BIOPESTICIDES REGISTRATION ACTION DOCUMENT

Tobacco mild green mosaic tobamovirus strain U2

Pesticide Chemical (PC) Code: 056705

U.S. Environmental Protection Agency

Office of Pesticide Programs

Biopesticides and Pollution Prevention Division

March 30, 2015
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TABLE OF CONTENTS

I. EXECUTIVE SUMMARY .........................................................................................................................4

II. ACTIVE INGREDIENT OVERVIEW .....................................................................................................6

III. REGULATORY BACKGROUND ............................................................................................................6

A. Application for Pesticide Product Registration .............................................................................6

B. Food Tolerance Exemption .............................................................................................................7

IV. RISK ASSESSMENT..................................................................................................................................7

A. Product Analysis Assessment (40 CFR § 158.2120) ......................................................................8

B. Human Health Assessment (40 CFR § 158.2140)..........................................................................8

C. Environmental Assessment (40 CFR § 158.2150)........................................................................12

V. ENVIRONMENTAL JUSTICE...............................................................................................................17

VI. RISK MANAGEMENT DECISION........................................................................................................17

VII. ACTIONS REQUIRED OF THE REGISTRANT .................................................................................18

VIII. GLOSSARY OF ACRONYMS AND ABBREVIATIONS ....................................................................19

IX. BIBLIOGRAPHY......................................................................................................................................20

A. Studies Submitted to Support the Tobacco mild green mosaic tobamovirus strain U2 

 Pesticide Product Registration ......................................................................................................20

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

C. Other References............................................................................................................................22

APPENDIX A. MICROBIAL PESTICIDES DATA REQUIREMENTS ........................................................25

APPENDIX B. PESTICIDE PRODUCTS...........................................................................................................31
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BIOPESTICIDES REGISTRATION ACTION DOCUMENT TEAM

Office of Pesticide Programs (OPP)

Biopesticides and Pollution Prevention Division

Microbial Pesticides Branch

Science Reviews

Shannon Borges Environmental Effects

Joel V. Gagliardi, Ph.D. Product Analysis, Human Health, and 

Environmental Effects

John L. Kough, Ph.D. Product Analysis and Human Health

Regulatory

ShaRon Carlisle Acting Associate Chief, Microbial Pesticides 

Branch

Jeannine Kausch Regulatory Action Leader

Kimberly Nesci Chief, Microbial Pesticides Branch
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I. EXECUTIVE SUMMARY

Background

In May 2013, BioProdex, Inc. (BioProdex), submitted an application for an end-use pesticide product

(SolviNix® LC, EPA File Symbol: 81179-G) to the U.S. Environmental Protection Agency (EPA) under 

section 3 of the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA). This pesticide product

contains a new active ingredient: Tobacco mild green mosaic tobamovirus strain U2 (TMGMV U2).

TMGMV is a tobamovirus, a type of plant virus, and is known as a pathogen of tobaccos (Nicotiana

spp.), peppers (Capsicum spp.), and about 20 other plant species (Brunt et al., 1996; Font et al., 2009;

Green and Kim, 1991; ICTVdB Management, 2006; Wetter, 1989). According to literature provided by 

BioProdex, TMGMV probably occurs in all tropical and subtropical regions in the world where tree 

tobacco (Nicotiana glauca), a natural host to this virus, occurs (Brunt et al., 1996; Wetter, 1989). In the 

U.S. specifically, this virus occurs in California (Bald and Goodchild, 1960; Bodaghi et al., 2000 and

2004), Florida (Baker and Adkins, 2004; Baker and Zettler, 1988; Zettler and Nagel, 1983), Georgia 

(McKinney, 1952; Wetter, 1984), Illinois (Knight et al., 1962; Miller and Thornberry, 1958), Ohio 

(Letschert et al., 2002), South Carolina (McKinney, 1952; Wetter, 1984), and Wisconsin (Johnson, 

1947; Siegel and Wildman, 1954; Weber, 1951). 

BioProdex isolated TMGMV U2 in Florida from horticultural materials and identified the virus by its 

host range and genomic sequence. Data demonstrate that TMGMV U2 infects and kills tropical soda 

apple (Solanum viarum). Tropical soda apple is a thorny plant native to South America (Argentina, 

Brazil, and Paraguay), is designated as a Federal Noxious Weed under the Plant Protection Act in the 

U.S., and crowds out native plant species and forage for livestock in the southeastern U.S. (UF – IFAS, 

2008; USDA, 2014). In light of TMGMV U2’s herbicidal capabilities, BioProdex proposed to register an

end-use pesticide product to control tropical soda apple in pastures and wooded areas that are fenced to 

contain grazing animals.

The EPA’s scientists reviewed product analysis, toxicology, and nontarget organism data and 

information (40 CFR §§ 158.2120, 158.2140, and 158.2150, respectively) submitted to support the

registration of the proposed TMGMV U2 pesticide product. Overall, such data and information are 

adequate for risk assessment purposes, fulfill the current microbial pesticide data requirements, and 

support registration of the proposed pesticide product under FIFRA section 3(c)(5).

Product Analysis

BioProdex fulfilled the product analysis data requirements for TMGMV U2, including product 

chemistry and composition, analysis of samples, and physical and chemical characteristics, by

submitting acceptable guideline studies.

Toxicology

BioProdex submitted adequate mammalian toxicology information to support the TMGMV U2 pesticide 

product. Based on BioProdex’s scientific rationale, the EPA waived acute toxicity/pathogenicity and cell 

culture testing for this active ingredient. The rationale included references to scientific literature and 

showed that plant viruses are ubiquitous in plants and food derived from plants, are not known or 

expected to cause toxicity, pathogenicity, or infectivity in mammals, and are unable to infect animal

cells. Moreover, BioProdex reported that no hypersensitivity incidents occurred during research, 

development, or testing of TMGMV U2. In light of the acceptability of the toxicological scientific 
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rationale and literature provided by BioProdex and the absence of hypersensitivity incidents, the EPA is 

not requiring testing at higher tiers (i.e., Tiers II and III).

Tolerance Exemption

The EPA concludes that there is a reasonable certainty that no harm will result to the U.S. population, 

including infants and children, from aggregate exposure to residues of TMGMV U2. The EPA does not 

expect dietary (food and drinking water) or other non-occupational risks from use of TMGMV U2 as an 

active ingredient in the proposed pesticide product. Virus-infected food plants have always been a part of 

the human diet and domestic animal food supply (Beemster and de Bokx, 1987; Dewan and Pearson, 

1995; Jones et al., 1934; McKinney, 1929; Palukaitis, 1991; Provvidenti and Gonsalves, 1984). To date, 

there have been no reports of adverse human or animal health effects associated with consumption of 

plant viruses in food. Furthermore, since applications of TMGMV U2 are limited to pastures and 

wooded areas that are fenced to contain grazing animals, increased exposures of the active ingredient to 

the general population through food and drinking water and in residential settings are not expected. 

Should TMGMV U2 be present in food or drinking water, supporting toxicological information indicates

that human exposure to this plant virus would not result in adverse effects.

Occupational Exposure

Despite the low toxicological profile of TMGMV U2, the EPA is requiring baseline protective clothing 

for individuals who, due to their occupation, may be exposed to the active ingredient for prolonged 

periods and/or multiple times. Individuals working with TMGMV U2 to treat tropical soda apple are 

directed to wear a long-sleeved shirt, long pants, socks, shoes, waterproof gloves, and a dust/mist 

filtering respirator meeting National Institute for Occupational Safety and Health (NIOSH) standards of 

at least N-95, R-95, or P-95. For future TMGMV U2 pesticide products, the EPA may require additional 

protective clothing (e.g., eyewear), other than the standard described above, on a product-specific basis. 

Nontarget Organisms

The EPA found that scientific rationale and nontarget plant studies submitted by BioProdex are 

sufficient to fulfill the nontarget organism data requirements and for risk assessment purposes. Further 

testing of nontarget organisms at higher tier levels (i.e., Tiers II, III, and IV) is not required. The EPA 

performed an environmental risk assessment based on information provided by BioProdex. Provided that 

limited use sites and application methods, mitigating label language, and certain manufacturing process 

steps are in place, the EPA has determined that unreasonable adverse effects to nontarget organisms are 

not expected from the proposed pesticidal uses of TMGMV U2. Moreover, the EPA made a “No Effect” 

determination for direct and indirect effects to federally listed, threatened and endangered species and 

their designated critical habitats resulting from these same proposed pesticidal uses. 

