Registration Dossier

Administrative data

Description of key information

HFIB is classified as Acute Tox. 3, H331 - Toxic if inhaled.

Key value for chemical safety assessment

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Published in 1986
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods with acceptable restrictions
Reference:
Composition 1
Principles of method if other than guideline:
- Principle of test: acute inhalation exposure of rats for 4 hours
- Short description of test conditions: single 4-hr exposure of different groups of rats in glass chambers
- Parameters analysed / observed: mortality and clinical signs, necropsy
GLP compliance:
not specified
Test type:
traditional method
Limit test:
no
Test material information:
Composition 1
Specific details on test material used for the study:
The test compound was supplied as a liquid (bp 11-13°C) in pressurized stainless-steeel cylinders. It was analyzed by gas chromatography-mass spectrometry prior to and immedaitely after the study, establishing the sample as being at least 99.9% pure HFIB and not containing any detectable PFIB (detection level < 1 ppm).
Species:
rat
Strain:
Fischer 344
Sex:
male/female
Details on test animals and environmental conditions:
Rats were obtained from Charles River Breeding Laboratory, Kingston, N.Y.
Animals were selected at random, from a dedicated larger population, on an "as needed" basis.
During nonexposure periods, all animals were housed individually in suspended stainless-steel mesh cages.
During exposure, animals were group-housed.
All animals were given food and water ad libitum during nonexposure periods only. Water was provided by an automatic watering system. Rats were given Purina Rat Chow 5001 feed.
Route of administration:
inhalation: gas
Type of inhalation exposure:
whole body
Vehicle:
other: prepurified compressed air
Details on inhalation exposure:
Acute inhalation exposures were conducted in 26.5-liter glass chambers operated on prepurified compressed air with a minimum air flow of 10 liters/min. This flow rate provided an equilibrium time (t99) of 12 min. The test atmosphere was generated through controlled release of HFIB from a pressurized cylinder and passing the vapor through a packed "T" tube flow meter after which it was diluted with prepurified compressed air to the desired exposure concentrations. The chambers were routinely monitored using a Wilks Scientific Miran 1-A ambient air analyzer. The HFIB exposure levels were verified periodically using a Perkin-Elmer Model Sigma 2 gas chromatograph with a multiple gas sampling valve attachment and Sigma 10 data station. Chamber exposure levels were measured 3 to 5 times during each acute exposure. Nominal concentrations were also calculated.
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
ca. 4 h
Concentrations:
1125, 1200, 1440, 1525, 2215, 2915, 3810 and 4510 ppm
No. of animals per sex per dose:
5 rats per sex per concentration
Control animals:
not specified
Details on study design:
Parameters analysed / observed: mortality and clinical signs, necropsy
Statistics:
The median lethal concentration (LC50) was estimated with approximate 95% confidence limits. Du to the phased exposure design of the study and small group sizes, no other parameters were evaluated statistically.
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
1 425 ppm
Based on:
test mat.
95% CL:
>= 1 345 - <= 1 505
Exp. duration:
4 h
Mortality:
Complete mortality was produced at 1525 ppm and above.
In groups exposed to 2215 ppm and higher, all deaths occurred within 24 hours of exposure.
In the 1525 ppm exposure group, deaths occurred from 3 to 5 days postexposure.
Partial mortality (3 out of 10) was observed at 1440 ppm, from 5 to 8 days postexposure.
No mortality was observed at 1125 or 1200 ppm.
Clinical signs:
Rapid or shallow breathing were noted at 1125 or 1200 ppm.
Body weight:
Body weight losses were noted at 1125 or 1200 ppm.
Gross pathology:
Not specified.
Other findings:
The clinical signs in animals which died were considered to be consistent with pulmonary edema in the higher levels and renal shut down in the lower level exposure groups.
Interpretation of results:
Category 3 based on GHS criteria
Conclusions:
Following 4-hour acute exposure of Fischer 344 rats (5 per gender), the LC50 was 1425 ppm (with [1345-1505] ppm 95% confidence interval).
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LC50
1 425

Additional information

Justification for classification or non-classification

Following 4-hour acute exposure of Fischer 344 rats (5 per gender), the LC50 was 1425 ppm (with [1345-1505] ppm 95% confidence interval), supporting classification of HFIB in Cat. 3.