**EPA REGISTRATION DIVISION COMPANY NOTICE OF FILING FOR**

**PESTICIDE PETITIONS PUBLISHED IN THE FEDERAL REGISTER EPA**  **Registration Division contact:**  **Mark Suarez (703 -**  **305 -**  **0120)**
**INSTRUCTION**

**S: Please utilize this outline in preparing the pesticide petition. In**  **cases where the outline element does not apply, please insert “NA -**  **Remove” and maintain the outline. Please do not change the margins, font, or format in your**  **pesticide petition. Simpl y replace the instructions that appear in**  **green , i.e., “[**  **insert company name**  **],” with the information specific to your action. TEMPLATE:**  **Bayer CropScience LLC [Insert petition number]**  EPA has received a pesticide petition **( [insert**  **petition number ]**  **)** from **Bayer CropScience LLC**  , **2 T. W. Alexander Drive, Research Triangle Park, NC 27709** proposing, pursuant to section 408(d) of the Federal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 346a(d), to amend 40 CFR part 180. b y establishing a tolerance for residues of deltamethrin [(1R, 3R)
- 3(2,2
- dibromovinyl)
- 2,2
- dimethylcy clopropane
carbox yl ic acid (S)
- alpha
- cy ano - 3
- phenox yb enzyl ester] and its major metabolites trans deltamethrin [(s)
- alpha
- cy ano - 3
- phenox yb enzyl
- (1R, 3S)
- 3
- (2,2
- dibromovinyl)
- 2,2
- dimeth yl cy clopropanecarboxylate] and alpha
- R
- deltamethrin [(R)
- alphacy ano - 3
- phenox yb enzyl
- (1R, 3R)
- 3
- (2,2
- dibromovinyl)
- 2,2
- dimethylcy clopropanecarboxylate] : in or on food and feed commodities at 0. 0 5 ppm following wide
- area mosquito adulticide applications
. EP A has determined that the petition contains data or information regarding the elements set forth in section 408 (d)(2) of the FDDCA; however, EPA has not fully evaluated the sufficiency of the submitted data at this time or whether the data supports granti ng of the petition. Additional data may be needed before EPA rules on the petition. A. Residue Chemistry 1. Plant metabolism. The metabolism of deltamethrin in plants is well understood. Deltamethrin metabolism studies in tomatoes, corn, apples, and cotton demonstrate the same metabolic pathway . The residues of concern are the parent cis
- deltamethrin, and its isomers, trans
- deltamethrin and alpha
- R
- deltamethrin. 2. Analytical method. Residues of deltamethrin (cis and trans isomers) were extracted fro m homogenous 10
- g samples of alfalfa forage, lettuce leaves, and grass forage using acetone/n
- hexane/ dichloromethane as the extraction solvent. Homogenous2

5
- g samples of alfalfa hay and grass hay

were soaked in water overnight prior to extraction. Resid

ues of cis
- deltamethrin and trans
- deltamethrin were extracted using acetone/ n
- hexane/dichloromethane as the extraction solvent with sonication. Samples were then filtered before an I S solution was added. After evaporation of the organic phase to dry

ness, the dry

residue was taken up with toluene. An aliquot of the toluene extract was concentrated to dry ness and dissolved in dichloromethane/acetone, followed by solid phase extraction (SPE) clean up with Varian MEGA BE SCX
- 2 GM cartridges. The extracts we re again concentrated to dry ness and dissolved in aqueous acetonitrile/10 mM ammonium acetate before anal ys is by HPL C/MS/MS. HPL C separation was performed with an Ascentis Express C18, 2.7 μm, 150 mm × 3 mm HPL C column. Quantitation of each analyte was based on the daughter ion transitions of the anal yt e and the respective internal standard analog. The responses of L C/MS/MS sy stem to each anal yt e and its internal standard were measured in samples and in standards, and a relative response was calculated (calculated as the ratio of the analy te and the stable isotopically

labeled internal standard responses). The relative response of the anal yt e in each sample was compared to the relative response of the analy te in the standards. The total deltamethrin r esidue is the sum of the individual measured residue of cis
deltamethrin and trans
- deltamethrin. 3. Magnitude of residues. Two field trials were conducted to measure the magnitude of deltamethrin residues in/on alfalfa, leaf lettuce, and grass following each of ten broadcast foliar ultra
- low volume (ULV) spray applications of BES0668 Insecticide. BES0668 Insecticide was applied to alfalfa, leaf lettuce, and grass at two different target rates of 0.75 g ai/ha/application and 1.5 g ai/ha/application. The interval between applications was 2 to 4 day s. All applications were made with ULV misters that produced droplets ty

