Page 2 of 18 

### Table of Contents

1. Executive Summary 3

2. Proposed Use Profile 6

3. Hazard Characterization 7

4. Residential Exposure and Risk 9

5. Occupational Exposure and Risk 9

5.1 Handler 9

5.2 Postapplication 14

6. Data Needs and Labels Recommendations 17Page 3 of 18 1.0 Executive Summary

The registrant, Nichino, has submitted a request for a Section 3 registration for a proposed use of the new active ingredient (ai) tolfenpyr ad to control thrips, aphids and scales on ornamental plants grown in greenhouses. Tolfenpyrad is a pyrazole insecticid e that inhibits respirati on of target pests through the inhibition of the respiratory el ectron transport chain. Inhibition results in ve ry rapid insecticidal responses, including cessation of movement and feedi ng, lack of fecundity, and eventual death of the

pest.

The end-use product (EP), Tolfenpyrad 15EC Insecticide is formulated as an emulsifiable concentrate (EC) and contains 15% of the ai, tolfenpyrad. It is applied by b ackpack sprayer, high pressure handwand, and low pressure handwand. Since the product is only applied commercially in greenhouses, there are no food or re sidential uses associated with this ai. The proposed maximum single application rate is 0.003 lb ai /gallon of water. The total app lication rates (AR) range from 0.003 – 0.006 lb ai per gallon, per crop cycle, or growing season. In addition, two separate spray volumes are specified on the label, resulting in a range of application rates from 0.68 to 1.36 lb ai/A. Based on the number of seasonal applications (2 applications per crop cycle, with a minimum re-treatment interval, RTI, of 10 days) indicated on product la bels and information provi ded by the registrant, nondietary exposures are expected to be of short-, intermediate and l ong-term durations for occupational handlers and for workers conducting pos tapplication activities in greenhou ses. No chemical specific data were submitted in support of the occupational exposure assessments for tolfenpyrad, so HED used default assumptions with respect to handler unit exposure, as well as for assessing postapplication exposure and risk (i.e., dissipation on ornamental plants, and standard transfer coefficients, TCs, for postapplication activities).

Hazard Profile and Points of Departure (POD)

The toxicology database for tolfenpyrad is adequate for risk assessment. The current toxicity database for tolfenpyrad indicates moderate to xicity (Category II) via the acute oral route of exposure and mild toxicity (Category III) via the de rmal and inhalation routes of exposure. Tolfenpyrad is mildly irritating (Category III) to the eye and slightly irrita ting (Category IV) to the skin. It is not a skin

sensitizer.

A variety of toxic effects were noted in the toxicology database for tolfenpyrad. The most consistent finding across species and studies was effects on body weight and body weight gain. Decreases in body weight and/or body weight gain were observed in adults of all sp ecies (rat, mice, rabbit, and dog) in the majority of the subchronic oral and dermal toxi city studies, and all chr onic toxicity studies. The rat species is most sensitive to body weight changes, with effects obser ved at much lower doses than in other species. In rats, signifi cant decreases in body weight and body weight gain were observed in subchronic oral, and acute and subc hronic neurotoxicity studies.

The body weight changes observed in the database were most often seen in the presence of decreased food consumption and in some studies, additional t oxicity including liver/kidne y effects and clinical signs. Moribundity and/or mortality were also noted in at least one study in all species. However, this was observed in the presence of body weight changes and mainly observed at the highest dose tested (HDT).Page 4 of 18 Although a possible increase in qu alitative susceptibility was observed in a developmental immunotoxicity study, there was no evidence of increa sed quantitative suscep tibility. Additionally, there was no evidence of increased quantitative or qualitative susceptibility in developmental toxicity or reproduction studies. Therefore, there is no residual concern for increased suscepti bility and no concern for immunotoxicity or neurotoxicity. Tolfe npyrad is classified as “not likely to be carcinogenic to humans.”

For purposes of the current risk assessment, endpoi nts were selected for occupational short- and intermediate-term inhalation exposures and short-, intermediate-, and long-term dermal exposures. For dermal exposures, a route-specific 21-day dermal toxi city study in rats was us ed for endpoint selection. However, an extra 3x uncertainty factor (UF, subchr onic to chronic) was app lied to long-term dermal

risk assessments since the short-te rm dermal study was used to asse ss long-term dermal exposure.

For short-and intermediate-term inhalation exposures , a 4-week inhalation study was used for endpoint

selection. No toxic effects were observed up to the no observed adve rse effect level (NOAEL) of 10 mg/m 3 (EPA calculated dose = 2.6 mg/kg/day) and the lowest observed adverse effect level (LOAEL) was not determined. However, it was stated in th e inhalation study that mort ality was observed in a range-finding study at 26 mg/m 3 (6.8 mg/kg/day). HED used th e NOAEL of 2.6 mg/kg/day from the 4-week inhalation study for risk assessment; regard less, the range-finding study should be submitted to the Agency for review as a condition of registration.

