Registration Dossier

Administrative data

Endpoint:
sub-chronic toxicity: oral
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
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:
OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity 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

Reference
Name:
Unnamed
Type:
Constituent

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

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.