### UNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASHINGTON, D.C. 20460

O ffice of Chemical Safety and Pollution Prevention



### MEMORANDUM 0 6 / 17 /201 5

SUBJECT : Application for registration of VBC

- 60347 Biological Insecticide Emulsifiable Suspension , an end use product that contains methyl salicylate

EPA File Symbol No.: 73049

- LNN
DP Barcode: 423840 , 426347
Decision No.: 489428 , 489428
PC Code: 076601; 006522

CAS No. 119

- 36

- 8

MRIDs: 49343601

– 29343639; 49484401

- 49484402



### FROM : Miachel Rexrode, Ph.D., Senior Biologist /s/ 0 6 / 17 /2015 Biochemical Pesticides Branch, Biopesticide & Pollution Prevention Division (7511P)

TO : Gina Burnett , Regula tory Action Leader
Biochemical Pesticides Branch Biopesticide & Pollution Prevention Division (7511P)

*CONTAINS CONFIDENTIAL BUSINESS INFORMATION*

ACTION REQUESTED

Valent Biosciences Corp. has submitted a request for registration for VBC

- 60347 Biological Insecticide Emulsifiable Suspension, an end use product that contains methyl salicylate (Oil of Wintergreen) and B acillus thuringiensis subsp kurstaki strain ABTS

- 351 as the active ingredie nt
to be used a s an insecticide for use against Lepidoptera caterpillars. Use of this end product will also induce a systemic response in treated plants that helps plants to resist disease. In support of the registration, the applicant has submitted product chemistry data, a Confidential Statement of Formula, acute Toxicological studies, Enforcement Analytical Methods, and waiver requests for Subchronic Toxicology studies and certain Tier I N on

- Target Organism testing.

### RECOMMENDATIONS AND CONCLUSIONS

Executive Summary
VBC -60347 Biological Insecticide Emulsifiable Suspension (EPA Reg. No. 73049- LNN) is an end use product to be used in the field or greenhouse to control larvae of lepidopterist insects. The active ingredients are 25.5% w/w Bacillus thuringiensis subsp. kurstaki strain ABTS -351 (supplied by ) and 5.9% w/w methyl salicylate ( oil of wintergreen).

is a registered product, the registrant provided a description of the manufacturing process for Bacillus thuringiensis subsp. kurstaki strai n ABTS

351

. An acceptable description of the starting materials and production process, the formation of impurities and a five -batch analysis are provided. The
certified limits for Bacillus thuringiensis subsp. kurstaki strain ABTS

- 351 exceed the OCSPP

recommended limits, but an acceptable explanation is provided. An acceptable description of the enforcement analytical method is provided. Toxicology and Ecotoxicity studies were submitted, as well as all physical chemistry characteristics for the unregistered methyl salicylate active ingredient. Since Bacillus thuringiensis subsp. kurstaki strai n ABTS -351 ) is previously registered all chemistry and toxicology and ecotoxicology studies for this active ingredient have been submitted and evaluated (USEPA 1998).

Methyl salicylate (MeSa) is exempt from the requirement of a tolerance when used in accordance with good agricu ltural practice as an inert or an occasional active ingredient in pesticide formulations applied to growing crops or agricultural commodities after harvest, as referred to in the MeSa RED and in 40CFR 180.1001 (c). Oil of wintergreen is also found on EPA's List 4A and thus considered a minimal risk inert ingredient. A tolerance exemption will need to be
obtained for Bacillus thuringiensis subsp. kurstaki strain ABTS

- 351 and for methyl salicylate applied to crops.

BPPD has reviewed the Toxicological information that was submitted to fulfill the registration requirements for methyl salicylate and the EP (VBC

- 60347 Biological Insecticide Emulsifiable Suspension). Based on this information methyl salicylate is nontoxic to mammalian species on an acute oral basis (LD 50 

### > 5,000 mg/kg; Toxicology Cat. IV ); can cause slight acute dermal effects (Toxicology Cat. III), and slight eye irritation (Toxicology Cat. III); no acute dermal or inhalation toxicity (LD 50 

### > 5,000mg/kg; LC 50 

### > 400 mg/m 3 

### ; Toxicology Cat. IV) ; Sensitization study showed that the MeSa was not a dermal sensitizer (Toxicology Cat. III). Studies on the

V BC -60347 ( ai. Bacillus thuringiensis subsp . kurstaki , Strain ABTS-351, 26.55% and Methyl Salicylate, 5.9%) show that the EP has a Toxicological Cat. IV for Acute Oral (LD 50 

### > 5,000 mg/kg), for Acute Dermal (LD 50 

### > 5,000 mg/kg), and Acute Inhalation (LC 50 

### > 5.15 mg/L).
VBC -60347 showed minimal effects in the Acute Eye Irritation test and slight irritation in the

### Acute Dermal Irritation study. The Skin Sensitization study showed that the EP was a dermal sensitizer (Toxicology Cat. III).

Ecotoxicity data on methyl salicylate (Table 6.0) show that the compound is slight to practically

non- toxic to avian species (LD 50 

### > 2,510 mg/kg; LC 50 

### > 5,620 ppm); slight to practically nontoxic to fish (LC 50 

### = 26 mg/L and LC 50 

### = 135 mg/L); slight toxicity to aquatic invertebrates (LC 50 

### = 38 mg/L); and not phytotoxic. A study on honey bees using the EP showed no toxic
effect with the 24- and 48- hr LD 50 

### f or contact toxicity greater than 125 μg ai/bee

. 

### A waiver is granted for plant studies 850.4100 (vegetative vigor and seedling emergence) because m ethyl salicylate has significant vapor pressure, resulting in volatilization and rapid losses from surfaces, is nontoxic to plants (efficacy studies) and is found in many plants.

Deficiencies but Upgradeable

Certified Limits

Deficiencies : An explanation must be provided for the excessive certified limits given for the inert, he name of the source material for Bacillus thuringiensis subsp. kurstaki
strain ABTS -351 is incomplete on the CSF. Box 7 (pounds/Gal or Bulk Density) and 8 (pH) on the CSF must be completed.

The name of the Bacillus active ingredient does not match exactly on the CSF and product label.
Label : Bacillus thuringiensis subsp. kurstaki strain ABTS -351 ; CSF: Bacillus thuringiensis subsp. kurstaki ATCC -1275, S train ABTS -351.

T he complete name of the source material for Bacillus thuringiensis subsp. kurstaki strain

ABTS -351 must be given on the CSF

The CAS No. for must be added to the

CSF

.

Physical/ Chemical Characteristics

Deficiencies : Outstanding data requirements on the EP ( VBC

- 60347 Biological Insecticide Emulsifiable Suspension) include pH, storage stability and corrosion characteristics.