For short-, and intermediate-term dermal and inhala tion assessments, a combined UF of 100x served as the basis for the level of concern (LOC) for occupati onal risk, or margins of exposure (MOEs). For the long-term dermal assessment, a combined UF of 300x se rved as the basis for th e LOC. Therefore, for short-, and intermediate term dermal and inhalation risk assessments, MOEs greater than 100 are not of concern. For long-term dermal risk assessments , MOEs greater than 300 are not of concern.

Occupational Handlers Exposure

No chemical-specific handler exposure data were s ubmitted in support of this registration. Therefore, data from the Pesticide Handlers Exposure Database (PHED) Version 1.1 were used to assess handler exposures (HED Science Advisory Council for Exposure (ExpoSAC), SOP No. 7, January 1999). A summary of the risks for occupa tional handlers is included in Ta ble 4. The maximum application rate for each exposure scenario was assessed (i.e., 0.003 lb ai/g al). All handler short- and

intermediate-term scenario s resulted in MOEs greater than th e level of concern (MOEs > 100) with risk mitigation (e.g., chemical-resistant gloves). L ong-term handler risks were also not of concern (MOEs > 300). HED recommends all handlers wear a long-sleeved shirt, long pants, socks, chemical-resistant gloves, and footwear as stated in the proposed label.

Occupational Postapplication Exposure

Dermal

No chemical-specific data, such as dislodgeable foliar residue (DFR) studies, were submitted for the purpose of conducting a postapplication exposure a ssessment. Therefore, HED used default assumptions with respect to dissipation on ornament al plants, standard TCs for various postapplicationPage 5 of 18 activities, and “day 0” foliar resi due values (i.e., residues after in itial treatment). The two spray volumes specified on the label were used to determin e the application rate on a per acre basis, in order to determine the potential exposure from contacting tr eated foliage; these per acre application rates were 0.68-1.36 lb ai/A. The same study (as well as dose and endpoint) was selected for assessing short- and intermediate-term dermal exposure. Si milarly, the same study was selected for short-and intermediate-term inhalation exposur e. Therefore, short-term expos ure and risk calculations were considered representative/protect ive of intermediate-term exposure and risk. Long-term exposure and

risk were also calculated.

The short- and intermediate-term postapplication risks for ornamental crops were not of concern. Long-term postapplication MOEs are not of concern for low-medium contact activities (i.e., pruning, tying, hand pinching, and nursery ac tivities). For long-term postappl ication high contact activities (i.e., cutting flowers), a REI of 4 days would be needed to reach the target MOE of 300 at the maximum spray volume/A (AR=1.36 lb ai/A). Ho wever, it should be noted that long-term ( ≥ 6 months-1 year) dermal postapplica tion exposure was estimated assumi ng the same residue calculated on the day of initial treatment. HED believes the re sidue available for exposure after 6 months or longer is likely to be lower than the residue value estimated on day of initial treatme nt. Considering

the nature of the residues used for risk assessm ent, the MOE = 210 (on da y 0) for high contact postapplication activities (A R=1.36 lb ai/A) is recognized as a cons ervative risk estimate. Submission of a chemical-specific DFR study for greenhouses is recommended to refine the residue values and reduce this uncertainty for high contact scenarios.

Inhalation

The Worker Protection Standard (WPS) for Agri cultural Pesticides contains requirements for protecting workers from inhalati on exposures during and after gree nhouse applications through the use of ventilation requirements. Tolfenpyrad has a vapor pressure of 3.0 x 10 -8 mm Hg. Although there is potential for postapplication inhalation exposure resulting from the us e of tolfenpyrad in greenhouses, with proper use of ventila tion, tolfenpyrad inhala tion exposure is expected to be negligible. Therefore, a quantitative postapplica tion inhalation exposure assessment was not performed. This approach may

be revisited in the future with potential changes in the Agency’s approach for assessing inhalation exposure and risk.

Restricted Entry Interval

The REI specified on the proposed label is based on the acute toxicity of th e tolfenpyrad technical

material. Based on the acute t oxicity profile of tolfenpyrad, the 24 hour REI appearing on the proposed label is appropriate for low, medium , and high contact postap plication activities.

Review of Human Research

This risk assessment relies in part on data from studies in which adult human subjects were intentionally exposed to a pesticide or other chemical. These studies, which comprise PHED and the Agricultural Reentry Task Force (ARTF), have been determined to require a review of their ethical conduct, have received that review, and have been determined to be ethically conducted.Page 6 of 18 Conclusions and Recommendations

Risks for occupational handlers who apply Tolfenpyr ad 15EC Insecticide on ornamental plants in greenhouses are not of concern to HED. Risks from short- and intermediate-term postapplication activities are also not of concern. Risks from long -term postapplication activities have been assessed

in a conservative manner and are detailed above.

Based on the current risk assessment, HED recommends:

• All handlers should wear a long-sleeved shirt, lo ng pants, socks, chemical-resistant gloves and

footwear as stated in the proposed label.

