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Toxicological information

Acute Toxicity: dermal

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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
24-hour application followed by 14-day observation period
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Study conducted prior to the introduction of Good Laboratory Practices; data from a summary report; limited number of animals; actual test report not available for review. Study was conducted by an internal Eastman Kodak Company method, developed prior to established guidelines. The results of this study are valid for classification insofar as the conditions of exposure (24 hours under an occlusive wrap) are at least as stringent as modern guidelines.
Cross-referenceopen allclose all
Reason / purpose for cross-reference:
reference to same study
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
single dose followed by 14-day observation period
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Study was conducted prior to introduction of Good Laboratory Practices; data from a summary report; limited number of animals; actual test report not available for review but raw data were reviewed for this entry. Study was conducted by an internal Eastman Kodak Company method, developed prior to established guidelines. The results of this study are valid for classification insofar as the conditions of exposure are at least as stringent as modern guidelines.
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to same study
Qualifier:
no guideline available
Principles of method if other than guideline:
A total of five male rats were administered a single dose (1 rat/dose level) of the undiluted test material at dose levels of 800, 1600, 3200, 6400, or 12800 mg/kg bw by oral gavage and observed for a period of two weeks. Clinical observations and mortality were noted during the study. Body weights were recorded prior to dosing and at termination of the observation period.
GLP compliance:
no
Test type:
other: Study conducted according to an internal Eastman Kodak Company laboratory method.
Limit test:
no
Species:
rat
Strain:
not specified
Sex:
male
Details on test animals or test system and environmental conditions:
no data
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
Single animals received one dose of undiluted test material by oral gavage.
Doses:
800, 1600, 3200, 6400, or 12800 mg/kg bw
No. of animals per sex per dose:
1 animal/dose
Control animals:
no
Details on study design:
One animal was assigned to each dose group (age and weights not provided). Rats were administered a single dose of the undiluted test material by oral gavage at dose levels of 800, 1600, 3200, 6400, or 12800 mg/kg bw. The rats were observed for a 14-day period for adverse clinical signs and mortality. Body weights were collected prior to dosing and at termination of the observation period.
Statistics:
no data
Sex:
male
Dose descriptor:
LD50
Effect level:
> 3 200 - < 6 400 mg/kg bw
Remarks on result:
other: The three highest dose levels (3200, 6400, and 12800 mg/kg bw) used in this study are higher than that used for a limit dose in present-day guideline studies.
Mortality:
The rats administered 6400 and 12800 mg/kg bw died on the day of administration of the test material. All rats administered doses of 800, 1600, or 3200 mg/kg bw survived to termination of the 14-day observation period.
Clinical signs:
Clinical signs of toxicity reported in the study summary included weakness, ataxia, and prostration. No other clinical abnormalities were reported during the study.
Body weight:
All surviving rats gained weight over the 14-day observation period.
Gross pathology:
Not performed
Interpretation of results:
other:
Remarks:
EU-GHS criteria not met
Conclusions:
Under conditions used in this study, methyl isoamyl ketone was only slightly toxic by the oral route in rats. The single-dose oral LD50 in rats was > 3200 mg/kg bw but < 6400 mg/kg bw.

Based on an acute oral LD50 value between 3200 and 6400 mg/kg bw in rats, methyl isoamyl ketone could be classified as Category V for classification and labeling for acute lethality by the oral route under GHS. As this REACH registration, however, requires the use of EU-GHS, no classification is warranted. This acute oral toxicity value is supported by similar clinical signs and an oral LD50 value of 3200 – 6400 mg/kg bw in a study conducted in mice by the same testing laboratory during the same time period.
Executive summary:

In an acute oral toxicity study, a total of five rats were administered a single dose of undiluted methyl isoamyl ketone by gavage at dose levels of 800, 1600, 3200, 6400, or 12800 mg/kg bw and observed for mortality and adverse clinical signs for a period of 14-days. Rats administered doses of 6400 and 12800 mg/kg bw died on the day of dosing. Clinical signs of toxicity reported in the study summary included weakness, ataxia, and prostration. All surviving rats gained weight over the 14-day observation period. The oral LD50 in rats is considered to be between 3200 and 6400 mg/kg bw. Based on the results of this study, methyl isoamyl ketone may be harmful by the oral route. Ingestion of large amounts may cause effects on the central nervous system. According to EU-GHS no classification is warranted for 5 -methylhexan-2 -one for acute oral toxicity.