Waiver Request Requests a waiver from the testing requirements for; Terrestrial Plant Toxicity Seedling Emergence Testing (O CSPP 850.4100) and Terrestrial Plant Toxicity Vegetative Vigor Testing (O CSPP 850.4150) for Methyl Salicylate and for VBC -60347, Agency Response: Acceptable

### Product Identity (OCSPP 830.1550)

I. M anufacturing Process :

### II. Discussion of Formation of U nintentional Ingredients (OCSPP 885.1300)

### F ive lots of VBC-60347 Biological Insecticide Emulsifiable Suspension were counted for viable aerobic bacteria, anaerobic spore forming bacteria, total coliforms, Streptococci/Enterococci, yeasts, and molds (Table 1). Aerobic bacteria counts ranged from

8.33 x 10 2 

### to 3.40 x 10 3 

### cfu/g. Anaerobic spore forming bacteria ranged from <100 to 2.33 x

10 2 

### cfu/g. Coliforms were not detected , with the results expressed as <100 cfu/g. Streptococci/Enterococci ranged from <100 to 3.80 x 10 2 

### cfu/g. Yeast and molds were <100 cfu/g.

TABLE 1. Viable counts for VBC

- 60347 Biological Insecticide Emulsifiable Suspension

Lot no. Viable counts (cfu/g)

Aerobic
bacteria Anaerobic

spore
- forming
bacteria Total
coliforms Streptococci/
Enterococci Yeast and
molds

25

- 006

- VB 3.40 x 10 3 1.00 x 10 2 <100 3.80 x 10 2 <100

25

- 007

- VB 1.93 x 10 3 1.33 x 10 2 <100 3.70 x 10 2 <100 d

25

- 008

- VB 1.27 x 10 3 <100 a < 100 <100 b 100

25

- 009

- VB 8.33 x 10 2 <100 <100 <100 c <100

25

- 011

- VB 1.77 x 10 3 2.33 x 10 2 <100 1.80 x 10 2 <100 Data from p. 14, MRID 49343624
<100 a represents a mean plate count of 67 cfu/g

<100 b represents a mean plate count of 60 cfu/g

<100 c represents a mean plate count of 50 cfu/g

<100 d represents a mean plate count of 67 cfu/g



### The five lots were also examined for the presence of E. coli

, Staphylococcus

, Pseudomonas aeruginosa and Salmonella (Table 2). E. coli, Staphylococcus , and P. aeruginosa were absent in 1 g, and Salmonella was absent in 25 g.

TABLE 2. Presence of microbial contaminants in VBC

- 63047 Biological Insecticide Emulsifiable Suspension

Lot no. Presence/absence per g or per 25 g

E. coli Staphylococcus Pseudomonas aeruginosa Salmonella

25

- 006

- VB Absent in 1 g Absent in 1 g Absent in 1 g Absent in 25 g

25

- 007

- VB Absent in 1 g Absent in 1 g Absent in 1 g Absent in 25 g

25

- 008

- VB Absent in 1 g Absent in 1 g Absent in 1 g Absent in 25 g

25

- 009

- VB Absent in 1 g Absent in 1 g Absent in 1 g Absent in 25 g

25

- 011

- VB Absent in 1 g Absent in 1 g Absent in 1 g Absent in 25 g Data from p. 15, MRID 49343624 

### Deficiencies : None.

### III. Analysis of Sample (OCSPP 885.1400)

Five batches of VBC -60347 Biological Insecticide Emulsifiable Suspension were analyzed for methyl salicylate and bioactivity (Table 4). The methyl salicylate content (determined using GC with an external standard) ranged from 5.8 to 6.1% w/w, which is within the certified limits given on the CSF. A dietary bioassay with larvae of a target pest, the cabbage looper ( Trichoplusia ni ), showed the biopotency ranged from 21708 to 22063 IU/mg (Table 4).

TABLE 4. Five batch analysis for biopotency and methyl salicylate content of VBC

- 60347 Biological Insecticide Emulsifiable Suspension

Batch no. Biopotency (IU/mg) Methyl salicylate (%w/w)

25

- 006

- VB 21,821 5.8

25

- 007

- VB 21,708 5.9

25

- 008

- VB 21,856 5.9

25

- 009

- VB 21,926 5.9

25

- 011

- VB 22,063 6.1 Data from p. 8, MRID 49343622 

### Deficiencies : None.

IV . C ertified Limits for VB -60347 Biological Insecticide Emulsifiable Suspension (OCSPP 885.1500)

Table 5 lists the nominal concentration and certified limits for the ingredients in VBC -60347 Biological Insecticide Emulsifiable Suspension as given on the CSF. The certified limits for methyl salicylate are within the OCSPP recommended guideline of ±5%. The certified limits for Bacillus thuringiensis subsp. kurstaki s train ABTS

- 351 exceed the OCSPP recommended limits of ±3% while the applicant has used about ( MRID 49343623).

### The certified limits for the inert ingredient exceeds the EPA recommend ation for upper and lower limits; while the applicant used The name of the source
material for Bacillus thuringiensis subsp. kurstaki strain ABTS -351 is incomplete on the CSF. Box 7 (pounds/Gal or Bulk Density) and 8 (pH) on the CSF must be completed

.

TABLE 5. Nominal concentration and certified limits for VBC

- 60347 Biological Insecticide Emulsifiable Suspension a

Ingredients (CAS number) PC
Code Purpose Concentration (% by weight)

Nominal Lower Upper

Active Ingredients

Methyl salicylate,
Methyl 2

- hydroxybenzoate

(119

- 36

- 8) 076601 Active ingredient 5.9

Bacillus thuringiensis subsp . kurstaki strain

ABTS

- 351,

ATCC

- 1275

(68038

- 71

- 1) 006552 Active ingredient 25.5

Inert Ingredients

a Data from CSF (3/17/2014) 

### Deficiencies : An explanation must be provided for the excessive certified limits given for the inert, The name of the source material for Bacillus thuringiensis subsp.
kurstaki strain ABTS -351 is incomplete on the CSF. Box 7 (pounds/Gal or Bulk Density) and 8 (pH) on the CSF must be completed.

IV. ENFORCEMENT ANALYTICAL METHOD (OCSPP 830.1800)

The analytical method to determine the content of methyl salicylate in VBC -60347 Biological Insecticide Emulsifiable Suspension is GC/FID, with results compared to those for an external standard. The method is described in MRID 49343622, but is not explici tly stated

### to be the enforcement analytical method for the product. The instrument is a Hewlett Packard
5890 GC with Chemstation software. The column is a DB

- 5 MS (25 m, 0.32 mm i.d., film thickness of 0.52 μm). The carrier gas is helium. The conditions ar e as follows:

Injection technique: Split (ratio 20:1) Injection temperature: 240°C Injection volume: 5 μL Oven temperature
Initial: 70°C for 1.2 min Ramp: 35°C/min to 300°C
Final: 300°C for 7.25 min

Detector: FID Detector gas flow
Air: 420 mL/min Hydrogen: 46 mL/min Auxiliary: 31 mL/min Detector temperature: 300°C
Retention time: ~ 5 min
Run time: 15 min

The samples are diluted in toluene, and duplicate standard solutions are prepared and used as bracketing standards for the test material sample solutions. The methyl salicylate content is calculated by reference to the bracketing standards. Sample chromatograms are provided in MRID 49343622. It is stated on p. 14 of MRID 49343622 that the method was validated at the test facility, with results given in Huntington Life Sciences Report No. ZAB0172, which
was not included in the submission.
Deficiencies : None

V. P hysical and Chemical Characteristics (OCSPP 830.6302

- 7950)

The data for the applicable physical/chemical charac teristics of methyl salicylate were provided (Table 6.0) and the applicable physical and chemical characteristics of VBC

- 60347 Biological Insecticide Emulsifiable Suspension are provided in Table 7.0

.TABLE 6 . Physical and Chemical Properties for Methyl Salicylate a

Guideline Reference No./Property Description of Result Methods

830.6302 Color Yellowish or reddish Visual observation

830.6303 Physical State Liquid Visual observation

830.6304 Odor Wintergreen

830.6313 Stability Stable under normal use and conditions of storage

830.6314 Oxidation/Reduction: Chemical Incompatibility Not applicable, the product does not contain oxidizing or reducing ingredients.

