Document ID: EPA-HQ-OPP-2011-0691-0004
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2011-09-30T04:00Z

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.

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.



Table 1. Product Identity and Composition for AVG



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.

 	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.

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

luding ω-N-acetyl-aminoethoxyvinylglycine and ethoxyvinylglycine. These
metabolites are then primarily excreted in urine.

 	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. 

 	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 non-occupational 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.

 	Occupational/Residential Exposure

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

 	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

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

Guideline No.	Physical and Chemical Properties	Status1	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

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.	--

A=Acceptable. N/A=Not Applicable.

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.

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Case #:  6070

129104

Aminoethoxyvinylglycine Hydrochloride			Case #:  6070

129104

Human Health Assessment—Registration Review

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