1-Propanaminium, N-(3-aminopropyl)-2-hydroxy-N,N-dimethyl-3-sulfo-, N-C12-14 acyl derivs., hydroxides, inner salts

Endpoint summary

Description of key information

There is no requirement to generate experimental toxicokinetic data under REACH. No toxicokinetic data are identified; however a theoretical assessment of the toxicokinetic properties of the substance is made, based on existing toxicity data, (Q)SAR, and taking into account the (physico)chemical properties of the substance. 

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Absorption rate - oral (%):

50

Absorption rate - dermal (%):

10

Absorption rate - inhalation (%):

100

Additional information

BETADET SHR

The substance is a UVCB; the two major components are structurally very similar (differing only in the carbon chain length) and account for the large majority of the substance composition. The toxicokinetic assessment is made for the major components C12 and C14 cocamidopropyl hydroxysultaine.

Absorption

Both of the major components of the substance are predicted to be bioavailable according to Lipinski’s rules (Oasis). The estimated Log Kow values for the C12 (-2.34) and C14 (-1.36) do not favour oral absorption; however the high water solubility means that oral absorption is likely. Hydrolysis and/or microbial metabolism may occur in the gastrointestinal tract, leading to the absorption of lower molecular weight breakdown products. The substance is a non-volatile liquid, therefore significant inhalation exposure is not predicted. The high water solubility of the substance favours absorption following inhalation exposure. The high water solubility of the substance favours dermal absorption; however the extent of dermal absorption is likely to be limited by the relatively high molecular weight (420 -460) of the major components and their very low lipid solubility. In the absence of experimental data, absorption values of 100% (inhalation), 50% (oral) and 10% (dermal) are assumed for the purposes of the risk assessment.

Distribution

Information from the OECD 422 screening study with the read-across substance C8-18 cocamidopropyl hydroxysultaine reports mild renal pathology, indicating that the substance and/or its metabolites are distributed to the kidneys. This finding therefore indicates systemic exposure. Additional findings in the study are consistent with local irritation of the gastrointestinal tract and secondary effects and do not provide any further evidence for systemic distribution.

Metabolism

The mammalian metabolism of C-12 cocamidopropyl hydroxysultaine is predicted using OECD QSAR Toolbox (v.4). The rat liver S9 metabolism simulator predicts twelve metabolites, resulting from the initial cleavage of the molecule at the amide linkage to produce the C12 carboxylic (lauric) acid. This carboxylic acid is predicted to be incorporated into normal fatty acid metabolism (β-oxidation) with the generation of acetate and correspondingly shorter fatty acids. The other product of the initial hydrolysis step is the amine, which is predicted to be subject to N-dealkylation. The in vivo rat metabolism simulator predicts two metabolites, arising from hydroxylation of the (ω-2)- and (ω-3)- carbons on the C12 sidechain. The skin metabolism simulator predicts the oxidation of the hydroxyl group on the hydroxysultaine moiety of the intact molecule to generate an aldehyde, as well as hydrolysis of the molecule at the amide group. The molecule is predicted to be hydrolytically stable at neutral pH; however hydrolysis at the amide group may occur under acidic and basic conditions; hydrolysis in the gastrointestinal tract may therefore occur to some extent. It is also notable that extensive microbial metabolism is predicted (~90 metabolites), indicating that metabolism by the gastrointestinal microflora may occur following oral exposure.

The mammalian metabolism of C-14 cocamidopropyl hydroxysultaine is predicted using OECD QSAR Toolbox (v.4). The rat liver S9 metabolism simulator predicts twelve metabolites, resulting from the initial cleavage of the molecule at the amide linkage to produce the C14 carboxylic (myristic) acid. This carboxylic acid is predicted to be incorporated into normal fatty acid metabolism (β-oxidation) with the generation of acetate and correspondingly shorter fatty acids. The other product of the initial hydrolysis step is the amine, which is predicted to be subject to N-dealkylation. The in vivo rat metabolism simulator predicts two metabolites, arising from hydroxylation of the (ω-2)- and (ω-3)- carbons on the C14 sidechain. The skin metabolism simulator predicts the oxidation of the hydroxyl group on the hydroxysultaine moiety of the intact molecule to generate an aldehyde, as well as hydrolysis of the molecule at the amide group. The molecule is predicted to be hydrolytically stable at neutral pH; however hydrolysis at the amide group may occur under acidic and basic conditions; hydrolysis in the gastrointestinal tract may therefore occur to some extent. It is also notable that extensive microbial metabolism is predicted (~100 metabolites), indicating that metabolism by the gastrointestinal microflora may occur following oral exposure.

Excretion

Histopathological findings in the kidneys in the OECD 422 screening study with the read-across substance C8-18 cocamidopropyl hydroxysultaine may indicate renal excretion. Based on the likely extensive cleavage and metabolism of the major components of the substance and incorporation into normal fatty acid metabolism, excretion may be limited to the amidopropyl hydroxysultaine portion of the molecule which is low molecular weight and water soluble and therefore likely to be excreted in the urine. 

Bioaccumulation

Bioaccumulation is not predicted, based on the likely extensive metabolism and excretion of the main components. Although it is likely that metabolites of the main components will enter normal fatty acid metabolism and consequently may be incorporated into endogenous molecules, this does not represent bioaccumulation.