Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Non-GLP, available as unpublished report, near guideline study, minor restrictions in design and/or reporting but otherwise adequate for assessment

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1980
Report Date:
1980

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
no
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: Strong smelling, colourless liquid with a specific gravity of 0.66
- Stability under test conditions: Stable for duration of experiment, expiry date 1 January 1981
- Storage condition of test material: In fridge

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Shell Toxicology Laboratory, Breeding Unit, Tunstall, UK
- Age at study initiation: 10-11 weeks
- Weight at study initiation: 260-366 g males, 177-248 g females
- Fasting period before study: 18 hours
- Housing: 3-4/cage in hanging polypropylene cages with stainless steel wire mesh floors and tops (33 x 21 x 17 cm)
- Diet: PRD (Labsure Animal Foods Ltd) ad libitum (except for pre-dose fast)
- Water: Filtered public supply ad libitum
- Acclimation period: 4 weeks

ENVIRONMENTAL CONDITIONS
- Temperature: 19-25 °C
- Humidity: 50-60%
- Air changes (per hr): Not reported
- Photoperiod: 12 hrs dark / 12 hrs light

IN-LIFE DATES: From: 7 May 1980 To: 18 July 1980

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Doses:
1.0, 1.6, 2.5, 4.0, 6.3 and 10.0 mL/kg
No. of animals per sex per dose:
6
Control animals:
no
Details on study design:
- Dose levels selected following a range-finding test in which 2 rats/sex/group were given a single oral dose at 0.5, 1.0, 5.0 or 10.0 mL/kg.
- Due to volatility of 2-methyl-2-butene, it was stored on ice, temperature of substance at dosing was approximately 5°C.
- Duration of observation period following administration: 14 days.
- Frequency of observations and weighing: Observations daily, weighed on days 7 and 14.
- Necropsy of survivors performed: no

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
1 - 4 mL/kg bw
Remarks on result:
other: equivalent to 700 - 2600 mg/kg. Further examination of data (SIDS, 2005) places in the range of 1000 - 1700 mg/kg
Mortality:
Cumulative mortality (over 14 days) was 0, 6, 4, 9, 9 and 12 (6 male and 6 females/group) for the 1.0, 1.6, 2.5, 4.0, 6.3 and 10.0 mL/kg dose levels respectively.
Clinical signs:
Virtually all animals, even at the lowest doses, had diarrhoea, bleeding from the anus and piloerection on the day of dosing. Most animals were also lethargic. Most deaths occurred within 3 days and most surviving animals had recovered by day 3. However, there were a few animals in which signs of intoxication persisted for up to a week after dosing.
Body weight:
All but one of the survivors had gained weight at the conclusion of the 14 day observation period.

Applicant's summary and conclusion

Interpretation of results:
harmful
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Acute oral LD50 of 2-methyl-2-butene to male and female rats was approximately 1-4 mL/kg (700 - 2600 mg/kg)
Executive summary:

Acute oral LD50 of 2-methyl-2-butene to male and female rats was approximately 1-4 mL/kg (700 - 2600 mg/kg). Further assessment of the data allows refinement to a range of 1000 - 1700 mg/kg (OECD SIDS, 2005).