pical of commercial equipment ( ≥80% of the droplets were <20 μm in diameter). Results: Alfalfa ; Based on the average residues in alfalfa forage, residues would be expected to remain b elow 0.050 ppm following multiple treatments at either rate. At the 1.5 g ai/acre/application treatment rate, total residues varied from 0.0174 ppm to 0.1205 ppm with the average residues remaining below 0.080 ppm at all time points. Since the dried matrix of alfalfa hay

is only used for animal feed, secondary residues in meat milk, and eggs arising from this use at either rate would be expected to be negligible. Leaf Lettuce ; At both the 0.75 g ai/acre/application and the 1.5 g ai/acre/application treatment rates, all residues in leaf lettuce at all time points were below the current food use tolerance (<0.050 ppm). Based on the average residues in leaf lettuce, residues would be expected to remain below 0.050 ppm following multiple treatments at eithe r rate. Grass ; Based on the average residues in grass forage, residues would be expected to remain at or below 0.050 ppm following multiple treatments at either rate. At the 1.5 g3

a i/acre/application treatment rate, total residues varied from 0.0298 p pm to 0.1495 ppm with the average residues remaining below 0.1200 ppm at all time points. Since the dried matrix of grass hay forage is onl y used for animal feed, secondary residues in meat milk, and eggs arising from this use at either rate would be ex pected to be negligible. B. Toxicological Profile 1. Acute toxicity. The acute oral toxic potency of deltamethrin depends on the vehicle that is used, with an LD50 in rats that ranges from 66.7 mg/kg (males) when administered in sesame oil to >5000 mg/kg (both sexes) in an aqueous methy lcellulose suspension. Deltamethrin technical is classified in Category II for acute oral and inhalation toxicity , Category I II for dermal toxicity and ey e irritation and Category I V for skin irritation. Deltamethrin is not a skin sensitizer but can cause transient paresthesia (a local itching, burning or tingling sensation of the skin) following skin contact to sensitive individuals. 2. Genotoxic i ty. There was no evidence of mutagenicity in a battery

of in vitro and in vivo studies with technical
- grade deltamethrin. Therefore, deltamethrin is classified as non
- mutagenic. 3. Reproductive and developmental toxicity. A rat development toxicity study conducted with deltamethrin indicated a maternal NOEL of 3.3 mg/kg/day based on clinical observations, decreased weight gain and mortality . The developmental NOEL was 11mg/kg/day

(HDT). In a rabbit development toxicity study with deltamethrin, the maternal NOEL was considered to be 10 mg/kg/day based on decreased body wei ghts at 32 mg/kg/day
. The developmental NOEL was > 32 mg/kg/day (HDT). In a developmental neurotoxicity study , the maternal NOAEL was 6.8 mg/kg bw/day , based on decreased bod y weight, weight gain and food consumption during gestation and decreased bod y weight and food consumption during lactation noted at 16 mg/kg/day
. The offspring NOAEL was 6.8 mg/kg bw/day , based on delay ed balanopreputial separation, reduced bod y weight and weight gain before weaning for both sexes, with recovery after weaning. Ther e was no evidence of neurodevelopment effects at an y dose level. In a two
- generation rat reproduction study with deltamethrin the parental NOAEL was 5.4 mg/kg/day

based on clinical signs and increased mortality . The offspring NOAEL was 5.8 mg/kg/day

based on decreased bod y weights, body weight gain and increased pup mortality . Deltamethrin was not a reproductive toxicant. 4. Subchronic toxicity. A 90
- day rat oral toxicity

study was conducted with deltamethrin administered by gavage. The NOEL was 1.0 mg/k g/day based on reduced body weight gain and slight hy persensitivity . In another 90
- day rat dietary study

with deltamethrin, the NOEL was 300 ppm (23.9 mg/kg/day for males, 30.5 mg/kg/day for4

females) based on uncoordinated movement, unstead y gait, tremors, increased sensitivity

to sound, shakes and spasmodic convulsions. The difference in the NOEL between the two studies is attributed to the different routes of exposure (gavage in oil vs. administered in diet). A 12
- week study

was conducted with deltamethr in in mice. The NOEL was 300 ppm (61.5 mg/kg/day

in males and 77.0 mg/kg/day in females) based on chronic contractions, convulsions, poor condition, decreased weight gain and mortality
. Two 13
- week dog studies were conducted with deltamethrin. In the fir st study , beagle dogs were administered deltamethrin by capsule using PEG 200 as a vehicle. The NOEL for this study

was 1 mg/kg/day

based on tremors, unsteadiness, jerking movements, salivation, vomiting, liquid feces and/or dilation of the pupils. In the second study , deltamethrin was administered by capsule without a vehicle to beagle dogs. The NOEL for this study was 10 mg/kg/day

