Registration Decision for a New Method of Delivery 

(First Foliar Spray Use) of Methyl Salicylate 

Update to the Previously Issued Methyl Salicylate 

Reregistration Eligibility Decision (RED) 

ofNovember, 2005 

Approved by: 

~ Robert McNally, Director 

Biopesticides and 

Pollution Prevention Division 

Date: 
1.0 Background 

On March 20, 2014. the U.S. Environmental Protection Agency (EPA) received a registration 

application from Valent Biosciences Corporation (Valent) for a new use of LEAP® Biological 

Insecticide Emulsifiable Suspension (LEA P®), formerly VBC-60347 Biological lnsectic ide 

Emulsifiable Suspension. to control army and pod worms in tomatoes and bell peppers in 

agricultural fie lds and greenhouses. LEAP® is formu lated as an emulsifiable suspension which 

contains 5.95% of the active ingredient (a.i.) methyl salicylate (CAS Number 11 9-36-8). 

Methyl salicylate is classified as a biochemical pesticide and is the primary constituent in oil of 

wintergreen, a natura ll y fragrant oil. It is characterized 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 macerated leaves from the low growing plant, Gaultheria 

procumhens Lime. (fam. Ericaceae) or from the bark of Betula lenta (Sweet Birch). Methyl 

salicylate can also be manufactured synthetically. 

Methyl sal icylate was first registered in 1972 for use as an animal repellant in impregnated twist 

tabs to be hung on plants to repel dogs and cats from tlower gardens. A subsequent registration 

of methyl salicylate fol lowed 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 necessitated the establishment of an exemption from the 

requirement of a tolerance (see 40 CFR § 180. 11 89). Methyl salicylate also has a long history of 

use in consumer products as a counterirritant and 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 

modifie r of blossom fragrances (EPA, 2005). 

The new use put forth by Valent (LEAP® Biological Insecticide Emulsifiable Suspension) is 

intended for use as a foliar application to tomatoes and bell peppers up to the flowering stage of 

growth. and is therefore a non-food use. LEAP® is a highly selective insecticide for use against 

listed caterpillars (larvae) of Lepidopterous insects. LEAP® is intended for application as foliar 

spray using ground or handheld equipment to bell peppers and tomatoes in fie lds and or 

greenhouses at an application rate of 1.0 to 4.0 pints/acre, up to a total of 16 pints per acre per 

season . Applications are to be applied up to the tlowering stage of growth and must not be 

applied more frequently than every 5 days. The personal protective equipment (PPE) statement 

on the label indicates that all applicators 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 fi ltering respirator meeting NIOSH standards of at least N-95, R-95, or P-95. 

Repeated exposure to high concentrations of microbial proteins from the second active 

ingredient, Bacillus thuringiensis, subsp. kurstaki, strain ABTS-35 1, listed on the label can cause 

an allergic sensitization. 

This new use of methyl salicylate represents the first use of methyl salicylate as de livered in a 

manner where it is not enclosed in materials. A copy of the product label and information 

relevant to EPA's risk assessment is available in Docket 10 EPA-HQ-OPP-2014-0898. 

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2.0 Eva luation 

In evaluating a pesticide registration application. the EPA assesses a wide va ri ety of pesticide 

specific information including where and how the pesticide is used. environmental fate (i.e .. 

what happens to the pesticide once it's applied). and tox icity studies (i.e .. ha7.ards) to determine 

the likelihood ofad ver e effects (i.e .. risk) from exposures assoc iated with th e usc of the product. 

The environmental fate properties of the pesticide arc characterized by EPA. Also. risk 

assessments are developed to evaluate the compound as to how it might affect a wide range or 

non-target organism including humans and terrestrial and aq uatic wildlife (plant and animals). 

On the basis of these as cssments, EPA evaluates and develops language lor each pesticide label 

to ensure the directi ons for usc and safety measures arc appropriate to mitigate any risks of 

concern. In this way. the pesticide label communicates to the user the essential limitations and 

mitigation measures to ensure no unreasonabl e adverse effects on human hea lth or the 

environment. Additiona lly, it is a FIFRA violation to use a pesticide in a way that in inconsistent 

with the label. 

