Amines, C12-18-alkyldimethyl, N-oxides

Endpoint summary

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Two reliable animal studies are available for C12 -14 AO. In the key study [Conine DL (1984)] performed according to OECD TG 406 (Buehler method) a group of 10 male and 10 female guinea pigs (Hartley) were treated with 2 % w/v of the test substance (containing 30.4 % AO) in distilled water for a period of 6 hours weekly for 3 induction exposures. The test substance was applied to the shaved left shoulder of each animal and covered occlusively for 6 hours. A group of 10 animals served as controls. The test animals and control animals were challenged with 1 % w/v of the test substance in distilled water two weeks after the final induction. The test substance was applied to the shaved left posterior quadrant of the side and back of the test animal and covered occlusively for 6 hours. Dermal reaction to the challenge was assessed 24 and 48 hours after the challenge exposure. No positive responses were noted at 24 or 48 hours. In the supporting study [Vinegar MB (1978)] also performed according to OECD TG 406 a group of 20 guinea pigs were treated with 0.4 mL of undiluted test substance (containing 27.8% AO) for a period of 6 hours weekly for 3 induction exposures. The test animals (and control animals) were challenged with 10 % w/v of the test substance in distilled water.At challenge, slight confluent or moderate patchy erythema (score 1) was observed in 2/20 test animals at the 24-hour reading. No positive responses were noted in the control animals. At 48 hours no positive responses were noted in the test and control animals.Thus, the responses observed at 24 hours were considered irritative in nature. Conclusion: the test substance (C12 -14 AO) is not a skin sensitiser in guinea pigs.

There are three reliable human patch test studies available. In the key study [MacLennan A (1982)] performed according to good clinical regulations 21CFR parts 50, 56 & proposed ICH guideline, 78 (male and female) subjects were exposed to 9 induction patches containing 0.75% aqueous C12 -14 AO (30% AO) under occlusion for a period of 3 weeks. Patches were removed 24 hours after each application and patch sites were graded at 48 hour after patch application prior to the next patch application. After a 2 week rest period, subjects were challenged with 0.75% aqueous test substance (30% AO) 24 hour patch exposure. Challenge patch sites were graded at 48 and 96 hours after patch application.31/78 subjects were observed with mild erythema grade1 during the challenge exposure. No positive responses indicative of delayed contact hypersensitivity was observed. A second human patch study [Cuthbert (1982)] using 0.5% aqueous C12 -14 AO (27.4% AO) conducted to the same study design also showed mild erythema grade 1 in 39/85 subjects during the challenge exposure. These skin responses resolved at the 96 hour challenge read and mild erythema was observed suggesting that these responses were irritative in nature. In a third human patch study [Yerker (1989)] using 0.1% aqueous C12 -14 AO (31.6% AO) conducted to the same study design none of the 106 subjects who completed the test produced visible response during the challenge test. All three reliable human patch test studies concluded that C12 -14 AO did not produce skin sensitisation in humans.

The results of these studies may be read across to C12 -18 AO based on the large overlap in alkyl chain length distributions and similar physico-chemical properties between C12 -14 and C12 -18 AO.

Migrated from Short description of key information:
C12-14 AO was not sensitising in three human patch test studies. It was also not sensitising to the skin of Guinea pigs in two Buehler tests. The results of these studies may be read across to C12 -18 AO based on the large overlap in alkyl chain length distributions and similar physico-chemical properties between C12 -14 AO and C12 -18 AO.

Justification for selection of skin sensitisation endpoint:
Study performed according to OECD TG 406 under GLP

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information:

No data are available regarding the potential of amine oxides to cause respiratory sensitisation.

Migrated from Short description of key information:
No information is available for this endpoint

Justification for classification or non-classification

Three repeat insult patch tests performed using C12 -14 AO are available in humans. None of these studies showed evidence of sensitisation. In addition, two Buehler tests are available which show C12 -14 AO is not sensitising to the skin of Guinea pigs. On the basis of these studies the C12 -14 AO does not require classification as a skin sensitiser. This result is read across to C12 -18 AO based on the large overlap in alkyl chain length distributions and similar physico-chemical properties.