830.6315 Flammability Flash point; 101 0 C EEC Method A9
Pensky

- Martens closed cup

830.6316 Explodability Not explosive EEC Method A14

830.6317 Storage Stability NA

830.6319 Miscibility NA

830.6320 Corrosion Characteristics NA

830.6321 Dielectric Breakdown Voltage NA

830.7000 pH 5.9 CIPAC MT 75

830.7050 UV light absorption 237 nm ECHA data base

830.7100 Viscosity 2.38 n/Pas at 20°C ECHA data base

830.7200 Melting Range 19.4 0 C ECHA data base

830.7220 Boiling Range 222 0 C ECHA data base

830.7300 Density/Relative Density/Bulk Density 1.184 @ 25 0 C

830.7370 Dissociation Constant in

Water NA

830.7550 Partition Coefficient 2.55 Kow Lyman et al. 1993

830.7840 Water Solubility 

### 0.74% w @ 30 0 

### C

830.7950 Vapor Pressure 0.0343 mm Hg @ 25 0 C

a MRID 49343603TABLE 7 . Physical and Chemical Properties for VBC

- 60347 Biological Insecticide Emulsifiable Suspension a

Guideline Reference No./Property Description of Result Methods

830.6302 Color Brown Visual observation

830.6303 Physical State Liquid Visual observation

830.6304 Odor Not required for EP

830.6313 Stability Not required for EP

830.6314 Oxidation/Reduction: Chemical Incompatibility Not applicable, the product does not contain oxidizing or reducing ingredients.

830.6315 Flammability None determinable, no flash point

observed EEC Method A9

Pensky

- Martens closed cup

830.6316 Explodability Not explosive EEC Method A14

830.6317 Storage Stability Storage stability study is required

830.6319 Miscibility Not applicable, the product is not

to be diluted with nonpolar

solvents.

830.6320 Corrosion Characteristics Corrosion characteristics study is required

830.6321 Dielectric Breakdown Voltage Not applicable, the product is not for use around electrical equipment

830.7000 pH Not provided. Requirement outstanding

830.7100 Viscosity Shows pseudoplastic behavior

170

- 3300 mPa/s at 20°C

97

- 2500 mPa/s at 40°C OECD 114

Brookfield rotational viscometer

830.7200 Melting Range Not required for EP

830.7220 Boiling Range Not required for EP

830.7300 Density/Relative Density/Bulk Density Relative density D 20 4 = 0.98 OECD Method 109

EE Method A3

830.7370 Dissociation Constant in Water Not required for EP

830.7550 Partition Coefficient Not required for EP

830.7840 Water Solubility Not required for EP

830.7950 Vapor Pressure Not required for EP

a Data from MRID 49343627 

### Deficiencies : Outstanding data requirements on the EP include pH, storage stability and
corrosion characteristics

.

### Toxicology

Toxicology Methyl Salicylate Summaries of the toxicology profile for methyl salicylate are shown in Table 8 .0. Based on this
information methyl salicylate is nontoxic to mammalian species on an acute oral basis (LD 50 

### > 5,000 mg/kg; Toxicology Cat. IV ); can cause slight acute dermal effects (Toxicology Cat. III), and slight eye ir ritation (Toxicology Cat. III); no acute dermal or inhalation toxicity (LD 50 

### > 5,000mg/kg; LC 50 

### > 400 mg/m 3 

### ; Toxicology Cat. IV).

Table 8 .0. Acute Toxicological Values for Methyl Salicylate a


### Guideline Results Category MRID # /Reference
Acute Oral Toxicity/ rat
OCSPP 870.1100 LD 50 = 887 mg/kg I II 49343605

Jenner et al . 1964

Acute Dermal Toxicity/

OCSPP 870.1200 LD 50 > 5 ,000 mg/kg IV 49 343606

Acute Inhalation/

OCSPP 870.1300 LC 50 > 400 mg/m 3 IV 49343607 Rumyantsev et al . (1992) Acute Eye Irritation/
OCSPP 870.2400 S evere irrita n t II 44213010

Acute Dermal Irritation/

OCSPP 870.2500 Mild irritant III 44213011

Skin Sensitization/

OCSPP 870.2600 Non sensitizer 49343610

90

- day Dermal

OCSPP 870.3250 Animals dosed with 4.0 ml/kg died after 6, 8

, and 28 days; the
animals had "anorexi a, weight loss, and depression. 49435404 Webb and Hansen (1963 )



### Acute Oral (rat) (OCSPP 830.1100) Valent BioSciences Corp. request that Acute Oral Toxicity presented in the literature be used to fulfill data requirements. The LD 50 

### value calculated for the rat was 887 mg/kg (MRID 4213005). Agency Response: Acceptable

Acute Dermal Toxicity (OCSPP 830.1200)
The acute dermal LD 50 

### value in rabbits was reported as exceeding 5 ,000 m g/kg (Moreno, 1973).

S ince methyl salicylate is metabolized to salicylic acid, a dermal study with salicylic acid was also performed. A 14

- day percutaneous study was performed in four groups of 3 male and 3
female New Zealand White rabbits administered topically at 2 g/kg/day of salicylic acid

containing solutions. The concentrations tested were 0%, 2%, 10% and 25% (corresponding to 0, 40, 200 and 500 mg/kg/day) of salicylic acid in a vehicle solution (8% p ropylene glycol butyl
ether in ethanol). After a 7

- hour period of daily exposure, the application site was washed with water and dried. No death was observed during the study. Dose

- related slight to marked erythema and edema were noted for all dosage group s. Desquamation was most often noted in the 25% salicylic acid group; fissuring of varying degree was observed in all dosage groups. Eschar was noted in the 10% and 25% dosage groups; exfoliation was noted on day 13 in a 25% dosage group. Atonia was predom inantly observed in the animals treated with 10% and 25%

### salicylic acid. These signs were generally noted on or between days 7 to 14. The changes in the body weights of animals were considered as not remarkable during the study. Concerning clinical finding s, no visible abnormalities were noted at necropsy in any animal beyond the dermal irritation observed at the test sites. Under the experimental conditions adopted, the test articles were considered as dermal irritants by the investigators ( MRID 49 343606 ). Agency Response: Acceptable

Acute Inhalation (OCSPP 830.1300) Valent BioSciences Corp. request that Acute Inhalation Toxicity presented in the literature be
used to fulfill data requirements. Rumyantsev et al

. (1992) found that m ethyl s alicylate, heated to 80°C and given by inhalation for an unknown duration to white mice and rats was not lethal; the

