Registration Dossier

Administrative data

Endpoint:
neurotoxicity: sub-chronic oral
Type of information:
other: SIDS
Adequacy of study:
other information
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
Effects of dietary supplementation of monosodium glutamate on infant monkeys, weanling rats, and suckling mice
Author:
Wen C-P, Hayes KC and Gershoff SN
Year:
1973
Bibliographic source:
The American Journal of Clinical Nutrition 26: 803-813.
Reference Type:
publication
Title:
SIDS for L-Glutamic acid
Author:
OECD
Year:
2013
Report Date:
2013

Materials and methods

Test guideline
Qualifier:
no guideline followed

Test material

Specific details on test material used for the study:
Test material equivalent to submission substance identity:
yes

Test animals

Species:
rat
Strain:
other: Charles River CD
Sex:
male

Administration / exposure

Route of administration:
oral: feed
Duration of treatment / exposure:
5 weeks
Frequency of treatment:
daily
Doses / concentrations
Dose / conc.:
174 000 mg/kg diet
Remarks:
nominal in diet
No. of animals per sex per dose:
6
Control animals:
yes
Details on study design:
[group 1] 100 g basal diet plus 20 g glucose;
[group 2] 100 g basal diet plus 20 g MSG;
[group 3] 100 g basal diet plus 40 g MSG;
[group 4] 100 g basal diet plus 17.4 g L-glutamic acid, the amount of glutamic acid in 20 g MSG;
[group 5] 100 g basal diet plus 1.5 g Na2S04, 1.5 g Na2CO3, 2 g NaHCO3, 2 g NaCl, 3 g glycine, 2.5 g L-alanine, 2.5 g L-glutamic acid, 1.3 g ammonium citrate, and 2.3 g L-serine (These supplements provided approximately the same quantity of sodium and nonessential amino acid nitrogen found in 20 g MSG).

Examinations

Observations and clinical examinations performed and frequency:
Weekly body weights, daily water consumption during the last 2 weeks, and the pH of the pooled urine samples from each group were recorded.After a 5-week period, the rats were fasted overnight and then fed ad libitum for 90 minutes prior to decapitation. Postprandial blood samples were collected from the neck for plasma glutamate determination.Organs of interest were weighed and brains and testes were fixed in 10% buffered formalin for histologic examination of hematoxylin- and eosin-stained sections. Serial frozen sections of formalin-fixed brain were also stained with the Fink and Heimer silver stain for degenerating axons.

Results and discussion

Results of examinations

Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Description (incidence and severity):
Average terminal body and brain weights were less than those of the control groups.
Description (incidence and severity):
Food intake was decreased in the four treatment groups.
Description (incidence and severity):
Rats fed free glutamic acid in group 4 had lower plasma glutamate than rats fed diets containing the same amount of glutamic acid as MSG.
Neuropathological findings:
no effects observed
Description (incidence and severity):
No specific endocrine or neurological defects were seen.
Description (incidence and severity):
The weights of adrenal glands and testes, expressed per 100 g body wt, were increased by supplements of either MSG or L-glutamic acid.The group fed L-glutamic acid consumed more water than the control group fed a similar amount of glucose.

Effect levels

Key result
Dose descriptor:
NOAEL
Effect level:
174 000 mg/kg diet

Applicant's summary and conclusion

Conclusions:
L-glutamic acid did not show specific endocrine or neurological defects.