L-Glutamic Acid (LGA) and Gamma-Amino butyric Acid (GABA) 

(PC Codes: 374350 and 030803) 

Preliminary Work Plan and Summary Document 

Registration Review: Initial Docket 

September 2014 

Case. 6025 

Approved by: 

Robert McNally, Director 

Biopesticides and 

Pollution Prevention Division 

Date: 
C. Background and Regulatory Information .............................................................................. 5 

D. Anticipated Data Needs and RiskAssessments ...................................................................... 8 

E. Risk to Threatened and Endangered Species ....................................................................... 1 0 

F. Endocrine Effects .................................................................................................................... 10 

G. 

H. 

I. 

J. 

Incidents .................................................................................................................................... 11 

Timeline ................................................................................................................................... 12 

Guidance for Commenters ..................................................................................................... 12 

Next Steps ................................................................................................................................ 14 

II. BIBLIOGRAPHY .. ; ........................................................................................................................ 14 

A. Studies Supporting Registration Review of L-Glutamic Acid and Gamma-Aminobutyric 

Acid ......................................................................................................................................... 15 

B. U.S. Environmental Protection Agency Risk Assessment Memoranda ............................. 21 

2 
DCI Data Call-In 

EDSP Endocrine Disruptor Screening Program EPA U.S. Environmental Protection Agency 

FFDCA Federal Food, Drug, and Cosmetic Act FIFRA Federal Insecticide, Fungicide, and Rodenticide Act FQPA Food Quality Protection Act FR Federal Register FWP Final Work Plan 

IDS Incident Data System 

MRIDNo. Master Record Identification Number: The EPA's system of recording and tracking studies submitted to the 

Office of Pesticide Programs 

MRL Maximum Residue Limit 

OPP The EPA's Office of Pesticide Programs 

PC Code Pesticide chemical code: a six-digit number assigned by OPP to identify pesticide chemicals 

PWP Preliminary Work Plan 

TGAI Technical grade ofthe active ingredient 

TMDL Total Maximum Daily Load 

us United States 

3 
(GABA) is now open, initiating the first public comment period for Registration Review Case 6025. 

Currently, there is one registered product containing LGA and GABA as active ingredients (Auxigro WP 

Plant Metabolic Primer, EPA Registration Number 70810-1 ), a plant growth regulator (PGR) intended 

for use to enhance development and growth in numerous plant species and induce plant resistance to 

certain plant pathogens. This Preliminary Work Plan (PWP) explains what the U.S. Environmental 

Protection Agency's (EPA) Office of Pesticide Programs (OPP) knows about LGA and GABA, 

highlights anticipated data and assessment needs, identifies types of information that would be 

especially useful to the Agency in conducting the review, and provides an anticipated timeline for 

completion of the registration review process. 

The registration review process was designed to include a public participation component to solicit input 

from interested stakeholders. By sharing this information in the docket, the EPA intends to inform the 

public of what it knows about LGA and GABA, and what types of new data or other information that 

would be helpful to receive as it moves toward a decision about LGA and GABA. The EPA encourages 

all interested stakeholders to review this PWP and to provide comments and additional information that 

will help the EPA's decision-making process for these biochemical pesticides. In addition to general 

areas on which persons may wish to comment, there are some areas identified in the PWP about which 

the EPA specifically seeks comments and information. Interested stakeholders could include the 

following: environmentai nonprofit or interest groups; pesticide manufacturers; agricultural labor or 

commodity groups; commercial, institutional, residential, and other users of pesticides; or the public at 

large. The PWP begins by describing the statutory and regulatory authorities for registration review. Next, it 

provides background on LGA and GABA, which includes a description of their mode of action, the 

currently registered pesticide product, application rates and methods, use sites, and tolerance exemption 

information. Then, it lists the anticipated data needs, risk assessments, and a projected registration 

review timeline for this case. Finally, the PWP provides guidance for commenters, explains the next 

steps EPA will be taking, summarizes background information, and lists supporting studies, risk 

assessments, and other documents. 