Reason / purpose for cross-reference:
reference to same study
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
single dose followed by 14-day observation period
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Study conducted prior to introduction of Good Laboratory Practices; data from a summary report; limited number of animals; actual test report not available for review but raw data were reviewed for this entry. Study was conducted by an internal Eastman Kodak Company method, developed prior to established guidelines. The results of this study are valid for classification insofar as the conditions of exposure are at least as stringent as modern guidelines.
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to same study
Qualifier:
no guideline available
Principles of method if other than guideline:
A total of five male mice were administered a single dose (1 mouse/dose level) of the undiluted test material at dose levels of 400, 800, 1600, 3200, or 6400 mg/kg bw by oral gavage and observed for a period of two weeks. Clinical observations and mortality were noted during the study. Body weights were recorded prior to dosing and at termination of the observation period. No gross pathology was performed at study termination.
GLP compliance:
no
Test type:
other: Study conducted according to an internal Eastman Kodak Company laboratory method.
Limit test:
no
Species:
mouse
Strain:
not specified
Sex:
male
Details on test animals or test system and environmental conditions:
no data
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
Single animals received one dose of undiluted test material by oral gavage.
Doses:
400, 800, 1600, 3200, or 6400 mg/kg bw
No. of animals per sex per dose:
1 animal/dose
Control animals:
no
Details on study design:
One animal was assigned to each dose group (age and weights not provided). Mice were administered a single dose of the undiluted test material by oral gavage at dose levels of 400, 800, 1600, 3200, or 6400 mg/kg bw. The mice were observed for a 14-day period for adverse clinical signs and mortality. Body weights were collected prior to dosing and at termination of the observation period.
Statistics:
no data
Sex:
male
Dose descriptor:
LD50
Effect level:
> 3 200 - < 6 400 mg/kg bw
Remarks on result:
other: The two highest dose levels (3200 and 6400 mg/kg bw) used in this study are higher than that used for a limit dose in present-day guideline studies.
Mortality:
The mouse administered 6400 mg/kg bw died 40 minutes after administration of the test material. All mice administered doses of 400, 800, 1600, or 3200 mg/kg bw survived to termination of the 14-day observation period.
Clinical signs:
Clinical signs of toxicity reported in the study summary included weakness, ataxia, prostration, and rolling over at the highest dose level (6400 mg/kg bw). No other clinical abnormalities were reported during the study.
Body weight:
All surviving mice gained weight over the 14-day observation period.
Gross pathology:
Not performed
Interpretation of results:
other:
Remarks:
EU-GHS criteria not met
Conclusions:
Under conditions used in this study, methyl isoamyl ketone was only slightly toxic by the oral route in mice. The single-dose oral LD50 in mice was > 3200 mg/kg bw but < 6400 mg/kg bw.

Based on an acute oral LD50 value between 3200 and 6400 mg/kg bw in mice, methyl isoamyl ketone could be classified as Category V for classification and labeling for acute lethality by the oral route under GHS. As this REACH registration, however, requires the use of EU-GHS, no classification is warranted. This acute oral toxicity value is supported by similar clinical signs and an oral LD50 value of 3200 – 6400 mg/kg bw in a study conducted in rats by the same testing laboratory during the same time period.
Executive summary:

