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Administrative data

Description of key information

4-hydroxy-4-methylpentan-2-one is associated with low acute toxicity in rats following oral exposure (LD50= 3002 mg/kg bw), dermal exposure (LD0> 2 ml/kg (equivalent to 1875 mg/kg bw) and inhalation (4-h LC0 > 7.6 mg/L).

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
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.
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
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
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).
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.
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.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
3 002 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
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.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
yes
Remarks:
-no data tables provided
GLP compliance:
no
Remarks:
Study pre-dates GLP
Test type:
standard acute method
Limit test:
yes
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, given ad libitum after exposure to test article
- 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
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: Whole body exposure in chambers
- Exposure chamber volume: 7 Litres
- Method of holding animals in test chamber: Glass chambers are fitted with carriers to accomodate 5 animals each.
- Source and rate of air: minimal rate of 10 L/min
- Method of conditioning air: Not reported
- System of generating particulates/aerosols: Test atmospheres were generated using a thermostatted wick-type saturator.
- Method of particle size determination: Not applicable
- Treatment of exhaust air: Not reported
- Temperature, humidity, pressure in air chamber: Not reported

TEST ATMOSPHERE
- Brief description of analytical method used: DAA concentrations were determined using a heated total hydrocarbon analyser. This instrument was calibrated using standard diacetone alcohol/air mixtures prepared in Teflon FEP plastic bags.
- Samples taken from breathing zone: yes

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: Not applicable
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): Not applicable

CLASS METHOD (if applicable)
- Rationale for the selection of the starting concentration: Not reported
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
7.6 mg/L (range 7.2 to 8.1 mg/L)
No. of animals per sex per dose:
5 animals/sex
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Initial and 14-day body weights were recorded.
- Necropsy of survivors performed: no
- Other examinations performed: Animals were observed daily for toxic signs over the following 14 days.
Sex:
male/female
Dose descriptor:
LC0
Effect level:
>= 7.6 mg/L air
Exp. duration:
4 h
Mortality:
Exposure to concentrations of 7.6 (range 7.2 to 8.1) mg/L did not result in any mortalities.
Clinical signs:
Rats showed no toxic signs either during exposure or during the 14-day observation period.
Body weight:
Body weight data were not reported.
Gross pathology:
Not conducted.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: other: CLP (EC 1272/2008)
Executive summary:

The potential acute inhalation toxicity of diacetone alcohol was assessed in Wistar rats in a study similar in methodology to OECD Guidelines for the Testing of Chemicals No. 403 (Cassidy and Blair, 1978). Groups of 5 male and 5 female Wistar rats were exposed to 7.6 mg diacetone alcohol vapour /L (range 7.2 to 8.1 mg/L) for 4 hours via whole-body exposure in test chambers. Test atmospheres were generated using a thermostatted wick-type saturator and the test atmosphere was passed through each chamber at 10 L/minute. During the exposure, continuous analysis of the atmosphere was performed. The animals were observed for toxic signs throughout exposure and for 14 days after. No animals died, and no adverse effects were reported during exposure or during the 14-day observation period. The inhalation LC0 of diacetone alcohol was reported to be greater than 7.6 mg/liter.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating conc.
7 600 mg/m³

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
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.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
-body weights not reported, and gross pathologic examinations were conducted but no data was presented in report
GLP compliance:
no
Remarks:
Study pre-dates GLP
Test type:
standard acute method
Limit test:
yes
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: Not reported
- Housing: Four animals/sex were housed in each cage.
- Diet (e.g. ad libitum): Rat food (PRD, Labsure Animal Foods Ltd.), ad libitum; however, during the 24 hr exposure period, food was withheld
- 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
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: dorsal
- % coverage: Not reported
- Type of wrap if used: The test substance was covered with a piece of aluminium foil and held in place by a double overwrap of waterproof adhesive tape.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The foil and plaster dressing was carefully removed and the skin was washed with warm dilute detergent solution and then dried.
- Time after start of exposure: at the end of the 24 hr exposure period

