Page 1 of 47 UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C. 20460 OFFICE OF PREVENTION, PESTICIDE S , AND TOXIC SUBSTANCES

MEMORANDUM DATE : 0 5
- JAN
- 20 10 SUBJECT: Boscalid. Human Health Risk Assessment for Proposed Use on Alf alfa and Citrus (Crop Group 10), and for Proposed Increase in Tolerance on Stone Fruits (Crop Group 12). PC Code: 128008 DP Barcode: 363305 Decision Number: 405556 Registration Number : NA Petition Number: 9F7527, 9F9529 Regulatory Action: Section 3 Risk Assessment Type: Single Chemical/Aggregate Case Number: NA T XR Number: NA CAS Number: 188425
- 85
- 6 Chemical Class: Carboxamide (Anilide) Fungicide 40CFR : §180.589 MRID Numbers: NA Trade Name s : Boscalid Technical, Endura® Fungicide, Pristine ® Fungicide FROM: Nancy

J. Tsaur, Risk Assessor Amelia Acierto, Chemist Barry O’Keefe, ORE Assessor Risk Assessment Branch 3 (RAB3) Health Effects Division (HE D), 7509 P THROUGH: Paula Deschamp, Branch Chief

Registration Action Branch 3 (RAB3 ) Health Effects Division (HED), 7509P TO: Tony

Kish and Bryant Crowe, RM Team 22 Fungicide Branch (FB) Registration Division (RD ) , 7505PPage 2 of 47

Introduction This document addresses three different uses regarding the active ingre dient (ai), boscalid, submitted to the Agency under two p etition s (PP#9F7527 and PP#9F9 529 ): to set a tolerance in/on alfalfa, to set a tolerance in/on citrus crop group 10 , and to increase the current established tolerance on stone fruit crop group 12. C oncomitant with setting a tolerance on alfalfa, livestock tolerances mu st also be set to account for an updated livestock dietary burden. BASF Corporation (BASF) has submitted a petition to register new uses o n alfalfa and citrus fruits for boscalid technical (EPA Reg. No. 7969
- 198 ) , a new use o n alfalfa for Endura® Fungicide (EPA Reg. No. 7969
- 197 ) , and new uses on alfalfa and citrus fruits for Pristine ® Fungicide ( EPA Reg. No. 7969
- 199 )
. Endura® is a water dispersible granular (WD G) formulation containing 70% boscalid and Pristine ® is a WD G formulation containing 25.2% boscalid and 12.8% py raclostrobin
. Onl y boscalid is addressed in this document; py raclostrobin is being evaluated separately
. Currently , permanent tolerances are established in the U.S. and Canada for residues of boscalid ( 3
- py

ridinecarboxamide, 2
- chloro
-N
- (4’
- chloro(1,1’
- biphenyl)
- 2
- yl ) ) in/on several crops. There are no tolerances for residues of boscalid in/on alfalfa and citrus crops. Boscalid tolerances are established in the U.S. f or residues of boscalid in/on s tone fruit crop group 12 at 1.7 parts per million (ppm) (40 CFR § 180.589). HED has examined the database for boscalid and concludes that pending submission of a revised Section B for alfalfa, and a revised Section F for alfalfa, citrus fruit, stone fruit , and livestock as noted below, there are no deficiencies that would preclude establishing permanent tolerances for b oscalid on alfalfa forage and hay and on the citrus crop group 10, for increasing the existing tolerance on the st one fruit crop group 12, and for increasing the existing tolerances on hog fat, poultry fat, and poultry

meat by products. However, the deficiencies noted below must be resolved as a condition of registration. Note to PM: HED recommends that the following tolerance definition entries in 40 CFR §180.589 be revised and that tolerances for the listed commodities be established, as follows: (a) General. (1) Tolerances are established for residues of the fungicide boscalid, including its metabolites and degradates , in or on the commodities listed below. Compliance with the tolerance levels specified below is to be determined by measuring only 3 - pyridinecarboxamide, 2 - chloro - N - (4' - chloro[1,1' - biphenyl] - 2 -yl). Alfalfa, forage
................................ ................................ ... 30.0 ppm Alfalfa, hay
................................ ................................ ....... 65.0 ppm Citrus, dried pulp
................................ ................................ . 4.5 ppm Citrus, oil
................................ ................................ ............ 85.0 ppm Fruit, citrus, group 10
................................ ........................... 1.6 ppm Fruit, stone, group 12
................................ ........................... 3.5 ppm (2) Tolerances are established for residues of the fungicide boscalid, including its metabolites and degradates , in or on the food commoditi es listed below. Compliance with the tolerance levels specified below is to be determined by measuring only thePage 3 of 47

sum of 3 - pyridinecarboxamide, 2 - chloro - N - (4' - chloro[1,1' - biphenyl] - 2 -yl) and metabolites 2 - chloro -

N - (4' - chloro - 5 - hydroxy- biphenyl - 2 -yl) nicotin amide and glucuronic acid conjugate of 2 - chloro - N - (4' - chloro - 5 - hydroxy- biphenyl- 2 -yl) nicotinamide , calculated as the stoichiometric equivalent of boscalid . Hog, fat
................................ ................................ .............. 0.20 ppm Poultry , fat ................................ ................................ .......... 0.20 ppm Poultry , meat b yproducts
................................ ................... 0.20 ppm The established tolerance s of the following commodities remain unchanged. Cattle, fat
................................ ................................ ............ 0.30 ppm Cattle, meat
................................ ................................ ........ 0.10 ppm Cattle, meat by

products
................................ ..................... 0.35 ppm Egg
................................ ................................ ..................... 0.02 ppm Goat, fat
................................ ................................ .............. 0.30 ppm Goat, meat
................................ ................................ .......... 0.10 ppm Goat , meat b yproducts
................................ ....................... 0.35 ppm Hog, meat
................................ ................................ ........... 0.05 ppm Hog , meat by

products
................................ ........................ 0.10 pp m Horse, fat
................................ ................................ ............ 0.30 ppm Horse, meat
................................ ................................ ........ 0.10 ppm Hor se, meat b yp roducts
................................ ..................... 0.35 ppm Milk
................................ ................................ .................... 0.10 ppm Poultry , meat ................................ ................................ ...... 0.05 ppm Sheep, fat
................................ ................................ ............ 0.30 ppm Sheep, meat
................................ ................................ ........ 0.10 ppm Sheep, m eat b yproducts
................................ ..................... 0.35 ppm (d) Indirect or inadvertent residues. Tolerances are established for residues of the fungicide boscalid, including its metabolites and degradates , in or on the commodities listed below. Compliance with the tolerance levels specified below is to be determined by measuring only 3 - pyridinecarboxamide, 2 - chloro - N - (4' - chloro[1 ,1' - biphenyl] - 2 -yl) . Animal feed, nongrass, group 18, forage, excluding alfalfa 1.0 ppm Animal feed, nongrass, group 18, hay , excluding alfalfa
.... 2.0 ppm Revision to Petitions for Tolerances The recommended tolerances in/on alfalfa, citrus , and stone fruit s are based on the crop field trial data. The appropriate tolerance levels were determined using the HED Standard Operating Proceedure (SOP) “Guidelines for Setting Pesticide Tolerances Based on Field Trial Data
. ” The adequacy

of the existing livestock tolerances were assessed using the available cattle and poultry feeding studies that cover the potential levels of dietary exposure of livestock to boscalid residues. The data indicate that the existing tolerances for meat (0.05 ppm) and meat b yproducts (0.10 ppm) of hogs are adequate; however, the tolerance for hog , fat should be increased to 0.20 ppm. Additionally, the data indicate that the existing tolerances for eggs (0.02 ppm) and poultry meat (0.05 ppm) are adequate; however, the tolerances for po ultry , fat and poultry, meat byproducts should each be increased to 0.20 ppm.Page 4 of 47

860.1200 Direction for Use  A revised Section B for alfalfa is required to amend the label direction for the 70% WDG formulation since it could not be supported b y the field trial data generated with a maximum seasonal use rate of 0.9 lb ai/A. The proposed label rate for the 70% WDG formulation is 1.7X higher; the label should be revised to match the field trial rate. 860.15 5 0 To lerances  Boscalid residues concentrate in citrus dried pulp ( 3.1X) and citrus oil (59X ). A revised Section F is required to propose separate tolerances for citrus, dried pulp at 4.5 ppm, citrus, oil at 85 ppm, and f ruit, citrus, group 10 at 1.6 ppm.  The available data for stone fruits will not support a tolerance level of 5.0 ppm. A revised Section F should be submitted with a tolerance for f ruit, stone, group 12 at 3.5 ppm.  The available data will not support the proposed tolerances for meat, meat by products, and fat of cattle goat, horse, and sheep at 0.2 ppm , 1.5 ppm, and 1.5 ppm , respectivel y. The existing tolerances will be maintained for meat, meat b yproducts , and fat of cattle, goat, horse , and sheep at 0.10 ppm, 0.35 ppm, and 0.30 ppm, respectivel y. The available data will not support the propo sed tolerance of 0.2 ppm for milk and the proposed tolerance of 1.5 ppm for milk fat. The existing tolerance of 0.10 ppm will be maintained for milk, and it is adequate to cover milk fat. The proposed tolerances of 0.20 ppm for hog, fat; poultry , fat; and poultry , meat b yp roducts are adequate. For all remaining livestock commodities, the proposed tolerances must be revised to reflect the recommended tolerance levels as specified in Table 9 .0
. 870.7800 Immunotox icity Study  A s part of the new 40CFR §158 Guidelines, an immunotoxicity study in rats and/or mice is required (see Appendix B). Note to PM: Revisions of the livestock commodities data collection methods have been included in the registrant’s submissions. However, BASF has not indicated wheth er any of the changes were made in their attempt to resolve any of the deficiencies noted by HED in the 2003 petition (M. Nelson, DP#278385, 0 8/15/2003). If the methods have been revised and finalized, this should be clarified and the entire final versio ns of the enforcement and the data collection methods should be submitted to the Office of Pesticide Programs ( OPP ) . Otherwise, registration for the new or amended use patterns for the boscalid products should be made conditional until the deficiencies no ted above are fully resolved. This document provides a summary of the findings from the data evaluation and subsequent assessment of human health risk resulting from these requests. The residue chemistry data review and dietary

exposure assessment were conducted by Amelia Acierto (RAB3) , the occupational exposure data review was conducted by Barry O’Keefe (RAB3) , and the human health risk assessment was conducted b y Nancy J. Tsaur (RAB3); additionally , the drinking water assessment was conducted b y David Lieu of OPP ’s Environmental Fate and Effects Division (EFED).Page 5 of 47 TABLE OF CONTENTS 1.0 EXECUTIVE SUMMARY
................................ ................................ ............................... 6 2.0 INGREDIENT PROFILE
................................ ................................ ............................... 10 2.1 Summary of Proposed New Uses
................................ ................................ ............. 10 2.2 Structure and Nomenclature/ Physical and Chemical Properties
......................... 11 3.0 HAZARD CHARACTERIZAT ION/ASSESSMENT
................................ .................. 12 3.1 FQ PA Safety Factor
................................ ................................ ................................ .. 14 3.2 Summary of Toxicolo gical Doses and Endpoints
................................ ................... 15 3.3 Endocrine disruption
................................ ................................ ................................ 16 4.0 DIETARY EXPOSURE/RIS K CHARACTERIZATION
................................ ........... 16 4.1 Nature of the Residue and Residue Analytical Methods
................................ ....... 17 4.2 Pesticide Metabolites and Degradates of Concern
................................ ................. 18 4.3 Drinking Water Residue Profile
................................ ................................ .............. 18 4.4 Food Residue Profile
................................ ................................ ................................ . 19 4.5 Dietary Exposure and Risk
................................ ................................ ...................... 25 4.5.1 Acute Dietary Exposure Results and Characterization
............................... 25 4.5.2 Chronic Dietary Exposure Results and Characterization
........................... 25 4.5.3 Cancer Dietary Exposure Results and Characterization
............................. 26 4.5.4 Results of Chronic Dietary Exposure Analysis
................................ ............. 26 4.6 Anticipated Residues and Percent Crop Treated
................................ .................. 26 5.0 RESIDENTIAL (NON - OCCUPATIONAL) EXPOSU RE AND RISK

CHARACTERIZATION
................................ ................................ ................. 26 5.1 Residential Handler Exposure
................................ ................................ ................. 27 5.2. Residential Postapplication Exposure
................................ ................................ ..... 27 6.0 AGGREGATE RISK ASSES SMENTS AND RISK CHAR ACTERIZATION
........ 29 6.1 Acute Aggregate Risk
................................ ................................ ............................... 29 6.2 Short- Term Aggregate Risk
................................ ................................ ..................... 29 6.3 Intermediate - Term Aggregate Risk
................................ ................................ ........ 29 6.4 Long - Term Aggregate Risk
................................ ................................ ..................... 29 6. 5 Cancer Aggregate Risk
................................ ................................ ............................. 30 7.0 Cumulative Risk Characterization/Assessment
................................ ............................ 30 8.0 OCCUPATIONAL EXPOSURE/RISK ASSESSMENT PA THWAY
........................ 30 8.1 Occupational Pesticide Handler Exposure and Risk
................................ ............. 30 8.2 Occupational Postapplication Worker Exposure and Risk
................................ .. 32 9.0 TOLERANCE HARMONIZAT ION AND RECOMMENDED TOLERANCE
....... 33 10.0 DATA NEEDS
................................ ................................ ................................ .................. 38 10.1 Toxicology Data Requirements
................................ ................................ ................ 38 10.2 Residue Chemistry Data Requirements
................................ ................................ .. 38 10.3 Occupational/Residential Exposure Data Requirements
................................ ...... 39 REFERENCES
................................ ................................ ................................ ............................. 39 APPENDIX A : TOXICITY PROFILES FOR BOSCALID TECHNIC AL
.......................... 41 APPENDIX B : RATIONALE FOR TOXICITY DATA REQUIREME NTS
....................... 45 APPENDIX C: INTERNATIONAL RESIDUE LIMIT STATUS
................................ .......... 46Page 6 of 47

1.0 EXECUTIVE SUMMARY The most recent human health risk assessment was prepared for the use of boscalid on imported coffee (W. Drew, DP# 354689, 03/25/2009). References may be made to this previous risk assessment for details concerning the toxicological, residue chemistry , toleran ce harmonization, environmental fate, drinking water, and residential aspects of the chemical. No new toxicological data have been submitted and no changes have been made to the endpoints selected for risk assessment. The submitted residue chemistry studies include crop field trials for alfalfa, citrus, and stone fruits; a processing study on citrus; and a cow feeding study . Apart from these submissions, no other changes have been made to the residue chemistry considerations, such as anal ytical enforcement methods, residues of concern (ROCs), environmental fate or drinking water information, etc. Background Boscalid, 2
- chloro
-N

- (4  ́
- chloro[1,1  ́
- biphenyl]
- 2
- yl )
- 3
- py ridinecarboxamide, is a carboxamide (anilide) class fungicide that inhibits mitochondrial respiration, thereb y inhibiting spore germination, germ tube elongation, mycelial growth, and sporulation in all major stages of fungal development and reproduction necessary for disease development in a variety of vegetable, fruit an d row crops. There are currentl y two WDG boscalid end
- use products (EPs) registered to BASF in the U.S. for use on food/feed crops, one containing onl y boscalid and one which is a mixture of two active ingredients. The single ai formulation is a 70% WDG (Endura ® Fungicide; EPA Reg. No. 7969
- 197) and the mixture formulation is a WDG containing 25.2% boscalid and 12.8% py raclostrobin (Pristine ® Fungicide; EPA Reg. No. 7969
- 199). Only boscalid is addressed in this document; py raclostrobin is being evaluated separately
. BASF has submitted several volumes of data in support of two petition s , PP# 9F7527 and PP# 9F 9 529 , to establish permanent tolerances for the combined resid ues of the fungicide boscalid [ 3
- py

ridinecarboxamide, 2
- chloro
-N
- (4’
- chloro(1,1’
- biphenyl)
- 2
- yl ) ] in/on the following crops: Alfalfa Forage
................................ ................................ ................... 35 ppm Alfalfa Hay
................................ ................................ ........................ 85 ppm Citrus Crop Group 10
................................ ................................ ....... 2.0 ppm Stonefruit Crop Group 12
................................ ................................ 5.0 ppm Use Profile The fungicide boscalid has been proposed for use on alfalfa and citrus crop group 10
. Broadcast f oli ar applications of boscalid may be applied to alfalfa (including alfalfa grown for seed) at a rate of 0.48 lb ai/A (Endura ® ) and 0.28 lb ai/A ( Pristine ® ) and to citrus at a rate of 0.29 lb ai/A ( Pristine ® ). For alfalfa, up to three applications can be mad e per season at retreatment intervals (RTI) of 14 to 21 day s. The pre
- harvest interval (PHI) is 14 days. For citrus, up to four applications can be made per season at RTIs of 10 to 21 days. The PHI is zero day s. Handlers may apply boscalid to alfalfa u sing aerial, chemigation, or groundboom equipment. To citrus, handlers may

appl y boscalid using aerial, chemigation , airblast, or handgun equipment. Toxicity /HazardPage 7 of 47

