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

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

July-November 2019

Reliability:

1 (reliable without restriction)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2021

Report date:

2021

Materials and methods

Objective of study:

other: comparative hydrolysis stability

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

The current study was performed to investigate the hydrolytic degradation of the the two test substances “L-Glutamic acid, N-coco acyl derivs. disodium salts” (BASF test substance number 12/0032-3) and “Reaction mass of sodium hydrogen N-(1-oxooctadecyl)-l-glutamate and stearic acid” (BASF test substance number 16/0435-2) in gastric juice simulant and liver S9 fraction of different species.

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

L-Glutamic acid, N-coco acyl derivs., disodium salts

EC Number:

269-085-1

EC Name:

L-Glutamic acid, N-coco acyl derivs., disodium salts

Cas Number:

68187-30-4

Molecular formula:

Not applicable (UVCB substance)

IUPAC Name:

Disodium (2S)-2-aminopentanedioate

Details on test material:

30-36% active matter

Radiolabelling:

no

Test animals

Species:

other: gastric juice simulant and liver S9 fraction

Results and discussion

Any other information on results incl. tables

When “L-Glutamic acid, N-coco acyl derivs. disodium salts” was incubated in gastric juice simulant, analyzed concentrations of glutamic acid in the incubates (including controls) ranged from 0.352 to 0.935 µg/mL (for incubates with a nominal test substance concentration of 10 ppm) and from 3.807 to 5.204 µg/mL (for incubates with a nominal test substance concentration of 100 ppm). There was no indication for the formation of glutamic acid during incubation of the test substance in gastric juice simulant.

For “Reaction mass of sodium hydrogen N-(1- oxooctadecyl)-l-glutamate and stearic acid”, corresponding values of glutamic acid ranged from 0.097 to 0.436 µg/mL (for incubates with a nominal test substance concentration of 10 ppm) and from 1.102 to 2.891 µg/mL (for incubates with a nominal test substance concentration of 100 ppm). There was no indication for the formation of glutamic acid during incubation of the test substance in gastric juice simulant.

When “L-Glutamic acid, N-coco acyl derivs. disodium salts” was incubated in S9 fraction of rats, rabbits and humans at a test substance concentration of 50 ppm, analyzed concentrations of glutamic acid in the incubates increased generally over time and yielded maximum concentrations of 8.221, 22.549 and 22.008 µg/mL, respectively after 120 min of incubation. For all incubations, buffer controls revealed concentrations of glutamic acid that were ≤ 2.5 µg/mL. For the rat in vitro systems, also medium controls and heat deactivated controls showed concentrations of glutamic acid that were ≤ 2.5 µg/mL. For the rabbit in vitro system, medium controls as well as heat deactivated controls revealed concentrations of glutamic acid of 6.429 and 8.696 µg/mL as well as 7.051 and 8.163 µg/mL. For the human in vitro system, medium controls as well as heat deactivated controls revealed concentrations of glutamic acid of 15.594 and 17.739 µg/mL as well as 16.676 and 17.379 µg/mL. Consequently, the increase of glutamic acid formation in the S9 liver fraction of rats was 5,35 µg/ml after 120 min incubation (see table below), in the S9 liver fraction of rabbits 14,06 µg/ml and in the S9 liver fraction of humans 4,1 µg/ml.

When “Reaction mass of sodium hydrogen N-(1-oxooctadecyl)-l-glutamate and stearic acid” was incubated in S9 fraction of rats, rabbits and humans at a test substance concentration of 50 ppm, analyzed concentrations of glutamic acid in the incubates increased generally over time and yielded maximum concentrations of 7.725, 18.987 and 19.592 µg/mL, respectively after 120 min of incubation. For all incubations, buffer controls revealed concentrations of glutamic acid that were ≤ 2.5 µg/mL. For the rat in vitro systems, also medium controls and heat deactivated controls showed concentrations of glutamic acid that were ≤ 2.5 µg/mL. For the rabbit in vitro system, medium controls as well as heat deactivated controls revealed concentrations of glutamic acid of 6.245 and 8.528 µg/mL as well as 5.992 and 7.183 µg/mL. For the human in vitro system, medium controls as well as heat deactivated controls revealed concentrations of glutamic acid of 16.937 and 17.337 µg/mL as well as 16.309 and 17.387 µg/mL. Consequently, the increase of glutamic acid formation in the S9 liver fraction of rats was 4,86 µg/ml after 120 min incubation (see table below), in the S9 liver fraction of rabbits 11,72 µg/ml and in the S9 liver fraction of humans 2,82 µg/ml.

 

 Taken together, the data of incubations of “L-Glutamic acid, N-coco acyl derivs. disodium salts” and “Reaction mass of sodium hydrogen N-(1-oxooctadecyl)-l-glutamate and stearic acid” in liver S9 fraction demonstrate that glutamic acid formation from both test substances in the applied in vitro systems is comparable. Under the test conditions used, highest amounts of glutamic acid were formed in liver S9 fraction of rabbits. In the liver S9 fractions of rats, the glutamic acid formation was lower than in the rabbit, but comparable for both substances. As the 90 day study and the teratogenicity study were performed with rats, the comparable hydrolysis of the target and the source substance supports the analogue justification (see attached document).

Applicant's summary and conclusion

Conclusions:

Taken together, the data of incubations of “L-Glutamic acid, N-coco acyl derivs. disodium salts” and “Reaction mass of sodium hydrogen N-(1-oxooctadecyl)-l-glutamate and stearic acid” in liver S9 fraction demonstrate that glutamic acid is formation from both test susbtances in the applied in vitro systems is comparable. Under the test conditions used, highest amounts of glutamic acid were formed in liver S9 fraction of rabbits. There was no indication for the formation of glutamic acid during incubation of the test substance in gastric juice simulant.