Page 2 of 6 I Background

On March 20, 2014, the U.S. Environmental Pr otection Agency (EPA) received a proposed registration application from Va lent Biosciences Corporation (V alent) for a new use of VBC60347 Biological Insecticide Em ulsifiable Suspension (VBC-60347) to control army and pod worms in tomatoes and bell peppers in agri cultural fields and greenhouses. VBC-60347 is formulated as an emulsifiable suspension which contains 5.95% of the active ingredient (a.i.) methyl salicylate (CAS Number 119-36-8).

Methyl salicylate is classified as a biochemical pesticide and is the primary constituent in oil of wintergreen, a naturally fragrant oil. It is charac terized as a colorless, yellowish or reddish, oily liquid with the distinct odor and taste of wintergreen or gaultheria . Methyl salicylate is naturally

extracted via steam distillation of macerat ed leaves from the low growing plant, Gaultheria procumbens Lime. (fam. Ericaceae ) or from the bark of Betula lenta (Sweet Birch). Methyl salicylate can also be ma nufactured synthetically.

Methyl salicylate was first regist ered in 1972 for use as an animal repellant in impregnated twist tabs to be hung on plants to repel dogs and cats from flower gardens. A subsequent registration of methyl salicylate followed in 1996 as an insect repellent to be used as a constituent of food and feed packaging material to repel insects in stored commodities. This registration was considered to be a “food use,” and thus necessita ted the establishment of an exemption from the requirement of a tolerance (see 40 CFR §180.1189). Methyl salicylate also has a long history of use in consumer products as a counterirritant a nd as an analgesic for the management of aching and painful muscles and joints as well as suntan lotions (as an UV-absorber) and perfumery as a modifier of blossom fragrances (EPA, 2005).

The new proposed use put forth by Valent (V BC-60347 Biological Insecticide Emulsifiable Suspension) is intended for use as a foliar applic ation to tomatoes and bell peppers up to the flowering stage of growth, and is therefor e a non-food use. VBC-60347 is a highly selective insecticide for use against list ed caterpillars (larvae) of Le pidopterous insects. VBC-60347 is proposed for application as foliar spray using gr ound or handheld equipment to bell peppers and tomatoes in fields and or greenhouses at an appli cation rate of 1.0 to 4.0 pi nts/acre, up to a total of 16 pints per acre per season. Applications are to be applie d up to the flowering stage of growth and must not be applie d more frequently than every 5 days. The personal protective equipment (PPE) statement on the proposed label indicates all applicat ors and other handlers must wear long sleeved shirt and long pants, chemical resistant gloves, socks and shoes. Mixer/loaders and applicators must wear a dust/mist filtering respirator meeting NIOSH standards of at least N-95, R-95, or P-95. Repeated exposure to high concen trations of microbial proteins from the second active ingredient, Bacillus thuringiensis, subsp. kurstaki , strain ABTS351, listed on the proposed label can cau se an allergic sensitization.

This proposed new use represents the first use of methyl salicylate as delivered in a manner

where it is not enclosed in materials. On October 1, 2009, EPA announced a new policy to provide a more meaningful opportunity for the public to participate on major registration decisions before they occur. According to this policy, EPA provides a public comment period prior to making a registration decision for th e following types of a pplications: new active ingredients, first food use, first outdoor use, fi rst residential use; and any registration decisionsPage 3 of 6 for which the Agency believes there may be substa ntial public interest. The Agency believes that the new use proposed for methyl sali cylate falls into the category of “substantial public interest.”

2.0 Evaluation

In evaluating a pesticide regi stration application, the EPA pe rforms risk assessments to determine the potential of adverse effects ( i.e ., risk) resulting from expos ures associated with the proposed use. The assessments evaluate a produ ct’s potential to affe ct a wide range of nontarget organisms including humans, terrestrial, an d aquatic wildlife (plants and animals) as well as the environmental fate of the compound ( i.e ., how the chemical will move in the environment). On the basis of these assessments , EPA evaluates and approves language for each pesticide label to ensure the directions for use and safety measures are appropriate to mitigate any potential risk. In this way, the pesticide’s label helps to communicate essential limitations and mitigations that are necessary for public sa fety. In fact, the pest icide law has a provision

which indicates that it is a viola tion to use a pesticide in a way th at conflicts with the label.

2.1 Assessment of Risk to Human Health

2.1.1 Toxicity

EPA requires a wide range of studies in order to assess a pesticide. For methyl salicylate, the toxicological database is ade quate to support the assessment of risk to human health from pesticidal use on tomatoes a nd peppers, pre-flowering:

 Methyl salicylate is moderately acutely toxic by the oral route, but non-toxic by the

dermal route. It is a severe skin a nd eye irritant (Toxicity Category II).