• The proposed label personal protective equipment (PPE) language should be revised to state the

use of: “ Chemical-resistant gloves made of materi als such as barrier laminate or polyvinyl

chloride. ”

• The default dislodgeable foliar re sidue (DFR) values and assumpti ons used in the assessment may be under or overestimated. Therefore, subm ission of a chemical-specific DFR study for greenhouses is recommended to reduce this uncerta inty, and could potentia lly result in reduced exposure and risk estimat es for all scenarios.

• To determine the exposure duration that needs to be assessed for future registration actions, the applicant could provide the Agency with informati on to characterize the use pattern for the end-use product (EP) containing tolfenpyrad. Such in formation might include specific seasonal information about the use to be assessed, major regions on which the product is applied and how the product fits with other act ive ingredients in pest resistance management programs.

• The Registration Division (RD) shoul d ensure that the appropriate re stricted reentry interval (REI) is included on the proposed label.

• Proprietary data from the Agricultural Reentry Task Force (ARTF) have been used in this assessment. The chemical review manager (CRM) is encouraged to pursue data compensation in the event the registrant is not a member of this respective task force.

2.0 Proposed Use Profile

The proposed use pattern and formulation specifie d in the EP containing tolfenpyrad for this registration request is summarized in Table 1. Applications of Tolfe npyrad 15EC Insecticide are to be made using foliar spray equipment. The proposed label has a PPE requirement that applicators and

other handlers wear a lo ng-sleeved shirt, long pants, socks, ch emical-resistant gloves, and footwear.Page 7 of 18 Table 1. Summary of Proposed Use Pa tterns and Formulations for Tolfenpyrad.

Formulation Method of Application Use Sites Application Rate Timing of Application

Tolfenpyrad 15EC

Insecticide

- emulsifiable

concentrate (15% a.i.)

For Commercial use EPA Reg #71711-XX
(1.25 lb ai/gal) foliar spray by low and high

pressure handwand, backpack

sprayer greenhouse-grown ornamental plants (ash, yew, rose, evening primrose, gladiolus, cherry, arrowood, marigold, moss rose, new guinea impatiens, petunia, gerbera, chrysanthemum, coleus, poinsettia, schefflera, lantana) Max single appl. rate = 0.00313 lb ai/gal
(0.68 - 1.36 lb ai/A)‡ 2 apps per crop cycle (0.006 lbs ai/gal); 24-hour REI; 10-day interval between apps; Apply uniformly.
Do not apply more than 100 gallons per 20,000 ft 2 (218 gal/A) up to 10 gallons per 1,000 ft 2 (436 gal/A).

‡ Lower Spray Volume = 0.68 lb ai/A (at 100 gal/20,000 ft 2 = 218 gal/A) 0.00313 lb ai/gal * 218 gal/A = 0.68 lb ai/A Higher Spray Volume = 1.36 lb ai/A (at 10 gal/1000 ft 2 = 436 gal/A) 0.00313 lb ai/gal * 436 gal/A = 1.36 lb ai/A

3.0 Hazard Characterization

The toxicology database for tolfenpyrad is adequate for risk assessment. The current toxicity database for tolfenpyrad indicates moderate to xicity (Category II) via the acute oral route of exposure and mild toxicity (Category III) via the de rmal and inhalation routes of exposure. Tolfenpyrad is mildly irritating (Category III) to the eye and slightly irrita ting (Category IV) to the skin. It is not a skin

sensitizer.

Decreases in body weight and body weight gain were also seen in chroni c rat studies but at lower doses

than observed in the other rat st udies. Although these effects we re seen at lower doses, the body weight decrements noted in the chronic study were not as pronounced as they were in the subchronic study or in the neurotoxicity st udies. Decreases in body weight and body weight gain were also observed in the reproduction study, the developmenta l toxicity, and the developmental immunotoxicity studies at doses comparable to th e chronic study. Decreases in body wei ght gain were also seen in a 21-day dermal toxicity study, but in the absence of any other systemic toxicity. The body weight changes observed in the database were most often s een in the presence of decreased food consumption and in some studies, additional toxic effects (liver/kidney eff ects, clinical signs, etc).

Body weight changes observed in other species were similar in magnitude to those in rats, but were observed at higher doses. Signifi cant decreases in body weight and body weight gain were seen in both mice and dogs after subchronic exposure; thes e effects were also noted in rabbits in a developmental study. Chronic exposure resulted in body weight and body weight gain decreases in mice and dogs at lower doses. The severity of body we ight changes increased with dose in mice while body weight effects in dogs were seen onl y at the highest dose tested (HDT).Page 8 of 18 Moribundity and/or mortality were noted in at least one study in all species and mainly observed at the HDT. In all cases, effects were observed in the pr esence of body weight cha nges, as well as other toxic effects in mice and dogs (liver/ki dney effects and clinical signs).

