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Description of key information

No experimental data on toxicokinetics, metabolism and distribution of the submission substance are available. Based on the physicochemical properties of the submission substance it is anticipated that the substance is bioavailable via the oral, dermal or inhalation route. Beta oxidation or direct hydrolysis are thought to be reasonable metabolism pathways leading to systemic exposure to 3,5,5-trimethylhexanoic acid. Given the results from repeated dose experiments no concern for bioaccumulation is raised.

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential

Additional information

The submission substance is a 2,2',2''-nitrilotriethanol (TEA) salt of 6 -(isononanoylamino)hexanoic acid. A spontaneous conversion to acid is expected in aqueous system or in biological fluid. The relevant chemical species for uptake and systemic exposure is the acid. Thus the kinetic profile will be derived for 6 -(isononanoylamino)hexanoic acid.

6 -(Isononanolyamino)hexanoic acid is pected to be bioavailable for oral/dermal/inhalation routes based on the given molecular size (MW of 422.6; MW of the corresponding acid 271.4 g/mol) and the octanol water partition coefficient (LogPow of -0.6; LogPow of the corresponding acid 2.47). No metabolism or kinetic study is available on the submission substance or its corresponding acid. Based on the structural analysis and the indication obtained in the microbial degradation study (metabolite identification in samples of Zahn-Wellens Test), two degradation pathways can be reasonably derived:

-      Beta oxidation at the terminal carboxylic acid moiety in combination with hydrolysis at amide bond

-      Direct hydrolysis at the amide moiety

Both pathways are leading to systemic exposure to 3,5,5-trimethylhexanoic acid, which serves as surrogates of the proposed read-across approach.

The submission substance as well as the presumed metabolite 3,5,5-trimethylhexanoic acid caused effects on liver and kidney upon 28-day oral treatment in rats and these effects were fully reversible within recovery period of 14 days. No concern with respect to the bioaccumulation can be derived.