2-methylbutyraldehyde

Endpoint summary

Description of key information

No valid data could be identified for assessment of the skin and eye irritating potential of 2-Methylbutanal. Based on available data on a related substance, 3-Methylbutanal, it is concluded that 2-Methylbutanal leads to slight and reversible skin irritation, and category 2 eye irritation according to GHS criteria.

Key value for chemical safety assessment

Skin irritation / corrosion

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Eye irritation

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Additional information

Skin irritation:

No valid study is known to exist for 2-methylbutanal. However, results from the related substance 3-methylbutanal (isovaleraldehyde) can be read across as follows:

 

In a primary dermal irritation study according to OECD test guideline 404 and conducted under GLP conditions, four albino rabbits were dermally exposed to 0.5 mL of isovaleraldehyde (3-methylbutyraldehyde) (purity 98.5 %) for 4 hours. Animals were then observed for 7 days. Irritation was scored by the method of Draize/OECD test guideline 404.

Skin reactions could be observed in all animals starting 1 h after removal of the patch with a maximum erythema and edema score of 2 and 2.5 respectively (day 1). Scores had subsided at day 7 but irritation effects had not completely disappeared. Considering the day 7 scores, it is estimated that irritation effects are reversible within 15 days.

Isovaleraldehyde is slightly irritating to the skin but it does not require classification according to EU regulations, based on irritation scores and reversibility of irritating effects (ECETOC, 1995).

 

In a non valid (RL3) primary dermal irritation study using 2-methylbutanalas test substance, marked erythema and desquamation were noted in rats following a 1, 5, 15 min, or 20 h exposure period. Observation times were 24 h and 8 d. In this report, important technical information is missing and not available (number of animals, test substance purity and volume, occlusive or non-occlusive application, pathological examination on the treated skin). The scoring system is different from the specifications of actual test guidelines. The study is therefore assessed to be not acceptable (BASF, 1977).

 

In summary, a read across to the structurally very similar substance 3-Methylbutanal can be made for skin irritation, and, based on this, it is assumed that 2-methylbutanal is slightly irritating to the skin, and that effects are reversible.

 

The results on skin irritation of the study of BASF (1977) with the test substance 2-methylbutyraldehyde are not reliable. They are disregarded due to severe methodological deficiencies and limited reporting.

 

Eye irritation:

No valid study is known to exist for 2-methylbutanal. However, results from the related substance 3-methylbutanal (isovaleraldehyde) may be read across as follows:

 

In a primary eye irritation/corrosion test, 3-methylbutanal was tested in two rabbits using a small volume of test substance (0.05 mL). Irritation reactions of cornea and conjunctivae were recorded 24, 48, 72 hours and 8 days after application.

Effects persisted not longer than 8 days. At the end of the observation period (8 days) all irritation effects had subsided. For one rabbit, mean conjunctivae score for the 24 to 72 h period was 2, thus reaching the EU criteria for classification (irritating to eyes – category 2) (BASF 1974).

 

This study bears some deviations from actual test guidelines (only two test animals, instillation of only 0.05 mL test substance, short observation period). Nevertheless, the data are assessed to be sufficiently valid to evaluate the eye irritation potential of the test substance. Considering the results after 8 days, it is estimated that EU criteria for classification (category 2) will be reached, but the effects will remain reversible within 21 days when the required amount of test substance (0.1 mL) had been applied in the test. Using the data available, the tiered testing and evaluation strategy is adhered to and further testing can be avoided.

 

The study result is supported by the results of a read across using the OECD Toolbox, where analysis of structurally related substances was used to derive the irritation potential of the test substance 2-methylbutyraldehyde. Proprietary data was loaded into the toolbox and the data set was reduced to the five closest analogs of the test substance. On this basis, an irritation score could be derived (32.2 of 110) by trend analysis, suggesting slight and reversible eye irritation (Oxea, 2010).

 

In a non valid (RL3) primary eye irritation study using 2-methylbutanal as test substance, considerable eye irritating effects were observed after instillation of 50 µL in the eye of rabbits (exposure period and number of test animals not reported, readings only after 1 h, 24 h, and 8d, scoring system different from actual test guidelines, limited reporting). Corneal opacity (slight), erythema (strong) and edema (strong) were observed. In addition, smeary discharge and after 24 h scar formation were noticed. Erythema and scar were still perceptible after 8 days (end of observation period). There are no data on the reversibility of effects within a 21 day period. Due to profound methodological deficiencies, this study is assessed to be not acceptable (BASF, 1977).

 

In summary, a read across to the structurally very similar substance 3-Methylbutanal can be made for eye irritation. Based on this and supported by read across using the OECD toolbox, it is estimated that 2-methylbutyraldehyde is irritating to the eye, and that effects are reversible. EU criteria for classification are met requiring classification as irritating to eyes (category 2).

 

The results on eye irritation of the study of BASF (1977) with the test substance 2-methylbutyraldehyde are not reliable. They are disregarded due to severe methodological deficiencies and limited reporting.

Effects on skin irritation/corrosion: slightly irritating

Effects on eye irritation: irritating

Justification for classification or non-classification

Skin irritation:

No valid data could be identified for assessment of the skin irritating potential of 2-methylbutyraldehyde. Based on available data on the related substance 3-methylbutyraldehyde, it is concluded that 2-methylbutyraldehyde leads to slight and reversible skin irritation.

According to EU regulations, 2-methylbutyraldehyde does not require classification for skin irritation.

 

Eye irritation:

No valid data could be identified for assessment of the eye irritating potential of 2-methylbutyraldehyde. Based on available data on the related substance 3-methylbutyraldehyde, as well as on read across results of the OECD Toolbox, it is concluded that 2-methylbutyraldehydel leads to eye irritation which is reversible within 21 days.

Available results suggest classification of 2-methylbutyraldehyde as irritating to eyes (category 2) according to EU regulations.