Registration Dossier

Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
24 May 2000 to 22 June 2000
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted under GLP conditions

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2000
Report Date:
2000

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
EPA OPPTS 870.1300 (Acute inhalation toxicity)
Deviations:
yes
Remarks:
For group 2 only, measurement of bodyweight was initiated 4 days prior to exposure and not 5 days as per protocol. This deviation from the protocol does not affect the scientific objectives or integrity or the study.
GLP compliance:
yes
Test type:
fixed concentration procedure

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report: T-7499; Perfluorobutyl sulfonyl fluoride
- Substance type: clear colorless liquid
- Physical state: liquid
- Analytical purity: 96-98 % Perfluorobutyl sulfonyl fluoride; 2-4% Perfluorosulfolane
- Lot/batch no.: none stated
- Expiration date of the lot/batch: none stated
- Storage condition of test material: In the dark at ambient room temperature and in the original container

Test animals

Species:
rat
Strain:
other: Sprague-Dawley, albino
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source:Charles River UK Limited, Maston Road, Margate, Kent, England.
- Age at study initiation: approximately 7 and 8 weeks old.
- Weight at study initiation: 198-281 g
- Housing:- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.5-29.5 degrees C
- Humidity (%): 33-69%
- Air changes (per hr): 15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours dark/12 hours light

Administration / exposure

Route of administration:
inhalation: vapour
Type of inhalation exposure:
nose only
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: vapor generator
- Exposure chamber volume:51 cm x 51 cm x 38 cm height.
- Method of holding animals in test chamber: held in stainless steel mesh exposure cage subdivided to provide 10 individual compartments for the rats.
- Source and rate of air: The test atmosphere entered the chamber through a port at the top centre of the chamber and was extracted through a port in the centre of the base, below the level of the rats. Each chamber was installed in a large fume cupboard exhausting through an absolute filter. The rate of air was 25 liters/minute.
- Method of conditioning air: test vapor passed through a glass column containing glass wool in order to prevent any condensate entering the exposure chamber. For group 4, the test vapour was passed through a condensor located upstream of the 'condensate trap'. A supply of water, maintained at ambient room temperature, was pumped through the condenser to cool the test vapour for exposure of rats.

TEST ATMOSPHERE
- Brief description of analytical method used: The test atmosphere entered the chamber through a port at the top centre of the chamber and was extracted through a port in the center of the base, below the level of the rats. Each chamber was installed in a large fume cupboard exhausting through an absolute filter.
- Samples taken from breathing zone: yes
Analytical verification of test atmosphere concentrations:
yes
Remarks:
The time weighted averages of chamber concentrations must be within 90% of the nominal concentration and is considered acceptable for generation systems of this design.
Concentrations:
1000, 5000 and 2000 ppm for groups 2, 3 and 4, respectively. The nominal concentrations were 1096 and 5635 ppm for groups 2 and 3, respectively.
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: All cages were checked twice daily to observe mortality and clinical signs. Clinical signs were recorded at the end of the chamber equilibration period, at 0.25, 0.5 and 1.0 hours then at hourly intervals during the exposure. Clinical signs were recorded immediately following the completion of the exposure and then at 1.0 and 2.0 hours post-exposure.
- Necropsy of survivors performed: yes
- Other examinations performed: mortality, clinical signs, body weight, lung weights, macroscopic pathology, food and water consumption.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LC50
Effect level:
ca. 999 - ca. 15 000 ppm
Exp. duration:
4 h
Remarks on result:
other: Group 4 was exposed to an estimated 15,000 ppm for a brief period of time before the exposure was stopped.
Mortality:
A single group 3 male rat was sacrificed for humane reasons, on Day 6 of the observation period, due to the deteriorating condition of an eye injury sustained during exposure.
Clinical signs:
Info on clinical signs : SEE Section "Any other information on results incl tables."
Body weight:
A mean bodyweight loss was evident for Groups 2 and 3 on Day 1 of the observation period and was marked for Group 3 male rats. A higher bodyweight gain was subsequently noted for Group 3 males on Day 2, compared with controls. Thereafter, although variable, the mean bodyweight gain of test rats was considered similar to control values. There were no treatment-related effects on the bodyweights of Group 4 rats, briefly exposed at approximately 15,00 ppm.
Gross pathology:
External findings noted for the rat sacrificed for humane reasons includede a damaged left eye. The eye and surrounding area were swollen and a clear discharge was noted from the eye.
Other findings:
A reduction in food consumption was evident for groups 2 and 3 on day 1 and was marked for group 3 males, persisting for approximately 5 days. A reduction in water consumption was evident for group 2 male rats and group 3 rats on day 1 and was marked for group 3 rats. There were no treatment related effects on lung weights.