Other toxic effects noted in the database included effects on the li ver and kidney in rats and dogs. Additionally, effects on the harderian gland and lymph nodes were seen in rats and testicular atrophy and clinical signs were seen in dogs . No treatment-related effects were noted in the liver or kidney in mice; however, rough coats, hunched posture, ataxia , hypoactivity, and clinical signs including missing ears and ear lesions (scabs, sores, ulcer ation, and inflammation) were noted.

A possible increase in qualitative susceptibility wa s seen in a developmenta l immunotoxicity study; however, there was no evidence of increased quantita tive susceptibility. Additionally, there was no evidence of increased quantitative or qualitative susceptibility in developmental toxicity and reproduction studies. As a result, there is no conc ern for increased quantita tive and/or qualitative susceptibility of young animals to tolfenpyrad. Th ere is also no concern for neurotoxicity or immunotoxicity.

There was no evidence of carcinogenicity in cance r studies with mice and rats. Therefore, in

accordance with EPA’s Final Guidelines for Carci nogen Risk Assessment (March, 2005), tolfenpyrad is classified as “not likely to be carcinogenic to humans.”

For short-, intermediate-, and long-term dermal e xposures, a route-specific 21-day dermal toxicity study in rats was used for endpoint selection. Howe ver, an extra 3x UF (subchronic to chronic) was applied to long-term dermal risk assessments sin ce the short-term dermal study was used to assess long-term dermal exposure.

For short-and intermediate-term inhalation exposures , a 4-week inhalation study was used for endpoint

selection. No toxic effects were observed up to the NOAEL of 10 mg/m 3 (EPA calculated dose = 2.6 mg/kg/day) and the LOAEL was not determined. Ho wever, it was stated in the inhalation study that mortality was observed in a range-finding study at 26 mg/m 3 (6.8 mg/kg/day). HED used the NOAEL of 2.6 mg/kg/day from the 4-week inhalation study for risk assessment; rega rdless, the range-finding study should be submitted to the Agency for review as a condition of registration.

Table 2. Acute Toxicity Profile –Tolfenpyrad (Technical Ingredient).

Guideline

No. Study Type MRID(s) Results Toxicity Category

870.1100 Acute oral –Rat 47457501 LD 50 Females => 386 mg/kg bw

LD 50 Females =>150 mg/kg bw

LD 50 Combined =>239 mg/kg bw II

870.1200 Acute dermal-Rat 47457503 LD 50 Males > 2000 mg/kg bw

LD 50 Females > 3000 mg/kg bw

LD 50 Combined > 2500 mg/kg bw III

870.1300 Acute inhalation-Rat 47447734 LC 50 Males >2.21 mg/L

LC 50 Females >1.50 mg/L

LC 50 Combined >1.82 mg/L III

870.2400 Acute eye irritation-Rabbit 47457505 Mildly irritating IIIPage 9 of 18 870.2500 Acute dermal irritation-Rabbit 47457507 Slightly irritating IV

870.2600 Skin sensitization-Guinea Pig 47447740 Not Sensitizing -

Table 3. Summary of Toxicological Doses and Endpoin ts for Tolfenpyrad for Us e in Occupational Human

Health Risk Assessments.

Exposure/

Scenario Point of Departure Uncertainty

Factors Level of Concern

for Risk

Assessment Study and Toxicological Effects

Dermal

Short-Term

And

IntermediateTerm (Up to 6 months of Exposure) NOAEL=

200 mg/kg/day UF A = 10 x

UF H =10 x Occupational LOC

for MOE = 100 No LOAEL determined in 21-day dermal study in rats; not tested up to the limit dose of 1000 mg/kg/day.

Only minimal changes in body weight gain (no absolute body weight changes) and food consumption were observed in the study and

not considered adverse

Dermal LongTerm (>6 months) NOAEL=

200 mg/kg/day UF A = 10 x

UF H =10 x

UF S =3 x Occupational LOC

for MOE = 300 No LOAEL determined in 21-day dermal study in rats; not tested up to the limit dose of 1000 mg/kg/day.

Only minimal changes in body weight gain (no absolute body weight changes) and food consumption were observed in the study and

not considered adverse

Inhalation

Short-Term

And

IntermediateTerm (Up to 6 months of Exposure) NOAEL= 2.6 mg/kg/day

IAF = 100% UF A = 10 x

UF H =10 x Occupational LOC

for MOE = 100 No LOAEL determined 4 week inhalation study in rats. No effects observed up to 2.6 mg/kg/day in main study. Mortality observed at 6.8 mg/kg/day in a range-finding study (not available).

Cancer (oral, dermal, inhalation) Classification: “Not likely to be Carcinogenic to Humans” based on the absence of significant tumor increases in two adequate r odent carcinogenicity studies.

NOAEL = no observed adverse effect level. LOAEL = lowest observed adverse effect level. UF = uncertainty factor. UF A = extrapolation from animal to human (interspecies). UF H = potential variation in sensitivity among members of the human population (intraspecies). UF S = use of a short-term study for long-term risk a ssessment. MOE = margin of exposure. LOC

= level of concern.

