SRC TR-10-122

HPV4 CHEMICAL DATA ADEQUACY REVIEW

Glycine, CAS No. 56-40-6

Prepared by:

Laura McIlroy, Justine Von Runnen, Teresa Manyin, and Joan D. Garey

Chemical, Biological, and Environmental Center

SRC, Inc.

7502 Round Pond Road

North Syracuse, NY 13212

Contract No. EP-W-09-027

Task FG007.0.009.002

Submitted to:

OPPT/RAD/HPVCB (7403M)

U.S. Environmental Protection Agency

1200 Pennsylvania Avenue

Washington, D.C. 20460

Elizabeth Margosches, Alternate Project Officer

Meena Sonawane, Work Assignment Manager

David Brooks, Alternate Work Assignment Manager

August 18, 2010
HPV4 Chemical Data Adequacy Review

Glycine, CAS No. 56-40-6

August 2010

Submitted to:

High Production Volume Chemicals Branch 

Risk Assessment Division 

Office of Pollution Prevention and Toxics 

Environmental Protection Agency 

WAM: Meena Sonawane

Alternate WAM: David Brooks

1200 Pennsylvania Avenue, NW 

Washington, DC 20460-0001

Prepared By:

SRC, Inc. 

Environmental Science Center 

2451 Crystal Drive, Suite 804 

Arlington, VA 22202
Draft HPV4 Chemical Data Adequacy Review CAS No. 56-40-6

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A. PREPARATION OF THE DATA ADEQUACY ASSESSMENTS

A-1. Source material used for assessment

For this unsponsored chemical, a comprehensive literature search was performed to 

identify available toxicity data for the following SIDS endpoints:

Acute toxicity to fish

Acute toxicity to Daphnia

Toxicity to aquatic plants

Acute (oral, dermal, inhalation) toxicity

Repeated-dose toxicity

Reproductive toxicity

Developmental toxicity

Gene mutation

Chromosomal aberrations

Studies relevant to non-SIDS endpoints (e.g., eye and skin irritation; neurotoxicity) conducted 

via oral, inhalation, or dermal routes were also identified through literature searching.

The following sources were searched for toxicity data:

PubMed - Bibliographic database that contains references to journal articles in the life 

sciences with a concentration on biomedicine

TOXNET -National Library of Medicine databases on toxicology, hazardous chemicals, 

environmental health, and toxic releases; includes: 

• TOXLINE with BIOSIS and NTIS;

• Development and Reproductive Toxicology File (DART);

• Chemical Carcinogenesis Research Information System (CCRIS) -

Carcinogenicity and mutagenicity test results for over 8000 

• chemicals);

• Hazardous Substances Data Bank (HSDB) - Comprehensive, peerreviewed toxicology data for about 5000 chemicals;

• Genetic Toxicology Data Bank (GENE-TOX) - Peer-reviewed genetic 

toxicology test data for over 3000 chemicals.

TSCATS - Unpublished technical reports submitted by industry to the EPA under the 

Toxic Substances Control Act]

Registry of toxic effects of chemical substances (RTECs)

Environmental Fate Database (EFDB)

ECOTOX -EPA’s peer-reviewed ecotoxicology database
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EPA’s Integrated Risk Information System (IRIS) website

Agency for Toxic Substances and Disease Registry (ATSDR) website

National Toxicology Program (NTP) website

International Program on Chemical Safety Concise International Chemical Assessment 

Documents (IPCS INCHEM or CICADs)

European Chemical Substances Information System (ESIS) - source of IUCLID Datasets

Any available IUCLID Datasets found through the ESIS website and robust summaries 

submitted to EPA by former sponsors on the assigned chemicals were retrieved. Original 

sources were obtained for any relevant toxicity data found for the assigned chemicals. 

While IUCLID Datasets sometimes contained studies of interest, certain study 

descriptions contained insufficient detail to assess adequacy. In these cases, the primary source 

of the study, if available and accessible, was obtained and reviewed.

A-2. Evaluating data adequacy

Using standard OECD testing guidelines and professional judgment as guides, available 

toxicity studies for the unsponsored chemical were reviewed for adequacy. Summaries were 

prepared for all relevant data found, even if little or no study detail was available. Each study 

was summarized according to a standard format and assigned a Klimisch reliability code; all 

study summaries for the chemical were combined into a single summary document. For studies 

already assigned Klimisch codes (e.g., studies summarized in IUCLID datasets), an explanation 

was provided if the reviewer’s assessment of data adequacy differed from the pre-assigned 

Klimisch code. A table summarizing data availability/adequacy for each SIDS endpoint is 

included at the end of the summary document. 

B. SPECIFIC INFORMATION ON THE AVAILABLE TOXICITY DATA

The available data for each of the SIDS toxicity endpoints are evaluated on the following 

pages. Studies for a common endpoint are grouped together in the document and an endpoint 

adequacy assessment is provided near the top of the first page of the summaries for that 

endpoint. If the data available for the endpoint is determined to be inadequate, a basis for that 

conclusion is supplied. 
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B- 1. TOXICITY TO AQUATIC VERTEBRATES

Summary of endpoint: Adequate

Study 1: Predicted toxicity to fish

Title: ECOSAR-estimated toxicity to fish

This study is: Adequate Not Adequate

TEST SUBSTANCE 

Identity: Glycine, CAS No. 56-40-6

Remarks: N/A

METHOD: 

Method/guideline followed: Estimated by ECOSAR version 1.00 

Molecular weight = 75.07

Log Kow = -3.21

Water solubility = 2.49E+005 mg/L

Test type: Acute 96-hour toxicity estimate

GLP compliant?: N/A

Year study was performed: N/A

Test species: Fish

Analytical monitoring: N/A

Exposure duration: 96 hours

Concentrations tested: N/A

Test method/conditions remarks: N/A

RESULTS

Endpoint value(s): 96h LC50 = 1.8e+005 mg/L

Results remarks: 

96-hour LC50 was estimated from ECOSAR version 1.00
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CONCLUSIONS:

The predicted 96h LC50 for fish is 1.8e+005 mg/L.

STUDY RELIABILITY

[2] Reliable with restrictions – endpoint value estimated using a modeling program.

REFERENCE

ECOSAR version 1.00
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B-2. TOXICITY TO AQUATIC INVERTEBRATES

Summary of endpoint: Adequate 

Study 1: Predicted toxicity to daphnids

Title: ECOSAR-estimated toxicity to daphnids

This study is: Adequate Not Adequate

TEST SUBSTANCE 

Identity: Glycine, CAS No. 56-40-6

Remarks: N/A

METHOD:

Method/guideline followed: Estimated by ECOSAR version 1.00

Molecular weight = 75.07

Log Kow = -3.21

Water solubility = 2.49E+005 mg/L

Test type: Acute 48-hour toxicity estimate

GLP compliant?: N/A

Year study was performed: N/A

Test species: Daphnids

Analytical monitoring: N/A

Exposure duration: 48 hours

Concentrations tested: N/A

Test method/conditions remarks: N/A

RESULTS

Endpoint value(s): 48h LC50 = 6178.061 mg/L

Results remarks:

48-hour LC50 was estimated from ECOSAR version 1.00
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CONCLUSIONS

The predicted 48h LC50 for daphnids is 6178.061 mg/L.

