Registration Dossier

Administrative data

Description of key information

4-hydroxy-4-methylpentan-2-one is not irritating for the skin but irritating for the eyes and the respiratory tract. Human volunteers exposed to 100 ppm 4-hydroxy-4-methylpentan-2-one for 15 min complained about eye, nose and throat irritation.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
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 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
-Observations at 1 hr and on Day 2 were not reported, occlusive dressing was used instead of semi-occlusive dressing
GLP compliance:
no
Remarks:
Study pre-dates GLP
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Ranch Rabbits, Crawley, Sussex
- Age at study initiation: 4 to 5 months
- Weight at study initiation: Not reported
- Housing: Housed individually in cages
- Diet (e.g. ad libitum): rabbit food (SG1 with vitamin C supplement, Grain Harvesters Ltd.) was replenished daily
- Water (e.g. ad libitum): Filtered but untreated water from the public supply was automatically replenished
- Acclimation period: 14 days

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
Preparation of test site:
other: shorn with fine electric clippers
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL or 500 mg
- Concentration (if solution): undiluted

Duration of treatment / exposure:
24 hours
Observation period:
7 days
Number of animals:
6 (3 animals/sex)
Details on study design:
TEST SITE
- Area of exposure: After the dorsal hair between shoulders and hindquarters was closely shorn, 2 test sites located lateral to the midline were selected. One of the test sites was abraded using a fine hypodermic needle giving injuries deep enough to disturb the stratum corneum without bleeding.
- % coverage: 2 x 2 cm
- Type of wrap if used: To each test site, a 2 x 2 cm lint patch was applied and 0.5 mL or 500 mg of the test material applied. The patches were occluded by an impervious polythene sheet held in place by means of an elastic adhesive bandage.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The wrappings and patches were removed and the residual test material washed from the skin with warm dilute detergent solution.
- Time after start of exposure: After 24 hours

SCORING SYSTEM: The intact and abraded test sites were examined and scored for erythema and oedema on a graded scale of 0 to 4 at 24 hours, 72 hours, and 7 days after application as detailed below:

Erythema scale: Score
No erythema: 0
Very slight erythema (barely perceptible, area not defined): 1
Well defined erythema (pale red, area well defined): 2
Moderate to severe erythema (bright red, area well defined): 3
Severe erythema (beet or crimson red): 4

Oedema scale: Score
No oedema: 0
Very slight oedema (barely perceptible, edges of area not defined): 1
Slight oedema (edges of area defined by raising): 2
Moderate oedema (area well defined, raised 1 mm): 3
Severe oedema (area raised more than 1 mm, extends beyond exposure area): 4

Injury in depth: Score
Escharosis, necrosis: 8

On the basis of the mean scores for erythema and oedema of the intact and abraded skin after 24 and 72 hours, the number of animals showing the responses and the persistence of the responses at 7 days, the irritation was transcribed into a grade and descriptive rating as follows:
1 = Non-irritating
2 = Minimally irritating
3 = Slightly irritating
4 = Mildly irritating
5 = Moderately irritating
6 = Severely irritating
7 = Extremely irritating
Irritation parameter:
erythema score
Basis:
mean
Time point:
24 h
Score:
0
Max. score:
4
Irritation parameter:
erythema score
Remarks:
erythema scorenon-abraded skin
Basis:
mean
Time point:
72 h
Score:
0
Max. score:
4
Irritation parameter:
erythema score
Remarks:
edema score non-abraded skin
Basis:
mean
Time point:
24 h
Score:
0
Max. score:
4
Irritation parameter:
erythema score
Remarks:
edema score non-abraded skin
Basis:
mean
Time point:
72 h
Score:
0
Max. score:
4
Interpretation of results:
other: minimally irritating (not classified)
Remarks:
Criteria used for interpretation of results: other: CLP (EC 1272/2008)
Conclusions:
A single 24 h application of the test material to occluded rabbit skin was minimally irritating.
Executive summary:

A skin irritation study on diacetone alcohol has been conducted in which no guidelines were followed; however, the study design was similar to OECD Guidelines for the Testing of Chemicals No. 404 with deviations.  In this study, 6 New Zealand White rabbits (3 animals/sex) were exposed to 0.5 mL of undiluted diacetone alcohol on the shorn dorsal region (intact and abraded) under occlusive conditions.  Animals were exposed to the test compound for 24 hours and observations were recorded at 24 and 72 hours, and 7 days after application of the test substance.  Skin reactions were scored according to a prescribed numerical system.  Very slight transient erythema was observed in 3 animals with abraded skin, which was fully reversible by Day 3 in all 3 animals.  The other rabbits with abraded skin did not display any dermal reactions.  No irritation was observed in animals with intact skin.  Based on the results of this study, the authors stated that diacetone alcohol was "minimally irritating to rabbit skin". However, the substance is considered to be non-irritating to intact skin.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline study without detailed documentations
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
not specified
Species:
rabbit
Strain:
not specified
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
0.1 ml
Observation period (in vivo):
1 hour and , 1, 2, 3, 4, 7 and 14 days
Number of animals or in vitro replicates:
3
Details on study design:
REMOVAL OF TEST SUBSTANCE
Any mass of material present in the conjunctival sac was removed at the 1h observation