Further information about this case, including background and supporting documents, is available at 

http://www.regulations.gov (under "SEARCH for: Rules, Comments, Adjudications or Supporting 

Documents," then enter the docket identification number, which is indicated above). 

B. Statutory and Regulatory Authority 

The Food Quality Protection Act (FQPA) of 1996 mandated a Registration Review program. All 

pesticides distributed or sold in the United States (U.S.) must generally be registered by the EPA, based 

on scientific data showing that they will not cause unreasonable risks to human health or the 

environment when used as directed on the product labeling. The registration review program is intended 

4 
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and Rodenticide Act (FIFRA) section 3(g) and will review each registered pesticide every 15 years to 

determine whether it continues to meet the FIFRA standard for registration. The regulations governing 

Registration Review begin at 40 C.F.R. § 155.40. The EPA will consider benefits information and data as 

required by FIFRA. The public phase of registration review begins when the initial docket is opened for 

each case. The docket is the EPA's opportunity to state what it knows about the pesticide and what 

additional risk analyses and data or information it believes are needed to make a registration review 

decision. After reviewing and responding to comments and data received in the docket during this initial 

comment period, the EPA will develop a Final Work Plan (FWP) and anticipated schedule for the 

registration review of LGA and GABA. 

C. Background and Regulatory Information 

i. Summary of the Active Ingredient, Usage and Associated Pesticide Products 

LGA and GABA are found in virtually all living organisms. In pure form, both active ingredients are 

powders. LGA is one of the major amino acids in plant and animal proteins. Enzymes in plants, humans, 

and animals convert LGA to GABA, and both active ingredients are involved in many physiological 

functions. For example, humans readily metabolize ingested LGA so that concentrations in the body 

remain constant, and LGA and GABA are neurotransmitters in the brain. LGA is "Generally Recognized 

as Safe" (GRAS) by the Food and Drug Administration (refer to 21 CFR §186.1256), and are registered 

PGRs for use on certain fruits and vegetables, tree nuts, peanuts, grains, animal feed crops, lawn and turf 

grasses, and ornamentals to increase both yield and quality. They also are registered for use to prevent 

powdery mildew on grapes, and suppress certain other crop diseases. The end-use product is applied by 

spraying from the ground or the air, by drenching the soil, or through certain irrigation systems. (U.S. 

EPA 1997, Fact Sheet and Technical Document, 1998). 

1 See http://www.epa.gov/oppsrrdl /registration review/. 

5 
Reregistration Eligibility LGA was registered after November 1984 and was not subject to reregistration. 

Decision (RED) 

Tolerance Reassessment LGA is exempt from the requirement of a tolerance and was not subject to a 

Eligibility Decision (TRED) tolerance reassessment. 

Cumulative group LGA is not a member of a cumulative group that shares a common mechanism of 

toxicity. 

40 CFR Citation 40 CFR § 180.1187 - Exemption from the requirement of a tolerance. 

Non-pesticidal uses LGA is a major amino acid in human, plant and animal proteins, and is a brain 

neurotransmitter in humans and animals. The daily intake in a 70 kg human is 

estimated to be 10.4 g or 150 mglkg. Human milk contains small amounts of free 

LGA; estimated intake by newborns is 20.6 rr1glkg/day. 

Table 2. Chemical Facts for GABA 

PC code 030802 

Case Number 6025 

CAS Number 56-12-2 

Year first registered 1998 

Pesticide Type Plant growth regulator 

Chemical class Biochemical 

Reregistration Eligibility GABA was registered after November 1984 and was not subject to reregistration. 

Decision (RED) 

Tolerance Reassessment GABA is exempt from the requirement for a tolerance and was not subject to a 

Eligibility Decision (TRED) tolerance reassessment. 

Cumulative group GABA is not a member of a cumulative group that shares a common mechanism 

of toxicity. 