STUDY RELIABILITY

[2] Reliable with restrictions – endpoint value estimated using a modeling program.

REFERENCE

ECOSAR version 1.00
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B- 3. TOXICITY TO AQUATIC PLANTS

Summary of endpoint: Adequate

Study 1: Predicted toxicity to green algae

Title: ECOSAR-estimated toxicity to green algae

This study is: Adequate Not Adequate

TEST SUBSTANCE 

Identity: Glycine, CAS No. 56-40-6

Remarks: N/A

METHOD: 

Method/guideline followed: Estimated by ECOSAR version 1.00

Molecular weight = 75.07

Log Kow = -3.21

Water solubility = 2.49E+005 mg/L

Test type: Acute 96-hour toxicity estimate

GLP compliant?: N/A

Year study was performed: N/A

Test species: Green algae

Exposure duration: 96 hours

Concentrations tested: N/A

Test method/conditions remarks: N/A

RESULTS

Endpoint value(s): 96h EC50 = 487.889 mg/L

Results remarks:

96-hour EC50 was estimated from ECOSAR version 1.00
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CONCLUSIONS

The predicted 96h EC50 for green algae is 487.889 mg/L.

STUDY RELIABILITY

[2] Reliable with restrictions – endpoint value estimated using a modeling program.

REFERENCE

ECOSAR version 1.00
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B- 4. ACUTE TOXICITY

Summary of endpoint: Adequate, based on a weight-of-evidence approach using studies from 

secondary sources with many study details missing. The studies summarized here demonstrate 

low toxicity of glycine.

Study 1: Acute oral toxicity study in rats

Title: Acute oral toxicity

The study is: Adequate Not Adequate

This study was considered inadequate due to missing critical study information; non-standard 

exposure route; secondary source.

TEST SUBSTANCE 

Identity: Glycine, CAS No. 56-40-6

Remarks: No data

METHOD

Method/guideline followed: No data

Test type: LD50

GLP compliant?: No data

Year study performed: No data

Test species: Rat, species/strain not provided

Number of animals/sex/dose: No data

Route of administration: Oral

Vehicle: No data

Doses/concentrations tested: No data

Statistical methods used: No data

Test method/conditions remarks: No data
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RESULTS

Endpoint value(s): 7930 mg/kg bw

Results remarks: No data

CONCLUSIONS

The acute oral LD50 in rats is 7930 mg/kg bw.

STUDY RELIABILITY

[4] Not assignable – no study detail provided; non-standard exposure route; secondary source.

REFERENCE

European Commission, European Chemicals Bureau. IUCLID Dataset. 18-Feb-2000

Yachds Yakuri to Chiryo. Pharmacology and Theraputics (Raifu Saiensu Shuppan K. K., 2-5-

13, Yaesu, Chuo-ku, Tokyo 104, Japan. V.1 – 1972-5, 1502, 77

Lewis, R.J., Food Additives Handbook p. 235-236 (1989); FASP Study No. 90
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Study 2: Acute oral toxicity study in mice

Title: Acute oral toxicity

The study is: Adequate Not Adequate

This study was considered inadequate due to missing critical study information; non-standard 

exposure route; secondary source.

TEST SUBSTANCE 

Identity: Glycine, CAS No. 56-40-6

Remarks: No data

METHOD

Method/guideline followed: No data

Test type: LD50

GLP compliant?: No data

Year study performed: No data

Test species: Mouse, species/strain not provided

Number of animals/sex/dose: No data

Route of administration: Oral

Vehicle: No data

Doses/concentrations tested: No data

Statistical methods used: No data

Test method/conditions remarks: No data

RESULTS

Endpoint value(s): 4920 mg/kg bw

Results remarks: No data
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CONCLUSIONS

The acute oral LD50 in rats is 4920 mg/kg bw.

STUDY RELIABILITY

[4] Not assignable – no study detail provided; non-standard exposure route; secondary source.

REFERENCE

European Commission, European Chemicals Bureau. IUCLID Dataset. 18-Feb-2000

Yachds Yakuri to Chiryo. Pharmacology and Theraputics (Raifu Saiensu Shuppan K. K., 2-5-

13, Yaesu, Chuo-ku, Tokyo 104, Japan. V.1 – 1972-5, 1502, 77
Draft HPV4 Chemical Data Adequacy Review CAS No. 56-40-6

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Study 3: Acute s.c. toxicity study in rats

Title: Acute s.c. toxicity

The study is: Adequate Not Adequate

This study was considered inadequate due to missing critical study information; non-standard 

exposure route; secondary source.

TEST SUBSTANCE 

Identity: Glycine, CAS No. 56-40-6

Remarks: No data

METHOD

Method/guideline followed: No data

Test type: LD50

GLP compliant?: No data

Year study performed: No data

Test species: Rat, species/strain not provided

Number of animals/sex/dose: No data

Route of administration: s.c.

Vehicle: No data

Doses/concentrations tested: No data

Statistical methods used: No data

Test method/conditions remarks: No data

RESULTS

Endpoint value(s): 5200 mg/kg bw

Results remarks: No data
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CONCLUSIONS

The acute s.c. LD50 in rats is 5200 mg/kg bw.

STUDY RELIABILITY

[4] Not assignable – no study detail provided; non-standard exposure route; secondary source.

REFERENCE

European Commission, European Chemicals Bureau. IUCLID Dataset. 18-Feb-2000

Yachds Yakuri to Chiryo. Pharmacology and Theraputics (Raifu Saiensu Shuppan K. K., 2-5-

13, Yaesu, Chuo-ku, Tokyo 104, Japan. V.1 – 1972-5, 1502, 77

Lewis, R.J., Food Additives Handbook p. 235-236 (1989); FASP Study No. 90
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Study 4: Acute i.p. toxicity study in mice

Title: Acute i.p. toxicity

The study is: Adequate Not Adequate

This study was considered inadequate due to missing critical study information; non-standard 

exposure route; secondary source.

TEST SUBSTANCE 

Identity: Glycine, CAS No. 56-40-6

Remarks: No data

METHOD

Method/guideline followed: No data

Test type: LD50

GLP compliant?: No data

Year study performed: No data

Test species: Mouse, species/strain not provided

Number of animals/sex/dose: No data

Route of administration: i.p.

Vehicle: No data

Doses/concentrations tested: No data

Statistical methods used: No data

Test method/conditions remarks: No data

RESULTS

Endpoint value(s): 4450 mg/kg bw

Results remarks: No data
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CONCLUSIONS

The acute i.p. LD50 in mice is 4450 mg/kg bw.