In an acute oral toxicity study, a total of five mice were administered a single dose of undiluted methyl isoamyl ketone by gavage at dose levels of 400, 800, 1600, 3200, or 6400 mg/kg bw and observed for mortality and adverse clinical signs for a period of 14-days. The mouse administered a dose of 6400 mg/kg bw died on the day of dosing (40 minutes post-dose). Clinical signs of toxicity reported in the study summary included weakness, ataxia, prostration, and rolling over at the highest dose level (6400 mg/kg bw). All surviving mice gained weight over the 14-day observation period. The oral LD50 in mice is considered to be between 3200 and 6400 mg/kg bw. Based on the results of this study, methyl isoamyl ketone may be harmful by the oral route. Ingestion of large amounts may cause effects on the central nervous system. According to EU-GHS no classification is warranted for 5 -methylhexan-2 -one for acute oral toxicity.

Reason / purpose for cross-reference:
reference to same study
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
6-hour exposure followed by 14-day observation period
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Study conducted prior to introduction of Good Laboratory Practices; data from a summary report; limited number of animals; actual test report not available for review. Study was conducted by an internal Eastman Kodak Company method, developed prior to established guidelines.
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to same study
Qualifier:
no guideline available
Principles of method if other than guideline:
Method is an in vivo study using a group of three rats (sex, strain, and weights not available) exposed to an atmosphere containing the test material for a period of six hours. After termination of exposure, the animals were observed for mortality and adverse clinical signs for a period of 14 days. Body weights were measured prior to exposure and at termination of the 2-week observation period. No gross pathology was performed at study termination.
GLP compliance:
no
Test type:
other: Study conducted according to an internal Eastman Kodak Company laboratory method, in which rats were exposed via inhalation for 6 hours.
Limit test:
no
Species:
rat
Strain:
not specified
Sex:
not specified
Details on test animals or test system and environmental conditions:
no data
Route of administration:
inhalation
Type of inhalation exposure:
whole body
Vehicle:
other: air
Details on inhalation exposure:
Rats were exposed (whole-body) to an ambient (room temperature) atmosphere containing 3.88 mg/L (calculated as 948 ppm) of the test material for a period of 6 hours. The atmosphere was generated by passing room air at ambient temperature at a rate of 0.5 L/minute through a washing bottle containing the test material. This air was blended with bypass air provided at 3.5 L/minute using a tee external to the exposure chamber. The atmosphere generated in this manner was then passed into the chamber containing the rats.
Analytical verification of test atmosphere concentrations:
not specified
Duration of exposure:
6 h
Concentrations:
3.88 mg/L (calculated as 948 ppm)
No. of animals per sex per dose:
3 (sex not specified)
Control animals:
no
Details on study design:
Three rats (sex, strain, and weights not available) were exposed (whole-body) to an ambient (room temperature) atmosphere containing 3.88 mg/L (calculated as 948 ppm) of the test material for a period of six hours. The atmosphere was generated by passing room air at ambient temperature at a rate of 0.5 L/minute through a washing bottle containing the test material. This air was blended with bypass air provided at 3.5 L/minute using a tee external to the exposure chamber. The atmosphere generated in this manner was then passed into the chamber containing the rats. Animals were observed for mortality and adverse effects during and subsequent to exposure.
Sex:
not specified
Dose descriptor:
LCLo
Effect level:
> 3.88 mg/L air
Mortality:
None
Clinical signs:
other: No signs of systemic toxicity or abnormal clinical signs were noted during the study.
Body weight:
All animals gained weight over the 14-day observation period.
Gross pathology:
Not performed
Interpretation of results:
other:
Remarks:
EU-GHS Criteria not met
Conclusions:
Under conditions used in this study, methyl isoamyl ketone was not acutely toxic by the inhalation route in rats when exposed to a concentration of 3.88 mg/L of air for 6 hours. Since no mortality was noted at this exposure level, the LCLo in rats was >3.88 mg/L of air/6h.