Public Participation

On October 1, 2009, the EPA announced a policy to provide a more meaningful opportunity for the 

public to participate in major registration decisions before they occur. According to this policy, the EPA 

provides a public comment period prior to making a registration decision for the following types of 

applications: new active ingredients; first food uses; first outdoor uses; first residential uses; or any other 

registration actions for which the EPA believes there may be significant public interest.

 

Consistent with the policy of making registration actions more transparent, the proposed pesticide 

product containing TMGMV U2, a new active ingredient, and allowing for this active ingredient’s first 

food and outdoor uses were subject to a 15-day comment period. During this comment period, the EPA 
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received 11 comments. Anonymous individuals submitted six of the comments and private citizens, 

some from the University of Florida, submitted the remaining comments. All of the comments were 

positive and indicated support for registration of TMGMV U2 in SolviNix® LC, citing to TMGMV U2’s

natural occurrence, TMGMV U2’s safety and unique mode of action when compared to conventional 

chemical alternatives, and non-native tropical soda apple’s ability to negatively impact agriculture and 

the environment. After considering these comments, the EPA maintains that, based upon the risk 

assessment and information submitted in support of SolviNix® LC, it is appropriate to issue this 

registration. The basis for this decision can be found in the risk assessment for TMGMV U2, which is 

characterized throughout this Biopesticides Registration Action Document (BRAD). 

II. ACTIVE INGREDIENT OVERVIEW

Biological Name: Tobacco mild green mosaic tobamovirus strain U2

Culture Deposit: American Type Culture Collection (ATCC) in Manassas, Virginia 

under Accession Number PV-1200

OPP Chemical Code: 056705

Type of Pesticide: Microbial Pesticide – Herbicide

See Appendix B for specific information (e.g.,

use sites, application rates, methods of application, 

formulation type, and target pest) regarding

the pesticide product containing this 

active ingredient.

III. REGULATORY BACKGROUND

A. Application for Pesticide Product Registration

In May 2013, BioProdex (address: 3131 NW 13th Street #54A; Gainesville, Florida 32609-2183)

submitted an application to register an end-use pesticide product SolviNix® LC (EPA File Symbol: 

81179-G) under FIFRA section 3. On January 17, 2014 (79 FR 3203), the EPA announced receipt of this

application to register a pesticide product containing a new active ingredient and opened a 30-day public 

comment period pursuant to the provisions of FIFRA section 3(c)(4). In response to this Notice of 

Receipt, the EPA received one comment that expressed concern over the lack of information provided in 

the Federal Register document and generally opposed both pesticide product applications (i.e., the 

SolviNix® LC application and an application for an antimicrobial pesticide product) summarized in that 

document. Specifically, the anonymous commenter cited concern for “conventional production 

practices” and the introduction of “new chemical agents” during these practices.

With publication of the Notice of Receipt, the EPA met the statutory requirement, as indicated in the 

previous paragraph, to inform the public of applications for pesticide products containing a new active 

ingredient, such as SolviNix® LC, with basic information (e.g., names and proposed uses of the active 

ingredients). At that time, the EPA had not yet completed its review of the data and information 
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submitted by BioProdex. Pursuant to its authority under FIFRA, the EPA has now conducted a 

comprehensive assessment of TMGMV U2 and concluded that this herbicide is not expected to cause 

any unreasonable adverse effects to human health or the environment. Further, the EPA emphasizes that

TMGMV U2 is not a conventional pesticide. Conventional pesticides generally consist of synthetic 

materials, may affect a broad spectrum of nontarget organisms, and may be inherently more toxic. 

Instead, the EPA considers TMGMV U2, a naturally occurring plant virus, to be a biopesticide. As 

described in section I of this document, this biopesticide will be used to control tropical soda apple, a 

noxious weed that adversely affects native plant species and forage for livestock in the southeastern U.S. 

 

B. Food Tolerance Exemption

Concurrent with BioProdex’s registration application and under Federal Food, Drug, and Cosmetic Act 

(FFDCA) section 408(d), Interregional Research Project Number 4 (IR-4) submitted a petition to 

establish an exemption from the requirement of a tolerance for TMGMV U2 (PP 3E8181). In the Federal 

Register of February 21, 2014 (79 FR 9870), the EPA announced that IR-4 proposed to establish an 

exemption from the requirement of a tolerance for residues of the herbicide TMGMV U2 in or on all 

commodities of crop groups 17 (grass forage, fodder, and hay group) and 18 (nongrass animal feeds 

group) and opened a 30-day comment period. The EPA received no comments on this publication. 

On December 19, 2014, the EPA amended an existing temporary tolerance exemption for Tobacco mild 

green mosaic tobamovirus by establishing a permanent exemption from the requirement of a tolerance 

for residues of Tobacco mild green mosaic tobamovirus strain U2 in or on all commodities of crop 

groups 17 and 18 when applied as a post-emergent herbicide and used in accordance with label 

directions and good agricultural practices (40 CFR § 180.1276; 79 FR 75754).

IV. RISK ASSESSMENT

In the Federal Registers of October 26, 2007 (72 FR 60988), and August 30, 2012 (77 FR 52610), the 

EPA issued Final Rules on the data requirements to support registration of microbial pesticides and 

updated the definition for microbial pesticides. The data and information evaluated for this BRAD were 

considered in light of these requirements.

The classifications that are found for each data submission are assigned by the EPA’s science reviewers 

and are an indication of the usefulness of the information contained in the documents for risk

assessment. A rating of “acceptable” indicates the study is scientifically sound and is useful for risk 

assessment. A “supplemental” rating indicates the data provide some information that can be useful for 

risk assessment. The studies may have certain aspects determined not to be scientifically acceptable 

(“supplemental: upgradeable”). If a study is rated as “supplemental: upgradeable,” the EPA always 

provides an indication of what is lacking or what can be provided to change the rating to “acceptable.” If 

there is simply a “supplemental” rating, the reviewer will often state that the study is not required by 40 

CFR Part 158. Both “acceptable” and “supplemental” studies may be used in the risk assessment process 

as appropriate. An “unacceptable” rating indicates that new data must be submitted.

For the acute toxicity data requirements, Toxicity Categories are assigned based on the hazard(s)

identified from studies and/or other information submitted to the EPA in support of a pesticide

registration. The active ingredient or particular product is classified into Toxicity Category I, II, III, or 
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IV, where Toxicity Category I indicates the highest toxicity and Toxicity Category IV indicates the 

lowest toxicity (see section II.B. of U.S. EPA (2014d)). 

A. Product Analysis Assessment (40 CFR § 158.2120)

BioProdex fulfilled all product analysis data requirements for TMGMV U2. Refer to Tables 1 and 2 in 

Appendix A for a summary of the data requirements, including both generic and product-specific 

information. 

B. Human Health Assessment (40 CFR § 158.2140)

1. Toxicity

BioProdex fulfilled all toxicology data requirements for TMGMV U2. Acceptable Tier I mammalian 

toxicology scientific rationale and literature support registration of the TMGMV U2 pesticide product. 

The EPA is not requiring Tier II and Tier III studies for TMGMV U2 based on the acceptability of the 

information provided by BioProdex for Tier I.

For a summary of the generic toxicology data requirements described in sections IV(B)(1)(a) and 

IV(B)(1)(b) of this document, as well as additional product-specific data submitted to support the 

individual registration, refer to Table 3 in Appendix A.

a. Acute Toxicity/Pathogenicity – Tier I

Acute Oral Toxicity/Pathogenicity (Harmonized Guideline 885.3050; Master Record Identification 

Numbers (MRID Nos.) 467416-02, 469187-01, 479232-01, and 480296-01): To fulfill this data 

requirement, BioProdex submitted supporting scientific rationale and public literature that show plant 

viruses, including TMGMV U2, are found in food ingested daily by humans and animals and that no 

known adverse effects or deaths have occurred in any species as a result of such dietary exposures. The 

EPA believes that this information indicates that this virus would not be toxic, infective, or pathogenic 

through the oral route of exposure and, as a result, has waived acute oral toxicity/pathogenicity testing 

for TMGMV U2.