4.0 Residential Exposure and Risk

Tolfenpyrad has no residential uses, and no occupational uses at resident ial sites are being requested at this time; therefore, no residential risk assessm ent has been conducted. Furthermore, no bystander exposure is expected since appli cations are only anticip ated to be made in greenhouses settings.

5.0 Occupational Exposure and Risk

5.1 Handlers

Tolfenpyrad 15EC Insecticide is formulated as an em ulsifiable concentrate (E C) and contains 15% of the ai, tolfenpyrad. The product is to be applied by backpack spra yer, high pressure handwand, and low pressure handwand equipment. The proposed ma ximum single application rate is 0.003 lb ai perPage 10 of 18 gallon. The application rates range from 0.003 – 0.006 lb ai per gallon pe r crop cycle. In addition, two separate spray volumes are specified on the label, re sulting in a range of a pplication rates of 0.68 to 1.36 lb ai/A. Based on the number of seasonal applic ations (2 applications per crop cycle, with a minimum 10-day RTI) indicated on product labels and information provided by the registrant, nondietary exposures are expected to be of short-, intermediate- and l ong-term durations for occupational

handlers.

However, based on integrated pest management pr actices and chemical rotations, long-term handler exposures are considered to be less likely and any assessments of such exposures are likely to be conservative. No handler activities are expected for more than 6 consecutive months. Since doses selected for short-, intermediate- and long-term a ssessments are the same, the short-term exposure and risk assessment is protective of long-term exposures.

The following handler exposures result from dermal and inhalation routes for the proposed greenhouse

uses:

• Mixing/Loading/Applying Liquid Formul ation for High Pressure Handwand

• Mixing/Loading/Applying Liquid Formul ation for Low Pressure Handwand

• Mixing/Loading/Applying Liquid Form ulation for Backpack Sprayer

5.1.1. Data and Assumptions for Handler Exposure Scenarios

The assumptions, parameters and factors us ed for the exposure calculations include:

• Application rates were based on the proposed label. Maximum application rate on proposed label = 32 oz/100 gal . Product contains 1.25 lb ai/gal (0.0098 lb ai/fl oz). Maximum Single Application Rate = 32 oz/ 100 gal * 0.0098 lb ai/fl oz = 0.00313 lb ai/gal

• Unit Exposures: Chemical-specific data for asse ssing exposure during pes ticide handling activities were not submitted to the Agency in support of this Section 3 application. It is HED policy to use data from PHED to assess handler exposures for regulatory actions when chemical-specific data are not available (HED ExpoSAC, SOP No. 7, January 1999).

The baseline clothing level was us ed as a starting point to calcula te handler exposures, even though the proposed label recommends the use of baseline clothing plus chemical -resistant gloves. Depending upon the need for additional dermal prot ection, additional PPE is added to obtain an MOE higher than the LOC. The baseline clothing level for occupational exposure scenarios generally represents an individua l wearing long pants, a long-sl eeved shirt, shoes, socks, no chemical-resistant gloves, and no respirator. As re flected in the calculations included herein, PPE may involve the addition of chemical-resistant gl oves. For handlers mixing/loading and applying liquids with high and low pressure handwand and backpack sprayer, no data are available to assess

risks at baseline attire. Therefor e, those handler scenarios were as sessed at baseline plus chemicalresistant gloves.

The proposed label has PPE recommendations which include:Page 11 of 18 • Applicators and other handlers mu st wear a long-sleeved shirt, long pants, socks, chemicalresistant gloves and footwear.

• Area Treated: Based on HED’s Exposure Science Advisory Comm ittee SOP Number 9.1, the following gallons per day were assumed:

• 40 gallons/day for mixing/lo ading/applying liquids using low-pressure handwand, and backpack sprayer.

• 1000 gallons/day for mixing/loading/applyi ng liquids using high pressure handwand.

• Body Weight: The average adult body weight of 70 kg was used for all calculations, since the endpoints selected for risk assessment were not sex-specific.

Equations and Calculations:

Daily Exposure: Daily handler expos ures are estimated for each applicable handler task with the application rate, the amount of acres treated or gallons applied in a day, and the applicable unit exposure using the following formula:

Daily Exposure (mg ai/day) = Unit Exposure (μg ai/lb ai handle d) * Application Rate (lbs ai/A or gal) * Daily Amount Handled (A or gal/day) * Conversion Factor (mg/1,000 μg)

Where:

Daily Exposure = Amount (mg ai/day) deposited on the surface of the skin that is available for dermal absorption or amount inhaled that is available for inhalation absorption, Unit Exposure = Unit exposure value (μg ai/day), Application Rate = Normalized application rate based on a logical unit treatment (lb ai/acre), and Daily Amount Handled = Normalized application area based on a logical unit treatment such as acres or gallons (A/day or gal/day).