40 CFR Citation 40 CFR § 180.1188 - Exemption from the requirement of a tolerance. 

Non-pesticidal uses GABA is an amino acid in human, plant and animal proteins, and is a brain 

neurotransmitter in humans and animals. 

6 
oz. per application, to a Soil, soil drench Terrestrial feed crops Terrestrial nonfood Auxigro WP Plant January 14, maximum annual rate of 1.5 Foliar/ground 70810-1 Metabolic Primer lb/acre (0.45 lbs of each Aerial crops 

(29.2%) 1998 ail acre) on food crops and 8 Chemigation - Aquatic food crops 

lbs/acre (2.4 lbs each potatoes only Greenhouse food crops 

ai/acre) on ornamentals. Lawn and turf grasses Ornamentals 

ii. Tolerance Actions 

LGA is exempt from the requirement of a tolerance as follows: 

40 C.F.R. § 180.1187 L-Glutamic Acid; exemption from the requirement of a tolerance: L-Glutamic 

Acid is exempt from the requirement of a tolerance on all food when used in accordance 

with good agricultural practices. 

Federal Register Citation- Final Rule 66 FR 33198, June 21, 2001. 

Gamma-Aminobutyric is exempt from the requirement of a tolerance as follows: 

40 C.F.R. § 180.1188 Gamma Aminobutvric Acid; exemption from the requirement of a tolerance: 

Gamma Amino butyric Acid is exempt from the requirement of a tolerance on all food commodities 

when used in accordance with good agricultural practices. 

Federal Register Citation- Final Rule 66 FR 33198, June 21, 2001. 

D. Anticipated Data Needs and Risk Assessments 

The following tables list the current data requirements for biochemical pesticides as set forth in 40 CFR 

§ 158, subpart U. They are arrayed by scientific discipline (i.e., product chemistry, human health 

assessment, nontarget organisms, and environmental fate) and descriptions are included regarding how 

the data requirements have been fulfilled (for example, with a study, public literature, or data waiver), 

not required, or are not satisfied. The most recent comprehensive risk assessment for LGA and GABA 

was completed October 6, 1997 (U.S. EPA, 1997) in support ofthe first biochemical registration ofLGA 

and GABA, which occurred on January 14, 1998. At this time, no data gaps (anticipated data needs) for 

LGA and GABA have been identified. Because there are no data gaps for L-Glutamic Acid and GABA, 

the Agency does not anticipate the need to conduct new human health or ecological risk assessments 

during registration review. 

7 
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880.1200 Description of Staring Materials, Production, Yes- Study 44296801 and Formulation Process 

880.1400 Discussion ofF ormation of Im_purities Yes- Study 44296801 

830.1700 Preliminary Analysis Yes- Study 44296801 

830.1750 Certified Limits Yes- Study 44296801 

830.1800 Enforcement Analytical Method Yes- Study 44296801 

Table 5. Summary of Physical and Chemical Characteristics for LGA and GABA 

Harmonized Has Data Requirement MRID No. or Other Guideline Data Requirement 

Number Been Addressed? How? Source 

830.6302 Color Yes- Study 44296801 

830.6303 Physical State Yes-Study 44296801 

830.6304 Odor Yes- Study 44296801 

830.6313 Stability to Normal and Elevated Yes- Study 44296801 Temperatures, Metals and Metal Ions 

830.6315 Flammability Not required- product does not contain combustible liquids 

830.6317 Storage Stability Yes-Study 46653801 

830.6319 Miscibility Not required -product is not an emulsifiable liquid 

and will not be diluted with petroleum distillates 

830.6320 Corrosion Characteristics Yes- Waived (Does not 44368801' 

interact with packaging 

materials) 

830.7000 pH Yes- Study 44296801 

830.7050 UVNisible Light Absorption Yes- Study 44296801 830.7100 Viscosity Not required- product is not a liquid 830.7200 Melting Point/Melting Range Yes- Study 44296801 

