UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C

. 20460

OFFICE OF C HEM ICAL SA FETY AND POLLUTION PREVEN TION

MEMORANDUM

DATE: September 30, 2014



### SUBJECT: Boscalid- H uman Health Risk Assessment for a Section 3 Registration of New
Uses on Herb Subgroup 19A and Dill Seed, Plus Crop Group Conversions on Stone Fruit Group 12-12 and Tree Nut Group 14-12.

PC Code: 128008 DP Barcode: 0416695,0416696 Registrat ion No.: 7969-199 Decis ion No.: 484932, 484933
Petition No. : 3E8215 Regu l atory Action : Section 3 Registration
Case No.: 7034 R i sk Assessment Type: Single ChemicaVAggregate

TXRNo.: NA CAS No.: 188425-85-6
40 CFR: 180.589 MRID No.: NA

FROM:

TO: Barry O ' Keefe

, Senior Biologist 

## B. () 'Wuv j)n
Myron S. Ottley : Senior

### ~iologist**~1)7~~** Steve Funk, Semor Chem1st 

### (X,.fc:;::t?:..,:_

Cassi Walls, Senior Biologist**~~** 

# t Wt/!h>

Risk Assessment Branch III (RAB III )
Health Effects Division (7509P)

Andrew Ert man, Risk Manager
Risk Int egrat ion

, Minor Use and Emergency Response Branch (RIMUERB) Registration Di v ision (7505P)

This document and attachments provide an assessment of the human health risk resulting from
the proposed and registered uses ofboscalid. The toxicology reevaluation was performed by Myron Ott le y, the drinking water assessment was conducted by Katrina White (EPA
Environmenta l Fate and Effects Division (EFED))

, the review of the residue chemistry data and dietary exposure assessment were conducted by Steve Funk

, the occupational and residentia l

exposure assessment was conducted by Cassi Walls, and the human health risk assessment was conducted by Barry O ' Keefe

.

Page 1 of4 5Table of Contents

1.0 Executive Summary

........................................................................................................... 4
2.0 HED Recommendations

. ..... .. ............................ .. .. ... .. .. ..................................................... 6
2.1 Data Deficiencies

............................................................................................................ 7
2

. 2. 1 Enforcement Analytical Method

.................................................................... .. .. .. .. ... 7
2.2.2 Recommended Tolerances

....................................................... . ... . ..... .. ...... ... .. .. ......... 7
2

. 2.3 Revisions to Petitioned-For Tolerances

............................................ . ....................... 8
2.2.4 Internationa l Harmonization

..................... .. ..... .. .. ... . ... .................................. . ........... 8
3

. 0 Introduction

......................................................................................... . .............................. 8
3.1 Chemical Identity

..................................................................................................... . ..... 9
3.2 Physical/Chemical Characteristics

.. .. .............................................................. . ....... . .. 10
3.3 Pesticide Use Pattern

.................................................................................................... 10

3.4 Anticipated Exposure Pathways

....................................................................... . ......... 11
3.5 Consideration of Environmental Justice

........ . ...... .. .. . .... . .. .. ....................................... 11
4.0 Hazard Characterization and Dose-Response Assessment..

................... . .. .. .. ... .. . ........ 12
4

. 1 Summary of Toxicological Effects

.................................... . .............. .. ... . .. . .................. 12
4.2 Safety Factor for Infants and Children (FQP A Safety Factor)

............................... 13
4

. 2. 1 Completeness of the Toxicology Database

............................................ . ....... . ........ . 13
4.2.2 Evidence of Neurotoxicity

............................. . ....... .. ...... .. ...... .. .. . .... . ...... . ... .. ............. 13
4

. 2

. 3 Evidence of Sensitivity/Susceptibility in the Developing or Young Animal..

...... 13
4.2

. 4 Residual Uncertainty in the Exposure Database

....................................... .. .......... 14
4.3 Toxicity Endpoint and Point of Departure Selections

.............................................. 15
4

. 3.1 Dose-Response Assessment

.... . ......... . ....................... .. .. .. .. . ...... ... ..... .. .. . .................... 15
4.3

. 2 Recommendation for Combining Routes of Exposure for Risk Assessment

...... 16
4.3

. 3 Cancer Classification and Risk Assessment Recommendation

.... . .. . .................... 16
4

. 3

. 4 Summary of Points of Departure and Toxicity Endpoints Used in Human Risk
Assessment

........................................................................................................ . ... . . . ................ 17
5.0 Dietary Exposure and Risk Assessment..

....................................................................... 18
5 .1 Residues of Concern Summary and Rationale

.. .. .. .. ......... ........... . .. .. ............ .. ...... . .... 18
5.2 Food Residue Profile

.................................................... . ............................................... 19
5.3 Water Residue Profile

...... . ...... .. .. . .. ... .. . .. . ..................................... . ............................... 19
5.4 Dietary Risk Assessment

............................. . ............... . .... . ........................................... 20

5.4.1 Description of Residue Data Used in Dietary Assessment

.................................... 20
5.4.2 Percent Crop Treated Used in Dietary Assessment

...................................... . ....... 21
5

. 4.3 Acute Dietary Risk Assessment..

....... . ........... . .. . ........ . .. . ....... .. .. .. .. .. .... .. ................... 21
5

. 4

. 4 Chronic Dietary Risk Assessments

.................................... . .............................. . ..... 22
5.4.5 Summary Table

................................................................................ . ........................ 22
6

. 0 Residentia l (Non-Occupational) Exposure/Risk Characterization

.. . ........... .. ............. 22
6.1 Residential Handler Exposure

.................................................................................... 23
6

. 2 Post-Application Exposure

................................................... . .......... . . . ... .. .. .. .. .. .. .. ... .. . .. 23
6.3 Combined Residential Risk Estimates (Multiple Exposure Scenarios)

................... 25
6

. 4 Residential Risk Estimates for Use in Aggregate Assessment..

.... . . .......................... 25
6.5 Residential Bystander Post-application Inhalation Exposure

.......... . .............. . ....... 26
6

. 6 Spray Drift

........... .. . ...... .. . ...... . ...... . ....... . ....... . ... . ......................... . ................................. 26

7

. 0 Aggregate Exposure/Risk Characterization

.......... . .. . .................................................... 27

Page 2 of45Page 3 of 45

7.1 Acute Aggregate Risk

................................ ................................ ................................ ... 27
7.2 Short

- Term Aggregate Risk

................................ ................................ ........................ 27
7.3 Chronic Aggregate Risk

................................ ................................ .............................. 28
8.0 Cumulative Exposure/Risk Characterization

................................ ............................... 28
9.0 Occupational Exposure/Risk Characterization

................................ ............................ 28
9.1 Short

- /Intermediate

- Term Handler Risk

................................ ................................ ... 28
9.2 Short

- and Intermediate

- Term Post

- Application Risk

................................ .............. 29
9.2.1 Dermal Post

- Application Risk

................................ ................................ ................. 30
9.2.2 Inhalation Post

- Application Risk

................................ ................................ ............ 31
10.0 References

................................ ................................ ................................ ......................... 32 Appendix A. Toxicology Profile and Executive Summaries

................................ .................. 33
A.1 Toxicology Data Requirements

................................ ................................ ................... 33
A.2 Toxicity Profiles

................................ ................................ ................................ ............ 34 Appendix B. Physicochemical Properties of Boscalid.

................................ ........................... 40 Appendix C. Review of Human Research

................................ ................................ ................ 40 Appendix D. Residential Handler and Post

- application Exposure and Risk Estimates

..... 41 Appendix E. Occupational Handler and Post

- application Exposure and Risk Estimates

.. 43 Appendix F. Summaries of Field Residue Data

................................ ................................ ...... 44 Appendix G. International Residue Limits Status Sheet

................................ ....................... 45Page 4 of 45

1.0 Executive Summary

Introduction Boscalid, 3

- pyridinecarboxamide, 2

- chloro

- N

- (4'

- chloro[1,1'

- biphenyl]

- 2

- yl), is a fungicide active ingredient (ai) that stops fungi from producing the energy they need to carry on basic
functions. It works inside the mitochondria and binds to the enzyme succinate ubiquinone
reductase , preventing energy production

. Boscalid is currently registered on numerous agricultural crops and on golf course turf

, residential ornamentals, landscape gardens, residential fruit and nut trees, and greenhouse grown tomato transplants for the home consumer market.

Use Profile The Interregional Research Project No. 4 (IR

- 4) is proposing new use s on herb subgroup 19A
and dill as additions to the Pristine ® Fungicide label (EPA Reg. No. 7969

- 199). Additionally,
IR

- 4 is proposing crop group conversions for the stone fruit group 12

- 12 and the tree nut group
14

- 1 2

. The Pristine ® Fungicide label also includes the active ingred ient pyraclostrobin. For pyraclostrobin, IR

- 4 is also proposing new use s on herb subgroup 19A and dill, and crop group conversions for the stone fruit group 12

- 12 and the tree nut group 14

- 1 2 . Therefore, a separate HED exposure and risk assessment docume nt will be completed for pyraclostrobin. The
Pristine ® label require s occupational handlers to wear the following personal protective equipment (PPE): long

- sleeved shirts, long pants, shoes

, socks, and chemical resistant gloves.
The 12 hour restricted entry interval (REI) listed on the label is a dequate to protect workers

.

Exposure Profile Exposure pathways include dietary (food and drinking water), residential, and occupational exposure sources. Dietary exposures are expected for acute and chronic durations. Existing
residential u se s result in short

- term handler dermal and inhalation exposures for adults, and
short

- term post

- application dermal exposures for adults, youths (11 to 16 years old), and children 6 to 11 years old

. Occupational handler a nd post

- application exposures are expected via dermal
and inhalation routes for short

- and intermediate

- term durations.

Hazard Assessment In subchronic and chronic feeding studies in rats, mice

, and dogs, boscalid generally caused decreased body weights and effects on the liver as well as on the thyroid. While the dog appeared to be the most sensitive species in the subchronic studies, the sensitivity of the dog and the rat was
similar in the ch ronic studies. Based on weak evidence of carcinogenic effects in male rats, boscalid is classified as, “suggestive evidence of carcinogenicity, but not sufficient to assess human carcinogenic potential.” Boscalid was negative in the mutagenicity battery

, the neurotoxicity battery and the immunotoxicity study. T here were no susceptibility concerns and
no residual uncertainties regarding developing offspring, and the Food Quality Protection Act ( FQPA ) Safety Factor (SF) was reduced to 1X. Boscalid has low acute toxicity via the oral, dermal, and inhalation routes of exposure and is not a dermal sensitizer, primary eye irritant, or
skin irritant. Endpoints and points of departure (PODs) were selected for chronic dietary, incidental oral (short

- and intermed iate

- term), dermal (all durations) and inhalation (all durations) exposure scenarios. As there were no toxic effects attributable to a single dose, an endpoint for acute dietary was not identified. Note that the requirement for a subchronic inhalation st udy remains outstanding.Page 5 of 45

Dietary Exposure The residue chemistry and environmental fate data are adequate to assess human dietary

exposure

. The assessments are based on reliable data and will not underestimate exposure or
risk. E stimated drinking water concentrations (EDWCs) were incorporated directly into the dietary exposure assessments.

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 con ducted

.

The results of the slightly refined chronic dietary (food and drinking water) analysis are below the Agency’s level of concern (LOC) for all population subgroups. The dietary exposure for food and drinking water for the general U.S. population is 1 2 % of the chronic Population Adjusted Dose (c PAD) and 25.5 % of the cPAD for all infants (< 1 year old ) , the population subgroup with the high est estimated chronic dietary exposure to boscalid

.

Residential Exposure
N o n ew residential uses were requested in this action

. However, boscalid is currently registered
for use on golf course turf , residential ornamentals and landscape gardens, and resi dential fruit
and nut trees . Residential exposure s from existing residential use s w ere previously assessed using the updated 2012 HED Residential Standard Operating Procedures 1 (SOPs). Residential exposure is expected to be short

- term only. Because the dermal and inhalation PODs are the

same , but the uncertainty factors are different , the dermal and inhalation handler exposure estimates were combined using the aggregated risk index (ARI) approach. All residential
handler dermal and inhalation exposure r isk estimates were not of concern to HED (i.e. all ARIs >1) , with ARI values rang ing from 24 to 3 30

. All residential post

- application dermal exposure risk estimates were also not of concern to HED, with margins of exposure ( M OEs ) rang ing from
6 8 0 to 16 ,00 0.

Aggregate Exposure There is potential for short

- term and chronic aggregate exposure to boscalid

. The short

- term aggregate exposure results from dietary (which is considered background exposure) and residential (which is considered primary ) exposure pathways. The chronic aggregate exposure is the same as chronic dietary exposure from food and drinking water, which are all below the HED’s level of concern. The short

- term aggregate MOEs are 46 0 for children 6 to 11 years old, 1,10 0 for youth s 11 to 16 years old, and 38 0 for adults. None of these short

- term aggregate risk
estimates are of concern to HED.

Occupational Exposure Based on the proposed agricultural use s , there is potential for short

- and intermediate

- term occupational exposure during handling and post

- application activities. The proposed labels require occupational handlers to wear the following PPE: long

- sleeved shirts, long pants, shoes

, socks, and ch emical resistant gloves. Because the dermal and inhalation PODs are the same

, but the uncertainty factors are different, the dermal and inhalation handler exposure estimates were combined using the ARI approach.

1 http://www.epa.gov/pesticides/science/residential

- exposure

- sop.htmlPage 6 of 45

All of t he occupational handler ARIs are greater than 1.0 (range from 1.3 to 480) when assessed using labeled PPE (gloves)

, and are not a concern to HED.

All post

- application scenarios resulted in dermal MOEs greater than 100 on day 0 (12 hours after application)

, and therefore

, are not of concern to HED . The dermal MOEs ranged from 94 0 to
2 6 ,000. Dislodgable foliar residue ( DFR ) studies are not required at this time for boscalid since the lowest dermal MOE ( 94 0) is greater than two times the LOC (100) based on default input

va lues.