LC 50 

### > 400 mg/m 3 

### (MRID 49343607) Agency Response: Acceptable

Acute Dermal Irritation (OCSPP 830.2500) Test material was suspended in water or dissolved in PEG 400, 70% ethanol, or 70% ethanol plus emollients at concentrations of 1, 3 or 6% and was applied to shaved intact skin of test rabbits. No irritation was observed at sites treated with 1% water suspension at 24 and 72 hours following application of tes t material. Primary irritation indexes are summarized as follows:

Methyl Salicylate in Various Vehicles: Rabbit Primary Irritation Indices On Skin Methyl Salicylate %

Vehicle 1 3 6

H2O 0.0 0.83 1.83

PEG 400 0.33 0.50 0.50
70% ethanol 1.17 4.17 4.00
70% ethanol + emollients 2.17 3.00 3.00

Results show mild irritation for all three concentrations of methyl salicylate. The two higher concentrations in 70% ethanol were moderate irritants which produced necrosis, the 70% plus
emollient were all modera tely irritating. The 1% solution was the least reactive, but all concentrations elicited necrosis and intradermal and subcutaneous hemorrhage (MRID 44213011). Agency Response: Acceptable

Sensitization (OCSPP 830.2600) Methyl salicylate (MeSa), a skin irritant was found to be negative in predictive human
sensitization tests (Bas ketter et al ., 1994; Arts et al 1996) (MRID 49343610). Agency Response: Acceptable

90

- Day Dermal (OCSPP 870.3250)
Webb and Hansen ( 1963 ) presented information that showed the following: three rabbits were dosed dermally with synthetic m ethyl s alicylate (99% pure) 5 days per week for up to 96 days. A dose of 0.5, 1.0, 2.0, or 4.0 ml/kg was applied to the clipped skin on the back of restraine d
animals for 6.5 h each day of dosing. The test sites were not wiped because the compound was

### absorbed. The three animals dosed with 4.0 ml/kg died after 6, 8, and 28 days of dosing; the
animals had "anorexia, weight loss, and depression." A "slight sloug hing of epidermal scales"
was observed for two of the animals dosed with 2.0 ml/kg. N o other observations were noted ( MRID 49435404 )

. Agency Response: Acceptable

Toxicology VBC

- 60347
Studies (Table 8.0) on VBC

- 60347 ( a.i.: Bacillus thuringiensis subsp

. kurstaki , Strain ABTS

351, 26.55% and Methyl Salicylate, 5.9%) show that the EP has a Toxicological Cat. IV for Acute Oral (LD 50 

### > 5,000 mg/kg), for Acute Dermal (LD 50 

### > 5,000 mg/kg), and Acute Inhalation (LC 50 

### > 5.15 mg/L). VBC

- 60347 showed minimal effects in the Acute Eye Irritation test and slight irritation in the Acute Dermal Irritation study. The Skin Sensitization study showed that
the EP was a dermal sensitizer (Toxicology Cat. III).

Table 9 .0. Acute Toxicological Val ues for VBC

- 60347
Guideline Results Category MRID #
Acute Oral Toxicity/

OCSPP 870.1100 LD 50 > 5 ,000mg/kg IV 49343628

Acute Dermal Toxicity/

OCSPP 870.1200 LD 50 > 5,00 0 mg/kg IV 49343629

Acute Inhalation/

OCSPP 870.1300 LC 50 > 5.15 mg/L IV 49343630

Acute Eye Irritation/OCSPP
870.2400 Minimal effects clearing in less than
24 hrs. III 49343631

Acute Dermal Irritation/

OCSPP 870.2500 slightly irritating I II 49363432

Skin Sensitization/

OCSPP 870.2600 dermal sensitizer III 49343633

Mutagenicity: In vitro Mammalian Cell Assay/

OCSPP 870.5300 Negative 40898201



### Toxicology VBC

- 60347

Acute Oral (rat) (OCSPP 830.1100) In an acute oral toxicity study three female Sprague

- Dawley rats (10 week old) were dosed by gavage with VBC

- 60347, Lot No. 25

- 006

- VB ( a.i.: Bacillus thuringiensis subsp . kurstaki , Strain

ABTS

- 351, 26.55% and methyl salicylate, 5.9% ) at 5

, 000 mg/kg, respectively (up and down procedure). Body weight was recorded prior to dosing, and on days 7 and 14. The test animals
were observed for mo rtality and clinical signs of toxicity during the first several hours post

dosing and at least daily thereafter for 14 day s. The Oral LD 50 

### > 5

, 000 mg/kg

, VBC

- 60347 is a

T oxicity Category IV (MRID 49343628 ). Agency Response: Acceptable

Acute Dermal (OCSPP 830. 12 00) In an acute dermal toxicity study five male and five female Sprague

- Dawley rats (10 week old) were dermally exposed to VBC

- 60347 , Lot No. 25

- 006

- VB (a.i.: Bacillus thuringiensis subsp

. kurstaki , Strain ABTS

- 351, 26.55% and Methyl Salicylate, 5.9% ) at a dose of 5000 mg/kg bw

### for 24 hours to an area of approximately 10% of body surface. Following exposure, the animals were observed for a period of 14 days. All animals were active and healthy during other days. No abnormalities were noted at necrop sy (MRID 49343629 ).

Dermal LD 50 

### Males > 5

, 000 mg/kg bw
Females > 5

, 000 mg/kg bw
Combined > 5

, 000 mg/kg bw (limit test)

This places VBC

- 60347 in T oxicity Category IV Agency Response: Acceptable

Acute Inhalation (OCSPP 830.1300) In an acute inhalation toxicity study groups of young adult Sprague

- Dawley rats (9

- 10 weeks old; 5/sex/group) were exposed nose

- only to VBC

- 60347, Lot No. 25

- 006

- VB (a.i.: Bacillus thuringiensis subsp . kurstaki , Strain ABTS

- 351, 26.55% and methyl salicylat e, 5.9% ) for 4 hours at a concentration of 5.15 mg/L. The animals were observed for 14 days. All animals survived to scheduled termination. Following exposure, all rats exhibited abnormal respiration and two
females exhibited ano

- genital staining and/or abnormal distention with recovery by day 7. All animals appeared active and healthy thereafter and through the end of the study. All rats lost weight by day 1 and one female lost weight through day 3; thereafter, all animals gained weight through the end o f the study. No gross abnormalities were no ted from any animal at necropsy (MRID 49343630).