Acute Pulmonary Toxicity/Pathogenicity (Harmonized Guideline 885.3150; MRID Nos. 467416-02, 

469187-01, 479232-01, and 480296-01): To fulfill this data requirement, BioProdex submitted 

supporting scientific rationale and public literature that show plant viruses, including TMGMV U2, are 

ubiquitous in plants and are not known or expected to cause acute pulmonary toxicity, pathogenicity, or 

infectivity in mammals. Upon consideration of all this information, the EPA has waived acute 

pulmonary toxicity/pathogenicity testing for TMGMV U2.

Acute Injection Toxicity/Pathogenicity (Harmonized Guideline 885.3200): Not required because 

TMGMV U2 is a virus (refer to test note #2 of 40 CFR § 158.2140(d)).

Hypersensitivity Incidents (Harmonized Guideline 885.3400; MRID Nos. 467416-02, 469187-01, 

479232-01, and 480296-01): BioProdex reported that no hypersensitivity incidents, including 

immediate-type or delayed-type reactions of humans and domestic animals, occurred during research, 

development, or testing of TMGMV U2. Any future hypersensitivity incidents must be reported to the 
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EPA (refer to test note #3 of 40 CFR § 158.2140(d)).

Cell Culture (Harmonized Guideline 885.3500; MRID Nos. 467416-02, 469187-01, 479232-01, and 

480296-01): To fulfill this data requirement, BioProdex submitted scientific rationale and supported it 

with public literature. Tobamoviruses are unable to infect animal cells since the cell surface plays an 

important role in infection of animal cells; during infection, animal viruses interact specifically with 

receptors on the animal cell surface. Plant viruses, on the other hand, lack recognition for these receptors 

and only enter plant cells through open wounds or via cell-to-cell transfer through intercellular 

connections (Fraenkel-Court et al., 1988). There is one report in the literature of growing Tobacco 

mosaic virus (TMV; a different tobamovirus from the one that is the subject of this action) in cultured, 

immune-suppressed, monkey kidney cell lines (Atherton, 1968); however, this was an artificial system 

and does not indicate that plant viruses can normally replicate in or infect animal cells. Upon 

consideration of all this information, the EPA has waived cell culture testing for TMGMV U2.

b. Acute Toxicology and Subchronic Toxicity/Pathogenicity – Tier II;

 Reproductive Fertility Effects, Carcinogenicity, Immunotoxicity, and 

 Infectivity/Pathogenicity Analysis – Tier III

The EPA is not requiring Tier II and Tier III studies for TMGMV U2 based on the acceptability of the 

information provided by BioProdex for Tier I.

c. Endocrine Disruptors

As required by the Administrator under 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 wildlife similar to an effect produced by a “naturally 

occurring estrogen, or other such endocrine effects as the Administrator may designate.” 

FFDCA section 408(p)(4) authorizes the Administrator, by order, to exempt from the requirements of 

the Estrogenic Substances Screening Program a biologic substance or other substance if a determination 

is made that the substance is not anticipated to produce any effect in humans similar to an effect 

produced by a naturally occurring estrogenic substance. 

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 

chemicals identified for EDSP screening was published on June 14, 2013,1 and includes some pesticides 

scheduled for registration review and chemicals found in water. TMGMV U2 is not among the group of 

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

The EPA believes that TMGMV U2, the active ingredient described in this document, is a substance 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 TMGMV U2 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. 

1 See http://www.gpo.gov/fdsys/pkg/FR-2013-06-14/pdf/2013-14232.pdf for the second list of chemicals.

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

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

http://www.epa.gov/endo/.

2. Federal Food, Drug, and Cosmetic Act (FFDCA) Considerations

Section 408(c)(2)(A)(i) of FFDCA allows the EPA to establish an exemption from the requirement for a 

tolerance (the legal limit for a pesticide chemical residue in or on a food) only if the EPA determines that 

the exemption is “safe.” Section 408(c)(2)(A)(ii) of FFDCA defines “safe” to mean that “there is a 

reasonable certainty that no harm will result from aggregate exposure to the pesticide chemical residue, 

including all anticipated dietary exposures and all other exposures for which there is reliable 

information.” This includes exposure through drinking water and in residential settings but does not 

include occupational exposure. Pursuant to FFDCA section 408(c)(2)(B), in establishing or maintaining 

in effect an exemption from the requirement of a tolerance, the EPA must take into account the factors 

set forth in FFDCA section 408(b)(2)(C), which require the EPA to give special consideration to 

exposure of infants and children to the pesticide chemical residue in establishing a tolerance or tolerance 

exemption, and to “ensure that there is a reasonable certainty that no harm will result to infants and 

children from aggregate exposure to the pesticide chemical residue . . . .” Additionally, FFDCA section 

408(b)(2)(D) requires that the EPA consider “available information concerning the cumulative effects of 

[a particular pesticide’s] . . . residues and other substances that have a common mechanism of toxicity.”

The EPA performs a number of analyses to determine the risks from aggregate exposure to pesticide 

residues. First, the EPA determines the toxicity of the pesticide. Second, the EPA examines exposure to 

the pesticide through food, drinking water, and other exposures that occur as a result of pesticide use in 

residential settings.

Consistent with FFDCA section 408(b)(2)(D), the EPA reviewed the available scientific data and other 

relevant information on TMGMV U2, and considered its validity, completeness, and reliability, as well 

as the relationship of this information to human risk. The EPA also considered available information 

concerning the variability of the sensitivities of major identifiable subgroups of consumers, including 

infants and children.

Based on the acute toxicity/pathogenicity information discussed previously and presented in Table 3 in 

Appendix A, the data required for a FFDCA risk assessment for TMGMV U2 have been fulfilled.

a. Aggregate Exposure

In examining aggregate exposure, FFDCA section 408 directs the EPA to consider available information 

concerning exposures from the pesticide residue in food and all other non-occupational exposures, 

including drinking water from ground water or surface water and exposure through pesticide use in 

gardens, lawns, or buildings (residential and other indoor uses).

Food Exposure and Risk Characterization: Virus-infected food plants have always been a part of the 

human diet and domestic animal food supply (Beemster and de Bokx, 1987; Dewan and Pearson, 1995; 

Jones et al., 1934; McKinney, 1929; Palukaitis, 1991; Provvidenti and Gonsalves, 1984). Most plants 

may be infected by at least one virus, and components of plant viruses are often found in the produce of 
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crop plants. Even plants that show no disease symptoms are often found to be infected with viruses 

(Fulton, 1986; Jones et al., 1934). In addition, a common agricultural practice used since the 1920s for 

protection against viral disease involves intentionally inoculating healthy plants with a mild form of a 

virus in order to prevent infection by a more virulent form (Fulton, 1986). A great deal of information 

supports the ubiquitous appearance of plant viruses in foods and, to date, there have been no reports of 

adverse human or animal health effects associated with consumption of plant viruses in food.

Furthermore, applications of TMGMV U2, which are limited to pastures and wooded areas that are 

fenced to contain grazing animals, are not expected to result in increased exposures of the active 

ingredient to the general population. The only residues anticipated on food with this limited use site are 

on grass, grass hay, and nongrass animal feeds (e.g., alfalfa and clover). These residues on grass, grass 

hay, and nongrass animal feeds would be incidental to applications to the target plant (tropical soda 

apple), given that grass and the nongrass animal feeds are not hosts for TMGMV U2 and that TMGMV 

U2 cannot infect or replicate in grass or in the nongrass animal feeds. In the remote likelihood that

TMGMV U2 is present in food, supporting scientific literature indicates that no toxicity, pathogenicity, 

or infectivity is likely to occur with any food exposure resulting from the use of this microbial herbicide

when applied in accordance with label directions and good agricultural practices (see section IV(B)(1)(a) 

of this document and Table 3 in Appendix A).