Based on the Agency's current practices, a quantitative non

- cancer occupational post

- application inhalation exposure assessment was not performed for boscalid at this time. If new policies or procedures are put into place, the Agency may revisit th e need for a quantitative occupational post

- application inhalation exposure assessment for boscalid

. The 12 hour restricted entry interval (REI) listed on the labels is a d e quate for worker protection

.

Review of Human Research
This risk assessment relies in part on data from studies in which adult human subjects were intentionally exposed to a pesticide or other chemical. These data, which include studies from the Pesticide Handlers Exposure Database

, Version 1.1 (PHED 1.1), the Agricultural Handle r Exposure Task Force (AHETF) database, the Outdoor Residential Exposure Task Force (ORETF) , and the Residential SOPs (lawns and turf) are subject to ethics review pursuant to 40 CFR 26, have received that review, and are compliant with applicable ethics r equirements. For certain studies that review may have included review by the Human Studies Review Board. Descriptions of data sources as well as guidance on their use can be found at http://www.epa.gov/pesticides/science/handler

- exposure

- data.html and http://www.epa.gov/pesticides/science/post

- app

- exposure

- data.html

.

Environmental Justice Cons iderations 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 Populat ions and Low

- Income Populations," ( http://www.eh.doe.gov/oepa/guidance/justice/eo12898.pdf

.

2.0 HED Recommendations

HED has examined the toxicology

, residue chemistry , and exposure database s for boscalid

. Pending submission of revised Section F, there are no toxicology or residue chemistry issues that would preclude granting Section 3 registration for the requested uses of boscalid, or
establishment of tolerances for residues of boscalid. Additional data are needed, as outlined below in Section 2.1. The specific tolerance recommendations a re discussed in Section 2.2

.Page 7 of 45

2.1 Data Deficiencies

870.3465 Subchronic Inhalation S tudy

 A subchronic i nhalation study is required because the use of an oral point of departure (POD) for inhalation exposure results in MOEs as low as 370 for occupational exposure,
which does not meet the target of 1000 for a waiver (TXR0056585. K. Rury. 03/04/2013). Therefore

, a 10X database uncertainty facto r has been added for inhalation

exposures in the absence of the required inhalation toxicity study

.

2.2 Tolerance Considerations

2.2.1 Enforcement Analytical Method

An adequate gas chromatography/mass spectrometry ( GC/MS ) method (Method D0008) is available for enforcing boscalid tolerances in plant commodities. Residues are extracted using an aqueous organic solvent mixture followed by liquid/liquid partitioning and column clean

- up. Quantitation is by GC/MS , using select ed ion monitoring (SIM) of major ions. The method lists monitoring ions of m/z 342, 142, or 140, and notes that any ion can be used for quantitation as appropriate to the situation . Quantitation is performed using an external calibration curve of
boscali d standards. Adequate validation data were submitted, including independent laboratory validation (ILV) data (MRID 45405101). The validated LOQ is reported to be 0.05 ppm for residues of boscalid in plant matrices. The Analytical Chemistry Branch (ACB) of the Biological and Economic Analysis Division ( BEAD ) concluded that the method is acceptable for enforcement purposes in plants (D284510; D. Swineford and E. Kolbe, 8/12/2003, PMV memo )

.

2.2. 2 Recommended Tolerances

Sufficient data are available to su pport tolerances for residues of the fungicide boscalid, including its metabolites and degradates, in or on dill seed and the herb subgroup 19A. Compliance with the tolerance levels is to be determined by measuring only boscalid

, 3

- pyridinecarboxamide, 2

- chloro

- N

- (4′

- chloro[1,1'

- biphenyl]

- 2

- yl). The tolerance expression is aligned with the requirements of the S. Knizner memo dated 05/27/2009. Additionally, the proposed crop group conversions for fruit, stone, group 12

- 12 and nut, tree, group 14

- 12 are
ap propriate.

Table 2.2.2 . Tolerance Summary for Boscalid Commodity Proposed Tolerance (ppm) Existing

Tolerance HED

- Recommended

Tolerance (ppm) Comments ( correct commodity definition ) Herb subgroup 19A 190

- 150 Dill, seed 300

- 100 Fruit, stone, group 12

- 3.5 Revoke Crop group conversion Fruit, stone, group 12

- 12 3.5

- 3.5 Crop group conversion Nut, tree, group 14

- 0.70 Revoke Crop group conversion Nut, tree, group 14

- 12 0.70

- 0.70 Crop group conversion

Pistachio

- 0.70 Revoke Crop group conversion. Member of group 14

- 12.Page 8 of 45

2.2. 3 Revisions to Petitioned

- For Tolerances

The required stone fruit and tree nut crop group conversions occur without modification of the existing tolerances.

The recommended tolerance for the herb subgroup 19A is 150 ppm, based on the highest average field trial ( HAFT ) data for basil and the processing factor for drying. Dried basil had residues in excess of those found on dillweed, fresh basil, and chives. T he petitioned for tolerance of 190 ppm is not supported by the field trial data and the processing data.

The recommended tolerance for dill seed is 100 ppm, based on evaluation of the 0 day pre

harvest interval ( PHI ) data with the Organization for Econom ic Cooperation and Development ( OECD ) calculation procedure. It appears that the petitioned for tolerance of 300 ppm was based

on data from an exaggerated application rate.

A revised Section F is needed for the herb subgroup 19A and for dill seed.

2.2. 4 International Harmonization

Canada and Codex have not established maximum residue limits (MRLs)/tolerances for herbs or dill seed, and therefore there is no harmonization issue (see Appendix G)

.

For stone fruit, Canada has an MRL of 1.7 ppm and Codex has an MRL of 3 ppm. The US tolerance is 3.5 ppm, based on the evaluation of peach, plum, and cherry data (D364447, A. Acierto, 10/16/ 20 09). The individual commodity tolerance estimates were 1.6 ppm for plum, 3.0 ppm for peach, and 3.5 ppm for cherry. T he Canada MRL of 1.7 ppm was the former US tolerance prior to the latest data review. The tolerance cannot be lowered to 3 ppm to harmonize with Codex, as the cherry data necessitate a higher value. The tree nut tolerance (0.7 ppm) is
harmonized with Can ada. The Codex tree nut MRL (0.05 ppm) is lower than the US tolerance, and harmonization is not possible.

3.0 In troduction

B oscalid , 3

- pyridinecarboxamide, 2

- chloro

- N

- (4'

- chloro[1,1'

- biphenyl]

- 2

- yl), is a fungicide active ingredient that works inside th e mitochondria of fungi and stops fungi from producing the energy that they need to carry on the basic functions such as obtaining food, growing and reproducing. Boscalid prevents energy production by binding to the enzyme succinate ubiquinone reductase.

Boscalid is currently registered on alfalfa, artichoke, beans, Belgium endive, berries, Brassica vegetables (subgroups 5A and 5B), bulb vegetables, canola, carrots, celery, certain root vegetables, citrus, cotton, cucurbit vegetables, edible peas, fruiting vegetables, herbs (herbs subgroup 19A), grapes, lettuce, Leafy Greens Subgroup 4A, except head and leaf lettuce, and leaf petioles subgroup 4B, mint, peanuts, persimmon, pistachios, pome fruits, potatoes, soybeans, spinach, stone fruit s , strawberr ies, tree nuts, tropical fruits (avocado, black sapote, canistel,Page 9 of 45

mamey sapote, mango, papaya, sapodilla, and star apple) sunflower, seed treatment of rapeseed, greenhouse grown tomatoes, imported bananas, and imported coffee, as well as golf course turf

,
r esidential fruit and nut trees , r esidential ornamentals and landscape gardens , and tomato transplants grown for the home consumer market

.

With the current action

, BASF is proposing new use s on herb subgroup 19A and dill seed as additions to the Pristine ® Fungicide label (EPA Reg. No. 7969

- 199). Additionally, BASF is proposing crop group conversions for the stone fruit group 12

- 12 and the tree nut group 14

- 1 2

.

3.1 Chemical Identity

The chemical structure and nomenclature of boscalid and its hydroxyl m etabolite are presented
in Table 3.1.

Table 3.1. Nomenclature of Boscalid and its Hydroxy Metabolite.

Compound

Common name Boscalid; Nicobifen Company experimental name BAS 510 F

IUPAC name 2

- chloro

- N

- (4 ׳

- chlorobiphenyl

- 2

- yl)nicotinamide

CAS name 2

- chloro

- N

- (4'

- chloro[1,1'

- biphenyl]

- 2

- yl)

- 3

- pyridinecarboxamide 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) Hydroxy

- metabolite

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 359.2Page 10 of 45

3.2 Physical/Chemical Characteristics

If released to air, a vapor pressure of 5.4 x 10

- 9 mm Hg at 20 o C indicates boscalid will exist solely in the particulate phase in the atmosphere. Particulate

- phase boscalid will be removed from the atmosphere by wet or dry deposition. Boscalid will not vol atilize from dry soil surfaces based upon its vapor pressure. Boscalid is stable to direct photolysis by sunlight. If released to soil, boscalid is expected to have low mobility based upon an estimated Koc of 970. Boscalid is stable to hydrolysis. The physiochemical properties of boscalid are summarized in Appendix B.

3.3 Pesticide Use Pattern

BASF is proposing new use s of boscalid on herb subgroup 19A and dill seed as additions to the
Pristine ® Fungicide label (EPA Reg. No. 7969

- 199). Pristine ® Fu ngicide is a multiple active ingredient water dispersible granule ( WDG ) fungicide containing 12.8% pyraclostrobin and
25.2% boscalid. Herbs and dill may be treated at a maximum single application rate of 0.292 lb ai/A (18.5 fl oz/A) using aerial, ground, or chemigation equipment. Pristine ® Fungicide may be applied two times per year at a maximum yearly application rate of 0.584 lb ai/A (37 fl oz/A). The label requires occupational handlers to wear the following PPE: long

- sleeved shirts, long pants, shoes and socks, and chemical resistant gloves. The 12 hour REI listed on the label is appropriate.

Additionally, BASF is proposing crop group conversions for the stone fruit group 12

- 1 2 and the tree nut group 14

- 1 2

.

The proposed uses of boscalid are summarized in Table 3.3

.

Table 3.3. Summary of Directions for the Proposed Uses of Boscalid.

Use Site Application

Method Maximum

Single Application
Rate (lb ai/A) Maximum

Number of Applications /
Year Maximum

Application
Rate/Acre/
Year (lb ai/A/yr) Minimum

Retreatment
Interval (days) PHI

(days)

Stone Fruit Group

Ground,

Aerial, or Chemigation 0.229 5 1.15 7 0

Tree Nut Group 0.229 4 0.916 7 (10 for pistachio) 14

(25 days for almond)

Herb Subgroup 0.292 2 0.584 7 0

Dill Seed 0.292 2 0.584 7 0Page 11 of 45

3.4 Anticipated Exposure Pathways

The Registration Division has requested an assessment of human health risk to support proposed

new use s of boscalid on the herb subgroup 19A and dill seed

. Humans may be exposed to
boscalid in food and drinking water, since boscalid may be applied directly to growing crops and application may result in boscalid reaching surface and ground water drinking water sources

. There are existing residential uses of boscalid so there is exposure to r esidential handlers and those entering treated areas following application. In occupational settings, applicators may be exposed while handling boscalid . There is a potential for post

- application exposure for workers

re

- entering treated fields and reside nts re

- entering treated areas

.

Risk assessments have been completed for proposed and existing uses of boscalid . This risk assessment considers all of the aforementioned exposure pathways based on the proposed new
uses of boscalid , but also considers ex isting uses of boscalid , particularly in the dietary and
residential exposure assessment s

.

3.5 Consideration of Environmental Justice

Potential areas of environmental justice concerns, to the extent possible, were considered in this
human health risk a ssessment, in accordance with U.S. Executive Order 12898, "Federal Actions to Address Environmental Justice in Minority Populations and Low

- Income Populations," ( http://www.eh.doe.gov/ oepa/guidance/justice/eo12898.pdf )

. 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 pest icide 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 U.S. Depar tment of Agriculture’s National Health and Nutrition Examination Survey, What We Eat in America, (NHANES/WWEIA) and are used in pesticide risk assessments for all registered food uses of a pesticide. These data are analyzed and categorized by subgroups ba sed on age and ethnic group. Additionally, OPP is able to assess dietary exposure to smaller, specialized subgroups 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 post

- application are evaluated. Further considerations are currently in development as OPP has
committed resour ces and expertise to the development of specialized software and models that consider exposure to bystanders and farm workers as well as lifestyle and traditional dietary patterns among specific subgroups.Page 12 of 45

4.0 Hazard Characterization and Dose

- Response A ssessment

4.1 S ummary of Toxicological Effects

Boscalid is a carboxamide (anilide) fungicide that acts in the fungal cell by inhibiting mitochondrial respiration and subsequent production of adenosine triphosphate ( ATP ) and by inhibiting the succinate

- ubiquinone oxidase reductase system in Complex II of the mitochondrial electron transport chain.

In mammals, the primary targets are the liver and the thyroid (indirectly from liver adaptive response). In subchronic and c hronic feeding studies in rats, mice and dogs, boscalid generally caused decreased body weights (primarily in mice) and effects on the liver (increase in weights, changes in enzyme levels and histopathological changes) as well as on the thyroid (increase i n weights and histopathological changes). Mode of action studies conducted in rats indicated that boscalid has a direct effect upon the liver and that the thyroid effects are secondary. A reversibility study in rats indicated that both liver and thyroid parameters returned to control values after the animals were placed on control diet. Absolute and/or relative thyroid weights were elevated in rats and dogs, but there were no histopathological changes observed in the thyroid in either mice or dogs.

