Registration Dossier

Diss Factsheets

Administrative data

basic toxicokinetics
Type of information:
other: expert statement
Adequacy of study:
key study
Study period:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study

Data source

Materials and methods

Principles of method if other than guideline:
The attached Toxicokinetic Assessment is meant to fulfill the requirement as defined in the REGULATION (EC) No 1907/2006 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL of 18 December 2006 requests in Annex VIII, point 8.8.1:
"Assessment of the toxicokinetic behaviour of the substance to the extent that can be derived from therelevant available information."

Results and discussion

Applicant's summary and conclusion

Interpretation of results: no bioaccumulation potential based on study results.

Sodium cocoyl apple amino acids is a colourless liquid and a mixture of N-acetylated amino acids. It is an anionic detergent with a water solubility of 395.4g/L. Based on the available data sodium cocoyl apple amino acids will probably be absorbed to a low extent via the skin and via inhalation and to a significant extent via the gastro-intestinal-tract. Actually, classical surfactants are reported to reversibly damage and alter the physiological nature of the stratum corneum reducing then its diffusional resistance. Thus, in a weight of evidence dermal absorption rate of Sodium cocoyl apple amino acids is assumed to be to be low considering the adverse effect noted in skin irritation test. Due to their high water solubility and their resemblance to amino acids the ingredients of the mixture (and their metabolites) can reach every tissue of the organism. In repeated dose toxicity study (OECD 422), the observed clinical, clinicochemical and (histo) pathological effects demonstrate bioavailability from the gastro-intestinal tract with report to the control group. However, there was no indication of a cumulative toxicity in this study.
Concerning metabolism, a significant metabolism of Sodium cocoyl apple amino acids in the liver can be expected when being absorbed from the gastrointestinal tract. Considering the chemical structure of Sodium cocoyl apple amino acids the metabolism may consist of:
- Hydrolysis of the ester binding by N-aminoacetylases, present in all cells of mammals and other eucariotic organisms, will hydrolyse the N-acetylated amino acids to acetate and the respective amino acid. These common metabolites will be included in the physiologic processes and metabolised accordingly.
- Oxidation of both hydrolysis products by cytochrome P450-dependent monooxygenases
- Cytochrome P450-dependent decarboxylation
- Glucurono/sulfo or GSH-conjugations of metabolic oxidation products.
Concerning excretion, an extensive metabolisation, leading to polar metabolites with low molecular weights, followed by renal excretion is to be expected
Therefore there is no potential of bioaccumulation of the constituents of this mixture.