Inhalation LC 50 

### Males > 5.15 mg/L Females > 5.15 mg/L Combined > 5.15 mg/L

VBC

- 60347 is in EPA Toxicity Category IV. Agency Response: Acceptable

Acute Eye Irritation (OCSPP 870.2400) In a primary eye irritation study 0.1 mL of VBC

- 60347, Lot No. 25

- 006

- VB (a.i.: Bacillus thuringiensis subsp . kurstaki , Strain ABTS

- 351, 26.55% and Methyl Salicylate, 5.9% ) as supplied was instilled into the conjunctival sac of the right eye of three female New Zealand
White rabbits. The contralateral eye was not treated and served as control. Animals were observed at 1, 24, 48, and 72 hours after test material instillation. No corneal opacity or iritis was noted on any rab bit throughout the study. Positive conjunctival irritation (redness score = 2) was noted on two rabbits one hour after test material instillation with resolution on one rabbit by 48 hours and on the other rabbit by 72 hours. The third rabbit had positive conjunctival irritation 24
hours after test material instillation. The maximum average score was 5.3 at one hour after test
material instillation

. In this study, VBC

- 60347 was minimally irritating to the eye and the test
material is in EPA Toxicity Category III for primary eye irritation (MRID 49343631 ). Agency Response: Acceptable

### Acute Dermal Irritation (OCSPP 830.25 00) In a p rimary dermal irritation study three female New Zealand White rabbits were dermally exposed to 0.5 mL of VBC

- 60347, Lot No. 25

- 006

- VB (a.i.: Bacillus thuringiensis subsp

. kurstaki , Strain ABTS

- 351, 26.55% and Methyl Salicylate, 5.9%) as supplied for 4 hours on an approximately 6 cm 2 

### clipped area of the dorsal area and trunk. The animals were observed at 1, 24, 48, and 72 h ours and day 7 after patch removal. One rabbit had no dermal irritation throughout the study. Another rabbit had well defined erythema with very slight edema at 48 hours after patch removal that became well defined erythema with slight edema by 72 hours w ith clearance by day 7. The third rabbit had well defined erythema with very slight edema at 48 and 72 hours after patch removal with clearance by day 7. Desquamation was noted on the third rabbit on day 7. The primary irritation index was 1.1

. In this study, VBC

- 60347 was slightly irritating and is represents EPA Toxicity Category III ( MRID 49363432)

. Agency Response: Acceptable

Skin Sensitization (OCSPP 870.2600) In a dermal sensitization study with VBC

- 60347, Lot No. 25

- 006

- VB (a.i.: Bacillus thuringiensis subsp . kurstaki , Strain ABTS

- 351, 26.55% and Methyl Salicylate, 5.9%), 33 female young adult CBA/J mice were tested using the local lymph node assay. Statistically significant increases in cell proliferation measurements compared to the vehicle control group were observed at 25%, 50%, and 100% test concentrations. SIs of > 3.0 were observed at all test concentrations (6.37, 8.28, and 8.11 for 25%, 50%, and 100% test concentrations, respectively). The positive control produced a dermal sensitization response (SI = 10.38) in mice. Under the conditions of this study, VBC

- 60347 produced a dermal sensitization response in mice. (MRID 49343633)

. Agency Response: Acceptable

Ecotoxicity

Acute Toxicity Ecotoxicity data on methyl salicylate (Table 6.0) show that the compound is slight to practically

non

- toxic to avian species (LD 50 

### > 2,510 mg/kg; L C 50 

### > 5, 620 ppm); slight to practically
nontoxic to fish (LC 50 

### = 26 mg/L and LC 50 

### = 135 mg/L); slight toxicity to aquatic invertebrates (LC 50 

### = 38 mg/L ); and not phytotoxic. A study on honey bees using the EP showed no toxic
effect with the 24

- and 48

- hr LD 50 

### for contact toxicity greater than 125 μg ai/bee

. 

### A waiver is granted for plant studies 850.4100 (vegetative vigor and seedling emergence) because m ethyl salicylate has significant vapor pressure, resulting in volatilization and rapid losses from surfaces, is nontoxic to plants (efficacy studies) and is found in many plants.

Table 6.0 Ecotoxicity Studies

Stud ies on Methyl Salicylate Results Reference/MRID

Acute Avian Oral (Bobwhite Quail)

OCSPP 850.2100 LD 50 > 1, 2 0 0 mg/kg

NOEL = 720 mg/kg 49343614

Acute Avian Dietary (Bobwhite Quail)

OCSPP 850.2200 LC 50 > 5,620 ppm NOEL = 5,620 ppm 49 484401

Daphnia magna

OCSPP 850.1010 48 hr EC 50 = 38 mg/ L (95% conf interval 24

– 59 mg/L) NOEL = 24 mg/L 49343618

Bluegill ( Lepomis macrochirus )
OCSPP 850.1075 96hr LC 50 = 26 mg/L NOEL = 16 mg/L 49343617Rainbow Trout ( Oncorhynchus mykiss )
OCSPP 850.1075 96hr LC 50 =135 mg/L (95% conf interval 23

– 35 mg/L); NOEL = 9.1 mg/L 49343616

Study on VBC

- 60347 Results Reference/MRID Honeybee Acute Toxicity

OCSPP 850.3020 The 24

- and 48

- hr LD 50 for contact toxicity was >125 μg ai /bee. 49343639

Waiver Request Results Reference/MRID

Terrestrial Plant Tox. (Seedling Emergence)

OCSPP 850.4100 Waiver acceptable. Both ai components are known to promote plant health. 49343619

Terrestrial Plant Tox. (Vegetative Vigor)

OCSPP 850.4100 Waiver acceptable. Both ai components are known to promot e plant health. 49343619



### Avian Acute Oral (OSCPP 850.2100)
The acute oral LD 50 

### value for northern bobwhite exposed to Methyl Salicylate as a single oral
dose was calculated to be 1703 m g/kg, with 95% confidence that it was greater than 1 200 mg a i

/kg. The no

- mortality level was 1200 mg ai/kg. The no

- obs erved

- effect level was 720 mg a i / kg based on signs of toxicity and a body weight effect observed at the 1200 mg a.i./kg dosage group (MRID 49343614)

. Agency Response: Acceptable

Avian Dietary (OSCPP 850. 2200) The dietary LC 50 

### for northern bobwhite quail exposed the methyl salicylate was determined to be greater than 5,620 ppm, the highest concentration tested. The no

- treatment related mortality
concentration and the no

- observed

- effect concentration were 5,620 ppm. The nominal
concentrations were 562, 1000, 1780, and 5,620 ppm ai and the estimated daily dietary doses

were 123, 213, 370, 647, 1,206 mg ai/kg (MRID 49484401). Agency Response: Acceptable

Fish Acute Toxicity (Rainbow trout) (OSCPP 850.1075) Rainbow trout ( Oncorhynchus mykiss ) were exposed for 96 hours under static

- renewal
conditions to five mean measured concentrations of methyl salicylate ranging from 6.3 to 110 mg ai /L. The 96

- hour LC 50 

### value was 35 mg a i/L, with a 95% confidence interval of 23 to 52 mg
ai/L and the NOEC was 9.1 mg a.i./L. Agency Response: Acceptable

Fish Acute Toxicity ( Bluegill ) (OSCPP 850.1075) Bluegill ( Lepomis macrochirus ) were exposed for 96 hours under static

- renewal conditions to
five mean measured concentrations of methyl salicylate ranging from 3.0 to 106 mg ai/L. The

96

- hour LC 50 

### value was 26 mg a i/L, with a 95% confid ence interval of 16 to 106 mg a i/L and the

NOEC w as 16 mg ai /L. Agency Response: Acceptable

Aquatic Invertebrate Acute Toxicity (O SCPP 850.1010) The cladoceran, Daphnia magna, was exposed for 48 hours under static conditions to five mean measured concentrations of methyl salicylate ranging from 5.5 to 117 mg/L. The 48

