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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
Study period:
1985
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
The study is reasonably well reported but there are deviations from an ideal protocol. It can be considered sufficiently well reported to be an acceptable study with sufficient basic documentation to demonstrate that it meets basic scientific principles and contains enough detail to be able to judge the results reliable.

Data source

Reference
Reference Type:
publication
Title:
Acute motor and lethal effects of inhaled toluene, 1,1,1-trichloroethane, halothane and ethanol in mice: effects of exposure duration.
Author:
Moser, V. and Balster
Year:
1985
Bibliographic source:
Toxicol Appl. Pharmacol 77:285-291.

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
yes
Remarks:
, Exposure period only 60 minutes. Species mouse rather than preferred rat. Observations reported for only 3 days rather than 14. Volume of chamber 29 litres (above 20 litres) . No detailed observations of effects. No pathology.
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Analytical purity: 95% USP

Test animals

Species:
mouse
Strain:
CD-1
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories, WIlmington, MA
- Age at study initiation: Not stated
- Weight at study initiation: 25 - 30 g
- Housing: standard mouse cages with wood chip bedding in groups of 6
- Diet at libitum (Rodent lab chow 5001, Ralston Purina Mills, St Louis, MO)
- Water ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature: 22 - 24°C
- Photoperiod (hrs dark / hrs light): 12 hour light/12 hour dark cycle

Administration / exposure

Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: glass chambers
- Exposure chamber volume: 29 litre
- Method of holding animals in test chamber: not restrained
- System of generating vapour: Solvent placed on a filter paper in the chamber which was suspended beneath a fan.

TEST ATMOSPHERE
- Brief description of analytical method used: verified using a single wavelength infrared spectrometer through a closed loop re-circulating pump
- Samples taken from breathing zone: no. Samples taken from different parts of the chamber prior to the study to ensure homogenous atmosphere so sampling could be done with confidence from the top of the chamber during the study.
Duration of exposure:
60 min
Concentrations:
40,000, 50,000 and 60,000 ppm for different exposure duration.
- One exposure period per exposure level.
- Exposure duration: 60, 30, and 10 minutes.
No. of animals per sex per dose:
6
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 72 days.
- Necropsy and target organs: not applicable.
Statistics:
Analysis by the probit analysis of Bliss (Quart J Pharmac, 11, 192, 1938) after log transformation and LC50 plus confidence limits calculated.

Results and discussion

Effect levelsopen allclose all
Sex:
male
Dose descriptor:
LC50
Effect level:
> 60 000 ppm
Exp. duration:
60 min
Sex:
male
Dose descriptor:
other: EC50
Effect level:
49 570 ppm
95% CL:
> 47 000 - < 52 600
Exp. duration:
10 min
Remarks on result:
other: based on motor performance test.
Sex:
male
Dose descriptor:
other: EC50
Effect level:
32 500 ppm
95% CL:
> 27 800 - < 37 750
Exp. duration:
30 min
Remarks on result:
other: based on motor performance test.
Sex:
male
Dose descriptor:
other: EC50
Effect level:
30 300
95% CL:
> 28 000 - < 32 750
Exp. duration:
60 min
Remarks on result:
other: based on motor performance test.
Mortality:
No LC50 was determined as no deaths occurred at any of the exposure concentrations.
Clinical signs:
other: Slight to moderate ataxia was observed and recovery from this exceeded 4 hours at all exposure levels.
Body weight:
no data
Gross pathology:
not performed

Any other information on results incl. tables

Recovery from the exposure as assessed using the motor performance test was slow. There was incomplete recovery up to 4 hours after exposure for all exposure period cohorts.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Whilst exposures were only for 1 hour, the evidence suggests that exposures for 4 hours would not have significantly reduced the motor performance results and that this would also apply to the LC50.
Executive summary:

In an acute toxicity inhalation study, mice were exposed to ethanol for different periods of time up to 1 hour in order to determine the LC50 and the EC50 for motor performance. An LC50 could not be obtained for inhalation exposure; no deaths were reported for exposures up to 60,000ppm (114mg/l), which can be considered the saturated vapour concentration. In the motor performance test, an EC50 60 min value of 30,300ppm was established, with a slope for the dose effect curve of 12.6. This result differered only slightly from the EC50 30 min. Whilst exposures were only for 1 hour, the evidence suggests that exposures for 4 hours would not have significantly reduced the motor performance results or the LC50. It should be noted that all of the reported EC50 values are above the lower explosive limit reported in chapter 4. On this basis and based on the result in mice, inhalation exposure poses little hazard at any feasible exposure concentration.