In a developmental toxicity study in rats, no developmental toxicity was observed in the fetuses at the highest dose tested ( l imit d ose). No effects were noted in the dams in this study. In a developmental toxicity study in rabbits, an increased incidence of abortions or early delivery was
observed at the l imit d ose. There was quantitative evidence of increased susceptibility in the

two

- generation reproduction study in rats, where decreases in body weights in male offspring
were seen at a dose that was lower than the dose that induced parental/systemic toxicity. There was quantitative evidence of increased susceptibility in the developmental neurotoxicity study in rats, where decreases in pup body weights on post natal day four (PND 4) and body weight gains (PND 1

- 4) were seen in the absence of any maternal toxicity.

In a two

- year chronic toxicity study and a two

- year carcinogenicity study in male and female rats, the combined data showed an increase d trend in thyroid follicular cell adenomas that appeared to be treatment

- related in males. This was supported by thyroid hypertrophy and hyperplasia of follicular cells at the same dose as well as increased thyroid weights plus mechanistic data. The mouse carcinogenicity study was negative. Boscalid w as negative in the mutagenicity battery.

There was no evidence of neurotoxicity in rats in the acute, subchronic or developmental studies up to the limit dose . No neurotoxic observations were noted in any of the other studies in any species.

In acute studies, there is relatively low toxicity ( T oxicity C ategories III or IV for oral, dermal, inhalation, primary eye irritation and primary skin irritation).Page 13 of 45

Dermal Absorption Based on the results of an available dermal absorption study in rats, the
d ermal a bsorption f

actor (DAF) of boscalid i s determined to be 15%, as represented by 11% being absorbed plus 4% found as bound residue on the skin following a 24 hr exposure and 24 hr
sacrifice.

4. 2 Safety Factor for Infants and Children (FQPA Safety Factor)

The toxicity database is considered complete and adequate for risk assessment. There was no evidence of neurotoxicity in the database; there is low or no concern for developmental or reproductive toxicity, and for susceptibility in the developing or young animal. There are no
residual uncertainties identif ied in the exposure databases. Therefore, the FQPA Safety Factor
has been reduced to 1 X

.

4.2.1 Completeness of the Toxicology Database

The toxicity database is considered complete and adequate for ris k assessment , with the exception of a subchronic inhalation study. All studies needed to assess susceptibility concerns, such as developmental and reproduction studies, have been submitted. Additional studies, such a developmental neurotoxicity study, ac ute and subchronic neurotoxicity studies and an immunotoxicity study are also available. The subchronic inhalation study is required because the use of an oral POD results in MOEs as low as 370 for occupational exposure, which is not
sufficient to allevia te concern (TXR0056585. K.Rury. 03/04/2013). Therefore, a 10 X database uncertainty factor has been added for inhalation exposure.

4.2.2 Evidence of Neurotoxicity

There was no evidence of neurotoxicity based on an acute neurotoxicity study, a 90

- day

neur otoxicity study and a developmental neurotoxicity study (all in rats). There was no evidence of neurotoxicity in the other subchronic and chronic studies in the database.

4.2.3 Evidence of Sensitivity/Susceptibility in the Developing or Young Animal

T he re is no evidence of susceptibility following in utero exposure to rats and there are low concern and no residual uncertainties in the developmental toxicity study in rabbits, in the 2

- generation reproduction study or in the developmental neurotoxicity stu dy after establishing toxicity endpoints and traditional uncertainty factors to be used in the risk assessment.

There was no evidence of increased susceptibility in the developmental rat study as no developmental toxicity was seen at the highest dose tes ted ( l imit d ose).

There was evidence of qualitative (not quantitative) increased susceptibility in the developmental rabbit study as characterized by an increased incidence of abortions or early delivery at the l imit
d ose. It could not be ascertained if the abortions were the result of a treatment

- related effect on either the dams, the fetuses

, or both. T he degree of concern is low because the increased abortions or early delivery was seen only at the Limit Dose and the abortions may have been due

to maternal stress.Page 14 of 45

There was quantitative evidence of increased susceptibility in the two

- generation reproduction study in rats, where decreases in body weights in male offspring were seen in the F 2 generation at
a dose that was lower than the dose that ind uced parental/systemic toxicity. However, the degree of concern is low because the dose selected for chronic dietary and non

- dietary exposure risk assessments would address the concern for the body weight effects.

There also was quantitative evidence of increased susceptibility in the developmental neurotoxicity study in rats, where decreases in pup body weights on post

- natal day four (PND 4) and body weight gains (PND 1

- 4) were seen in the absence of any maternal toxicity. However, the degree of concern is low because the decreases in pup body weights seen on PND 1

- 4 (and not at any other time periods) were reversible, in that no treatment

- related effects on body weight, body weight gain or any other parameter were noted at PND 21.

HED has concluded tha t there are no residual uncertainties for pre

- and post

- natal toxicity as the degree of concern is low for the susceptibility seen in the above studies, and the dose and endpoints selected for the overall risk assessments will address the concerns for the body weight effects seen in the offspring. Although the dose selected for overall risk assessments (21.8 mg/kg/day) is higher than the NOAELs in the two

- generation reproduction study (10.1 mg/kg/day) and the developmental neurotoxicity study (14 mg/kg/day ), these differences are considered to be an artifact of the dose selection process in these studies. For example, there is a
10

- fold difference between the LOAEL (106.8 mg/kg/day) and the NOAEL (10.1 mg/kg/day) in the two generation reproduction study. A similar pattern was seen with regard to the developmental neurotoxicity study, where there is also a 10

- fold difference between the LOAEL (147 mg/kg/day) and the NOAEL (14 mg/kg/day). There is only a 2

- 3 fold difference between the LOAEL (57 mg/kg/day) and the NOAEL (21.8 mg/kg/day) in the critical study used for risk assessment. Because the gap between the NOAEL and LOAEL in the 2

- generation reproduction and developmental neurotoxicity studies was large and the effects at the LOAELs were minimal,
the t rue no

- observed

- adverse

- effect

- level was probably considerably higher. Therefore, the selection of the NOAEL of 21.8 mg/kg/day from the 1

- year dog study is conservative and appropriate for the overall risk assessments. In addition, the endpoints for risk assessment are based on thyroid effects seen in multiple species (mice, rats and dogs) and after various exposure durations (subchronic and chronic exposures) which were not observed at the LOAELs in either
the two

- generation reproduction or the developme ntal neurotoxicity studies. Based on these data, it is concluded that there are no residual uncertainties for pre

- and post

- natal toxicity (D290022 A. Levy. 09/08/2003).

4.2.4 Residual Uncertainty in the Exposure Database

There are no residual uncertain ties identified in the exposure databases. The chronic dietary food exposure assessments were performed us ing tolerance

- level residues, conservative average percent crop treated (CT) estimates for existing crops and 100% CT assumptions (for proposed

crops ). EPA made conservative (protective) assumptions in the ground and surface water modeling used to assess exposure to boscalid in drinking water. EPA used similarly conservative assumptions to assess post

- application exposure of adults and children . In addition, the residential exposure assessment is based on the updated 2012 Residential SOPs employingPage 15 of 45

surrogate study data, including conservative exposure assumptions based on Day 0 contact to turf and surfaces treated at the maximum application rate. Th ese data are reliable and are not expected to underestimate risks to adults or children. The Residential SOPs are based upon reasonable “worst

- case” assumptions and are not expected to underestimate risk. Although some
of the residue values used in the d ietary exposure assessment were slightly refined, these

assessments will not underestimate the exposure and risks posed by boscalid.

4.3 Toxic ity Endpoint and Point of Departure Selections

4.3.1 Dose

- Response Assessment

The endpoints and points of departure for this risk assessment as based on those of the previous risk assessment. The rationales for each selection, along with a detailed description of the toxicity studies used for various exposure scenarios are presented in that document (D290022. Y. Donovan 09/08/2003). Following is a summary:

Acute dietary endpoint : As there were no toxic effects attributable to a single dose, including the developmental toxicity studies, an endpoint of concern was not identified to quanti fy acute

dietary risk to the general population or to the subpopulation females 13

- 49 years old. The changes in brain morphometrics seen in the developmental neurotoxicity study were not selected as they were observed only at a dose exceeding the l imit d ose (1442 mg/kg/day). Therefore, an acute RfD was not established for any population for boscalid

.

Chronic dietary endpoint : HED selected the NOAEL of 21.8 mg/kg/day for establishing the chronic RfD based on the combined results of the following three studies: chronic rat,

c arcinogenicity rat and chronic dog. While this NOAEL is higher than the NOAELs in the 90

- day study in dogs (7.6 mg/kg/day), the two

- generation reproduction study (10.1 mg/kg/day) and the developmental neurotoxicity study (14 mg/kg/day), these differences are considered an artifact of the dose selection process in these studies as shown below:

Study NOAEL (mg/kg/day) LOAEL

(mg/kg/day) L OAEL:NOAEL

Ratio

90

- day

- dog 7.6 78.1 10.3

2

- generation reproduction

- rat 10.1 101.6 10.0 developmental neurotoxicity

- rat 14.0 147 10.5

1

- year

- dog 21.8 57.4 2.6

Because the gap between the NOAEL and LOAEL in these studies was large and the effects at the LOAELs were minimal (dog : = increased alkaline phosphatase activity and hepatic weights;
2

- generation : = decreased body weights in offspring; developmental neurotoxicity : = decrease in pup body weight gains on post

- natal days 1

- 4), the true no

- observed

- adverse

- effect

- level was probably considerably higher. Therefore, the selection of the NOAEL of 21.8 mg/ kg/day from
the 1

- year dog study is conservative and appropriate for the overall risk assessments. In addition, the endpoints for risk assessment are based on thyroid effects seen in multiple species (mice, rats and dogs) and after various exposure durati ons (subchronic and chronic exposures)Page 16 of 45

which were not observed at the LOAELs in either the two

- generation reproduction or the developmental neurotoxicity studies.

Occupational and Residential endpoints: All of the incidental oral, dermal

, and inhalation endpoints are based on the co

- critical chronic toxicity rat, carcinogenicity rat

, and 1

- year dog
studies. N either dermal nor systemic toxicity was seen at the l imit d ose (1000 mg/kg/day) in the
28

- day dermal toxicity study in rats. T he ora l NOAEL of 21.8 mg/kg/day was selected to be protective of the decreases in the body weight seen in the offspring in the two

- generation reproduction and the developmental neurotoxicity studies. Additionally, this dose is protective
of the thyroid and hepa totoxicity seen via the oral route in multiple species (mice, rats and dogs) after various exposure durations (90

- day, 1

- year and 2

- years). There are no concerns that the effects will worsen following longer treatment.

For the dermal endpoints, a dermal study is available; however, the selected endpoint addresses potential effects on offspring, which are not normally examined in the dermal study. This endpoint is likely to be conservative because no systemic effects were observed in the dermal study up t o the limit dose of 1000 mg/kg/day. In the reproduction study, the parental NOAEL is 112.6/1180.8 mg/kg/day based on decreases in body weight as well as hepatocyte degeneration in males only. No such effects were observed in the 28

- day dermal study.

The use of an oral POD for inhalation exposure results in MOEs as low as 370 for occupational exposure, which does not meet the target MOE of 1000 for a waiver (TXR0056585

, K. Rury

, 03/04/2013). Therefore

, a 10X database uncertainty factor has been added for inhalation

exposures.

4.3.2 Recommendation for Combining Routes of Exposure for Risk Assessment

W hen there are potential exposures to a pesticide, aggregate risk assessment must consider exposures from three major sources: oral, dermal and inhalation ex posures. Since all endpoints
are from the same stud ies , exposures from oral, dermal and inhalation exposure routes can be aggregated.

4.3.3 Cancer Classification and Risk Assessment Recommendation

The Cancer Assessment Review Committee (CARC) classified boscalid as “suggestive evidence of carcinogenicity, but not sufficient to assess human carcinogenic potential”, and, therefore, the quantification of human cancer risk is not recommended (TXR 0051289

, J. Kidwell

, 11/14/2002 )

. The classification was based on data which were combined from two 2

- year rat studies where males had a significant increasing trend and significant differences in pair

- wise comparison with the controls for thyroid follicular cell adenomas. The increased incidence of these adenomas exceeded the historical control mean and range. This was supported by thyroid hypertrophy and hyperplasia of follicular cells, increased thyroid weights and mechanistic data. Combined study data for female rats showed only a borderline significant increasing trend for thyroid follicular
cell adenomas. No increase over 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

mu tagenic studies were negative with or without activation. Based on the overall weak evidencePage 17 of 45

of carcinogenic effects, the CARC indicated that a dose

- response assessment for cancer (either
linear low

- dose extrapolation or margin of exposure calculation) wa s not needed.

4.3.4 Summary of Points of Departure and Toxicity Endpoints Used in Human Risk
Assessment

Table 4. 3 .4.1

. Summary of Toxicological Doses and Endpoints for Boscalid for Use in Dietary and Non

Occupational Human Health Risk Assessments.

