Aminoethoxyvinylglycine Hydrochloride Case #: 6070

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Human Health Assessment—Registration Review

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C. 20460

August 8, 2011

OFFICE OF CHEMICAL SAFETY AND POLLUTION PREVENTION

MEMORANDUM

SUBJECT: Product Chemistry Scoping Document for the Registration Review of 

Aminoethoxyvinylglycine Hydrochloride. 

Registration Review Case #: 6070

PC Code: 129104 

CAS Numbers: 55720-26-8

Chemical Class: Biochemical

FROM: Jacob Moore, Chemist /s/ 07/27/2011

Biochemical Pesticides Branch

Biopesticides & Pollution Prevention Division (7511P)

TO: John Fournier, Regulatory Action Leader

Biochemical Pesticides Branch

Biopesticides & Pollution Prevention Division (7511P) 

ACTION REQUESTED

A preliminary assessment of available information on product chemistry data associated with

the biopesticide aminoethoxyvinylglycine hydrochloride in support of the development of a 

Registration Review Work Plan.
Aminoethoxyvinylglycine Hydrochloride Case #: 6070

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Introduction

The EPA has made the determination that there is adequate information available on 

aminoethoxyvinylglycine hydrochloride, commonly known as AVG, and does not foresee the 

need to require additional data from products currently registered that contain AVG as the active 

ingredient. AVG is a plant growth regulator used on apples, pears, and ornamentals. In apples, it

may delay fruit maturity, leading to benefits such as a reduction in pre-harvest fruit drop and 

improved fruit quality. In pears, AVG may help maintain fruit firmness. For specific ornamentals 

(miniature carnations, hibiscus, and rooted geranium cuttings and seedlings), AVG may reduce 

problems, such as flower senescence and flower bud abscission, that occur during shipping. AVG

products have been registered with the EPA since 1997. Currently there are 11 active 

registrations containing AVG, including two technical grade active ingredient registrations, six 

end-use or manufacturing-use products, and three experimental use permits. The technical 

registration contain 86% active ingredient by weight with the balance consisting of impurities. 

The Agency exempts AVG from the requirement of a tolerance under the following conditions 

under 40 CFR §180.502.

The tolerances for residues was established by the Agency on May 7, 1997 in 62 FR 24838 and 

further amended up to February 18, 2004, the current version, and can be read in 69 FR 7606. 

The biochemical human health assessment data requirements of technical grade AVG have been 

satisfied and are summarized in Table 2. While no further toxicity data are necessary for the 

products currently registered, future products must adequately address all of the biochemical 

pesticides human health assessment data requirements.
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Table 1. Product Identity and Composition for AVG

Common Name Aminoethoxyvinylglycine Hydrochloride (AVG)

Chemical Name, IUPAC (3E)-2-amino-4-(2-aminoethoxy)-3-butenoic acid

hydrochloride

Molecular Weight 196.6 g/mol

PC Code 129104

CAS Registry Number 55720-26-8

Empirical Formula C6H13N2 O3Cl

Registration Review Case Number 6070

Chemical Structure
Aminoethoxyvinylglycine Hydrochloride Case #: 6070

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Human Health Assessment

The Agency has conducted a review of the available human health assessment data and 

information. These data are summarized below and in Table 2.

I. Toxicology

 Acute and Short-term Toxicity:

The Agency has reviewed all toxicity studies for AVG and has determined that the 

toxicological database is sufficient. The toxicological database for AVG is currently

comprised of published and unpublished studies submitted to the Agency or obtained from 

published literature.

AVG is considered Toxicity Category IV for Acute Oral, Primary Eye Irritation, and Primary

Dermal Irritation. It is considered Toxicity Category III for Acute Dermal and Acute 

Inhalation. AVG is not a dermal sensitizer.

Genotoxicity:

AVG was tested in a gene mutation assay (Ames), a lymphoma assay (mouse) and a 

micronucleus assay. No mutagenic activity was observed.

Reproductive and Developmental Toxicity:

In a rat reproduction study, AVG exposure decreased viability of F1 pups and retarded growth 

in F1 and F2 pups (NOAEL=2.5 mg/kg-day; LOAEL=4 mg/kg-day). Higher doses 

(NOAEL=4 mg/kg-day; LOAEL=8 mg/kg-day) decreased testicular weight, changed sperm 

morphology and increased the incidence of testicular histopathology. Parental system effects 

in the same study were induced at 2.5 mg/kg-day and 4 mg/kg-day.

A developmental study in rats revealed decreased body weight gain, food consumption, 

defecation and red perinasal material in dams (NOAEL=1.77 mg/kg-day; LOAEL=8.06 

mg/kg-day). A rabbit developmental study reported decreased body weight gains and food 

consumption in dams (NOAEL=0.4 mg/kg-day; LOAEL=0.7 mg/kg-day) and developmental 

malformations in fetuses (NOAEL=0.2 mg/kg-day; LOAEL=0.4 mg/kg-day).

Subchronic Toxicity:

Subchronic studies were performed on mice, rats and dogs and were deemed acceptable by

the Agency. In studies conducted on mice, rats, and dogs, AVG primarily induced liver 

pathologies such as increased weight, hepatocellular vacuolation, fat accumulation, 

inflammatory cell infiltration, hypertrophy, and reduced ALT and AST activity at LOAELs 

that ranged from 1.2 to 9.4 mg/kg-day. Body weight, weight gain, and food consumption 

were also affected at similar concentrations.
Aminoethoxyvinylglycine Hydrochloride Case #: 6070

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Chronic Toxicity/Cancer:

A one year chronic rat toxicity study reported increased testicular atrophy in males, chronic 

renal nephropathy in females and decreased food consumption and body weight gain in both 

sexes at LOAEL of 7.0 mg/kg-day. A NOAEL was recorded at 0.7 mg/kg-day in males and 

females.

