Glutens, hydrolyzates, reaction products with lauroyl chloride, sodium salts

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics

Type of information:

other: expert statement

Adequacy of study:

key study

Study period:

2010-12-10

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline study

Data source

Reference

Reference Type:

other: expert statement

Title:

Unnamed

Year:

2010

Report date:

2010

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."

GLP compliance:

not specified

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:

Proteol OAT has a boiling point of 108.6 °C at ca. 98.5 kPa and a vapour pressure of 2751 Pa
at 25°C. With these values the ECETOC TRA tool calculates a medium fugacity. Thereby at
normal pressure significant amounts of inhalable vapour can be expected.
Proteol OAT is hydrophilic with a log Pow of ca. – 2.7 and a water solubility of 277.6 g/L. This
value is usually associated with a low tendency for absorption through passive diffusion via
membranes. Nevertheless as anionic detergents the ingredients of Proteol OAT are able to
integrate in lipid bilayers and pass them by the flip-flop mechanism. The ability to be absorbed
through this mechanism varies due to the side chain character of the specific acetylated amino
acid.

Details on distribution in tissues:

Distribution
After absorption due to their high water solubility the N-acetylated amino acids or their
metabolites (see below) can diffuse freely in the cytosol of cells and in the blood stream and
thereby reach every tissue of the body.

Details on excretion:

Excretion
In a healthy organism amino acids and acetate will be included in the physiologic processes and
metabolised and excreted accordingly.

Metabolite characterisation studies

Details on metabolites:

Metabolism
N-aminoacetylases are expressed in every cell in the mammalian organism as N-acetylated
amino acids are common products of protein metabolism and occur in every cell of mammals
and other eucariotic organisms. N-aminoacetylase hydrolyses N-acetylated amino acids to
acetate and the respective amino acids. Both products are common physiologic metabolites and
thereby exhibit no noticeable toxicity. This is resembled by the absence of any toxic effect seen
in any of the conducted studies, except for irritation. The resulting metabolites will be included in
physiologic processes.

Bioaccessibility (or Bioavailability)

Bioaccessibility (or Bioavailability) testing results:

- Oral route:
No toxicity is seen after acute oral or dermal exposures up to 2000 mg/kg bw. In a repeated
dose study according to OECD 422 the NOAEL was found to be at the highest dose of 1000
mg/kg bw. Nevertheless it is assumed that this is rather an effect of the low inherent toxicity of
the ingredients and their metabolites (see below). The same argument is applicable for the
absence of effects in the sensitization test and the genotoxicity assays. As the ingredients of
Proteol OAT are N-acetylated amino acids that act as anionic detergents they might either be
absorbed via passive diffusion or via amino acid specific uptake mechanisms in the intestine.
Therefore absorption of significant amounts of the substances via the oral route can be
expected.
- Dermal route:
Generally the absorption potential for anionic tensids is assumed to be low (Reichl 2002).
Nevertheless the significant potential to induce skin irritation, seen in the both dermal studies,
might increase the dermal penetration of the mixture. The skin penetration potential of Proteol
OAT is expected to be low but measurable.
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- Inhalation: Based on the vapour pressure of the substance, inhalation exposure is not unlikely.
As for the dermal route the inhalation absorption potential of Proteol OAT is expected to be low
but measurable. The mechanism would be passive diffusion.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): no bioaccumulation potential based on study results
Proteol OAT is a slightly yellowish liquid and a mixture of N-acetylated amino acids. It is an anionic detergent with a water solubility of 277.6 g/L. Based on the available data Proteol OAT will probably be absorbed to a low extent via the skin and via inhalation and to a significant extent via the gastro-intestinal-tract. 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. 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 and excreted accordingly.
Therefore there is no potential of bioaccumulation of the constituents of this mixture.