based on unstead y gait, tremors, head shaking, vomiting and salivation. The difference in toxicity between the two studies is attributed to the enhanced absorption resulting from the use of PEG 200 as a vehicle in the first study
. A 21
- day dermal toxicity

study was conducted with deltamethrin in rats. The NOEL for sy stemic toxicity

was determined to be 1000 mg/kg/day
. Ina s ubchronic inhalation study , rats were exposed to aerosolized deltamethrin for 6 hours per day , 5 day s per week, for a total of 14 days over 3 weeks. Based on slightly decreased bod y weights and neurological effects at higher dose levels, it was concluded that 3 pg/Lwas the NOEC for s ys temic effects in this study
. 5. Chronic toxicity. Deltamethrin was administered in the diet to beagle dogs for 2 y ears. No treatment
- related effects were observed and the NOEL was judged to be 40 ppm (1.1 mg/kg/day). In an other stud y, deltamethrin was administered b y capsule (without a vehicle) to beagle dogs for 1 ye ar. The NOEL in this study was determined at 1 mg/kg/day

based on clinical signs, decreased food consumption and changes in several hematology

and blood chemis try

parameters. Two rat chronic toxicity

/oncogenicit y studies were conducted with deltamethrin. In the first study , the test substance was administered via the diet to rats for 2 y ears. The NOEL for this study

was 20 ppm (1 mg/kg/day) based on slightly d ecreased weight gain. In a more recent study , deltamethrin was administered to rats in the diet for 2 y ears. The NOEL for this study

was 25 ppm (1.1 and 1.5 mg/kg/day for males and females, respectivel y) based on neurological signs, weight gain effects and increased incidence of histopathological changes to the liver. No evidence of carcinogenicity was noted in either study
. Two mouse oncogenicit y studies were conducted with deltamethrin. In the first study , deltamethrin was administered in the diet for tw o y ears. No adverse effects were observed and the NOEL was 100 ppm (12 and 15 mg/kg/day , respectivel y, for males and females). In another study, deltamethrin was administered in the diet to mice for 975

weeks. The NOEL was 1000 ppm (15.7 and 19.6 mg/kg/day) based on a higher incidence of poor ph ys ical condition and a slight transient weight reduction. There was no evidence of oncogenicit y in either study. 6. Neurotoxicity. Deltamethrin was administered by single gavage in rats. The NOAEL was 5 mg/kg/day, based on salivation, soiled fur, impaired mobility , no response to approach or touch in several animals at 15 mg/kg. There was no evidence of neuropathological effects. In a subchronic neurotoxicity study , deltamethrin was administered in the diet of rats for 13 weeks. The NOAEL was 15 mg/kg/day , based on mortality , clinical signs of toxicity , FOB findings, and decreased bod y weights, body weight gains, and food consumption at 56 mg/kg/day . There was no evidence of neuropathological effects. 7

. Animal metabolism. The absorption of deltamethrin appears to be highl y dependent upon the route and vehicle of administration. Once absorbed, deltamethrin is rapidly and extensively

m etabolized and excreted, primarily w ithin the first 48 hours, in feces and an ap proximately e qual amount in urine. Absorbed deltamethrin is cleaved by hy drol ys is at the ester site followed b y rapid sulfate and glucuronide conjugation. 8. Metabolite toxicology
. N
- A Remove 9

. Endocrine disruption
. No special studies have been con ducted to investigate the potential of deltamethrin to induce endocrine effects. However, the standard battery of required toxicity

studies include an evaluation of the potential effects on reproduction and development, and an evaluation of the pathology o f the endocrine organs following repeated or long
- term exposure. There is no evidence that deltamethrin induces endocrine disruption. C. Aggregate Exposure 1. Dietary exposu re. As reported in the 2/17/2010 Human Health Assessment Scoping Document, the dietary exposure database is adequate to support the registration review of deltamethrin. Addition of Wide Area Mosquito Control use of deltamethrin s hould be covered b y existing food handling area tolerances
. Oral exp osure to BES0668 Insecticide product would be practically non - existent, because the product would not be applied directl y to food crops. Therefore, additional dietary exposure would be negligible, such that there is no need to include this use in the dietary assessment for deltamethrin. 2
. Non

- dietary exposure . a. Occupational exposure Deltamethrin for public health mosquito adulticide uses on food/feed c ommodities are to be applied by PCOs only , using ULV aerial applications. The potential exposures and associated risks for handlers mi xing, loading and applying deltamethrin as a mosquito adulticide are based on the proposed label for BES0668 Insecticide ( deltamethrin 2% liquid formulation). The maximum application rate is6