STUDY RELIABILITY

[4] Not assignable – no study detail provided; non-standard exposure route; secondary source.

REFERENCE

European Commission, European Chemicals Bureau. IUCLID Dataset. 18-Feb-2000

Yachds Yakuri to Chiryo. Pharmacology and Theraputics (Raifu Saiensu Shuppan K. K., 2-5-

13, Yaesu, Chuo-ku, Tokyo 104, Japan. V.1 – 1972-5, 1502, 77
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Study 5: Acute s.c. toxicity study in mice

Title: Acute s.c. toxicity

The study is: Adequate Not Adequate

This study was considered inadequate due to missing critical study information; non-standard 

exposure route; secondary source.

TEST SUBSTANCE 

Identity: Glycine, CAS No. 56-40-6

Remarks: No data

METHOD

Method/guideline followed: No data

Test type: LD50

GLP compliant?: No data

Year study performed: No data

Test species: Mouse, species/strain not provided

Number of animals/sex/dose: No data

Route of administration: s.c.

Vehicle: No data

Doses/concentrations tested: No data

Statistical methods used: No data

Test method/conditions remarks: No data

RESULTS

Endpoint value(s): 5060 mg/kg-bw

Results remarks: No data
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CONCLUSIONS

The acute s.c. LD50 in mice is 5060 mg/kg bw.

STUDY RELIABILITY

[4] Not assignable – no study detail provided; non-standard exposure route; secondary source.

REFERENCE

European Commission, European Chemicals Bureau. IUCLID Dataset. 18-Feb-2000

Yachds Yakuri to Chiryo. Pharmacology and Theraputics (Raifu Saiensu Shuppan K. K., 2-5-

13, Yaesu, Chuo-ku, Tokyo 104, Japan. V.1 – 1972-5, 1502, 77
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Study 6: Acute i.v. toxicity study in rats

Title: Acute i.v. toxicity

The study is: Adequate Not Adequate

This study was considered inadequate due to missing critical study information; non-standard 

exposure route; secondary source.

TEST SUBSTANCE 

Identity: Glycine, CAS No. 56-40-6

Remarks: No data

METHOD

Method/guideline followed: No data

Test type: LD50

GLP compliant?: No data

Year study performed: No data

Test species: Rat, species/strain not provided

Number of animals/sex/dose: No data

Route of administration: i.v.

Vehicle: No data

Doses/concentrations tested: No data

Statistical methods used: No data

Test method/conditions remarks: No data

RESULTS

Endpoint value(s): 2600 mg/kg-bw

Results remarks: No data
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CONCLUSIONS

The acute i.v. LD50 in rats is 2600 mg/kg bw.

STUDY RELIABILITY

[4] Not assignable – no study detail provided; non-standard route; secondary source.

REFERENCE

European Commission, European Chemicals Bureau. IUCLID Dataset. 18-Feb-2000

Yachds Yakuri to Chiryo. Pharmacology and Theraputics (Raifu Saiensu Shuppan K. K., 2-5-

13, Yaesu, Chuo-ku, Tokyo 104, Japan. V.1 – 1972-5, 1502, 77
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Study 7: Acute i.v. toxicity study in mice

Title: Acute i.v. toxicity

The study is: Adequate Not Adequate

This study was considered inadequate due to missing critical study information; non-standard 

exposure route; secondary source.

TEST SUBSTANCE 

Identity: Glycine, CAS No. 56-40-6

Remarks: No data

METHOD

Method/guideline followed: No data

Test type: LD50

GLP compliant?: No data

Year study performed: No data

Test species: Mouse, species/strain not provided

Number of animals/sex/dose: No data

Route of administration: i.v.

Vehicle: No data

Doses/concentrations tested: No data

Statistical methods used: No data

Test method/conditions remarks: No data

RESULTS

Endpoint value(s): 2370 mg/kg-bw

Results remarks: No data
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CONCLUSIONS

The acute i.v. LD50 in mice is 2370 mg/kg bw.

STUDY RELIABILITY

[4] Not assignable – no study detail provided; non-standard exposure route; secondary source.

REFERENCE

European Commission, European Chemicals Bureau. IUCLID Dataset. 18-Feb-2000

Yachds Yakuri to Chiryo. Pharmacology and Theraputics (Raifu Saiensu Shuppan K. K., 2-5-

13, Yaesu, Chuo-ku, Tokyo 104, Japan. V.1 – 1972-5, 1502, 77
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Study 8: Acute i.v. toxicity study in the cat

Title: Acute i.v. toxicity

The study is: Adequate Not Adequate

This study was considered inadequate due to missing critical study information; non-standard 

exposure route; secondary source.

TEST SUBSTANCE 

Identity: Glycine, CAS No. 56-40-6

Remarks: No data

METHOD

Method/guideline followed: No data

Test type: LDL0

GLP compliant?: No data

Year study performed: No data

Test species: Cat, species/strain not provided

Number of animals/sex/dose: No data

Route of administration: i.v.

Vehicle: No data

Doses/concentrations tested: No data

Statistical methods used: No data

Test method/conditions remarks: No data

RESULTS

Endpoint value(s): 3 g/kg

Results remarks: No data
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CONCLUSIONS

The acute i.v. LDL0 in cats is 3 g/kg.

STUDY RELIABILITY

[4] Not assignable – no study detail provided; non-standard species and exposure route; 

secondary source.

REFERENCE

European Commission, European Chemicals Bureau. IUCLID Dataset. 18-Feb-2000

Journal of the American Pharmaceutical Association Scientific Edition (Washington DC) V.29-

49, 1940-60. 31, 306, 42
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B-5: REPEATED-DOSE TOXICITY

Summary of endpoint: Inadequate

Study 1: Repeated-dose dietary toxicity study in rats

Title: Pteroylglutamic Acid, Ascorbic Acid, and Injectable Liver Extract on Dietary Glycine 

Toxicity in the Rat

The study is: Adequate Not Adequate

This study is not considered adequate to fulfill the repeated-dose toxicity endpoint because it is 

not a standard protocol study, only one dose level was tested and LOAEL/NOAEL values were 

not reported. Additionally, limited study details were provided.

TEST SUBSTANCE 

Identity: Glycine, CAS No. 56-40-6

Remarks: Purity not reported

METHOD

Method/guideline followed: None stated

Test type: Short term dietary study

GLP compliant?: Not stated

Year study performed: 1949

Test species: Sprague-Dawley weanling rats

Number of animals/sex/dose: 4/sex/group

Route of administration: Oral, diet

Vehicle: Food 

Exposure duration: 46 days

Doses/concentrations tested: 0% (group I) or 10% (groups II – VI)

Statistical methods used: The differences in weight gains among the various groups were 

statistically treated by the analysis of variance method.
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Test method/conditions remarks: Six groups of weanling Sprague-Dawley rats, 4 males and 4 

females in each group, were fed a standard purified diet, and a similar diet containing 10% 

glycine replacing an equal amount of sucrose. Groups of rats were given the glycine-containing 

diet supplemented respectively with PGA, Injectable liver extract, PGA plus liver extract, and 

ascorbic acid. The rats were fed ad libitum and food intake was measured. Complete blood 

counts were made on the 37th and 46th days of the experiment. 