2. 1 Assessment of Risk to Huma n Hea lth 

2. 1.1 Toxicity 

EPA requires a wide range of studies in order to assess a pesticide. For methyl salicylate, the 

toxicological database is adequate to support the assessment of risk to human health from 

pesti cidal use on tomatoes and peppers. pre-nowering: 

• Methyl salicylate is moderately acutely toxic by the oral route. but non-toxic by the 

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

• Subchronic studies indicate no toxic effects in 90-day oral. dermal or inhalation studies. 

However. a No Observed Adverse Effect Level (NOAEL) for reproducti ve effects was 

established at 250 milligrams per kilograms (mg/kg) and a Lowest Observed Adverse 

Effect Level (LOAEL) was establ ished at 500 mg/kg based on the decreased number of 

litters per breeding pair and reduced live litter size. The available mutagenicity studies 

were negative. 

• The evaluation of the chronic toxicity studies indicates that methyl salicylate is not 

carcinogenic. 

2.1.2 Exposu rc 

In the new use of methyl salicylate as a foliar spray on field and greenhouse pre-flowering 

tomatoes and peppers, the 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 methyl sal icy late wi II not be present on the crop at time of 

harvest. 

• Methyl salicylate has a half-life of less than two and a half hours on foliage. 

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• Methyl salicylate is readily biodegradable in screening tests and may be expected to 

biodegrade in soils and surface waters. 

• Methyl salicylate is likely to hydrolyze in water, especially at alkaline pH . 

Residential and occupational exposure are also expected to be negligible for the new use: 

• The LEAP® label is for agricultural use only. The 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 navoring ingredient 

in foods. 

• The low level of potential exposures (dermal and inhalation) during the mixing/loading 

and application process of this biochemical are more than adequately mitigated by the use 

of personal protective equipment and precautionary language statements placed on enduse product labels. 

2.1.3 Human Health Conclusions 

Although reproduction effects were seen for methyl salicylate at a LOAEL of 500 mg/kg, 

significant human exposure to this biochemical is not expected under the conditions of approved 

past or new product use. Previously approved registered products are ready to use, self-contained 

impregnated twist tabs and food packing material. The new product is a foliar spray for peppers 

and tomatoes pre-nowering with PPE required on the product label and appropriate 

precautionary language statements, ·which mitigates the low level of potential exposure for the 

new use. 

Acute toxicity studies performed on the end-use product (EP) LEAP® Biological Insecticide 

Emulsifiable Suspension (ai. Bacillus thuringiensis subsp. kurstaki, Strain ABTS-35 1, 26.55% 

and Methyl Salicylate, 5.9%) demonstrate labeling precautionary signal word must be 

"CAUTION:· 

Based on these considerations and those I isted in the previously described hazard assessments. an 

assessment of an aggregate exposure for all pesticidal uses of methyl sali cylate would result in 

minimal additional exposure beyond what consumers already receive from other uses. Expected 

exposure levels from these uses would be well below defined acceptable levels. even considering 

methyl salicylate sensiti vity to infants and children. 

2.2 Ecological Exposure and Risk 

The battery of tests required to assess the environmental fa te and ecological effects of methyl 

salicylate is complete. The biochemical is readily biodegradable in screening tests and may be 

expected to biodegrade in soils and surface waters (HSDB, 1996). Moreover, methyl sali cylate is 

li kely to hydrolyze in water. especially 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 photolysis under environmental conditions (HSDB. 

1996); the photolysis half-life was reported to be 48 minutes in one study (HSDB, 1996). In the 

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atmosphere, methyl salicylate reacts with photochemically produced hydroxyl radicals with an 

estimated rate constant of 11.6 x I o·' 2

cm3 /molecule. Assuming a hydroxyl radical concentration 

of 5 x I o-s radicals/cm3

• the ha lf-l ife of methyl salicylate in the atmosphere would be 1.4 days 

(HSOB, 1996). 

Ecotoxicity data on methyl salicylate show that the compound is: 

• slightly to practically non-toxic to avian species; 

• slightly to practically non-toxic to fish: 

• slight toxicity to aquatic invertebrates; 

• not phytotoxic; 

A contact toxic ity study on honey bees using the new EP showed no toxic effects (24-hr and 48-

hr LDso for contact toxicity was greater than 125 11g ai/bee). 