830.7220 Boiling Point/Boiling Range Not required- TGAI is not a liquid at room temperature 

830.7300 Density/Relative Density/Bulk Density Yes- Study 44296801 (Specific Gravity) 

830.7520 Particle Size, Fiber Length, and Diameter Not required- TGAis are water soluble, not fibrous Distribution 

830.7550 Not required for organic chemicals that completely 830.7560 Partition Coefficient (n-Octanol Water) 

830.7570 dissociate in water 830.7840 Water Solubility Yes- Study 44296801 

830.7950 Vapor Pressure Waived- TGAis are crystalline solids 

8 
Subchronic mammalian toxicity studies were waived based upon the natural occurrence of LGA and 

GABA in humans, animals and plants; the rapid metabolism in humans of ingested glutamate; no effects 

on neurological or hepatic function in human adult males given up to 13 7 g glutamic acid daily for 14-

41 days; and the lack of persistence/short half-life of these amino acids in the environment. (U.S. EPA, 

1997). 

Table 6. Summary of Human Health Assessment Data for LGA and GABA 

Harmonized Has Data Requirement MRID No. or Other Guideline Data Requirement 

Number Been Addressed? How? Source 

870.1100 Acute Oral Toxicity - Rat Yes- Study 44296802 

870.1200 Acute Dermal Toxicity Yes - Study 44296803 

870.1300 Acute Inhalation Toxicity - Rat Yes - Study 44296804 

870.2400 Primary Eye Irritation Yes - Study 44296805 

870.2500 Primary Dermal Irritation Yes - Study 44296806 

870.2600 Dermal Sensitization Yes - Study 44296807 

870.3100 90-Day Oral (one species) Yes - Data Waiver 44296206 870.3250 90-Day Dermal - Rat Yes - Data Waiver U.S. EPA, 1997 

870.3465 90-Day Inhalation - Rat Yes - Data Waiver U.S. EPA, 1997 870.3700 Prenatal Developmental - Rat Preferably Yes - Public literature 44296410 

Not required since the use is not likely to result in 

significant human exposure, and neither LGA nor 

870.5100 Bacterial Reverse Mutation Assay GABA are structurally related to a known mutagen or 

belongs to a chemical class of compounds containing a 

known mutagen 

Not required since the use is not likely to result in 

870.5300 significant human exposure, and neither LGA nor 870.5375 n vitro Mammalian Cell Assay GABA are structurally related to a known mutagen or belongs to a chemical class of compounds containing a 

known mutagen. 

9 
850.2200 Avian Dietary Toxicity Yes - Data Waiver U.S. EPA, 1997 850.1010 Aquatic Invertebrate Acute Toxicity, Yes- Study 44405701 Freshwater 

850.1075 Fish Acute Toxicity, Freshwater Yes- Study 44405702 

880.4300 Nontarget Plants Yes - Data Waiver U.S. EPA, 1997 880.4350 Nontarget Insect Testing Yes - Data Waiver U.S. EPA, 1997 

E. Risk to Threatened and Endangered Species 

The data requirements for nontarget birds (avian acute oral and dietary toxicity studies), plants, and 

insects were waived, based upon the low acute toxicity of LGA and GABA in mammalian species, their 

natural occurrence, biodegradability in the environment2, and the presence of these substances in 

virtually all living animals, plants, and humans. From the submitted studies, the 96 hour LC50 in 

freshwater fish (species tested was the rainbow trout, Oncorhynchus mykiss) and the 48 hour EC50 value 

for the freshwater invertebrate, Daphnia magna, are > 100 mg/L. The No Observed Effect 

Concentration (NOEC) value was determined to be 100 mg/L, based upon no mortality at the highest 

concentration tested in these studies, which classifies LGA and GABA as practically nontoxic to these organisms. 

