Date:

Subject: UNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASHINGTON, 

### D.C. 20460

June 24, 2014 OFFICE OF CHEMICAL SAFETY

AND POLLUTION PREVENTION

Saflufenacil. Occupational and Residential Exposure Assessment for Proposed

Uses on Grass Forage/Hay/Grass Grown for Seed and Olives, and an Amended

Use on Wheat and Barley.

PC Code: 118203 DP Barcode: 0418586

Decision No.: 480698,481309

Petition No.: N/A

Risk Assessment Type: Occupational/Residential Exposure Assessment

TXRNo.:NA

MRIDNo.: NA Registration No.: 7969-278, 7969-297, 7969-276 Regulatory Action: Section 3

Case No.: 7277

CAS No.: 372137-35-4

40 CFR: §180.649

From: Kelly M. Lowe, Environmental ScientiC---G)

## ~ Risk Assessment Branch 1 (RAB 1)

Health Effects Division (7509P)

Through: Charles W. Smith, Branch Chief

Health Effects Division (7509P)

To: and

Matthew Lloyd, Reviewer

Kristin Rury, Reviewer 

# ¥J

Exposure Science Advisory Committee

Kathryn Montague, RM23 Bethany Benbow

Herbicide Branch Registration Division (7505P)

Introduction

The Registration Division (RD) requested that the Health Effects Division (HED) conduct an

exposure and risk assessment for three actions related to saflufenacil:
(1) a new use on grass forage/hay/grass grown for seed;
(2) a new use on olives; and
(3) amended uses on barley and wheat.

Page 1 of22Page 2 of 22 A quantitative assessment of occupational exposur e has been conducted for all of the proposed uses of saflufenacil; however, it was determin ed that an updated exposure assessment was not necessary for the amended uses on wheat and barley since both are registered use sites and have been assessed previously (Memo, K. Lowe , 18-May-2009, D349939). The proposed amendment (adding a use pattern for dessication/harvest ai d purposes) does not change the maximum application rate previously a ssessed, and would not impact th e occupational post-application assessment. The only relevant activity occurri ng at or after harvest would be mechanical harvesting, which is expected to result in negligible exposure. The previous assessment provides the exposure and risk estimates relevant for the amended uses on wheat and barley.

It is HED policy to use the best available data to assess exposure. Several sources of generic data were used in this assessment as surrogate data in the absence of chemical-specific data, including Pesticide Handlers Exposure Database Version 1.1 (PHED 1.1); the Agricultural Handler Exposure Task Force (AHETF) database ; the Outdoor Residential Exposure Task Force (ORETF) database; and the Agricultural Reentry Task Force (ARTF) database. Some of these data are proprietary, and subject to the data pr otection provisions of th e Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA).

Note: This memorandum was reviewed by th e Exposure Science Advisory Committee (ExpoSAC) on 27-FEB-2014.Page 3 of 22 Table of Contents

1.0 Executive Summary ............................................................................................................. 4

2.0 Risk Assessment Conclusions and Recommendations ........................................................ 6

2.1 Summary of Risk Estimates ............................................................................................. 6

2.2 Label Recommendations .................................................................................................. 6

2.3 Data Deficiencies and Requirements ............................................................................... 6

3.0 Hazard Characterization ....................................................................................................... 6

4.0 Exposure and Use Profile..................................................................................................... 8

5.0 Residential Exposure and Risk Estimates .......................................................................... 10

5.1 Spray Drift ................................................................................................................... ... 10

5.2 Residential Bystander Post-Appli cation Inhalation Exposure ....................................... 10

6.0 Occupational Exposure and Risk Estimates ...................................................................... 10

6.1 Occupational Handler Expos ure/Risk Estimates............................................................ 10

6.2 Occupational Post-application Exposure/Risk Estimates .............................................. 16

6.2.1 Occupational Post-application Inhala tion Exposure/Risk Estimates ...................... 16

6.2.2 Occupational Post-application Derm al Exposure/Risk Estimates .......................... 16 Appendix A. Summary of Occupa tional Non-cancer Algorithms ............................................... 20Page 4 of 22 1.0 Executive Summary

Saflufenacil is a pre- and post-emergence herb icide that acts by inhi biting protoporphyrinogen IX oxidase, which leads to ch lorophyll destruction by photooxida tion and causes bleaching of emerging foliar tissue. It is curre ntly registered for use on legume vegetables, citrus fruit, pome fruit, stone fruit, tree nuts, cereal grains, cotton, sunflowers, grapes, and soybean. BASF Corporation is requesting three actions rela ted to saflufenacil: (1) a new use on grass forage/hay/grass grown for seed, (2) a new use on olives; and (3) amended uses on barley and wheat. While the new uses have been quant itatively assessed in this document, it was determined that an exposure assessment was not necessary for the amended uses on wheat and barley since both are registered use sites and have been assessed previously (Memo, K. Lowe, 18-May-2009, D349939). There are no changes to the exposure profile for these uses, therefore, the previous assessment provides the exposure and risk estimates relevant for the amended uses on wheat and barley.

Exposure and Proposed Use Profile The proposed new uses involve three labels : Sharpen® (EPA Reg. #: 7969-278), HeatTM X (EPA Reg. #: 7969-297), and Treevix® Powered by Kixor® Herbicide (EPA Reg. #: 7969-276). The proposed uses are on forage grasses grown in pastures and rangeland, or in fields grown for forage, silage and hay production, and for posteme rgence-directed broadleaf weed control in olive trees. The grass/forage uses are proposed at a maximum si ngle application rate of 0.089 lb ai/A during the dormant season and 0.045 lb ai/A fo r in-season weed control, to be made to the foliage via aerial or groundboom applications; it may also be applied via dry-bulk fertilizer. Multiple applications can be made during the dormant season (not to exceed a maximum of 0.089 lb ai/A) and in season (not to exceed 0.134 lb ai /A), with a retreatment interval of 14 days. The olive use is proposed at a maximum applicati on rate of 0.044 lb ai/A, to be made as a postemergence spray directed at the base of the trunk targeting emerged weeds via groundboom or handheld equipment. Multiple applications can be made up to four times per year, with a retreatment interval of 21 days. Application vi a aerial equipment is prohibited for the proposed olive use. None of the proposed uses allow fo r application via chemigation. The amended use on barley, wheat, and triticale is for the addition of a harvest aid/dessication use pattern to the

label. The amended use direc tions recommend a maximum applic ation rate of 0.045 lb ai/A by aerial or groundboom equipment. The restricted entry interval for th e proposed and amended uses is 12 hours. Based on the proposed use pa ttern, it has been determined that the potential exposure scenarios that will n eed to be assessed include short- and intermediate-term occupational exposures (handler and post-application).

