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Category name:
Amine Oxides

Justifications and discussions

Category definition:
The Amine Oxide (AO) category comprises monoconstituent and UVCB surfactant substances known as alkyl dimethylamine oxides that contain even-numbered linear saturated alkyl chains ranging from C10 to C18. Also known as fatty alkyl dimethylamine oxides, they are usually produced by reacting alkyldimethyl amines with hydrogen peroxide in water. The exact composition of the amine oxide is determined by the composition of the tertiary amine used as feedstock for oxidation by hydrogen peroxide. The tertiary amines are predominantly manufactured from plant-derived alcohols, which typically contain only even-numbered alkyl chain lengths. The amine oxides are produced, transported and used in aqueous solutions, typically at 25-40 %w/v AO. The AOs are produced and used either as single chain length substances (monoconstituents) or as a mixture of different chain lengths (UVCBs). There is a high degree of overlap between the chain length ranges represented by the AOs in this category.
Category order description:
Toxicological properties are consdered to be uniform across the category members, with the exception of skin irriation where the C10 AO is not classified and all other members are classified as Skin Irritation 2.
Category rationale:
1. CATEGORY HYPOTHESIS
Common structure and functional groups: the substances of the category are surfactants consisting of a polar head (the dimethylamine oxide group) and a relatively inert hydrophobic tail (the C10-C18 straight chain alkyl substituent).

Similar physico-chemical properties: While the variation in alkyl chain length does not affect chemical reactivity of the molecule, it does somewhat affect the relative physical chemical properties of the compound with increased lipophilicity with increasing chain length. However, prediction of Octanol Water Partitioning is difficult for substances in this category because of their surface activity. Therefore, in some cases the Partition Coefficient is predicted using measured and/or literature values of Octanol Solubility and Critical Micellar Concentration (CMC). The CMC provides a conservative estimate of water solubility with decreasing values with increasing alkyl chain lengths. Individual AOs with chain lengths C14 or less are predicted to have log Kow between 0.95 and 2.7. C12-18 AO has a measured log Kow of 1.05.
Similar metabolic pathways: The predominant metabolic pathway for all AOs in this category involves ω-hydroxylation of the terminal carbon of the alkyl chain followed by oxidation to form an acid metabolite that may undergo chain-shortening β-oxidation. Reduction of the N-oxide to the dimethylamine followed by oxidation back to the N-oxide also is possible. Based on the finding that the relative log N-oxidizability of C10-18 alkyldimethylamines varied by only 0.4 over the range of alkyl chain lengths in this category, it is reasonable to expect that if it occurred, the rates of N-oxidation/N-reduction should be comparable across the category.
Common levels and mode of human health related effects: Available data for category members shows consistency in toxicological properties and a lack of potency change of properties across the category with the exception of skin irritation where C10 AO was not classified, whereas the other members are classified as category 2. All category members are classified as Eye Damage 1. Acute toxicity data results in a category 4 classification for the oral route and no classification for the dermal route. The category members are not mutagenic or clastogenic. Repeated exposures in systemic toxicity studies result in a generalized adverse response of decreased body weight gain over time. In reproductive and developmental studies this maternal toxicity can lead to generalized effects of developmental toxicity including implantation loss and reduced body weights in offspring. The consistency in dose levels that elicit the observed effects indicates that the uptake/bioavailability across category members is similar and supports the hypothesis that there is no significant potency difference across category members.

Please refer to the Amine Oxide Category Justification report attached for further information


2. CATEGORY JUSTIFICATION
Please refer to the Amine Oxide Category Justification report attached for further information.

3. APPLICABILITY DOMAIN OF THE CATEGORY
The category includes monoconstituent and UVCB amine oxides with saturated, linear, even-numbered alkyl chain lengths from C10 to C18 only. Amine oxides with odd-numbered, unsaturated or branched alkyl chains are excluded.