Registration Dossier

Diss Factsheets

Administrative data

Endpoint:
repeated dose toxicity: inhalation, other
Remarks:
10 exposures of 4 h/day
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
1966, no further information.
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
significant methodological deficiencies

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1966
Report date:
1966

Materials and methods

Test guideline
Qualifier:
no guideline available
Principles of method if other than guideline:
- Principle of test:
Daily 4 h exposures to the test substance were made over a period of 10 days. Observations were made in comparison to a control group that was similarly exposed without the test substance.
- Short description of test conditions:
The test substance was metered into a T-tube, volatilized, diluted with air, and passed into an exposure chamber containing 6 rats. The same group of rats was exposed 4 h per day for 10 exposures, averaging 300 ppm. Half of the rats were sacrificed for histopathologic examination after the tenth exposure, and the other half were sacrificed after a 14-day recovery period. A control group of 6 rats was exposed to air, and sacrificed according to the same schedule. The chamber atmosphere was analysed by a gas chromatographic procedure an average of 4 times per exposure, with results averaging 300 ± 24 ppm test substance.
- Parameters analysed / observed:
Initial body weights were measured, exposure chamber atmosphere was analyzed, and histopathologic examinations were conducted at the end of the exposure period, and at post-recovery, findings were recorded.
GLP compliance:
no
Remarks:
pre-GLP
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
1,1,1,3,3,3-hexafluoropropan-2-ol
EC Number:
213-059-4
EC Name:
1,1,1,3,3,3-hexafluoropropan-2-ol
Cas Number:
920-66-1
Molecular formula:
C3H2F6O
IUPAC Name:
1,1,1,3,3,3-hexafluoropropan-2-ol
Test material form:
liquid

Test animals

Species:
rat
Strain:
other: ChR-CD
Details on species / strain selection:
None specified
Sex:
male
Details on test animals or test system and environmental conditions:
None specified

Administration / exposure

Route of administration:
inhalation
Type of inhalation exposure:
other: vapour
Vehicle:
air
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
gas chromatographic procedure, four times per exposure.
Duration of treatment / exposure:
4 h
Frequency of treatment:
daily / ten exposures
Doses / concentrations
Dose / conc.:
300 ppm (analytical)
Remarks:
standard deviation of ±24 ppm
No. of animals per sex per dose:
6 male
Control animals:
yes

Examinations

Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: no data

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: no data

BODY WEIGHT: Yes
- Time schedule for examinations: initial body weights taken before first exposure
Sacrifice and pathology:
GROSS PATHOLOGY: Yes / No further information given
HISTOPATHOLOGY: Yes / Tissues examined: trachea, lung, kidney, liver, epididymis, testis, adrenal, brain, pituitary, esophagus, stomach, duodenum, pancreas, heart, bone marrow, thymus, thyroid and parathyroid, spleen, eye and lymph node. Special organ removal and sectioning techniques were used to examine for evidence of oligospermia or aspermia.

Results and discussion

Results of examinations

Clinical signs:
effects observed, treatment-related
Description (incidence and severity):
The first week the test rats exhibited blinking, lacrimation, salivation, nasal discharge, unresponsiveness, irregular breathing and mild hyperaemia during the exposure. Mild exophthalmos was observed immediately after the first few exposures. During the second week, mild chromodacryorrhea and eye discharge also were evident. No abnormal signs were observed during the recovery period. Growth was normal and comparable to that of the control rats. The vapours of HFIP at an atmospheric level of 300 ppm caused clinical signs indicative of respiratory irritation. However, repeated exposure at this level did not cause any discernible tissue changes that correlated to the clinical signs observed.
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Description (incidence and severity):
Initial body weights: 242-278 g. Growth was normal and comparable to that of the controls.
Food consumption and compound intake (if feeding study):
not examined
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
not examined
Haematological findings:
not examined
Clinical biochemistry findings:
not examined
Urinalysis findings:
not examined
Behaviour (functional findings):
not examined
Immunological findings:
not examined
Organ weight findings including organ / body weight ratios:
not examined
Gross pathological findings:
no effects observed
Neuropathological findings:
not specified
Histopathological findings: non-neoplastic:
no effects observed
Histopathological findings: neoplastic:
not specified
Other effects:
no effects observed
Description (incidence and severity):
No evidence of oligospermia or aspermia.

Effect levels

Key result
Dose descriptor:
NOAEC
Effect level:
ca. 300 ppm (analytical)
Based on:
test mat.
Sex:
male
Basis for effect level:
clinical signs

Applicant's summary and conclusion

Conclusions:
CLP/EU GHS criteria are not met, no classification required according to Regulation (EC) No 1272/2008. This study was conducted prior to publication (1981) of the OECD Test Guideline requirements for either acute, or repeated dose inhalation studies. Although the in vivo data is old and study reliability may be that of reliability 3, results of repeated exposure to the test substance at this level showed evidence of initial respiratory irritation, but did not cause any discernable tissue changes.