The Agency has concluded that the AVG data are inadequate for an assessment of human 

carcinogenic potential. A two year study conducted on rats produced non-cancer effects. This 

is based on guideline studies that the Agency no longer requires.

Metabolic Studies

Evidence suggests that AVG rapidly metabolizes into less toxic polar metabolites including 

ω-N-acetyl-aminoethoxyvinylglycine and ethoxyvinylglycine. These metabolites are then 

primarily excreted in urine.

II. Dietary Assessment

The majority of dietary exposures to residues of AVG occur through ingestion of apples, 

pears and stonefruit. A dietary exposure and risk assessment for AVG revealed no adverse 

effects to various populations. 

III. Aggregate and Cumulative Exposure

In examining aggregate exposure, the Agency has taken into account the available and 

reliable information concerning exposures to AVG in food, drinking water and other nonoccupational pesticide activities. AVG is unlikely to contaminate drinking water. In food, 

EPA internal testing concluded that dietary risk was below the level of concern for both acute 

and chronic exposures.

IV. Occupational/Residential Exposure

AVG has no product registrations for residential non-food uses and exposure from nonoccupational, non-dietary sources is negligible. Exposures from applications of AVG are 

below EPAs level of concern.

V. Tolerances

AVG has an established tolerance for residues. The information is presented below:

Commodity Parts Per Million

Apple 0.08

Fruit, stone, group 12, except cherry 0.170

Pear 0.08

40 CFR §180.502
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VI.Conclusion

The Agency has reviewed the hazard and exposure databases for AVG and anticipates that no 

additional toxicity and exposure data will be needed for registration review. In addition, the 

EPA anticipates that no additional occupational and residential handler assessments will be 

needed to ensure that the AVG registration review case meets the safety standards established 

by FFDCA, as amended by FQPA. 

However, registrants presenting new products to the Agency must continue to meet all 

biochemical pesticides human health assessment data requirements. Simple citation of this 

document may or may not be adequate to address current and future data requirements. This 

document speaks to currently registered technical grade AVG only.

Table 2. Biochemical Pesticides Human Health Assessment Data Requirements for AVG

Guidelin

e No.

Physical and Chemical 

Properties

Status

1

Value MRID

870.1100 Acute oral toxicity—rat A LD50 = 6480 mg/kg—IV 42672203

870.1200 Acute dermal toxicity A LD50>2000 mg/kg—III 42672204

870.1300 Acute inhalation toxicity—

rat 

A LC50 = 1.13 mg/L— III 42672205

870.2400 Primary eye irritation—

rabbit 

A Conjunctival redness, chemosis, and 

discharge at 1 hr post exposure, resolved by

day 7, no significant iridal or corneal 

effects—IV

42672206

870.2500 Primary dermal irritation A Very slight to well defined erythema at 30-

60 min PE and 24 hr after patch removal. 

No significant dermal irritation at 4 hr PE—

IV

42672207

870.2600 Dermal sensitization A No dermal sensitivity 43556801

870.3100 90-day oral—rat A NOAEL= 2.2 mg/kg-day

LOAEL = 9.4 mg/kg-day

43183609

870.3200 21-day dermal—rat A NOAEL = 1000 mg/kg-day (limit dose). 43846506

870.3465 90-day inhalation—rat N/A No likelihood of significant levels of 

repeated inhalation exposure to TGAI as a 

gas, vapor, or aerosol. Does not apply to

MPs/EPs.

--

870.3700 Prenatal developmental—rat A Maternal: NOAEL= 1.77 mg/kg-day; 

 LOAEL=8.06 mg/kg-day

Developmental: NOAEL= 1.77 mg/kg-day;

 LOAEL= 8.06 mg/kg-day

43206902
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870.5100 Bacterial reverse mutation 

test

A No mutagenic activity 42672209

870.5375 In vitro mammalian cell 

assay

A No mutagenic activity 42672210

870.5385 In vivo Mammalian 

Cytogenetics

A No mutagenic activity 42672211

875.1100

875.1200

875.1300

875.1400

875.1500

Application/User Exposure N/A Not required; the data used for the human 

health assessment indicate that the 

biochemical will not pose a potential hazard 

to the applicator/user.

--

870.3800 Reproduction and fertility

effects

A Parental/systemic:

 NOAEL = 0.8 mg/kg-day(males)

 NOAEL = 2.5mg/kg-day(females)

 LOAEL = 2.5 mg/kg-day

Reproductive:

 NOAEL = 4 mg/kg-day

 LOAEL = 8 mg/kg-day

Offspring:

 NOAEL = 2.5 mg/kg-day

 LOAEL = 4 mg/kg-day

44946501

870.4100 Chronic oral—rodent and 

non-rodent

A NOAEL = 0.7 mg/kg-day

 LOAEL = 7.0 mg/kg-day

45359605

870.4200 Carcinogenicity—two 

species—rat and mouse 

preferred

A NOAEL = 0.7 mg/kg-day 45698801

870.5380 Mammalian spermatogonial 

chromosome aberration test

N/A No indication of potential chromosomal 

aberration.

--

1. A=Acceptable. N/A=Not Applicable.
Aminoethoxyvinylglycine Hydrochloride Case #: 6070

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References

Carlson, K., Gardner, R. Memorandum to D. Greenway. 12/15/2005.

Devisetty, B., Bade, T. Product Identity, Manufacturing Process, VBC-30102 (AVG HCL Liquid 

Formulation). Private Study by Valent Biosciences Corp Submitted to EPA. MRID 

477707-01. 2009.

Merck Index, Online. 07/19/2011.

PubChem. http://pubchem.ncbi.nlm.nih.gov/summary/summary.chi?cid=6434508. 07/25/2011.