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2 mL/kg body weight
- Concentration (if solution): undiluted
- Constant volume or concentration used: yes
Duration of exposure:
24 hours
Doses:
2 mL/kg body weight (1875 mg/kg body weight)
No. of animals per sex per dose:
6 animals/sex
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 or 21 days
- Frequency of observations and weighing: Body weights were recorded initially, Day 7, and on Day 14.
- Necropsy of survivors performed: yes
- Other examinations performed: Animals were observed for signs of toxicity over 14 or 21 days.
Sex:
male/female
Dose descriptor:
LD0
Effect level:
> 1 875 mg/kg bw
Mortality:
The application of undiluted chemical for 24 hours to groups of 6 male and 6 female rats did not result in any mortalities at a dose level of 2 mL/kg body weight, the largest volume that could be applied to the skin.
Clinical signs:
Rats showed no toxic signs.
Body weight:
Results were not reported.
Gross pathology:
Results were not reported.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: other: CLP (EC 1272/2008)
Conclusions:
The acute (24 h) percutaneous LD50 of the test material in rats was greater than 2 mL/kg body weight, the largest volume that could be applied to the skin (equivalent to greater than 1875 mg/kg body weight).
Executive summary:

The potential acute dermal toxicity of diacetone alcohol was assessed in Wistar rats in a study similar in methodology to OECD Guidelines for the Testing of Chemicals No. 402 (Cassidy and Blair, 1978). Undiluted diacetone alcohol was applied for 24 hours to 6 male and 6 female rats at 2 mL/kg body weight (equivalent to 1875 mg/kg body weight) for 24 hours. The test substance was applied to the shaved dorsal skin of the animals andcovered with a piece of aluminium foil held in place by a double overwrap of waterproof adhesive tape. After 24 hours, the foil and plastic dressing were removed, and the skin was washed with warm dilute detergent and dried. The animals were observed for signs of toxicity for 14 or 21 days and necropsy was performed. There were no reactions or clinical signs of toxicity, and the dermal LD0 of diacetone alcohol was reported to be greater than 2 mL/kg body weight (equivalent to 1875 mg/kg body weight).

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
1 875 mg/kg bw

Additional information

Acute Toxicity: Oral

The potential acute oral toxicity of 4-hydroxy-4-methylpentan-2-one 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 4-hydroxy-4-methylpentan-2-one died, 1 male and 1 female administered 2369 mg/kg body weight 4-hydroxy-4-methylpentan-2-one died, and all animals administered 3002, 3760, or 5969 mg/kg body weight 4-hydroxy-4-methylpentan-2-one died. Based on the mortality rate, the oral LD50value of 4-hydroxy-4-methylpentan-2-one was calculated as 3002 mg/kg body weight, with 95% fiducial limits of 2738-3290 mg/kg body weight.

Acute Toxicity: Dermal

The potential acute dermal toxicity of 4-hydroxy-4-methylpentan-2-one was assessed in Wistar rats in a study similar in methodology to OECD Guidelines for the Testing of Chemicals No. 402 (Cassidy and Blair, 1978). Undiluted 4-hydroxy-4-methylpentan-2-one was applied for 24 hours to 6 male and 6 female rats at 2 mL/kg body weight (equivalent to 1875 mg/kg body weight) for 24 hours. The test substance was applied to the shaved dorsal skin of the animals and covered with a piece of aluminium foil held in place by a double overwrap of waterproof adhesive tape. After 24 hours, the foil and plastic dressing were removed, and the skin was washed with warm dilute detergent and dried. The animals were observed for signs of toxicity for 14 or 21 days and necropsy was performed. There were no reactions or clinical signs of toxicity, and the dermal LD0of 4-hydroxy-4-methylpentan-2-one was reported to be greater than 2 mL/kg body weight (equivalent to 1875 mg/kg body weight).

A LD50-value of 14.5 ml/kg b. w. (equivalent to 13750 mg/kg) was reported in rabbits (Smyth Jr. and Carpenter 1948).

Acute Toxicity: Inhalation

The potential acute inhalation toxicity of 4-hydroxy-4-methylpentan-2-one was assessed in Wistar rats in a study similar in methodology to OECD Guidelines for the Testing of Chemicals No. 403 (Cassidy and Blair, 1978). Groups of 5 male and 5 female Wistar rats were exposed to 7.6 mg 4-hydroxy-4-methylpentan-2-one vapour /L (range 7.2 to 8.1 mg/L) for 4 hours via whole-body exposure in test chambers. Test atmospheres were generated using a thermostatted wick-type saturator and the test atmosphere was passed through each chamber at 10 L/minute. During the exposure, continuous analysis of the atmosphere was performed. The animals were observed for toxic signs throughout exposure and for 14 days after. No animals died, and no adverse effects were reported during exposure or during the 14-day observation period. The inhalation LC0 of 4-hydroxy-4-methylpentan-2-one was reported to be greater than 7.6 mg/liter.

Justification for classification or non-classification

The substance does not meet the criteria for classification and labelling for these endpoints, as set out in Regulation (EC) NO. 1272/2008.