Composition of Experimental Diets

Dietary component

Groups

I II III IV V VI

Casein, % 18 18 18 18 18 18

Sucrose, % 75 65 65 65 65 65

Crisco, % 3 3 3 3 3 3

Cod liver oil, % 2 2 2 2 2 2

Salt mix, % 2 2 2 2 2 2

Glycine, % 0 10 10 10 10 10

PGA—mg/100 g 0 0 0.5 0 0.5 0

Liver extr.—cc/kilo 0 0 0 8 8 0

Ascorbic acid—mg/100 g 0 0 0 0 0 100

RESULTS

Endpoint value(s): Not reported

Results remarks: It may be observed that the inclusion of 10% glycine in the purified diet 

resulted in a greatly decreased rate of growth. PGA markedly improved the growth of rats 

receiving the high glycine diet. The addition of liver extract to the high glycine diet resulted in 

some growth improvement but less than that produced by PGA. The liver extract used was 

assayed for PGA and found to contain2.62 y per cc; this amounted to approximately 0.2 y of 

PGA per rat per day. This and the fact that the group receiving PGA plus liver extract grew no 

faster than those receiving PGA alone would indicated that some of the growth improvement 

resulting from the liver extract may have been due to its content o PGA. 

Ascorbic acid had little effect on the growth of the rats. The difference in rate of gain between 

the group receiving ascorbic acid and the group receiving high glycine alone was not statistically 

significant. Weight gains per gram of food eaten were calculated for the various groups and the 

average values were: control 0.295, high glycine 0.152, high glycine plus PGA 0.282, high 

glycine pl us liver extract 0.205, high glycine plus PGA plus liver extract 0.291, and high glycine 

plus ascorbic acid 0.213. With the exception of reversal between the ascorbic acid and liver 

extract groups, efficiency of gain ranked the same in the various groups as did total weight 

changes. 

The feeding of the high glycine diet did not produced a significant leucopenia in these rats when 

compared o the controls; however, addition of PGA to this diet did elevate the white cell count. 

Addition of liver extract and liver extract plus PGA to the high glycine diet resulted in an 

increased white count in male rats but was without effect in the females. 
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Although the red cell counts of rats receiving the high glycine diet were lower than the control 

group, none of the supplements tested were effective in restoring the counts to the level of the 

controls. Hemoglobin values were also reduced by the high glycine diet and were improved only 

by the addition of the combination of PGA plus liver extract or by ascorbic acid. There were no 

consistent differences in hematocrit or differential white cell count among the various groups. 

The rats receiving ascorbic acid were found to have a higher mean corpuscular volume than any 

of the other groups. It may also be noted that rats receiving ascorbic acid had the lowest red 

count of any of the groups, but had a higher hemoglobin level than any of the others except the 

control group and the group receiving liver extract plus PGA.

There is not sufficient evidence available at present to permit an explanation of the growthpromoting effect of PGA when added to a high glycine diet for rats. 

CONCLUSIONS

Overall, the growth of rats receiving the high glycine diet was greatly reduced as compared to 

the control group. Supplementation of the high glycine diet with PGA and with PGA plus liver 

extract resulted in a marked improvement in growth rate; liver extract alone was less effective; 

and ascorbic acid did not significantly improve rate of growth of rats receiving the 10% glycine 

diet. Rats receiving the high glycine diet did not develop a marked leucopenia when compared 

with control rats. 

STUDY RELIABILITY

[4] Not assignable – not a standard protocol study, limited study details were provided, only one 

dose level was tested and LOAEL/NOAEL values were not reported.

REFERENCE

Dinning et al. “Pteroylglutamic Acid, Ascorbic Acid, and Injectable Liver Extract on Dietary 

Glycine Toxicity in the Rat (17400)”. Proc. Soc. Exp. Biol. Med. 72: 262-264 (1949). FDA 

PAFA profile for Glycine (7/29/2010). FASP Study No. 93.
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B-6: CARCINOGENICITY

Study 1: Chronic toxicity/carcinogenicity study in rats

Title: Carcinogenicity study of glycine in Fischer 344 rats

TEST SUBSTANCE 

Identity: Glycine, CAS No. 56-40-6

Remarks: Lot No. 001103, produced by Yuhkigosei Yakuhin Kogyo Co. as a white crystalline 

powder with a sweet taste 

METHOD

Method/guideline followed: United States National Cancer Institute Guidelines for Carcinogen 

Bioassay in Small Rodents (NCI, Bethesda, MD. 1974)

Test type: Chronic toxicity/carcinogenicity

GLP compliant?: Not stated

Year study performed: 1994

Test species: Fischer (344 DuCrj) rats obtained from Charles River Co. Japan, Inc. Atsugi. Rats 

used in this study were 6 weeks old at the start of the study. 

Number of animals/sex/dose: 50/sex/dose

Route of administration: Oral, drinking water

Vehicle: Drinking water

Exposure duration: 108 weeks

Doses/concentrations tested: 0%, 2.5% or 5.0%

Statistical methods used: Effective numbers of rats included both those killed at week 108 and 

those which died with tumors earlier. The data were evaluated by the Wilcoxon t-test or the x2

test.

Test method/conditions remarks: The rats were divided into three groups of 50 males and 

females each when 6 weeks old: group I was given 5% GL and group II 2.5% GL in the drinking 

water, while the control (group III) received the drinking water without GL. The feed and 

drinking water, with or without GL, were freely available. The rats were weighed every one or 

two weeks and their diet consumption recorded every 4 weeks. All survivors were killed at week 

108, blood samples being then taken from all animals of both sexes in each group for 
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measurement of white blood cells, red blood cells, hemoglobin (Hb), hematocrit (Ht), GOT, 

GPT, LDH, CPK, BUN, CRE, and Urea at the Ina Clinical Laboratory Inc., Iga Ueno. 

Complete autopsy was performed on all animals, including those that died or were sacrificed 

upon becoming moribund during the experiment. All organs were carefully examined and 

samples were fixed in 10% buffered neutral formalin, embedded in paraffin, and routinely 

stained with hematoxylin and eosin. Histological analysis of tumors in renal pelvis was 

conducted. Effective numbers of rats included both those killed at week 108 and those which 

died with tumors earlier. 

RESULTS

Results: Growth curves, mortality and diet consumption: A slight dose-dependent inhibition of 

mean body weight gain was observed in both sexes. At the end of the administration period, the 

numbers of surviving male animals were 40 in the 5.0% group, 45 in the 2.5% group and 40 in 

the control group, and for females 31, 46, and 41, respectively.

Urinalysis: The pH of urine samples from 6.0 to 7.5 for all female groups and male rats treated 

with 5.0 or 2.5% GL and from 6.5 to 7.0 for control males. There were no significant differences 

in urinalysis data between treated and control rats.