0.00 134 lb ai/acre per day , or 0.036 lb ai/acre per y ear . A maxi mum of 25 applications are allowed per ye ar. Aerial mixer/loaders are expected to have the highest exposure potential resulting from the occupational use of BES0668. There will be no residential non
- occupational applications. Unit dermal and inhalation e xposures of 37.6 μg/lb a.i. and 0.219 μg/lb a.i., respectivel y for a mixer/loader wearing long pants, a long
- sleeved shirt, and protective gloves were obtained from the EPA Occupational Pesticide Handler Unit Exposure Surrogate Reference Table March 2013 v ersion. A mixer/loader preparing spray solution to treat 1200 acres/day

will handle 1.6 lb a.i./day . The dermal and inhalation daily exposures for an 80
- kg individual are calculated as follows with a 1% dermal absorption. Daily Dermal Exposure: 37.6 μg/lb a.i. x 1.6 lb a.i./day x 0.01 ÷ 80 kg = 0.0075 μg/kg/day Daily I nhalation Exposure: 0.219 μg/lb a.i. x 1.6 lb a.i./day ÷ 80 kg = 0.0044 μg/kg/day The dermal and inhalation toxicity endpoints for risk assessment are 1.0 mg/kg/day and 0.9 mg/kg/day

from the 90
- day

rat oral toxicity

and the 21
- day

rat inhalation toxicity studies, respectivel y. The MOEs for dermal and inhalation exposure are 133,000 for dermal exposure and 204,500 for inhalation exposure. Pilots and ground mixer/loaders and applicators will have larger MOEs. b. Residential (Non

- occupational) exposure and risk Since applications for public health mosquito control are to be made b y professional personnel (i.e., not residential) a residential handler exposure assessment is not required; howev er, there are potential post application exposures to adults and children from the ULV aerial applications of etofenprox uses in the vicinity of residential dwellings. Based on spray drift residue deposition testing submitted with this application, an adu lt whole body surface area is approximately 18,000 cm2 so that the spray drift potential exposure to an 80 kg adult 100 feet downwind would range from 6.3 μg/kg to 15 μg/kg. Based on the Agency ’s 1% dermal absorption factor and the short
term dermal expo sure NOAEL of 1 mg/kg/day the MOEs for b ys tanders would range from 67,000 to 160,000 showing minimal risk potential from drift. It is important to note that applications are not supposed to occur in a manner that could directly exposure someone to the drif

t. These residues would yield MOEs for toddlers in excess of 1000 based on the Residential SOP defaults. D. Cumulative Effects Deltamethrin is a p yrethroid insecticide. In the cumulative risk assessment for py rethroids, the EPA determined that py rethro ids perturb the kinetics of neuronal voltage
- gated sodium ion channels (VGSC) following an action potential in vertebrates as a common mode of action. However, exposure to deltamethrin according to the proposed use pattern is expected to be negligible and therefore would not contribute to aggregate exposure or cumulative exposure assessment. T he Agency currently retains a7

3x FQPA safety

factor for all py

rethroid insecticides, as per the Cumulative Risk Assessment for Py

rethroids (2012) , based on evidence o f underdeveloped clearance mechanisms in neonatal rats reported in the published literature.
. E. Safety Determination 1. U.S. population. Based on the negligible potential for exposure and completeness of the toxicology database, it can be concluded that aggregate exposure to residues of deltamethrin present a reasonable certainty of no harm. The proposed mosquito adulticide use pattern will produce onl y negligible dietary or drinking water exposures. Thus, there is a reasonable certaint y that the use o f deltamethrin in BES0668 Insecticide as a mosquito adulticide will present no harm from aggregate exposure. 2. Infants and children
. FFDCA section 408 provides that EPA shall apply an additional ten
- fold safety factor for infants and children in the ca se of threshold effects to account for pre and post natal toxicity and the completeness of the database, unless EPA determines there is sufficient evidence to support a different safety . The database is complete for FQPA purposes and there are no residua l uncertainties for pre
- /post
- natal toxicity for deltamethrin, with submission of the immunotoxicity study (OPPTS 870.7800). However, the Agency currentl y retains a 3x FQPA safet y factor for all py rethroid insecticides, as per the Cumulative Risk Assessme nt for Py rethroids (2012), based on evidence of underdeveloped clearance mechanisms in neonatal rats reported in the published literature. The use pattern for the mosquito adulticide provides expectation of negligible exposure to infants or children. Thu s, it can be concluded that there is a reasonable certainty

that no harm will result from aggregate exposure to deltamethrin residues. F. International Tolerances Deltamethrin is a broad spectrum insecticide used throughout the world to control pests of livestock, crops, ornamentals plants and turf, and household, commercial, and industrial food use areas. As a consequence a large number of CODEX MRL s exist for deltamethrin. The MRLs can be found at the following link; http://www.codexalimentarius.net/pestres/data/pesticides/details.html?id=135