The toxicity

database for boscalid is complete and provides sufficient information to determine whether boscalid p oses a human health hazard. Boscalid has a low acute toxicity and is not an eye or skin irritant. The target organs for boscalid are the liver and thy roid
. An acute endpoint was not selected because no adverse effects attributable to a single exposure to boscalid were seen in the database, including the developmental toxicity studies
. The chronic dietary , incidental oral, dermal, and inhalation endpoints were all selected from combined results of the three studies: chronic rat , carcinogenicity rat, and chronic dog

. The dose selected for regulation of oral, dermal and inhalation risk at all durations, for all populations is the NOAEL of 21.8 mg/kg/day

based on thyr oid and hepatic toxicity seen in rats and dogs at higher dose l evels. A dermal absorption factor of 15% was derived from an in vivo dermal penetration study in the rat. An inhalation absorption factor of 100% was assumed for the inhalation risk assessments. The standard UF of 100 X to account for inter
- and intra
- species variability was applied to all risk assessments. The Food Quality Protection Act ( FQPA) safety factor (SF) for boscalid was reduced to 1 X
. With the exception of an immunotoxicity study , the boscalid toxicity database is complete; there are no rep roductive, developmental or developmental neurotoxic concerns. While the data did show increased quantitative and qualitative sensitivity, the effects noted were either transient or inconsistent , or occurred at the limit dose in the presence of maternal toxicity
. There are clear NOAELs for these effects and EPA is regulating based on a point of departure ( PoD ) below where these effects are seen. Additionally , the estimates of exposure are unlikely to underestimate risk. Therefore, EPA has concluded that the application of an additional SF to protect infants and children is not needed
. Boscalid is classified as "suggestive evidence of carcinogenicity " and the chronic PoD is protective of any tumor response seen in the boscalid cancer studies. Recent changes to 40CFR §158 make immunotoxicity testing (OPPTS Guideline 870.7800) required for pesticide registration. The available data for boscalid do not show potential for immunotoxic effects. However, the 870.7800 immunotoxicity study is required, and should be considered confirmatory

(see Appendix B). Dietary Exposure (food/drinking water) Residues of Concern : For purposes of both the tolerance expression and dietary risk assessment, HED has concluded that the residues of concern in plant commodities include only boscalid, and the residues of concern in livestock commodities include boscalid , its 5
- hydrox y metabolite, and the glucuronide conjugate of the 5
- hydroxy metabolite. Acute Dietary Exp osure/Risk : S ince no observed effects could be attributed to a single dose, an acute endpoint was not established; therefore, a n acute dietary

exposure assessment was not conducted
. Chronic Dietary Exposure/Risk : The chronic dietary anal ys i s was performed using tolerance level residues and 100% crop treated ass umptions. Dietary risk estimates were determined considering exposures from food plus drinking water. Boscalid exposure from the existing uses, the proposed new use s on citrus and alfalfa , the recommended tolerance increase for stone fruits, and the esta

blished and recommenced tolerances on livestock results in estimated risk s that arePage 8 of 47

below the Agency ’s LOC for food plus drinking water. The highest exposure and risk estimates for food plus drinking water are 1 1 % of the chronic population adjusted dose ( cPAD) for the U.S. population and 3 7 % for children 1
- 2 years old, the most highly exposed population subgroup
. Cancer Dietary Risk : A cancer dietary assessment was not conducted since boscalid was classified by HED as “ suggestive evidence of carcinogenici ty” and quantification of human cancer risk is not recommended. Residential Exposure Residential Handler Exposure : There are no residential uses associated with this action and application of boscalid by homeowners is not anticipated . Therefore, residential handler exposure was not evaluated. Residential Postapplication Exposure : For existing uses on registered labels, there is potential for exposure to homeowners in residential settings from “pick
- your own” (PYO) operations and from entering areas previously treated with boscalid , such as lawns where children might play , or golf courses that could lead to exposures for adults. Given the 1
- day duration for PYO activities, a exposure/risk assessment was not conduct ed since there are no toxic effects anticipated from a single exposure to boscalid. The margins of exposure ( MOEs ) for residential postapplication exposure to boscalid are all above 100, and therefore, do not exceed HED's LOC
. There are no risks o f concern from residential post application exposure during golfing. Aggregate Risk Acute Aggregate Risk : Acute exposures were not considered because an adverse effect attributable to a single dose was not identified. Short

- Term and Intermediate

- Term Aggregate Risk : There is potential short
- and intermediate
term exposure to boscalid via the dietary (which is considered background exposure) and residential (which is considered primary) pathways. For adults, these pathway s lead to exposure via the oral (background) and dermal (primary) routes. F or children, these pathway s lead to exposure via the oral (background), and incidental oral and dermal (primary) routes. All MOEs are greater than 100, which indicates that exposure and risk do not exceed HED’s LOC
. Long
- Term Aggregate Risk : There is po tential chronic exposure via dietary (food and drinking water) exposure. Refer to Chronic Dietary Exposure/Risk
. Cancer Risk : Boscalid is classified as “ suggestive evidence of carcinogenicity” and therefore, an aggregate cancer assessment was not conducted. Occupational Exposure/Risk Dermal : The results of the occupational handler exposure and risk assessment indicate that short
- and intermediate
- term dermal MOEs were greater than the LOC (MOEs ≥ 100) at the baseline clothing level , when baseline data are available
. The short
- and intermediate
- term dermal risks do not exceed HED ’s LOC for mixing/loading/appl ying with handgun equipmentPage 9 of 47

when baseline attire plus chemical
- resistant gloves are used. The short
- and intermediate
- term dermal risks do not ex ceed HED ’s LOC for pilots using enclosed cockpits and wearing baseline attire. Inhalation : The short
- and intermediate
- term inhalation risks to handlers do not exceed HED ’s LOC at baseline (no respirator) for any of the handler scenarios. Onl y engineering control (enclosed cockpit) data are available to assess short
- and intermediate
- term inhalation risks to handlers operating aircraft. The short
- and intermediate
- term inhalation risks do not exceed HED ’s LOC for pilots using enclosed cockpits and wearing no respirator. Combined: Combined dermal plus inhalation risks do not exceed HED ’s LOC , provided personal protective equipment (PPE) listed under the short
- and intermediate
- term dermal risks are worn. Postapplication : Short
- and intermediate
- term d ermal postapplication exposures and risks to occupational workers were estimated using standard values established b y HED since no chemical
- specific data were submitted. Using HED default assumptions and surrogate dislodgeable foliar residue (DFR) data, all scenarios resulted in MOEs greater than 100 on day 0 (12 hours after application) , and therefore risks do not exceed HED ’s LOC
. Restricted Entry Interval (REI) : Since postapplication risks were not a concern on day 0 (12 hours following application), the REI is based on the acute toxicity of boscalid technical material. Boscalid is classified as t oxicity c ategory I II b y the dermal route of exposure and category IV for eye irritation and skin irritation potential. Under the Worker Protection Standard (WPS) for Agricultural Pesticides, active ingredients classified as acute toxicity categories III or IVfor these routes are assigned a 12
- hour REI. Therefore, the 12
- hour REI that appears on the proposed label is adequate. International Harmonization The Codex Alimentarius Commission , Canada, and Mexico have not established any maximum residue limits (MRL s) for residues of boscalid in/on alfalfa forage and hay or citrus fruits (Appendix I). However, there is an existing Codex MRLfor stone fruits at 3 mg/kg, and Canada has established MRL s at 1.7 mg/kg for the various member of the stone fruits crop group. Canada also has also established MRL s for various livestock commodities. The Canadian MRLs for stone fruits and livestock commodities are currently harmonized with the respective U.S. tolerances; however, once the recommended increases are made to U.S. tolerances, the U.S. tolerances on stone fruits, poultry fat and meat b yproducts , and hog fat will no longer be harmonized with the Canadian MRL s. Environmental Justice Considerations Potential areas of environmental justice concerns, to the extent possible, were considered in this human health risk assessment, in accordance with U.S. Executive Order 12898, "Federal Actions to Address Environmental Justice in Minority Populations and L ow - Income Populations," http://www.eh.doe.gov/oepa/guidance/justice/eo12898.pdf
.Page 10 of 47

As a part of every

pesticide risk assessment, OPP considers a large variety of consumer subgroups according to well
- established procedures. In line with OPP policy , HED estimates risks to population subgroups from pesticide exposures that are based on patterns of that subgroup’s food and water consumption, and activities in and around the home that involve pesticide use in a residential setting. Extensive data on food consumption patterns are compiled by the USDA under the Continuing Survey of Food Intake by

Individuals (CSFII) and are used in pesticide risk assessments for all registered food uses of a pesticide. These data are anal yz ed and categorized by

subgroups based on age, season of the year, ethnic group, and region of the country . Additionally , OPP is able to assess dietary exposure to smaller, specialized s ubgroups and exposure assessments are performed when conditions or circumstances warrant. Whenever appropriate, non
- dietary

exposures based on home use of pesticide products and associated risks for adult applicators and for toddlers, youths, and adults entering or playing on treated areas postapplication are evaluated. Further considerations are currentl y in development as OPP has committed resources and expertise to the development of specialized software and models that consider exposure to b ys tanders and farm workers as well as lifestyl e and traditional dietary patterns among specific subgroups. 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 o ther chemical. These studies, which comprise the Pesticide Handlers Exposure Database (PHED), have been determined to require a review of their ethical conduct and have received that review. 2.0 INGREDIENT PROFILE Reference :

- Boscalid; Petition for Es tablishing Permanent Tolerances on Alfalfa and the Citrus Crop Group 10, and Amending the Established Tolerance on the Stone Fruit Crop Group 12. Summary of Analytical Chemistry and Residue Data . A. Acierto, DP#364447, 10/16/2009. Boscalid is a carboxami de (an anilide) fungicide that inhibits mitochondrial respiration, thereb y inhibiting spore germination, germ tube elongation, mycelial growth, and sporulation of pathogenic fungi on the leaf surface. Boscalid is currentl y registered to BASF as WDG formul ations for use on a wide variety of food/feed crops. 2.1 Summary of Proposed New Uses BAS F is proposing new uses for the 70% WDG (Endura® ) formulation on alfalfa and for the 25% WDG (Pristine ® ) on alfalfa and citrus fruits . Supplemental labels were provided. The use directions for alfalfa and citrus, including the directions for stone fruits, are summarized below in Table 2.1
.Page 11 of 47 Table 2 . 1 .` Summary of Directions for Use of Boscalid. Application Timing, Ty pe, and Equipment 1 Trade Name Form ulation [EPA Reg. No.] Application

Rate (lb ai/A) Max. No.

Applic ation per Season Max. Seasonal

Application Rate (lb ai/A) PHI

(days) Use Directions and

Limitations 2 Alfalfa 3 Broadcast foliar applications when conditions are favorable to disease development; ground, aerial , or chemigation equipment
. Endura® 70% WDG [7969
- 197] 0.09
- 0.48 3 (2 per cutting) 1.44 14 The minimum RTI is 14 days. For aerial applications, use a minimum of 10 gal/A Do not make more than 2 applications per cutting or 3 applications per s eason. Pristine ® 25.2% WDG [7969
- 199] 0.19
- 0.28 3 (2 per cutting) 0.85 14 Citrus Fruits Broadcast foliar application s prior to infection; ground, aerial , or chemigation equipment
. Pristine ® 25.2% WDG [7969
- 199] 0.25
- 0.29 4 1.17 0 The minimum RTI i s 10 days. For aerial applications, use a minimum of 10 gal/A
. Stone Fruits Broadcast foliar applications from pink bud thro ugh fruit development; ground, aerial, or chemigation equipment
. Pristine ® 25.2% WDG [7969
- 199] 0.17
- 0.23 5 1.14 0 The minimum RT I is 7 days. For aerial applications, use a minimum of 10 gal/A
.
1 Chemigation may be made through the followin g types of irrigation systems: center pivot, lateral move, end tow, side wheel roll, traveler, big gun, solid set, or hand move. 2 Use directio ns allow for the use of spray adjuvants and specify a 14
- day plant
- back interval for rotational crops without registered uses for boscalid. 3 For stand establishment of fall seeded alfalfa, begin applications in fall through early winter prior to first sno wfall or extended cool, wet conditions. For seed pod protection, begin applications at 10% to 30% bloom. 2.2 Structure and Nomenclature/ Physical and Chemical Properties The chemical structure and nomenclature of boscalid and its hydrox ylmetabolite and phy sicochemical properties of the technical grade of boscalid are presented in Tables 2.2.1 and 2.2.2. Table 2.2.1. Nom enclature of Boscalid and its Hydroxy Metabolite . Compound

N N O

Cl

Cl Common name Boscalid; Nicobifen Company experimental name BAS 510 F IUPAC name 2
- chloro
-N
- (4'
- chlorobiphenyl
- 2
- yl)
- nicotinamidePage 12 of 47

Table 2.2.1. Nom enclature of Boscalid and its Hydroxy Metabolite . CAS name 3
- pyridinecorboxamide,2
- chloro
-N
- (4'
- chloro[1,1'
- biphenyl]
- 2
- yl Molecular weight 343.2 CAS registry number 188425
- 85
- 6 End
-use product (EPs) 25.2% WDG (Pristine ® Fungicide; EPA Reg. No. 7969
- 199, also contains 12.8% pyraclostrobin) 70% WDG (Endura® Fungicide; EPA Reg. No. 7969
- 197) Hydroxy
- metabolite

N N O

Cl

Cl O H

Common name Boscalid hydroxy metabolite Company experimental name M510F01 (glucuronide conjugate

– M510F02) CAS name 2
- chloro
-N
- (4'
- chloro
- 5
- hydroxy
- biphenyl
- 2
- yl)nicotinamide Molecular weight 359.2 Table 2.2.2. Physicochemical Properties of Boscalid. Parameter Value References Melting point/rang e 142.8
- 143.8 ° C MRIDs 45404802 and 45404804
- 45404809 pH NA (does not dissociate in water) Relative Density (20oC) 1.381g/cm3 Water solubility (20oC) 4.64 mg/L at pH 6 Solvent solubility (g/100 mL at 20oC) acetone 16
- 20 ethyl acetate 6.7
- 8.0 methano l 4
- 5 2
- propanol <0.01 acetonitrile 4
- 5 dichloromethane 20
- 25 toluene 2
- 5 n - heptane <0.01 1
- octanol <0.01 olive oil 2.9 N,N
- DMF >25 Vapor pressure 7 x 10 - 9 hPa Dissociation constant, pKa None (does not dissociate in water) Octanol/water parti tion coefficient, Log(KOW) 2.96 UV/visible absorption spectrum UV molecular extinction (ε[Lmol - 1 cm- 1 ]): 3.15 x10 4 at 228 nm; 1.53 x10 3 at 290 nm 3 .0 HAZARD CHARACTERIZAT ION/ASSESSMENT References:

- BAS 510 F
- Report of the Hazard Identification Assessment Review Committee . A. Levy, TXR#0051613, 03/07/2003.

- BAS 51 0 F: Report of the Cancer Assessment Review Committee
. J. Kidwell, TXR# 0051289, 11/1 4 /2002
.

- Boscalid. Human Health Risk Assessment for a Section 3 Tolerance on Endive, an Amendment to the Tolerances for Strawberries and Berries, Crop Group 13, and an Incre ase in Tolerances in/on Cucumber and Vegetable, Root, Subgroup 1A, except Sugar Beet, Garden Beet, Radish, and Turnip. B . Hanson, DP#327906, 07/10/2007.

