Registration Dossier

Administrative data

Endpoint:
carcinogenicity: 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:
SIDS for L-Glutamic acid
Author:
OECD
Year:
2013
Report Date:
2013
Reference Type:
publication
Title:
The dietary administration of L-monosodium glutamate, DL-monosodium glutamate and L-glutamic acid to rats
Year:
1979
Bibliographic source:
Toxicology letters, 3, 71-78

Materials and methods

Test guideline
Qualifier:
no guideline followed
GLP compliance:
not specified

Test material

Specific details on test material used for the study:
International Minerals and Chemical Corp., Chicago

Test material equivalent to submission substance identity:
yes

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: 11-13 weeks old
- Weight at study initiation: 250-300 g
- Housing: housed in wire-mesh cages each holding 7 or 8 animals
- Diet: ad libitum
- Water: ad libitum

Administration / exposure

Route of administration:
oral: feed
Duration of treatment / exposure:
2 years
Doses / concentrationsopen allclose all
Dose / conc.:
0.1 other: %
Remarks:
L-glutaminic acid nominal in diet, equal to 199 and 542 mg/kg bw/day for males, and 125 and 348 mg/kg bw/day for females
Dose / conc.:
0.4 other: %
Remarks:
L-glutaminic acid nominal in diet, equal to 199 and 542 mg/kg bw/day for males, and 125 and 348 mg/kg bw/day for females
No. of animals per sex per dose:
control: 61 for male and 89 for female
0.1% L-glutamic acid: 40 for male and 35 for female
0.4% L-glutamic acid: 35 for male and 40 for female
Control animals:
yes, plain diet

Examinations

Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: Yes
- Cage side observations checked in table [No.2] were included.
DETAILED CLINICAL OBSERVATIONS: Yes
BODY WEIGHT: Yes
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Daily group food intake was assessed.
OPHTHALMOSCOPIC EXAMINATION: Yes
HAEMATOLOGY: Yes
- Time schedule for collection of blood: 241, 567 and 681 days
- Anaesthetic used for blood collection: No data
- Animals fasted: No data
- How many animals: No data
- Parameters checked in table [No.3] were examined.
NEUROBEHAVIOURAL EXAMINATION: Yes
Sacrifice and pathology:
After 63 days, 6 males and 6 females from the control group and 3 males and 3 females from each of the treated groups were killed and examined for gross and histological changes. Since none were observed, further planned interim sacrifices were abandoned, except for a group of 23 rats after 68 days.
Histological studies were made on the lungs, heart, thyroid, trachea, oesophagus, stomach, intestine, kidneys, liver, spleen, gonads and on any other tissue that appeared abnormal, and on any tumour.
Other examinations:
Any individual that appeared on regular examination to have any abnormality, such as a tumour, dental anomaly, paralysis, pneumonia, atypical eye condition or general debility, was killed if survival appeared to be threatened.

Results and discussion

Results of examinations

Clinical signs:
no effects observed
Mortality:
no mortality observed
Description (incidence):
Combined % survival at this time was 57.3 for all test animals and 59.3 for controls.
Body weight and weight changes:
no effects observed
Description (incidence and severity):
Bodyweight gains of all rats proceeded at a normal rate and there were no significant between-group differences for either females or males, althoughthe supplemented groups were consistently ahead of controls.
Food consumption and compound intake (if feeding study):
no effects observed
Description (incidence and severity):
Nor were there any significant differences in general behaviour or estimated food intake.
Haematological findings:
no effects observed
Description (incidence and severity):
There were no between-group haematological variations. In males and females of all groups there was a slight tendency to monocytosis throughout the study, and in all female groups at 681 days a slight eosinophilia.
Organ weight findings including organ / body weight ratios:
no effects observed
Description (incidence and severity):
There were no between-group differences in organ weight analysis or in any other findings.
Gross pathological findings:
no effects observed
Description (incidence and severity):
The combined incidence of tumours was 40.1% for all test animals, and 42.4% for conrols. The tumours in females were almost all mammary adenomata, some of which were actively secreting and some fibrosed. In males, most tumours were of dermal origin and classified as benign.
Description (incidence and severity):
The only significant difference was a 6.9% incidence of dental abnormalities in control rats, contrasted with 3.5% for all test rats combined.

Applicant's summary and conclusion

Conclusions:
There was no evidence that L-glutamic acid, at either dose level, exerted any adverse effect upon survival, weight increase, food intake, haematology, tumor incidence or age-related pathological changes in either sex. Motor activity and general behavioural patterns appeared unaffected.