Daily Dose: Daily dose (inhalation or dermal) wa s calculated by normalizing the daily dermal or inhalation exposure value by body weight.

Average Daily Dose (mg/kg/day) = Daily Exposure (mg ai/day)/Body Weight (kg)

Where:

Average Daily Dose = Absorbed dose received from exposure to a pesticide in a given scenario (mg pesticide active ingredient/kg body weight/day), Daily Exposure = Amount (mg ai/day) deposited on the surface of the skin that is availabl e for dermal absorption or amount inhaled that is available for inhalation absorption, and Body Weight = Body weight determined to represent the population of interest in a risk assessment.

Margin of Exposure (MOE): The daily dermal dose and daily inhalation dose received by occupational handlers were compared to the appropriate POD (i.e., NOAEL) to assess the risk to occupational handlers for each exposure route. All MOE values were calculated separately for dermal and inhalation exposure levels us ing the following formula:Page 12 of 18 MOE = NOAEL (mg/kg/day)/Average Daily Dose (mg/kg/day)

Where:

MOE = Margin of exposure value used by HED to represent risk or how close a chemical exposure is to being a concern (unitless), ADD = Average daily dose (ADD) is absorbed do se received from exposure to pesticide, and NOAEL = Dose level in a toxicity study, where no observed adverse effects occurred in the study.

5.1.2. Exposure and Risk

Summaries of the short-term risks (MOEs) at baselin e (a long-sleeved shirt, long pants, shoes, and socks), and at baseline plus chemical-resistant gloves for handlers, are included in Table 4. The results

indicate that dermal and inhala tion risks do not exceed HED’s LOC, with MOEs greater than 100 at the baseline clothing scenario with the addition of chemical-resistant gloves, which are already specified on the proposed label.

HED recommends that the proposed label PPE language be amended from:

“Chemical-resistant gloves made of any waterproof material su ch as barrier laminate or polyvinyl chloride” to “Chemical-resistant gloves made of materials such as barrier laminate or polyvinyl chloride.”Page 13 of 18Table 4. Short- and Intermediate-Term Handler Exposure for Tolfenpyrad.ExposureScenarioMitigationLevelaDermal UnitExposureb(mg/lb ai)InhalationUnitExposureb(mg/lb ai)CropApplicationRatecAmountTreateddDermalDosee(mg/kg/day)DermalMOEfInhalationDoseg(mg/kg/day)InhalationMOEhShort- and Intermediate-TermMixing/Loadingand Applyingliquids for highpressurehandwandapplication(PHED data)Singlelayer,Gloves2.5 0.120 mg/lbaiOrnamentals 0.00313 lbai/gal1,000gallons/day0.11179 1,800 0.00537 480Mixing/Loadingand Applyingliquids for lowpressurehandwand(PHED data)Singlelayer,Gloves0.43 0.03 mg/lbaiOrnamentals 0.00313 lbai/gal40gallons/day0.00077 260,000 0.00005 48,000Mixing/Loadingand Applyingliquids forbackpacksprayerapplication(PHED data)Singlelayer,Gloves2.50 0.03 mg/lbaiOrnamentals 0.00313 lbai/gal40gallons/day0.00447 45,000 0.00005 48,000a. Baseline Dermal: Long-sleeve shirt, long pants, and no gloves.Baseline plus Gloves Dermal: Baseline plus chemical-resistant gloves.b. Unit Exposures based on PHED Version 1.1.c. Application Rates based on proposed use on label for tolfenpyrad.d. Exposure Science Advisory Council Policy No. 9.1.e. Dermal Dose (mg/kg/day) = Daily Unit Exposure (mg/lb ai) x Application Rate (lb ai/gal) x Gallons Treated / Body Weight (70kg).f. Dermal MOE = NOAEL (200 mg/kg/day) / Dermal Daily Dose (mg/kg/day). Short- and Intermediate-Term LOC = 100; Long-term LOC =300.g. Inhalation Dose (mg/kg/day) = Daily Unit Exposure (μg/lb ai) x Application Rate (lb ai/acre)x Acres Treated / Body Weight (70 kg).h. Inhalation MOE = NOAEL (2.6 mg/kg/day) / Inhalation Daily Dose (mg/kg/day). Level of concern = 100.Page 14 of 18 5.2 Postapplication

Based on the number of seasonal applications indicated on thes e product labels, the proposed greenhouse use pattern, and information provided by the registrant, postapplication exposures are expected to be short- (1-30 days), inte rmediate- (1-6 months), and long-term ( ≥ 6 months-1 year) in duration. However, only shor t-term and long-term exposures were quantitatively assessed.

Since doses selected for short- and intermediate -term assessments are the same, the short-term exposure and risk assessment is therefore protective of inte rmediate-term exposures. Since tolfenpyrad is going to be used on multiple rotati onal ornamental crops, workers are expected to conduct nursery postapplication activities and will pot entially be exposed to foliar residues more than 6 consecutive months per year.