Expos ure/
Scenario Point of

Departure Uncertainty/F

QPA Safety
Factors RfD, PAD,

Level of
Concern for
Risk
Assessment Study and Toxicological Effects

Acute Dietary (All Populations, including Infants and
Children and Females
13

- 49 years of age) NA NA NA No appropriate endpoint attributable to a single dose was not identified

Chronic Dietary (All Populations) NOAEL=

21.8 mg/kg/day UF A = 10x

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

0.218 mg/kg/day
cPAD = 0.218 mg/kg/day Co

- critical chronic rat, carcinogenicity rat,

and 1

- year dog studies
LOAEL = 57

- 58 mg/kg/day based on liver and thyroid effects

Incidental Oral
Short

- Term (1

- 30 days) &
Intermediate

- Term (1

- 6 months) NOAEL=

21.8 mg/kg/day UF A = 10x

UF H =10x FQPA SF= 1x Residential

LOC for MOE
= 100 Co

- critical chronic rat, carcinogenicity rat,

and 1

- year dog studies
LOAEL = 57

- 58 mg/kg/day based on liver and thyroid effects

Dermal Short

- Term (1

- 30 days) &
Intermediate

- Term (1

- 6 months) NOAEL=

21.8 mg/kg/day UF A = 10x

UF H =10x FQPA SF= 1x Residential

LOC for MOE
= 100 Co

- critical chronic rat, carcinogenicity rat,

and 1

- year dog studies
LOAEL = 57

- 58 mg/kg/day based on liver and thyroid effects
Inhalation a Short

Term (1

- 30 days)
& Intermediate

Term (1

- 6 months) NOAEL=

21.8 mg/kg/day UF A = 10x

UF H = 10x
UF DB = 10x FQPA SF= 1x Residential

LOC for MOE
= 10 0 0 Co

- critical chronic rat, carcinogenicity rat,

and 1

- year dog studies
LOAEL = 57

- 58 mg/kg/day based on liver and thyroid effects Cancer (oral, dermal, inhalation) Classification: “suggestive evidence of carcinogenicity, but not sufficient to assess human

carcinogenic potential”; quantification of human cancer risk is not recommended. Point of Departure (POD) = A data point or an estimated point that is derived fr om observed dose

- response data and used to mark the beginning of extrapolation to determine risk associated with lower environmentally relevant human exposures. NOAEL = no observed adverse effect level. LOAEL = lowest observed adverse effect level. UF = uncertainty factor. UF A = extrapolation from animal to human (interspecies). UF H = potential variation in sensitivity among members of the human population (intraspecies). UF DB = to account for the absence of key data (i.e., lack of a critical study). FQPA SF = FQPA Safety Factor. PAD = population adjusted dose (a = acute, c = chronic). RfD = reference dose. MOE = margin of exposure. LOC = level of concern. N/A = not applicable. a = Inhalation toxicity assumed to be equivalent to oral toxicity.Page 18 of 45

Table 4. 3 .4.2

. Summary of Toxicological Doses and Endpoints for Boscalid for Use in Occupational Human
Health Risk Assessments

Exposure/
Scenario Point of

Departure Uncertainty

Factors Level of Concern

for Risk
Assessment Study and Toxicological Effects

Dermal Short

Term (1

- 30 days) and
Intermediate

Term (1

- 6 months)
DAF = 15% NOAEL=

21.8 mg/kg/day UF A = 10x

UF H =10x FQPA SF= 1x Occupation al

LOC for MOE =
100 Co

- critical chronic rat, carcinogenicity rat,

and 1

- year dog studies
LOAEL = 57

- 58 mg/kg/day based on liver and thyroid effects

Inhalation a Short

- Term (1

- 30 days) and
Intermediate

term (1

- 6 months) NOAEL=

21.8 mg/kg/day UF A = 10x

UF H =10x
UF DB = 10x FQPA SF= 1x Occupation al

LOC for MOE =
100 0 Co

- critical chronic rat, carcinogenicity rat,

and 1

- year dog studies
LOAEL = 57

- 58 mg/kg/day based on liver and thyroid effects

Cancer (oral, dermal, inhalation) Classification: “suggestive evidence of carcinogenicity, but not sufficient to assess human

carcinogenic potential”; quantification of human cancer risk is not recommended.

Point of Departure (POD) = A data point or an estimated point that is derived fr om observed dose

- response data and used to mark the beginning of extrapolation to determine risk associated with lower environmentally relevant human exposures. NOAEL = no observed adverse effect level. LOAEL = lowest observed adverse effect level. UF = uncertainty factor. UF A = extrapolation from animal to human (interspecies). UF H = potential variation in sensitivity among members of the human population (intraspecies). UF DB = to account for the absence of key data (i.e., lack of a critical study). MOE = margin of exposure. LOC = level of concern. N/A = not applicable.

. a = Inhalation toxicity assumed to be equivalent to oral toxicity.

5.0 Dietary Exposure and Risk Assessment

5.1 Residues of Concern Summary and Rationale

The residues of concern for dietary risk assessment and the tolerance expression are summarized
in Table 5.1 (HED MARC, D2 86786

, M

. Nelson

, 0 1/ 0 9/ 20 0 3 )

. HED has concluded that the residue of concern in plants i s boscalid for purposes of tolerance enforcement and risk

ass essment. T he nature of boscalid residues in livestock is adequately understood

, based upon acceptable 14 C metabolism studies conducted on lactating goat s and laying hens. In both goat s and hen s , parent boscalid, M510F01 (hydroxy met abolite), and M510F02 (M510F01 glucuronide) were identified as the major residues, each with ≥10% TRR. N o amide bridge cleavage products were identified. Based on the structural similarity of boscalid and M510F 01, and the fact that the enzymatic hydroly sis step in the proposed enforcement method will release M510F 02 back to free M510F 01, HED concluded that the combined residues of parent
boscalid , M510F 01 and M510F02 are the residues of concern in livestock matrices for purposes
of risk assessment and the tolerance expression.

For drinking water, the resid u e of concern for boscalid is the parent only.Page 19 of 45

Table 5.1. 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 Boscalid Boscalid

Rotational Crop Boscalid Boscalid

Livestock (Ruminants and Poultry) Boscalid, M510F01 & M510F02 Boscalid, M510F01 & M510F02

Drinking Water Boscalid Not Applicable

5 .2 Food Residue Profile

IR

- 4 submitted field trial data on basil (MRID 47014803), chives (MRID 47014802), and dill (MRID 47014801). The data reflect the proposed use patterns. The number of trials and geographic distribution are acceptable. The analytical method used is adequate for determination of the residue of concern, and the samples were stored frozen for intervals supported by the storage stability results. A summary of the residue data from the crop field trials is prese nted in Appendix F, Table F.1. The existing field trial data for the crop group conversions are adequate.

Processed Food and Feed
Basil from each of the four field trials was dried. The median processing factor for the conversion of fresh basil to dry basil is 6.0 X . The four processing studies conducted for the production of dried basil are adequate to estimate a processing factor for the boscalid residue. In each of the trials, the fresh basil contained quantifiable residues of boscalid.

Livestock
T here are no feed items associated with dill seed or herbs from the herb subgroup 19A

. Therefore, the previous livestock dietary intake calculations and resulting tolerance recommendations are not changed.

Rotational Crops Adequate limited and extensive field rotational crop studies are available supporting the existing tolerances for indirect residues in rotational crops. These data support the label

- specific plant

back interval of 14 days for crops without boscalid uses. No additional rotational crop data are required for purposes of this petition.

5.3 Water Residue Profile

EFED determined that a new drinking water assessment is not needed for the proposed new uses
on herbs and dill (E. Arnold , Email to S. Funk, 07/08/ 2014)

, and the EDWC values determined
with the last assessment (D409880, K. White, 04/17/2013) should be used i n the current dietary
risk assessment

. These EDWCs were incorporated directly into th e dietary assessment. Water residues were incorporated in the DEEM

- FCID into the food categories “water, direct, all sources” and “water, indirect, all sources.”Page 20 of 45

The drinking water assessment considered new uses and a ll existing uses. Surface water
estim ated drinking water concentrations ( EDWC ) were determined in previous assessments. See Tier I Drinking Water Exposure Assessment for the Section 3 New Use of Boscalid on Various Agricultural Crops Including Cranberries ( White, 2012, D4050 64 ) for a discussion of modeling and estimating surface water concentrations. The EDWCs for boscalid in surface water were calculated using the screening model FIRST (FQPA Index Reservoir Screening Tool; v.1.1.1; dated 03/25/08)

. Screening Concentrati on in Ground Water (SCI

- GROW v2.3, Jul. 29, 2003) is a regression model used as a screening tool to estimate pesticide concentrations found in ground

water used as drinking water. Tier 1 ground water EDWCs for boscalid were derived with
PRZM

- GW (Pesticide Root Zone Model for Ground W ater, version 1.0, August 31, 2012 ), using
the GW

- GUI (Graphical User Interface, version 1.0, August 31, 2012 ). PRZM

- GW is a one

dimensional, finite

- difference model that estimates the conc entrations of pesticides in groundwater. It accounts for pesticide fate in the crop root zone by simulating pesticide transport and degradation through the soil profile after a pesticide is applied to an agricultural field.
PRZM

- GW permits the assessment of multiple years of pesticide application (up to 100 years) on a single site. Six standard scenarios, each representing a different region known to be vulnerable to ground water contaminations, are available for use with PRZM

- GW for risk assessment purp oses.

The maximum Tier 1 estimated chronic ground water EDWC is 697 ppb. The maximum Tier 1
estimated chronic surface water EDWC is 26.4 ppb. This is based on turf use. The ground water value is higher than the surface water value and was therefore use d in the assessment. The EFED models and their descriptions are available at the EPA internet site : http://www.epa.gov/oppefed1/models/water/

. See Table 5.3.1

.

Table 5.3.1

. Tier I EDWCs B ased on B oscalid U se on Turf

. 1

Source of Drinking Water Acute (μg/L) Annual Average or Post Breakthrough Average (μg/L)

Surface water 97.3 26.4
Ground water 773 697

1 These are the highest EDWCs for the proposed and relevant previously evaluated use scenarios.

5.4 Dietary Risk Assessment

5.4.1 Description of Residue Data Used in Dietary Assessment

The dietary exposure analysis incorporates all current and proposed tolerances for residues of
boscalid , including its metabolites and degradates.

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

.

The chronic dietary assessment is slightly refined. The chronic dietary exposure and risk
assessment is based on tolerance

- level residues for all commodities . The data used in the 2 013 dietary assessments were also used in this current analysis except for the addition of tolerances
fo r herb subgroup 19A and dill seed. BEAD has provided %CT information for boscalid ( S.Page 21 of 45

Haddad, BEAD, 02/19/2014). As a refinement, the weighted average %CT was incorporated

. One hundred percent crop treated was assumed for commodities with out % CT data. Note that %CT was not incorporated in the previous (2 013) assessment, i.e., 100% CT was assumed for all
commodities.

Crop group conversions included a consideration of harmonization of tolerances with Codex
MRLs and/or Canadian MRLs . This resulted in no changes in tolerances

.

A value of 0.5 ppm was used for honey, based on the existing tolerance in the European Union.

No new experimental processing data were incorporated into this analysis. The processing factors from earlier dietary assessments were derived as follows. For processed commodities where data were available to show no concentration (apple juice, dried plum prunes , rice bran, wheat flour, sunflower oil, mint oil, tomato puree, tomato juice, soybean oil

, and cottonseed oil), the processing factor was set to 1. For processed commodities where the raw agricultural commodity ( RAC ) tolerance is adequate to cover the very slight concentration seen in the processing study (wheat germ, wheat bran, and tomato paste), the residue was set at the RAC level and the proces sing factor was reduced to 1. For processed commodities with established tolerances (raisin, peanut oil , and citrus oil ), the processed commodity tolerance was used and the processing factor was set to 1.0

. For all other processed commodities for which d ata were not available, DEEM (version 7.81) processing factors were used ( DP336633, D. Davis, 12/17/2007).

Boscalid is classified as “ not lik ely to be carcinogenic to humans”

. Therefore, a cancer dietary exposure assessment was not conducted.

5.4.2 Perc ent Crop Treated Used in Dietary Assessment

BEAD has provided percent crop treated information for boscalid ( S. Haddad , BEAD,
0 2 / 19 /201 4 ). As a refinement, the weighted average %CT was incorporated

. One hundred percent crop treated was assumed for commodities with no % CT data.

The following average percent crop treated estimates were used in the chronic dietary risk assessments for the crops that are currently registered for boscalid: almonds 40% ; apples 15%; apricots 25%; green beans 5%; blueberries 35%; broccoli <2.5%; cabbage 5%; caneberries 45%; cantaloupes 5%; carrots 15%; cauliflower 5%; celery 5%; cherries 45%; cucumbers 5%; dry beans/dry peas <2.5%; garlic 5%; grapes 30%; hazelnuts 5%; let tuce 25%; nectarines 15%; onions 20%; oranges <1%; peaches 20%; peanuts <1%; pears 15%; green peas <1%; peppers <2.5%; pistachios 30%; plums/prunes 5%; potatoes 20%; pumpkins 10%; squash 5%;
strawberries 60 %; sugar beets <1%; tomatoes 5%; walnuts <1%; wat ermelons 25%.

5.4.3 Acute Dietary Risk Assessment

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

.Page 22 of 45

5.4.4 Chronic Dietary Risk Asses sment s

Boscalid exposure from the existing uses and the proposed new uses on dill seed and the herbs of crop subgroup 19A results in estimated risk s that are below the Agency’s level of concern for food plus drinking water. The highest exposure and risk estimates for food plus drinking water
utilized 1 2 % of the chronic population adjusted dose (cPAD) for the U.S. population and 2 6 %
for all infants (< 1 year old ) , the most highly exposed population subgroup.

5.4. 5 Summary Table

Table 5. 4. 5. Summary of Dietary (Food and Drinking Water) Exposure and Risk for Boscalid 1,2

Population Subgroup Acute Dietary Chronic Dietary

Dietary Exposure (mg/kg/day) % aPAD Dietary Exposure (mg/kg/day) % cPAD

General U.S. Population

N/A N/A 0.025787 1 2

All Infants (< 1 year old) 0.055525 2 6

Children 1

- 2 years old 0.053267 24

Children 3

- 5 years old 0.041445 19

Children 6

- 12 years old 0.025564 1 2

Youth 13

- 19 years old 0.018134 8.3

Adults 20

- 49 years old 0.024325 11

Adults 50

- 99 years old 0.024330 11

Females 13

- 49 years old 0.024334 11

1 The population subgroup with the highest estimated chronic dietary (food + drinking water) exposure and risk is indicated by
bold text.

2 NA = not applicable

.