Drinking Water Exposure and Risk Characterization: TMGMV U2 is not intended for use in drinking 

water. In the unlikely event that TMGMV U2 reaches water consumed by humans (e.g., through spray 

drift), for the reasons enumerated previously, the EPA concludes that no toxicity, pathogenicity, or 

infectivity is likely to occur with any drinking water exposure resulting from the use of this microbial 

herbicide when applied in accordance with label directions and good agricultural practices (see section 

IV(B)(1)(a) of this document and Table 3 in Appendix A).

Non-occupational, Residential Risk Characterization: Dermal or inhalation exposure to the general 

population due to use of TMGMV U2 is not likely to occur, based on the limited use site and application 

methods. Moreover, the general population, including infants and children, are exposed to plant viruses 

daily in food with no known adverse effects ever being reported. Therefore, the EPA concludes that, 

should there be non-occupational, non-dietary exposures to TMGMV U2, such exposures would pose no 

risks to the general population, including infants and children (see section IV(B)(1)(a) of this document 

and Table 3 in Appendix A).

b. Cumulative Effects from Substances with a Common Mechanism of Toxicity

Section 408(b)(2)(D)(v) of FFDCA requires that, when considering whether to establish, modify, or 

revoke a tolerance, the EPA consider “available information concerning the cumulative effects of [a 

particular pesticide’s] . . . residues and other substances that have a common mechanism of toxicity.”

The EPA has not found TMGMV U2 to share a common mechanism of toxicity with any other 

substances, and TMGMV U2 does not appear to produce a toxic metabolite. For the purposes of the 

tolerance action, therefore, the EPA has assumed that TMGMV U2 does not have a common mechanism 

of toxicity with other substances. Following from this, therefore, the EPA concludes that there are no 

cumulative effects associated with TMGMV U2 that need to be considered. For information regarding 

the EPA’s efforts to determine chemicals that have a common mechanism of toxicity and to evaluate the 

cumulative effects of such chemicals, see the EPA’s website at 

http://www.epa.gov/pesticides/cumulative.
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c. Determination of Safety for the U.S. Population, Infants and Children

U.S. Population: For all of the reasons discussed previously, there is reasonable certainty that no harm 

will result to the U.S. population, including infants and children, from aggregate exposure to residues of

TMGMV U2. This includes all anticipated dietary exposures and all other exposures for which there is 

reliable information.

Infants and Children: FFDCA section 408(b)(2)(C) provides that the EPA shall apply an additional 

tenfold (10X) margin of safety for infants and children in the case of threshold effects to account for 

prenatal and postnatal toxicity and the completeness of the database on toxicity and exposure, unless the 

EPA determines based on reliable data that a different margin of safety will be safe for infants and 

children. This additional margin of safety is commonly referred to as the Food Quality Protection Act 

Safety Factor. In applying this provision, the EPA either retains the default value of 10X or uses a 

different additional safety factor when reliable data available to the EPA support the choice of a different 

factor. Humans, including infants and children, have been exposed to plant viruses through food, where 

they are commonly found, with no known or reported adverse effects. As discussed above, the EPA has 

concluded that TMGMV U2 is not toxic, pathogenic, or infective to mammals, including infants and 

children. Because there are no threshold levels of concern to infants, children, and adults when TMGMV 

U2 is used according to label directions and good agricultural practices, the EPA concludes that no 

additional margin of safety is necessary to protect infants and children.

3. Occupational Exposure and Risk Characterization

Worker exposure to TMGMV U2 is not expected to pose any undue risk. Regardless, the EPA is 

requiring appropriate protective clothing and precautionary statements on the pesticide product label to 

mitigate any potential risks to pesticide handlers and applicators due to prolonged and/or multiple 

exposures. Individuals working with TMGMV U2 to treat tropical soda apple are directed to wear a 

long-sleeved shirt, long pants, socks, shoes, waterproof gloves, and a dust/mist filtering respirator 

meeting NIOSH standards of at least N-95, R-95, or P-95. For future TMGMV U2 pesticide products, 

the EPA may require additional protective clothing (e.g., eyewear), other than the standard described 

above, on a product-specific basis. 

4. Human Health Risk Characterization

The EPA considered human exposure to TMGMV U2 in light of the standard for registration in FIFRA 

and the relevant safety factors in FFDCA. When the TMGMV U2 pesticide product is applied as a postemergent herbicide to tropical soda apple in accordance with the EPA’s approved labeling, the EPA has 

determined that no unreasonable adverse effects to human health are expected and that there is a 

reasonable certainty that no harm will result to the U.S. population, including infants and children.

C. Environmental Assessment (40 CFR § 158.2150)

The EPA found that scientific rationale and nontarget plant studies submitted by BioProdex are 

sufficient to fulfill the nontarget organism data requirements and for risk assessment purposes. Further 

testing of nontarget organisms at higher tier levels (i.e., Tiers II, III, and IV) is not required. The EPA 

performed an environmental risk assessment based on information provided by BioProdex. Provided that 
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limited use sites and application methods, mitigating label language, and certain manufacturing process 

steps are in place, the EPA has determined that unreasonable adverse effects to nontarget organisms are 

not expected from the proposed pesticidal uses of TMGMV U2. Moreover, the EPA made a “No Effect” 

determination for direct and indirect effects to federally listed, threatened and endangered species and 

their designated critical habitats resulting from these same proposed pesticidal uses. 

For a summary of the generic data requirements described in sections IV(C)(1) of this document, refer to 

Table 4 in Appendix A.

1. Ecological Exposure and Risk Characterization 

The active ingredient in SolviNix® LC is TMGMV U2, a naturally occurring plant virus. TMGMV 

occurs widely in the U.S., primarily in Solanaceae (nightshade family) plants and especially in tree 

tobacco (Nicotinia glauca), some commercial tobacco (Nicotinia tabacum), and pepper (Capsicum spp.) 

varieties. This virus is mechanically transmitted and spreads by physical contact; it is not vector 

transmitted or seedborne.

SolviNix® LC is intended for use against a single target weed (tropical soda apple, Solanum viarum) in 

which TMGMV U2 elicits a lethal hypersensitive response that produces wilting and death of the entire 

tropical soda apple plant, including the roots. Use sites are restricted to pastures and wooded areas that 

are fenced to contain grazing animals, and applications are to be made only by backpack sprayer or a 

dedicated wiper system. Use according to the proposed label is expected to minimize exposure and 

therefore risk to nontarget organisms.

a. Birds (Harmonized Guidelines 885.4050 and 885.4100) (MRID Nos. 467416-02 and 

478955-03)

TMGMV U2 is a plant virus and is not known to infect or produce toxicity in birds. Due to the 

application methods and low use rates, direct avian exposure is expected to be extremely limited. 

SolviNix® LC is to be applied prior to tropical soda apple flowering, which would prevent any exposure 

via fruit. BioProdex’s search of the public literature found no information on adverse effects of 

TMGMV or any other tobamovirus on avian species. Furthermore, TMGMV was not found on any list 

of avian pathogens or in a volume on avian viruses (Ritchie, 1995). Chickens can be immunized with 

purified tobamoviruses for the production of antisera without developing infection or toxic reactions. 

The optimal temperature for replication of tobamoviruses in plants generally ranges from 24oC to 35oC 

and, in tests conducted by BioProdex, typical hypersensitive death of tropical soda apple did not develop 

in plants maintained at ˃32oC (normal avian body temperature is approximately 40oC to 42oC).

b. Wild Mammals (Harmonized Guideline 885.4150) (MRID Nos. 467416-02 and 

478955-03) 

TMGMV U2 is a plant virus and is not known to infect or produce toxicity in mammals. Due to the 

application methods and low use rates, direct exposure to wild mammals is expected to be extremely 

limited. Mammals are not known to eat the tropical soda apple foliage, which is covered with sharp 

thorns, and the pre-flowering application of SolviNix® LC kills the plant prior to formation of the fruit. 