Hazard Profile For all occupational risks, the poi nt of departure (POD) for short- and intermediate-term dermal and inhalation exposure/risk assessment is a no- observed adverse-effect level (NOAEL) of 5 mg/kg/day based on decreased fetal body weights and increased skelet al variations at the lowestobserved adverse-effect level (L OAEL) of 20 mg/kg/day in the developmental study in rats. Since an oral study was used, a dermal absorption factor of 3% was used for the dermal risk assessment derived from a dermal penetr ation study (MRID 47128214). Since no inhalation absorption data are available, toxicity by the inhala tion route is considered to be equivalent to the estimated toxicity by the oral route of exposur e. A 69 kg body weight was used for all adultPage 5 of 22 exposure calculations because the endpoint is fr om a development study and was observed in the fetuses. Chronic exposures are not expected. Saflufenacil was classifi ed as not carcinogenic

based on the lack of tumors in the mouse and rat carcinogenicity studies and lack of mutagenicity. The total uncertainty factor (UF) that was applied to occupational risk

assessments is 100 for short- and intermedia te-term risks (10x interspecies factor, 10x intraspecies factor). Since the POD for the de rmal and inhalation routes of exposure are based on the same effect, the exposures from these r outes can be combined to estimate total risk.

Residential Exposure and Risk There are no residential uses proposed or curren tly registered for saflufenacil. Therefore, residential handler and po st-application exposure/risk were not assessed.

Occupational Exposure and Risk The occupational handler exposure a nd risk estimates indicate that the short- and intermediateterm dermal and inhalation combined margins of exposure (MOEs) are not of concern to HED (i.e., MOE > 100). At the baseline level of pers onal protection (i.e., no gl oves and no respirator), all scenarios result in combined MOEs (dermal + inhalation) ≥ level of concern (LOC; MOEs ≥ 470).

The occupational post-application dermal exposure and risk estimates are greater than the LOC of 100 on the day of application, ranging from 6,000 to 10,000 depending on crop and activity. Since the post-application assessment is not a concer n on Day 0 (12 hours following application), the restricted entry interval (RE I) is based on the acute t oxicity of saflufenacil

technical material. Saflufenacil is classified as toxicity category III for acute oral, acute dermal toxicity, and acute eye irritation. It is classified as toxicity category IV for acute inhalation toxicity and acute dermal irritati on. It is not a dermal sensitizer. Therefore, the acute toxicity categories for this chemical require a 12 hour REI under 40 CFR 156.208 (c) (2) (iii). The 12- hour REI, which currently appears on the la bels, is adequate for the proposed uses.

Based on the Agency's current practices, a quant itative non-cancer occupational post-application inhalation exposure assessment was not performed for saflufenacil at this time. If new policies or procedures are put into place, the Agency may revisit the need for a quantitative occupational post-application inhalation exposur e assessment for saflufenacil.

Human Studies Review This risk assessment relies in part on data from studies in which adult human subjects were intentionally exposed to a pesticide or other chemical. Thes e data, which include studies from the PHED 1.1, the AHETF database, and the ARTF database are (1) subject to ethics review pursuant to 40 CFR 26, (2) have re ceived that review, and (3) ar e compliant with applicable ethics requirements. For certain studies, the ethics review may have included review by the

Human Studies Review Bo ard. Descriptions of data sources , as well as guidance on their use, can be found at the Agency website 1

.

1 http://www.epa.gov/pesticides/science/handler-exposure-data.html and http://www.epa.gov/pesticides/science/post-app-exposure-data.htmlPage 6 of 22 2.0 Risk Assessment Conclusions and Recommendations

2.1 Summary of Risk Estimates

There are no occupational risk esti mates of concern for the proposed uses for saflufenacil. At the baseline level of personal prot ection (i.e., no gloves and no respir ator), all scenarios result in combined MOEs (dermal + inhalation) ≥ LOC (MOEs ≥ 470). The occupational postapplication dermal exposure and risk estimates are greater than the LO C of 100 on the day of application, ranging from 6,000 to 10,000 depending on crop and activity.

2.2 Label Recommendations

There are no label recommendations based on the proposed uses.

2.3 Data Deficiencies and Requirements

There are no data deficiencies based on th e proposed or currently registered uses.

3.0 Hazard Characterization

Saflufenacil is classified as toxicity category II I for acute oral, acute dermal toxicity, and acute eye irritation. It is classified as toxicity category IV for acute inhalation toxi city and acute dermal

irritation. It is not a dermal sensitizer. Tabl e 3.1 presents a summary of the acute toxicity

information for saflufenacil.

Table 3.1. Acute Toxicity Profile – Saflufenacil

Guideline No. Study Type MRID(s) Results Toxicity Category Purity

870.1100 Acute oral [rat] 47128101 LD50 was >2000 mg/kg bw III 93.8%

870.1200 Acute dermal [rat] 47128102 LD 50 > 2000 mg/kg III 93.8%

870.1300 Acute inhalation [rat] 47128103 LC 50 > 5.3 mg/L IV 93.8%

870.2400 Acute eye irritation [White New Zealand rabbit] 47128105 minimal irritation III 93.8%

870.2400 Acute eye irritation [White New Zealand rabbit] 47128104 minimal irritation III 93.8%

870.2500 Acute dermal irritation [rabbit] 47128106 Slightly irritating IV 93.8% 870.2600 Skin sensitization [Guinea Pig] 47128107 Not a Sensitizer N/A 93.8%

Subchronic and chronic toxicity studies for saflufenacil in rats , mice, and dogs identified the hematopoietic system as the primary target of sa flufenacil. Decreased hematological parameters were seen at about the same dose level across sp ecies, except dogs, where the effects were seen at a slightly higher dose. Th ese effects occurred around the same dose level from short- through long-term exposures without increasing in severity. Effects were also seen in the liver in mice, the spleen in rats, and in both th ese organs in dogs. These effects also occurred around the same dose level from short- through long-term e xposures without incr easing in severity.Page 7 of 22 Increased fetal susceptibility was observed in th e developmental toxicity studies in the rat and rabbit and in the 2-generation re production study in the rat. Developmental effects such as decreased fetal body weights and increased skeletal variations occurred at doses that were not maternally toxic in the developmental study in rats, indicating in creased quantitative susceptibility. In rabbits, developmental eff ects such as increased liver porphyrins were observed at doses that were not maternally toxic, indicating increased quantitative susceptibility. In the 2-generation reproductive to xicity study in rats, the reporte d offspring effects were more

severe than the maternal effects at the same dose level, indicating evidence for increased qualitative susceptibility.

