Amines, C12-18-alkyldimethyl, N-oxides

Endpoint summary

Description of key information

Studies are available that show C12-18 AO is irritating to the skin  and, by read across to C12-14 AO, corrosive to the eyes 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)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation

In the key study, performed according to OECD TG 404 [Hollander & Rupprich (1983)], C12-18 AO (0.5 mL, 30 %AO) was applied to the intact skin of 3 female rabbits (New Zealand White) and covered with a semi-occlusive dressing for 4 hours. At the end of the exposure period the treatment sites were cleaned and reactions noted over a 14 day period. Well-defined to severe erythema was observed in all three test animals at 24 and 48 hours. At 72 hours barely perceptible to well-defined erythema was observed. These reactions had completely cleared by 14 days. Barely perceptible oedema was observed in two animals up to 48 hours and was completely cleared by 7 days. 

In a study, performed according to OECD TG 404 [Fulfs JC (1978)], C12-14 AO (0.4 mL, 27.8 %AO) was applied to the intact and abraded skin of 3 female rabbits (New Zealand White) and covered with an occlusive dressing for 24 hours. At the end of the exposure period the treatment sites were wiped with a wet paper towel and reactions noted over a 72 hour period. Very slight to well defined erythema was observed at the intact and abraded sites of all the test animals at 24 hours. At 72 hours severe erythema (beet redness) to slight eschar formation were observed at the intact and abraded sites of all test animals. No oedema was observed at any time point. Similar results were obtained in a supporting study [Dean WP (1978)].

In three further supporting studies, performed according to US Federal Register, vol 41(188): 42572 (27^thSeptember 1976), C12-14 AO (0.5 mL, 30 % AO) was applied to the intact skin of 6 rabbits (albino) and covered with an occlusive dressing for 4 hours. At the end of the exposure period the test substance was removed by wiping with a paper towel moistened with sterile distilled water. The sites were scored immediately and after 48 hours. Erythema and oedema scores increased during the 48 hour observation period. No destruction of intact skin was observed after the four hour exposure.

Three further studies are available performed using lower concentrations of C12-14 AO. In the first of these [Nicholas P & Jones JR (1976)] performed according to US Federal Register Vol 38 (187): 1500:41 (1973) the substance (0.5 mL, 6 %w/w AO) was applied to the intact and abraded skin of 6 rabbits (New Zealand White) and covered with an occlusive dressing for 24 hours. Very slight to moderate to severe erythema and very slight to slight oedema was observed at the intact and abraded sites of all test animals at 24 hours. At 72 hours no to slight erythema and no to very slight oedema was observed at the intact and abraded sites of all test animals. In the second study the substance (0.5 mL, 0.6 % AO) was applied to the intact and abraded skin of 8 rabbits (New Zealand White) and covered with an occlusive dressing for 24 hours. No to very slight erythema and oedema was observed at the intact and abraded sites of all test animals at 24 and 72 hours. In the third study [Kukulinski M (1997)] performed according to FHSA/CPSC Design, 16 CFR1500 the substance (0.5 mL, 2.5 or 5 %AO) was applied to the intact and abraded skin of 3 rabbits (New Zealand White). At 5 % AO one rabbit had no erythema at 24 hours on had very slight and the third had well defined erythema at the intact sites. At 72 hours two rabbits had no erythema and the third very slight erythema. No oedema was observed at either 24 or 72 hours. At 2.5 % AO very slight erythema was observed in one rabbit at 24 hours. All other scores were zero at both 24 and 72 hours.

Eye irritation

Only one study is available for C12-18 AO, the reliability of which cannot be properly assessed. In this study [Bullens P (1984)] C12-18 AO (0.1 mL, 5 % AO) was instilled into the right eye of 6 rabbits. The untreated left eye served as a control for each rabbit. Both the treated and untreated eyes were examined at 24, 48 and 72 hours. Based on the effects seen, the solution containing 5 % AO was an eye irritant in this study.