- PP# 1F06313
--Human Health Risk Assessment for New Fungicide BAS 510 F (Common Name: Boscalid)

-- Proposal for Tolerances for Residues in/on Numerous Crops and Livestock Commodities
. Y. Donovan, DP#290022, 0 9/0 8/2003
.Page 13 of 47

The toxicity

database for boscalid is adequate for risk assessment purposes. However, as part of the new 40 CFR § 158 Guidelines, an immunotoxicity study (OPPTS Guideline 870.7800) in rats and/or mice is required (see Appendix B). No indication of immunotoxicity was observed in the toxicity database; therefore, an additional 10X database UF is not warranted. Boscalid appeared to have effects on the liver and/or thy roid of several species. In a 90
- day mouse study , there were increased liver weights and increased incidences in marked fatty change in the liver. These liver changes were not noted in the 18
- month mouse study . In 90
- day as well as in 2
- ye ar rat studies, there were thy roid changes (increase in weights and incidence of follicular cell hyperplasia and hypertrophy) . The thy roid changes were considered to have been the result of liver adaptive responses. The 90
- day and one
- ye ar dog studies showed increases in the levels of alkaline phosphatase as well as hepatic weights. In three mechanistic rat studies, the following were observed: increase in liver microsomal activity , induction of total cy tochro me P450 activity , disruption of thy roid homeostasis by

decreasing circulating T 3 and T 4 and increasing TSH (likel y the result of hepatic microsomal glucuronyltransferase), and reversal of liver and thy

roid effects with the cessation of test article adminis tration (it was concluded that the induction of liver microsomal enzy me s ys tem resulted in increased glucuronidation of thy roxine, resulting in an increase in TSH secretion as a compensatory response of the phy siological negative feedback s ys tem; increased TSH resulted in increased thy roid weight). There were little or no effects on body weights or body weight gains. In the developmental toxicity studies, no effects were noted in rats; whereas, in the rabbit study , abortions or early

delivery were observe d at the highest dose tested (1000 mg/kg/day). Regarding the 2
- generation reproduction study in rats, decreased body weights and/or body weight gains and hepatocy te degeneration were noted in males only . No reproductive effects were observed. The onl y eff ects noted in pups of both generations were decreases in body weights (both sexes of both generations) at the highest dose tested (>1000 mg/kg/day). There was no evidence of neurotoxicity based on an acute neurotoxicity study , a 90
- day

neurotoxicity study , and a developmental neurotoxicity study (all in rats). There was no evidence of increased susceptibility

in the developmental rat study (Limit Dose). Qualitative, but not quantitative, increased susceptibility

was noted in the developmental rabbit study a s characterized by

an increased incidence of abortions or earl y delivery at the highest dose tested (1000 mg/kg/day)
. There was quantitative evidence of increased susceptibility in the two
- generation reproduction rat study where decreases in body weights and body

weight gains in male offspring were seen in the F 2 generation and in females from both generations at a dose that was lower than the dose that induced parental/sy stemic toxicity . Quantitative evidence of increased susceptibility was noted in the developmental neurotoxicity study in rats where decreases in pup body weights (PND 4) and body weight gains (PND 1
- 4) were seen in the absence of any maternal toxicity. The degree of concern is low for the qualitative evidence of susceptibility seen in the rabbit developmental study as the increased abortions or earl y delivery was seen onl y at the Limit Dose and the abortions may

have been due to maternal stress. The degree of concern is low for the quantitative evidence of susceptibility seen in the two
- generation reproduction study in rats because the decreases in body weight and body weight gains were seen onl y in the F 2 generation in males and in females in both generations. The degree of concern is low for the quantitative evidence of susceptibility

in th e developmental neurotoxicity study because the decreases in pup bodyPage 14 of 47

weights seen on post natal day s 1 through 4 (at no other time periods) were most likely due to maternal toxicity
. Boscalid has low acut e toxicity via the oral, dermal , and inhalation routes of exposure , and is not an eye or skin irritant (see Appendix A, Table A.1) . Dermal sensitization could not be determined because the skin sensitization study was inadequate. The target organs for boscalid are the liver and thy

roid. An acute diet ary endpoint was not selected because no adverse effects attributable to a single exposure to boscalid were seen in the database, including the developmental toxicity studies. The chronic dietary , incidental oral, dermal, and inhalation endpoints were all selected from combined results of the three studies: chronic rat , carcinogenicity rat , and chronic dog

. The dose selected for regulation of oral, dermal , and inhalation risk at all durations, for all populations , is the no observed adverse effect level (NOAEL) of 21.8 mg/kg/day , based on thy roid and hepatic toxicity seen in rats and dogs at higher dose levels. A dermal absorption factor of 15% was derived from an in vivo dermal penetration study in the rat. An inhalation absorption factor of 100% was as sumed for the inhalation risk asse ssments. Boscalid is classified as exhibiting “suggestive evidence of carcinogenicity, but not sufficient to assess human carcinogenic potential, ” and, therefore, the quantification of human cancer risk is not recommended. The classification was based on data which were combined from two 2
- ye ar rat studies where males had a significant increasing trend and significant differences in pair
- wise comparison with the controls for thy roid follicular cell adenomas. This was supported by thy roid hy pertrophy and hyp erplasia of follicular cells, increased thyroid weights and mechanistic data. Combined study

data for female rats showed onl y a borderline significant increasing trend for thy roid follicular cell adenomas. No increase o ver controls was noted in males or females for carcinomas. There was no increase in the incidence of any tumors of either sex in the 18
- month mouse study . All mutagenic studies were negative with or without activation. Based on the overall weak evidence of carcinogenic effects, the CARC indicated that a dose
- response assessment for cancer (either linear low
- dose extrapolation or MOE calculation) was not needed. Thus, evidence of carcinogenicity was seen in males (significant trend and pair
- wise at the high dose) and in females (trend only) ; however , no malignancies were seen in either sex . O nly benign tumors were observed , and these occurred at dose levels above the dose level used to establish the cPAD
. Additionally, there is no concern for mutagencity. The PoD for chronic risk assessment is protective of any tumor response seen in the boscalid cancer studies. The toxicological profile s for boscalid are outlined in Appendix A of this document. 3 .1 FQ PA Safety Factor The standard UF of 100 X to acco unt for inter
- and intra
- species variability was applied to all risk assessments. The FQPA SF for boscalid was reduced to 1X for the reasons listed below.Page 15 of 47

1. The toxicity

database for boscalid is adequate for risk assessment, however an immunotoxicity

study (OPPTS Guideline 870.7800) in rats and/or mice is required under the new 40 CFR part 158 data regulations. No indication of immunotoxicity was observed in the toxicity database; therefore, an additional 10X database UF is not warranted. 2. There is no indi cation that boscalid is a neurotoxic chemical and there is no need for additional UFs to account for neurotoxicity . There is no evidence of neurotoxicity in the acute subchronic, or developmental neurotoxicity studies. The toxicity

studies for boscalid dem onstrate that, in general, the chemical has low mammalian toxicity , and the database reveals no reproductive, developmental, or developmental neurotoxicity concerns. 3. Data involving the testing of young animals did show increased quantitative sensitivity

in the young with regard to body weight effects, and qualitative sensitivity was seen in one developmental study . However, clear NOAELs were identified for all of these effects. Moreover, the body weight effects at the LOAELs in these studies were either transient or inconsistent, and qualitative sensitivity occurred at the limit dose in the presence of maternal toxicity . Additionally , EPA is regulating based on a Po D below where these effects are seen. EPA concludes that there are no residual uncertainties f

or pre - and/or post
- natal toxicity
. 4. There are no residual uncertainties identified in the exposure databases. EPA has conservativel y estimated human exposure to boscalid, relying on worst case exposures in food (assuming all registered crops contain residu es at the tolerance level), and conservative models, as well as pesticide
- specific data, in estimating exposure from residues in drinking water, and from residential uses. These assessments will not underestimate the exposure and risks posed by boscalid. Based on consideration of all of these data, HED has concluded that i t has reliable evidence to show that infants and children would be adequately protected without application of an additional 10X SF
. 3 .2 Summary of Toxicological Doses and Endpoints The endpoints and doses selected for risk assessment purposes are summarized in Table 3 .2
. T ABLE 3 .2 . Summ ary of Toxicological Doses and Endpoints for Boscalid . Exposure [ Scenario ] P o D Uncertainty and FQPA Safety Factors RfD/PAD/

LOC Study and Toxic ological Effects Ac ute Dietary [ All Populations ] No appropriate endpoint attributable to a single dose was available in the current database,

including the developmental toxicity studies. Therefore, an acute RfD and acute PAD w ere not established for any population. Chronic Dietary [ All Po pulations] NOAEL = 21.8

mg/kg/day UF A = 10X

UF H = 10X FQPA SF = 1X Chronic RfD =

0.218 mg/kg/day Chronic PAD = 0.218 mg/kg/day Com bined results of c hronic rat, carcinogenicity rat , and 1
- year dog studies
. LOAEL = 57 mg/kg/day , based on liver and thyroid effects
. Incidental Oral , Short
- and NOAEL = 21.8

mg/kg/day UF A = 10X

UF H = 10X Residential

LOC = C om bined results of c hronic rat, carcinogenicity rat , and 1
-Page 16 of 47

T ABLE 3 .2 . Summ ary of Toxicological Doses and Endpoints for Boscalid . Exposure [ Scenario ] P o D Uncertainty and FQPA Safety Factors RfD/PAD/

LOC Study and Toxic ological Effects Intermediate
Term FQPA SF = 1X MOE < 100 year dog studies
. LOAEL = 57 mg/kg/day , based on liver and thyroid effects
. Dermal [ All Durations ] Oral study NOAEL

= 21.8 mg/kg/day D ermal absorption = 1 5% UF A = 10X

UF H = 10X FQPA SF = 1X Residential and

Occupational LOC = MOE < 100 C om bined results of c hronic rat, carcinogenicity rat , and 1
- year dog studies
. LOAEL = 57 mg/kg/day , based on liver and thyroid effects
. Inhalation [ All Durations ] Oral study NOAEL

= 21.8 mg/kg/day Inhalation absorption = 100% UF A = 10X

UF H = 10X FQPA SF = 1X Residential and

Occupational LOC = MOE < 100 C om bined results of c hronic rat, carcinogenicity rat , and 1
- year dog studies
. LOAEL = 57 mg/kg/day , based on liver and thyroid effects
. Cancer Classified as exhibiting “suggestive evidence of carcinogenicity
. ” Quanti fication of human

cancer risk is not recommended
. Po D = Point o f Departure , a data point ( or estimated point) that is derived from observed dose
- response data , and used to mark the beginning of extrapolation to determine risk associated with lower environme ntally relevant human exposures. NOAEL = N o Observed Adverse E ffect Level. LOAEL = L ow est Observed Adverse E ffect Level . UF = Uncertainty F actor. UF A = extrapolation from animal to human (int e rspecies). UF H = potential variation in sensitivity among members of the human population (intra species). FQPA SF = FQPA Safety Factor. PAD = Population Adjusted Dose. RfD = Reference Dose. LOC = Level O f Concern. MOE = Margin Of Exposure. 3.3 Endocrine disruption EP A is required under the FFDCA, as amended by FQPA, to develop a screening program to determine whether certain substances (including all pesticide active and other ingredients) “may have an effect in humans that is similar to an effect produced b y a naturally occurring estrogen, or other such endocrine effects as the Administrator may designate.” Following recommendations of its Endocrine Disruptor and Testing Advisory Committee (EDSTAC), EPA determined that there was a scientific basis for including, as p art of the program, the androgen and thy roid hormone s ys tems, in addition to the estrogen hormone s ys tem. EPA also adopted EDSTAC’s recommendation that the Program include evaluations of potential effects in wildlife. For pesticide chemicals, EPA will us e FIFRA and, to the extent that effects in wildlife may help determine whether a substance may have an effect in humans, FFDCA authority to require the wildlife evaluations. As the science develops and resources allow, screening of additional hormone sy st ems may

be added to the Endocrine Disruptor Screening Program (EDSP). When additional appropriate screening and/or testing protocols being considered under the Agency ’s EDSP have been developed, boscalid may be subjected to further screening and/or testing to better characterize effects related to endocrine disruption. 4 .0 DIETARY EXPOSURE /RISK CHARACTERIZATION A residue chemistry

summary document has been prepared for the proposed uses on alfalfa, citrus fruits, and increased tolerance on stone fruits (A. Acierto, D P# 364447 , 10/16/2009 ).Page 17 of 47

Reference may

be made to this document for details concerning residue chemistry consideration s associated with the current use request , such as a summary of registered uses, boscalid nomenclature, phys ical and chemical properties, use directions, metabolism in plants and animals, anal ytical methods, storage stability , field trial results, etc
. 4 .1 Nature of the Residue and Residue Analytical Methods Boscalid residues in all samples associated with the current field trials and livestock studies were determined using the methods described below. For purposes of both the tolerance expression and dietary

risk assessment, HED has concluded that the ROC in plant commodities include only boscalid, and the ROC in livestock commodities include boscalid , its 5
- hydrox y metabolite, and the glucuronide conjugate of the 5
- hydroxy metabolite. 860.1300 Nature of the Residue and 860.1340 Residue Analytical Methods

– Plants The nature of boscalid residues in primary crops is adequate ly

understood, based upon acceptable grape, lettuce, and bean metabolism studies; these studies were reviewed in the initial boscalid petition, PP#1F6313 (M. Nelson, DP#278385, 08/15/2003 ). An adequate gas chromatography with mass spectrometric detection ( GC/MS ) method ( BASF Method D0008) is available for enforcing boscalid tolerances in plant commodities. The Analy tical Chemistry Branch (ACB) of the Biological and Economic Analysis Division ( BEAD ) concluded that the method is acceptable for enforcement purposes in plants , without the need for an EPA validation. An adequate high
- performance liquid chromatography with ultraviolet detection (HP LC /UV) method (BASF Method 441/0 ) is also available for collecting residue data on plant commodities. 860.1300 Nature of the Residue and 860.1340 Residue Analytical Methods

– Livestock The nature of boscalid residues in livestock is adequately understood, based upon acceptable 14 C metabolism studies conducted on lactating goats and laying hens. An enforcement method (BASF Method DFG S19) is available for determining the residues of concern in livestock and has been successfull y validated by ACB/BEAD. For the current livestock feeding study , residues of boscalid and its hydrox ylmetabolite M510F01 (including the g lucoronide conjugate M510F02) were determined using a L C/MS/MS method (BASF Method 471/0, modified) which was previousl y reviewed in conjunction with earlier feeding studies. For calculating combined residues, Metabolite M510F01 residues are converted into parent equivalents using a conversion factor of 0.96. The above method was adequately validated prior to and in conjunction with the anal ys is of feeding study samples, using control samples fortified with boscalid and M510F01 at 0.01 ppm

– 2.5 ppm for m ilk, skim milk, and cream, and 0.025 ppm
– 2.5 ppm for liver, kidmey , muscle, and fat samples. 860.1360 Multiresidue Methods Residues of boscalid and its metabolite M510F01 were not adequatel y recovered using the Multiresidue methods. 860.1380 Storage StabilityPage 18 of 47

Adequate storage stability studies are available indicating that boscalid is relatively stable at ≤20°C in fortified samples of cabbage (leafy vegetables) , canola seed (oil seed), peach (fruit/fruiting vegetable), sugar beet roots (root crop), peas (legume vegetable, wheat grain (non
oily grain), wheat forage (foliage), and wheat straw (dry feed) for up to 24 months. Inaddition to the above date, a concurrent storage stability study was conducted in conjunction with the orange processing study (MRID 47584402.der). The available storage stability data are adequate and support the storage conditions and durations for samples of alfalfa, citrus fruits, and stone fruits from the current field trials and the acceptable citrus processing study. 4 .2 Pesticide Metabolites and Degradates of Concern Boscalid is a persistent compound with low mobility in most soils. The primary degradation pathway is aerobic soil metabolism, which proceeds slowly and results in the formation of intermediates which are relatively rapidl y transformed into CO 2 or bound soil residues. Boscalid is stable to hydrol ys is and to photolysis on soil and in water. The compound is also not transformed to any significant extent in either aerobic or anaerobic aquatic systems. The residues of concern to be included in the tolerance expression and for risk assessment purposes are summarized below in Table 4.2. Table 4.2. Summary of Metabolites and Degradates to be included in the Risk Assessment and

Tolerance Expression . Matrix Residues included in Risk Assessment Residues included in Tolerance Expression Plants Primary Crop Parent only Parent only

Rotational Crop Parent only Parent only Livestock Ruminant Parent and hydroxy and glucuronic acid metabolites Parent and hydroxy and g lucuronic acid metabolites Poultry Parent and hydroxy and glucuronic acid metabolites Parent and hydroxy and glucuronic acid metabolites Drinking Water Parent only Not Applicable 4 . 3 Drinking Water Residue Profile References:

- Drinking Water Exposu re Assessment for New Uses of Boscalid on Alfalfa Forage and Hay, Citrus group 10, and an Increase in Tolerance on Stone Fruit group 1 2. D. Lieu , DP# 367184 , 0 9/24 /200 9
.