In a 28-day dermal toxicity study in rats, safl ufenacil did not induce a ny type of dermal or systemic toxicity up to the limit dose of 1,000 mg/kg/day. The Hazard and Science Policy Council (HASPOC) met on July 18, 2013 to discuss the need for a subchroni c inhalation toxicity study for saflufenacil (TXR 0056720). Based on a weight-of-evidence approach, the HASPOC

concluded that a subchronic inhala tion toxicity study is not needed for saflufenacil at this time for the following reasons: 1) th e physical/chemical properties of saflufenacil including its low volatility (3.4 x 10 -17 mmHg, 20°C); (2) its low acute inhalati on toxicity (Toxicity Category IV); and (3) the use of an oral POD resulting in MOEs that are ≥ 9,800, and are above the Agency’s

level of concern.

The toxicity endpoints and the PODs for various exposure scenarios are presented in Table 3.2. For all occupational risks, the POD for short- and intermediate-term dermal and inhalation exposure/risk assessment is a NOAEL of 5 mg/k g/day based on decreased fetal body weights and

increased skeletal variations at 20 mg/kg/day (LOAEL) in the developmental study in rats. For overall risk, the dermal and inhalation exposures were added together and compared to the same NOAEL. Chronic exposures are not expected.

Table 3.2. Summary of Toxicological Doses and Endpoints for Saflufenacil for Use in Occupational Human Health

Risk Assessments.

Exposure/

Scenario Point of Departure (POD) Uncertainty Factors Level of Concern

for Risk

Assessment Study and Toxicological Effects

Dermal ShortIntermediate-Term (1- 30 days, 1-6 months, and > 6 months, respectively) NOAEL=5 mg/kg/day UF A = 10X

UF H = 10X

Dermal absorption

Factor = 6% Occupational LOC

for MOE = 100 Prenatal developmental in (rat) Developmental NOAEL = 5 mg/kg/day LOAEL = 20 mg/kg/day based on based on decreased fetal body weights and

increase skeletal variations.

Inhalation ShortIntermediate-Term (1- 30 days, 1-6 months, and > 6 months, respectively) NOAEL=5 mg/kg/day UF A = 10X

UF H = 10X

Inhalation-absorption assumed equivalent to

oral Occupational LOC

for MOE = 100 Prenatal developmental in (rat) Developmental NOAEL = 5 mg/kg/day LOAEL = 20 mg/kg/day based on based on decreased fetal body weights and

increase skeletal variations.

Cancer (oral, dermal, inhalation) Classification: Classification: Not carcinogenic based on the lack of tumors in the mouse and rat carcinogenicity studies and lack of mutagenicity.
Point of Departure (POD) = A data point or an estimated point that is derived from obs erved dose-response data and used to mar k the beginning of extrapolation to determine risk associ ated with lower environmentally relevant human exposures. NOAEL = no observed adverse effect level. LOAEL = lowest observed adverse effect level. UF = uncertainty factor. UF A = extrapolation from animal to human (intraspecies). UF H = potential variation in sensitivity among members of the human popula tion (interspecies). FQPA SF = FQPA Safety Factor. MOE = margin of exposure. LOC = level of concern.Page 8 of 22 The Agency’s LOC for risks (i.e., target level for MOE) is defined by the uncertainty factors that are applied to the assessment. The Agency appl ies a factor of 10X to account for interspecies extrapolation to humans from the animal test sp ecies and another factor of 10X to account for intra-species sensitivity. The total uncertainty fa ctor that has been applied to occupational risk

assessments is 100 for short- and intermediate -term dermal and inha lation exposures.

Absorption

A DAF of 6% was estimated for saflufenacil based on the highest degree of skin penetration at

the lowest dose tested in a rat dermal abso rption study. Immediately after a 10-hour exposure, the estimated DAF was 3.4%. However, about 50% of the radioactivity remaining at the end of exposure penetrated through the skin during a 120-hour (5-day) observational period, indicating

that skin-bound residues of safl ufenacil are available for derm al absorption. With skin-bound residues included, a DAF of 6% should be applied fo r converting oral doses to dermal equivalent doses to assess the potential risk associated with dermal exposur es to saflufenacil.

Body Weight

Since the dermal and inhalation PODs are based on developmental and/or fetal effects, the body weight appropriate for dermal and inhalation assessments is 69 kg.

4.0 Exposure and Use Profile

Saflufenacil is currently registered for use on legu me vegetables, citrus fruit, pome fruit, stone fruit, tree nuts, cereal grains, cotton, sunflowers , grapes, and soybean. BASF Corporation is requesting new uses on grass forage/hay/grass gr own for seed and olive trees. It is also requesting amended uses on barley and wheat. As noted above, it was determined that an updated exposure assessment was not necessary fo r the amended uses on wheat and barley since both are registered use sites and have been assessed previously (Memo, K. Lowe, 18-May-2009, D349939). The proposed amendment, adding a use pattern for dessication/harvest aid purposes, could potentially result in occupa tional handler exposure; however, the amended use pattern does not change the maximum application rate previo usly assessed. In addi tion, the only relevant activity occurring at or after harvest would be m echanical harvesting, which is expected to result in negligible exposure. The previous asse ssment provides the exposur e and risk estimates relevant for the amended uses on wheat and barley.

Based on the proposed new uses, it has been dete rmined that the potential exposure scenarios

that will need to be assessed include short- and intermediate-term occupational exposures (handler and post-application). A summary of the proposed and amende d use directions are

included in Table 4.1 below.Page 9 of 22 Table 4.1. Summary of Proposed and Am ended Use Directions for Saflufenacil.