- hour EC 50 

### value was 38 mg methyl salicylate/L and the NOEC w as 24 mg methyl salicylate/L. Agency Response: Acceptable

### Honeybee Acute Toxicity (850.3020)
The 48

- hr LD 50 

### for oral toxicity was >118 μg VBC

- 60347/bee. Response of the reference control group was appropriate. For the contact exposure, the bees were treated individually by topical application of 2 μL of mineral water containing a nominal dose of 7.8, 15.6, 31.3, 62.5, or 125 μg of product/bee to the thorax and observed for 48 hours. Control bees received 2 μL of mineral
water or dimethoate in mineral water. Mortality at test end ranged from 2.5% to 15.0% in the test material groups compared to 0.0% in the untreated control group, but was likely not

- treatment related, as there was no dose

- response relationship. The 24

- and 48

- hr LD 50 

### for contact toxici t y was >125 μg VBC

- 60347 42/bee (MRID 49343639). Agency Response: Acceptable

Vegetative Vigor, Seedling Emergence (OCSPP 850.4100; 850.4150) Valent BioSciences Corp. requests a waiver from the testing requirements for; Terrestrial Plant Toxicity Seedling Emergence Testing (O CSPP 850.4100) and Terrestrial Plant Toxicity Vegetative Vigor Testing (O CSPP 850.4150) for Methyl Salicylate and for VBC

- 6 0347, (a liquid formulation of m ethyl salicylate and Bacillus thuringiensis subsp. kurstaki strain ABTS

- 351).

Fellows et al

. (1991) using a wind tunnel experiment

, found a lower threshold for plant phytotoxicity of 1 to 2 ug methyl salicylate /cm 2 

### leaf. Phytotoxicity was transient and began resolving within 2 days. Severe plant contact toxicity was observed at level s above 4 ug m ethyl salicylate /cm 2 

### of leaf. Fellows et al. showed that foliar deposited m ethyl salicylate has an initial rapid loss phase with a half

- life of 0.9 to 2.4 h on sagebrush, tall

- and short

- needle pine foliage.

M ethyl salicylate has significant vapor pressure, so volatilization accounts for some rapid losses
from surfaces with half

- lives in terms of hours, and littl e absorption to organic matter. E xposure of non

- target seeds is highly unlikely and the development of phytotoxicity woul d not be expected.

Actual VBC

- 600347 use rates: Worst case scenario: 4 pints/acre 1 acre = 40,468,564.2 cm 2 

### Product is 6%, at 4 pints ~ 120 g m ethyl salicylate Results in: 2.96 ug m ethyl salicylate /cm 2 

### (for a planar surface) Tomato plant contains 700

- 800cm 2 

### of leaf area Agency Response: Acceptable

### Magnitude of Residues of Methyl Salicylate in Tomato Plants Following Applications


## VBC

- 60347 ( MRID 49484402 )



## The purpose of this study was to generate magnitude of the residue data for methyl salicylate and salicylic acid in/on tomato plants treated at the proposed labeled use rate of 2 pints VBC

60347 end use product/A/application at a various time points after a single application. The residue data gen erated in this study will be used to describe the natural levels, and the increase and decline of both methyl salicylate and salicylic acid, to establish tolerance exemptions for methyl salicylate residues in/on treated tomato in support of its US EPA and Canadian PMRA registration.

The residue data produced from the treated plants of this study are appropriate for supporting registration of the Methyl Salicylate active ingredient. Samples were analyzed for Methyl Salicylate and Salicylic Acid residues usi ng well

- controlled appropriate methods. Test substance applications for this study were consistent and appropriate to obtain good residue samples. Plant samples were properly taken and extracted immediately for analysis. No unusual weather phenomena, agric ultural, or analytical practices were experienced during the conduct of this study.

Endogenous levels of Methyl Salicylate averaged 489 ppb before application of VBC

- 60347. The levels in the leaves increased to an average of 1087 ppb one hour after appli cation of the test formulation at the proposed label rate of 2 pints per acre. By four hours after application the residue level had decreased to 954 ppb, and by 25 hours the level (560 ppb) had returned
to the time

- 0 level. A similar profile was seen for the Salicylic Acid results, except that the endogenous levels are lower, and levels in treated plants were also lower throughout the time
interval. Time

- 0 values averaged 51 ppb. One

- hour after application the levels rose to 246 ppb but had returned to the background level (30 ppb) by 25 hours after application. There is considerable variation within all of this data. This due to plant to plant variation the time

- 0 values represent endogenous levels before treatment. However, this data does demonstrate
the trend of rapid disappearance of methyl Salicylate and no accumulation in the form of salicylic acid. Agency Response: Supplemental

### References

Arts

, J

. H

. , Droege

, S

. C

. , Spanhaak

, S

. , Bl oksma, N., Penninks, A.H., Kuper, C.F. 1997. Local lymph node activation and IgE responses in brown Norway and Wistar rats after dermal application of sensitizing and non

- sensitizing chemicals. Toxicology. 117, 2

- 3: 229

- 34.

Basketter, D.A. , Scholes, E.W. and Kimber, I. 1994. The performance of the local lymph node assay with chemicals identified as contact allergens in the human maximization test. Food Chem. Toxicol. 32, 543

- 547

.

Hazardous Substances Data Bank (HSDB), D atabase of the National Library of Medicine's TOXNET sys tem (http://toxnet.nlm.nih.gov) on February 17, 2014.

Jenner, P. M., Hagan, E. C., Taylor, J. M., Cook, E. L. & Fitzhugh, O. G. 1964. Fd Cosmet. Toxicol., 3, 327

M ayer D. F. 1997. Effects of methyl salicylate on honey bee ( Apis mellifera L)

F oraging New Zealand Journal of Crop and Horticultural Science, 25: 291

- 294

USEPA, 1998. Reregistration, Eligibility Decision (RED): Bacillus thuringiensis. EPA 738

- R

98

- 004

Webb, W. K., and W. H. Harisen. 1963. Chronic and subacute toxicology and pathology of

me thyl salicylate in dogs, rats, and rabbits. Toxicol. Appl. Pharmacol. 5:576

- 587.