- Drinking Water Assessment for the IR

- 4 Petition for the Use of Boscalid on Tropical Fruits and Fresh Herbs, and a Proposed New Use on Cotton . C. Sutton, DP#33 6183 , 0 8/08/2007
. EFED completed a drinking water assessment (DWA) for boscalid ( D
. Li eu , DP#3 67184, 09/24 /20 09), indicating that the previous assessment conducted by C. Sutton (DP#3 3 6183 , 0 8 / 08 /2007 ) yields higher EDWCs. The highest EDWC s were based on the turf use. The current requests for new uses on alfalfa and citrus and the increase of tolerance s for stone fruit crop group 12 do not affect the EDWCs. As a result, the EDWCs use d in the previous assessment were used in this assessment as well. The EDWCs were incorporated directly intoPage 19 of 47

th e dietary

assessment via the food categories “water, direct, all sources” and “w ater, indirect, all sources.” The EDWCs for boscalid in surface water and ground water were calculated using the screening model FIRST (FQPA Index Reservoir Screening Tool , Version 1.1
. 0, dated 12/12/2005) , and the regression model SCI
- GROW (Screening Concentration in Ground Water, Version 2.3, dated 07/29/2003), resp ectivel y. An acute dietary risk assessment was not conducted
. The maximum estimated chronic ground water EDWC wa s 0.63 ppb. The maximum estimated chronic surface water EDWC wa s 29.6 ppb. The surface water value is higher than the ground water value and was , therefore , used in the dietary assessment. 4 . 4 Food Residue Profile References:

- Boscalid; Petition for Establishing Permanent Tolerances on Alfalfa and the Citrus Crop Group 10, and Amending the Established Tolerance on the Stone Fruit Crop Grou p 12. Summary of Analytical Chemistry and Residue Data
. A. Acierto, DP#364447, 10/16/2009
. BASF is proposing new uses for boscalid on alfalfa using the 25% WDG and 70% WDG formulations and on citrus fruits using the 25% WDG formulation. The proposed uses on alfalfa are for repeated broadcast foliar applications at up to 0.28 lb ai/A for the 25% WDG and 0.48 lb ai/A for the 70% WDG, with a minimum RTIof 14 day s, for a maximum of 0.85 lb ai/A/season and 1.44 lb ai/A/season for the 25% WDG and 70% WDG, resp ectively . A maximum of 3 applications to alfalfa are allowed per season with no more than 2 applications per cutting. The proposed use on citrus fruits is for up to four broadcast foliar applications during fruit development at rates up to 0.29 lb ai/A with a minimum RTIof 10 day s, for a maximum of 1.17 lb ai/A/season. All applications can be made using ground, aerial , or chemigation equipment, and the proposed PHIs are 14 day s for alfalfa and 0 day s for citrus fruits. 860.1480 Meat, Milk, Poultry, a nd Eggs Adequate cattle and poultry feeding studies are available. The maximum dietary burden for poultry was originally calculated to be 1.85 ppm ( M. Nelson, DP#278385, 8/15/2003), and the maximum dietary

burdens for other livestock were most recentl y calculated to be 16.4 ppm for beef cattle, 13.2 ppm for dairy cattle, and 1.79 ppm f

or swine ( D. Dotson, DP#322235, 11/03/2005). A summary of the combined residue data from the 2008 dairy cattle feeding study and the poultry

feeding studies are summarized in DP#364447 (A. Acierto, 10/16/2009)
. Cattle Feeding Studies. BASF submitted a new cattle feeding study conducted in 2008 in which two groups of lactating dairy cows were administered with encapsulated boscalid via balling gun for 29 consecutive day s at the target doses of 35 ppm (Group 2; 3 cows) or 105 ppm (Group 3; 7 cows). These dose levels are intended to represent 1X and 3X the anticipated European Union ( EU) dietary

burden of 35 ppm in the feed on a dry weight basis. Poultry Feeding S

tudy. In the poultry

feeding study , three groups of l aying hens w ere dosed orally once a day for 29 consecutive day s with boscalid at levels equivalent to 1.02 ppm , 5.31 ppm , and 19.6 ppm in the diet, which are respectively equivalent to 0.25X , 1.3X, and 4.8X of the maximum dietary burden of poultry to boscalid
.Page 20 of 47

Livestock Dietary Burdens. As alfalfa forage and hay are major livestock feedstuffs, the dietary burdens for livestock were recalculated for this petition. Based on the recent changes in calculating res idues in reasonably balanced livestock diets ( Table 1, Feedstuffs , June 2008), the dietary burden for livestock from boscalid residues were recalculated to be 1 0.8 ppm for beef cattle, 22.5 ppm for dairy cattle, 4. 0 ppm for poultry , and 5.3 ppm for swine ( Table 4 .4. 3 ). TABLE 4 .4.3 . Calculation of Dietary Burdens of Boscalid Residues to Livestock. Feedstuff Type 1 % Dry Matter 2 % Diet 2 Recommended Tolerance (ppm) Dietary Contribution (ppm) 3 Beef Cattle Alfalfa, hay R 89 10 65 7.3 Cotton, gin byproducts R 90 5 55 3.06 Field corn, grain CC 88 80 0.2 0.18 Canola, meal PC 88 5 3.5 4 0.2 TO TAL BURDEN
-- -- 100
-- 10.8 Dairy Cattle Alfalfa, forage R 35 20 30 17.2 Grass, hay R 88 25 8.0 2.27 Apple, wet pomace CC 40 10 10 2.50 Field corn, grain CC 88 35 0 .2 0.08 Canola, meal P 88 10 3.5 4 0.4 TO TAL BURDEN
-- -- 100
-- 22.5 Poultry Field corn, grain CC 88 75 0.2 0.15 Alfalfa, meal PC 90 5 65 4 3.25 Canola, meal PC 89 15 3.5 4 0.53 Peanut, meal PC 85 5 0.15 0.0075 TO TAL BURDEN
-- -- 100
-- 4.0 Swine Field corn, grain CC 88 85 0.2 1.70 Alfalfa, meal PC 90 5 65 4 3.25 Canola, meal PC 89 10 3.5 4 0.35 TO TAL BURDEN
-- -- 100
-- 5.3 1 R: Roughage; CC: Carbohydrate concentrate; PC: Protein concentrate. 2 OPPTS 860.1000 Table 1 Feedstuffs (June 2008 ). 3 Contribution = ([tolerance /% DM] X % diet) for beef and dairy cattle; contribution = ([tolerance] X % diet) for poultry and swine. 4 The tolerance for canola seed (3.5 ppm) was used for meal, and the tolerance for alfalfa hay (65 ppm) was used for alfalfa meal. Conclusions
. The available cattle and poultry feeding studies are adequate and cover the potential levels of dietary exposure of livestock to boscalid residues. The magnitude of the residues of boscalid and M510F01 was adequately determine d in the new (2008) feeding study
.Page 21 of 47

For hogs, the adequacy

of the existing tolerances were assessed using residue data from the 5.9 ppm dose group in the cattle feeding studies; this group represents 1. 1X the calculated dietary burden for swine. The data indicate that the existing tolerances for meat (0.05 ppm) and meat by products (0.10 ppm) of hogs are adequate; however, the tolerance for hog fat should be increased to 0.20 ppm. For poultry , the adequacy of the existing tolerances were assessed using res idue data from the 5.31 ppm dose group in the poultry feeding studies; this group represents 1. 3X the calculated dietary burden for poultry . These data indicate that the existing tolerances for eggs (0.02 ppm) and poultry

meat (0.05 ppm) are adequate; how ever, the tolerances for poultry fat and meat by products should each be increased to 0.20 ppm. 860.1500 Crop Field Trials References:

- Boscalid. Petition for a Tolerance for Belgian Endive; Petition for Increased Tolerances on Strawberry and the Berries C rop Group; Submission of Requested Field Trial Data on Cucumber, Mustard Greens, and Sunflower; and Supplemental Field Trial Data on Fruiting Vegetables, Radishes, Spearmint, Peppermint, Grapes, and Stone Fruits; and Submission of Field Trials and a Processing Study for Cotton. Summary of Analytical and Residue Data
. D. Soderberg, DP#323288, 0 6/14/2007.

- Boscalid; Petition for Establishing Permanent Tolerances on Alfalfa and the Citrus Crop Group 10, and Amending the Established Tolerance on the Stone Fruit Crop Group 12. Summary of Analytical Chemistry and Residue Data . A. Acierto, DP # 364447 , 10/1 6 /200 9
.

- PP#1F06313. BAS 510 F (Common Name: Boscalid), New Fungicide Active Ingredient. Residue Chemistry Summary Document. M. Nelson, DP#278385, 08/15/2003. BASF submitted field trial data on alfalfa, oranges, lemons , and grapefruits in support of new uses for boscalid (WDG formulations) on alfalfa and the citrus fruits crop group. BASF also submitted new stone fruit field trial data supporting an amended tolerance for stone fruits. The results from the new field trials and the previously submitted stone fruit field trails are summarized in Table 4 .4. 4 and discussed below. Adequate storage stability studies and acceptable analy

tical methods are available. TABLE 4 .4. 4 . Summary of Residue Data fromCrop Field Trials with Boscalid (WDG). Crop M atr ix (DER) Treatm ent

Info. Total Applic.

Rate (lb ai/A) PHI

(days) 1 Residue Levels (ppm) 2

n Min. Max. HAFT 3 Median Me an Std. Dev. Citrus Fruits (proposed use = 1.1 7 lb ai/A total application rate, 0 - day PHI) 4 Orange ( 45903601 .de 1 ) Concentrated 1.19
- 1.22 0 12 0.179 1.425 1.393 0.388 0.610 0.467

Dilute 1.20
- 1.21 0 14 0.238 0.676 0.588 0.353 0.418 0.146 Grapefruit ( 45903601 .de 1 ) Concentrated 1.20 0 6 0.115 0.847 0.836 0.143 0.365 0.364

Dilute 1.20 0 6 0.064 0.272 0.261 0.125 0.155 0.086 Lemon ( 45903601 .de 1 ) Concentrated 1.18
- 1.23 0 6 0.522 1.51 1.239 0.671 0.822 0.370

Dilute 1.18
- 1.20 0 4 0.600 0.936 0.872 0.775 0.771 0.140 Stone Fruits (proposed use = 1.1 5 lb ai/A total application rate, 0 - day PHI) 5 Cherry (47470201.de2) NA 1.15 0 14 <0.05 2.98 1.63 1.47 1.57 0.89 1 14 <0.05 2.69 1.95 1.09 1.28 0.81 Peach (47470201.de2) 1.15 0 12 0.56 3.79 1.94 0.76 1.15 1.03 1 12 0.46 3.87 2.74 0.75 1.19 1.1 5Page 22 of 47

TABLE 4 .4. 4 . Summary of Residue Data fromCrop Field Trials with Boscalid (WDG). Crop M atr ix (DER) Treatm ent

Info. Total Applic.

Rate (lb ai/A) PHI

(days) 1 Residue Levels (ppm) 2

n Min. Max. HAFT 3 Median Me an Std. Dev. Plum (47470201.de2) 1.15 0 10 <0.05 0.79 0.67 0.14 0.34 0.31 1 10 <0.05 0.57 0.71 0.11 0.26 0.24 Cherry (45405121.der) NA 1.35 0 2 1.28 1.70 1.49 1.49 1.49 NA Peach (45405121.der) 1.14
- 1.17 8 0.47 1.20 1.19 0.74 0.77 0.29 Plum (45405121.der) 1.15
- 1.17 8 0.09 0.85 0.70 0.50 0.47 0.23 Cherry ( 46665505 .der) Concentrated 1.15
- 1.16 0 6 0.641 1.635 1.635 0.999 1.056 0.370

Dilute 1.15 0 6 0.736 1.505 1.505 1.313 1.229 0.309 Peach ( 46665505 .der) Concentrated 1.14
- 1.16 0 9 0.157 0.663 0.663 0.47 9 0.450 0.157

Dilute 1.14
- 1.17 0 9 0.193 0.746 0.746 0.422 0.434 0.203 Plum ( 46665505 .der) Concentrated 1.14
- 1.15 0 6 0.081 0.566 0.566 0.154 0.214 0.182

Dilute 1.14
- 1.15 0 6 0.103 0.344 0.344 0.198 0.211 0.105 Alfalfa (proposed use = 0.85 lb ai/A t otal application rate, 14 - day PHI) 6 Alfalfa Forage (47584401.der) Trt #2 7 0.88 - 0.92 12 - 15 24 1.10 20.30 17.67 5.04 7.05 5.20 12 - 16 24 0.81 19.40 17.23 4.98 6.25 5.09 43
- 73 22 < 0.05 0.53 0.37 0.12 0.17 0.14 Trt #3 0.86
- 0.93 19
- 23 24 0.11 6.1 6 6.10 1.94 2.05 1.66 20
- 23 24 0.32 5.59 5.06 2.12 2.29 1.62 49
- 76 22 <0.05 0.50 0.50 0.11 0.16 0.13 Trt #4 0.59
- 0.62 12
- 15 24 0.97 15.68 14.47 3.95 4.94 3.78 12
- 16 24 0.85 15.32 15.07 3.59 5.56 4.51 43
- 70 22 <0.05 0.38 0.32 0.08 0.12 0. 09 Trt #5 0.57
- 0.62 19
- 23 24 0.05 5.44 5.38 1.21 1.75 1.58 20
- 23 24 0.29 3.64 3.46 2.12 2.03 1.07 49
- 76 22 <0.05 0.44 0.44 0.07 0.14 0.14 Alfalfa Hay (47584401.der) Trt #2 7 0.88 - 0.92 12 - 15 24 3.36 43.02 42.62 14.00 17.37 11.19 12 - 16 24 5.2 2 51.12 48.91 16.10 20.93 13.64 43
- 73 22 0.07 3.63 2.38 0.37 0.62 0.78 (Trt #3 0.86
- 0.93 19
- 23 24 0.14 20.84 19.84 6.37 6.97 5.93 20
- 23 24 1.52 15.26 14.72 6.72 7.24 4.44 49
- 76 22 <0.05 1.36 1.17 0.24 0.49 0.45 Trt #4 0.59
- 0.62 12
- 15 24 3. 11 33.78 31.34 10.80 15.30 9.21 12
- 16 24 4.48 40.06 39.33 16.89 18.23 11.40 43
- 70 22 <0.05 0.72 0.70 0.27 0.31 0.19 Trt #5 0.57
- 0.62 19
- 23 24 0.42 12.46 12.23 3.80 5.29 4.45 20
- 23 24 1.88 21.60 18.31 7.44 7.50 4.76 49
- 76 22 <0.05 1.12 1.1 0 0.25 0.45 0.40 1 For the alfalfa field trials, the three separate harvest intervals are the PHIs for the 1 st , 2 nd and 3 rd cuttings. 2 The validated LOQ for boscalid is 0.05 ppm in plant commodities. For all calculations, the LOQ (0.05 ppm) was used for all values reported as <LOQ.Page 23 of 47 3 HAFT = Highest average field trial result. 4 The citrus field tri als were conducted using either concentrate or dilute spray volumes. 5 For stone fruits, the data are reported separately for the three MRIDs (47470201, 466655 05, and 45405121). In MRID 45405121, applications to stone fruits were made using either concentrate or dilute sp ray volumes. 6 For the alfalfa field trials, T reatments #2 and #3 included three boscalid applications at ~0.3 lb ai/A/application with the first and second applications made prior to the 1st cutting and the final application made prior to the 2nd cutting. Treatments #4 and #5 included two applications at ~0.3 lb ai/A/application, with the first application made prior to the 1st cutting and the second application made prior to the 2nd cutting. 7 Treatment #2 represents the worse case use on alfalfa and reflects the proposed use pattern. As residues (bolded) from the 1 st and 2 nd cutting were similar in magnitude and both reflected the proposed 1 4
- day PHI, all values from these two cutting were used to access tolerances for forage and hay. Citrus Fruits, Crop Group 10. BASF submitted field trial data for boscalid on citrus fruits. The submitted field trial data are adequate and support the use of boscalid (WDG) on citrus fruits as either dilute or concentrated broadcast foliar applications during fruit development and maturation at rates of up to 0.29 lb ai/A. The highest residues which were found were 1.43 ppm in oranges, 0.85 ppm in grapefr uit, and 1.51 ppm in lemons
. The data support a maximum of 4 applications per season and a maximum seasonal use rate of 1.16 lb ai/A, a minimum RTIof 10 day s, and a minimum PHI of 0 day s. Some of the oranges were separated into wet peel and pulp. As co mpared to the whole fruit, b oscalid residues were lower in orange pulp and higher in peel
. Stone Fruits, Crop Group 12 . Adequate field trial data supporting the use of boscalid (WDG) on stone fruits were previously submitted (M. Nelson, DP#278385, 8/15 /2003 ; and D. Soderberg, DP# 323288, 6/14/2007). BASF has submitted additional field trial data for boscalid on stone fruits and the available stone fruit field trial data are adequate to supp ort a tolerance increase from 1.7 ppm to 3.5 ppm for the stone f ruit crop group 12. The recommended tolerance is based on the tolerance spreadsheet using the pooled data from field trials for representative crops of cherries, peaches, and plum treated at 1X rate with the PHIof 0 day
. When residue data from all the adequate stone fruit field trials ( 1X rate with 0
- day PHI) are pooled by crop, the data support the use of boscalid (WDG) on stone fruits for up to five broadcast foliar applications during fruit development at 0.23 lb ai/A/application, for a total application rate of 1.15 lb ai/A. The data support a minimum RTIof 7 days and a minimum PHI of 0 day s. Alfalfa. BASF submitted field tri al data for boscalid and the submitted alfalfa field trial data are adequate and would support the use of two or three bro adcast foliar applications of boscalid (25.2%, WDG formulation) to alfalfa at up to ~0.30 lb ai/A/application, with no more than two applications per cutting, for maximum seasonal use rates 0.6 or 0.9 lb ai/A. The data also support a minimum RTIof 14 d ay s and minimum PHI s of either 14 or 21 day s. However, the alfalfa field trial data will not support the proposed use rates of the 70% WDG as the proposed maximum single (0.48 lb ai/A) and seasonal (1.44 lb ai/A) application rates for th e 70% WDG are approximately