In the key study for this endpoint, performed according to OECD TG 405 [Fulfs JC (1978)] C12-14 AO (0.1 mL, 27.8 % AO) was instilled into the eyes of two groups of three rabbits (New Zealand White). The eyes of the first group of 3 rabbits were not rinsed and the eyes of the second group of 3 rabbits were rinsed, approximately 4 seconds following instillation of the test substance, with 20 ml of lukewarm distilled water. In the first group the maximum average score was 4.0 at one day. The observable response included irreversible corneal opacity in all three animals up to 35 days. No iridic response was observed. Conjunctival redness with grade 1 and conjunctival chemosis up to grade 2 were observed and fully reversed within 14 days. In the second group the maximum average score was 3.67 at one day. The observable response included irreversible corneal opacity in one animal up to 35 days. No iridic response was observed. Conjunctival redness with grade 1 and conjunctival chemosis up to grade 2 were observed and fully reversed within 2 days. From these observations it is concluded that C12-14 AO caused irreversible damage to the rabbit eye.

In a supporting study performed according to OECD TG 405 [Dean WP (1978)] C12-14 AO was instilled into the eyes of two groups of three rabbits (New Zealand White). Group I and Group II received 0.1 mL of 28 % AO. Group III received 0.1 mL of a 10 % dilution, i.e. 2.8 % AO. The eyes of the Group I and Group III rabbits were not rinsed and the eyes of the Group II rabbits were rinsed, approximately 4 seconds following instillation of the test material, with 20 mL of lukewarm distilled water. For Group I the maximum average score was 8.0 on 4th day. The observable response included irreversible corneal opacity in all three animals till 35 days. Iridic response with grade 1 was observed. Conjunctival redness up to grade 2 was observed and conjunctival chemosis up to grade 3 (swelling with lids about half closed) was observed. The reactions were not fully reversed up to 35 days. For Group II the maximum average score was 6.0 on the third day. The observable response included irreversible corneal opacity in one animal up to 35 days. Iridic response up to grade 1 was observed. Conjunctival redness up to grade 2.5 (more diffuse beefy red areas) and conjunctival chemosis up to grade 2.5 were observed which were not fully reversed within 35 days. For Group III the maximum average score was 4.8 on the second day. The observable response included corneal opacity which was reversed within 7 days. Iridic response up to grade 1 was observed. Conjunctival redness up to grade 2 (more diffuse crimson red areas) and conjunctival chemosis up to grade 2 were observed. All reactions were fully reversed within 21 days in all animals. In this group one rabbit was found dead and the cause of death was unable to be determined. From these observations it can be concluded that C12-14 AO at a concentration of 28 %AO caused irreversible damage to the rabbit eye. A 10 % dilution of the test substance (i.e. 2.8 % AO) caused irritation that was reversible within 21 days. Two further studies are available performed on lower concentrations of C12-14 AO. In both of these studies, which used 6 % AO [Nicholas P & Jones JR (1976)] and 5 % or 2.5 % AO [Kukulinski M (1997)] the test substance induced eye irritation effects that were not fully reversible within a 7 -day period. It is not possible to conclude for certain from the 7 -day scores whether the effects would be fully reversed if the observation period had been extended to 21 days, however based on the study performed with 2.8 % AO this seems likely.

Justification for selection of skin irritation / corrosion endpoint:
Study performed according to OECD TG 404 under GLP (K=1)

Justification for selection of eye irritation endpoint:
Study performed to OECD TG 405 and has a Klimisch score of 2. Read across from C12-14 AO.

Effects on skin irritation/corrosion: highly irritating

Effects on eye irritation: corrosive

Justification for classification or non-classification

The substance is classified as Skin Irritant Category 2 on the basis of the reactions seen in the skin irritation studies.

C12 -14 AO caused damage to the eyes of rabbits that did not fully reverse during the 21 day observation period and is therefore classified as Eye Damage Category 1. This classification is read across to C12 -18 AO.