Based upon the low toxicity of LGA and GABA demonstrated in the mammalian acute toxicity studies 

(see section D. ii. of this document) and the nontarget freshwater invertebrate and fish studies, their 

ubiquity in living organisms, and the low application rates as PGRs, the Agency has concluded that the 

risks to nontarget species, including federally listed threatened or endangered species (listed species) 

and/or their designated critical habitat, from the use ofLGA and GABA as PGRs are negligible, and will 

have "no effect" on listed species and/or their designated critical habitat. EPA anticipates conducting no 

further analysis of potential risks to endangered or threatened species, unless data or information are 

obtained during the registration review process that would indicate such an assessment would be needed 

to inform the Agency's decision. 

F. Endocrine Effects 

As required by the Administrator under the Federal Food, Drug, and Cosmetic Act (FFDCA) section 

408(p ), the EPA has developed the Endocrine Disruptor Screening Program (EDSP) and has begun to 

implement the screening program that is to be used to test all pesticides in order to determine whether 

certain substances (including pesticide active and other ingredients) may have an effect in humans or 

2 Half-life in water = 8.7 days; in soil = 17.3 days - Level III Fugacity Model, generated using USEPA's "EPISuiteTM" 

http://www.chemspider.com/Chemical-Structure.116.html 

10 
Between October 2009 and February 2010, the EPA issued test orders/data call-ins for the first group of 

67 chemicals, which contains 58 pesticide active ingredients and 9 inert ingredients. A second list of 

chemicals3 identified for EDSP screening was published on June 14, 2013, and includes some pesticides 

scheduled for registration review and chemicals found in water. LGA and GABA are not among the 

group of pesticide active ingredients on the lists to be screened under the EDSP. 

The EPA, as part of this Preliminary Work Plan, believes that LGA and GABA are substances that 

would not likely produce any effect in humans similar to an effect produced by a naturally occurring 

estrogenic substance. As such, pursuant to Section 408(p)(4), the EPA will determine in the future 

whether it can exempt LGA and GABA from the requirements of the Section 408(p) EDSP. In the event 

the EPA does determine to exempt this substance from the EDSP, an order will be issued. 

For further information on the status of the EDSP, the policies and procedures, the lists of chemicals, 

future lists, the test guidelines and the Tier 1 screening battery, please visit our website at 

http://www. epa.govlendo/. 

G. Incidents 

From January 14, 1998 (the first date ofLGA and GABApesticide registration) through January 29, 

2014, the Office of Pesticide Programs' (OPP's) Incident Data System (IDS) indicates two reports of 

adverse effects in humans from the use of a pesticide product containing LGA and GABA as their active 

ingredients. The reported incidents involved an adult man developing migraines, vertigo, tinnitus, 

dizziness and blurred vision after being exposed to the product containing both active ingredients, and 

an adult woman that developed sensitivity to glutamate and monosodium glutamate food coloring and 

found that she became sick after eating Mexican vegetables that were exposed to the registered product 

containing LGA and GABA as its active ingredients. There were no reported incidents to domestic 

animals, drinking water, surface water, groundwater, plants, wildlife or other non-targets during that 

same time period. A search of OPP's Environmental Incident Information System (EllS) revealed no 

incidents associated with LGA and GABA. The database contains information dating back to the 1970s. 

The EPA will consider any incident data or comments submitted in response to this Preliminary Work 

Plan. 

3 See http://www.regulations.gov/#!documentDetaii;D=EPA-HQ-OPPT-2009-04 77-0074 for the second list of chemicals. 

11 
Ope

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ay 

ub

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t 

e

od September 2014 

Close Public Comment Period November 2014 

Case Development 

Issue Final Work Plan March 2015 

Issue Data Call-in N/A 

Data Submission NIA 

Open 30-Day Public Comment Period for Draft Risk Assessments NIA Close Public Comment Period NIA 

Registration Review Decision 

Open 60-Day Public Comment Period for Proposed Registration Review December 20 15 

Decision 

Close Public Comment Period February 2016 

Final Decision June 2016 

Estimated Total (years) 1 year and 9 months 

.. * This schedule IS subject to revision. Should unforeseen Issues anse durmg the registration review process (I.e., newly 

anticipated data needs or the failure to acquire an EDSP exemption), the new schedule will be set forth in the Final Work 

Plan or an amended Final Work Plan for this case. 