1.6X higher than the rates used in the alfalfa field trials
. 860.1520 Processed Food and FeedPage 24 of 47

BASF submitted residue data from an orange processing study conducted in FL (Zone 3) during 2008 . A 70% WDG formulation of boscalid was applied to V alencia orange trees during fruit maturation as two broadcast foliar applications at rates of 0.30 lb ai/A/application at a RTI of 10 day s, for a total rate of 0.60 lb ai/A. The data collection LC /MS/MS method (BASF Method D9908 , Version II) used to analy ze boscalid residues in/on orange fruit and processed commodities was adequately validated prior to and in conjunction with the anal ys is of processing samples. The average boscalid residues in the process ed commodities were 0.694 ppm in dried pulp, <0.0 5 ppm in juice, and 13.1 ppm in oil. These data indicate that boscalid residues were reduced in juice by 0.23 X , but concentrated 3.1X in dried pulp and 59 X in oil. The theoretical processing factors for citrus are 2X for juice , 3.3 X for dried pulp , and 10 00 X for oil (OPPTS 860.1520, Table 3)
. For the storage stability

study , whole orange fruit s , dried pulp , and oil were stored at < - 5°C f or up to 3.6 months prior to anal ys is
. After 3.6 months of frozen storage, the corrected recoveries of boscalid were 109
- 126% from all four citrus matrices. Table 4 .4.5. Residue Data fromOrange Processing Study with Boscalid (WDG) . RAC Processed

Commodity Total Rate

(lb ai/A) PHI

(days) Residues (ppm) 1 Processing Factor3 Orange Fruit (RAC) 0.602 1 0.2210, 0.2209 (0.22 10)
--

Dried Pulp 0.5884, 0.8002 (0.694) 2 2.7X, 3.6X ( 3.1X ) Juice <0.05, <0.05 (<0.05) <0.23X, <0.23X (<0.23X ) Oil 13.6 , 12.49 (13.05) 2 6 1X , 57X (59 X ) 1 The LOQ is 0.05 ppm for all commodities. 2 Residues are average s of 3 replicates each. Mean s of multiple processing study analyses are in parenthesis. 3 The processing factor was calculated by dividing the residue in the processed commodity by the residue in the associated RAC sample. The LOQ was used to calculate the processing factor fo r the value below the LOQ. Mean processin g factors are in parenthesis. Conclusions
. The orange processing study is adequate. As boscalid residues were reduced in juice (<0.2 X ), a separate tolerance is not required for citrus juice. However, separate tolerances are required for citrus dried pulp and oil. Based on the processing factors fo r dried pulp ( 3.1X) and oil (59X) and the HAFT residues (see Table 4 .4.5 ) for citrus fruits (orange

– 1.39 ppm), the maximum expected boscalid residues would be 4.31 ppm in dried pulp and 82 ppm in oil. These data support tolerances of 4.5 ppm for dried citrus pulp and 85 ppm for citrus oil. 860.1850 and 860.1900 Rotational Crops The nature of the residue in rotational crops is adequately understood and was summarized in a previous residue chemistry summary document. HED has concluded that the residue of concern in rotated crops for purposes of risk assessment and the tolerance expression is parent compound. Adequate limited and extensive field rotational crop studie s are available supporting the existing tolerances for indirect residues in rotational crops. These data support the label
- specific plantPage 25 of 47

back interval of 14 days for crops without boscalid uses. No additional rotational crop data are required for purpos es of this petition. 4 . 5 Dietary Exposure and Risk References:

- Boscalid; Petition for Establishing Permanent Tolerances on Alfalfa and the Citrus Crop Group 10, and Amending the Established Tolerance on the Stone Fruit Crop Group 12. Summary of Analytical Chemistry and Residue Data . A. Acierto, DP# 364447 , 10/16/2009.

- Boscalid. Chronic Aggregate Dietary (Food and Drinking Water) Exposure and Risk Assessment for the Section 3 Registration on the Citrus Crop Group 10 and Alfalfa, and an Increase in the T olerance on the Stone Fruit Crop Group 12
. A. Acierto , DP#365262, 11 / 19 /20 09.

- PP#1F06313. BAS 510 F (Common Name: Boscalid), New Fungicide Active Ingredient. Residue Chemistry Summary Document . M. Nelson, DP#278385, 08/15/2003.

- HED MARC Decision Memo , DP #286786, 0 1/0 9/20 03
. A dietary exposure memorandum has been prepared for the proposed new uses on alfalfa and citrus and subsequent amendment of Section 3 registrations of BAS 510F (EPA Reg. No. 7969
- 198), Endura ® (EPA Reg. No. 7969
- 197), and Pristine ® (E PA Reg. No. 7969
- 199), and the proposed increase of tolerances for the stone fruit crop group 12 (A. Acierto, DP#365262, 11/19/2009 ). Reference may be made to this document for details concerning the dietary exposure anal ys is that was performed in s upport of the new proposed tolerances in alfalfa and citrus, and the increased tolerance in stone fruits
. A chronic aggregate dietary (food and drinking water) exposure and risk assessment was conducted using the Dietary Exposure Evaluation Model DEEM
- FCIDTM ( Version 2.03 ) which uses food consumption data from the U.S. Department of Agriculture’s Continuing Survey s of Food Intakes b y Individuals (CSFII) from 1994 to 1996 , and 1998. The analy sis was performed to support the establishment of toleran ce s for residues of boscalid in alfalfa and citrus , and the increased tolerance in stone fruits
. 4 . 5 .1 Acute Dietary Exposure Results and Characterization No toxic effects attributable to a single dose of boscalid have been identified. As a result, an acute reference dose (RfD) was not established for this chemical ; therefore, acute dietary risk is not of concern. Thus , an acute dietary exposure assessment was not conducted. 4 . 5 .2 Chronic Dietary Exposure Results and Characterization A chronic dietary (food and drinking water) exposure and risk assessment was conducted for boscalid using tolerance level residues and 100% crop treated (%CT) assumptions. Boscalid exposure from the existing uses, the proposed new use s on citrus and alfalfa , the recommended tolerance increase for stone fruits, and the established and recommended tolerances on livestock results in estimated risk s that are below HED ’s LOC for food plus drinking water. The highest exposure and risk estimates for food plus drinking water are 1 1 % of the cPAD for the general U.S. population and 3 7% of the cPAD for children 1
- 2 years old, the most highl y exposed population subgroup.Page 26 of 47

4 . 5 .3 Cancer Dietary Exposure Results and Characterization HED has classified b oscalid as demonstrating “ s uggestive evidence of carcinogenicity” and has recommended against the quantification of human cancer risk (J. Kidwell, TXR#0051289 , 11/14/2002) . No change has been made to the cancer classification. Quantification of human cancer risk is not required. As a result, dietary cancer risk is not of concern; thus , a dietary cancer assessment was not conducted
. 4 . 5 .4 Re sults of C hronic D ietary E xposure A nalysis The results of the dietary exposure anal ys is (food and drinking water) for the general U.S. population , and all regulated population subgroups are listed below in Table 4
. 5 .4
. TABLE 4 . 5 . 4 . Summary of Dietary (Food and Drinking Water) Exposure and Risk for Boscalid . Population Subgroup 1 Acute Dietary Chronic Dietary Cancer Exposure (m g/kg/day) % aPAD Exposure (m g/kg/day) % cPAD Exposure (m g/kg/day) Risk General U.S. population

NA 2 NA 0.024694 11

NA NA All infants (< 1 year old) 0.052987 24 Children 1 - 2 years old 0.081585 37 Children 3
- 5 years old 0.057899 27 Children 6
- 12 years o ld 0.030924 14 Youth 13
- 19 years old 0.017901 8 Adults 20
- 49 years old 0.018608 8 Adults 50+ years old 0.020774 10 Females 13
- 49 years old 0.019007 9 1 Values for the population subgroup with the highest estimated chronic exposure and risk are in bold ty pe . 2 NA = Not Applicable. 4 . 6 Anticipated Residues and Percent Crop Treated The chronic dietary

exposure anal ys is was based on tolerance level residues and 100%CT assumptions for all commodities. As there were no risks of con cern, the generation of anticipated residues was not needed, and %CT data were not incorporated into the assessment. 5 .0 RESIDENTIAL (NON - OCCUPATIONAL) EXPOSU RE AND RISK CHARACTERIZATION For a discussion of the residential exposures and risks associated with the use of boscalid, reference may

be made to the previous risk assessment on coffee (W. Drew , D P# 354689 , 0 3 /25 /200 9 ) , or to the occupational and residential exposure (ORE) memo prepared in support ofPage 27 of 47

this risk assessment ( B. O’Keefe, DP#364449, 10/23/2009)
. 5 .1 Residential Handler Exposure There are no new residential (non
- occupational) uses proposed for boscalid as a result of the request ed use s o n alfalfa forage, citr us fruits, and increased tolerance on stone fruits
. C urrent label s specif

y that boscalid is to be applied to golf courses onl y, and is not for use on residential turfgrass or turfgrass being grown for sale or other commercial use such as sod production. Additionally , boscalid is n either packaged n or marketed for home orchard use. As the product is not intended for homeowner use, residential handler exposure and risk assessment s are not required ( B. O’Keefe, DP#364449, 10/23/2009 )
. 5 .2. Residential Pos t a pplication Exposure Reference:

- Boscalid: Human Health Risk Assessment to Support Proposed New Uses on Fresh Herbs (Herbs Subgroup 19A), Avocado, Black Sapote, Canistel, Mamey Sapote, Mango, Papaya, Sap odilla, Star Apple and Cotton. D. Davis, DP#33618 2, 02/13/2008. There are no new residential postapplication exposure scenarios resulting from the proposed use s on alfalfa forage, citrus fruits, or increased tolerance on stone fruits
. Potential non
- occupational post application exposure scenarios identi fied for boscalid , based on the established uses , include post application exposure to golfers and persons harvesting fruit at “pick
- yo ur- own ” ( PYO ) farms and orchards. Exposure can occur during contact with treated golf course turf , or while picking strawberries, caneberries, and tree fruit at a PYO facility
. Based on the low vapor pressure of boscalid ( 7 x 10 - 9 hPa), the outdoor nature of the uses , and the weight of evidence from available residue studies, HED do es not anticipate post application inhalation exposures from the currentl y approved uses of boscalid. PYO activities are considered to be one
- time (<1 day) event s . As no adverse effects were seen in the boscalid toxicity

database resulting from a single exposure to the chemical, a post application exposure and risk assessment is not required for this scenario. HED co nducted a post application exposure and risk assessment for golfers exposed to treated turf. Duration of exposure wa s anticipated to be short
- term. The registrant, BASF, submitt ed a turf transferable residue (TTR) study (MRID #45405301) that HED previously reviewed and found acceptable to use in assessing postapplication exposure ( S. Wang, D P# 290072 , 06/23/2003 ). Subsequent to this review, HED Exposure Science Advisory Council ( ExpoSAC) determined that the method used in the study for collecting residues (the modified California Roller method) can not be used with the standard turf transfer coefficients (TCs). Therefore, the TTR residue data from this study is no longer used to assess golfers exposure to turf treated with boscalid. HED considered it more appropriate to use the standard transfer coefficient ( 500 cm2/h our) for golfers , along with the standard SOP TTR value of 5% . Additionally , the assessment assumed that boscalid would be present on all of the turf throughout the course , and that the duration of exposure was estimated to be 4 hours. Details of the assessment can be found in the ORE memoranda cited above.Page 28 of 47

The postapplication dermal MOE for golfers exposed to bo sc alid is 1 8 ,000. This value exceeds 100, and thus does not exceed HED’s LOC ( i.e., the LOC is an MOE = 100 )
. Table 5 .2 summarizes the inputs for the assessment and th e exposure and risk results to golfers. TABLE 5 .2 . Derm al Posta pplication Exposure an d Risk from Boscalid for Adults and Youth Golfers . Scenario TTR 1

(ug/cm2 ) CF1

(m g/ug) T C 2

(cm2/hr) ET

(hr/day) %DA BW

(kg) Daily Dose 3 (m g/kg/day) Derm al

MOE 4 Golf course turf 0. 28 0.001 500 4 15 70 0.00 1 2 1 8 ,000 TTR = T urf T ransferable Residue on day 0 (mg/day). CF1 = unit Conversion F actor to convert μ g units in the TTR to mg for dai ly

exposure (0.001 mg/ug). TC = Transfer Coefficient. ET = Exposure Time. DA = Dermal Absorption. BW = B ody W eight. 1 TTR = use rate (0.5 lb ai/A) x [4.54E+8  g/lb] x [24.7E
- 9 A/cm 2 ] x 0.05. 2 Based on ExpoSAC SOP # 3.1
. 3 D aily dose (mg/kg/day) = [ TT R x CF1 x T C x ET x %DA ] ÷ BW
. 4 Dermal MOE = NOAEL (21.8 mg/kg/day) ÷ d aily d ose (mg/kg/day)
. Golfing is considered to be a lifetime sport. As a result , individuals of all ages, excluding very small children, are assumed to play routinely . Children who are 12 years of age or older are likely to represent the vast majority of the youth who play golf on a routine basis. However, the popularity

of golf as a recreational pastime has increased steadil y over the last several ye ars, which has resulted in more young children (less than 12 years old) becoming involved in the sport. Risk assessments for these children are more difficult to complete because of th e increased uncertainties associated with extrapolation of adult dermal exposure data, and because of the increased likelihood of other behaviors that might contribute to exposure, such as mouthing contaminated hands or golf balls. Therefore, the risk ass ociated with children in a golfing scenario is addressed qualitatively in the following discussion. Five
- ye ar- old children were selected as the target group for this exercise because younger children are not believed to be a viable population for the purp oses of assessing risk from a golfing scenario. The surface area to body weight ratio (SA/BW) for male children 5 years of age (i.e., the difference is larger for males compared to female making the value more protective) was calculated b y using the 95th percentile body surface area and the 50th percentile for body weight. The ratio was intentionally skewed to account for the uncertainties that would be expected with calculating dose levels for children if more definitive data were available, and for potential additional exposure that may occur from mouthing behaviors. This skewed SA/BW for children was compared to that of the average adult, and found to be approximately 70% greater. Based on this parameter alone, the child’s exposure could be almost twi ce that of the adult golfer, however, it should be noted that a child is not expected to use the golf course for the same length of time as an adult. While an adult is likely to play a full round of golf (i.e., 18 holes), which takes approximately 4 hours , a child would probably only spend about 2 hours (i.e., the 75th percentile for time spent playing on grass by children aged 1
- 4 years and 5
- 11 years) on the course. Thus, the child’s shorter duration on the golf course offsets the higher SA/BW, and therefore, the child golfer’s exposure is likely to be similar to that of the adult golfer. [Note: The values used to calculate SW/BW and estimate time spent playing on grass were obtained from the EPA Exposure Factors Handbook (1997)].Page 29 of 47