Applic. Timing, Type, and Equip. Formulation [EPA Reg. No.] Application

Rate Max No. Applications per Season Max Seasonal Application

Rate Use Directions

and Limitations

Sharpen® 1 (7969-278) 2.85 lb ai/gal (29.74% ai)

HeatTM X 1 (7969-297) 2.85 lb ai/gal (29.74% ai) Treevix® Powered by Kixor® Herbicide (7969-276) (70% ai)

Forage Grasses Grown in Pastures and Rangeland, or in Fields Grown for Forage , Silage and Hay Production

Apply as broadcast burn-down spray to weeds in the dormant season (i.e., when grasses are not actively growing in the fall (postharvest), during the winter dormancy period, or in the early spring before green-up)

Groundboom, Aerial, or Dry Bulk Fertilizer Liquid

(7969-278 and 7969-297) 4 fl oz/A =

0.089 lb

ai/A

0.89 lb

ai/ton

fertilizer Not specified 0.089 lb ai/A (0.134 lb ai/A

for entire season; both

dormant and in season apps) Do not apply via chemigation.

REI = 12 hours.

RTI = 14 days.

PHI = 7 days Apply as broadc ast postemergence spray to control weeds in season (i.e., actively growing cool-season forage grasses). Can be made in the spring after green-up.

Groundboom, Aerial, or Dry Bulk Fertilizer Liquid

(7969-278 and 7969-297) 2 fl oz/A =

0.045 lb

ai/A

0.45 lb

ai/ton

fertilizer Not specified 0.045 lb ai/A (0.134 lb ai/A

for entire season; both

dormant and in season apps)

Olive Trees

Apply as broadcast, banded, or spot application directed at the base of the

tree trunk

Groundboom, Manually-pressurized handwand, Backpack Water Dispersible

Granule (WDG) or Dry Flowable (DF)

(7969-276) 1 oz/A =

0.044 lb

ai/A

0.01 oz/gal

= 0.00044 lb ai/gal Max of 4 apps only if

one or two occur during the period of postharvest

to the beginning of bloom; Max of 3 apps

while trees

are in fruiting stage until crop

harvest 0.131 lb ai/A/crop

season or 0.175 lb ai/A/crop

season when

one or more applied during postharvest period.

0.175 lb ai/A/year Do not apply via

aerial or chemigation equipment.

Do not use in

tree nurseries.

REI = 12 hours.

RTI = 21 days.

PHI = 0 days

Barley, Wheat, Triticale

Apply for harvest aid/dessication to dessicate the crop and weeds and to facilitate crop harvest

Aerial and Groundboom Liquid

(7969-278) 2 fl oz/A =

0.045 lb

ai/A Not specified 2 fl oz/A =

0.045 lb ai/A REI = 12 hours

PHI = 3 days

1. PPE = long-sleeved shirt and long pants, shoes plus socks, chemical-resistan t gloves, protective eyew ear such as face shiel d, goggles, or safety glasses.Page 10 of 22 5.0 Residential Exposure and Risk Estimates

There are no residential uses proposed or curren tly registered for saflufenacil. Therefore, residential handler and po st-application exposure/risk were not assessed.

5.1 Spray Drift

Spray drift is a potential source of exposure to those nearby pest icide applications. This is particularly the case with aerial application, but, to a lesser exte nt, spray drift can also be a potential source of exposure from the ground application methods (e.g., groundboom and airblast) employed for saflufenacil. The Agency has been working with the Spray Drift Task Force (a task force composed of various regist rants which was developed as a result of a Data Call-In issued by EPA), EPA Regi onal Offices and State Lead Agencies for pesticide regulation and other parties to develop the best spray drif t management practices (see the Agency’s Spray Drift website for more information). 2 The Agency is also taki ng means to qualitatively and qualitatively address spray drif t as a potential source of expo sure in risk assessments for pesticides through existing programs such as Ag Drift and chemical specific properties of pesticides. The potential for spray drift will be quantitatively evaluated for each pesticide during

the Registration Review process which ensures that all uses fo r that pesticide will be considered concurrently.

5.2 Residential Bystander Post-Application Inhalation Exposure

Based on the Agency's current practices, a quant itative post-application inhalation exposure assessment was not performed for saflufenacil at this time primarily because of the low acute inhalation toxicity (Toxicity Category IV) and the low vapor pressure (3.4 x 10 -17 mmHg, 20°C). However, volatilization of pestic ides may be a source of post-application i nhalation exposure to individuals nearby pesticide app lications. The Agency sought expert advice and input on issues

related to volatilization of pesticides from its Federal Insec ticide, Fungicide, and Rodenticide Act Scientific Advisory Panel (S AP) in December 2009, and received the SAP’s final report on March 2, 2010 3 . The Agency is in the process of evaluating the SAP report and may, as appropriate, develop policies and procedures to identif y the need for and, subsequently, the way to incorporate post-application i nhalation exposure into the Agency 's risk assessments. If new policies or procedures are developed, the Agen cy may revisit the need for a quantitative postapplication inhalation exposure assessment for saflufenacil.

6.0 Occupational Exposure and Risk Estimates

6.1 Occupational Handler Ex posure/Risk Estimates

HED uses the term handlers to describe those individuals who are invo lved in the pesticide application process. HED believe s that there are distinct job functions or tasks related to applications and exposures can vary depending on the specifics of each task. Job requirements (amount of chemical used in each application), the kinds of equipment used, the target being

2 Available: http://www.epa.gov/opp00001/factsheets/spraydrift.htm

3 Available: http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.htmlPage 11 of 22 treated, and the level of protection used by a ha ndler can cause exposure levels to differ in a manner specific to each application event.

Based on the anticipated use patter ns, and the current labeling re garding types of equipment and techniques that can be used, occupational ha ndler exposure is expect ed. The quantitative exposure/risk assessment developed for occupa tional handlers is based on the following

scenarios:

1) Mixing/loading liquids for aer ial and groundboom applications; 2) Mixing/loading dry flowables for groundboom applications; 3) Applying sprays via aerial and groundboom equipment; 4) Flagging for aerial applications; 5) Mixing/loading/applying dry flowables via backpack or manually-p ressurized handwand; 6) Impregnating liquids onto dry bulk fertilizer in commercial and on-farm settings; and 7) Applying impregnated dry bulk fertilizer w ith commercial equipment and grower-owned equipment.