Blood analysis: The Hb in male rats given 5.0% GL was significantly higher than that in control 

male rats but that in the female case 5.0% GL administration was associated with a significant 

reduction. The Ht in female rats given 5.0% GL was also significantly lower than in control 

female rats. The CPK values for both sexes given 5.0% or 2.5% GL were significantly lower 

than the respective control values and the BUN in both male and females on 5.0% GL 

significantly increased.

Final body and organ weights, and total glycine intake: The final body weights of both sexes 

given 5.0% GL were significantly lower than those of controls. However, there were no 

significant intergroup differences in relative organ weights. The total glycine intake was directly 

related to the dietary dose in both sexes. 

Tumor incidence: For the males, tumors were found in 90% of the 5.0% GL group, in 97% of 

the 2.5% and in 90% of the controls, while the corresponding figures for females were 59, 65, 

and 39%. These high proportions of tumor-bearing rats were mainly due to testis, thyroid, 

pituitary gland, pancreas, and uterine lesions. Kidney papillomas were found in 8% of the 2.5% 

GL and 6% of the 5.0% GL group females, but not in other groups. A renal cell tumor was seen 

in one of 40 male rats fed on 5.0% GL. A transitional cell tumor of the pelvis was seen in one of 

40 male control rats. 

Non –malignancy histological findings for the urinary system: The incidences of calcification in 

kidney were 39, 32, and 42% in females of the 0, 2.5 and 5% GL groups, respectively. The 

incidences of papillary necrosis in male rats fed on 2.5 and 5.0% GL were 4 and 7%, while the 

corresponding figures for females were 30 and 32%. Hyperplasia of transitional cells in renal 

pelvis was seen in 2 of 46 female rats fed 2.5% GL.
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CONCLUSIONS

Glycine was carcinogenic to rats in this study.

STUDY RELIABILITY

[1] Reliable without restrictions.

REFERENCE

Kitahori et al., 1994. Carcinogenicity Study of Glycine in Fischer 344 Rats. J Toxicol Pathol 7: 

471-480. FDA PAFA profile for Glycine (7/29/2010). FASP Study No. 98.
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B-7: GENE MUTATION STUDIES

Summary of endpoint: Adequate

Study 1. In vitro gene mutation study in Salmonella

Title: Genetic Toxicity in vitro

The study is: Adequate Not Adequate

TEST SUBSTANCE 

Identity: Glycine, CAS No. 56-40-6

Remarks: Not stated

METHOD

Method/guideline followed: Preincubation protocol

Test type: Ames Salmonella assay

GLP compliant?: Yes

Year study performed: 1979

Test species: Salmonella typhimurium strains TA98, TA100, TA1535 and TA1537

Metabolic activation: With and without S9 (Aroclor 1254-induced male Sprague-Dawley rat or 

Syrian hamster liver)

Concentrations tested: 0, 100, 333, 1000, 3333 and 10,000 μg/plate

Statistical methods used: Not stated

Test method/conditions remarks: Salmonella typhimurium strains TA98, TA100, TA1535 and 

TA1537 were exposed to glycine in water at 0, 100, 333, 1000, 3333 and 10,000 μg/plate 

without and without metabolic activation. A positive control was tested concurrently.

RESULTS

Genotoxicity result: Negative

Cytotoxic concentration (if applicable): With metabolic activation, toxicity was observed in 

strain TA1537 at a concentration of 3333 μg/plate only.
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Results remarks: Not stated

CONCLUSIONS

Glycine was not mutagenic in this assay.

STUDY RELIABILITY

[1] Reliable without restrictions.

REFERENCE

NTP (1979). Salmonella (152901). Citation: Haworth, S., Lawlor, T., Mortelmans, K., Speck, 

W., and Zeiger, E. Salmonella mutagenicity test results for 250 chemicals Environ. Mutagen. 

Vol. 5 (Suppl 1) (1983) 3-142.
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Study 2: In vitro gene mutation study in Salmonella

Title: Genetic Toxicity in vitro

The study is: Adequate Not Adequate

TEST SUBSTANCE 

Identity: Glycine, CAS No. 56-40-6

Remarks: Not stated

METHOD

Method/guideline followed: Preincubation protocol

Test type: Ames Salmonella assay

GLP compliant?: Yes

Year study performed: 1979

Test species: Salmonella typhimurium strains TA98, TA100, TA1535 and TA1537

Metabolic activation: With and without S9 (Aroclor 1254-induced male Sprague-Dawley rat or 

Syrian hamster liver)

Concentrations tested: 0, 10, 33, 100, 333 and 1000 μg/plate

Statistical methods used: Not stated

Test method/conditions remarks: Salmonella typhimurium strains TA98, TA100, TA1535 and 

TA1537 were exposed to glycine in water at 0, 10, 33, 100, 333 and 1000 μg/plate without and 

without metabolic activation. A positive control was tested concurrently.

RESULTS

Genotoxicity result: Negative

Cytotoxic concentration (if applicable): No cytotoxicity was observed.

Results remarks: Not stated

CONCLUSIONS

Glycine was not mutagenic in this assay.
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STUDY RELIABILITY

[1] Reliable without restrictions.

REFERENCE

NTP (1979). Salmonella (709932). Citation: Haworth, S., Lawlor, T., Mortelmans, K., Speck, 

W., and Zeiger, E. Salmonella mutagenicity test results for 250 chemicals Environ. Mutagen. 

Vol. 5 (Suppl 1) (1983) 3-142.
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Study 3: In vitro gene mutation in Escherichia coli

Title: Mutagenesis by normal metabolites in Escherichia coli: phenylalanine mutagenesis is 

dependent on error-prone DNA repair

The study is: Adequate Not Adequate

This study was not considered adequate to fulfill this endpoint because the article and main study 

focused on the mutagenicity of phenylalanine, not glycine. Additionally, only one test substance 

concentration was tested in the absence of metabolic activation.

TEST SUBSTANCE 

Identity: L-glycine, CAS No. 56-40-6

Remarks: Eastman Organic

METHOD

Method/guideline followed: Not stated

Test type: Mutagenicity in Escherichia coli

GLP compliant?: Not stated

Year study performed: 1985

Test species: Escherichia coli strain uvrB umuC

Metabolic activation: No

Concentrations tested: 2 mM

Statistical methods used: Not stated

Test method/conditions remarks: Plate assay for mutagenesis: Logarithmic-phase cells were 

prepared by diluting overnight cultures 1:50 into warm SMM1, and shaking the cultures at 37°C 

until a concentration of 4 x 108 colony-forming units (CFU) per ml was attained. Cells were 

pelleted by centrifugation, washed once, and resuspended in PB (phosphate buffer) at 1.5 x 108

CFU/ml. Cells (0.1 ml) were spread on Glu-600 plates (lactose plates containing a growthlimiting amount of glucose, i.e., 600 μg/mL) ± the test compound at 2 mM and Glu-0 plates. 