BioProdex’s search of the public literature found no information on adverse effects of TMGMV or any 

other tobamovirus on mammalian species, and TMGMV was not found on any list of mammalian
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pathogens or in a standard reference on plant viruses (Hull, 2002). Wild mammals, particularly 

herbivores, are naturally exposed to plant viruses such as TMGMV and other tobamoviruses without any 

adverse effects. Rabbits, mice, goats, and horses can be immunized with purified tobamoviruses for

antiserum production without causing toxic reactions or infection. The optimal temperature for 

replication of tobamoviruses in plants generally ranges from 24oC to 35oC and, in tests conducted by 

BioProdex, typical hypersensitive death of tropical soda apple did not develop in plants maintained at 

˃32oC (normal mammalian body temperature is approximately 37oC). 

c. Freshwater Fish (Harmonized Guideline 885.4200) (MRID Nos. 467416-02 and 

478955-03)

TMGMV U2 is a plant virus and is not known to infect or produce toxicity in fish. SolviNix® LC will 

not be applied in aquatic sites, since tropical soda apple does not grow or survive in wetlands. The low 

application rates and methods of application will limit the amount of pesticide product reaching

nontarget sites, making direct exposure to freshwater fish extremely limited. No aquatic plant has been 

found to be susceptible to TMGMV. BioProdex’s search of the public literature found no information on 

adverse effects of TMGMV or any other tobamovirus on fish. Furthermore, TMGMV was not found on 

any list of fish pathogens, and no mention of toxicity to fish was found in either of two standard 

reference books (Wolf, 1988; Woo and Bruno, 1999). There are no reports of isolation of TMGMV from 

water from streams, ponds, or lakes. BioProdex conducted a study in which purified TMGMV U2 was 

diluted with sterile deionized water, tap water, or lake water stored at room temperature. Nicotiana 

sylvestris plants (a local lesion host to TMGMV U2) were inoculated with the stored solutions after 19 

days and monthly thereafter for one year. Local lesions were counted 3 to 5 days after each inoculation. 

At the end of one year, the number of lesions/inoculation ranged from 0 to 38 for TMGMV U2 in tap 

water, 1 to 168 for TMGMV U2 in deionized water, and 0 to 2 for TMGMV U2 in lake water. 

BioProdex concluded that TMGMV U2 is unlikely to persist and remain infective in natural waters 

where microbial activity and other factors contribute to its degradation. 

d. Freshwater Invertebrates (Harmonized Guideline 885.4240) (MRID Nos. 467416-02 and 

478955-03)

TMGMV U2 is a plant virus and is not known to infect or produce toxicity in freshwater aquatic

invertebrates. SolviNix® LC will not be applied in aquatic sites, since tropical soda apple does not grow 

or survive in wetlands. The low application rates and methods of application will limit the amount of 

pesticide product reaching nontarget sites, making direct exposure to freshwater aquatic invertebrates

extremely limited. No aquatic plant has been found to be susceptible to TMGMV. BioProdex’s search of 

the public literature found no information on adverse effects of TMGMV or any other tobamovirus on 

freshwater aquatic invertebrates. Furthermore, TMGMV was not found on any list of invertebrate

pathogens. There are no reports of isolation of TMGMV from water from streams, ponds, or lakes, and 

BioProdex’s testing (see freshwater fish, directly above) indicates that TMGMV U2 is unlikely to persist 

and remain infective in natural waters. 

e. Estuarine/Marine Fish and Invertebrates (Harmonized Guideline 885.4280) (MRID Nos. 

467416-02 and 478955-03)

TMGMV U2 is a plant virus and is not known to infect or produce toxicity in estuarine/marine fish and

invertebrates. SolviNix® LC will not be applied in aquatic sites, since tropical soda apple does not grow 
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or survive in wetlands. The low application rates and methods of application will limit the amount of 

pesticide product reaching nontarget sites, making direct exposure to estuarine/marine fish and 

invertebrates extremely limited. No aquatic plant has been found to be susceptible to TMGMV.

BioProdex’s search of the public literature found no information on adverse effects of TMGMV or any 

other tobamovirus on estuarine/marine fish and invertebrates. Furthermore, TMGMV was not found on 

any list of fish or invertebrate pathogens. There are no reports of isolation of TMGMV from water from 

streams, ponds, or lakes, and BioProdex’s testing (see freshwater fish, directly above) indicates that 

TMGMV U2 is unlikely to persist and remain infective in natural waters. 

f. Nontarget Plants (Harmonized Guideline 885.4300) (MRID Nos. 467416-04, 478955-04, 

491377-01, and 492315-01)

In a nontarget plant study, over 400 plant species and varieties representing 61 families were tested to 

determine their susceptibility to TMGMV U2. Seedlings were hand-inoculated with either TMGMV U2 

or a sodium phosphate buffer control and observed over time for hypersensitive lesions on the inoculated 

leaves and for systemic symptoms on new growth. Additionally, new growth was tested for TMGMV U2 

using enzyme-linked immunosorbent assay (ELISA). Of the plants tested, 57.70% were immune (no 

symptoms or infection), 11.03% were resistant (hypersensitive local lesions), 8.74% were asymptomatic 

but positive in ELISA, 14.94% were susceptible (mild, systemic chlorosis), and 7.59% were highly 

susceptible (severe damage or death). All the highly susceptible plants were members of the Solanaceae 

family. Only 2% of plants (seven species representing five unrelated families) outside the Solanaceae 

family were susceptible to TMGMV U2. 

Since TMGMV U2 and other plant viruses can infect certain nontarget plants, BioProdex has agreed to 

limit SolviNix® LC’s use sites to pastures and wooded areas that are fenced to contain grazing animals 

and the methods of application to backpack sprayers and dedicated wiper systems to reduce exposure. 

Further, the SolviNix® LC label bears (and must continue to bear) the following mitigating language:

(1) “The virus in SolviNix® LC has no natural means of spread other than by physical and abrasive 

contact between infected and healthy plants. A remote possibility is through workers (via 

contaminated clothes, shoes, hands) and contaminated application equipment. To prevent 

unwanted virus spread, avoid contacting skin and clothing with SolviNix® LC; thoroughly wash 

skin with soap and water and clothes with laundry detergent after handling SolviNix® LC; and 

thoroughly wash application equipment after using SolviNix® LC. See the EQUIPMENT 

CLEANING INSTRUCTIONS section for more details on how to properly wash application 

equipment.”

(2) “Stop any pruning or mechanical activities in treated areas, such as mowing or tillage, 48 hours 

before and after application of SolviNix® LC.”

(3) “May infect some non-woody flowering plants, including Solanaceous crop plants (eggplant, 

pepper, tobacco, and tomatillo).”

(4) “Apply only when tropical soda apple plants are actively growing.”

(5) “Do not apply within 300 feet of greenhouse and grafting operations.”
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(6) “Spray directly at the target plant – Avoid any crops and nontarget plants.”

(7) “Do not re-use the spray equipment for other uses without thorough cleaning as specified.”

(8) “Do not apply this product through any type of irrigation system.”

(9) “For any surviving treated TSA plants, re-apply according to label instructions. If there are still 

surviving plants, consider other means of control (i.e., mechanical or chemical), consult local 

extension recommendations, and contact the registrant. The registrant will notify EPA under 

FIFRA 6(a)(2) for assessment of pesticide resistance in tropical soda apple.”

Finally, BioProdex is implementing particular manufacturing process steps to ensure that no other plant 

viruses are introduced into SolviNix® LC.

g. Nontarget Insects (Harmonized Guideline 885.4340) and Honey Bees (Harmonized 

Guideline 885.4380) (MRID Nos. 467416-02 and 478955-03)

TMGMV U2 is a plant virus and is not known to infect or produce toxicity in insects. Nontarget insects, 

including honey bees, are naturally exposed to plant viruses, including tobamoviruses. BioProdex’s 

search of the public literature found no information on adverse effects of TMGMV or any other 

tobamovirus on insects or honey bees. TMGMV was not found in any list of insect or honey bee 

pathogens or in a standard reference on plant virology (Hull, 2002). A study cited by BioProdex reported 

that bumble bees transmitted TMV from tomato to tomato under greenhouse conditions, but there was 

no mention of toxicity to the insect. Due to the application methods and low use rates, direct exposure of 

TMGMV U2 to nontarget insects and honey bees is expected to be extremely limited. 

h. Conclusions for Nontarget Organisms

Based on the expected lack of exposure and data demonstrating no effects, as discussed above, 

unreasonable adverse effects to nontarget organisms are not anticipated as a result of the proposed use

patterns of the SolviNix® LC pesticide product, containing TMGMV U2, as labeled. 