6.0 Residential (Non

- Occupational) Exposure/Risk Characterization

The re are no residential uses proposed for boscalid with this action. However, there are existing residential uses on golf course turf

, ornamentals and garden landscapes, and on residential fruit and nut trees. These existing residential uses were assessed in the last HED exposure and risk assessment to reflect updates to HED’s 2012 Residential SOPs 2 along with policy changes for body weight assumptions ( D405063, B. O’Keefe, 0 8/22/2013). Registered products do not lead to any residential handler or residential post

- application risk estimates of concern. In order to incorporate residential exposure into the short

- term aggregate risk assessment, a summary of the residential exp osure and risk estimates resulting from the residential uses of boscalid are provided below.

2 Available: http://www.epa.gov/pesticides/science/residential

- exposure

- sop.htmlPage 23 of 45

6.1 Residential Handler Exposure

The residential handler assessment include d short

- term exposures via the dermal and inhalation

routes from treating gardens and trees (D405533, C. Wall s , 04 / 30/13)

. Intermediate

- term exposures are not likely because of the intermittent nature of applications by residential handlers.

The LOC for residential dermal exposure is an MOE of 100. For inhalation exposures, an
additional 10X uncertainty factor is added because of the database gap for lack of an available subchronic inhalation toxicity study. Therefore, the total uncertainty factor that has been applied
to the inhalation assessments of boscalid is 1000X for residential ha ndler inhalation exposure (i.e., LOC is an MOE = 1000).

Dermal and inhalation risk estimates were co mbined because the PODs are based on the same toxicological study, thus the effects for th ese exposure routes are the same . Dermal and inhalation risk estimates were combined using the total ARI methodology since the LOCs for dermal exposure (100) and inhalation exposure (1

, 000) ar e different. The LOC ARI is 1; therefore, ARIs of less than 1 are risk estimates of concern.

Detail s of the inhalation and dermal exposure risk estimates for residential handlers a re included
in Appendix D

. The maximum application rate for each exposure scenario is presented as the
worst case scenario. The residential handler ARIs range from 2 4 to 330 . The refore, the dermal
and inhalation risk estimate s to residential handlers are not of concern to HED for any of the
residential handler scenarios.

6.2 Post

- Application Exposure

There is the potential for dermal post

- application exposure for individuals as result of being in an environment that has been previously treated with boscalid . Short

- term dermal exposures were previously assessed for adults, youth 11 to 16 years old, and children 6 to 11 years old. All the
short

- term MOEs for each scenario are greater than the LOC of 100 , ranging from 690 to 16,000

, and therefore are not of concern (D405533, C. Walls, 04/30/13)

. Detail s of the residential dermal post

- application exposure risk estimates a re included in A ppendix D

. A TTR study is not required at this time for boscalid since the lowest dermal MOE (10,000) is greater than 10 times the LOC based on default values for the fraction of application rate available for transfer after a turf application. Additiona lly, DFR studies are not required at this time for boscalid since the lowest dermal MOE (690) is greater than two times the LOC based on default input values.

Turf Transferrable Residue (TTR) Data
In accordance with 40 CFR § 158, TTR data are required for all occupational (e.g., sod farms, golf courses, parks, and recreational areas) or residential turf uses that could result in post

application exposure to turf. In the absence of chemical

- specific TTR data, EPA uses default
values. The 2012 Standard Operating Procedures for Residential Pesticide Exposure
Assessment includes an analysis of all TTR data, available at the time, which resulted in the selection of revised liquid and granular default values for the fraction of the application rate
availabl e for transfer after a turf application (F AR ). These values are based on an analysis of 59Page 24 of 45

TTR studies performed with the Modified California Roller Method (36 studies using liquids, 11 studies using wettable powders/water dispersible granules, and 12 stu dies using granules). The liquid results (N=131) indicate a range of F AR values from 0.0005% to 6.1% and the granular results (N=37) indicate a range of 0.00064% to 0.69%. In both the liquid and granular data, a large range of transferability is observed and this variability can potentially be attributable to many factors such as active ingredient; formulation; field conditions in the studies; weather conditions (e.g., humidity); or many other difficult to quantify factors. Although witnessed
across mult iple chemicals, this range in F AR values is not expected when considering TTR data for a single chemical. HED selected 1% and 0.2% as high

- end default values for liquid and granular products, respectively. Because TTR data are not available for boscalid

, EPA is using
the default value of 1% for liquid boscalid product s

. Although there may be a small degree of uncertainty in the use of the default TTR value for boscalid (i.e., there is a small chance that the
F AR value may exceed the applicable default va lue ), it is likely that the health

- protective aspects of EPA’s residential post

- application turf assessment methodology will more than compensate for this potential uncertainty (i.e., the methodology is likely to overestimate exposure by a factor greater than the factor than the highest measured F AR values exceed the defaults ). For example, when assessing residential post

- application turf exposure, EPA assumes the following: exposures

occur to zero

- day (i.e., day of application ) residues every day of th e assessed exposure duration (i.e., EPA assumes that no dissipation or degradation occurs, it doesn’t rain, the grass is not mowed, etc); individuals perform the same post

- application activities performed in the turf transfer coefficient study day after da y (e.g., tumbling, playing on turf with toys, etc.); and individuals engage in these post

- application activities for a high

- end amount of time every day that is represented by data reflecting time children spend outdoors and not specifically engaged
in act ivities on turf, when in actuality children do not spend all of their outdoor time on turf and high

- end levels of activity will not occur every day.

Given the conservatisms discussed above and the potential compounding nature of these conservatisms, EPA is able to rely upon the calculated exposure estimates with confidence that exposure is not being underestimated. Since the estimated residential turf post

- application

exposure for golfers using default TTR values for boscalid is minimal in comparison to the level of concern (i.e., the calculated MOE is greater than 10 times higher than the level of concern,
lowest dermal MOE = 10,000 compared to the LOC of 100 ); EPA is waiving the 40 CFR §158 TTR data requirement. In this instance, it is unlikely that ch emical

- specific TTR data would be needed to further refine exposure assessments or would add appreciably to our general understanding of the availability of turf transferable pesticide residues for boscalid.

D islodgeable Foliar Residue (DFR) Data
In accor dance with 40 CFR § 158, DFR data are required for all occupational (e.g., crop, nursery, greenhouse use sites) or residential (e.g., ornamental and vegetable gardens, pick your own farms, retail tree farms) uses that could result in post

- application exposu re to foliage. In the
absence of chemical

- specific DFR data, EPA uses default values. The 2012 Standard Operating Procedures for Residential Pesticide Exposure Assessment includes an analysis of a number of DFR studies, which resulted in the selection of a revised default values for the fraction of the application rate available for transfer after a foliar application (F AR ). These values are based on an analysis of 19 DFR studies. Since that time, the Agricultural Re

- entry Task Force has
submitted infor mation (MRID 49299201) that corrects an application rate error made in thePage 25 of 45

original submission of “ARF039

– Determination of Dermal and Inhalation Exposure to Reentry Workers During Chrysanthemum Pinching in a Greenhouse” (EPA MRID 45344501). As a result, the range of F AR values was revised from 2%

- 89% to 2%

- 47%. In the data, a large range of transferability is observed and this variability can potentially be attributable to many factors such as active ingredient; formulation; field conditions in the studies; weather conditions (e.g., humidity); or many other difficult to quantify factors. Although witnessed across multiple chemicals, this range in F AR values is not expected when considering DFR data for a single chemical. At this time, the ARTF subm ission did not alter the selection of 25% as the reasonable, high

- end default value. Because DFR data are not available for boscalid , EPA is using the default value of 25%. Although there may be a small degree of uncertainty in the use
of the default DFR value for boscalid (i.e., there is a small chance that the F AR value may exceed the applicable default value ), it is likely that the health

- protective aspects of EPA’s residential
post

- application assessment methodology will more than compensate for this potential uncertainty. For example, when assessing residential post

- application exposure to gardens and ornamentals, EPA assumes the following: exposures occur to zero

- day (i.e., day of application ) residues every day of the assessed exposure duration (i .e., EPA assumes that no dissipation or degradation occurs, it doesn’t rain, etc); individuals perform the same post

- application activities performed in the transfer coefficient study day after day (e.g., weeding, harvesting, pruning, etc.); and individual s engage in these post

- application activities for a high

- end amount of time every day (represented by data reflecting time spent gardening based on survey data).

Given the conservatisms discussed above and the potential compounding nature of these conservatisms, EPA is able to rely upon the calculated exposure estimates with confidence that exposure is not being underestimated. Since the estimated residential post

- application exposure
for residential gardens using default DFR values for boscalid is minimal in comparison to the level of concern (i.e., the calculated MOE is greater than 2 times higher than the level of

concern, MOE = 690 compared to the LOC of 100 ); EPA is waiving the 40 CFR §158 DFR data requirement. In this instance, it is unlikely that chemical

- specific DFR data would be needed to further refine exposure assessments or would add appreciably to our overall understanding of the availability of dislodgeable foliar pesticide residu es for boscalid

.

6.3 Combined Residential Risk Estimates (Multiple Exposure Scenarios)

Because dermal post

- application exposure s to treated gardens , fruit or nut trees, and turf could conceivably co

- occur within the same day for adult s and child ren 6 t o 11 year olds , combined

exposures from these scenarios were co nsidered

. However, all four of these use sites/scenarios are proposed on different labeled products containing boscalid; therefore, the probability of co

occurrence is considered improbable. Therefore, assessments of these combined exposures were
not conducted.

6.4 Residential Risk Estimates for Use in Aggregate Assessment

The scenarios with the highest exposures and corresponding lowest MOEs

, provided in Appendix D, reflect the residential risk estimates that are recommended for use in the agg regate assessment for boscalid. Table 6.4 presents the residential risk estimates that are recommended for use in the agg regate assessment for boscalid

.Page 26 of 45

 The recommended residential de rmal exposure for use in the adult aggregate assessment reflects dermal exposure from post

- application activities on treated gardens.

 The recommended residential dermal exposure for use in the youth (11

- 16 yr) aggregate assessment reflects dermal exposure from post

- application golfing on treated turf

.

 The recommended residential dermal exposure for use in the child (6

- 11 yr) aggregate assessment reflects dermal exposure from post

- application activities in trea ted gardens.

Table 6. 4 . Recommendations for the Residential Exposures for the Boscalid Short

- term Aggregate Assessments.

Lifestage Route of

Exposure Scenario Dose 1 (mg/kg/day) MOE 2

Adult Dermal Post

- application activities in treated gardens 0.032 6 8 0

Youth (11

- 16 yr old ) Dermal Post

- application golfing on treated turf 0.0018 12,000

Child (6

- 11 yr old ) Dermal Post

- application activities in treated gardens 0.022 99 0

1 Daily Dose = See T able D

. 2 in Appendix D for adult handler scenarios and Table 6.2 for post

- application scenarios.

2 MOE = NOAEL (21.8 mg/kg/day) ÷ Daily Dose

6.5 Residential Bystander Post

- application Inhalation Exposure

Volatilization of pesticides may be a source of post

- application inhalation exposure to individuals nearby pesticide applications. The agency sought expert advice and input on issues related to volatilization of pesticides from its Federal Insecticide, Fu ngicide, and Rodenticide Act Scientific Advisory Panel (SAP) in December 2009, and received the SAP’s final report on March 2, 2010 (http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html). The agency has evaluated the SAP report and has develope d a Volatilization Screening Tool and a subsequent Volatilization Screening Analysis (http://www.regulations.gov/#!docketDetail;D=EPA

- HQ

- OPP

- 2014

- 0219). During Registration Review, the agency will utilize this analysis to determine if data (i.e., flux

st udies, route

- specific inhalation toxicological studies) or further analysis is required for
boscalid.

6.6 Spray Drift

Spray drift is a potential source of exposure to those nearby pesticide applications. This is particularly the case with aerial applica tion, but, to a lesser extent, spray drift can also be a potential source of exposure from the ground application methods (e.g., groundboom and airblast) employed for boscalid. The agency has been working with the Spray Drift Task Force (a task force comp osed of various registrants which was developed as a result of a Data Call

- In issued by EPA), EPA Regional Offices and State Lead Agencies for pesticide regulation and other parties to develop the best spray drift management practices (see the agency’s Spr ay Drift website for more information). 3 The agency has also developed a policy on how to appropriately consider spray drift as a potential source of exposure in risk assessments for pesticides. The potential for spray drift will be quantitatively evaluated for each pesticide during
the Regist ration Review process which ensures that all uses for that pesticide will be considered

3 Available: http://www.epa.gov/opp0 0001/factsheets/spraydrift.htmPage 27 of 45

concurrently. The approach is outlined in the revised (2012) Standard Operating Procedures For Residential Risk Assessment (SOPs)

- Residential Exposure Assessment Sta ndard Operating Procedures Addenda 1: Consideration of Spray Drift. This document outlines the quantification
of indirect non

- occupational exposure to drift.

7.0 Aggregate Exposure/Risk Characterization

In accordance with FQPA, HED must consider and aggrega te (add) pesticide exposures and risks from three major sources: food, drinking water, and residential exposures. In an aggregate assessment, exposures from relevant sources are added together and compared to quantitative estimates of hazard (e.g., a NOAE L or PAD), or the risks themselves can be aggregated. When aggregating exposures and risks from various sources, HED considers both the route and duration of exposure. For boscalid , potential exposures from food, drinking water, and
residential scenarios were aggregated.

7.1 Acute Aggregate Risk

The aggregate acute risk estimates include exposure to residues of boscalid in food and drinking water, and does not include dermal, inhalation

, or incidental oral exposure. However, since no
observed effects could be attributed to a single dose, an acute endpoint was not established. Therefore, an acute dietary exposure assessment was not conducted.

7.2 Short

- Term Aggregate Risk

There is potential short

- term exposure to boscalid via dietary (which is considered background exposure) and residential (which is considered primary) exposure pathways. For adults, these pathways lead to exposure via oral (background) as well as dermal and inhalation (primary)
routes. The most conserva tive scenario s w ere chosen for each. For a description of the residential exposure scenarios considered in the aggregate assessment, see Section 6.4.

