Distillation residues of butyraldehyde, 2-ethylhexenal and isobutanal hydrogenation by-products

Endpoint summary

Description of key information

Distillation residues of butyraldehyde, 2-ethylhexenal and isobutanal hydrogenation by-products, was irritating for the skin and slightly irritating for the eye of rabbits.

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

The potential of the test item, distillation residues of butyraldehyde, 2-ethylhexenal and isobutanal hydrogenation by-products, to induce skin irritation was evaluated following a single topical application to rabbits according to OECD (No. 404, 24th April 2002) and Commission Regulation (EC) (No. 440/2008, B.4, 30 May 2008) guidelines (Gerbeix, 2010b). The study was conducted in compliance with the principles of Good Laboratory Practice.

The test item, distillation residues of butyraldehyde, 2-ethylhexenal and isobutanal hydrogenation by-products, was first applied for periods of 3 minutes, 1 hour and 4 hours to a single male New Zealand White rabbit. Since the test item was not severely irritant or corrosive to the skin on the first animal, it was then applied for 4 hours simultaneously to two otheranimals. The quantity of the test item administered was 0.5 mL. The test item was placed on a dry gauze pad, which was then applied to an area of the skin of approximately 6 cm² of the animals. The gauze pad was held in place by a non-irritation semi-occlusive dressing and a restraining bandage. After required period of contact with the skin, the dressings were removed.

For each exposure period, cutaneous reactions were evaluated approximately 1 hour, 24, 48 and 72 hours after removal of the dressing and then daily until the reversibility of cutaneous reactions (day 7) or the end of the observation period. Body weight was recorded at the beginning and the end of the observation period. On completion of the observation period, the animals were used subsequently for the evaluation of the ocular irritation potential of the same test item. The mean values of the scores for erythema and edema were calculated for each animal.  

After a 3-minute exposure (one animal), a very slight or well-defined erythema was noted from day 1 until the end of the observation period (day 15). Dryness of the skin was observed from day 4 until day 15. After a 1-hour exposure (one animal), a very slight or well-defined erythema was noted from day 1 until the day 14. Dryness of the skin was observed from day 3 until day 15. After a 4-hour exposure (three animals), a very slight or well-defined erythema was noted in one animal (female No. 520) from day 1 until day 5. In addition, a very slight edema (grade 1) was noted on day 4 and dryness of the skin was observed from day 4 until day 6. In the two other animals, a very slight to moderate erythema was noted from day 1 until day 10 (male No. 521) or 11 (male No. 517). A very slight or slight edema was observed from day 2 until day 8 (No. 517) or from day 4 until day 7 (No. 521). Dryness of the skin was recorded from day 3 or 4 until the end of the observation period (day 15). Mean scores over 24, 48 and 72 hours for each animal were 3.0, 1.3 and 2.3 for erythema and 1.3, 0.3 and 0.3 for edema.

Under the experimental conditions of the study, distillation residues of butyraldehyde, 2-ethylhexenal and isobutanal hydrogenation by-products, was irritant when applied topically to rabbits.

Eye irritation

The potential of the test item, distillation residues of butyraldehyde, 2-ethylhexenal and isobutanal hydrogenation by-products, to induce irritation was evaluated following a single ocular administration in rabbits according to OECD (No. 405, 24th April 2002) andCommission Regulation (EC) (No. 440/2008, B.5, 30 May 2008) guidelines (Gerbeix, 2010c). The study was conducted in compliance with the principles of Good Laboratory Practice.

The test item, distillation residues of butyraldehyde, 2-ethylhexenal and isobutanal hydrogenation by-products, was first administered to a single male New Zealand White rabbit. Since the test item was not severely irritant on this first animal, it was then evaluated simultaneouslyon two other animals.

The quantity of the test item administered was 0.1 mL. The test item was introduced into the conjunctival sac of the left eye. The right eye, which remained untreated, served as control. The eyes were not rinsed after administration of the test item. Ocular reactions were observed approximately 1 hour, 24, 48 and 72 hours after the administration and then daily until the reversibility of the ocular reactions (at least day 7).

Body weight was recorded at the beginning and the end of the observation period. On completion of the observation period, the animals were sacrificed then discarded without macroscopic post‑mortem examination. The mean values of the scores for chemosis, redness of the conjunctiva, iris lesions and corneal opacity were calculated for each animal.

Slight to marked chemosis and redness of the conjunctiva (grades 1 to 3) were observed in all animals from day 1 until day 2, 4 or 6. Clear and/or whitish purulent discharge was observed in two animals from day 2 until day 3 or 4. Iris lesions were noted in one animal from day 1 until day 3.

A slight or moderate corneal opacity was recorded in two animals on days 2 and 3. Mean scores calculated for each animal over 24, 48 and 72 hours were 1.0, 2.3 and 0.3 for chemosis, 1.7, 2.3 and 0.3 for redness of the conjunctiva, 0.0, 0.7 and 0.0 for iris lesions and 1.0, 1.3 and 0.0 for corneal opacity.

Under the experimental conditions of the study, distillation residues of butyraldehyde, 2-ethylhexenal and isobutanal hydrogenation by-products, was slightly irritant when administered by ocular route to rabbits.

Effects on skin irritation/corrosion: irritating

Effects on eye irritation: slightly irritating

Justification for classification or non-classification

According to the classification criteria laid down in Regulation (EC) N° 1272-2008C and Council Directive 67/548/EEC (and subsequent adaptations), distillation residues of butyraldehyde, 2-ethylhexenal and isobutanal hydrogenation by-products should be classified as irritating for the skin. No classification is warranted for eye irritation.