Plates were incubated for 3 days at 37°C before scoring Lac+ mutants. To determine the relative 

mutagenesis, the mean number of mutants on 5 Glu-0 plates (i.e., preexisting mutants) was 

subtracted from the mean number of mutants on 10 Glu-600 plates (i.e., plate mutants) and from 

the mean number of mutants on 5 Glu-600 plates containing the test compound (i.e., plate plus 

induced mutants). Then the ratio (test/control) was determined. The mean numbers of 
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preexisting mutants per plate were 1(wild-type), 15(uvrB), and 0(uvrB umuC and uvrB lexA), 

while the mean number of plate mutants per control plate were 60(wild-type), 355(uvrB), 

21(uvrB umuC), and 20(uvrB lexA). For Glu-600 control plates, the total Laccells per plate was

3.4 X 1010 for both the uvrB and uvrB umuC strains.

RESULTS

Genotoxicity result: Negative

Cytotoxic concentration (if applicable): Not stated

Results remarks: Glycine had no significant effect on Lac reversion in a uvrB umuC strain

CONCLUSIONS

Glycine was not mutagenic in this assay.

STUDY RELIABILITY

[3] Not reliable – only one test substance concentration was tested in the absence of metabolic 

activation.

REFERENCE

Sargentini, N.J., and Smith, K.C. "Mutagenesis by normal metabolites in Escherichia coli: 

phenylalanine mutagenesis is depended on error-prone DNA repair", 1986. Mutation Research, 

161: 113-118. FASP Study No. 83
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Study 4: In vitro gene mutation in Salmonella

Title: Mutagenicity of heated solutions of Vitamin K1 with amino compounds

The study is: Adequate Not Adequate

This study was not considered adequate to fulfill this endpoint because only one Salmonella

strain was tested in the presence of metabolic activation, the test substance was a mixture with 

vitamin K1, and limited study details were provided.

TEST SUBSTANCE 

Identity: Glycine, CAS No. 56-40-6

Remarks: None stated

METHOD

Method/guideline followed: Not stated

Test type: gene mutation in Salmonella

GLP compliant?: Not stated

Year study performed: 1983

Test species: Salmonella strain TA98

Metabolic activation: with S9

Concentrations tested: 500 μmoles with aliquots of 2, 10 and 50 μmoles assayed for 

 mutagenicity.

Statistical methods used: Not stated

Test method/conditions remarks: Since vitamin K1 reacted with creatine to yield exceptionally 

high mutagenic activity, further reactions with this compound were carried out against creatinine, 

arginine, threonine and glycine. 

Heat induced reactions between the amino compounds and various fat constituents were carried 

out using a model system which has been used to study browning reactions. In this procedure 

the reactants are heated in ethylene glycol, a high boiling neutral solvent which allowed the 

reactions to take place under homogeneous conditions while minimizing the loss of mutagens 

due to volatilization. 500 μmoles each of the reactants were added to ethylene glycol: water (9: 

1) in a 125-ml Erlenmeyer flask and heated for 90 min on a hot plate kept at 200°C. After 

cooling, the reaction mixture was diluted with 200 ml 1 N HCl. It was extracted once with 100 
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ml methylene chloride and the organic layer discarded. The aqueous layer was adjusted to pH 11 

with sodium hydroxide and the basic mutagens were extracted twice with 100-ml aliquots of 

methylene chloride. After removal of traces of moisture by filtering through anhydrous sodium 

sulfate, the methylene chloride extracts were taken to dryness, under vacuum at 40°C. The 

residue was taken up in DMSO and aliquots representing 2, 10 and 50 μmoles of the original 

reactant(s) were assayed for mutagenic activity against S. typhimurium strain TA98 in the 

presence of Aroclor-induced rat-liver microsome (S9) preparation according to the standard 

Ames procedure. 

RESULTS

Genotoxicity result: Positive

Results remarks: While glycine yielded only moderate activity the other 3 amino compounds 

reacted with vitamin K1 to produce mutagens at significant levels.

CONCLUSIONS

Glycine yielded moderate mutagenic activity in Salmonella strain TA98 when tested with 

vitamin K1.

STUDY RELIABILITY

[3] Not reliable – only one Salmonella strain was tested in the presence of metabolic activation, 

the test substance was a mixture with vitamin K1, and limited study details were provided.

REFERENCE

Vithayathil et al., "Heat-induced mutagen formation from creatine and fat-soluble constituents of 

food", 1983. Mutation Research 121: 167-170. FASP Study No. 85
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Study 5: In vitro gene mutation in Salmonella

Title: Primary mutagenicity screening of food additives currently used in Japan 

The study is: Adequate Not Adequate

TEST SUBSTANCE 

Identity: Glycine, CAS No. 56-40-6

Remarks: crystal; 99.8% purity

METHOD

Method/guideline followed: Methods of Ames, McCann & Yamasaki (1975)

Test type: Ames

GLP compliant?: Not stated

Year study performed: 1983

Test species: Salmonella strains TA92, TA1535, TA100, TA1537, TA94 and TA98 

Metabolic activation: with S9 

Solvent: phosphate buffer

Concentrations tested: up to 35 mg/plate (highest non-cytotoxic dose used in the 

experiment)

Statistical methods used: Not stated

Test method/conditions remarks: Cells cultured overnight were pre-incubated with both the 

test sample and the S-9 mix for 20 min at 37oC before plating. Duplicate plates were used for 

each of six different concentrations of the sample. The number of revertant (his+

) colonies was 

scored after incubation at 37°C for 2 days. The result was considered positive if the number of 

colonies found was twice the number in the control (exposed to the appropriate solvent or 

untreated). If no reasonable dose response was detected, additional experiments using different 

doses or induced mutation frequency assays were performed.

RESULTS

Genotoxicity result: Negative
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Results remarks: No significant increases in the numbers of revertant colonies were detected in 

any S. typhimurium strains at the maximum dose tested. 

CONCLUSIONS

Glycine was not mutagenic in this assay.

STUDY RELIABILITY

[1] Reliable without restrictions.

REFERENCE

Ishidate et al., "Primary Mutagenicity Screening of Food Additives Currently Used in Japan". 

Fd. Chem. Toxic. Vol. 22, No. 8. pp. 623-636, 1984. FASP Study No. 86 & 86.1
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Study 6: In vitro gene mutation in Salmonella

Title: Development and validation of the spiral Salmonella assay: an automated approach to 

bacterial mutagenicity testing

The study is: Adequate Not Adequate

TEST SUBSTANCE 

Identity: Glycine, CAS No. 56-40-6

Remarks: from BioRad

METHOD

Method/guideline followed: Standard Plate-Incorporation Assay and Spiral Salmonella Assay

Test type: Reverse mutation

GLP compliant?: Not stated

Year study performed: 1988

Test species: Salmonella strains TA98 and TA100

Metabolic activation: With and without S9

Solvent: Sterile water

Concentrations tested: 0.373 – 7.345μg/plate

Statistical methods used: See test methods remarks section

Test method/conditions remarks: The performance of the spiral Salmonella assay was 

compared to that of the conventional plate-incorporation assay using 13 mutagens and 7 

nonmutagens selected from a variety of I chemical classes.