MRID Citation Receipt
Date

49343600 Valent Biosciences Corporation (2014) Submission of Product Chemistry, Toxicity, and Fate Data in Support of the Application for Registration of VBC

60347. Transmittal of 39 Studies. 20

- Mar

2014

49343601 Bade, T.; Herrero, M. (2013) Product Identity: Manufacturing Process: Methyl Salicylate. Project Number: MESA/12/2013. Unpublished study prepared by Valent Biosciences Corporation. 43p. 20

- Mar

2014

49343602 Marin, J. (2013) Analysis and Certification of Product Ingredients in Five Batches of Technical Methyl Salicylate. Pro ject Number: 2412W. Unpublished study prepared by PTRL West, Inc. 31p. 20

- Mar

2014

49343603 Herrero, M. (2014) Methyl Salicylate: Scientific Justification to Use Current Data to Satisfy the Biochemical Pesticide Registration Requirements for Physical and Chemical Characteristics. Project Number: MESA/214/PC. Unpublished study prepared by Valent Biosciences Corporation. 33p. 20

- Mar

2014

49343604 Herrero, M. (2014) Methyl Salicylate Stability to Normal and Elevated Temperatures, Metals and Metal Ions, Reque st for No Further Testing. Project Number: MESA/214/PC2. Unpublished study prepared by Valent Biosciences Corporation. 26p. 20

- Mar

201449343605 Herrero, M. (2014) Methyl Salicylate: Scientific Justification to Use Current Data to Satisfy the Biochemical Pesticide Registration Requirements for Acute Oral Toxicity Testing. Project Number: MESA/214/01. Unpublished study prepared by Valent Biosciences Corporation. 60p. 20

- Mar

2014

49343606 Herrero, M. (2014) Methyl Salicylate: Scientific Justification to Use Current Data to Satisfy the Biochemical Pesticide Registration Requirements for Acute Dermal Toxicity Testing. Project Number: MESA/214/02. Unpublished study prepared by Valent Biosciences Corporation. 125p. 20

- Mar

2014

49343607 Herrero, M. (2014) Methyl Salicylate: Scientific Justification to Use Current Data to Satisfy the Biochemical Pesticide Registration Requirements for Acute Inhalation Toxicity Testing. Project Number: MESA/214/03. Unpublished study prepared by Valent Biosciences Corporation. 137p. 20

- Mar

2014

49343608 Herrero, M. (2014) Methyl Salicylate: Scientific Justification to Use Current Data to Satisfy the Biochemical Pesticide Registration Requirements for Primary Ocular Irritation Toxicity Testing. Project Number: MESA/214/03. Unpublishe d study prepared by Valent Biosciences Corporation. 14p. 20

- Mar

2014

49343609 Herrero, M. (2014) Methyl Salicylate: Scientific Justification to Use Current Data to Satisfy the Biochemical Pesticide Registration Requirements for Primary
Dermal Irritation T oxicity Testing. Project Number: MESA/214/05. Unpublished study prepared by Valent Biosciences Corporation. 142p. 20

- Mar

2014

49343610 Herrero, M. (2014) Methyl Salicylate: Scientific Justification to Use Current Data to Satisfy the Biochemical Pesticide Registration Requirements for Dermal Sensitization Testing. Project Number: MESA/214/06. Unpublished study prepared by Valent Biosciences Corporation. 23p. 20

- Mar

2014

49343611 Herrero, M. (2014) Methyl Salicylate: Scientific Justification to Use Current Data to Satisfy the Biochemical Pesticide Registration Requirements for 90

- day Oral Toxicity Testing. Project Number: MESA/214/90D, EMEA/MRL/696/99/FINAL. Unpublished study prepared by Valent Biosciences Corporation. 108p. 20

- Mar

2014

49343612 Herrero, M. (2014) Methyl Salicylate: Scientific Justification to Use Current Data to Satisfy the Biochemical Pesticide Registration Requirements for Pre

- Natal Developmental Toxicity Testing. Project Number: MESA/214/TER. Unpublished study prepared by Valent Bioscien ces Corporation. 111p. 20

- Mar

2014

49343613 Herrero, M. (2014) Methyl Salicylate: Scientific Justification to Use Current Data to Satisfy the Biochemical Pesticide Registration Requirements for Mutagenicity Toxicity Testing. Project Number: MESA/214/MU. U npublished study prepared by Valent Biosciences Corporation. 223p. 20

- Mar

2014

49343614 Hubbard, P.; Beavers, J. (2014) Methyl Salicylate: An Acute Oral Toxicity Study with the Northern Bobwhite. Project Number: 529/126. Unpublished study prepared by Wild life International, Ltd. 55p. 20

- Mar

2014

49343615 Herrero, M. (2014) Methyl Salicylate: Justification for No Further Testing in Regard to Avian Dietary Toxicity. Project Number: MESA/1/AD, PNL/SA/19765, DE91/012775. Unpublished study prepared by Valent Biosciences Corporation. 23p. 20

- Mar

2014

49343616 Brougher, D.; Martin, K.; Gallagher, S.; et al. (2013) Methyl Salicylate: A 96

- Hour Static

- Renewal Acute Toxicity Test with the Rainbow Trout (Oncorhynchus mykiss): Final Report. Project Number: 529A/126, 20

- Mar

2014529/012813/RBT/96H3/100P/628. Unpublished study prepared by Wildlife International, Ltd. 59p.

49343617 Brougher, D.; Bodle, E.; Martin, K.; et al. (2014) Methyl Salicylate: A 96

- Hour Static Renewal Acute Toxicity Test with the Bluegill (Lepom is macrochirus): Final Report. Project Number: 529A/127, 529/042913/BLU/96H3/SUB529. Unpublished study prepared by Wildlife International, Ltd. 57p. 20

- Mar

2014

49343618 Brougher, D.; Martin, K.; Gallagher, S. (2014) Methyl Salicylate: A 48

- Hour Static Ac ute Toxicity Test with the Cladoceran (Daphnia magna): Final Report. Project Number: 529A/125, 529/032613/DAP/48H1/OECD/OPPTS/100P/601. Unpublished study prepared by Wildlife International, Ltd. 56p. 20

- Mar

2014

49343619 Herrero, M. (2014) Methyl Salicyla te: Justification for a Waiver from: Terrestrial Plant Toxicity Seedling Emergence Testing: Terrestrial Plant Toxicity Vegetative Vigor Testing. Project Number: MESA/1/14, PNL/9818, TD2089. Unpublished study prepared by Valent Biosciences Corporation. 178p

. 20

- Mar

2014

49343620 Herrero, M. (2014) Methyl Salicylate: Scientific Justification to Use Current Data to Satisfy the Biochemical Pesticide Registration Requirements for: Non

- target Insect Toxicity Testing: Honey Bee Acute Toxicity. Project Number: MESA/214/HBA. Unpublished study prepared by Valent Biosciences Corporation. 86p. 20

- Mar

2014

49343621 Herrero, M. (2014) Methyl Salicylate: Scientific Justification to Use Current Data to Satisfy the Biochemical Pesticide Registration Requirements for Res idue Data Testing. Project Number: MESA/214/01R, PNL/9818, TD/2089. Unpublished study prepared by Valent Biosciences Corporation. 519p. 20

- Mar

2014

49343622 Comb, A. (2013) VBC

- 60347: Five

- Batch Analysis (Chemical and Bioassay). Project Number: ZAB0173, VBC/60347. Unpublished study prepared by Huntingdon Life Sciences, Ltd. 39p. 20

- Mar

2014

49343623 Devisetty, B. (2014) VBC

- 60347: Product Identity, Manufacturing Process, and Formation of Unintentional Ingredients. Project Number: VBC/60347/MA. Unpublishe d study prepared by Valent Biosciences Corporation. 70p. 20

- Mar

2014

49343624 Paterson, K. (2013) VBC

- 60347: Bioburden Analysis on 5 Batches. Project Number: ZAB0174. Unpublished study prepared by Huntingdon Life Sciences, Ltd. 16p. 20

- Mar

2014

49343625 Comb, A. (2013) VBC

- 60347: Method Validation. Project Number: ZAB0172. Unpublished study prepared by Huntingdon Life Sciences, Ltd. 48p. 20