Occupational Handler Exposur e Data and Assumptions

A series of assumptions and exposure factors serv ed as the basis for completing the occupational handler risk assessments. Each assumption and fact or is detailed below on an individual basis.

Application Rate : The application rates used in this assessment are provided in Table 4.1.

Unit Exposures: It is the policy of HED to use the best av ailable data to assess handler exposure. Sources of generic handler data, used as surrogate data in the absence of chemical-specific data, include PHED 1.1, the AHETF database, the Outdoor Residential Exposure Task Force (ORETF) database, or other registrant-submitted occupational exposure studies. Some of these data are proprietary (e.g., AHETF data), and subject to the data protection provisions of FIFRA. The standard values recommended for use in pred icting handler exposure that are used in this assessment, known as “unit exposures”, are outlin ed in the “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table 4 ”, which, along with additional information on HED policy on use of surrogate data, including descriptions of the various sources, can be found at the Agency website 5

.

For the dry bulk fertilizer s cenarios, HED assumed a closed mixing/loading scenario for commercial impregnation of dry bul k fertilizer, and an open mixing /loading scenario for growerowned equipment impregnation of dry bulk fertili zer. For all applications of dry bulk fertilizer, HED assumed the use of an open-cab spreader.

Area Treated or Amount Handled: The inputs for area treated were mostly base d on information in ExpoSAC Policy 9.1. HED does not have data regarding the mixing/loading or the application of saflufenacil-impregnated dry

4 Available: http://www.epa.gov/opp00001/science/handler-exposure-table.pdf

5 Available: http://www.epa.gov/pesticides/science/handler-exposure-data.htmlPage 12 of 22 bulk fertilizer. The mixing/loading processing rate for commercial impregnation of dry bulk

fertilizer has been estimated to be 960 tons of fertilizer processed per 8 hour day based on information supplied by a registra nt concerning the chemical alachlor (as referenced in its reregistration eligibility document (RED) document 6 ). Mixing/loading for on-farm impregnation of dry bulk fertilizer was then assessed using an estimate of 160 acres/day. Application of dry bulk fertilizer was assessed assuming applica tion to up to 320 acres/day for commercial equipment and 160 acres/day for grower-owned equipment. The following summarizes the inputs used for estimating handler exposures:

 1,200 acres for aerial applica tion to high acreage crops

 200 acres for groundboom applicat ion to high acreage crops

 80 acres for groundboom applicati on to typical acreage crops

 350 acres for flaggers

 40 gallons for backpack and manually -pressurized handwand applications

 960 tons of fertilizer per day for mixing/loading for commerci al impregnation of dry bulk

fertilizer

 160 acres/day for mixing/loading for grower-o wned equipment impregnation of dry bulk

fertilizer

 320 acres/day for commercial applic ation of dry bulk fertilizer

 160 acres/day for grower-owned equipmen t application of dry bulk fertilizer

Exposure Duration: HED classifies exposures from 1 to 30 days as sh ort-term and exposures 30 days to six months as intermediate-term. Exposure duration is determined by many things, including the exposed population, the use site, the pest pressure triggeri ng the use of the pesticide, and the cultural practices surrounding that use site. For most agri cultural uses, it is reason able to believe that occupational handlers will not apply the same ch emical every day for more than a one-month time frame; however, there may be a large agribusiness and/or commercial applicators who may apply a product over a period of weeks.

For the proposed use patterns, short- and inte rmediate-term exposures are anticipated for the following reasons: (1) up to three in-season and two dormant season foliar applications can be made per crop season 14 days apart; and (2) co mmercial applicators may apply this product at

various locations within a re gion over a period of weeks. In addition, the short- and intermediate-term PODs are the same; therefore, short-term risk estimates are protective of longer-term exposures.

Mitigation/Personal Protective Equipment: Estimates of dermal and inhalation exposure were calculated for various levels of personal protect ive equipment (PPE). Results are presented for “baseline,” defined as a single la yer of clothing consisting of a l ong sleeved shirt, long pants, shoes plus socks, no protective gloves, and no respir ator, as well as baseline with various levels of PPE as necessary (e.g., gloves, respirator, etc). The saflufen acil product labels direct mixers, loaders, applicators and other handlers to wear long-sleeved shirt and l ong pants, shoes plus

6 http://www.epa.gov/oppsrrd1/REDs/0063.pdfPage 13 of 22 socks, chemical-resistant gloves, and protective eyewear such as face shield, goggles, or safety glasses.

Occupational Handler Non-Cancer E xposure and Risk Estimate Equations The algorithms used to estimat e non-cancer exposure and dose fo r occupational handlers can be found in Appendix A.

Combining Exposures/Risk Estimates:

Dermal and inhalation risk estimates were combin ed in this assessment, since the toxicological effects for these exposure routes were similar. Dermal and inhalation risk estimates were combined using the following formula:

Total MOE = Point of Departure (mg/kg/day) ÷ Combined dermal + inhalation dose (mg/kg/day)

Summary of Occupational Handler Non-Cancer Exposure and Risk Estimates The occupational handler exposure a nd risk estimates indicate that the short- and intermediateterm dermal and inhalation combined MOEs are not of concern to HED (i.e., MOE > 100). At the baseline level of personal protection (i.e., no glove s and no respirator), all scenarios result in combined MOEs (dermal + inhalation) ≥ LOC (MOEs ≥ 250).

HED has no data to assess exposures to pilots using open cockpits. The only data available is for exposure to pilots in enclosed cockpits. Ther efore, risks to pilots are assessed using the engineering control (enclosed coc kpits) and baseline attire (long- sleeve shirt, long pants, shoes, and socks); per the Agency’s Worker Protection Standard stipulations fo r engineering controls, pilots are not required to wear protective gloves for the dura tion of the application. With this level of protection, there are no risk es timates of concern for applicators.

