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Description of key information

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation / corrosion
Remarks:
other: Study conducted according to an internal Eastman Kodak Company laboratory method.
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 introduction of Good Laboratory Practices; no information on number of animals used; data from a summary report; actual test data 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 are at least as stringent as modern guidelines.
Qualifier:
no guideline available
Deviations:
not specified
Principles of method if other than guideline:
Method is an in vivo study using guinea pigs. Following depilation of the abdomen of each animal, a single dose of the undiluted test material was applied under an occlusive cuff. Animals were exposed to test material for 24 hours, then 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 recorded.
GLP compliance:
no
Species:
guinea pig
Strain:
Hartley
Details on test animals and environmental conditions:
no data
Type of coverage:
occlusive
Preparation of test site:
other: The abdomen of each animal was depilated.
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
no data
Duration of treatment / exposure:
24 hours
Observation period:
14 days
Number of animals:
no data
Details on study design:
Following depilation of the abdomen of each animal, a single dose of the undiluted test material (doses not reported) 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. Animals were observed following removal of the cuff, and on Days 7 and 14. Observations for mortality and dermal reactions were recorded.
Irritation parameter:
other: Numerical grading was not used. Skin irritation was graded as slight, moderate, or severe. Signs of absorption were recorded as either evident or not evident based on observations of systemic effects.
Basis:
other: overall
Reversibility:
no data
Remarks on result:
other: Numerical grades of irritation (erythema and edema) were not provided in the study report. Overall irritation was reported as slight on a scale of slight to strong.
Irritant / corrosive response data:
The test material was considered to cause slight irritation with some signs of desquamation.
Other effects:
Signs of skin absorption were not evident.
Interpretation of results:
slightly irritating
Remarks:
Migrated information Criteria used for interpretation of results: expert judgment
Conclusions:
Following 24-hour occlusive exposure of the test material to the depilated abdominal skin of the guinea pig, methyl isoamyl ketone was slightly irritating, but not corrosive. Methyl isoamyl ketone is not a primary skin irritant. Only minimal irritation and some signs of desquamation were noted during the study. Skin absorption was not evident. The conditions of exposure in this non-guideline study were significantly more stringent than those used in present day guideline skin irritation studies, i.e., 24-hr exposure versus 4-hr exposure currently used. Based on the results of this study, the degree of irritation was insufficient to classify methyl isoamyl ketone as a skin irritant according to GHS guidelines.
Executive summary:

In a primary dermal irritation study, guinea pigs were exposed to methyl isoamyl ketone under an occlusive wrap for 24 hours. Animals were then observed for signs of irritation. Signs of irritation were scored as slight, moderate, or severe. Methyl isoamyl ketone caused minimal irritation with some signs of desquamation, but no signs of corrosion. Signs of skin absorption were not evident. Methyl isoamyl ketone is not considered a dermal irritant under conditions used in this study.

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

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation
Remarks:
other: Study conducted according to an internal Eastman Kodak Company laboratory method.
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Single ocular exposure followed by a 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; actual test data 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 are at least as stringent as modern guidelines.
Qualifier:
no guideline available
Deviations:
not specified
Principles of method if other than guideline:
Method is an in vivo study using six rabbits. One drop of the test substance was administered into the conjunctival sac of one eye of each of the rabbits. Three of the treated eyes were immediately washed with running distilled water; the other three eyes were not irrigated. The treated eyes of the rabbits were examined for signs of irritation. Over a 14-day observation period, ocular reactions and signs of irritation were recorded and graded.
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
no data
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
1 drop administered to one eye
Duration of treatment / exposure:
single application
Observation period (in vivo):
14 days
Number of animals or in vitro replicates:
6
Details on study design:
Method is an in vivo study using rabbits. One drop of undiluted methyl isoamyl ketone was administered into the conjunctival sac of one eye of each of six rabbits. After instillation, the lids were held together briefly to insure adequate distribution of the test material. The untreated eye of each rabbit served as a control. Three of the treated eyes were immediately washed with running distilled water; the other three eyes were not irrigated. The treated eyes of the rabbits were examined for signs of irritation immediately after test material administration, at 24 hours post dose, and at termination of the study. In addition, the treated eyes of all rabbits were examined with sodium fluorescein at 24 hours post-dose. Additional examinations of the eye, if any, were not defined in the study report. Ocular reactions were recorded at each examination and graded as slight, moderate, or strong. The general health of the rabbits was monitored at each observation time.
Irritation parameter:
other: Ocular reactions were graded as slight, moderate, or strong. No numerical scores were reported in the study report.
Basis:
other: unwashed treated eyes
Time point:
other: Initial, 24, and 14 days
Score:
> 1 000
Max. score:
1 000
Reversibility:
not specified
Remarks on result:
other: For the three unwashed eyes, signs of irritation noted during the observation were described as, at most, slight. Fluorescein staining of the adnexa was evident for two of three unwashed eyes at the 24-hour examinations.
Irritation parameter:
other: Ocular reactions were graded as slight, moderate, or strong. No numerical scores were reported in the study report.
Basis:
other: washed treated eyes
Time point:
other: Initial, 24, and 14 days
Score:
> 1 000
Max. score:
1 000
Reversibility:
not specified
Remarks on result:
other: For the three washed eyes, signs of irritation noted during the observation were described as, at most, slight. Fluorescein staining was not evident for the three washed eyes at the 24-hour examinations.
Irritant / corrosive response data:
For unwashed eyes, signs of irritation were reported as, at most, slight. Fluorescein staining of the adnexa was evident for two of the three unwashed eyes. For washed eyes, signs of irritation noted during the observation were described as, at most, slight. No fluorescein staining was evident for the washed eyes. Based on the lack of staining in washed eyes, irrigation of the eyes was palliative.

