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Toxicological information

Acute Toxicity: inhalation

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Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: 1a GLP Guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1992

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Pentafluoroethane
EC Number:
206-557-8
EC Name:
Pentafluoroethane
Cas Number:
354-33-6
Molecular formula:
C2HF5
IUPAC Name:
1,1,1,2,2-pentafluoroethane
Details on test material:
- Name of test material (as cited in study report): HFC-125
- Substance type: fluorinated alkane
- Physical state: gasseous
- Analytical purity: 99.558%
- Impurities (identity and concentrations): not reported
- Composition of test material, percentage of components: pure substance
- Isomers composition: n/a
- Purity test date: not reported
- Lot/batch No.: BR131
- Expiration date of the lot/batch: not reported
- Stability under test conditions: Stability of the test material was confirmed by GC analysis on 3 days before and after the dosing day.
- Storage condition of test material: Sample stored for 3 days at room temperature in a gas cylinder

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Japan, Inc.
- Age at study initiation: 6 week old
- Weight at study initiation: males 190-215 g; females 140-155 g
- Fasting period before study: no fasting before the dosing day
- Housing: Stainless steel cage (1 animal/cage)
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 1 week


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23 +/-2 (during quarantine, exposure period and recovery period)
- Humidity (%): 55 +/- 10% (during quarantine and recovery period); 22 +/- 2% (during the 4-h exposure period)
- Air changes (per hr): 15-17/hr (during quarantine and recovery period); 12/hr (during the 4-h exposure period)
- Photoperiod (hrs dark / hrs light): 12 hr/12 hr


IN-LIFE DATES: From:8 Oct 1991 To: 29 Oct 1991

Administration / exposure

Route of administration:
inhalation: gas
Type of inhalation exposure:
whole body
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Exposure chamber (whole body exposure)
- Exposure chamber volume: 520 L
- Method of holding animals in test chamber: individual cages
- Source and rate of air: Room air filtered through an HEPA filter (control animals); Mixture of HFC-125/oxygen 80/20% (exposure group)
- Method of conditioning air:
- System of generating particulates/aerosols: HFC-125 released from the gas cylinder was diluted with oxygen in a line mixer and the mixture was
conveyed to the exposure chamber.
- Method of particle size determination: n/a
- Treatment of exhaust air: no information reported
- Temperature, humidity, pressure in air chamber: parameters were constantly monitored during the exposure period


TEST ATMOSPHERE
- Brief description of analytical method used: GC analysis:
Instrument: Shimadzu GC-8AIF
Column: CDC-200, 3m, 3mm diameter
Column oven temperature: 60°C
Carrier: N2, 1.5 kg/cm2
Detector: flame ionization, 60°C
Injection volume: 0.2 ml exhaust atmosphere from the exposure chamber
- Samples taken from breathing zone: yes

CLASS METHOD (if applicable)
- Rationale for the selection of the starting concentration: Maximal applicable concentration
Analytical verification of test atmosphere concentrations:
yes
Remarks:
the exposure concentration was monitored via GC analysis during the exposure period.
Duration of exposure:
4 h
Concentrations:
800000 ppm (3,927,000 mg/m3)
No. of animals per sex per dose:
5
Control animals:
yes
Details on study design:
Parameter evaluated:  Observation of clinical signs and mortality were carried out during the  exposure period, 1, 3 and 6 hours after the end of 
exposure and more than once a day for 14 days. Body weights were measured prior the exposure and on day 1, 3, 7, 10 and  14. Gross pathology
examinations were carried out at the end of exposure  period.
- Duration of observation period following administration: 14 days
- Frequency of observations: Quarantine period: more than once a day. Exposure period: every 15 minutes during the first hour and every hour
onward. Recovery period: 1, 3 and 6 hour after the exposure termination; more than once a day from day 1 to day 14.
- Body weight: 2 times during quarantine and adaptation period, on the exposure day and on day 1, 3, 7, 10 and 14 of the post exposure period
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: no

Results and discussion

Preliminary study:
No mortality was observed during the study. During the exposure clinical signs such as ataxic gait, and abnormal  respiration were observed in all 
exposed rats. The clinical signs  disappeared one hour after the exposure. There was a slight decrease in mean body weight of exposed males in
comparison to control value. No findings were observed during pathology examinations.
Effect levels
Sex:
male/female
Dose descriptor:
LCLo
Effect level:
> 800 000 ppm
Exp. duration:
4 h
Mortality:
No mortality observed
Clinical signs:
other: Signs of anesthesy (ataxic gait and abnormal respiration) observed during the exposure period.
Body weight:
No significant changes
Gross pathology:
No findings

Applicant's summary and conclusion

Interpretation of results:
practically nontoxic
Remarks:
Migrated information
Conclusions:
The lowest lethal dose (LDLo) was > 800,000 ppm (highest dose tested) for this study.
Executive summary:

In an OECD guideline study (Nakayama et al., 1992a), 10 Sprague Dawley rats (5 males and 5 females) were exposed to 800,000 ppm (3,927,000 mg/m3) HFC-125 in atmosphere for 4 hours.  Another 10 animals were exposed to normal air for control.  No mortality was observed within 14 days after the exposure.  During the exposure, clinical signs typical of an anaesthetic effect, such as abnormal respiration and ataxic gait, were observed.  These effects disappeared within 1 hour after the end of the exposure period.  A slight decrease in mean body weight was registered in the exposed males, in comparison with the control males.  No findings were observed during the autopsy.  The lowest lethal dose (LDLo) was > 800,000 ppm (highest dose tested) for this study.