The Agency matches quantitative occupatio nal exposure assessment with appropriate characterization of exposure potentia l. While HED presents quantitative risk estimates for human flaggers where appropriate, agricultural aviati on has changed dramati cally over the past two decades. According the 2012 Natio nal Agricultural Av iation Association (NAAA) survey of their membership, the use of G PS for swath guidance in agricultu ral aviation has grown steadily from the mid 1990’s. Over the same time period, the use of human flaggers for aerial pesticide applications has decreased steadily from ~15% in the late 1990’s to only 1% in the most recent (2012) NAAA survey. The Agency will continue to monitor all available information sources to best assess and characterize the exposure potenti al for human flaggers in agricultural aerial applications.Page 14 of 22Table 6.1.1. Occupational Handler Non-Cancer Exposure and Risk Estimates for Saflufenacil.Exposure ScenarioCrop or TargetDermal UnitExposure(μg/lb ai)1InhalationUnitExposure(μg/lb ai)1MaximumApplicationRate (lbai/A)2AreaTreated(acres)3Dermal(LOC = 100)Inhalation(LOC = 100)Total(LOC =100)MitigationLevelMitigationLevelDose(mg/kg/day)4MOE5Dose(mg/kg/day)6MOE7MOE8Mixer/LoaderAerial application of liquidformulationForage Grasses Grownin Pastures andRangeland, or in FieldsGrown for Forage,Silage and HayProduction220(baseline)0.219(baseline)0.08912000.0204 250 0.000339 15,000 250Groundboom application ofliquid formulation2000.00341 1,500 0.0000565 88,000 1,500Groundboom application ofdry flowable formulationOlive trees227(baseline)8.96(baseline)0.044 800.000695 7,200 0.000457 11,000 4,400Commercial Impregnationof Dry Bulk Fertilizers(closed system)Forage Grasses Grownin Pastures andRangeland, or in FieldsGrown for Forage,Silage and HayProduction8.6 (engineeringcontrol)0.083(engineeringcontrol)0.89 lbai/ton960 tons0.00639 780 0.00103 4,900 670On-farm Impregnation ofDry Bulk Fertilizers220(baseline)0.219(baseline)0.089 1600.00272 1,800 0.0000452 110,000 1,800ApplicatorAerial spray applicationForage Grasses Grownin Pastures andRangeland, or in FieldsGrown for Forage,Silage and HayProduction2.08(engineeringcontrol)0.0049(engineeringcontrol)0.08912000.000193 26,000 0.00000758 660,00025,000Groundboom sprayapplication78.6(baseline)0.34(baseline)2000.00122 4,100 0.0000877 57,0003,800Olive trees 0.044 800.000241 21,000 0.0000174 290,00020,000Commercial Impregnationof Dry Bulk FertilizersForage Grasses Grownin Pastures andRangeland, or in FieldsGrown for Forage,Silage and HayProduction9.9(baseline)1.2(baseline)0.0893200.000245 20,000 0.000496 10,0006,700On-farm Impregnation ofDry Bulk Fertilizers1600.000123 41,000 0.000248 20,00013,000Page 15 of 22Table 6.1.1. Occupational Handler Non-Cancer Exposure and Risk Estimates for Saflufenacil.Exposure ScenarioCrop or TargetDermal UnitExposure(μg/lb ai)1InhalationUnitExposure(μg/lb ai)1MaximumApplicationRate (lbai/A)2AreaTreated(acres)3Dermal(LOC = 100)Inhalation(LOC = 100)Total(LOC =100)MitigationLevelMitigationLevelDose(mg/kg/day)4MOE5Dose(mg/kg/day)6MOE7MOE8FlaggerFlagger for aerial sprayapplicationForage Grasses Grownin Pastures andRangeland, or in FieldsGrown for Forage,Silage and HayProduction11(baseline)0.35(baseline)0.089 3500.000298 17,000 0.000158 32,000 11,000Mixer/Loader/ApplicatorMixing/loading/applyingdry flowables via backpackapplicationsOlive trees(ground-directed)8260 2.580.00044 lbai/gallon40 gallons0.000126 40,000 0.000000658 7,600,000 40,000Mixing/loading/applyingdry flowables via manuallypressurized handwandapplications100,000 300.00153 3,300 0.00000765 650,000 3,3001 Based on the “Occupational Pesticide HandlerUnit Exposure Surrogate Reference Table”(March 2013); Level of mitigation: Baseline, Eng. Controls.2Based on proposed labels (Reg. No. 7969-278, 7969-276 and 7969-297).3 Exposure Science Advisory Council Policy #9.1 and Registrant information.4 Dermal Dose = Dermal Unit Exposure (μg/lb ai) × Conversion Factor (0.001 mg/μg) × Application Rate (lb ai/acre) × Area Treated (A/day) × DAF (6 %) ÷ BW (69 kg).5 Dermal MOE = Dermal NOAEL (5 mg/kg/day) ÷ DermalDose (mg/kg/day).6 Inhalation Dose = Inhalation Unit Exposure (μg/lb ai) × Conversion Factor (0.001 mg/μg) × Application Rate (lb ai/acre) × Area Treated (A/day) ÷ BW (69 kg).7 Inhalation MOE = Inhalation NOAEL (5 mg/kg/day) ÷ InhalationDose (mg/kg/day).8 Total MOE = NOAEL (5 mg/kg/day)÷ (Dermal Dose + Inhalation Dose).Page 16 of 22 6.2 Occupational Post-applicat ion Exposure/Risk Estimates

HED uses the term post-application to describe exposures that occur when individuals are present in an environment that has been previously treated with a pe sticide (also referred to as reentry exposure). Such exposures may occur when workers enter previously treated areas to perform job functions, including ac tivities related to crop producti on, such as scouting for pests or harvesting. Post-application e xposure levels vary over time and depend on such things as the type of activity, the nature of the crop or target that was trea ted, the type of pesticide application, and the chemical’s degradation properties. In addition, the timing of pesticide applications, relative to harvest activities, can greatly reduce the potential for post-application exposure.