Since no chemical-specific data such as DFR st udies were submitted to estimate postapplication exposure, postapplication activ ities were assessed using derm al TCs from ExpoSAC: ARTF Ornamental Plants Transfer Coefficients, Ap ril 2002, summarized in Table 5. In addition, default assumptions with respect to the fraction av ailable for transfer and residue dissipation (as described below) were used, along with the following:

• Application Rate = 0.68 – 1.36 lb ai/A, repr esenting the lower and higher spray volumes specified on the label and shown in Table 1.

• Exposure Duration = 8 hours per day

• Body Weight = 70 kg

The fraction of ai retained on foliage surfaces is assumed to be 20% (0.2) of the application rate on the day of initial treatment. This fraction is assumed to further dissipate at the rate of 10% (0.1) per day. These are standard values esta blished by HED ExpoSAC when no information is known about possible bonding to soil and foliar su rfaces and dissipation of the active ingredient

over time.

HED generally assesses exposure at “day 0” (i.e., on the day of treatment), and if MOEs are below the LOC, HED determines how many days w ould be needed in order to achieve an MOE

>100. These calculations take into consideration the type of reen try activities likel y to occur for a given scenario. Higher contact activities (suc h as hand harvesting or harvesting cut flowers) result in higher exposures, and ma y require longer reentr y intervals to be specified on the label.

Table 5. Anticipated Postapplication Activities and Dermal Transfer Coefficients for Greenhouse Use of Tolfenpyrad.

Proposed Crops Policy Crop/Group Category Transfer

Coefficients (cm 2 /hr) Activity Reference†

110 outdoor ornamental pruning, tying MRID 454695-01; ARTF Study No.

ART043 Ornamentals ash, yew, rose, evening primrose, gladiolus, cherry, arrowood, marigold, moss rose, new guinea impatiens, petunia, gerbera, 175 greenhouse hand pinching ornamentals;

nurseries activities MRID 453445-01; ARTF Study No.

ART039Page 15 of 18 chrysanthemum, coleus, poinsettia, schefflera,

lantana 400 harvest (workers moved plants to trucks and reorganized the gallon pots or containers) MRID 454695-02; ARTF Study No.

ART044

5100 (short-term) Cut flowers

2700(intermediateand long term) hand-harvesting MRID 465139-01

† The information in the table is based on proprietary and non-proprietary data.

5.2.1. Exposure and Risk

Inhalation

The WPS for Agricultural Pest icides contains requirements for protecting workers from inhalation exposures during and after greenhouse appli cations through the use of ventilation requirements. Tolfenpyrad has a vapor pressure of 3.0 x 10 -8 mm Hg. Although there is potential for postapplication inha lation exposure resulting from the use of tolfenpyrad in greenhouses, with proper use of ve ntilation, tolfenpyrad inhalation e xposure is expected to be negligible. Therefore, a quantitative postappl ication inhalation exposure assessment was not performed. This approach may be revisited in th e future with potential changes in the Agency’s approach for assessing inhalation exposure and risk.

Dermal

A summary of the postapplication MO Es and respective reentry interv als is provided in Table 6.

Based on the number of seasonal applications indicated on th e proposed product labels, and information provided by the registrant, postapplic ation exposures are expe cted to be shortintermediate- and long-term in dur ation for all ornamentals plants. Standard assumptions with respect to body weight, area trea ted, and TCs were used to calculate the MOEs for occupational reentry. Since the same endpoint was selected fo r short- and intermediate-term exposure, shortterm exposure and risk are representative/protec tive of intermediate-term exposures. For longterm exposures, HED provided a comparison of the estimated number of days required before an

MOE reached the LOC.

Two spray volumes were assessed with applicat ion rates ranging from 0.68-1.36 lb ai/A; the default approach was used for estimating REIs, since no DFR data were submitted.

The short- and intermediate-term postapplication assessments for ornamental crops resulted in MOEs of 100 or greater on “day 0” (immediately after application) fo r low, medium and high contact exposure activiti es (i.e., pruning, tying, hand pinchi ng, nursery activities, and cutting flowers) and were not of concern.

Long-term postapplication MOEs are not of concern for low-me dium contact activities (i.e., pruning, tying, hand pinching, and nursery activi ties). For long-term postapplication high contact activities (i.e., cu tting flowers), a REI of 4 days woul d be needed to reach the target MOE of 300 at the maximum spray volume/A (AR=1.36 lb ai/A). However, it should be noted that long-term ( ≥ 6 months-1 year) dermal postapplica tion exposure was estimated assuming thePage 16 of 18 same residue calculated on day of initial treatment (i.e., day “0” residue value). HED believes the residue available for exposure after 6 months or longer is likely to be lower than the residue value estimated on the day of initial treatment. The day “0” residue value used for long-term postapplication dermal assessment represents a hi gh-end assumption. Considering the nature of the residues used for the long-term postapplica tion risk assessment, the MOE = 210 (on day 0) for high contact activities at the maximum spray volume/A (1.36 lb ai/A) is recognized as a

conservative risk estimate.