6 .0 AGGREGATE RISK AS SESSMENTS AND RISK C HARACTERIZATION Reference :

- Boscalid. Chronic Aggregate Dietary (Food and Drinking Water) Exposure and Risk Assessment for the Section 3 Registration on the Citrus Crop Group 10 and Alfalfa, and an Increase in the Tolerance on the Stone Fruit Crop Group 12
. A. Acierto, DP#365262, 11/19/2009. 6 .1 Acute Aggregate Risk No toxic effects attributable to a single dose of boscalid have been identified. Therefore, an acute Rf D has not been established for boscalid and acute aggregate risk is not of concern
. 6 .2 Short- Term Aggregate Risk The boscalid short
- term aggregate exposure and risk assessments combine average dietary (food and drinking water) exposures with short
- term postapplication exposures of adult and youth golfers. MOEs ranged from 840 to 1140
. The L OC for this assessment is for MOEs that are below 100. Therefore, there are no short
- term aggregate risks of concern. Short
- term aggregate risks are summarized below in Table 6 .2
. TABLE 6 .2 . Short - Term Aggregate Risk Calculations for Boscalid . Population Short - Term Scenario

NOAEL ( mg/kg/day) LOC 1 Maxim um Allowable Exposure 2 ( mg/kg/day) Average

Dietary Exposure ( mg/ kg/day) Residential

Exposure 3 ( mg/kg/day) Aggregate

(Dietary and Rresidential) MOE 4 U.S. Population 21.8 100 0.218 0.024694 0.0012 840 Females (13
- 49 years) 21.8 100 0.218 0.019007 0.0012 1080 Adults (50+ years) 21.8 100 0.218 0.020774 0.0012 1 0 00 Y outh (13
- 19 years) 21.8 100 0.218 0.017901 0.0012 114 0 1 T he LOC includes the standard inter
- and intra species UF s totaling 100 ; the FQPA SF = 1. 2 Maximum allowab le exposure (mg/kg/day) = NOAEL ÷ LOC
. 3 Residential e xposure = d ermal exposure ; the r e sidential exposure value wa s taken from Table 5 .2 , above
. 4 Aggregate MOE = NOAEL ÷ [ av erag e dietary e xposure + r esidential exposure ]
. 6 .3 Intermediate - Term Aggregate Risk There are no intermediate
- term residential scenarios; therefore, intermediate
- term aggregate exposure and risk are not of conce rn . 6 .4 Long - Term Aggregate Risk There are no long
- term residential scenarios for boscalid; therefore the long
- term aggregate risk assessment would incorporate onl y dietary ( food and drinking water) resi dues. The long
- termPage 30 of 47

aggregate risk assessment is identical to the chronic dietary risk assessment for which there are no concerns , as shown in Section 4
. 5 .2 of this memorandum. 6 .5 Cancer Aggregate Risk HED classified boscalid as demonstrating “ suggestive evidence of carcinogenicity” and noted that quantification of human cancer risk wa s not recommended . As a result, aggregate cancer exposure and risk are not of concern
. 7.0 Cumulative Ri sk Characterization/Assessment Unlike other pesticides for which EPA has followed a cumulative risk approach based on a common mechanism of toxicity, EPA has not made a common mechanism of toxicity finding as to boscalid and any other substances and boscalid does not appear to produce a toxic metabolite produced b y other substances. For the purposes of this tolerance action, therefore, EPA has not assumed that boscalid has a common mechanism of toxi city with other substances. For information regarding EPA's efforts to determine which chemicals have a common mechanism of toxicity

and to evaluate the cumulative effects of such chemicals, see the policy statements released b y EPA's Office of Pesticide P rograms concerning common mechanism determinations and procedures for cumulating effects from substances found to have a common mechanism on EPA's website at http://www.epa.gov/pesticides/cumulative/. 8 .0 OCCUPATIONAL EXPOSURE/RISK ASSESSMENT PA THWAY Refe rence :

- Boscalid: Occupational and Residential Exposure Assessment for proposed field uses of boscalid on alfalfa (including alfalfa grown for seed) and citrus fruits (crop group 10). B. O’Keefe, DP#364449, 10/23/2009
. 8 .1 Occupational Pesticide Handler Exposure and Risk Broadcast f

oliar applications of boscalid may be applied to alfalfa (including alfalfa grown for seed) at a rate of 0.48 lb ai/A (Endura ® ) and 0.28 lb ai/A ( Pristine ® ) and to citrus at a rate of 0.29 lb ai/A ( Pristine ® ). For alfalfa, up to three applications can be made per season at RTI of 14 to 21 day s. The PH I is 14 day s. For citrus, up to four applications can be made per season at RTIs of 10 to 21 days. The PHI is zero day s. Handlers may apply boscalid to alfalfa using aerial, c hemigation, or groundboom equipment. To citrus, handlers may appl y boscalid using aerial, chemigation , airblast, or handgun equipment. Agricultural Handlers No chemical
- specific handler exposure data were submitted in support of this registration. It i s the policy of the HED to use data from the Pesticide Handlers Exposure Database (PHED) Version 1.1 as presented in PHED Surrogate Exposure Guide (8/98) to assess handler exposures for regulatory

actions when chemical
- specific monitoring data are not avai lable (HED ExpoSAC SOP # 7, dated 1/28/99). Additionally , data from Outdoor Residential Exposure Task Force (ORETF) were used to assess some scenarios. Handler exposure is expected to be short
- or intermediate
- term based on information provided on propose d labels.Page 31 of 47

Dermal
. The results of the occupational handler exposure and risk assessment indicate that short
- and intermediate
- term dermal MOEs were greater than the LOC (MOEs ≥ 100) at the baseline clothing level , when baseline data are available
. There are no data to assess the m ix ing/loading/appl ying handgun scenario at baseline attire. The short
- and intermediate
- term dermal risks do not exceed HED ’s LOC for m ix ing/loading/appl ying with handgun equipment when baseline attire plus chemical
- resistant gl oves are used. Additionally , o nly engineering control (enclosed cockpit) data are available to assess dermal risks to handlers operating aircraft. The short
- and intermediate
- term dermal risks do not exceed HED ’s LOC for pilots using enclosed cockpits an d wearing baseline attire. Inhalation
. The short
- and intermediate
- term inhalation risks to handlers do not exceed HED ’s LOC at baseline (no respirator) for any of the handler scenarios. Onl y engineering control (enclosed cockpit) data are available to assess short
- and intermediate
- term inhalation risks to handlers operating aircraft. The short
- and intermediate
- term inhalation risks do not exceed HED ’s LOC for pilots using enclosed cockpits and wearing no respirator. Combined

. Combined dermal plus inhalation risks do not exceed HED ’s LOC , provided personal protective equipment (PPE) listed under the short
- and intermediate
- term dermal risks are worn. HED’s LOC for the MOE is defined by the UF s that are applied to the assessment. HED applies a 10X factor to account for interspecies extrapolation and a 10X factor to account for intraspecies sensitivity . The total UF that has been applied to the non
- cancer risk assessment for boscalid is 100 X for occupational exposure. Occupational exposure and ris k resulting in MOEs greater than or equal to 100 will not exceed HED ’s LOC
. Summaries of the risks for occupational handlers are included in Table 8 .1 . The maximum application rate for each exposure scenario is presented a s the worst
- case scenario. All handler scenarios resulted in MOEs greater than the LOC (MOEs ≥ 100) at some level of risk mitigation. TABLE 8 . 1 . Short - and Intermediate - Term Agricultural Handler Exposure and Risk for Boscalid . Exposure Scenario Crop

or Target App

Rate a (lb ai/A) Acres Treated Daily b Mitigation

Level c Unit Exposure d Dose (m g/kg/day) MOE (Target MOE = 100)

Dermal (mg/lb ai) Inhalation

(μg/lb ai) Dermal e Inhalation f Dermal g Inhalation h Combined Dermal + Inhalation i M ixing/Loading Dry Flowables for Aerial Applications Al falfa 0.48 1200 Baseline 0.066 0.77 0.081 0.0063 270 3 , 400 250 0.28 1200 0.066 0.77 0.048 0.0037 460 5 , 900 430 Citrus 0.29 350 0.066 0.77 0.014 0.0011 1 , 500 20 , 000 1 , 400 M ixing/Loading Dry Flowables for Chemigation Applications Al falfa 0.48 350 Baseline 0.066 0.77 0.024 0.0018 920 12 , 000 850 0.28 350 0.066 0.77 0.014 0.0011 1 , 600 20 , 000 1 , 500 Citrus 0.29 350 0.066 0.77 0.014 0.0011 1 , 500 20 , 000 1 , 400 M ixing/Loading Dry Flowables for Groundboom Applications Al falfa 0.48 200 Baseline 0.066 0.77 0.014 0.0011 1 , 600 21 , 000 1 , 500 0.28 200 0 .066 0.77 0.0079 0.00062 2 , 800 35 , 000 2 , 600 M ixing/Loading Dry Flowables for Airblast Applications Citrus 0.29 40 Baseline 0.066 0.77 0.0016 0.00013 13 , 000 170 , 000 12 , 000Page 32 of 47 TABLE 8 . 1 . Short - and Intermediate - Term Agricultural Handler Exposure and Risk for Boscalid . Exposure Scenario Crop

or Target App

Rate a (lb ai/A) Acres Treated Daily b Mitigation

Level c Unit Exposure d Dose (m g/kg/day) MOE (Target MOE = 100)

Dermal (mg/lb ai) Inhalation

(μg/lb ai) Dermal e Inhalation f Dermal g Inhalation h Combined Dermal + Inhalation i Applying Sprays via Aerial Equipment Al falfa 0.48 1200 Engineering Controls 0.005 0 .068 0.0062 0.00056 3,500 39,000 3,200 0.29 1200 0.005 0.068 0.0037 0.00034 5,800 64,000 5,400 Citrus 0.29 350 0.005 0.068 0.0011 0.000099 20,000 220,000 18,000 Applying Sprays via Groundboom Equipment Al falfa 0.48 200 Baseline 0.014 0.74 0.0029 0. 001 7 , 600 21 , 000 5 , 600 0.28 200 0.014 0.74 0.0017 0.00059 13 , 000 37 , 000 9 , 600 Applying Sprays via Airblast Equipment Citrus 0.29 40 Baseline 0.36 4.5 0.0089 0.00075 2 , 400 29 , 000 2 , 200 Flagging for Aerial Sprays Applications Al falfa 0.48 350 Baseline 0.011 0.35 0.004 0.00084 5 , 500 26 , 000 4 , 500 0.28 350 0.011 0.35 0.0023 0.00049 9 , 400 44 , 000 7 , 800 Citrus 0.29 350 0.011 0.35 0.0024 0.00051 9 , 100 43 , 000 7 , 500 M ixing/Loading/ Applying Dry Flowables Concentrates with a Handgun Sprayer Citrus 0.29 5 D ermal: Baseline Plus Gloves Inhalation: Baseline 0.58 22 0.0018 0.00046 12,000 48 , 000 9,600

a Application Rates based on proposed uses on boscalid labels for Endura® (EPA Reg. No. 7969
- 197 ) and Pristine® (EPA Reg. No. 7969
- 198 ). b Science Advisory Counci l Policy # 9.1 c Baseline Dermal: Long
- sleeve sh irt, long pants, and no gloves. Baseline Inhalation: no respirator. Engineering control unit exposure for applying sprays via aerial equipment = enclosed cockpit. Baseline plus Gloves Dermal: Baseline plus chemical
- resistant gloves. d Unit Exposures based on PHED Version 1.1 or ORETF data. e Dermal Dose (mg/kg/day) = daily unit exposure (mg/ lb ai) x application rate (lb ai/acre) x acres treated x dermal absorption factor ( 15 %) / body weight (70 kg adu lt). f Inhalation Dose (mg/kg/day) = daily unit exposure (μg/lb ai) x application rate (lb ai/acre) x acres treated x inhalation absorption (100%) / body weight (70 kg adult). g Dermal MOE = NOAEL ( 21.8 mg/kg/day) / dermal daily dose (mg/kg/ day). L evel of concern = 100. h Inhalation MOE = NOAEL ( 21.8 mg/kg/day) / inhalation daily dose (mg/kg/ day). Level of concern = 100. i Combined Baseline Dermal + Inhalation MOE = 1 / (1/Baseline Dermal MOE) + (1/Baseline Inhalation MOE). 8 .2 Occupational Post a pplication Worker Exposure and Risk HED assumes that inhalation exposures are minimal following outdoor applications of an ai with low vapor pressure. Since the proposed uses of b oscalid are applied onl y in outdoor settings and b oscalid has a low vapor p ressure, postapplication inhalation exposures and risks were not assessed. Short
- and intermediate
- term dermal postapplication exposures and risks to occupational workers were estimated using standard values established by HED since no chemical
- specific data were submitted. The T C s used for all postapplication activities were established by ExpoSAC SOP # 3.1. The DFR levels were estimated using HED standard values where it is assumed that the initial residue on treated foliage is 20% of the application rate and the residues degrade at a rate of 10 % per day
. Using HED default assumptions and surrogate DFR data, all scenarios resulted in MOEs greater than 100 on day 0 (12 hours after application) , and therefore risks do not exceedPage 33 of 47

HED ’s LOC
. Table 8 .2.1 p resents the default DFR values on day 0 (12 hours after application) that were used for this postapplication exposure and risk assessment.
TABLE 8 .2.1 . Summary of DFRs by Crop Grouping Based on HED Default Assumptions . 1 Crop Application

rate (lb ai/ac re) Fraction of

ai retained on the foliage Conversion

Factor 1 ( μg/lb) Conversion

Factor 2 (A/cm 2 ) Day after

Application Default DFR

(μg/cm2 ) Alfalfa 0.48 20% (Default) 4.54E+8 2.47E
- 8 0 (12 hours) 1.077 0.28 0.628 Citrus 0.29 0.651 1 Default DFR (μg/cm2 ) = application rate (lb ai/A) x (1
- daily dissipation rate) t x 4.54E8 μg/lb x 24.7E
- 9 A/cm2 x 20% DFR after in i tial treatment. The postapplication exposure associated with agricultural crops is summarized in Table 8 .2.2. Using HED defa

ult assumptions and surrogate DFR data, all scenarios resulted in MOEs greater than 100 on day

0 (12 hours after application) and , therefore , risks do not exceed HED ’s LOC
. TABLE 8 . 2.2 . Summary of Occupational Postapplication Risks (Short - and Intermedi ate - Term) with HED

Default Assumptions . Crop Grouping Application

rate (lb ai/acre) Default

DFR (μg/cm2 ) Maximum Transfer Coefficient (μg/cm2 ) Day after Application MOE

( LOC = 100) Alfalfa 0.48 1.077 1,500 (Irrigating, Scouting) 0 (12 hours) 790

0.28 0.628 0 (12 hours) 1,300 Citrus 0.29 0.651 3,000 (Pruning) 0 (12 hours) 650 Notes: Crops were assessed using the highest transfer coefficient available
. Since postapplication risks were not a concern on day 0 (12 hours following application), the restricted entry

interval (REI) is based on the acute toxicity of boscalid technical material. Boscal id is classified as t oxicity c ategory III by the dermal route of exposure and category IV for eye irritation and skin irritation potential. Under the Worker Protection Standard (WPS) for Agricultural Pesticides, active ingredients classified as acute toxi city categories III or IV for these routes are assigned a 12
- hour REI. Therefore, the 12
- hour REI that appears on the proposed label is adequate. 9 .0 TOLERANCE HARMONIZAT ION AND RECOMMENDED TOLE RANCE For purposes of both the tolerance expression and dietary risk assessment, HED has concluded that the ROC in plant commodities include only boscalid, and the residues of concern in livestock commodities include boscalid , its 5
- hydroxy metabolite, and the glucuronide conjugate of the 5
- hydrox y metabolite. Ac cording to the memo Interim Guidance on Tolerance Expressions by S. Knizner, the tolerances should be expressed as follows:Page 34 of 47