I. Guidance for Commenters 

The public is invited to comment on the EPA's Preliminary Work Plan and rationale. The areas below 

highlight topics of special interest to the EPA where comments, information and data, or reference to 

sources of additional information could be of particular use. The EPA will consider all comments, as 

well as any additional information or data provided in a timely manner, prior to issuing a Final Work 

Plan for this case. 

i. Environmental Justice 

The EPA seeks to achieve environmental justice, the fair treatment and meaningful involvement of all 

people, regardless of race, color, national origin, or income, in the development, implementation, and 

enforcement of environmental laws, regulations, and policies. To help address potential environmental 

justice issues, the EPA seeks information on any groups or segments of the population who, as a result of 

their location, cultural practices, or other factors, may hav.e unusually high exposure to the pesticidal use 

of LGA or GABA, compared to the general population. Please comment if you are aware of any 

subpopulations that may have atypical, unusually high exposure compared to the general 

population. 

12 
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p

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f 

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y 

Quality Data in OP P s Registration Review Risk Assessment and Management Process 7 to ensure they 

can be used quantitatively or qualitatively in pesticide risk assessments. 

iii. Trade Irritants 

Through the Registration Review process, the EPA intends to solicit information on trade irritants and, to 

the extent feasible, take steps toward facilitating irritant resolution. The EPA will work to harmonize 

tolerance and international Maximum Residue Limits (MRLs ), and, if necessary, may modify tolerance 

levels to do so. Growers and other stakeholders are asked to comment on any trade irritant issues 

resulting from the lack ofMRLs or disparities between U.S. tolerances and MRLs in key export 

markets, providing as much specificity as possible regarding the nature of the concern. 

Pesticidal use of LGA and GABA in or on food and animal feed commodities are covered under an 

existing exemption from the requirement of a tolerance. Moreover, there are no known MRLs for LGA 

or GABA. Therefore, the EPA does not anticipate that current uses of LGA and GABA will pose 

concerns as trade irritants. 

iv. Additional Information 

Stakeholders are also specifically asked to provide information and data that will assist the EPA in 

refining the risk assessments. The EPA is also interested in obtaining the following information 

regarding-Glutamic Acid and Gamma-Amino butyric Acid: 

.,.. Comments regarding the clarity of the directions for use on the label for Auxigro WP Plant 

Metabolic Primer (EPA Registration Number 70810-1 ): 

- Sites of application 

-Application methods and equipment 

- Maximum application rates 

-Application timing (frequency of application, application intervals, and maximum 

number of applications) 

- Reentry intervals 

- Pre-harvest intervals 

.,.. Monitoring data .,.. Use restrictions (State and local) 

4 Based on information provided at http://www.epa.gov/owowltmdll. 

5 Based on information provided at http://iaspub.epa.gov/tmdl waterslO/text search.tmdl search (orm. 

6 See http://www.epa.govlowowltmdl/. 

7 This document can be found at http://www.epa.gov/oppsrrdl/registration review/water qualitv sop.htm. 

13 
aminobutyric acid. 

14 
44268800 Application for Experimental Use Permit for AuxiGro Plant Growth Enhancer. Transmittal of 28-Apr-1997 

7 Studies. 

44268801 Mahler, H.; Cordes, E. (1966) General aspects of amino acid metabolism. P. 685 in Biological 28-Apr-1997 Chemistry. New York, NY: Harper & Row. 

44268802 McGilvery, R. ( 1979) Amines. P. 616-618 in Biochemistry: A Functional Approach, 2nd ed. 28-Apr-1997 Philadelphia: W.B. Saunders Co. 

144268803 

Tower, D. (1960) The administration of gamma-aminobutyric acid to man: Systemic effects 

and anticonvulsant action. P. 562-578 in Inhibition in the Central Nervous System and 28-Apr-199.7 

Gamma-Aminobutyric Acid. Ed. by E. Roberts. New York, NY: Pergamon Press. 