Non-target plant data requirements were addressed with approved waiver rationales based upon 

1) methyl salicylate· s high vapor pressure. which results in volatilization and rapid losses from 

surfaces. 2) its demonstrated nontoxicity of the compound to plants in the applicant-submitted 

efficacy studies. and 3) its natural occurances in many plant species. 

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

environment in effluents and emissions as a result of it production, disposal and use as a 

fl avoring in foods and beverages, 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 methyl salicylate. including 

the new use as a foliar spray, wi ll not contribute significantly to ecological exposure of this 

biochemical. Furthermore. based on low toxicity and this the lack of a significant increase in 

ecological exposure. the Agency concludes a ''No Effect" determination for direct and indirect 

effects to listed species and their habitats. 

3.0 Alternatives 

Methyl salicylate can be used 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 (I PM) system. The use of this 

biochemical animal and insect repellent and insecticide may displace and reduce the amount of 

conventional active ingredients required for these purposes. Growers may prefer to use methyl 

salicylate as a viable alternative to conventional products since methyl salicylate products 

contain shorter Re-Entry Interva ls (REI) and short half- life (less than two and a ha lf hours on 

foliage). 

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4.0 Benefits and Public Comments 

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

conventional alternatives because biochemicals are natura lly-occurring substances (or substances 

structurally-similar and functiona lly identical to naturally-occurring substances) with a history of 

exposure to humans and the environment demonstrating minimal toxicity and a non-toxic mode 

of action to the target pest(s). Benefits of biochemical pesticides as compared to conventional 

pesticides typically include lower toxicity profiles for humans and non-target organisms, and 

faster degradation in the environment. As outlined above, methyl salicylate is a viable alternative 

to conventional animal and insect repellents and plant growth regulators due to its low toxicity 

profile and half-life of less than two and a half hours on foliage. 

On January 14, 20 IS, EPA published in the Federal Register a Notice of Receipt of the Valent 

application for registration of methyl salicylate as a foliar spray and announced a public 

comment period of 30 days. No comments were received in response to this Notice of Receipt. 

EPA announced the proposed decision of the unconditional registration of methyl sal icy late as a 

foliar spray on tomatoes and peppers pre-flowering on September I 0, 2015, and held a public 

comment period for IS days, closing September 24, 2015, at I I :59 pm. No comments were 

received to the docket (Docket ID: EPA-I-IQ-OPP-2014-0898). 

5.0 Regulatory Decision 

The Agency's methyl salicylate database, which includes guideline studies and scientific 

literature reviews, is complete. The new use of methyl salicylate as a foliar spray on tomatoes 

and bell peppers in agricultural fields and greenhouse is well supported by this database. In 

considering the assessed risk to human health and the environment, the Agency concludes that 

methyl salicylate meets the regulatory standard under the Federal Insecticide, Fungicide and 

Rodenticide Act (FIFRA). There are no outstanding data requirements for this biocbemical. 

Therefore, the EPA is granting the unconditional registration ofthis use of methyl salicylate 

under Section 3(c)(S) of FIFRA. 

One product will be registered: ·'LEAP® Biological Insecticide Emulsifiable Suspension'" is an 

end-use product (EP) containing the active ingredient Bacillus thuringiensis subsp. kurstaki 

strain ABTS-351 in addition to methyl salicylate. Application of this product is approved for use 

outdoors on tomato and pepper plants, pre-flowering. The application rate is 1.0-4.0 pints of 

product per acre. up to a total of 16 pints per acre per season. Application must not be made 

more frequently than every 5 days. 

The risk assessments supporting this decision can be found at EPA-I-IQ-OPP-20 14-0898; 

Document 10: EPA-I-IQ-OPP-2014-0898-0002 and Document ID: EPA-I-IQ-OPP-2014-0898-

0003 ; http://,, ww.cpa.gov/pcsticides/reregistration/REDs/meth yl salicy late red.pdf 

and lmp://\\W\\ .epa.gov/opprdOO 1/inerts/vvintcrgrecn.pdf 

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