Registration Dossier

Toxicological information

Exposure related observations in humans: other data

Administrative data

Endpoint:
exposure-related observations in humans: other data
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:
Serum glutamic acid levels and the occurrence of nausea and vomiting after the intravenous administration of amino acid mixtures
Author:
Levey S, Harroun JE, Smyth CJ, and Mich D
Year:
1949
Bibliographic source:
Journal of Laboratory and Clinical Medicine, 34, p.1238-1248

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

Method

Ethical approval:
not specified
Details on study design:
The first eight subjects received infusions of solutions containing 5.05 gm. of partially neutralized glutamic acid per 400 mL of solution; the next nine subjects received infusions of a solution containing 10.1 gm. of glutamic acid for 400 mL.

Results and discussion

Results:
Only two of these subjects had serum free glutamic acid levels exceeding 12 mg per 100 mL. Nine subjects received the stronger solution, five of whom became nauseated or vomited. Forty-five percent of the subjects who had levels of glutamic acid above 12 mg per 100 mL became nauseated or vomited (Table 1, upper half) .Since many of the commercial protein digests are sterilized by filtration rather than autoclaving and since heat promotes the conversion of glutamic acid to pyrrolidone carboxylic acid, it was decided to repeat these studies using only glutamic acid solutions which had been sterilized by filtration, employing both the lower and higher doses (Table 1, lower half). When the lower dose was administered, two of the six subjects tested became nauseated or vomited; with the higher doses all of the eight subjects tested became ill. One subject vomited but had a blood glutamic acid level of only 7.5 mg per 100 mL.

Applicant's summary and conclusion

Conclusions:
There was a direct relationship between free serum glutamic acid and the occurrence of toxic effects following intravenous administration. When the serum free glutamic acid level reached 12-15 mg/100 mL, nausea and vomiting occurred in more than half of the subjects.