Based on an acute inhalation LCLo value of > 3.88 mg/L of air/6h, methyl isoamyl ketone is not classified for "Acute Toxicity" by the inhalation route according to EU-GHS. Based on an absence of clinical signs or other systemic effects, the test material is also not classified for "Specific Target Organ Toxicity - Single Exposure" according to EU-GHS.

Methyl isoamyl ketone carried an R20 Risk Phrase (Harmful if Inhaled) under Annex 1 of the European Union Dangerous Substances Directive. Now it is listed in Annex VI of the Regulation (EC) No 1272/2008 of the European Parliament and of the Council on classification, labelling and packaging of substances and mixtures (the CLP Regulation) as Flam Liq. 3 (H226) and Acute Tox 4 (H332 - harmfull if inhaled).
Executive summary:

In an acute inhalation toxicity study, 3 rats were exposed to methyl isoamyl ketone at a concentration of 3.88 mg/L of air (948 ppm) for a period of 6 hours. Under the conditions of this study, no deaths occurred and the LCLo was considered to be greater than 3.88 mg/L. No abnormal clinical signs or signs of systemic toxicity were evident during a 14-day observation period. All animals gained weight over the course of the study. Based on the results of this study, methyl isoamyl ketone is not classified for toxicity by the inhalation route at this exposure concentration. However, Methyl isoamyl ketone carried an R20 Risk Phrase (Harmful if Inhaled) under Annex 1 of the European Union Dangerous Substances Directive. Now it is listed in Annex VI of the Regulation (EC) No 1272/2008 of the European Parliament and of the Council on classification, labelling and packaging of substances and mixtures (the CLP Regulation) as Flam Liq. 3 (H226) and Acute Tox 4 (H332 - harmfull if inhaled).

Reason / purpose for cross-reference:
reference to same study
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
4-hour and 13-minute exposure (study terminated due to 100% mortality). Study was originally scheduled for a potential 6-hour exposure.
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Study conducted prior to introduction of Good Laboratory Practices; data from a summary report; limited number of animals; actual test report not available for review. Study was conducted by an internal Eastman Kodak Company method, developed prior to established guidelines.
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to same study
Qualifier:
no guideline available
Principles of method if other than guideline:
Method is an in vivo study using a group of three rats (sex, strain, and weights not available) exposed to an atmosphere containing the test material for a period of, potentially, 6 hours. The study was actually conducted for 4 hours and 13 minutes, at which time, the study was terminated due to 100% mortality. Animals were scheduled for observation during exposure and for a period of 14 days for adverse clinical signs. No gross pathology was performed at study termination.
GLP compliance:
no
Test type:
other: Study conducted according to an internal Eastman Kodak Company laboratory method, using a projected 6-hour inhalation exposure period to rats.
Limit test:
no
Species:
rat
Strain:
not specified
Sex:
not specified
Details on test animals or test system and environmental conditions:
no data
Route of administration:
inhalation
Type of inhalation exposure:
whole body
Vehicle:
other: air
Details on inhalation exposure:
Rats were exposed (whole-body) to an ambient (room temperature) atmosphere containing 31.57 mg/L (calculated as 7718 ppm) of the test material for a period of 4 hours and 13 minutes. The atmosphere was generated by passing room air at a rate of 1.5 L/minute through a washing bottle containing the test material. The atmosphere generated in this manner was then passed into the chamber containing the rats.
Analytical verification of test atmosphere concentrations:
not specified
Duration of exposure:
> 4 - < 5 h
Remarks on duration:
Duration of exposure lasted 4 hours and 13 minutes.
Concentrations:
31.57 mg/L (calculated as 7718 ppm)
No. of animals per sex per dose:
3 (sex not specified)
Control animals:
no
Details on study design:
Three rats (sex, strain, and weights not available) were exposed (whole-body) to an ambient (room temperature) atmosphere containing 31.57 mg/L (calculated as 7718 ppm) of the test material for a period of four hours and 13 minutes. The atmosphere was generated by passing room air at a rate of 1.5 L/minute through a washing bottle containing the test material. The atmosphere generated in this manner was then passed into the chamber containing the rats. Animals were observed for mortality and adverse effects.
Sex:
not specified
Dose descriptor:
LC100
Effect level:
<= 31.57 mg/L air
Exp. duration:
4.2 h
Remarks on result:
other: Exposure period was 4 hours and 13 minutes. Calculated atmospheric concentration = 7718 ppm.
Mortality:
100%
Clinical signs:
other: Abnormal clinical signs noted during the exposure period prior to death included loss of coordination, gasping, prostration, and narcosis.
Gross pathology:
Not performed
Interpretation of results:
study cannot be used for classification
Remarks:
Insufficient data were available from this study to provide a definitive GHS classification for Acute Toxicity or for Specific Target Organ Toxicity – Single Exposure
Conclusions:
Under conditions used in this study representing an extremely high exposure concentration, methyl isoamyl ketone was toxic by the inhalation route in rats exposed to a concentration of 31.57 mg/L of air for 4.2 hours. Since 100% mortality was noted at this exposure level, the LC100 in rats was ≤ 31.75 mg/L of air/4.2 h. Insufficient data were available from this study to provide a definitive GHS classification for Acute Toxicity or for Specific Target Organ Toxicity – Single Exposure.