(a) General. (1) Tolerances are established for residues of the fungicide boscalid, including its metabolites and degradates , in or on the commodities listed below. Compliance with the tolerance levels specified below is to be determined by measuring only 3 - pyridinecarboxamide, 2 - chloro - N - (4' - chloro[1,1' - biphenyl] - 2 -yl). Alfalfa, forage
................................ ................................ ... 30.0 ppm Alfalfa, hay
................................ ................................ ....... 65.0 ppm Citrus, drie d pulp
................................ ................................ . 4.5 ppm Citrus, oil
................................ ................................ ............ 85.0 ppm Fruit, citrus, group 10
................................ ........................... 1.6 ppm Fruit, stone, group 12
................................ ........................... 3.5 ppm (2) Tolerances are established for residues of the fungicide boscalid, including its metabolites and degradates , in or on the food commodities listed below. Compliance with the tolerance levels specified below is to be determined by measuring only the sum of 3 - pyridinecarboxamide, 2 - chloro - N - (4' - chloro[1,1' - biphenyl] - 2 -yl) and metabolites 2 - chloro -

N - (4' - chloro - 5 - hydroxy- biphenyl - 2 -yl) nicotinamide and glucuro nic acid conjugate of 2 - chloro - N - (4' - chloro - 5 - hydroxy- biphenyl- 2 -yl) nicotinamide , calculated as the stoichiometric equivalent of boscalid . Hog, fat
................................ ................................ .............. 0.20 ppm Poultry , fat
................................ ................................ .......... 0.20 ppm Poultry , meat b yproducts
................................ ................... 0.20 ppm The established tolerances of the followin g commodities remain unchanged. Cattle, fat
................................ ................................ ............ 0.30 ppm Cattle, meat
................................ ................................ ........ 0.10 ppm Cattle, meat by

products
................................ ..................... 0.35 ppm Egg
................................ ................................ ..................... 0.02 ppm Goat, fat
................................ ................................ .............. 0.30 ppm Goat, meat
................................ ................................ .......... 0.10 ppm Goat, meat b yproducts
................................ ....................... 0.35 ppm Hog, meat
................................ ................................ ........... 0.05 ppm Hog, meat b yproducts
................................ ........................ 0.10 ppm Horse, fat
................................ ................................ ............ 0.30 ppm Horse, meat
................................ ................................ ........ 0.10 ppm Horse, meat b yp roducts
................................ ..................... 0.35 ppm Milk
................................ ................................ .................... 0.10 ppm Poultry , meat ................................ ................................ ...... 0.05 ppm Sheep, fat
................................ ................................ ............ 0.30 ppm Sheep, meat
................................ ................................ ........ 0.10 ppm Sheep, meat b yproducts
................................ ..................... 0.35 ppm (d) Indirect or inadvertent residues. Tolerances are established for residues of the f ungicide boscalid, including its metabolites and degradates , in or on the commodities listed below. Compliance with the tolerance levels specified below is to be determined by measuring only 3 - pyridinecarboxamide, 2 - chloro - N - (4' - chloro[1,1' - biphenyl] - 2 -yl) . Animal feed, nongrass, group 18, forage, excluding alfalfa 1.0 ppmPage 35 of 47 Animal feed, nongrass, group 18, hay , excluding alfalfa
.... 2.0 ppm Permanent tolerances are established for residues of boscalid in/on various plant commodities at levels ranging from 0. 05 to 60 ppm [40 CFR §180.589(a)(1)]. Separate tolerances are also established for indirect or inadvertent residues of boscalid in rotational crops at levels ranging from 0.05 to 8.0 ppm [40 CFR §180.589(d)]. Tolerances are also established for the combined residues of boscalid, its 5
- hydroxy metabolite , and the glucuronic acid conjugate of the 5
- hydrox y m etabolite, at levels ranging from 0.02 ppm to 0.35 ppm [40 CFR §180.589(a)(2)]. The proposed and recommended tolerances for bo scalid are presented in T able 9 .0
. An adequate number o f field trials conducted at ~1X the existing or proposed use rate s are available on alfalfa, citrus fruits (orange, lemon, grapefruit) , and stone fruits (cherry , peach, plum) to support permanent tolerances. The Agency ’s SOP “ Guidelines for Setting Pesticide Tolerances Based on Field Trial Data” w as utilized for determining the appropriate toleranc e level for each commodity
. For alfalfa forage and hay , residue data from both the 1 st and 2 nd cuttings of Treatment #2 ( 1X rate) were used to assess tolerances as both cuttings were collected around the proposed 14
- day PHI , and residue levels were similar for the two cuttings. The recommended tolerances for alfalfa forage and hay are 30 and 65 ppm, respectivel y. For the citrus fr

uits, the residue data were pooled by crop, and separate possible tolerances were calculated for oranges (1.6 ppm), lemons (1.6 ppm), and grapefruits (1.1 ppm) using the tolerance spreadsheet. As the minimum and maximum recommended tolerances differ b y le ss than 5X , a crop group tolerance is appropriate for citrus, and the recommended tolerance is 1.6 ppm. For stone fruits, all the adequate residue data were pooled b y crop (including previously reviewed studies), and separate possible tolerances were calculated for cherry (3.5 ppm), peach (3.0 ppm) , and plum (1.6 ppm) using the tolerance spreadsheet. As the minimum and maximum recommended tolerances differ by less than 5X , a crop group tolerance is appropriate for stone fruits, and the recommended toleran ce is 3.5 ppm. As boscalid residues were reduced in orange juice (<0.2 X), a separate tolerance is not required for citrus juice. However, boscalid residues were shown to concentrate in dried pulp ( 3.1X) and oil (59X). Based on these processing factors and the HAFT residues for citrus fruits (1.39 ppm), the maximum expected boscalid residues would be 4.31 ppm in dried pulp and 82 ppm in oil. These data support tolerances of 4.5 ppm for dried citrus pulp and 85 ppm for citrus oil. For assessing the existing tolerances on livestock commodities, adequate cattle and poultry feeding studies are available that cover the potential levels of dietary exposure of livestock to boscalid residues. The 35.8 ppm do se group (1X dietary burden) from the cattle feeding s tudy was used to assess the current tolerances on milk (0.10 ppm) and on the fat (0.30 ppm), meat (0.10 ppm) , and meat b yproducts (0.35 ppm) of cattle, goats, horses, and sheep. For this dose group, the maximum combined residues of boscalid and M510F01 (f ree and conjugated) were <0.03 ppm in milk, <0.08 ppm in cream, ≤0.11 ppm in liver and kidney s, <0.05 ppm in muscle , and <0.24 ppm in fat. These data indicate that the existing tolerances for milk and fat, meat , andPage 36 of 47

meat by products of cattle, goats, horses , and sheep are mor e than adequate. Separate tolerances for liver and kidney

are not required. For hogs, the adequacy

of the existing tolerances were assessed using residue data from the 5.9 ppm dose group (1.1 X dietary burden for swine) in the cattle feeding studies. Max imum combined residues for this dose group were <0.064 ppm in liver, <0.090 ppm in kidney , <0.05 ppm in muscle, and <0.12 ppm in fat. These data indicate that the existing tolerances for meat (0.05 ppm) and meat b yp roducts (0.10 ppm) of hogs are adequate; however, the tolerance for hog fat should be increased to 0.20 ppm. Separate tolerances of hog liver and kidney are not necessary . For poultry , the adequacy of the existing tolerances were assessed using residue data from the 5.31 ppm dose group in the p oultry feeding studies; this group represents 1.3 X the calculated dietary burden for poultry . Maximum combined residues for this dose group were <0.02 ppm in eggs, <0.175 ppm in liver, <0.05 ppm in muscle, and <0.124 ppm in fat. These data indicate that the existing tolerances for eggs (0.02 ppm) and poultry meat (0.05 ppm) are adequate; however, the tolerances for poultry fat and meat b yp roducts should each be increased to 0.20 ppm. A separate tolerance for liver is not necessary
. The Codex Alimentarius Commission , Canada , and Mexico have not established any maximum residue limits (MRL s) for residues of boscalid in/on alfalfa forage and hay or citrus fruits (Appendix C ). However, there is an existing Codex MRLfor stone fruits at 3 mg/kg, and Canada h as established MRL s at 1.7 mg/kg for the various member of the stone fruits crop group. Canada also has also established MRL s for various livestock commodities. The Canadian MRL s for stone fruits and livestock commodities are currently harmonized with th e respective U.S. tolerances; however, once the recommended increases are made to U.S. tolerances, the U.S. tolerances on stone fruits, poultry fat and meat b yproducts , and hog fat will no longer be harmonized with the Canadian MRL s. While not officially part of the Codex Alimentarius Commission structure, the Joint FAO/WHO Meetings on Pesticide Residues (JMPR) provide independent scientific expert advice to the Commission and its specialist Committee on Pesticide Residues. To determine MRL s for the ston e fruit crop group, both the U.S. and JMPR used the same database of field trial studies in 2006 . The resulting values are not in harmony because the U.S. uses the averages of duplicate samples for a given trial, whereas JMPR uses the highest value from e ach trial site. Additionally , the U.S. used the NAFTA statistical calculation method whereas the JMPR did not routinely use statistical calculation methods in 2006.Page 37 of 47

TABLE 9 .0 . Tolerance Summary for Boscalid. Comm odity Proposed Tolerance (ppm) Existing

Tolerance (ppm) Recommended

Tolerance (ppm) Comments; Correct Commodity

Definition 40 CFR 180.589(a)(1) Alfalfa, forage 35
-- 30 Adequate alfalfa forage and hay residue data are available. Alfalfa, hay 85
-- 65 Citrus, dried pulp None
-- 4.5 An adequate orange processing study is available indicating that boscalid residues can concentrate in dried pulp ( 3.1X ) and oil (5 9X )
. Citrus, oil None
-- 85 Fruit, citrus, group 10 2.0
-- 1.6 Adequate orange, grapefruit, and lemon residue data are available. F ruit, stone, group 12 5.0 1.7 3.5 An increase in the established tolerance is required based on adequate cherry, peach , and plum residue data. 40 CFR 180.589(a)( 2 ) Cattle, fat 1.5 0.30 0.30 Based on the residue data from the 35.8 ppm dose group in the cattle feeding studies and the calculated dietary burden for dairy cattle (35.2 ppm), the existing tolerances are adequate. Separate tolerances for liver and kidney are not necessary. Cattle, kidney 1.0
-- None Cattle, liver 1.0
-- None Cattle, meat 0. 2 0.10 0.10 Cattle, meat byproducts 1.5 0.35 0.35 Egg 0.02 0.02 0.02 The existing tolerance on eggs is adequate. Goat, fat 1.5 0.3 0 0.30 See Cattle above. Goat, kidney 1.0
-- None Goat, liver 1.0
-- None Goat, meat 0.2 0.1 0 0.10 Goat, meat byproducts 1.5 0.35 0.35 Hog, fat 0.2 0.1 0 0.20 Based on the residue data from the 5.9 ppm dose group in the cattle feeding studies and the calculated dietary burden for swine (5.30 ppm), the existing tolerances on hog meat and meat byproducts are adequate. However, the tolerance for hog fat should be increased to 0.20 ppm. Hog, meat 0.05 0.05 0.05 Hog, meat byproducts 0.2 0.1 0 0.10 Hog, kidney 0.2
-- None Hog, liver 0.2
-- None Horse, fat 1.5 0.3 0 0.30 See Cattle above. Horse, kidney 1.0
-- None Horse, liver 1.0
-- None Horse, meat 0.2 0.1 0 0.10 Horse, meat byproducts 1.5 0.35 0.35 Milk 0.2 0.10 0.10 The existing tolerance for milk willPage 38 of 47

TABLE 9 .0 . Tolerance Summary for Boscalid. Comm odity Proposed Tolerance (ppm) Existing

Tolerance (ppm) Recommended

Tolerance (ppm) Comments; Correct Commodity

Definition Milk , fat (cream) 1.5
-- None adequately cover residues in both whole milk and milk fat Poultry, liver 0.2
-- None Based on the residue data from the 5.31 ppm dose group in the poultry feeding study and the calculated dietary burden for poultry (4.10 ppm), the existing tolerance for meat is adequate and the tolerances of fat and meat byproducts should be increased to 0.20 ppm. A separate tolerance for liver is not necessary. Poultry, fat 0.2 0.05 0.20 Poultry, meat 0.05 0.05 0.05 Poultry, meat byproducts 0.2 0.1 0 0.20 Sheep, fat 1.5 0.3 0 0.30 See Cattle above. Sheep, kidney 1.0
-- None Sheep, liv er 1.0
-- None Sheep, meat 0.2 0.1 0 0.10 Sheep, meat byproducts 1.5 0.35 0.35 10 .0 DATA NEEDS 10 .1 Toxicology Data Requirements 870.7800 Immunotoxicity Study  A s part of the new 40CFR §158 Guidelines, an immunotoxicity study in rats and/or mice is required (see Appendix B). 10 .2 Residue Chemistry Data Requirements 860.1200 Direction for Use  A revised Section B for alfalfa is required to amend the label direction for the 70% WDG formulation since it could not be supported b y the field trial data generated with a maximum seasonal use rate of 0.9 lb ai/A. The proposed label rate for the 70% WDG formulation is 1.7X higher; the label should be revised to match the field trial rate. 860.1550 Proposed Tolerances  Boscalid residues concentrate in citru s dried pulp ( 3.1X) and citrus oil (59X). A revised Section F is required to propose separate tolerances for citrus, dried pulp at 4.5 ppm, citrus, oil at 85 ppm, and f ruit, citrus, group 10 at 1.6 ppm.  The available data for stone fruits will not support a tolerance level of 5.0 ppm. A revised Section F should be submitted with a tolerance for f ruit, stone, group 12 at 3.5 ppm.  The available data will not support the proposed tolerances for meat, meat by products, and fat of cattle goat, horse, and sheep at 0.2 ppm, 1.5 ppm, and 1.5 ppm, respectivel y.Page 39 of 47

The existing tolerances will be maintained for meat, meat by products, and fat of cattle, goat, horse, and sheep at 0.10 ppm, 0.35 ppm, and 0.30 ppm, respectivel y. The available data will not support the proposed tolerance of 0.2 ppm for milk and the proposed tolerance of 1.5 ppm for milk fat. The existing tolerance of 0.10 ppm will be maintained for milk, and it i s adequate to cover milk fat. The proposed tolerances of 0.20 ppm for hog, fat; poultry , fat; and poultry , meat b yp roducts are adequate. For all remaining livestock commodities, the proposed tolerances must be revised to reflect the recommended tolerance levels as specified in Table 9 .0
. 10 .3 Occupational/Residential Exposure Data Requirements N one . REFERENCES BAS 510 F
- Report of the Hazard Identification Assessment Review Committee . A. Levy, TXR#0051613, 03/07/2003. BAS 510 F: Report of the Cancer Assessment Review Committee . J. Kidwell, TXR#0051289, 11/14/2002. Boscalid. Human Health Risk Assessment for a Section 3 Tolerance on Endive, an Amendment to the Tolerances for Strawberries and Berries, Crop Group 13, and an Increase in Tolerances in/on Cucumber and Vegetable, Root, Subgroup 1A, except Sugar Beet, Garden Beet, Radish, and Turnip. B. Hanson, DP#327906, 07/10/2007. Boscalid: Human Health Risk Assessment to Support Proposed New Uses on Fresh Herbs (Herbs Subgroup 19A), Avocado, Black Sapote, Canistel, Mamey Sapote, Mango, Papaya, Sapodilla, Sta r Apple and Cotton. D. Davis, DP#336182, 02/13/2008. Boscalid Occupational/Residential Exposure Memorandum . S. Wang, DP#290072, 06/23/20 03
. Boscalid. Petition for a Tolerance for Belgian Endive; Petition for Increased Tolerances on Strawberry and the Berries Crop Group; Submission of Requested Field Trial Data on Cucumber, Mustard Greens, and Sunflower; and Supplemental Field Trial Data on Fruiting Vegetables, Radishes, Spearmint, Peppermint, Grapes, and Stone Fruits; and Submission of Field Trials and a Processing Study for Cotton. Summary of Analytical and Residue Data
. D. Soderberg, DP#323288, 06/14/2007. Boscalid; Petition for Establishing Permanent Tolerances on Alfalfa and the Citrus Crop Group 10, and Amending the Established Tolerance on the Stone Fruit Crop Group 12. Summary of Analytical Chemistry and Residue Data . A. Acierto, DP#364447, 10/16/2009. Drinking W

ater Assessment for the IR

- 4 Petition for the Use of Boscalid on Tropical Fruits and Fresh Herbs, and a Proposed New Use on Cotton . C. Sutton, DP#336183, 08/08/2007.Page 40 of 47