Note that no irritation scores were used in this study. The values of 1000 were used only as a placeholder, as numerical values are required to pass the completeness check

Interpretation of results:
slightly irritating
Remarks:
Migrated information Criteria used for interpretation of results: expert judgment
Conclusions:
Methyl isoamyl ketone was, at most, a slight irritant by the ocular route under conditions used in this study. Prompt washing of the eyes was palliative. This is consistent with minimal effects observed following single and repeated application to the clipped skin of guinea pigs. Based on minimal signs of eye irritation with no signs of corrosion, methyl isoamyl ketone is not classified for eye irritation/corrosion under GHS.
Executive summary:

In a primary eye irritation study, one drop of undiluted methyl isoamyl ketone was instilled into the conjunctival sac of one eye of each of 6 New Zealand albino rabbits. Of these, three had their eyes washed immediately after treatment and three were unwashed. Animals were then observed for 14 days. Ocular reactions were recorded and descriptors (slight, moderate, strong, severe) were assigned for grading severity of ocular lesions. The eyes of all rabbits were examined with fluorescein dye at 24 hours. Methyl isoamyl ketone was reported to cause, at most, slight irritation in unwashed and washed eyes. Immediate washing of the eyes was palliative. Based on the results of this study, methyl isoamyl ketone is, at most, a slight ocular irritant.

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

Respiratory irritation

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

Additional information

Skin Irritation

Although a study conducted according to current regulatory guidelines for a skin irritation study was not available for review, two non-guideline skin irritation studies and two non-guideline dermal toxicity studies were considered in this evaluation. All studies were conducted with guinea pigs. In three of the studies, exposure was for 24 hours on depilated skin under occlusive contact, conditions much more stringent than those used in current skin irritation testing protocols. In the fourth study, the test material was applied uncovered to the application site daily for 7 days over a 10-day period. In a single-dose skin irritation study, application of an unspecified volume of methyl isoamyl ketone caused, at most, slight irritation and some signs of desquamation following 24-hr occluded contact. Skin absorption was not evident. In the repeat-exposure non-occluded skin irritation study, slight erythema was observed at the application site in 1 of 5 animals on Day 1. On Day 4, dry skin was evident in all animals. On Day 10, slight to moderate erythema was noted on 2 of 5 application sites and dry skin with cracked eschars was observed for all animals. In two dermal toxicity studies in which animals received up to 16 g/kg bw under occluded contact for 24 hr, signs of irritation at the application site were limited to slight erythema after termination of exposure and no signs of edema at dose levels up to 8 g/kg bw. Based on the observations made in two skin irritation studies and two dermal toxicity studies, methyl isoamyl ketone is not classified as a primary skin irritant.

Eye Irritation

The potential for methyl isoamyl ketone to cause eye burns/irritation is well understood. Although an eye irritation study conducted according to OECD Guideline 405 was not available for review, an eye irritation study conducted according to generally accepted scientific principles and using conditions of exposure at least as stringent as modern guidelines was used for evaluation. In this study, a drop of the test material was instilled into the conjunctival sac of one eye of each of 6 New Zealand white rabbits and the animals were observed for 14 days. Three of the treated eyes were immediately flushed with water while the other three eyes were not irrigated. For both washed and unwashed eyes, signs of irritation noted during the observation period were described as, at most, slight. Fluorescein staining of the adnexa was evident for 2 of 3 unwashed eyes at the 24-hr examination but not in washed eyes. Signs of eye irritation were reported at high airborne concentrations in an acute inhalation toxicity study. Based on the results of these data, methyl isoamyl ketone is considered to be, at most, a slight ocular irritant. Exposure to high vapor concentrations may cause transient irritation.

Respiratory Tract Irritation

The potential for methyl isoamyl ketone to cause respiratory tract irritation is well understood. In a series of five non-guideline acute inhalation toxicity studies in which rats were exposed to up to approximately 7700 ppm for 4-hours, no clinical signs suggestive of respiratory tract irritation were observed. In addition, no signs of irritation were observed in rats exposed to up to 2000 ppm methyl isoamyl ketone for 6-hr/day, 5 days/week for a total of 12 or 69 exposures.  

Justification for classification or non-classification

In a primary dermal irritation study, slight irritation and some signs of desquamation were observed following 24-hr occluded contact. Repeat application of the test material did not significantly exacerbate the irritative effects. In addition, irritative effects were minimal in two dermal toxicity studies using conditions significantly more severe, i.e., 24-hr exposure and much higher dose levels (10 mL) than current OECD guideline specifications for a skin irritation/corrosion study. Based on a weight-of-the-evidence assessment, methyl isoamyl ketone may cause slight, transient skin irritation but is not classified for “Skin irritation/corrosion” according to GHS guidelines.

The only clinical signs in rabbit eyes following instillation of 1 drop of the test material into the conjunctival sac of the eye were, at most, slight irritation and fluorescein staining at the 24-hr examination. In addition, methyl isoamyl ketone is not classified under GHS guidelines for either skin corrosivity or irritation following 24-hr occluded contact with intact skin. Based on a weight-of the-evidence assessment, methyl isoamyl ketone is not classified for “Serious Eye Damage/Eye Irritation” according to GHS guidelines.

There were no clinical signs indicative of respiratory tract irritation in rats following acute exposure to up to 7700 ppm or subacute or subchronic exposure to up to 2000 ppm methyl isoamyl ketone. In addition, the test material is not classified as a skin irritant according to GHS guidelines. Based on a weight-of-the-evidence assessment, methyl isoamyl ketone is not classified for respiratory tract irritation according to GHS guidelines.