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Administrative data

Description of key information

Skin irritation (Read-across) – Irritating

Eye irritation (equivalent to OECD 405): corrosive

Respiratory irritation: not data available

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Justification for type of information:
The read-across was performed based on a common functional group (oxime). According to the harmonized classification and labeling (ATP15) approved by the European Union, the test substance causes skin irritation. However, the studies available performed with the test substance do not support this classification. Therefore, an analogue substance from the same functional class group was used to report the skin irritation profile, representative of the oximes, that give rise to this health concern.
Reason / purpose for cross-reference:
read-across source
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: average score a 1, 24, 48 hours
Score:
3.6
Reversibility:
not fully reversible within: 14 days
Irritation parameter:
erythema score
Basis:
mean
Time point:
24 h
Score:
ca. 1.7
Max. score:
2
Irritation parameter:
edema score
Basis:
mean
Time point:
24 h
Score:
ca. 1
Max. score:
2
Irritation parameter:
erythema score
Basis:
mean
Time point:
48 h
Score:
ca. 2
Max. score:
3
Irritation parameter:
edema score
Basis:
mean
Time point:
48 h
Score:
ca. 2
Max. score:
3
Irritation parameter:
erythema score
Basis:
mean
Time point:
72 h
Score:
ca. 1.7
Max. score:
3
Reversibility:
not fully reversible within: 14 days
Irritation parameter:
edema score
Basis:
mean
Time point:
72 h
Score:
ca. 2
Max. score:
3
Reversibility:
not fully reversible within: 14 days
Interpretation of results:
other: Category 2 based on CLP criteria (EU criteria according to Regulation (EC) No. 1272/2008)
Conclusions:
As explained in the 'Justification for type of information', it is considered that the target and the source substances are unlikely to lead to differences in skin irritating potential.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (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:
comparable to guideline study with acceptable restrictions
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Vehicle:
unchanged (no vehicle)
Controls:
other: contralateral eye used as untreated control
Observation period (in vivo):
72 hours
Number of animals or in vitro replicates:
6
Irritation parameter:
other: necrosis
Basis:
mean
Time point:
other: 24-72 hours
Score:
>= 2
Reversibility:
not reversible
Remarks on result:
other: necrosis observed in two of six animals
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Remarks on result:
not determinable because of methodological limitations
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Remarks on result:
not determinable because of methodological limitations
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Remarks on result:
not determinable because of methodological limitations
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Remarks on result:
not determinable because of methodological limitations
Irritant / corrosive response data:
MEKO was determined to be a corrosive eye irritant in rabbits. Corneal opacity, iritis, conjunctival hyperaemia and necrosis were observed 24, 48, and 72 hours post exposure.


Interpretation of results:
other: Category 1 based on CLP criteria (EU criteria according to Regulation (EC) No. 1272/2008)
Conclusions:
Methyl ethyl ketoxime was corrosive to the eye of rabbits when applied undiluted.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritating properties of MEKO were evaluated in two skin irritation studies. In a study conducted by Allied Chemical Corporation (1978b), undiluted test substance was applied to 3 non-abraded and 3 abraded skin sites of six rabbits for 24 hours under occlusive conditions. Only slight skin irritation was observed; the primary irritation index was 1.5. However, no individual scores were provided. Therefore, no decision on classification can be drawn based on this study. In the other study, performed by BASF Toxicology Department (1971b) by a protocol similar to OECD Guideline 404, no irritation was observed in rabbits following a 4 hour exposure under semiocclusive conditions. Again, no detailed information on this study are availabel thus this study cannot be used for classification.

A reliable study with a structural analogue substance butan-2-one O,O',O''-(methylsilanetriyl)oxime (CAS 22984 -54 -9) is available. This study, dated 1991, conducted according to guidelines and GLP. Butan-2 -one O,O',O''-(methylsilanetriyl)oxime was applied to New Zealand White rabbits (n = 3) under
occlusive conditions for 4 hours and they were observed for a period of 14 days. Mean scores for erythema and oedema at 24, 48 and 72 hours were provided (scores for erythema = 1.8 and oedema = 1.7). A score of 3 for erythema and oedema was observed in at least one animal at the 48 h and 72 h timepoints. These findings were not reversible within the 14 day observation period. No individual scores are provided, therefore it is unclear whether the mean scores observed meet the criteria for classification, however the findings were not reversible in at least 2/3 animals at the end of the 14 day observation period. Therefore, the classification as Skin irritant 2 is appropriate.

In the available study on eye irritation, performed by Allied Chemical Corporation (1978c), MEKO was applied undiluted in the eyes of 6 rabbits. Corneal opacity, iritis and conjunctival hyperaemia were observed 24, 48, and 72 hours post exposure (average scores 2 or above) in all animals. In addition, necrosis was observed in 2 of 6 rabbits at 24, 48, and 72 hours following exposure. Based on these results, MEKO is concluded to cause serious damage to eyes.

Although available repeated dose inhalation toxicity studies indicate (reversible) degeneration of nasal olfactory epithelium in experimental animals (see section on repeated dose toxicity for more details), this effect is most likely associated with a toxic effect related to the metabolism of MEKO by the olfactory epithelium and not a direct irritant action of MEKO on the respiratory tissue. The substance is also not classified as irritating to respiratory tract on Annex I of EU Directive 67/548/EEC and Annex VI of EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.

Justification for classification or non-classification

Based on the available skin and eye irritation studies, butanone oxime is classified as skin irritant Category 2 (H315) and eye damaging Category 1 (H318) according to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.

As butanone oxime is irritating to the eyes, there is the possibility that it may also be irritating to the respiratory tract. Respiratory tract irritation has not been reported in humans. Neither single dose nor repeated dose studies in animals show evidence of respiratory tract irritation i.e. no hyperemia, oedema or inflammation has been observed. There were no reports of significant discomfort of animals following inhalation exposure to butanone oxime. Therefore, no classification for respiratory irritation is necessary.