Drinking W

ater Exposure Assessment for New Uses of Boscalid on Alfalfa Forage and Hay, Citrus group 10, and an Increase in Tolerance on Stone Fruit group 12. D. Lieu, DP#367184, 09/24/2009. PP# 1F06313
--Human Health Risk Assessment for New Fungicide BAS 510 F (Common Name: Boscalid)

-- Proposal for Tolerances for Residues in/on Numerous Crops and Livestock Commodities . Y. Donovan, DP#290022, 09/08/2003. PP#1F06313. BAS 510 F (Common Name: Boscalid), New Fungicide Active Ing redient. Residue Chemistry Summary Document. M. Nelson, DP#278385, 08/15/2003
.Page 41 of 47

APPEND IX A : TOXICITY PROFILE S F OR BOSCALID TECHNICAL TABLE A. 1 . Acute Toxicity Profile f or Boscalid . Guideline N umber Study Type MRID Number Results Toxicity Category 8 70. 11 00 Ac ute Oral 45404814 LD 50 =>5,000 mg/kg IV 8 70. 1 200 Ac ute Dermal 45404815 LD 50 =>2000 mg/kg III 8 70. 1 300 Ac ute Inhalation 45404816 LC 50 =>6.7 mg/L IV 8 70.2400 Primary Eye Irritation 45404817 Not irritating IV 8 70.2500 Primary Skin Irritation 4540 4818 Not irritating IV 8 70.2600 Dermal Sensitization 45404819 1 Could not be determined NA 2 1. Unacceptable because the 5% concentration used for the challenge was inadequate. 2. NA = Not Applicable. TABLE A. 2 . Subchronic, Chronic and Other Toxicity Profile of Boscalid Technical Guideline Number Study Type Results 870.3100 90
- Day

oral toxicity rodents (rats) NOAEL : 34/159 mg/kg/day (M/F) LOAEL : 137/395 mg/kg/day (M/F): M = increases in absolute and relative thyroid weights and increased incidence of thyroid hyperplasia as well as follicular epithelial hypertrophy; F = increases in absolute and relative thyroid weights. 870.3100 90
- Day

oral toxicity rodents (mice) NOAEL : 197/2209 mg/kg/day (M/F) LOAEL : 788/2209 mg/kg/day (M/F): M = increased liver weights and increased incidence of marked fatty change in the liver; F = not attained 870.3150 90
- Day

oral toxicity in nonrodents (dogs) NOAEL : 7.6/8.1 mg/kg/day (M/F) LOAEL : 78.1/81.7 mg/kg/day (M/F): M = increased alkaline phosphatase activity and hepatic weights; F = increased alkaline phosphatase activity and hepatic weights. 870.3200 21/28
- Day dermal toxicity

(rats) NOAEL : 1000 mg/kg/day (HDT) LOAEL : >1000 mg/kg/day 870.3700 Prenatal developmental in

rodents (rats) Maternal NOAEL : 1000 mg/kg/day Maternal LOAEL : cannot be established Developm ental NOAEL : 1000 mg/kg/day Developm ental LOAEL : cannot be established 870.3700 Prenatal developmental in

nonrodents (rabbit) Maternal NOAEL : 300 mg/kg/day Maternal LOAEL : 1000 mg/kg/day based on abortions or early delivery. Developm ental NOAEL : 300 mg/kg/day Developm ental LOAEL : 1000 mg/kg/day based on abortions or early delivery.Page 42 of 47

TABLE A. 2 . Subchronic, Chronic and Other Toxicity Profile of Boscalid Technical Guideline Number Study Type Results 870.3800 Reproduction and fertility

effects (rat) Parental systemic NOAEL :112.6/1180.8 mg/kg/day (M/F) Parental systemic LOAE L :1165.0/>1180.8 mg/kg/day (M/F) decreased body weight and body weight gain (F 1 ) as well as hepatocyte degeneration ( F 0 and F 1 ) in males only. Offspring systemic NOAEL :11.2/115.8 mg/kg/day (M/F) Offspring systemic LOAEL :112.6/1180.8 mg/kg/day (M/F): decrea sed body weight for F 2 pups in males and females of both generations. Reproductive NOAEL :1165.0/1180.8 mg/kg/day (M/F) Reproductive LOAEL :>1165.0/1180.8 (M/F) 870. 4 100 a Chronic toxicity rodents (rat) NOAEL : 21.9/30.0 mg/kg/day (M/F) LOAEL : 110.0/150.3 mg/kg/day (M/F): M = thyroid toxicity (weights and microscopic changes); F = thyroid toxicity (weights and microscopic changes). Thyroid follicular cell adenomas: M = 0/20, 0/20, 2/20,1/20; F = 0/20, 0/20, 1/20,0/20. 870. 4 100 Chronic toxicity dogs NOAEL : 2 1.8/22.1mg/kg/day (M/F) LOAEL :57.4/58.3 mg/kg/day (M/F): M = elevated ALP activities and elevated hepatic weights; F = no effects 870.42 00 Carcinogenicity rats NOAEL : 23.0/29.7 mg/kg/day (M/F) LOAEL : 116.1/155.6 mg/kg/day (M/F): M = increased incidence o f thyroid follicular cell hyperplasia and hypertrophy; F = decrease in body weight gain and increased incidence of thyroid follicular cell hyperplasia and hypertrophy. Thyroid follicular cell adenomas: M = 0/50, 0/50, 1/50, 4/50; F = 0/50, 1/50, 0/50, 3/5 0. 870.4200 Carcinogenicity mice NOAEL :65/443 mg/kg/day (M/F) LOAEL : 331/1804 mg/kg/day (M/F): M = decreases in body weight and body weight gains F = decreases in bo dy weight and body weight gains No evidence of carcinogenicity. 870.43 00 Chronic

feedin g/Carcinogenicity rat See 870.4100a and 870.4200.
870.5 100 Gene Mutation bacterial

reverse mutation assay Negative without and with S
- 9 activation up to limit dose of 5000 μg/plate. 870.53 00 In vitro mammalian cell

forward gene mutation assay (CHO cell s/HGPRT locus) Negative without and with S
- 9 activation up to the limit of solubility of 25 μg/mL.
870.5375 In vitro mammalian

cy togenetics assay in Chinese hamster V79 cells Negative without and with S
- 9 activation up to 3500 μg/mL with precipitation s howing at concentrations of 100 μg/mL and higher.Page 43 of 47

TABLE A. 2 . Subchronic, Chronic and Other Toxicity Profile of Boscalid Technical Guideline Number Study Type Results 870. 5395 Cy

togenetics
- mammalian erythrocyte micronucleus test in the mouse Negative at doses up to 2000 mg/kg.

870. 5500 In vitro unscheduled DNA

synthesis (primary rat hepatocytes) Negative response up to 50 μg/mL. Cytotoxicity at 100
- 500 μg/mL.
870.62 00 Ac ute neurotoxicity

screening battery (rat) NOAEL :1050.0/1272.5 mg/kg/day (M/F) LOAEL : >1050.0/1272.5 mg/kg/day (M/F) 870.62 00 Subchronic neurotoxicity

screening battery (rat) NOAEL :1050.0/1272 .5 mg/kg/day (M/F) LOAEL : >1050.0/1272.5 mg/kg/day (M/F) 870.63 00 Developmental neurotoxicity

(rat) Maternal NOAEL: 1442 mg/kg/day Maternal LOAEL: >1442 mg/kg/day Offspring NOAEL: 14 mg/kg/day Offspring LOAEL: 147 mg/kg/day (decreased body weights on PND 4 and decreased body weight gain on PNDs 1
- 4) 870. 7485 Metabolism and

pharmacokinetics (rat) BAS 510 F was readily absorbed and excreted following single oral 50 mg/kg; at single 500 mg/kg or 15 doses of 500 mg/kg, absorption was saturated. Excretion mainly by feces (80
- 98%). Biliary excretion 40
- 50% of fecal activity at 50 mg/kg, 10% at 500 mg/kg. Urine, about 16% at 50 mg/kg, 3
- 5% at 500 mg/kg. Absorption about 56% at 50 mg/kg and 13
- 17% at 500 mg/kg. Excretory patterns similar by gender or radiol abel position. Metabolites (hydroxylation and conjugation products) were consistent with Phase I oxidation reactions followed by Phase II conjugation with glucuronic acid or sulfate, or by conjugation of the parent with glutathione with cleavage to sulfate metabolites. 870. 7600 Dermal Penetration (rat) Maximum % absorption: 0.01 mg/cm2 = 10.93 (24 hour exposure, 24 hour sacrifice) 0.10 mg/cm2 = 3.76 (24 hour exposure, 24 hour sacrifice) 1.00 mg/cm2 = 1.48 (10 hour exposure, 72 hour sacrifice) None SPEC IAL STUDY: Hepatic

enzyme induction (rat) 1. hypertrophy of zone III hepatocytes 2. >20% increase in liver weight 3. increase in CYP450 activity 4. slight to extensive microscopic SER proliferation 5. not a peroxisome proliferator 6. enzymes in CYP450 sub family not induced 7. no notable microscopic increase in size or number of peroxisomes CONCLUSION: inducer of total CYP450 activityPage 44 of 47

TABLE A. 2 . Subchronic, Chronic and Other Toxicity Profile of Boscalid Technical Guideline Number Study Type Results None SPECIAL STUDY: Hormone

and enzyme induction (rat) 1. slight (statistically significant) decrease in circulating T 3 and T 4 only in males 2. increase in circulating TSH levels both sexes 3. increase in all 3 liver microsomal glucuronyltransferases CONCLUSION: disruption of thyroid homoeostasis by decreasing circulating T 3 and T 4 and increasing TSH; likely the result of hepatic microsomal glucuronyltransferase induction None SPECIAL STUDY:

Reversibility study (dietary): 4
- week administration followed by 4 weeks recovery or 13 weeks recovery (rat) 4 weeks dosing: at 2500 and 15000 ppm: increase in TSH (68% and 87%); increas e in absolute and relative thyroid weights, hypertrophy of thyroid follicular epithelial cells and diffuse follicular hyperplasia, increase in absolute and relative liver weights and centrilobular hypertrophy as well as liver portal fatty changes. 4 weeks dosing + 4 weeks recovery: no increases in TSH; increase in absolute and relative thyroid weights; thyroid hypertrophy and hyperplasia decreased to control values; all liver effects reversed to control. 4 weeks dosing + 13 weeks recovery: no increases in TSH; increase in absolute and relative thyroid weights; thyroid hypertrophy and hyperplasia decreased to control values; all liver effects reversed to control. CONCLUSION: induction of liver microsomal enzyme system resulting in increased glucuronidation of thyroxine, resulting in an increase in TSH secretion as a compensatory response of the physiological negative feedback system; increased TSH resulted in increased thyroid weight.Page 45 of 47

APPEND IX B : RATIONALE FOR TOXICITY DATA REQUIREME NTS OPPTS Guidelin e Number: 870.7800 Study Title: Immunotoxicity Rationale for Requiring the Data The immunotoxicity

study is a new data requirement under 40 CFR § 158 as a part of the data requirements for registration of a pesticide (food and non
- food uses). The Immunotoxicity

Test Guideline (OPPTS 870.7800) prescribes functional immunotoxicity

testing , and is designed to evaluate the potential of a repeated chemical exposure to produce adverse effects ( such as suppression) on the immune sy stem. Immunosuppression is a deficit in the ability of the immune system to respond to a challenge of bacterial or viral infections , such as tuberculosis (TB), Severe Acquired Respiratory S yndrome (SARS), or neoplasia. Because the immune sy stem is highly complex, studies not speci ficall y conducted to assess immunotoxic endpoints are inadequate to characterize a pesticide’s potential immunotoxicity . While data from hematology , l ymphoid organ weights, and histopathology

in routine chronic or subchronic toxicity studies may

offer use ful information on potential immunotoxic effects, these endpoints alone are insufficient to predict immunotoxicity
. Practical Utility of the Data How will the data be used? Immunotoxicity

studies provide critical scientific information needed to characterize potential hazard to the human population on the immune sy stem from pesticide exposure. Since epidemiologic data on the effects of chemical exposures on immune parameters are limited , and are inadequate to characterize a pesticide’s potential immunotoxicity in humans, animal studies are used as the most sensitive endpoint for risk assessment. These animal studies can be used to select endpoints and doses for use in risk assessment of all exposure scenarios , and are considered a primary data source for reliable reference dose calculation. For example, animal studies have demonstrated that immunotoxicity in rodents is one of the more sensitive manifestations of TCDD (2,3,7,8
- tetrachloro dibenzo
- p - dioxin) among developmental, reproductive and endocrinologic toxicities. Additionally , the EPA has established an oral reference dose (RfD) for tributyltin oxide (TBTO) , based on observed immunotoxicity in animal studies (IRI S, 1997). How cou ld the data impact the Agency's future decision - making? If the immunotoxicity

study shows that the test material poses either a greater or a diminished risk than that given in the interim decision’s conclusion, the risk assessments for the test material may

need to be revised to reflect the magnitude of potential risk derived from the new data. If the Agency

does not have these data, a 10X database UF may be applied for conducting a risk assessment from the available studies.Page 46 of 47

APPEND IX C: INTERNAT IONAL RESIDUE LIMIT STATUS 

## INTERNATIONAL RESIDUE LIMIT STATUS Chemical Name: 3
- pyridinecarboxamide, 2
- chloro
-N
- (4'
- chloro[1,1'
- biphenyl]
- 2
- yl Common Name: Boscalid X Proposed tolerances

X Reevaluated tolerance □ Other Date: 8/05/09 

### Codex Status (Maximum Residue Limits) 

### U. S. Tolerances □ No Codex proposal step 6 or above □ No Codex proposal step 6 or above for the crops requested Petition Numbers: PP#9F7527 and PP#9F9529 DP#: 364447 Other Identifier: Res idue definition (step 8/CXL): Boscalid Revie wer/Branch: P. Deschamp/RAB3 Residue definition: boscalid for plant commodities; and combined residues of boscalid and M510F01 (free and conjugates) for animal commodities Crops/Commodities MRL (mg/kg) Crop s/Commodities Recommended Tolerance (ppm) Alfalfa, forage 30 Alfalfa, hay 65 Fruit, citrus, group 10 1.6 Stone fruits 3.0 Fruit, stone, group 12 3.5 Egg 0.02 Egg 0.02 Fat of cattle, goat, horse and sheep 0.30 Meat (mammalian other than marine) 0.7 Meat of cattle, goat, horse and sheep 0.1 0 Edible offal, mammalian 0.2 Meat byproducts (cattle, goat, horse and sheep) 0
. 3 5 Milks 0.1 Milk 0. 1 0 Hog, Fat 0.20 Hog, kidney None Hog, meat byproducts 0. 35 Hog, liver None Poultry fat/meat 0.02 Poultry, fat 0.20 Poultry, liver None Poultry, edible offal 0.02 Poultry, meat byproducts 0.20Page 47 of 47



## INTERNATIONAL RESIDUE LIMIT STATUS Chemical Name: 3
- pyridinecarboxamide, 2
- chloro
-N
- (4'
- chloro[1,1'
- biphenyl]
- 2
- yl Common Name: Boscalid X Proposed tolerances

X Reevaluated tolerance □ Other Date: 8/05/09 Limits for Canada Limits for Mexico □ No Limits □ No Limits for the crops requested X No Limits □ No Limits for the crops requested Residue definition: boscalid for plant commodities; and combined residues of boscalid and M510F01 (free and conjugates) for animal commodities Residue defi nition: NA. Mexico defers to U.S. tolerances or Codex MRLs for its export purposes. Crops/Commodities MRL (mg/kg) Crops/Commodities MRL (ppm) apricot, plumcot, plum, peach, sweet cherry, and tart cherry 1.7 Eggs 0.02 Fat of cattle, goats, hogs, ho rses, and sheep 0.3 Fat of poultry 0.05 Meat of cattle, goats, hogs, horses, and sheep 0.1 Meat of poultry 0.05 Meat byproducts of cattle, goats, hogs, horses, and sheep 0.35 Meat byproducts of poultry 0.1 Milk 0.1 Notes/Special Instructions: S.Funk, 10/14/2009.