2. Environmental Fate Data 

As the rationale, literature, and data provided are sufficient to fulfill the Tier I nontarget organism data 

requirements and allow for nontarget organism risk assessment for TMGMV U2, the EPA is not 

requiring testing at higher tier levels (i.e., Tiers II, III, and IV). 

3. Threatened and Endangered Species Assessment

Since the EPA has determined that no effects are anticipated to nontarget species from TMGMV U2 in 

SolviNix® LC as a result of the proposed labeled uses, effects to federally listed threatened and

endangered species and their designated critical habitats are also not expected. Therefore, a “No Effect” 

determination is made for direct and indirect effects to federally listed, threatened and endangered 

species and their designated critical habitats for the proposed pesticidal uses of TMGMV U2, as labeled.
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V. 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—with respect to the development, 

implementation, and enforcement of environmental laws, regulations, and policies. Fair treatment means 

that no group of people, including racial, ethnic, or socioeconomic groups, should bear a

disproportionate share of the negative environmental consequences resulting from industrial, municipal, 

and commercial operations or the execution of federal, state, local, and tribal environmental programs 

and policies. Meaningful involvement means that (1) potentially affected community residents have an 

appropriate opportunity to participate in decisions about a proposed activity that will affect their 

environment and/or health; (2) the public’s contribution can influence the regulatory agency’s decision; 

(3) the concerns of all participants involved will be considered in the decision-making process; and (4) 

the decision-makers seek out and facilitate the involvement of those potentially affected. The EPA has 

this goal for all communities and persons across the United States. 

To help address potential environmental justice issues, during the 15-day public participation comment 

period, the EPA sought information on any groups or segments of the population who, as a result their 

location, cultural practices, or other factors, may have atypical, unusually high exposure to TMGMV U2, 

compared to the general population. The EPA received no public comments on this particular matter.

For additional information regarding environmental justice issues, please visit the EPA’s website at 

http://www.epa.gov/compliance/environmentaljustice/index.html.

VI. RISK MANAGEMENT DECISION

Section 3(c)(5) of FIFRA permits for the registration of a pesticide provided that all the following 

determinations are made:

(1) Its composition is such as to warrant the proposed claims for it;

(2) Its labeling and other material required to be submitted comply with the

 requirements of FIFRA;

(3) It will perform its intended function without unreasonable adverse effects on 

 the environment; AND

(4) When used in accordance with widespread and commonly recognized 

 practice, it will not generally cause unreasonable adverse effects on the 

 environment.

To satisfy criterion 1, the EPA understands that TMGMV U2 is well known to have herbicidal 

capabilities. The EPA has no knowledge that would contradict the claims made on the SolviNix® LC

label, and this pesticide product is not expected to cause unreasonable adverse effects on the

environment when used according to its label instructions. Criterion 2 is satisfied by the product label, as 

well as the data and information presented in this document. It is believed that the TMGMV U2

pesticide product will not cause any unreasonable adverse effects on the environment, and SolviNix® LC

is likely to control tropical soda apple, satisfying criterion 3. Criterion 4 is satisfied in that the TMGMV 

U2 pesticide product is not expected to cause unreasonable adverse effects when used according to label 

instructions. Therefore, the EPA believes SolviNix® LC, containing TMGMV U2 as a new active 
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ingredient, is eligible for registration under FIFRA section 3(c)(5) for the labeled uses. 

VII. ACTIONS REQUIRED OF THE REGISTRANT

A. Final Printed Labeling

Before releasing the pesticide product containing TMGMV U2 for shipment, BioProdex is required to 

provide appropriate final printed labeling to the EPA.

B. Terms of Registration

No additional data are being required as terms of the SolviNix® LC registration.

C. Reporting of Adverse Effects and Hypersensitivity Incidents

Notwithstanding the information stated in the previous sections, it should be clearly understood that 

certain specific data are required to be reported to the EPA as a requirement for maintaining the federal 

registration for a pesticide product. A brief summary of these types of data are described below.

Reports of all incidents of adverse effects to the environment must be submitted to the EPA under the 

provisions stated in FIFRA section 6(a)(2). Additionally, all incidents of hypersensitivity (including both 

suspected and confirmed incidents) must be reported to the EPA under the provisions of 40 CFR § 

158.2140(d).
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VIII. GLOSSARY OF ACRONYMS AND ABBREVIATIONS

ATCC American Type Culture Collection

BRAD Biopesticides Registration Action Document

CFR Code of Federal Regulations

EDSP Endocrine Disruptor Screening Program

ELISA enzyme-linked immunosorbent assay

EP end-use pesticide product

EPA United States Environmental Protection Agency 

FFDCA Federal Food, Drug, and Cosmetic Act

FIFRA Federal Insecticide, Fungicide, and Rodenticide Act

FR Federal Register

MOE margin of exposure

MRID No. Master Record Identification Number

NIOSH National Institute for Occupational Safety and Health

OPP Office of Pesticide Programs

PC Code Pesticide Chemical Code

PP Pesticide Petition

TGAI technical grade of the active ingredient

TMGMV Tobacco mild green mosaic tobamovirus

TMGMV U2 Tobacco mild green mosaic tobamovirus strain U2

TMV Tobacco mosaic virus

UF – IFAS University of Florida – Institute of Food and Agricultural Sciences

U.S. United States

USDA United States Department of Agriculture
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IX. BIBLIOGRAPHY

A. Studies Submitted to Support the Tobacco mild green mosaic tobamovirus strain U2 Pesticide 

Product Registration

MRID No. Study Information

467416-02 Braverman M. 2005. Group C – Toxicology Data Waiver Requests: Solvinix. Project 

Number: 0364B. Unpublished study prepared by Interregional Research Project No. 4, 18 

pages.

467416-03 Braverman M. 2005. Group D – Nontarget Data Waiver Request: Solvinix. Project 

Number: 03754B. Unpublished study prepared by Interregional Research Project No. 4, 69

pages.

467416-04 Braverman M. 2005. Group D – Nontarget Plant Studies: Solvinix. Project Number: 

0374B. Unpublished study prepared by Interregional Research Project No. 4, 29 pages.

467588-01 Braverman M. 2005. Group A – Product Analysis Test Guidelines: Solvinix (Amended 

Report). Unpublished study prepared by Interregional Research Project No. 4, 24 pages.

469187-01 Braverman M. 2006. Group C – Toxicology Data Waiver Requests: Solvinix. Project 

Number: 0364B. Unpublished study prepared by Interregional Research Project No. 4, 22 

pages.

478955-01 Braverman M. 2009. Solvinix: Group A – Product Analysis Test Guidelines 

(Amendment). Project Number: IR/4/PR/NO/0364B. Unpublished study prepared by

Interregional Research Project No. 4, 33 pages.

478955-03 Braverman M. 2009. Solvinix: Group D – Nontarget Data Waiver Request (Amendment). 

Project Number: IR/4/PR/NO/0364B. Unpublished study prepared by Interregional 

Research Project No. 4, 102 pages.

478955-04 Braverman M. 2009. Solvinix: Group D – Nontarget Plant Studies (Amendment). Project 

Number: IR/4/PR/NO/0364B. Unpublished study prepared by Interregional Research 

Project No. 4, 27 pages.

479232-01 Braverman M. 2009. Group C – Toxicology Data Waiver Requests: Solvinix. Project 

Number: 0364B. Unpublished study prepared by Interregional Research Project No. 4, 18 

pages.

480296-01 Braverman M. 2010. Group C – Toxicology Data Waiver Requests: Solvinix 

(Amendment). Project Number: 0364B. Unpublished study prepared by Interregional 

Research Project No. 4, 18 pages.
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MRID No. Study Information

491377-01 Charudattan R, Braverman M. 2013. Solvinix: Tobacco Mild Green Mosaic Virus. Project 

Number: 0364B. Unpublished study prepared by BioProdex, Inc., and Interregional 

Research Project No. 4, 451 pages.