Any other information on results incl. tables

Clinical signs :

During exposure, groups 2 and 3 experienced exaggerated breathing and a decreased breathing rate were evident in group 3 rats from 30 minutes into exposure and in group 2 rats from 30 minutes and 3 hours into exposure respectively. Other clinical signs noted during exposure included initial restless behaviour followed by reduced motor activity, and sudden movements characterised by pronounced jumping. The onset of these signs occured earlier during exposure of rats at the higher concentration (group 3). As a consequence of the pronounced jumping, the snout/limbs of of group 3 rats were observed to protuding through the bars of the confinement cage, resulting on occasions in a trapped snout. Fine muscle tremors and vocalising were also noted for a group 2 male and female, respectively. In group 4, clinical signs evident during the equilibrium period included restless behaviour, vocalisation, convulsions and a pronounced jumping, resulting in protrusion of snout/limbs and entrapment of snouts through the bars of the confinment cange. Exposure of group 4 rats was suspended during the equilibration period due to the nature and severity of these signs. During the observation perioud, exaggerated breathing was evident in all the test rats immediately following exposure, persisting up to days 1 and 2 for groups 2 and 3 respectively. A slow breathing rate was also noted for Group 3 rats following exposure, persisting for at least 2 hours post exposure. Additional clinical signs noted post exposure included the following: lethargy (all test groups), immobility (groups 3 and 4), hyperacitivity when handled (group 2 female), sensitive to touch and vocalisation when handled (groups 2 and 4), extremities cold to touch (group 3), labrimation (group 3 females), yellow staining around uro-genital area (group 2 and a group 3 male), yellow substance on fur of snout/jaws (group 3).

Clinical signs noted following exposure and considered associated with the pronounced jumping evident during exposure included the following: an apparent swelling under the left eye ( a group 2 male), left eye damaged and dark in colour ( a group 3 male) a cut to upper lip (a group 4 male) apparent swelling of the muzzle (a group 2 female). Brown staining on body was noted for all group 3 females on days 1 and 2 of the observattion period. One group 3 rat was sacrificed on day 6, for humane rasons, due to the deterioration in the condition of an eye injury sustained during exposre. The left eye was damaged, dark in colour and swollen. A clear discharge from the eye was noted and the area around the eye was also swollen. These observations are considered consistent with infection of the eye, 6 days after injury.

Applicant's summary and conclusion

Conclusions:
The LC50 (4-hour) of the test article was not determined for humane reasons, due to the nature and severity of the clinical signs evident during exposure of rats at concentrations in excess of approximately 5,000 ppm
Executive summary:

The acute (four-hour) inhalation toxicity was assessed in albino Sprague-Dawley rats. Three test groups and 1 control group (each of 5 female and 5 male rats) were exposed via inhalation of the vaporized test substance.Groups 1 to 3 were exposed to four-hour continuous snout-only exposure and observed for 14 days post exposure. Group four was terminated during equilibrium period an discarded on day 7. Groups 2 and 3 were exposed to a time-weighted average chamber concentrations of 999 ppm and 5,054 ppm for groups 2 and 3, respectively. Exposure of group 4 (at 20,000 ppm) was not performed due to humane reasons. A single group 3 male rat was sacrificed for humane reasons on day six of the observation period due to the deteriorating condition of an eye injury sustained during exposure. The LC50 (4-hour) of the test article was not determined for humane reasons, due to the nature and severity of the clinical signs evident during exposure of rats at concentrations in excess of approximately 5000 ppm.