4-hydroxy-4-methylpentan-2-one

Acute Toxicity: oral

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

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

Test material information

Constituent 1

Reference substance name:

4-hydroxy-4-methylpentan-2-one

EC Number:

204-626-7

EC Name:

4-hydroxy-4-methylpentan-2-one

Cas Number:

123-42-2

Molecular formula:

C6H12O2

IUPAC Name:

4-hydroxy-4-methylpentan-2-one

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 or test system 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:

other: 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.

Gross pathology:

Results were not reported.

Applicant's summary and conclusion

Interpretation of results:

not classified

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.