I Kuhn, J. (1997) Acute Oral Toxicity Study in Rats: AuxiGro: Final Report: Lab Project 44268804 Number: 3288-97: S9-FF81-1. Unpublished study prepared by Stillmeadow, Inc. 11 p. 28-Apr-1997 

144268805 Kuhn, J. (1997) Acute Dermal Toxicity Study in Rabbits: AuxiGro: Final Report: Lab Project 28-Apr-1997 Number: 3289-97: S9-FF81-2. Unpublished study prepared by Stillmeadow, Inc. 13 p. 

I Kuhn, J. (1997) Primary Dermal Irritation Study in Rabbits: AuxiGro: Final Report: Lab 144268806 Project Number: 3292-97: S9-FF81-5. Unpublished study prepared by Stillmeadow, Inc. 13 p. 28-Apr-1997 

144268807 Narayan, V.; Nair, P. (1990) Metabolism, enzymology and possible roles of 4-aminobutyrate 28-Apr-1997 in higher plants: Review article number 51. Phytochemistry 29(2):367-375. 

I 

Auxein Corp. (1997) Submission of Metabolism and Toxicology Data in Support of the 

44296200 Petition for Tolerance for gamma-Aminobutyric Acid on All Agricultural Commoditi,es. 12-Jun-1997 

Transmittal of 6 Studies. 

144296201 Meldrum, B. (1982) Pharmacology of GAB A. Clinical Neuropharmacology 5(3):293-316. 12-Jun-1997 

144296202 McGilvery, R.; Goldstein, G. (1979) Amines. P. 616-618 in Biochemistry, A Functional 12-Jun-1997 Approach, 2nd ed. Philadelphia/London/Toronto: W.B. Saunders Co. 

I 

Meister, A. (1979) Biochemistry of glutamate: Glutamine and glutathione. P. 69-84 in 

44296203 Glutamic Acid: Advances in Biochemistry and Physiology by L. Filer, eta!., ed. New York, 12-Jun-1997 

I NY: Raven Press. 

Munro, H. (1979) Factors in the regulation of glutamate metabolism. P. 55-68 in Glutamic 

44296204 Acid: Advances in Biochemistry and Physiology by L. Filer, eta!., ed. New York: Raven 12-J un-1997 

Press. Fonnum, F.; Hassel, B. (1995) Glutamate synthesis, metabolism, and uptake. P. 19-34 in CNS 

44296205 Neurotransmitters and Neuromodulators: Glutamate by T. Stone, ed. New York, NY: CRC 12-Jun-1997 

Press. 

Tower, D. (1960) The administration of gamma-aminobutyric acid to man: Systemic effects 

44296206 and anticonvulsant action. P. 562-578 in Inhibition in the Central Nervous System and 12-Jun-1997 

gamma-Aminobutyric Acid. New York, NY: Pergamon Press. 

15 
Meister, A. (1979) Biochemistry of glutamate: glutamine and glutathione. P. 69-84 in 

44296402 Glutamic Acid: Advances in Biochemistry and Physiology by L. J. Filer, et al., ed. New York, 12-Jun-1997 

NY: Raven Press. 

I 

Munro, H. (1979) Factors in the regulation of glutamate metabolism. P. 55-68 in Glutamic 

44296403 Acid: Advances in Biochemistry and Physiology by L. J. Filer, Jr., et al., ed. New York, NY: 12-Jun-1997 

Raven Press. 

44296404 Fonnum, F.; Hassel, B. (1995) Glutamate synthesis, metabolism, and uptake. P. 19-34 in CNS 12-Jun-1997 Neurotransmitters and Neuromodulators: Glutamate by T. Stone, ed. New York: CRC Press. 