492315-01 Braverman M. 2013. Supplement Information. Amendment #1 to MRID No. 491377-01: 

Tobacco Mild Green Mosaic Virus (Administrative Volume). Project Number: 

IR/4/PR/NO/0364B. Unpublished study prepared by Interregional Research Project No. 4, 

110 pages.

494002-01 Charudattan R, Braverman M. 2014. Solvinix, Tobacco Mild Green Mosaic Tobamovirus: 

TMGMV U2. Project Number: 0364B. Unpublished study prepared by BioProdex, Inc.,

and Interregional Research Project No. 4, 90 pages.

494291-01 Charudattan R, Braverman M. 2014. Solvinix, Tobacco Mild Green Mosaic Tobamovirus: 

TMGMV U2 – Supplement to MRID Nos. 491377-01, 491377-02, 492315-01, and 

494002-01. Project Number: 0364B. Unpublished study prepared by BioProdex, Inc., and 

Interregional Research Project No. 4, 7 pages.

B. Environmental Protection Agency Risk Assessment Memoranda

U.S. EPA. 2014a. SolviNixTM LC Containing Tobacco Mild Green Mosaic Virus, ATCC PV-1200. 

Memorandum from J.V. Gagliardi, Ph.D. through J.L. Kough, Ph.D. to J. Kausch, dated March 13, 

2014.

U.S. EPA. 2014b. SolviNixTM LC Containing Tobacco Mild Green Mosaic Virus, ATCC PV-1200. 

Memorandum from J.V. Gagliardi, Ph.D. through S. Borges to J. Kausch, dated July 2, 

2014.

U.S. EPA. 2014c. SolviNixTM LC Containing Tobacco Mild Green Mosaic Virus, ATCC PV-1200. 

Memorandum from J.V. Gagliardi, Ph.D. through J.L. Kough, Ph.D. to J. Kausch, dated July 3, 

2014.

 

U.S. EPA. 2010. SolviNixTM LC Containing Tobacco Mild Green Mosaic Virus, ATCC PV-1200. 

Memorandum from J.V. Gagliardi, Ph.D. through J.L. Kough, Ph.D. to J. Kausch, dated November 

9, 2010.

U.S. EPA. 2006a. Solvinix Containing TMGMV (Tobacco Mild Green Mosaic Tobamovirus). 

Memorandum from J.V. Gagliardi, Ph.D. through J.L. Kough, Ph.D. to R. Edelstein, Ph.D., dated 

May 23, 2006.

U.S. EPA. 2006b. Review of Environmental Effects Data and Justifications for Data Waivers Submitted 

in Support of BioProdex, Inc.’s Solvinex [sic] Bioherbicide, Which Contains the Active Ingredient

TMGMV. Memorandum from T. Milofsky through Z. Vaituzis, Ph.D. to R. Edelstein, Ph.D., dated 

June 21, 2006. 
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U.S. EPA. 2006c. Replacement Data Waiver Reviews for Solvinix Containing TMGMV (Tobacco Mild 

Green Mosaic Tobamovirus). Memorandum from J.V. Gagliardi, Ph.D. through J.L. Kough, Ph.D. to 

R. Edelstein, Ph.D., dated September 7, 2006.

C. Other References

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Bald JG, Goodchild DJ. 1960. Tobacco mosaic virus in Nicotiana glauca. Phytopathology 50:497–499.

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Braverman M. 2010. Administrative Materials for Solvinix from M. Braverman of Interregional

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UF – IFAS. 2008. Solanum viarum Dunal. In: Identification and Biology of Nonnative Plants in 

Florida’s Natural Areas (2nd Edition, Pub. SP 257). Available from 

http://plants.ifas.ufl.edu/misc/pdfs/SP257/Solanum_viarum(SP257-125).pdf. 

 

USDA. 2014. Plants Species Profiles – Tropical Soda Apple (Last Modified July 1, 2014). Available 

from http://www.invasivespeciesinfo.gov/plants/tropicalsoda.shtml.

U.S. EPA. 2014d. Chapter 7 of the Label Review Manual (Precautionary Statements) (Revised July 

2014). Available from http://www2.epa.gov/sites/production/files/2014-

07/documents/chapter7_revised_final_0714.pdf.

Weber PVV. 1951. Inheritance of a necrotic-lesion reaction to a mild strain of tobacco mosaic virus.

Phytopathology 41:593–609.

Wetter C. 1989. Tobacco mild green mosaic virus. In: AAB Description of Plant Viruses No. 351. 

Available from http://www.dpvweb.net/dpv/showdpv.php?dpvno=351.

Wetter C. 1984. Serological identification of four tobamoviruses infecting pepper. Plant Disease

68:597–599.

Wolf K. 1988. Fish Viruses and Fish Viral Diseases. Comstock Publishing Association, Cornell 

University Press, Ithaca, New York.

Woo PTK, Bruno DW. 1999. Fish Diseases and Disorders, Volume 3, Viral, Bacterial and Fungal 

Infections. CABI Publishing, Oxon, United Kingdom.

Zettler FW, Nagel J. 1983. Infection of cultivated gesneriads by two strains of tobacco mosaic virus. 

Plant Disease 67:1123–1125.
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Biopesticides Registration Action Document

APPENDIX A. MICROBIAL PESTICIDES DATA REQUIREMENTS 

(40 CFR PART 158 – SUBPART V)

TABLE 1. Product Analysis Data Requirements for the Technical Grade of the Active Ingredient (TGAI), TMGMV U2, and Its Enduse Pesticide Product (EP), SolviNix® LC (40 CFR § 158.2120)

Harmonized 

Guideline 

Number 

Data Requirement

Results

MRID No. TGAI EP

885.1100 Product Identity N/A

Submitted data fulfill the requirement 

for product identity. SolviNix® LC 

contains 2.9% by weight TMGMV U2

(contains a minimum of 1.25 x 1016

virions per fluid ounce).

467588-01

478955-01

885.1200 Manufacturing Process Submitted data fulfill the requirement for manufacturing process.

467588-01

478955-01

491377-01

494002-01

494291-01

885.1250

Deposition of a Sample in 

a Nationally Recognized 

Culture Collection

TMGMV U2 is on deposit with 

the American Type Culture 

Collection in Manassas, Virginia 

under Accession Number PV1200.

N/A 467588-01

478955-01

885.1300

Discussion of Formation 

of Unintentional 

Ingredients

Submitted data fulfill the requirement for discussion of formation of 

unintentional ingredients.

467588-01

478955-01

885.1400 Analysis of Samples Submitted data fulfill the requirement for analysis of samples.

467588-01

478955-01

491377-01

492315-01

885.1500 Certification of Limits N/A

Limits listed on the confidential 

statement of formula are 

adequate/acceptable.

478955-01

491377-01
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TABLE 2. Physical and Chemical Characteristics for the Technical Grade of the Active Ingredient (TGAI), TMGMV U2, and Its Enduse Pesticide Product (EP), SolviNix® LC (40 CFR § 158.2120)

Harmonized 

Guideline Number Data Requirement Results MRID No. or 

TGAI EP Other Reference

830.6302 Color

See EP column.1

Light green (birefringent)

830.6303 Physical State Liquid Braverman (2010)

830.6304 Odor No odor

830.6313

Stability to Normal and Elevated 

Temperatures, Metals, and Metal 

Ions

Stable for greater than three

years, but the SolviNix® LC 

label will bear a date 

mandating that the product 

be sold or used one year 

from the day of the 

herbicide’s assay and batch 

certification. 

Braverman (2010)

478955-01

491377-01

492315-01

830.6317 Storage Stability 494002-01

830.6319 Miscibility N/A Water soluble

Braverman (2010)

830.6320 Corrosion Characteristics Not corrosive

830.7000 pH See EP column.1 5.0

830.7100 Viscosity N/A 1 poise

830.7300 Density/Relative Density/Bulk 

Density (Specific Gravity) See EP column.1 8.35 pounds/gallon

1 According to 40 CFR § 158.2120, these data are required for the TGAI. BioProdex provided data on the EP instead of the TGAI. The EPA 

 considers these EP data to be acceptable because no separate TGAI is produced in this case and because the TGAI is equivalent to the EP. See 

40 CFR § 158.30 and 40 CFR § 158.120(b)(5)(iii). 
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Biopesticides Registration Action Document

TABLE 3. Toxicology Data Requirements for the Technical Grade of the Active Ingredient (TGAI), TMGMV U2, and Its End-use 

Pesticide Product (EP), SolviNix® LC (40 CFR § 158.2140)

Harmonized

Guideline 

Number

Data Requirement

Results

MRID No.