 Subchronic studies indicate no to xic effects in 90-day oral, de rmal or inhalation studies. However, a No Observed Adverse Effect Level (NOAEL) for reproductive effects was established at 250 milligrams per kilograms (mg/kg) and a Lowest Observed Adverse Effect Level (LOAEL) was established at 500 mg/kg based on the decreased number of litters per breeding pair and reduced live litte r size. The available mutagenicity studies were negative.

 The evaluation of the chronic toxicity studies indicates that methyl salicylate is not carcinogenic.

2.1.2 Exposure

In the proposed new use of methyl salicylat e as a foliar spray on field and greenhouse preflowering tomatoes and peppers, th e potential for dietary exposure is negligible and this is considered by the Agency to be a non-food use based on the following:

 Residue data indicate that met hyl salicylate will not be pr esent on the crop at time of

harvest.

 Methyl salicylate has a half-life of le ss than two and a half hours on foliage.

 Methyl salicylate is readily biodegradable in screening te sts and may be expected to biodegrade in soils and surface waters.Page 4 of 6  Methyl salicylate is likely to hydrolyze in water, es pecially at alkaline pH.

Residential and occupational exposur e are also expected to be ne gligible for the proposed new

use:

 The VBC-60347 label is for agri cultural use only. The proposed product is not for use in

residential sites.

 The exposure to humans from the pesticidal use of methyl salicylate is expected to be minimal, compared with the widespread use of methyl salicylate as a flavoring ingredient

in foods.

 The low level of potential exposures (derma l and inhalation) duri ng the mixing/loading and application process of this biochemical ar e more than adequately mitigated by the use of personal protective equipment and precau tionary language statements placed on enduse product labels.

2.1.3 Human Health Conclusions

Although reproduction effects were seen for me thyl salicylate at a LOAEL of 500 mg/kg, significant human exposure to this biochemical is not expected unde r the conditions of current or proposed product use. Current products are ready to use, self-contained impregnated twist tabs and food packing material. The proposed product is a foliar spray for peppers and tomatoes preflowering with PPE required on the proposed product label and appropriate precautionary language statements, which mitigates the low level of potential exposure for the proposed new

use.

Acute toxicity studies performed on the propos ed end-use product (E P) “VBC-60347 Biological

Insecticide Emulsifiab le Suspension” (ai. Bacillus thuringiensis subsp . kurstaki , Strain ABTS351, 26.55% and Methyl Salicylate, 5.9%) demonstr ate labeling precautionary signal word must

be “CAUTION.”

Based on these considerations and those listed in the previously described hazard assessments, an assessment of an aggregate exposure for all pesticid al uses of methyl salicylate would result in minimal additional exposure beyond what consumers already receive from other uses. Expected exposure levels from these uses would be well be low defined acceptable levels, even considering methyl salicylate sensitivity to infants and children.

2.2 Ecological Exposure and Risk

The battery of tests required to assess the envi ronmental fate and ecological effects of methyl salicylate is complete. The biochemical is read ily biodegradable in scr eening tests and may be expected to biodegrade in soils and surface waters (HSDB, 1996). Moreover, methyl salicylate is likely to hydrolyze in water, es pecially at alkaline pH (HSDB, 1996). At pH 7.5, its hydrolysis half-life is estimated to be 14.1 days (HSDB, 1996). Methyl salicylate absorbs UV radiation >2990 nm and therefore may undergo direct photol ysis under environmental conditions (HSDB, 1996); the photolysis half-life wa s reported to be 48 minutes in one study (HSDB, 1996). In the atmosphere, methyl salicylate reacts with phot ochemically produced hydroxyl radicals with anPage 5 of 6 estimated rate constant of 11.6 x 10 -12 cm 3 /molecule. Assuming a hydroxyl radical concentration

of 5 x 10 -5 radicals/cm 3 , the half-life of methyl salicylate in the atmosphere would be 1.4 days (HSDB, 1996).

Ecotoxicity data on methyl salicyla te show that the compound is:

 slightly to practically non- toxic to avian species;

 slightly to practically non-toxic to fish;

 slight toxicity to a quatic invertebrates;

 not phytotoxic;

A contact toxicity study on honey b ees using the proposed EP showed no toxic effects (24-hr and

48-hr LD 50 for contact toxicity was great er than 125 μg ai/bee).

Non-target plant data requirements were addr essed with approved waiver rationales based upon 1) methyl salicylate’s high vapor pressure, which results in vola tilization and rapid losses from surfaces, 2) its demonstrated nontoxicity of th e compound to plants in the applicant-submitted efficacy studies, and 3) its natural occurances in many plant species.

