskal-Wallis test and Mann-Whitney U test were applied as appropriate.

Results and discussion

Results of examinations

Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
no effects observed
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
no effects observed
Haematological findings:
no effects observed
Clinical biochemistry findings:
no effects observed
Urinalysis findings:
no effects observed
Behaviour (functional findings):
no effects observed
Organ weight findings including organ / body weight ratios:
no effects observed
Gross pathological findings:
no effects observed
Histopathological findings: non-neoplastic:
no effects observed
Histopathological findings: neoplastic:
no effects observed
Details on results:
In addition, no evidence of peroxisome proliferation was seen. While the no-observed-effect-concentration was 40,000 ppm, the highest level tested, this level was selected as being one-half of the lower flamability limit. Thus, from a safety consideration, it was the highest level that could be tested.

Effect levels

Dose descriptor:
NOEC
Effect level:
> 40 000 ppm
Based on:
test mat.
Remarks:
exposure
Sex:
male/female
Basis for effect level:
other: The highest level tested, 40000 ppm, was selected as approximately 60% of the lower flamability level to provide a safety margin by not exposing test animals in a flamable atmosphere.

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
Rats were exposed to HFC-143a as a gas for 6 -hr/day, 5 days/wk for 13 weeks at levels up to 40,000 ppm. A post exposure observation group was included. No treatment related effects were seen in any of the parameters evaluated. The NOAEC was therefore 40000 ppm.
Executive summary:

Rats were exposed to HFC-143a as a gas for 6 -hr/day, 5 days/wk for 13 weeks at levels up to 40,000 ppm. A post exposure observation group was included. No treatment related effects were seen in any of the parameters (including reproductive organs) evaluated. The NOAEC was therefore 40000 ppm.