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Toxicological information

Repeated dose toxicity: inhalation

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Administrative data

Endpoint:
short-term repeated dose toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Cross-reference
Reason / purpose:
read-across: supporting information

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2013
Report Date:
2013

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 412 (Subacute Inhalation Toxicity: 28-Day Study)
GLP compliance:
yes
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
other: Crl:CD(SD)
Sex:
male/female

Administration / exposure

Route of administration:
inhalation: gas
Type of inhalation exposure:
whole body
Vehicle:
other: air and supplemental oxygen
Analytical verification of doses or concentrations:
yes
Remarks:
gas chromatography
Duration of treatment / exposure:
approximately 20 days of exposure followed by approximately 28 days of no-exposure (recovery)
Frequency of treatment:
6 hours/day, 5 days/week
Doses / concentrationsopen allclose all
Dose / conc.:
0 ppm
Dose / conc.:
2 500 ppm
Dose / conc.:
10 000 ppm
Dose / conc.:
50 000 ppm
No. of animals per sex per dose:
5 rats/sex/dose (subchronic with recovery subset)
Control animals:
yes

Examinations

Observations and examinations performed and frequency:
Body weight, clinical signs, food consumption were recorded throughout the study (during the treated period and the recovery period). Two ophtalmology evaluations were conducted by a veterinary ophtalmologist. Both eyes were examined by focal illumination and indirect ophtalmoscopy after mydriasis was produced.
On test day 29, blood and urine samples were collected from 5 male and 5 female rats per group for measurement of hematology, clinical chemistry and urinalysis parameters and again near the end of the recovery period on test day 57.
An abbreviated neurobehavioral evaluation was conducted on the 5 males and 5 females prior to test substance administration in order to obtain baseline measurements. This neurobehavioral evaluation was conducted again following approximately 4 weeks of exposure for the animals.
Sacrifice and pathology:
Following collection of terminal blood samples from the rats, the rats were euthanized, selected organs were weighed and selected tissues were evaluated microscopically.
The following organs were weighed fresh at necropsy from all adult animals: adrenals, brain, heart, kidneys, liver, lungs, spleen, thymus, ovaries, uterus, testes, epididymides, prostate, seminal vesicles, accessory sex organs.
Statistics:
yes

Results and discussion

Results of examinations

Clinical signs:
effects observed, non-treatment-related
Description (incidence and severity):
No test substance-related clinical signs of toxicity were observed in males or females.
Incidental clinical signs common to the age and strain of rat were occasionaly observed during the exposure and/or recovery periods.
Mortality:
no mortality observed
Description (incidence):
Unscheduled deaths did not occur in the animals.
Body weight and weight changes:
effects observed, non-treatment-related
Description (incidence and severity):
No adverse test substance-related effects on body weight or weight gain occurred in males or females.
The body weight changes observed at 10000 ppm (females) and 2500 ppm (females) were not dose-dependent and were considered to be spurious.
Food consumption and compound intake (if feeding study):
no effects observed
Description (incidence and severity):
No test substance-related effects or statistically differences in food consumption were observed for males or females.
Food efficiency:
no effects observed
Description (incidence and severity):
No test substance-related effects or statistically differences in food efficiency were observed for males or females.
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
no effects observed
Description (incidence and severity):
No adverse test substance-related ophtalmologic effects occurred in males or females.
Haematological findings:
effects observed, non-treatment-related
Description (incidence and severity):
No exposure-related changes in any group mean hematology parameter in male or female rats.
The following statistically significant difference was not considered to be related to exposure to the test substance: absolute large unstained cells were statistically significantly higher in female rats exposed to 50000 ppm. There were no other statistically significant differences in other white blood cell parameter in any subsets of male or female rats at any concentration tested. Therefore, this change was considered unrelated to exposure and non-adverse.
Clinical biochemistry findings:
effects observed, non-treatment-related
Description (incidence and severity):
No exposure-related changes in group mean clinical chemistry parameters in male or female rats.
The following statistically significant difference was not considered to be related to exposure to the test substance: blood urea nitrogen (BUN) was minimally lower in female rats exposed to 50000 ppm. However, there were no statistically significant differences in other kidney-related clinical pathology parameters and no exposure-related changes in renal histopathology in this group. Therefore, the lower BUN in the 50000 ppm females was considered unrelated to exposure and non-adverse.
Urinalysis findings:
no effects observed
Description (incidence and severity):
There were no statistically significant differences in group mean urinalysis parameters in male or female rats at any concentration tested.
Behaviour (functional findings):
no effects observed
Description (incidence and severity):
No test substance-related or statistically significant effects occurred on :
- on forelimb or hindlimb grip strength
- on any behavioral parameter evaluated
- on motor activity
for males and females exposed to the substance.
Immunological findings:
not examined
Organ weight findings including organ / body weight ratios:
effects observed, non-treatment-related
Description (incidence and severity):
No test substance-related organ weight effects. All individual and mean organ weight differences were considered spurious and unrelated to test substance exposure.
Gross pathological findings:
no effects observed
Description (incidence and severity):
No test substance-related gross observations in either male or female rats.
Neuropathological findings:
not examined
Histopathological findings: non-neoplastic:
not examined
Histopathological findings: neoplastic:
not examined
Other effects:
no effects observed
Description (incidence and severity):
Microscopic findings: no test substance-related microscopic findings in either male or female rats in the 50000 ppm inhalation exposure group.

Effect levels

Key result
Dose descriptor:
NOAEC
Effect level:
ca. 50 000 ppm
Based on:
test mat.
Sex:
male/female
Basis for effect level:
clinical signs
mortality
body weight and weight gain
food consumption and compound intake
food efficiency
ophthalmological examination
haematology
clinical biochemistry
urinalysis
behaviour (functional findings)
organ weights and organ / body weight ratios
gross pathology

Target system / organ toxicity

Key result
Critical effects observed:
no

Applicant's summary and conclusion

Conclusions:
Under the conditions of the study, the NOAEC of perfluoroethane for systemic toxicity in male and female rats was 50000 ppm, the highest concentration tested, based on the absence of effects in all endpoints.