SCORING SYSTEM: Draize scale

TOOL USED TO ASSESS SCORE: fluorescein
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1.7
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
2.3
Max. score:
3
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1.3
Max. score:
3
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1.7
Max. score:
3
Reversibility:
fully reversible within: 4 days
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1.7
Max. score:
3
Reversibility:
fully reversible within: 4 days
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.3
Max. score:
2
Reversibility:
fully reversible within: 2 days
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 4 days
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.7
Max. score:
2
Reversibility:
fully reversible within: 3 days
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1.3
Max. score:
4
Reversibility:
fully reversible within: 4 days
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1.7
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 21 days (according to Gautheron et al., 1994)
Interpretation of results:
irritating
Remarks:
Migrated information Criteria used for interpretation of results: other: REGULATION (EC) No 1272/2008
Conclusions:
Diacetone alcohol is irritating for the eyes.
Executive summary:

In a test performed by the French Health National Laboratory of the Medicine Agency following OECD Guideline # 405, 0.1 mL of undiluted diacetone alcohol was instilled into the eyes of 3 rabbits. It was observed a slight to moderate conjunctival irritation, which cleared in 7 days, a slight iritis which cleared in 4 days and a slight to moderate corneal opacity which cleared in 21 days. The mean individual score over 24, 48 and 72 hours were 1.3, 1.7 and 1.7 for chemosis, 1.7, 2.3 and 2.0 for conjunctival redness, 0.3, 1.0 and 0.7 for irritis and 1.3, 1.0 and 1.7 for corneal opacity.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Additional information

Skin irritation

A skin irritation study on 4-hydroxy-4-methylpentan-2-one has been conducted in which no guidelines were followed; however, the study design was similar to OECD Guidelines for the Testing of Chemicals No. 404 with deviations (Cassidy and Blair, 1978). In this study, 6 New Zealand White rabbits (3 animals/sex) were exposed to 0.5 mL of undiluted 4-hydroxy-4-methylpentan-2-one on the shorn dorsal region (intact and abraded) under occlusive conditions. Animals were exposed to the test compound for 24 hours and observations were recorded at 24 and 72 hours, and 7 days after application of the test substance. Skin reactions were scored according to a prescribed numerical system. Very slight transient erythema was observed in 3 animals with abraded skin, which was fully reversible by Day 3 in all 3 animals. The other rabbits with abraded skin did not display any dermal reactions. No irritation was observed in animals with intact skin. Based on the results of this study, the authors stated that 4-hydroxy-4-methylpentan-2-one was "minimally irritating to rabbit skin". However, the substance is considered to be non-irritating to intact skin.

Eye Irritation

In a key eye irritation test performed by the French Health National Laboratory of the Medicine Agency (Giroux, 1992) following OECD Guideline # 405, 0.1 mL of undiluted 4-hydroxy-4-methylpentan-2-one was instilled into the eyes of 3 rabbits. It was observed a slight to moderate conjunctival irritation, which cleared in 7 days, a slight iritis which cleared in 4 days and a slight to moderate corneal opacity which cleared in 21 days. The mean individual score over 24, 48 and 72 hours were 1.3, 1.7 and 1.7 for chemosis, 1.7, 2.3 and 2.0 for conjunctival redness, 0.3, 1.0 and 0.7 for irritis and 1.3, 1.0 and 1.7 for corneal opacity.

A supportive eye irritation study on 4-hydroxy-4-methylpentan-2-one has been performed in which no guidelines were followed; however, the study design was similar to OECD Guidelines for the Testing of Chemicals No. 405 (Cassidy and Blair, 1978). In this study, 0.2 mL of undiluted 4-hydroxy-4-methylpentan-2-one was instilled into one conjunctival sac of each of 3 New Zealand White rabbits. Ocular changes were assessed 1 to 2, 24, 48, 72 hours, and 7 days after treatment, and scoring was performed using the same scale as the OECD guideline, with the exception of 1 criteria (changes related to discharge were included in addition to other parameters evaluated). Immediately on instillation into the rabbit eyes, a moderate pain response was observed. Conjunctival redness and conjunctival chemosis were observed from 1 to 2 hours following instillation of the test substance to 3 days following treatment. These findings were fully resolved by 7 days after treatment. Corneal opacity and irritation and conjunctival discharge were also observed from 1 to 2 hours after instillation to 2 days after treatment. These findings were fully resolved by 3 days after treatment. Irritation observed in the iris from 1 to 2 hours after instillation to 1 day after treatment also was fully resolved by 2 days following treatment.

Respiratory tract irritation

A study with human volunteers (Nelson et al., 1943; Silverman et al., 1946), 12 subjects of both sexes were exposed by inhalation to 100 ppm 4-hydroxy-4-methylpentan-2-one (equivalent to 483 mg/m3) for 15 minutes. The majority of them found the odour and taste objectionable and complained about eye, nose and throat irritation although they indicated that they could work an 8 hour-day in 100 ppm.

Justification for classification or non-classification

According to the criteria for classification and labelling as set out in Regulation (EC) NO. 1272/2008, diacetone alcohol must be classified as eye irritant (category 2) and STOT (category 3, respiratory tract irritation).