- Mar

2014

49343626 Comb, A. (2013) VBC

- 60347: Two Year Storage Stability (Interim Report, Initial Data). Project Num ber: ZAB0175. Unpublished study prepared by Huntingdon Life Sciences, Ltd. 59p. 20

- Mar

2014

49343627 Pointer, C. (2013) VBC

- 60347: Physico

- Chemical Properties. Project Number: ZAB0185, 54454/5. Unpublished study prepared by Huntingdon Life Sciences,
Ltd. 39p. 20

- Mar

2014

49343628 Durando, J. (2013) VBC

- 60347: Acute Oral Toxicity Up and Down Procedure in Rats. Project Number: 35864, P320/UDP, 130124/4D. Unpublished study prepared by Product Safety Laboratories. 28p. 20

- Mar

201449343629 Durando, J. (2013) VBC

- 60347: Acute Dermal Toxicity Study in Rats. Project Number: 35865, 130124/4D, P322/RAT. Unpublished study prepared by Product Safety Laboratories. 27p. 20

- Mar

2014

49343630 Durando, J. (2013) VBC

- 60347: Acute Inhalation Toxicity Study in Rats. Projec t Number: 35866, 130124/4D, P330. Unpublished study prepared by Product Safety Laboratories. 35p. 20

- Mar

2014

49343631 Durando, J. (2013) VBC

- 60347: Primary Eye Irritation Study in Rabbits. Project Number: 35867, 130124/4D, P324. Unpublished study prepare d by Product Safety Laboratories. 30p. 20

- Mar

2014

49343632 Durando, J. (2013) VBC

- 60347: Primary Skin Irritation Study in Rabbits. Project Number: 35868, 130124/4D, P326. Unpublished study prepared by Product Safety Laboratories. 30p. 20

- Mar

2014

49343633 Durando, J. (2013) VBC

- 60347: Local Lympth Node Assay (LLNA) in Mice. Project Number: 35869,130124/4D, P327. Unpublished study prepared by Product Safety Laboratories. 39p. 20

- Mar

2014

49343634 Herrero, M. (2014) VBC

- 60347: Justification for No F urther Testing in Regard to Avian Acute Oral Toxicity. Project Number: MESA/1F/AD, PNL/SA/19465, DE91/012775. Unpublished study prepared by Valent Biosciences Corporation. 21p. 20

- Mar

2014

49343635 Herrero, M. (2014) VBC

- 60347: Justification for No Furthe r Testing in Regard to Avian Dietary Toxicity. Project Number: MESA/2F/AD, PNL/SA/19465, DE91/012775. Unpublished study prepared by Valent Biosciences Corporation. 22p. 20

- Mar

2014

49343636 Herrero, M. (2014) VBC

- 60347: Justification for No Further Testin g in Regard to Fish Acute Toxicity. Project Number: MESA/1F/AF, MESA/1F/AD. Unpublished study prepared by Valent Biosciences Corporation. 49p. 20

- Mar

2014

49343637 Herrero, M. (2014) VBC

- 60347: Justification for No Further Testing in Regard to Aquatic Invertebrate Acute Toxicity. Project Number: MESA/1DA/AD. Unpublished study prepared by Valent Biosciences Corporation. 49p. 20

- Mar

2014

49343638 Herrero, M. (2014) Justification for a Waiver from Terrestrial Plant Toxicity Seedling Emergence Testing Terr estrial Plant Toxicity Vegetative Vigor Testing with VBC

- 60347 (Containing Methyl Salicylate (MeSa). Project Number: MESA/1/14, PNL/SA/19465, DE91/012775. Unpublished study prepared by Valent Biosciences Corporation. 178p. 20

- Mar

2014

49343639 Verge, E. ( 2013) Final Report: VBC

- 60347

- Acute Oral and Contact Toxicity to the Honeybee, Apis Mellifera L. under Laboratory Conditions. Project Number: S13/03504, S13/03504/L1. Unpublished study prepared by Eurofins Agroscience Services EcoChem GmbH. 45p. 20

- Mar

2 014

49435400 Valent BioSciences Corporation (2014) Submission of Product Chemistry and Toxicity Data in Support of the Application for Registration of VBC

- 60347 Biological Insecticide Emulsifiable Suspension and the Petition for Tolerance of Methyl Salicy late. Transmittal of 5 Studies. 25

- Jul

2014

49435401 Herrero, M. (2014) VBC

- 60347: Miscibility

- Request for No Further Testing. Project Number: MESA/214/M. Unpublished study prepared by Valent BioSciences Corporation. 4p. 25

- Jul

201449435402 Herrero, M. (2014) Methyl Salicylate: Particle Size

- Request for No Further Testing. Project Number: MESA/214/PS. Unpublished study prepared by Valent BioSciences Corporation. 11p. 25

- Jul

2014

49435403 Nair, A.; Lopez, J. (2014) Methyl Salicylate pH Measurements. Project Number: MESA/214/PH. Unpublished study prepared by Valent BioSciences Corporation. 5p. 25

- Jul

2014

49435404 Herrero, M. (2014) Methyl Salicylate: Scientific Justification to Use Current Data to Satisfy the Biochemical Pesticide Registration Requi rements for 90

- Day Inhalation Toxicity Testing. Project Number: MESA/214/90DINH. Unpublished study prepared by Valent BioSciences Corporation. 40p. 25

- Jul

2014

49435405 Herrero, M. (2014) Methyl Salicylate: Scientific Justification to Use Current Data

to Satisfy the Biochemical Pesticide Registration Requirements for 90

- Day Dermal Toxicity Testing. Project Number: MESA/214/90DD. Unpublished study prepared by Valent BioSciences Corporation. 184p. 25

- Jul

2014

49484400 Valent BioSciences Corporation (2014) S ubmission of Toxicity and Residue Data in Support of the Application for Registration of VBC

- 60347. Transmittal of
2 Studies. 09

- Oct

2014

49484401 Hubbard, P.; Schutt, W.; Beavers, J.; et al. (2014) Methyl Salicylate: A Dietary LC50 Study with the Norther n Bobwhite. Project Number: 529/129, 529/072414/QLC/100P/401. Unpublished study prepared by Wildlife International Limited. 80p. 09

- Oct

2014

49484402 Heiman, D. (2014) Magnitude of Residues of Methyl Salycilate in Tomato Plants Following Applications of V BC

- 60347. Project Number: MESA/TLRD/LG/001. Unpublished study prepared by Valent Biosciences Research Center. 40p. 09

- Oct

2014

49586400 Valent BioSciences Corporation (2015) Submission of Product Chemistry Data in Support of the Application for Registration of Methyl Salicylate. Transmittal of
2 Studies. 12

- Mar

2015

49586401 Richard, K. (2014) Preliminary Analysis of Technical Methyl Salicylate. Project Number: 546G822. Unpublished study prepared by EPL Bio

- Analytical Services (EPL

- BAS). 71p. 12

- Mar

2015

49586402 Herrero, M. (2015) Product Identity Manufacturing Process: Methyl Salicylate. Project Number: MESA/03/2015. Unpublished study prepared by Valent BioSciences Corporation. 168p. 12

- Mar

2015