6.2.1 Occupational Post-application I nhalation Exposure/Risk Estimates

Based on the Agency's current practices, a quant itative post-application inhalation exposure assessment was not performed for saflufenacil at this time primarily because of the low acute inhalation toxicity (Toxic ity Category IV) and low vapor pressure (3.4 x 10 -17 mmHg, 20°C). However, there are multiple potential sources of post-application inhalation exposure to individuals performing post-applica tion activities in previously treated fields. These potential

sources include volatilization of pesticides and resuspension of dus ts and/or particulates that contain pesticides. The Agency sought expert advice and input on i ssues related to volatilization of pesticides from its Federal Insecticide, F ungicide, and Rodenticide Act Scientific Advisory Panel (SAP) in December 2009, and receive d the SAP’s final report on March 2, 2010 7 . The Agency is in the process of evaluating the SAP report as well as available post-application inhalation exposure data generated by the ARTF and may, as appropriate, develop policies and procedures, to identify the need for and, subsequently, the way to incorporate occupational postapplication inhalation exposure in to the Agency's risk assessments. If new policies or procedures are put into place, the Agency may revisit the need for a quantitative occupational post-application inhalation exposur e assessment for saflufenacil.

Although a quantitative occupational post-applic ation inhalation exposure assessment was not performed, an inhalation exposure assessment was performed for occupational/commercial handlers. Handler exposure resultin g from application of pesticides outdoors is likely to result in higher exposure than post -application inhalati on exposure. Therefore, it is expected that these handler inhalation exposure estima tes would be protective of most occupational post-application inhalation exposure scenarios.

6.2.2 Occupational Post-application Dermal Exposure/Risk Estimates

A post-application exposure asse ssment has not been conducted for the proposed use on olive

trees since the use directions indi cate that the product is to be a pplied to the base of the tree trunk and is not to contact the foliage . Currently, HED has no transfer coefficients or other data to assess post-application dermal e xposures to soil by occupational workers. In general, such exposures are considered to be negligible. Ther efore, for the soil-direct ed uses, post-application exposures and risks to occupati onal workers were not assessed.

7 Available: http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.htmlPage 17 of 22 The proposed uses on grass/forage are not specifica lly soil directed and, therefore, could result in potential post-application exposures. These e xposures have been assessed in this memo.

Occupational Post-application Dermal Exposure Data and Assumptions

A series of assumptions and exposure factors serv ed as the basis for completing the occupational post-application risk assessments. Each assumpti on and factor is detailed below on an individual

basis.

Exposure Duration: HED classifies exposures from 1 to 30 days as short-term and exposures 30 days to six months as intermediate-term. For saflufenacil, short- and intermediate-term exposures are expected since up to three in-sea son and two dormant season foliar applications can be made per crop season 14 days apart. In addition, the short- and intermediate-term PODs are the same; therefore, short-term risk estim ates are protective of longer-term exposures.

Transfer Coefficients: It is the policy of HED to use the best available data to assess postapplication exposure. Sources of generic post-application data, us ed as surrogate data in the absence of chemical-specific data, are derived from ARTF exposure monitoring studies, and, as proprietary data, are subject to the data protection provisions of FIFRA. The standard values recommended for use in predicting post-applicati on exposure that are used in this assessment, known as “transfer coefficients”, ar e presented in the ExpoSAC Policy 3 8 ” which, along with

additional information about the ARTF da ta, can be found at the Agency website 9 . Activities such as non-handset irrigation, fer tilizing, and mechanical harvesti ng are expected to occur, but are anticipated to result in negligible expos ure and, therefore, are not quantitativel y assessed.

Table 6.2.2.1. Summary of Post-Application Activities and Dermal Transfer Coefficients.

Crop Policy Crop Group Category Crop Height Foliage Density Transfer

Coefficients

(cm 2 /hr ) Activities

Forage Crop Field / row crop, low /

medium Low/High Full 0 Irrigation (non handset), Fertilizing,

Mechanical Harvesting

Low Full/Min 1,100 Scouting

Low Full 1,900 Irrigation (hand set)

Application Rate: The application rate used in th is assessment is provided in Table 4.1. Only the in-season rate was used to assess post-application activities, since it was assumed that these activities would only occur in season. It is not expected that these activities would be occurring during the

dormant season.

8 Available: http://www.epa.gov/pesticides/science/exposac_policy3.pdf

9 Available: http://www.epa.gov/pesticides/scien ce/post-app-exposure-data.htmlPage 18 of 22 Exposure Time: The average occupational workda y is assumed to be 8 hours.

Dislodgeable Foliar Residues: In accordance with 40CFR158, DFR data are required for all occupational (e.g., crop, nursery, gr eenhouse use sites) or reside ntial (e.g., ornamental and vegetable gardens, pick your ow n farms, retail tree farms) uses that could result in postapplication exposure to foliage. In the absence of chemical-specific DFR data, EPA uses default

values. The 2012 Standard Operating Procedures for Residential Pesticide Exposure

Assessment includes an analysis of a number of DFR st udies, which resulted in the selection of a revised default values for the fraction of the appl ication rate available fo r transfer after a foliar application (F AR ). These values are based on an analysis of 19 DFR studies. Since that time, the Agricultural Re-entry Task Force has submitted information (MRID 49299201) that corrects an application rate error made in the original submission of “ARF039 – Determination of Dermal and Inhalation Exposure to Reentry Workers Du ring Chrysanthemum Pinching in a Greenhouse” (EPA MRID 45344501). As a result, the range of F AR values was revised from 2% - 89% to 2%

- 47%. In the data, a large range of transferability is observed and this variability can potentially be attributable to many factors such as active ingredient; formulation; field conditions in the studies; weather conditions (e .g., humidity); or many other difficult to quantify factors. Although witnessed across multiple chemicals, this range in F AR values is not expected when considering DFR data for a single chemical. At this time, the ARTF submission did not alter the

selection of 25% as the reasonabl e, high-end default value. Because DFR data are not available for saflufenacil, EPA is using the default value of 25%. Although there may be a small degree of uncertainty in the use of the default DFR value for saflufenacil (i.e., there is a small chance that

the F AR value may exceed the applicable default value ), it is likely that the health-protective aspects of EPA’s occupational post-applic ation assessment methodology will more than compensate for this potential uncertainty. Fo r example, when asse ssing residential and occupational post-application exposu re to gardens and ornamentals, EPA assumes the following: exposures occur to zero-day (i.e., day of app lication ) residues every day of the assessed exposure duration (i.e., EPA assume s that no dissipation or degrad ation occurs, it doesn’t rain, etc); individuals perform the same post-application activities performed in the transfer coefficient study day after day (e.g., weeding, harv esting, pruning, etc.); a nd individuals engage in these post-applicati on activities for a high-end amount of time every day (represented by data reflecting time spent gardening based on survey data).

