Reaction mass of sodium hydrogen N-(1-oxooctadecyl)-L-glutamate and stearic acid

Endpoint summary

Description of key information

It is likely that the test substance forms two physiological cleavage products: fatty acids and glutamic acid.

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Additional information

Metabolism

In the following, the available information on the toxicokinetic properties for the target substanceReaction mass of sodium hydrogen N-(1-oxooctadecyl)-L-glutamate and stearic acid (EC 939-201-1)and the source substancesL-Glutamic acid, N-coco acyl derivs., disodium salts (CAS 68187-30-4) and L-Glutamic acid, N-coco acyl derivs., disodium salts (CAS 68187-32-6)is assessed. Both substances are amino acid alkyl amides. A likely metabolic pathway for these substances includes reactions catalyzed by amidases resulting in the release of the amino acid glutamic acid and the fatty acid (stearic acid or coconut acid) (CIR 2013) which are both part of the daily dietand are consumed by humans on a gram scale.

Glutamic acid will be then degraded via transamination, in which the amino group of the amino acid is transferred to a ketoacid, typically catalyzed by a transaminase.Transamination can thus be linked to deamination, effectively allowing nitrogen from the amine groups of amino acids to be removed, via glutamate as an intermediate, and finally excreted from the body in the form of urea.

 

Fatty acids, like stearic acid and coconut acid, will be metabolized via ß-oxidation which is the catabolic process to break down fatty acids in the mitochondria to generate acetyl-CoA finally entering in the citric acid cycle (CIR 1987).

 

It can be concluded that the metabolism of both substances should be comparable due to the structural similarity.

 

 

Absorption, distribution and excretion

The bioavailability of the target and the source substances is related to the efficiency of absorption which depends on pancreatic function, biliary secretion to form mixed micelles with the hydrolysed fat, and the transfer across intestinal membranes. Both substances have a low log Pow and a good water solubility.

Oral absorption

Due to the high water solubility and the low log Pow of the substances, systemic uptake via passive diffusion is possible within the gastrointestinal (GI) tract. Furthermore, water soluble substances will readily dissolve in the GI fluids, which enhance the contact with the intestinal mucosa. Following oral intake, and once in contact with the digestive fluids of the stomach and uptake in the body, it is assumed that the target and source substance will comparably degrade into fatty acid and glutamic acid. For this reason, a studywas performed to investigate the hydrolytic degradation of the two test substances “L-Glutamic acid, N-coco acyl derivs. disodium salts” and “Reaction mass of sodium hydrogen N-(1-oxooctadecyl)-l-glutamate and stearic acid” in gastric juice simulant and liver S9 fraction of different species (see IUCLID chapter 7.1.1). As glutamic acid is the most likely hydrolysis product for the target and the source substance, the glutamic acid concentration was measured in the respective samples.There was no indication for the formation of glutamic acid during incubation in gastric juice simulant for both substances. When using liver S9 fraction from different species (rat, rabbit, human), it is concluded that the target and the source substance demonstrate a comparable glutamic acid formation in the different S9 liver fractions.

 

Dermal absorption

Based on the good water solubility of the reaction product, dermal uptake is negligible. It is commonly known that substances with a good water solubility are too hydrophilic to cross the lipid rich environment of the stratum corneum.

Distribution 

Once absorbed it is expected that the reaction products and its metabolites are distributed within the blood stream. Here the transport efficiency to the body tissues is limited by the rate at which the highly water soluble substances cross cell membranes. More specifically, access to the central nervous system or the testes is likely to be restricted by the blood-brain and blood-testes barriers (Rozman and Klaassen 1996). Due to the high water solubility and the low log Pow accumulation is unlikely (see Bioaccumulation assessment). 

Excretion 

Based on the expected biotransformation reactions, molecular size and water solubility, it is most likely that the final metabolites are excreted via the urine.

Conclusion

It is expected that both amino acid alkyl amides after oral intake behave similar. A dermal intake is not expected for both target and source substances due to their physico-chemical properties.