Moreover, with regards to ecological toxicity, me thyl salicylate is currently released to the

environment in effluents and emissions as a re sult of it production, di sposal and use as a flavoring in foods and beverage s, as a fragrance agent in cosmetics and perfumes, as a pharmaceutical agent (counterirritant) in ointments and oral rinses, as a UV-absorber in suntan lotions, as a carrier for fabric dyes, and as a UV-stabilizer in acrylic resins. The Agency estimates that pesticidal use of methyl salicylate is very small in comparison to its current nonpesticidal uses. Therefore, the Agency believes that pesticidal use of met hyl salicylate, including the proposed new use as a foliar spray, will not cont ribute significantly to ecological exposure of

this biochemical.

4.0 Alternatives

Methyl salicylate can be us ed alone or alongside currently registered biochemical or conventional animal or insect repellents and plant growth regulators; methyl salicylate can be an important component of an Integrated Pest Management (IPM) system. The use of this biochemical animal and insect repellent and in secticide may displace an d reduce the amount of conventional active ingredients re quired for these purpos es. Growers may prefer to use methyl salicylate as a viable altern ative to conventional products si nce methyl salicylate products contain shorter Re-Entry Intervals (REI) and shor t half-life (less than two and a half hours on foliage).

5.0 Benefits and Public Comments

By definition alone, biochemicals are favorable when compared to currently registered

conventional alternatives because biochemicals ar e naturally-occurring subs tances (or substances structurally-similar and functionally identical to naturally-occurring substanc es) with a history of exposure to humans and the environment demons trating minimal toxicity and a non-toxic mode of action to the target pest(s). Benefits of bi ochemical pesticides as compared to conventionalPage 6 of 6 pesticides typically include lower toxicity pr ofiles for humans and non-target organisms, and faster degradation in the environment. As outline d above, methyl salicylate is a viable alternative to conventional animal and insect repellents and plant growth regulators du e to its low toxicity profile and half-life of less than two and a half hours on foliage.

On January 14, 2015, EPA published in the Federal Re gister a Notice of Receipt of the Valent application for registration of methyl salicylate as a fo liar spray and announced a public comment period of 30 days. No comments were rece ived in response to this Notice of Receipt.

6.0 Regulatory Decision

The Agency’s methyl salicylate database is co mprised of 40 studies and is considered to be complete. The proposed use of met hyl salicylate as a foliar spray on tomatoes and bell peppers in agricultural fields and greenhouse is well supported by this database . In consideri ng the assessed risk to human health and the environment, the Ag ency concludes that methyl salicylate meets the regulatory standard under the Federal Insecticid e, Fungicide and Rode nticide Act (FIFRA). There are no outstanding data requirements for th is biochemical. Therefore, the EPA is granting the unconditional registration of this use of methyl salicylate under Section 3(c)(5) of FIFRA.

One product will be registered: “VBC-60347 Biologica l Insecticide Emulsifiable Suspension” is an end-use product (EP) cont aining the active ingredient Bacillus thuringiensis subsp. kurstaki strain ABTS-351 in addition to methyl salicylate. Application of this produ ct is approved for use outdoors on tomato and pepper plants, pre-flower ing. The application ra te is 1.0-4.0 pints of product per acre, up to a total of 16 pints per acre per season. A pplication must not be made more frequently than every 5 days.

The risk assessments supporting this decisi on can be found at the following locations:

 Memorandum from Michael Rexrode to Gina Burnett. June 17, 2015. Regulatory docket EPA-HQ-OPP-2014-0898; Document ID: EPA-HQ-OPP-2014-0898-0002

 Exposure and Risk Considerations for Methyl Salicylate for use on Pre-flowering Bell Peppers and Tomatoes. September 3, 2015. Regulatory docket EPA-HQ-OPP-2014-0898; Document ID: EPA-HQ-OPP-2014-0898-0003

 Reregistration Eligibility Decision (RED) Document for Methyl Salicylate, United States Environmental Protection Agency (U.S . EPA). November, 2005. Available at: http://www.epa.gov/pesticides/reregis tration/REDs/methyl_salicylate_red.pdf

 Inert Reassessments: One Exemption from the Requirement of a Tolerance for Wintergreen oil (CAS Reg. No. 119-36-8). Me morandum from Pauline Wagner to Lois

A. Rossi. United States Environmental Pr otection Agency (U.S. EPA). June 8, 2006.

Available at: http://www.epa.gov/opprd001 /inerts/wintergreen.pdf