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

Repeated dose toxicity: oral

Administrative data

Endpoint:

sub-chronic toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Klimisch criteria. The registered substance is a UVCB material which contains substances of varying chain length. Read across was performed to an analogous material whose carbon chain length differs by an average of two CH2-groups from the registered substance. Because of the UVCB nature of these substances, the components of the registered substance were also present in the test material, albeit at slightly different concentration levels.

Data source

Reference

Reference Type:

publication

Title:

Toxicological properties of N-lauryl-L-glutaminic acids - surface active substances in the food industry

Author:

Zaitsev et al.

Year:

1984

Bibliographic source:

(1984), Vopr. Pitan. (4), p. 58-60

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)

Principles of method if other than guideline:

112 treatment days. Relative organ weights investigated: liver, kidneys, spleen, adrenals, testes. Biochemical parameters: Hb, Total protein, ascorbic acid, cholinesterase, ALT, AST

GLP compliance:

no

Limit test:

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

Test animals

Species:

rat

Strain:

not specified

Sex:

male

Administration / exposure

Route of administration:

oral: gavage

Analytical verification of doses or concentrations:

no

Duration of treatment / exposure:

112 days

Frequency of treatment:

once per day

Doses / concentrations

Remarks:

Doses / Concentrations:
1200 mg/kg bw
Basis:
actual ingested

No. of animals per sex per dose:

no data.

Control animals:

yes

Details on study design:

112 treatment days. Relative organ weights investigated: liver, kidneys, spleen, adrenals, testes. Biochemical parameters: Hb, Total protein, ascorbic acid, cholinesterase, ALT, AST

Examinations

Statistics:

Student t-Test

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

not specified

Food efficiency:

not specified

Water consumption and compound intake (if drinking water study):

not specified

Ophthalmological findings:

not specified

Haematological findings:

no effects observed

Clinical biochemistry findings:

no effects observed

Urinalysis findings:

not specified

Behaviour (functional findings):

not specified

Organ weight findings including organ / body weight ratios:

no effects observed

Gross pathological findings:

not specified

Histopathological findings: non-neoplastic:

not specified

Histopathological findings: neoplastic:

not specified

Effect levels

Dose descriptor:

NOAEL

Effect level:

ca. 1 200 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

male

Basis for effect level:

other: No treatment-related adverse effects observed up to and including the highest dose.

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

The NOAEL in this study was 1200 mg/kg bw.

Executive summary:

The repeated dose toxicity of N-cocoacyl glutaminic acid, sodium salts, a close homologue of the registered substance, has been investigated in male albino rats. The animals received 0 or 1200 mg/kg bw per day for a treatment period of 112 days. No mortality or clinical signs were observed during treatment. No mortality occured. The body weight development statistically did not differ between dose and control group.

After necropsy the following parameters were assessed: relative organ weights of liver, kidneys, testes, adrenals, spleen. The following clinical chemical and hematological parameters were: hemoglobin, total serum protein, total liver protein, ascorbic acid in adrenals, testes and liver tissue. All values were statistically not different between control and dose groups or were within historical controls. The authors conclude that the NOAEL is 1200 mg/kg bw.

Although the study has its restrictions in terms of documentation and parameters assessed, the result reflects the fact that during hydrolysis the test substance forms two physiological cleavage products: Coco fatty acids and glutamic acid. Both are natural constituents of conventional foods which are consumed on a gram per day level. Under these circumstances it is scientifically not justified to repeat the subchronic study in order to fill potantial data gaps (histopathology, missing organ weights and clinical chemical and hematological parameter, missing female animals). Therefore, the NOAEL of 1200 mg/kg bw is considered to be a valoid point of departure.