TGAI EP

Tier I

885.3050 Acute Oral 

Toxicity/Pathogenicity

Testing waived based on BioProdex’s 

scientific rationale, which included 

references to scientific literature and 

showed that plant viruses, including

TMGMV U2, are found in food 

ingested daily by humans and animals 

with no known adverse effects or 

deaths as a result of such dietary 

exposures. 

Classification: Acceptable

N/A

467416-02

469187-01

479232-01

480296-01

885.3150 Acute Pulmonary 

Toxicity/Pathogenicity

Testing waived based on BioProdex’s 

scientific rationale, which included 

references to scientific literature and 

showed that plant viruses, including

TMGMV U2, are ubiquitous in plants 

and are not known or expected to cause 

acute pulmonary toxicity, 

pathogenicity, or infectivity in 

mammals. 

Classification: Acceptable

885.3200 Acute Injection 

Toxicity/Pathogenicity

Not required because TMGMV U2 is a 

virus (refer to test note #2 of 40 CFR § 

158.2140(d)). N/A

885.3400 Hypersensitivity

Incidents

BioProdex reported that no hypersensitivity incidents, including immediate-type or 

delayed-type reactions of humans and domestic animals, occurred during research, 

development, or testing of the TGAI/EP. Any future hypersensitivity incidents must 

be reported to the EPA (refer to test note #3 of 40 CFR § 158.2140(d)). 

467416-02

469187-01

479232-01

480296-01 885.3500 Cell Culture

Testing waived based on BioProdex’s 

scientific rationale, which included 

references to scientific literature and 

showed that plant viruses, including

TMGMV U2, enter plant cells only 

through open wounds or by cell-to-cell 

transfer and are unable to infect animal 

cells because they lack the cell surface 

binding site recognition common to 

animal viruses. 

Classification: Acceptable

N/A
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TABLE 3. Toxicology Data Requirements for the Technical Grade of the Active Ingredient (TGAI), TMGMV U2, and Its End-use 

Pesticide Product (EP), SolviNix® LC (40 CFR § 158.2140)

Harmonized

Guideline 

Number

Data Requirement

Results

MRID No.

TGAI EP

870.1100 Acute Oral Toxicity

N/A

Testing waived based on BioProdex’s 

scientific rationale, which included 

references to scientific literature and 

showed that plant viruses, including

TMGMV U2, are found in food ingested 

daily by humans and animals with no 

known adverse effects or deaths as a 

result of such dietary exposures, and 

because this formulation contains an inert 

ingredient that is not expected to be of 

toxicological concern (refer to test note 

#5 of 40 CFR § 158.2140(d)).

Classification: Acceptable

TOXICITY CATEGORY III

480296-01 870.1200 Acute Dermal 

Toxicity

Testing waived based on BioProdex’s 

scientific rationale, which included 

references to scientific literature and 

showed that plant viruses, including

TMGMV U2, are ubiquitous in plants 

and are not known or expected to cause 

acute dermal toxicity in mammals, and 

because this formulation contains an inert 

ingredient that is not expected to be of 

toxicological concern (refer to test note 

#5 of 40 CFR § 158.2140(d)).

Classification: Acceptable

TOXICITY CATEGORY III

870.1300 Acute Inhalation 

Toxicity

Testing waived based on BioProdex’s 

scientific rationale, which included 

references to scientific literature and 

showed that plant viruses, including

TMGMV U2, are ubiquitous in plants 

and are not known or expected to cause 

acute inhalation toxicity in mammals, and 

because this formulation contains an inert 

ingredient that is not expected to be of 

toxicological concern (refer to test note 

#5 of 40 CFR § 158.2140(d)).

Classification: Acceptable

TOXICITY CATEGORY III
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TABLE 3. Toxicology Data Requirements for the Technical Grade of the Active Ingredient (TGAI), TMGMV U2, and Its End-use 

Pesticide Product (EP), SolviNix® LC (40 CFR § 158.2140)

Harmonized

Guideline 

Number

Data Requirement

Results

MRID No.

TGAI EP

870.2400 Acute Eye Irritation

N/A

Testing waived based on BioProdex’s 

scientific rationale, which included 

references to scientific literature and 

showed that plant viruses, including

TMGMV U2, are ubiquitous in plants 

and are not known or expected to cause 

acute eye irritation in mammals, and 

because this formulation contains an inert 

ingredient that is not expected to be of 

toxicological concern (refer to test note 

#5 of 40 CFR § 158.2140(d)).

Classification: Acceptable

TOXICITY CATEGORY III 469187-01

479232-01

480296-01

870.2500 Primary Dermal 

Irritation

Testing waived based on BioProdex’s 

scientific rationale, which included 

references to scientific literature and 

showed that plant viruses, including

TMGMV U2, are ubiquitous in plants 

and are not known or expected to cause 

primary dermal irritation in mammals, 

and because this formulation contains an

inert ingredient that is not expected to be 

of toxicological concern (refer to test note

#5 of 40 CFR § 158.2140(d)).

Classification: Acceptable

TOXICITY CATEGORY III

Tiers II and III

Not required for TMGMV U2 based on the acceptability of the scientific rationale and literature provided by BioProdex for Tier I.
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TABLE 4. Nontarget Organism Toxicity and Environmental Fate Data Requirements for the Technical Grade of the Active 

Ingredient (TGAI), TMGMV U2 (40 CFR § 158.2150)

Harmonized Guideline 

Number Data Requirement Results MRID No.

Tier I

885.4050 Avian Oral Toxicity

Testing waived based on BioProdex’s scientific 

rationale, which included references to scientific 

literature and showed that plant viruses, including

TMGMV U2, are not known or expected to cause 

toxicity or pathology to any organism other than 

plants and possibly insect vectors.

Classification: Acceptable

467416-02

478955-03

885.4100 Avian Inhalation 

Toxicity/Pathogenicity

885.4150 Wild Mammal 

Toxicity/Pathogenicity

885.4200 Freshwater Fish 

Toxicity/Pathogenicity

885.4240 Freshwater Invertebrate 

Toxicity/Pathogenicity

885.4280 Estuarine/Marine Fish and 

Invertebrate Testing

885.4300 Nontarget Plant Testing

Some plants are susceptible to TMGMV U2. 

Limited use sites and application methods, 

mitigating label language, and certain 

manufacturing process steps will minimize risk to 

nontarget plants. 

Classification: Acceptable

467416-04

478955-04

491377-01

492315-01

885.4340 Nontarget Insect Testing

Testing waived based on BioProdex’s scientific 

rationale, which included references to scientific 

literature and showed that plant viruses, including 

TMGMV U2, are not known or expected to cause 

toxicity or pathology to any organism other than 

plants and possibly insect vectors.

Classification: Acceptable

467416-02

478955-03

885.4380 Honey Bee Testing

Tiers II, III, and IV

Not required for TMGMV U2 based on the acceptability of the scientific rationale, literature, and data provided by BioProdex for Tier I.
Tobacco mild green mosaic tobamovirus strain U2 (TMGMV U2) Page 31 of 31

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APPENDIX B. PESTICIDE PRODUCTS

EPA 

Registration 

Number

Registration 

Name

Percentage 

Active 

Ingredient

Formulation 

Type

Use Site(s) Method(s) of 

Application

Application Rate(s) Target Pest

81179-3 SolviNix® LC 2.9% End Use –

Liquid

Pastures and 

wooded areas that 

are fenced to 

contain grazing 

animals

High-pressure 

backpack 

sprayer and 

hand-held 

herbicide 

applicators

0.05 fluid ounce (1.5 

milliliters) of 

SolviNix® LC per 1 

gallon of water

Tropical soda apple 

(Solanum viarum)

0.34 fluid ounce (10 

milliliters) of 

SolviNix® LC per 6.5 

gallons of water

1.2 fluid ounce (35 

milliliters) of 

SolviNix® LC per 23 

gallons of water