Submission of a chemical-specific DFR study for greenhouses is recommended to refine the

residue values and reduce the uncertain ty for high contact scenarios.

Table 6. Short-, Intermediate- and Long-Term Po stapplication Exposure and Risk for Tolfenpyrad.

Crops Activity Application

Rate

(lb ai/A) DAT a

(TC - cm 2 /hr) DFR b (ug/cm 2 ) Daily Dose c (mg/kg/day) MOE d

Short- and Intermediate-term

0.68 0

(110 cm 2 /hr) 1.523 0.0191 10,000 pruning, tying

1.36 0

(110 cm 2 /hr) 3.046 0.0383 5,200

0.68 0

(175 cm 2 /hr) 1.523 0.0305 6600 hand pinching,

nursery activities 1.36 0

(175 cm 2 /hr) 3.046 0.0609 3,300

0.68 0

(400 cm 2 /hr) 1.523 0.0696 2,900 harvesting (workers moved plants

to trucks and reorganized the gallon

pots or containers) 1.36 0

(400 cm 2 /hr) 3.046 0.1393 1,400

0.68 0

(5100 cm 2 /hr) 1.523 0.8878 230 Ornamentals

hand harvesting; cutting

flowers 1.36 0

(5100 cm 2 /hr) 3.046 1.7756 110

Long-Term

0.68 0

(110 cm 2 /hr) 1.523 0.0191 10,000 Ornamentals pruning, tying

1.36 0

(110 cm 2 /hr) 3.046 0.0383 5,200Page 17 of 18 0.68 0

(175 cm 2 /hr) 1.523 0.0305 6,600 hand pinching,

nurseries

activities 1.36 0

(175 cm 2 /hr) 3.046 0.0609 3,300

0.68 0

(400 cm 2 /hr) 1.523 0.0696 2,900 harvesting (workers moved plants

to trucks and reorganized the gallon

pots or containers) 1.36 0

(400 cm 2 /hr) 3.046 0.1393 1,400

0.68 0

(2700 cm 2 /hr) 1.523 0.4700 430

0

(2700 cm 2 /hr) 3.046 0.9400 210handharvesting

1.36

4

(2700 cm 2 /hr) 1.999 0.6168 320

Note: a. DAT = Days After Treatment. TC = Transfer Coefficient. b. Dislodgeable Foliar Residue (DFR) = Applicati on Rate (lb ai/A) x (1- Daily Dissipation Rate) t x 4.54E8 ug/lb x 2.47E-8

A/cm 2 x 0.2

c. Short- and Intermediate-t erm Daily Dose = [DFR (ug/cm 2 ) x TC (cm 2 /hr) x 0.001 mg/ug x 8 hrs/day] ÷ Body Weight (70 kg); Long-term Daily Dose = [DFR (ug/cm 2 ) x TC (cm 2 /hr) x 0.001 mg/ug x 8 hrs/day] ÷ Body Weight (70 kg)

d. Short- and Intermediate-term MOE = NOAEL/ Daily Dose (NOAEL = 200 mg/kg/day; LOC = 100). e. Long-term MOE = NOAEL/Daily Dose (NOAEL = 200 mg/kg/day; LOC = 300).

5.2.2 Restricted Entry Interval

The REI specified on the proposed label is based on the acute toxicity of tolfenpyrad technical material which is classified as Category III fo r acute dermal and inhala tion toxicity, Category IV for dermal and eye irritation, and Category II for acu te oral toxicity. Base d on the acute toxicity profile of tolfenpyrad, the 24 hour REI appearing on the proposed label is appropriate for low, medium, and high contact pos tapplication activities.

6.0 Data Needs and Label Recommendations

Based on the current risk assessment:

• All handlers should wear a long-sleeved shirt, long pants, socks, chemical-resistant gloves and footwear as stated in the proposed label.

• The proposed label personal protective equipmen t (PPE) language should be revised to state

the use of: “ Chemical-resistant gloves made of ma terials such as barrier laminate or polyvinyl chloride. ”

• The default dislodgeable foliar re sidue (DFR) values and assump tions used in the assessment may be under or overestimated. Therefore, s ubmission of a chemical-specific DFR study for greenhouses is recommended to reduce this un certainty, and could pot entially result in reduced exposure and risk estimates for all scenarios.Page 18 of 18 • To determine the exposure duration that needs to be assessed for futu re registration actions, the applicant could provide the Agency with information to characterize the use pattern for the end-use product (EP) containing tolfenpyrad. Such information might include specific

seasonal information about the use to be a ssessed, major regions on which the product is applied and how the product fits with other active ingredients in pest resistance management

programs.

• The Registration Division (RD) s hould ensure that the appropriate restricted reentry interval (REI) is included on the proposed label.