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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.

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

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Type:
Constituent
Details on test material:
no data

Test animals

Species:
guinea pig
Strain:
Hartley
Sex:
not specified
Details on test animals 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:
study cannot be used for classification
Remarks:
Migrated information
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 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.