Standard Plate-Incorporation Assay

The plate-incorporation assay was performed as recommended by Maron and Ames (1983) 

except that minimal histidine and biotin were added to the plating medium rather than to the soft 

agar overlay. Doses were selected so as to match the data points specified along the spiral assay 

dose-response curve (i.e., the average dose-equivalent administered per revolution of the spiral). 

Duplicate plates were poured at each dose. 2-Aminoanthracene (0.5 μg/plate with S9 for strains 

TA98 and TA100; 3 μg/plate with S9 for strain TA1537), 2-nitrofluorene (3 μg/plate without S9 

for strain TA98), sodium azide (3 μg/plate without S9 for strain TA100), and 9-aminoacridine 

(100 μg/plate without S9 for strain TA1537) served as positive controls to verify the reversion 
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properties of the tester strains and to monitor the activity of the exogenous activation system. 

Dimethyl sulfoxide or water was used as the negative control. Plates were inverted and 

incubated for 48 h at 37oC. Replicate experiments were performed to demonstrate

reproducibility. Revertant colonies were counted with the vidicon colony counter as well as with 

the laser scanner in the pour-plate counting mode with no count corrections other than colonies 

added for the excluded area of the agar meniscus. (Although corrected counts can be generated 

for standard pour plates counted on the laser scanner using the computer program provided by 

Spiral System Instruments, Inc. 

Spiral Salmonella Assay

Prior to its use, the sample delivery system of the spiral plater was sterilized by aspirating 

ethanol (70%) into the stylus tip and through the Teflon tubing. The tubing was then flushed with 

sterile water to remove traces of ethanol. Between applications of different bacterial strains, the 

stylus assembly was flushed with ethanol and sterile water to prevent cross-contamination. 

Between applications of different chemical compounds, the

tubing was flushed repeatedly with DMSO.

The concentrated tester strain was delivered onto a rotating pre-poured agar plate using the

uniform cam. When the liquid had absorbed into the agar and the deposition pattern was no 

longer visible (< 2 min), solutions of the test compounds or controls were deposited onto the 

same spiral track using the variable cam, generating a chemical concentration gradient along the 

bacterial spiral. The S9 mix - when required – was dispensed along the same spiral path using 

the variable cam. This technique allowed a uniform density of bacteria to be exposed to 

continuously decreasing dilutions of the chemical compound and a gradient of S9. 

Duplicate plates were prepared for each compound and control tested, and experiments were

replicated to demonstrate assay reproducibility. Prepared plates were inverted and incubated for

48 h at 37oC. Fig. 3 illustrates a typical mutagenic response on a spiral plate.

Revertant colonies were counted using the laser scanner in the variable-dilution count mode and 

a count-correction algorithm based on crowding and colony size was utilized as discussed 

previously. Dose-response data were generated for each spiral plate using the data analysis 

program provided by Spiral System Instruments, Inc., and corresponding data points from 

duplicate plates were averaged to produce a single plot. Spontaneous control values were 

obtained by averaging the 13 data points generated by each control plate, and then averaging 

replicate control plates to produce a single spontaneous value.

RESULTS

Genotoxicity result: Negative

Results remarks: In general, toxicity was expressed at a lower dose in the spiral assay, and the 

mutagenic potencies were greater in the spiral assay relative to the plate-incorporation assay. 
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CONCLUSIONS

Glycine was not mutagenic in this assay

STUDY RELIABILITY

[2] Reliable with restrictions- The primary purpose of this research was to determine the validity 

of test results generated by an automated approach to bacterial mutagenicity testing by 

comparing responses obtained using the automated method to responses obtained using the 

conventional plate-incorporation assay.

REFERENCE

Houk et al., "Development and validation of the spiral Salmonella assay: An automated approach 

to bacterial mutagenicity testing". Mutation Research 223: 49-64, 1989. FASP Study No. 91
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B-8. CHROMOSOMAL ABERRATIONS STUDY

Summary of endpoint: Adequate

Study 1: Chromosomal aberration study

Title: Primary mutagenicity screening of food additives currently used in Japan

The study is: Adequate Not Adequate

TEST SUBSTANCE 

Identity: Glycine, CAS No. 56-40-6

Remarks: crystal, 99.8% purity

METHOD

Method/guideline followed: Not stated

Test type: in vitro chromosomal aberration assay

GLP compliant?: Not stated

Year study performed: 1983

Test species: Chinese hamster fibroblast cell line

Metabolic activation: Not stated

Solvent: physiological saline

Concentrations tested: up to 1.0 mg/mL (highest non-cytotoxic dose used in the experiment)

Statistical methods used: Not stated

Test method/conditions remarks: Chromosomal aberration tests were carried out on 242 food

additives using a Chinese hamster fibroblast cell line; (CHL). The cells were exposed to each 

sample at three different doses for 24 and 48 h ours. In the present studies, no metabolic 

activation systems were applied. The maximum dose of each sample was selected by a 

preliminary test in which the dose needed for 50% cell-growth inhibition was estimated using a 

cell densitometer. 

Chromosome preparations were made as follows: Colcemid (final concentration 0.2 μg/ml) was 

added to the culture 2 hr before cell harvesting. The cells were then trypsinized and suspended 

in a hypotonic KC1 solution (0.075 M) for 13 min at room temperature. After centrifugation the 
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cells were fixed with acetic acid-methanol (l:3, v/v) and spread on clean glass slides. After airdrying, the slides were stained with Giemsa solution (1.5%, at pH 6.8; E. Merck) for 12-1 5 min. 

A hundred well-spread metaphases were observed under the microscope (x 600 with a no-cover 

objective lens). The incidence of polyploid cells as well as of cells with structural chromosomal 

aberrations such as chromatid or chromosome gaps, breaks, exchanges, ring formations, 

fragmentations, and others, was recorded on each culture plated. Untreated cells and solventtreated cells served as negative controls, in which the incidence of aberrations was usually less 

than 3.0%. The results were considered to be negative if the incidence was less that 4.9%, 

equivocal if it was between 5.0 and 9.9% and positive it was more than 10.0%. When no 

reasonable dose-response relationships were found, additional experiments were carried out at 

similar dose levels. 

RESULTS

Genotoxicity result: Negative

Cytotoxic concentration (if applicable): > 1.0 mg/mL

Results remarks: Incidence of polyploid cells at 48 hours after treatment: 1.0%; Incidence of 

cells with structural chromosomal aberrations at 48 hours after treatment: 1%.

CONCLUSIONS

Glycine did not induce chromosomal aberrations in this assay.

STUDY RELIABILITY

[1] Reliable without restrictions.