Methyl isoamyl ketone carried an R20 Risk Phrase (Harmful if Inhaled) under Annex 1 of the European Union Dangerous Substances Directive. Now it is listed in Annex VI of the Regulation (EC) No 1272/2008 of the European Parliament and of the Council on classification, labelling and packaging of substances and mixtures (the CLP Regulation) as Flam Liq. 3 (H226) and Acute Tox 4 (H332 - harmfull if inhaled).
Executive summary:

In an acute inhalation toxicity study, 3 rats were exposed to methyl isoamyl ketone at a concentration of 31.75 mg/L of air for a period of 4.2 hours. Under the conditions of this study, 100% mortality occurred and the LC100 was considered to be ≤ 31.75 mg/L of air/4.2 h. Abnormal clinical signs noted during the exposure period prior to death included loss of coordination, gasping, prostration, and narcosis. Based on the results of this study, methyl isoamyl ketone was lethal by the inhalation route to all rats exposed to 31.57 mg/L of air (7718 ppm) for 4.2 hours.

However, insufficient data were available from this study to provide a definitive GHS classification for Acute Toxicity or for Specific Target Organ Toxicity – Single Exposure. Methyl isoamyl ketone carried an R20 Risk Phrase (Harmful if Inhaled) under Annex 1 of the European Union Dangerous Substances Directive. Now it is listed in Annex VI of the Regulation (EC) No 1272/2008 of the European Parliament and of the Council on classification, labelling and packaging of substances and mixtures (the CLP Regulation) as Flam Liq. 3 (H226) and Acute Tox 4 (H332 - harmfull if inhaled).

Data source

Reference
Reference Type:
other: Eastman Kodak Company Summary Report
Title:
Unnamed
Year:
1956
Report date:
1956

Materials and methods

Test guideline
Qualifier:
no guideline available
Principles of method if other than guideline:
Method is an in vivo study using two guinea pigs. A single dose of 5 or 10 mL/kg bw of test material was held in contact with the depilated abdomens of the animals under an occlusive cuff for 24 hours. After termination of exposure, animals were observed for mortality, dermal reactions and weight changes for a total of 14 days.
GLP compliance:
no
Test type:
other: Study conducted according to an internal Eastman Kodak Company laboratory method.
Limit test:
no

Test material

Constituent 1
Reference substance name:
5-methyl-2-hexanone
IUPAC Name:
5-methyl-2-hexanone
Constituent 2
Chemical structure
Reference substance name:
5-methylhexan-2-one
EC Number:
203-737-8
EC Name:
5-methylhexan-2-one
Cas Number:
110-12-3
Molecular formula:
C7H14O
IUPAC Name:
5-methylhexan-2-one
Constituent 3
Reference substance name:
MIAK; Isoamyl methyl ketone
IUPAC Name:
MIAK; Isoamyl methyl ketone
Details on test material:
no data