44296405 Meldrum, B. (1982) Pharmacology of GAB A. Clinical Neuropharmacology 5(3):293-316. 12-Jun-1997 

Committee on Gras List Survey-Phase III ( 1976) Estimating distribution of daily intake of 

44296406 monosodium glutamate (MSG), Appendix E. P. 1-10 in Estimating Distribution ofDaily 12-Jun-1997 

Intakes of Certain GRAS Substances. Washington DC: National Academy of Sciences. 

44296407 Ebert, A. ( 1970) Chronic toxicity and teratology studies of L-monosodium glutamate and 12-Jun-1997 related compounds. Toxicology and Applied Pharmacology 17:274. 

44296408 Owen, G.; Cherry, C.; Prentice, D.; et al. (1978) The feeding of diets containing up to 4% 12-Jun-1997 monosodium glutamate to rats for 2 years. Toxicology Letters 1 :221-226. 

44296409 Owen, G.; Cherry, C.; Prentice, D.; et al. (1978) The feeding of diets containing up to 10% 12-Jun-1997 monosodium glutamate to Beagle dogs for 2 years. Toxicology Letters 1:217-219. 

44296410 Semprini, M.; D'Amicis, A.; Mariani, A. (1973) Effect of monosodium glutamate on fetus and 12-Jun-1997 newborn mouse. Nutr. Metab 16:276-284. 

Semprini, M.; Conti, L.; Ciofi-Luzzatto, A.; et al. (1974) Effect of oral administration of 

44296411 monosodium glutamate (MSG) on the hypothalamic arcuate region of rat and mouse: A 12-Jun-1997 

histological assay. Biomedicine 21 :398-403. 

I 

Wen, C.; Kenneth, C.; Gershoff, S. (1973) Effects of dietary supplementation ofMSC on 

44296412 infant monkeys, weanling rats and suckling mice. The American Journal of Clinical Nutrition 12-Jun-1997 

26:803-813. 

US Department of Health and Human Services. (1986) (Summary toxicity data). P. 2522-

44296413 2527 in NIOSH Registry of Toxic Effects of Chemical Substances (RTECS)-(1985-1986), v. 12-Jun-1997 

3 

44296414 Olney, J. (19?.?) Brain lesions, obesity and other disturbances in mice treated with 12-Jun-1997 monosodium glutamate. Science 164:719-721. 

Heywood, R.; Worden, A. (1979) Glutamate toxicity in laboratory animals. P. 203-215 in 

44296415 Glutamic Acid: Advances in Biochemistry and Physiology, by L.J. Filer, Jr., et al., ed. New 12-Jun-1997 

York: Raven Press. 

44296416 Oser, B.; Morgareidge, K.; Carson, S. (1975) Monosodium glutamate studies in four species 12-Jun-1997 of neonatal and infant animals. Food Cosmet. Toxicol. 13:7-14. 

16 
44296419 Stegink, L.; Pitkin, R.; Reynolds, A.; eta!. (1974) Placental transfer of glutamate and its 12-Jun-1997 metabolites in the primate. Am J. Obstet. Genecol., I22:70-78. 

Airoldi, L.; Bizzi, A.; Salmona, M.; eta!. (1979) Attempts to establish the safety margin for 

44296420 neurotoxicity of monosodium glutamate. P. 321-331 in Glutamic Acid: Advances in 12-Jun-1997 

Biochemistry and Physiology by L. Filer, Jr., et a!., ed. New York: Raven Press. 

Adams, C. (1975) Nutritive Value of American Foods in Common Units, Agriculture 

44296421 Handbook No. 456. Prepared by United States Department of Agriculture; available from the I2-Jun-I997 

Government Printing Office. 

144296800 

Auxein Corp. (1997) Submission of Product Chemistry and Toxicity Data in Support of the I2-Jun-I997 Application for Registration of AuxiGro WP End-Use Product. Transmittal of7 Studies. 

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830.7300,830.7000,830.6313, 830.6320} 

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830.6303, 830.6304, 830.7300, 830.7000, 830.6313, 830.6320} 

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17 
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I 

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18 
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