Registration Dossier

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other: GLP compliant, guideline study, available as unpublished report, no restrictions, fully adequate for assessment

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1982
Report Date:
1982

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
EPA OPP 81-3 (Acute inhalation toxicity)
Deviations:
not specified
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): 2-methyl-2-butene
- Physical state: Volatile colourless liquid
- Batch number: 9200/9315
- Source: Shell Nederland Chemie, Rotterdam, The Netherlands
- Expiration date of the lot/batch: 11 November 1981
- Specific gravity at 20°C: 0.65
- Boiling range: 28-40°C
- Vapour pressure at 20°C: 459 mm Hg
- Saturated vapour concentration at 20°C: 60.4% v/v
- Explosive limits in air: 1.5-8.3% v/v
- Odour threshold: 1-10 mg m-3
- 2-methyl-2-butene is capable of forming explosive mixtures with air in concentrations above 1.5% (v/v) and below 8.3% (v/v)

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Shell Toxicology Laboratory, Tunstall Unit
- Age at study initiation: Approximately 9 weeks
- Weight at study initiation: 302 - 318g (males) and 221 - 239 g (females)
- Fasting period before study: none
- Housing: Individually in hanging stainless steel cages with wire mesh floor and top
- Diet: PRD, Labsure Animal Foods Ltd ad libitum except during exposure
- Water: ad libitum
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
- Temperature: Approximately 20°C
- Humidity: Approximately 55%
- Air changes (per hr): no data
- Photoperiod: 12 hrs dark / 12 hrs light

IN-LIFE DATES: From: 25 November 1980 to 9 December 1980

Administration / exposure

Route of administration:
inhalation
Type of inhalation exposure:
whole body
Vehicle:
other: air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: The test atmospheres were generated by means of a wick-type saturator maintained at 0°C in an ice/water bath, and were supplied to two identical, glass inhalation chambers
- Exposure chamber volume: 7 litres
- Method of holding animals in test chamber: The animals were housed in two 7 litre tubular glass chambers fitted with stainless steel mesh carriers to accommodate five animals each.
- The test atmosphere was supplied to the chambers at a rate in the range 5.0 to 13.5 litres per minute.
- The chambers were located in a fume cupboard together with the atmosphere generator.
- The air flow rate through each chamber was approximately 6 litres min-1.

TEST ATMOSPHERE
- Brief description of analytical method used: The atmospheric concentration of the 2-methyl-2-butene was measured continuously throughout the exposure by means of a MIRAN infra red analyser. The instrument was calibrated by injecting known volumes of test substance into a closed loop recycle system of known volume, which included the 5.6 litre analyser gas cell.
- Samples taken from breathing zone: yes
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
6.1% (v/v) (range 3.3-9.4%) (nominal 61,000 ppm equivalent to 175,000 mg/m3)
No. of animals per sex per dose:
5
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observed for toxic signs continuously for the first 30 min and thereafter at 15 min intervals throughout the exposure. Immediately following exposure, they were observed for 3 hrs at 15 minute intervals. Over the following 14 days, the animals were observed twice daily.
- Initial, 7 day and 14 day body weights were recorded.
- Necropsy of survivors performed: yes
- The current recommendation for the minimum concentration of oxygen in test atmospheres for use in inhalation toxicity testing is 19% (v/v). Whilst larger concentrations of the test substance in air can be generated, a concentration of 9.5% (v/v) test substance would reduce the oxygen content to 19% (v/v).

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 6.1 other: %
Remarks on result:
other: >175000 mg/m3
Mortality:
None.
Clinical signs:
During the exposure period both male and female rats first became ataxic, this condition also being associated with body tremors. After approximately 40 min of exposure both male and female animals became narcotized whilst exhibiting intermittent movements of front and hind limbs. The animals remained narcotized for the remainder of the exposure period. On removal from the exposure chambers, all the animals regained consciousness within 90 sec although symptoms of ataxia persisted for a further 10 to 15 min. Within 30 min, all the animals had fully recovered and no further signs of toxicity were observed throughout the 14 day observation period.
Body weight:
No effects on body weight.
Gross pathology:
No compound related effects.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute 4 hour inhalation LC50 of 2-methyl-2-butene in rats is greater than 6.1% (v/v) equivalent to 175,000 mg/m3.
Executive summary:

A group of 5 male and 5 female rats was exposed for 4 hours to a test atmosphere containing 6.1% (v/v) 2-methyl-2-butene. During the exposure the animals became narcotized, but revived within 30 min of cessation of exposure. There were no deaths. Macroscopic and microscopic examination of animals killed 14 days after exposure revealed no compound related effects. The acute 4 hour inhalation LC50 of 2-methyl-2-butene in rats is greater than 6.1% (v/v) (175,000 mg/m3).