REFERENCE

Ishidate et al., "Primary Mutagenicity Screening of Food Additives Currently Used in Japan". 

Fd. Chem. Toxic. Vol. 22, No. 8. pp. 623-636, 1984. FASP Study No. 86 & 86.1
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Study 2: Sister chromatid exchange study

Title: Genetic Toxicity in vitro

The study is: Adequate Not Adequate

This study was considered inadequate due to missing critical study information. 

TEST SUBSTANCE 

Identity: Glycine, CAS No. 56-40-6

Remarks: None stated

METHOD

Method/guideline followed: Not stated

Test type: Sister chromatid exchange assay

GLP compliant?: Not stated

Year study performed: Not stated

Test species: human lymphocytes

Metabolic activation: Not stated

Concentrations tested: 100 mg/L

Statistical methods used: Not stated

Test method/conditions remarks: Not stated

RESULTS

Genotoxicity result: Positive

Cytotoxic concentration (if applicable): Not stated

Results remarks: Not stated

CONCLUSIONS

Glycine does initiate sister chromatid exchange in human lymphocytes at a concentration of 100 

mg/L.
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STUDY RELIABILITY

[4] Not assignable – no study detail provided.

REFERENCE

European Commission, European Chemicals Bureau. IUCLID Dataset. 18-Feb-2000.

Mutation Research (Elsevier Science Pub. B.V., POB 211, 1000 AE Amsterdam, Netherlands) 

V.1- 1964-280, 279, 92.
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CAS No. 56-40-6: Summary of Endpoints

Endpoint Study Information 

Available

Acceptable Data Gap1

Aquatic Effects

Acute Toxicity to Fish No No No

Acute Toxicity to Daphnia No No No

Toxicity to Aquatic Plants No No No

Health Effects

Acute Toxicity Yes No No

Repeated-Dose Toxicity Yes No No

Gene Mutation Yes Yes No

Chromosomal Aberrations Yes Yes No

Reproductive Toxicity No No No

Developmental Toxicity No No No

 1 High-protein foods, such as fish, meat, beans, milk, and cheese, are the best dietary sources of 

glycine. Glycine is also available in capsule and powder forms, and as part of many combination 

amino acid supplements. There have been no toxic effects associated with glycine, although 

some people have reported that taking this supplement causes stomach upset. Therefore, the 

aquatic and health effects endpoints with inadequate or no available data were not considered to 

be data gaps. See the “Supporting Information” section for excerpts from public literature which 

supports this claim. Although no experimental data exist on aquatic toxicity of glycine, based on 

the above information, the aquatic toxicity of glycine is expected to be low.
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SUPPORTING INFORMATION

Glycine is a non-essential amino acid. It is found primarily in gelatin and silk fibroin and used 

therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter. (MeSH)

Glycine is a food additive permitted for direct addition to food for human consumption, as long 

as 1) the quantity of the substance added to food does not exceed the amount reasonably required 

to accomplish its intended physical, nutritive, or other technical effect in food, and 2) any 

substance intended for use in or on food is of appropriate food grade and is prepared and handled 

as a food ingredient. [21 CFR 172.320 (4/1/2000)] 

Aminoacetic acid used as a nutrient and/or dietary supplement in animal drugs, feeds, and related 

products is generally recognized as safe when used in accordance with good manufacturing or 

feeding practice. [21 CFR 582.5049 (4/1/2000)]

Aromatic carboxylic acids are detoxicated in animals by combination with amino acids to form 

peptide conjugates. Principal amino acid used in this conjugation is glycine... [Parke, D.V. The 

Biochemistry of Foreign Compounds. Oxford: Pergamon Press, 1968. 130]

Major evidence that favors glycine as mediator of intraspinal postsynaptic inhibition is the 

selective antagonism of its effects by strychnine. Glycine also appears to be most likely 

transmitter for inhibitory interneurons in reticular formation but not in cuneate nucleus. 

[Gilman, A.G., L.S. Goodman, and Gilman. (eds.). Good man and Gilman’s The 

Pharmacological Basis of Therapeutics. 6th ed. New York: Macmillan Publishing Co., Inc. 1980. 

247]

Glycine is a nonessential amino acid derived from the alkaline hydrolysis of gelatin. Glycine is 

the simplest of the 20 natural amino acids. Glycine is the only amino acid that does not have 

optical isomers. Glycine is a protein amino acid found in the protein of all life forms. It is the 

simplest amino acid in the body and the only protein amino acid that does not have chirality. 

Glycine is not considered an essential amino acid because the cells in the body can synthesize 

sufficient amounts of glycine to meet physiological requirements. The body uses it to help the 

liver in detoxification of compounds and for helping the synthesis of bile acids. It has a sweet 

taste and is used for that purpose. Glycine is very evolutionarily stable at certain positions of 

some proteins, because mutations that change it to an amino acid with a larger side chain could 

break the protein's structure. Glycine is also similar to gamma-aminobutyric acid and glutamic 

acid in the ability to inhibit neurotransmitter signals in the central nervous system.

Glycine is essential for the synthesis of nucleic acids, bile acids, proteins, peptides, purines, 

adenosine triphosphate (ATP), porphyrins, hemoglobin, glutathione, creatine, bile salts, onecarbon fragments, glucose, glycogen, and l-serine and other amino acids. Glucagon is a hormone 

that causes glycogen (stored in the liver) to convert to glucose which is needed by the body for 

energy. Glycine increases the release of glucose into the blood stream by stimulating the 

glucagon hormone. Glycine is an inhibitory neurotransmitter in the central nervous system, 

especially in the spinal cord. Glycine systems may be important in controlling epilepsy and other 
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CNS disorders. Glycine also enhances the activity of neurotransmitters (chemical messengers) in 

the brain that are involved in memory and cognition. Glycine may be indicated to help alleviate 

the symptoms of spasticity. Glycine is an inhibitory amino acid with important functions 

centrally and peripherally. Molecular analogs and precursors can be used to augment these 

systems. The charged species have difficulty passing the blood-brain barrier and must be carried 

by transport pumps. Glycine helps convert many potentially harmful substances including toxic 

phenolic materials such as benzoic acid (sodium benzoate) into harmless forms. [Vitamins & 

Helath Supplements Guide. http://www.vitamins-supplements.org/amino-acids/glycine.php]

NOTE: According to the National Library of Medicine HSDB Database, glycine does exhibit 

toxicity with therapeutic use as a hypotonic glycine irrigation solution. Absorption of this 

solution, especially during genitourinary surgical procedures such as transurethral resection of 

the prostate (TURP), has been reported to cause visual disturbances, transient blindness and 

hyponatremia, which can be fatal. Other reported effects include hypotension, 

hyperammonemia, metabolic acidosis, increased osmolal gap, hypocalcemia, hemolytic anemia, 

ECG changes, headache, coma, seizures, dyspnea, and cerebral edema. The volume of irrigation 

solution required to cause these effects in cases of absorption is not clear.