The short

- term aggregate MOE s are 4 6 0 for children 6 to 11 years old, 1, 1 00 for youths 11 to 16 years old, and 38 0 for adults. None of these aggregate risk estimates are of concern to HED.

Table 7.2.1

. Short

- Term Aggregate Risk Calculations

Lifestage Residential Exposure
Scenario Dermal Exposure Oral Exposure Total
Combined
MOE 2 NOAEL mg/kg/day Exposure

mg/kg/day MOE 1 NOAEL mg/kg/day Chronic Dietary

(Food + Water) mg/kg/day MOE 1

Child 6

- 11 yrs Post

- application activities

in treated gardens 21.8 0.022 990 21.8 0.0 25564 850 460

Youth 11

- 16 yrs Post

- application golfing on
treated turf 21.8 0.0018 12,000 21.8 0.0 18134 1,200 1,10 0

Adult Post

- application activities

in treated gardens 21.8 0.032 680 21.8 0.0 2 5787 845 38 0

1 The Level of Concern MOE is 100.

2 Total Combined MOE = 1/ [(1/MOE Dermal ) + (1/MOE Oral )]Page 28 of 45

7.3 Chronic Aggregate Risk

Chronic exposure from the residential pathway is not anticipated based on the current boscalid use pattern. The chronic aggregate risk (food and drinking water) is below HED’s LOC (i.e.,
<100% cPAD for the general U.S. populati on and all population subgroups )

. The dietary exposure is estimated at 0.0 25 787 mg/kg/day for the general U.S. population ( 12 % of the cPAD)
and 0. 055525 mg/kg/day ( 26 % of the cPAD) for all infants < 1 year old, the population subgroup with the highest estimated chronic dietary exposure to boscalid . See Section 5. 4.4 for details.

8.0 Cumulative Exposure/Risk Characterization

Unlike other pesticides for which EPA has followed a cumulative risk approach b ased 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 by other substances. For the purposes of this toler ance action, therefore, EPA has not
assumed that boscalid has a common mechanism of toxicity with other substances. For information regarding EPA’s efforts to determine which chemicals have a common mechanism of toxicity and to evaluate the cumulative eff ects of such chemicals, see the policy statements released by EPA’s Office of Pesticide Programs concerning common mechanism determinations and procedures for cumulating effects from substances found to have a common mechanism on EPA’s website at http://ww w.epa.gov/pesticides/cumulative/.

9.0 Occupational Exposure/Risk Characterization

Boscalid is proposed for new uses on dill seed and herb subgroup 19A. Application methods, maximum application rates, and use sites are summarized in Section 3.3 and Table 3.3 . Based on the proposed use pattern s , there is a potential for short

- and intermediate

- term occupational exposure to boscalid during handling (mixing, loading, and applying) and post

- application
activities. Boscalid use is propos ed for up to two applicat ions, with a minimum retreatment interval of 7 days. Additionally, for both dermal and inhalation exposures the same endpoint and point of departure were selected for short

- and intermediate

- term durations, and therefore, short

term exposure and risk estimates are considered to be protective of intermediate

- term exposure and risk estimates

. The proposed label require s occupational handlers to wear the following PPE: long

- sleeved shirts, long pants, chemical resistant gloves, and shoes plus socks . The 12 hour REI listed on the label is appropriate.

9.1 Short

- /Intermediate

- Term Handler Risk

HED uses the term handlers to describe those individuals who are involved in the pesticide application process. HED believes that there are distinct job functio ns or tasks related to applications and exposures can vary depending on the specifics of each task. Job requirements (amount of chemical used in each application), the kinds of equipment used, the target being treated, and the level of protection used by a handler can cause exposure levels to differ in a manner specific to each application event.Page 29 of 45

Based on the anticipated use patterns from the proposed label, types of equipment and techniques that can potentially be used, occupational handler exposure is expected from the proposed uses. HED’s LOC for the MOE is defined by the uncertainty factors that are applied to the assessment. HED applies a 10X fa ctor to account for variability among species and a 10X factor to account for variability within species. The total uncertainty factor that has been applied to the boscalid occupational dermal exposure assessment is 100X. Occupational dermal exposure and risk resulting in MOEs greater than or equal to 100 will not be of concern to HED.

For inhalation exposures, an additional 10X uncertainty factor is added because of the lack of an
available subchronic inhalation toxicity study. Therefore, the total u ncertainty factor that has been applied to the non

- cancer inhalation assessments of boscalid is 1000X for residential handler exposure. Occupational inhalation exposure and risk resulting in MOEs greater than or equal to 1000 will not be of concern to HED (LOC = 1000).

Dermal and inhalation risk estimates were co mbined in this assessment because the PODs are
based on the same toxicological study, thus the effects for th ese exposure routes are the same

. Dermal and inhalation risk estimates were combined using the total aggregated risk index (ARI) methodology since the LOCs for dermal exposure (100) and inhalation exposure (1

, 000) ar e different. The LOC ARI is 1; therefore, ARIs of less than 1 are risk estimates of concern.

Summaries of the short

- and intermediate

- term risk estimate s for occupational handlers applying
boscalid are provided in Appendix E

, Table E

. 1

. The dermal MOEs range from 1 5 0 (mixing/loading /applying of WDG formulation to support applications by mechanically pressurized handgun ) to 5

, 5 00 ( for applying with aerial equipment) at baseline PPE. All of the dermal MOEs are greater than the LOC of 100 when assessed using labeled PPE (baseline + gloves) and are not a concern to HED.

The inhalation MOEs range from 1 ,9 00 (mixing/loadi ng of WDG formulation to support aerial and chemigation applications) to 3,5 00,000 (applying with aerial equipment ) at baseline PPE (no respirator). All of the inhalation MOEs are greater than the LOC of 1

, 00 0 when assessed at baseline PPE and are not a c oncern to HED. F urthermore, all of the ARIs for combined dermal and inhalation exposures all scenarios are greater than 1.0 (range from 1.3 to 480) when assessed using labeled PPE (baseline + gloves)

, and are not a concern to HED.

9.2 Short

- and Intermediate

- Term Post

- Application Risk

HED uses the term post

- application to describe exposures that occur when individuals are present in an environment that has been previously treated with a pesticide (also referred to as re

entry exposure). Such exp osures may occur when workers enter previously treated areas to perform job functions, including activities related to crop production, such as scouting for pests or harvesting. Post

- application exposure levels vary over time and depend on such things as the type of activity, the nature of the crop or target that was treated, the type of pesticide application, and the chemical’s degradation properties. In addition, the timing of pesticide applications, relative to harvest activities, can greatly reduce th e potential for post

- application exposure.Page 30 of 45

9.2.1 Dermal Post

- Application Risk

Based on the proposed use patterns, short

- and intermediate

- term post

- application dermal exposures to workers re

- entering treated areas is possible. Therefore, a post

- appli cation risk

assessment for dermal exposures is needed

All post

- application scenarios resulted in MOEs greater than 100 on day 0 (12 hours after application) and therefore are not of concern to HED . The MOEs for boscalid ranged from 9 40
to 2 6 ,000. DFR studies are not required at this time for boscalid since the lowest dermal MOE (400) for all existing or proposed crops is greater than two times the LOC based on default input
values. The short

- and intermediate

- term non

- cancer post

- application risk estimates for workers are provided in Appendix E , Table E .2

.

Turf Transferrable Residue (TTR) Data
I n accordance with 40 CFR § 158, TTR data are required for all occupational (e.g., sod farms, golf courses, parks, and recreational areas) or residential turf uses that could result in post

application exposure to turf. In the absence of chemical

- specific TTR data, EPA uses default
values. As detailed in the Residential Post

- Application section of this document for existing use of boscalid on golf course turf

, the estimated occupation al turf post

- application exposure for
workers using default TTR values for boscalid is minimal in comparison to the level of concern (i.e., the calculated occupational MOE is greater than 10 times higher than the level of concern,
lowest dermal MOE = 3,9 00 compared to the LOC of 100 ); HED recommends waiving the 40
CFR §158 TTR data requirement. In this instance, it is unlikely that chemical

- specific TTR data would be needed to further refine exposure assessments or would add appreciably to our general understanding of the availability of turf transferable pesticide residues for boscalid.

D islodgeable Foliar Residue (DFR) Data
In accordance with 40 CFR § 158, DFR data are required for all occupational (e.g., crop, nursery, greenhouse use sites) or residential (e.g., ornamental and vegetable gardens, pick your own farms, retail tree farms) uses that could result in post

- applicatio n exposure to foliage. In the
absence of chemical

- specific DFR data, EPA uses default values. As explained in detail in the
Residential Post

- Application section of this document, and it is also the case for the highest estimated occupational post

- applica tion exposure fr om use on agricultural crops using default
DFR values for boscalid the exposure is minimal in comparison to the level of concern (i.e., the calculated MOE is greater than 2 times higher than the level of concern, MOE = 400 compared
to the LOC of 100 ); and therefore, HED recommends waiving the 40 CFR §158 DFR data requirement. In this instance, it is unlikely that chemical

- specific DFR data would be needed to further refine exposure assessments or would add appreciably to o ur overall understanding of the availability of dislodgeable foliar pesticide residues for boscalid

.

Restricted Entry Interval The REI specified on the proposed label is based on the acute toxicity of boscalid

. Boscalid is classified as Toxicity Catego ry III via the dermal route and Category IV for eye and for skin irritation potential. Short

- and intermediate

- term post

- application risk estimates were not a concern on day 0 (12 hours following application) for all post

- application activities. Under 40Page 31 of 45

CFR 156.208 (c) (2) (iii), a

. i

. ’s classified as Acute III or IV for acute dermal, eye irritation and primary skin irrigation are assigned a 12

- hour REI. Therefore, the [156 subpart K] Worker Protection Statement interim REI of 12 hours is adequate to pro tect agricultural workers from post

- application exposures to boscalid.

9.2.2 Inhalation Post

- Application Risk

There are multiple potential sources of post

- application inhalation exposure to individuals performing post

- application activities in previously treated fields. These potential sources include volatilization of pesticides and resuspension of dusts and/or particulates that contain pesticides. The agency sought expert advice and input on issues related to volatilization of pesticides from its Feder al Insecticide, Fungicide, and Rodenticide Act Scientific Advisory Panel (SAP) in December 2009, and received the SAP’s final report on March 2, 2010 ( http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html ). The agency has evaluated the SAP repor t and has developed a Volatilization Screening Tool and a subsequent Volatilization Screening Analysis ( http://www.regulations.gov/#!docketDetail;D=EPA

- HQ

OPP

- 2014

- 0219 ). During Registration Review, the agency will utilize this analysis to determine if data (i.e., flux studies, route

- specific inhalation toxicological studies) or further analysis is required for boscalid.

In addition, the Agency is continuing to evaluate the available post

- application inhalation exposure data generated by the Agricultural Reentry Task Force. Given these two efforts, the Agency will continue to identify the need for and, subsequently, the way to incorporate occupational post

- application in halation exposure into the agency's risk assessments.

Although a quantitative occupational post

- application inhalation exposure assessment was not performed, an inhalation exposure assessment was performed for occupational/commercial
handlers. Handler ex posure resulting from application of pesticides outdoors is likely to result in higher exposure than post

- application exposure. Therefore, it is expected that these handler inhalation exposure estimates would be protective of most occupational post

- applic ation inhalation exposure scenarios.Page 32 of 45

10.0 References

S. Funk, 0 6 / 30 / 20 1 4 , DP4 21150

. Boscalid: Petition for the Establishment of Permanent Tolerances and Registration for Use on Herb Subgroup 19A and Dill Seed. Request for Crop Group Expansions/Revisions for Stone Fruit Group 12

- 12 and Tree Nut Group 14

- 12. Summary of Analytical Chemistry and Residue Data

.

S. Funk, 0 7 / 16 / 20 1 4 , DP4 21151 . Boscalid. Chronic Aggregate Dietary (Food and Drinking Water) Exposure and Risk Assessment for the Section 3 Registration For Herbs Subgroup 19A and Dill Seed and Crop Group Conversions for Stone Fruit Group and Tree Nut Group.

C. Walls, 0 7 / 31 / 20 1 4 , DP4 21152 . Boscalid. Occupational and Residen tial Exposure Assessment for proposed new uses of boscalid on dill seed and the herb subgroup 19A.

C. Walls, 0 4/30/ 20 13, DP 405533

. Boscalid . Occupational and Residential Exposure Assessment for proposed new uses of boscalid on globe artichoke, Belgium e ndive, persimmon, greenhouse grown tomato transplants grown for home consumer market, and residential ornamentals, landscape gardens, fruit trees and nut trees.

K

. White

, 0 4/ 17 / 20 13, DP40 9880

. Tier I Drinking Water Exposure Assessment for the Section 3
New Uses of Boscalid on Various Agricultural Crops and Homeowner Use s.Page 33 of 45

A ppendix A

. Toxicology Profile and Executive Summaries

A.1 Toxicology Data Requirements

The requirements (40 CFR 158.500) for food uses of boscalid are in the table below. Use of the new guideline numbers does not imply that the new (1998) guideline protocols were used.

