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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1978
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline study without detailed documentation.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1978
Report Date:
1978

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
-body weights not reported and gross pathologic examinations were conducted but no data was presented in the report
GLP compliance:
no
Remarks:
Study pre-dates GLP
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): diacetone alcohol (DAA)
- Physical state: Stated in the report as a "widely used solvent"
- Analytical purity: Not reported
- Lot/batch No.: Reference PER 47657/2
- Expiration date of the lot/batch: Not reported
- Stability under test conditions: Not reported

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Shell Toxicology Laboraotry (Tunstall) Breeding Unit
- Age at study initiation: Approximately 10 weeks
- Weight at study initiation: Not reported
- Fasting period before study: 18 h overnight
- Housing: Four animals/sex were housed in each cage.
- Diet (e.g. ad libitum): Rat food (PRD, Labsure Animal Foods Ltd.), ad libitum
- Water (e.g. ad libitum): Filtered but untreated water from the public supply, provided by means of water bottles refilled every other day.
- Acclimation period: Not reported

ENVIRONMENTAL CONDITIONS
- Temperature (°C): room temperature, 22 ± 2
- Humidity (%): 55 ± 5
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 6.35 mL/kg body weight

DOSAGE PREPARATION (if unusual): Not reported

Doses:
2.00, 2.52, 3.18, 4.00, and 6.35 mL/kg body weight
No. of animals per sex per dose:
6 animals/sex/group
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Body weight measurements were recorded initially, on Day 7, and Day 14.
- Necropsy of survivors performed: yes
- Other examinations performed: Animals were observed for toxicological signs over 14 days.
Statistics:
Acute LD50 values and 95% confidence limits were calculated using the probit transformation of Finney (1962).

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
3 002 mg/kg bw
95% CL:
2 738 - 3 290
Mortality:
All 12 animals dosed 3.18, 4.00, and 6.35 mL/kg body weight died over a period of 14 days.
Two (2) out of the 12 animals administered 2.52 mL/kg body weight died over a period of 14 days.
All 12 animals administered 2.00 mL/kg body weight survived the test period.
See attached table 1 for further details.
Clinical signs:
Within a few hours of dosing the rats were lethargic and showed piloerection; one day later they were ataxic and at the higher dose levels, comatose.
Body weight:
Results were not reported.
Gross pathology:
Results were not reported.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: other: CLP (EC 1272/2008)
Conclusions:
The acute oral LD50 of the test material in rats was 3.2 mL/kg body weight (2.9 to 3.5 mL/kg body weight - 95% fiducial limits) [equivalent to 3002 mg/kg body weight (2738 to 3290 - 95% fiducial limits)].
Executive summary:

The potential acute oral toxicity of diacetone alcohol was assessed in Wistar rats in a study similar in methodology to OECD Guidelines for the Testing of Chemicals No. 401 (Cassidy and Blair, 1978). Groups of 6 male and 6 female rats were orally administered the compound at doses of 1880, 2369, 3002, 3760, or 5969 mg/kg body weight by gavage. Within a few hours of dosing, the rats were lethargic and showed piloerection, and 24 hours after dosing, the animals were ataxic; at higher dose levels the animals were comatose. No animals administered 1880 mg/kg body weight diacetone alcohol died, 1 male and 1 female administered 2369 mg/kg body weight diacetone alcohol died, and all animals administered 3002, 3760, or 5969 mg/kg body weight diacetone alcohol died. Based on the mortality rate, the oral LD50 value of diacetone alcohol was calculated as 3002 mg/kg body weight, with 95% fiducial limits of 2738-3290 mg/kg body weight.