Test animals

Species:
guinea pig
Strain:
Hartley
Sex:
not specified
Details on test animals or test system and environmental conditions:
no data

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
Following depilation of the abdomen of each animal, a single dose of 5 or 10 mL/kg bw of the undiluted test material was applied under an occlusive wrap prepared from a pad of gauze held in place with an impervious cuff made of rubber dental dam. The cuff was wrapped securely around the torso and held in place using non-irritating tape. After an exposure period of 24 hours, the cuffs and wrappings were removed.
Duration of exposure:
24 hours
Doses:
One animal each was exposed to a single application of 5 or 10 mL/kg bw of the undiluted test material.
No. of animals per sex per dose:
1 animal/dose (sex not determined)
Control animals:
no
Details on study design:
Two guinea pigs (sex, age, and initial weights not provided) were used. Following depilation of the guinea pig abdomens, a single application of either 5 or 10 mL/kg bw of the undiluted test material was applied under an occlusive wrap prepared from a pad of gauze held in place with an impervious cuff made of rubber dental dam material. The cuff was wrapped securely around the torso of the guinea pig and held in place with non-irritating tape. Animals were exposed for 24 hours, and then the cuffs were removed. Animals were observed following removal of the cuff, and on Days 7 and 14. In addition to observations for mortality, dermal reactions were also noted. Guinea pigs were weighed prior to administration of the test substance and at termination of the 14-day observation period.

Based on the specific gravity of methyl isoamyl ketone (0.814), the administered doses in this study were approximately 4 and 8 g/kg bw.
Statistics:
no data

Results and discussion

Effect levels
Sex:
not specified
Dose descriptor:
LDLo
Effect level:
> 10 mL/kg bw
Mortality:
None
Clinical signs:
No signs of test material absorption or systemic toxicity were noted during the study. Signs of irritation at the application site were limited to slight erythema after termination of exposure. No signs of edema were evident during the study.
Body weight:
Although one animal lost weight, the remaining animal gained weight over the 14-day observation period.
Gross pathology:
Not performed

Applicant's summary and conclusion

Interpretation of results:
other:
Remarks:
EU-GHS criteria not met
Conclusions:
Methyl isoamyl ketone was not acutely toxic by the dermal route in guinea pigs under conditions used in this study. The dermal LDLo in guinea pigs for the undiluted substance was > 10 mL/kg bw, equivalent to approximately 8 g/kg bw.

Based on an acute dermal LDLo value of > 10 mL/kg bw in guinea pigs, methyl isoamyl ketone is not expected to be classified for Acute Toxicity by the dermal route under GHS. However, insufficient data were available in this study to provide a definitive value for dermal LD50. In the absence of signs of systemic toxicity and/or skin absorption, methyl isoamyl ketone is not classified under GHS for Specific Target Organ Toxicity – Single Exposure. Based on minimal signs of irritation after an extreme exposure period of 24 hours under an occlusive wrap to depilated abdominal skin of guinea pigs, methyl isoamyl ketone is not classifiable for Skin Irritation/Corrosion according to EU-GHS.
Executive summary:

In an acute dermal toxicity study, two Hartley guinea pigs were exposed to either 5 or 10 mL/kg bw of undiluted methyl isoamyl ketone under occlusive contact for 24 hours. Under the conditions of this study, no deaths occurred and the dermal LDLo was considered to be > 10 mL/kg bw. No signs of skin absorption or systemic toxicity were evident during the study. At the application sites, signs of skin irritation were limited to slight erythema after termination of exposure. One animal lost weight and one animal gained weight over the 2-week observation period. Based on the results of this study, methyl isoamyl ketone presents a low toxicity hazard upon skin contact under conditions of normal use.