Table A.1: Toxicology Studies Required Submitted Satisfied

870.1100 Acute Oral Toxicity

................................ ................................ ................................ ... 870.1200 Acute Dermal Toxicity

................................ ................................ ............................... 870.1300 Acute Inhalation Toxicity

................................ ................................ .......................... 870.2400 Acute Eye Irritation

................................ ................................ ................................ .... 870.2500 Acute Dermal Irritation

................................ ................................ .............................. 870.2600 Skin Sensitization

................................ ................................ ................................ ....... yes
yes
yes
yes
yes
yes yes

yes
yes
yes
yes
yes yes

yes
yes
yes
yes

no a
870.3100 90

- Day Oral Toxicity in Rodents

................................ ................................ ............... 870.3150 90

- Day Oral Toxicity in Non

- Rodents

................................ ................................ ....... 870.3200 21/28

- Day Dermal Toxicity

................................ ................................ ....................... 870.3250 90

- Day Dermal Toxicity

................................ ................................ ............................ 870.3465 90

- Day Inhalation Toxicity

................................ ................................ ........................ yes
yes
yes no (CR)

yes (CR) yes

yes
yes

no

no yes

yes
yes

---

no 870.3700 Prenatal Developmental Toxicity Study (Rodent)

................................ ...................... 870.3700 Prenatal Developmental Toxicity Study (Non

- Rodent)

................................ .............. 870.3800 Reproduction and Fertility Effects

................................ ................................ ............. yes
yes
yes yes

yes
yes yes

no
yes 870.4100 Chronic Toxicity (Rodent)

................................ ................................ ......................... 870.4100 Chronic Toxicity (Non

- Rodent)

................................ ................................ ................. 870.4200 Carcinogenicity ( Two Rodent Species; Rat and Mouse )

................................ ............ 870.4300 Combined Chronic Toxicity/Carcinogenicity

................................ ............................ yes

no
yes

no yes

yes
yes

no yes

--- yes
yes 870.5100 Bacterial Reverse Mutation Test

................................ ................................ ................ 870.5300 i n vitro Mammalian Cell Gene Mutation Test

................................ ............................ 870.5375 i n vitro Mammalian Chromosome Aberration Test

................................ .................... 870.5385 Mammalian Bone Marrow Chromosomal Aberration Test

................................ ........ 870.5395 Mammalian Erythrocyte Micronucleus Test

................................ .............................. 870.5550 Unscheduled DNA Synthesis in Mammalian Cells in Culture

................................ ... yes
yes
yes

--- yes

no yes

yes
yes

no
yes
yes yes

yes
yes

--- yes

- -- 870.6100 Delayed Neurotoxicity of Organophosphorus Substances (Acute, Hen)

.................... 870.6100 Delayed Neurotoxicity of Organophosphorus Substances (28

- Day, Hen)

................. 870.6200 Neurotoxicity Screening Battery (Acute, Rat)

................................ ........................... 870.6200 Neurotoxicity Screening Battery (Subchronic, Rat)

................................ ................... 870.6300 Developmental Neurotoxicity Study

................................ ................................ .......... no (CR) no (CR)

yes
yes no (CR) no

no
yes
yes

no - --

- -- yes
yes

- -- 870.7200 Companion Animal Safety

................................ ................................ ......................... 870.7485 Metabolism and Pharmacokinetics

................................ ................................ ............. 870.7600 Dermal Penetration

................................ ................................ ................................ ....

in vitro Dermal Penetration

................................ ................................ ........................ 870.7800 Immunotoxicity

................................ ................................ ................................ .......... no (CR)

yes no (CR)

no
yes no

yes
yes

no
yes -- -

yes

---

---

---

a Submitted study was classified Unacceptable/Nonguideline
CR : Conditionally RequiredPage 34 of 45

A.2 Toxicity Profile s Table A.2.1. Acute Toxicity of Boscalid

Table A.2.1. Acute Toxicity Profile

– Boscalid (BAS 510 F) Technical.

Test
Material Guideline

No. Study Type MRID Results Toxicity Category

Technical 870.1100 Acute Oral

- rat 45404814 LD 50 > 5000 mg/kg IV

Technical 870.1200 Acute Dermal

- rat 45404815 LD 50 > 2000 mg/kg III

Technical 870.1300 Acute Inhalation 45404816 LC 50 (M & F): > 6.7 mg/L IV

Technical 870.2400 Primary Eye
Irritation 45404817 Not irritating to the eye IV

Technical 870.2500 Primary Dermal
Irritation 45404818 Not irritating to the skin IV

Technical 870.2600 Dermal
Sensitization 4 6270102 Not a dermal sensitizer N/A

Table A.2.2. Non

- acute Toxicity Profile for Boscalid

Table A.2.2 Repeated Dose Toxicity Profile of Boscalid (BAS 510 F) Technical.

Guideline No. and Study Type MRID (date)
Dose Levels Study Classification Results

870.3100

90

- Day oral toxicity rodents (rat) 45404822 (2000) 0, 100, 500, 2000, 5000, 15,000 ppm 0, 7, 34, 137, 347, 1055 mg/kg bw/day Males 0, 8, 40, 159, 395, or 1225 mg/kg bw/day Females

Acceptable/Guideline 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 epithelia l hypertrophy; F = increases in absolute and relative thyroid weights.

870.3100

90

- Day oral toxicity rodents (mouse) 45404821 (2000) 0, 150, 1000, 4000, 8000 ppm 0, 29, 197, 788, and 1518 mg/kg bw/day Males 0, 42, 277, 1184, and 2209 mg/kg bw/day Female s

Acceptable/Guideline 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 attainedPage 35 of 4 5

Table A.2.2 Repeated Dose Toxicity Profile of Boscalid (BAS 510 F) Technical.

Guideline No. and Study Type MRID (date)
Dose Levels Study Classification Results

870.3150

90

- Day oral toxicity in nonrodents (dog) 45404823 (2000) 0, 250, 2500, 25,000 ppm 0, 7.6, 78.1, 728.9 mg/kg/day
Males 0, 8.1, 81.7, 824.8 mg/kg/day
Females

Acceptable/Guideline 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 (rat) 45404824 (2000) 0, 100, 250, or 1000 mg/kg bw/day

Acceptable/Guideline NOAEL : 1000 mg/kg/day (HDT)
LOAEL : >1000 mg/kg/day

870.3700

Prenatal developmental in rodents (rat) 45404904 (2000) 0, 100, 300, 1000 mg/kg bw/day Acceptable/Guideline Maternal NOAEL : 1000 mg/kg/day
Maternal LOAEL : cannot be established Developmental NOAEL : 1000 mg/kg/day Developmental LOAEL : cannot be established

870.3700

Prenatal developmental in nonrodents (rabbit) 45404905 (2000) 0, 100, 300, 1000 mg/kg bw/day

Acceptable/Guideline Maternal NOAEL : 300 mg/kg/day
Maternal LOAEL : 1000 mg/kg/day based on abortions or early delivery. Developmental NOAEL : 300 mg/kg/day Developmental LOAEL : 1000 mg/kg/day based on abortions or early delivery.

870.3800

Reproduction and fertility effects (rat) 45404906 (2001) 0, 100, 1000, 10,000 ppm
F 0 parental animals 10.1, 101.2, 1034.5 mg/kg/day Males 10.7, 106.8, an d 1062.0 mg/kg/day F emales

Acceptable/Guideline Parental systemic NOAEL :112.6/1180.8 mg/kg/day (M/F) Parental systemic LOAEL :1165.0/>1180.8 mg/kg/day (M/F) decreased body weight (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): decreased 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)

870.4100a

Chronic toxicity rodents (rat) 45404827, 45723501 (2001)

0, 100, 500, 2500, 15,000

ppm 0, 4.4, 21.9, 110.0, 739.0 mg/kg bw/day for males and 0, 5.9, 30.0, 150.3, 1000.4 mg/kg bw/day for females

Acceptable/Guideline 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.Page 36 of 45

Table A.2.2 Repeated Dose Toxicity Profile of Boscalid (BAS 510 F) Technical.

Guideline No. and Study Type MRID (date)
Dose Levels Study Classification Results

870 .4100

Chronic toxicity ( dog ) 45404826 (2000) 0, 200, 800, 2000, 20,000

ppm 0, 5.5, 21.8, 57.4, 544.0 mg/kg bw/day Males 0, 5.8, 22.1, 58.3,592.9 mg/kg bw/day Females

Acceptable/Guideline NOAEL : 21.8/22.1mg/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

870.4200

Carcinogenicity ( rat ) 45404828 (2001)

0, 100, 500, 2500, 15,000

ppm 0, 4.6, 23.0, 116.1, 768.8 mg/kg bw/day for males and 0, 6.0, 29.7, 155.6, 1024.4 mg/kg bw/day for females)

Acceptable/Guideline NOAEL : 23.0/29.7 mg/kg/day (M/F)
LOAEL : 116.1/155.6 mg/kg/day (M/F): M = increased incidence of thyroid follicular cell hyperplasia and hypertrophy; F = decrease in increased incidence of thyroid follicular cell hyperplasia a nd hypertrophy. Thyroid follicular cell adenomas: M = 0/50, 0/50, 1/50, 4/50; F = 0/50, 1/50, 0/50, 3/50.

870.4200

Carcinogenicity ( mouse ) 45404901 (2001)

0, 80, 400, 2000, 8000 ppm 0, 13, 65, 331, 1345 mg/kg bw/day Males 0, 18, 90, 443, 1804 mg/kg bw/day Females)

Acceptable/Guideline NOAEL :65/443 mg/kg/day (M/F)
LOAEL : 331/1804 mg/kg/day (M/F): M = decreases in body weight; F = decreases in body weight. No evidence of carcinogenicity.

870.5100

Gene Mutation
bacterial reverse mutation assay 45404913 (1998)
Initial concentrations: 22, 110, 550, 2750

, 5500 μg/plate Repeat assay: 20, 100, 500,
2500

, 5000 μg/plate

Acceptable/Guideline Negative without and with S

- 9 activation up to limit dose of 5000 μg/plate.

870.5300

In vitro mammalian cell forward gene mutation assay (CHO cells/HGPRT locus) 45404914 (2000)
Initial concentrations: 15.625, 31.25, 62.5, 125, 250 or 500 μg/mL in the presence
and absence of mammalian metabolic activation (S9

- mix) Repeat concentrations: 10.24,
25.6 , 64, 160, 400 1000 μg/mL with and without S9

- mix with a repeat of the non

activated test at

conc entrations of 3.125, 6.25, 12.5, 25, 50, 100 μg/mL

Acceptable/Guideline Negative without and with S

- 9 activation up to the limit of solubility of 25 μg/mL.Page 37 of 45

Table A.2.2 Repeated Dose Toxicity Profile of Boscalid (BAS 510 F) Technical.

Guideline No. and Study Type MRID (date)
Dose Levels Study Classification Results

8 70.5375

In vitro mammalian cytogenetics assay in
Chinese hamster V79
cells 45404915 (1999) Initial exposure: 0, 20.0, 100.0 500.0 μg/mL with and
without metabolic activation Second exposure: 0, 31.25, 62.5, 125.0 μg/mL in the
absence of S9

- mix

Acceptable/Guideline Negative without and with S

- 9 activation up to 3500 μg/mL with precipitation showing at concentrations of 100 μg/mL and higher.

870.5395

Cytogenetics

- mammalian erythrocyte
micronucleus test in
the mouse 45404916 (1999) 0, 500, 1000 , 2000 mg/kg bw

Acceptable/Guideline Negative at doses up to 2000 mg/kg.

870.5500

In vitro unscheduled DNA synthesis (primary rat hepatocytes) 45404917 (2000)
First: 0, 5, 10, 50, 100, 250, 500, 750, 1000 μg/mL Repeat d ue to excess cytotoxicity : 0, 0.5, 1.0, 5.0, 10.0, 50.0, 100.0, 250.0, 500.0 μg/mL A second experiment was conducted at 1.563, 3.125, 6.250, 12.500, 25.000, 50.000 μg/mL

Acceptable/Guideline Negative response up to 50 μg/mL. Cytotoxicity at 100

- 500 μg/mL.

870.6200a

Acute neurotoxicity screening battery (rat) 45404820 (2000) 0, 500, 1000 or 2000 mg/kg
bw

Acceptable/Guideline NOAEL :2000/1000 mg/kg/day (M/F)
LOAEL : >2000/2000 mg/kg/day (M/F): F = piloerection

870.6200b

Subchronic neurotoxicity screening battery (rat) 4540 4825 (2001) 0, 150, 1500, 15000 ppm 0, 10.5, 103.1 1050.0 mg/kg bw/day for males 0, 12.7, 124.5 or 1272.5 mg/kg bw/day for females

Acceptable/Guideline NOAEL :1050.0/1272.5 mg/kg/day (M/F)
LOAEL : >1050.0/1272.5 mg/kg/day (M/F)Page 38 of 45

Table A.2.2 Repeated Dose Toxicity Profile of Boscalid (BAS 510 F) Technical.

Guideline No. and Study Type MRID (date)
Dose Levels Study Classification Results

870.6300

Developmental neurotoxicity (rat) 45404907 (2001) 45800101 (2002)

45800102 (2002) 0, 100, 1000 10000 ppm 0, 14, 147 1442 mg/kg/day

Acceptable/Guideline 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) 45404918 (2001) 45404919 (2000) 45692401 (2002)

a single 50 or 500 mg/kg oral dose, or a 14

- day repeated dose (500 mg/k g/day)

Acceptable/Guideline 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 radiolabel position. Metabolites (hydroxylation and conjugation p roducts) 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) 45404920 (2001)

0.01, 0.10, 1.0 mg/cm 2 for 1, 4, 10, or 24 hours

Acceptable/Guideline Maximum % absorption: 0.01 mg/cm 2 = 10.93 (24 hour exposure, 24 hour sacrifice) 0.10 mg/cm 2 = 3.76 (24 hour exposure, 24 hour sacrifice) 1.00 mg/cm 2 = 1.48 (10 hour exposure, 72 hour sacrifice)

870.7800

Immunotoxicity MRID 48203801 (2003)

0, 100, 1000, or 10000 ppm 0, 7.45, 73.1, or 736.2

m g / g k/d ay

Acceptable / Guideline NOAEL = 736.2 mg/kg/day
LOAEL = not established

Non

- guideline

Hepatic enzyme induction (rat) 45404902 (1999)

0 or 15,000 ppm (equivalent to 0 or ~1500 mg/kg bw/day)
for two weeks

Acceptable/Non

- guideline 1. hypertrophy of zone III hepatocytes 2. >20% increase in liver weight 3. increase in CYP450 activity 4. slight to ext ensive microscopic SER proliferation 5. not a peroxisome proliferator 6. enzymes in CYP450 subfamily not induced 7. no notable microscopic increase in size or number of peroxisomes CONCLUSION: inducer of total CYP450 activityPage 39 of 45

Table A.2.2 Repeated Dose Toxicity Profile of Boscalid (BAS 510 F) Technical.