Given the conservatisms discussed above a nd the potential compounding nature of these conservatisms, EPA is able to re ly upon the calculated exposure estimates with confidence that exposure is not being underestimated.

Since the highest estimated occupational post- application exposure using default DFR values for saflufenacil is minimal in comparison to the level of concern (i.e., the calc ulated MOE is greater than 2 times higher than the level of concern, MOE = 3,000 compared to the LOC of 100); EPA is waiving the 40CFR DFR data requirement. In this instance, it is unlikely that chemicalspecific DFR data would be needed to furthe r refine exposure assessments or would add appreciably to our overall unders tanding of the availability of dislodgeable foliar pesticide

residues for saflufenacil.Page 19 of 22 Occupational Post-application Non-Cancer Derm al Exposure and Risk Estimate Equations The algorithms used to estimat e non-cancer exposure and dose fo r occupational post-application workers can be found in Appendix A.

Occupational Post-application Non- Cancer Dermal Risk Estimates The short- and intermediate-term post-applica tion exposure scenarios associated with the proposed uses for saflufenacil ar e summarized in Table 6.2.2.2. All scenarios resulted in MOEs greater than the LOC of 100 (rangi ng from 3,000 to 5,200) on day 0 (12 hours after application) and, therefore, are not of concern to HED.

Table 6.2.2.2. Occupational Post-application Non-Cancer Exposure and Risk Estimates for Saflufenacil.

Crop/Site Activities Transfer

Coefficient

(cm 2 /hr) Proposed Application Rate (lb ai/A) DFR 1 Dermal Dose (mg/kg/day) 2 MOE 3
(LOC =

100)

Short- and Intermediate-term

Forage crop Scouting 1,100 0.045 0.13 0.00097 5,200

Irrigation (hand set) 1,900 0.00167 3,000

1 DFR = Application Rate × F × (1-D) t × 4.54E8 μg/lb × 2.47E-8 acre/cm 2 ; where F = 0.25 and D = 0.10 per day. 2 Daily Dermal Dose = [DFR (μg/cm 2 ) × Transfer Coefficient × 0.001 mg/μg × 8 hrs/day × dermal absorption (6%)]  BW (69 kg). 3 MOE = POD (5 mg/kg/day) / Daily Dermal Dose.

Restricted Entry Interval The REI specified on the proposed label is base d on the acute toxicity of saflufenacil. Saflufenacil is classified as toxicity category II I for acute oral, acute dermal toxicity, and acute eye irritation. It is classified as toxicity category IV for acute inhalation toxi city and acute dermal

irritation. It is not a dermal sensitizer. Short- and intermed iate-term post-application risk estimates were not a concern on day 0 (12 hours following application) fo r all post-application activities. Under 40 CFR 156.208 (c) (2 ) (iii), ai’s classified as Ac ute III or IV for acute dermal, eye irritation and primary skin irrigation are assi gned a 12-hour REI. Therefore, the [156 subpart K] Worker Protection Statement interim REI of 12 hours is adequate to protect agricultural workers from post-application expos ures to saflufenacil.Page 20 of 22 Appendix A. Summary of Occupational Non-cancer Algorithms

Occupational Non-cancer Handler Algorithms

Potential daily exposures for occupational handler s are calculated using the following formulas:

E=UE * AR * A * 0.001 mg/ug

where:

E = exposure (mg ai/day), UE = unit exposure (μg ai/lb ai), AR = maximum application rate according to pr oposed label (lb ai A or lb ai/gal), and

A = area treated or amount ha ndled (e.g., A/day, gal/day).

The daily doses are calculated using the following formula:

ADD= E * AF

BW

where:

ADD = average daily dose absorbed in a given scenario (mg ai/kg/day), E = exposure (mg ai/day), AF = absorption factor (der mal and/or inhalation), and BW = body weight (kg).

Margin of Exposure: Non-cancer risk estimates for each application handler scenario are calculated using a Margin of Exposure (MOE), whic h is a ratio of the to xicological endpoint to the daily dose of concern. The daily dermal and inhalation dose received by occupational handlers are compared to the a ppropriate POD (i.e., NOAEL) to a ssess the risk to occupational handlers for each exposure route. All MOE values are calculated using the following formula:

MOE= POD

ADD

where:

MOE = margin of exposure: value used by HE D to represent risk estimates (unitless), POD = point of departure (mg/kg/day), and ADD = average daily dose absorbed in a given scenario (mg ai/kg/day).

Occupational Non-cancer Post -application AlgorithmsPage 21 of 22 Potential daily exposures for occupational post- application workers are calculated using the following formulas:

DFR t =AR * F* (1-D) t * ቀ 4.54E8 ug

lb ቁ * ൬ 2.47E-8 A

cm 2 ൰

where:

DFR t = dislodgeable foliage residue on day "t" (μg/cm 2 ), AR = application rate (lb ai/acre),

F = fraction of ai retained on foliage or 25% (unitless), D = fraction of residue that dissipa tes daily or 10% (unitless), and t = number of days afte r application day (days).

E=TC * DFR t * ET * 0.001 mg

ug

where: E = exposure (mg ai/day), TC = transfer coefficient (cm 2 /hr),

DFR t = dislodgeable foliar re sidue on day “t” (μg/cm 2 ), and ET = exposure time (hours/day).

The daily doses are calculated using the following formula:

ADD= E * AF

BW

where:

ADD = average daily dose absorbed in a given scenario (mg ai/kg/day), E = exposure (mg ai/day), AF = absorption factor (der mal and/or inhalation), and BW = body weight (kg).

Margin of Exposure: Non-cancer risk estimates for each sc enario are calculated using a Margin of Exposure (MOE), which is a ratio of the toxico logical endpoint to the daily dose of concern. The daily dermal dose received by occupational po st-application workers is compared to the appropriate POD (i.e., NOAEL) to assess the risk to occupational post-application workers. All

MOE values are calculated using the following formula:

MOE= POD

ADDPage 22 of 22 where:

MOE = margin of exposure: value used by HE D to represent risk estimates (unitless), POD = point of departure (mg/kg/day), and ADD = average daily dose absorbed in a given scenario (mg ai/kg/day).