Guideline No. and Study Type MRID (date)
Dose Levels Study Classification Results

Non

- guideline

Hormone and enzyme induction (rat) 45404903 (2001)

0 or 15,000 ppm 0 or ~1000 mg/kg bw/day
For four weeks

Acceptable/Non

- guideline 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

Non

- guideline

Reversibility study (dietary): 4

- week
administration followed by 4 weeks recovery or 13 weeks recovery (rat) 45550601 (2001)

0, 100, 2500, 15000 ppm 0, 7.7, 190.3, 1137.4 mg/kg/day)

Acceptable/Non

- guideline 4 weeks dosing: at 2500 and 15000 ppm: increase in TSH (68% and 87%); increase 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 w eeks 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 40 of 45

Appendix B. Physicochemical Properties of Boscalid

.

Table B. Physicochemical Properties of Boscalid.

Parameter Value References
Melting point/range 142.8

- 143.8  C MRIDs 45404802 and
45404804

- 45404809 pH NA (does not dissociate in water) Relative Density (20oC) 1.381g/cm 3 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
methanol 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, pK a None (does not dissociate in water) Octanol/water partition coefficient, Log(K OW ) 2.96

UV/visible absorption spectrum UV molecular extinction (e[lmol

- 1 cm - 1 ]): 3.15
x10 4 at 228 nm; 1.53 x10 3 at 290 nm

Appendix C

. Review of Human Research

The PHED Task Force, 1995. The Pesticide Handlers Exposure Database, Version 1.1. Electronic Database. Task Force Members: Health Canada, U.S. EPA, and the National Agricultural Chemicals Associations, released February 1995.

The Agricultural Handler Exposure Task Force (AHETF) , 2011. The Occupational Handler Unit Exposure Surrogate Reference Table. U.S. EPA. Released June 21, 2011.

Data from the Outdoor Residential Exposure Task Force (ORETF).

HED Residential Standard Operating Procedures (2012).Page 41 of 45

Appendix D. Residential Handler and Post

- application Exposure and Risk Estimates

Table D .1. Residential Handler Non

- cancer Exposure and Risk Estimates for Boscalid.

Exposure Scenario Dermal
Unit Exposure (mg/lb ai) Inhalation

Unit Exposure (mg/lb ai) Maximum

Application Rate 1 Area

Treated or
Amount
Handled Daily 2 Dermal Inhalation

Total ARI 7

Dose (mg/kg/day) 3 MOE 4 Dose (mg/kg/day) 5 MOE 6

Mixer/Loade r/Applicator
Liquid Garden/Trees : manually pressurized handwand 63 0.018 0.0076 lb ai/gal 5 gal 0.0045 4,900 0.0000086 2,500,000 48

Liquid Garden/Trees : manually pressurized handwand 63 0.018 0.0000051 lb ai/ft 2 1200 ft 2 0.00072 30,000 0.0000014 16,000,000 300

Liquid Garden/Trees :

hose

- end sprayer 58 0.0014 0.0000051 lb ai/ft 2 1200 ft 2 0.00067 33,000 0.00000011 200,000,000 330

Liquid Garden/Trees :

hose

- end sprayer 58 0.0014 0.0076 lb ai/gal 11 gal 0.0091 2,400 0.0000015 15,000,000 24

Liquid Garden/Trees : backpack sprayer 130 0.14 0.0000051 lb ai/ft 2 1200 ft 2 0.0015 15,000 0.000011 2,000,000 140

Liquid Garden/Trees : backpack sprayer 130 0.14 0.0076 lb ai/gal 5 gal 0.0093 2,400 0.000067 330,000 22

Liquid Garden/Trees : sprinkler can 58 0.0014 0.0000051 lb ai/ft 2 1200 ft 2 0.00067 33,000 0.00000011 200,000,000 330

Liquid Garden/Trees : sprinkler can 58 0.0014 0.0076 lb ai/gal 5 gal 0.0041 5,300 0.00000067 33,000,000 53

1 Based on the proposed garden/tree use on Bonide FT09 label (EPA Reg. No. 4

- UII)
2 Based on HED’s 2012 Residential SOPs ( http://www.epa.gov/pesticides/science/residential

- exposure

- sop.html ).
3 Dermal Dose = Derma l Unit Exposure (mg/lb ai) × Application Rate (lb ai/acre or gal) × Area Treated or Amount Handled (A/day or gallons/day) × D ermal Absorption Factor (15%) ÷ Body Weight (80 kg).
4 Dermal MOE = Dermal NOAEL (21.8 mg/kg/day) ÷ Dermal Dose (mg/kg/day).
5 Inhalation Dose = Inhalation Unit Exposure (21.8 mg/lb ai) × Application Rate (lb ai/acre or gal) × Area Treated or Amount Ha ndled (A/day or gallons/day) ÷ BW (80 kg).
6 Inhalation MOE = Inhalation NOAEL (mg/kg/day) ÷ Inhalation Dose (mg/kg/day).
7 Aggrega te Risk Index (ARI) = 1÷ (1 ÷ RI dermal ) + (1 ÷ RI inhalation ) Risk Index (RI) = MOE ÷ LOC ; Inhalation LOC = 1,000 and Dermal LOC = 100Page 42 of 45

Table D .2. Residential Post

- application Non

- cancer Exposure and Risk Estimates for Boscalid.

Lifestage Post

- application Exposure Scenario Application
Rate 1 Dose

(mg/kg/day) MOEs 2 Use Site Route of Exposure

Adult Gardens Dermal 0.33 lb ai/A 0.032 6 8 0

Child (6

- 11 yrs) 0.022 99 0

Adult Fruit and Nut Trees Dermal 0.22 lb ai/A 0.0019 11,000
Child (6

- 11 yrs) 0.0013 16,000

Adult

Lawn/Turf Dermal Golfing

0. 3 5 lb ai/A 0.0015 14,000

Youth (11

- 16 yrs) Dermal Golfing 0.0018 12,000

Child (6

- 11 yrs) Dermal Golfing 0.0021 10,000

1 Based on the proposed tree use on Bonide FT09 label (EPA Reg. No. 4

- UII); the proposed garden use on Homeowner Garden Spray SC ( EPA Reg. No. 7969

- GLG); the proposed tomato transplant use on Pagent® Fungicide (EPA Reg. No.7969

- 251); and the registered golf turf use on Emerald® Fungicide la bel (EPA Reg. No. 7969

- 196).
2 Dermal MOE = Dermal NOAEL (21.8 mg/kg/day) ÷ Dermal Dose (mg/kg/day).Page 43 of 45

Appendix E. Occupational Handler and Post

- application Exposure and Risk Estimates

Table E .1. Baseline Occupational Handler Non

- Cancer Exposu re and Risk Estimates for Boscalid.

Exposure Scenario Crop Dermal Unit Exposure (μg/lb ai) 1 Inhalation

Unit Exposure (μg/lb ai) 1 Max

Applic Rate 2
(lb ai/A) Area Treated

or Amount
Handled Daily 3 Dermal Inhalation

ARI 8

Baseline Baseline Dose (mg/kg/day) 4 MOE 5

(LOC=100) Dose

(mg/kg/day) 6 MOE 7

(LOC=1,000)

Mixer/Loader of WDG
Aerial applications

and Chemigation application Herbs

Dill 227 8.96 0.29 350 0.043 510 0.011 1,900 1.4

Groundboom application Herbs 227 8.96 0.29 80 0.010 2,200 0.0026 8,400 6.1
Groundboom application Dill 227 8.96 0.29 200 0.025 880 0.0065 3,400 2.5
Applicator of Liquids

Aerial application Herbs

Dill 2.08 0.0049 0.29 350 0.00040 55,000 0.0000062 3,500,000 480

Groundboom application Herbs 78.6 0.34 0.29 80 0.0034 6,400 0.000010 220,000 50
Groundboom application Dill 78.6 0.34 0.29 200 0.0086 2,500 0.00025 89,000 20
Flagger

Flagger Herbs

Dill 11 0.35 0.29 350 0.0021 10,000 0.00044 49,000 33

Mixer/Loader/Applicator of WDG

Mechanically pressurized handgun Herbs

Dill 1300 3.9 0.0058 lb ai/gal 1000

gal 0.14 150 0.0033 7,700 1.3

1 Based on the “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table” (March 2013);
2 Based on proposed label (See Table 4).
3 Exposure Science Advisory Council Policy #9.1.
4 Dermal Dose = Dermal Unit Exposure (μg/lb ai) × Conversion Factor (0.001 mg/μg) × Application Rate (lb ai/acre or gal) × Area Treated or Amount Handled Daily (A or gal/day) × DAF (%) ÷ BW (kg).
5 Dermal MOE = Dermal NOAEL (mg/kg/day) ÷ Dermal Dose (mg/kg/day).
6 Inhalation Dose = Dermal Unit Exposure (μg/lb ai) × Conversion Factor (0.001 mg/μg) × Application Rate (lb ai/acre or gal) × Area Treated or Amount Handled Daily (A or gal/day) ÷ BW (kg).
7 Inhalation MOE = Inhalation NOAEL (mg/kg/day) ÷ I nhalation Dose (mg/kg/day). 8 Aggregate Risk Index (ARI) = 1÷ (1 ÷ RI dermal ) + (1 ÷ RI inhalation ) Risk Index (RI) = MOE ÷ LOC; Inhalation LOC = 1,000 and Dermal LOC = 100Page 44 of 45

Table E. 2. Occupational Post

- application Non

- Cancer Exposure and Risk Estimates for Boscalid.

Crop/Site Activities Transfer Coefficient (cm 2 /hr) DFR 1

(μg/cm

2 ) Dermal Dose (mg/kg/day) 2 MOE 3

Dill and Herbs Irrigation (Hand Set) 1,900

0.81 0.023 940

Scouting 1,100 0.013 1,600

Hand weeding 70 0.00085 26,000

1 DFR = Application Rate × F × (1

- D) t × 4.54E8 μg/lb × 2.47E

- 8 acre/cm 2 ; where F = 0.25 and D = 0.10 per day

2 Daily Dermal Dose = [DFR (μg/cm 2 ) × Transfer Coefficient × 0.001 mg/μg × 8 hrs/day × dermal absorption (15%)]  BW (69 kg).

3 MOE = POD (mg/kg/day) / Daily Dermal Dose. Daily Dermal Dose = [DFR (μg/cm 2 ) × TC × 0.001 mg/μg × 8 hrs/day × dermal absorption factor (15%)]  BW (80 kg).

Appendix F . Summaries of Field Residue Data

Table F .1. Summary of Residue Data from Field Trials with Boscalid

Crop Matrix Total Applic.

Rate (lb ai/A) PHI

(days) Residue Levels of Boscalid (ppm) 1

n Min. Max. HAFT Median (STMdR) Mean

(STMR) Std. Dev.

BASIL Proposed use pattern: Two foliar sprays at 0.29 lb ai/A/application for a seasonal rate of 0.58 lb ai/A with a 0

- day PHI.

Fresh Basil 0.60

- 0.63 0 8 11.3 30.6 24.1 15.5 17.7 7.2

3

- 4 8 2.0 16.0 13.5 9.3 8.7 4.9

Dried Basil 0 4 60.6 142.0 142.0 117.7 109.5 36 CHIVES. Proposed use pattern: Two foliar sprays at 0.29lb ai/A/application for a seasonal rate of 0.58 lb ai/A with a 0

- day PHI.

Chives 0.60

- 0.62 0 8 1.6 13.2 12.8 11.6 9.5 4.8 DILL. Proposed use pattern: Two foliar sprays at 0.29 lb ai/A/application for a seasonal rate of 0.58 lb ai/A with a 0

- day PHI.

Fresh Dill (dillweed) 0.60

- 0.61 0 8 5.88 29.2 28.6 15.6 16.3 8.5

Dill Seed 0.59

- 0.62 0 6 5.70 42.2 41.2 10.6 22.5 16
Dill Seed 0.91 0 2 117 129 123 N/A N/A N/A

1 n = number of samples, typically 2X number of trials. Min = lowest replicate sample value. Max = highest replicate sample value. HAFT = highest average field trial. STMdR = median of average field trials. Mean = mean of average field trials.Page 45 of 45

Appendix G . International Residue Limits Status Sheet



### Boscalid (128008; 06/30/2014)
Summary of US and International Tolerances and Maximum Residue Limits Residue Definition : US Canada Mexico 2 Codex 3

40 CFR §180.589. Plant commodities: boscalid, 3

- pyridinecarboxamide, 2

- chloro

- N

- (4 ′

- chloro[1,1'

- biphenyl]

- 2

- yl), Plant commodities:
2

- chloro

- N

- (4'

- chloro[1,1'

- biphenyl]

- 2

- yl)

- 3

- pyridinecarbox

amide - Plant commodities: boscalid.

Commodity 1 Tolerance (ppm) /Maximum Residue Limit (ppm)
US Canada Mexico 2 Codex 3
Herbs subgroup 19A (fresh and dried) 150 None None

Dill, seed 100 None None Nut, tree, group 14

- 12 0.70 0.7 0.05 (*) Fruit, stone, group 12

- 12 3.5 1.7 3

1 Includes only commodities of interest for this action. Tolerance values should be the HED recommendations and not those proposed by the applicant.

2 Mexico adopts US tolerances and/or Codex MRLs for its export purposes.

3 * = absent at the limit of quan titation; Po = postharvest treatment, such as treatment of stored grains. PoP = processed postharvest treated commodity, such as processing of treated stored wheat. (fat) = to be measured on the fat portion of the sample. MRLs indicated as proposed have n ot been finalized by the CCPR and the CAC.