
                 UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
                            WASHINGTON, D.C.  20460
                                                                      OFFICE OF
                                                            CHEMICAL SAFETY AND
\* MERGEFORMAT
                                                           POLLUTION PREVENTION


MEMORANDUM

DATE:  	August 22, 2013

SUBJECT:	Boscalid  -  Human Health Risk Assessment for a Section 3 Registration of New Uses on Globe Artichoke, Belgium Endive, Persimmon, Greenhouse Grown Tomato Transplants for the Home Consumer Market, and Residential Ornamentals, Landscape Gardens, Fruit Trees and Nut Trees; Plus Crop Group Expansions/Revisions for Bulb Vegetable Group 3-07, Fruiting Vegetable Group 8-10, Citrus Fruit Group 10-10, Pome Fruit Group 11-10, Berry Subgroups 13-07A, B, F, and G, Vegetable Root Subgroup 1B Except Sugar beet, and Oilseed Group 20.

PC Code:  128008
DP Barcode:  D405063, D398877, 406471, D406506 
Decision No.:  459294, 470110, 467106, 468292 
Registration No.:  7969-199, 7969-251, 7969-GLG, 4-UII
Petition No.:  2E8068 
Regulatory Action:  Section 3
Risk Assessment Type:  Single Chemical/Aggregate
Case No.:  NA
TXR No.:  NA
CAS No.:  188425-85-6
MRID No.:  NA
40 CFR:  180.589

FROM:	Barry O'Keefe, Senior Biologist
		Myron S. Ottley, Senior Biologist
		Steve Funk, Senior Chemist
		Cassi Walls, Senior Biologist
		Risk Assessment Branch III (RAB III)
		Health Effects Division (7509P)

THROUGH:	Christine Olinger, Branch Chief 
		Risk Assessment Branch III (RAB III) 
		Health Effects Division (7509P)

TO:		Heather Garvie, Risk Manager
		Dominic Schuler, Risk Manager
      Robert Westin, Risk Manager
		Fungicide Branch
		Registration Division (7505P)
			and
      Andrew Ertman, Risk Manager
		Risk Integration, Minor Use and Emergency Response Branch
		Registration Division (7505P)

This document and attachments provide an assessment of the human health risk resulting from the proposed and registered uses of boscalid.  The toxicology reevaluation was performed by Myron Ottley, the drinking water assessment was conducted by Katrina White (EPA Environmental Fate and Effects Division (EFED)), the review of the residue chemistry data an dietary exposure assessment were conducted by Steve Funk, the occupational and residential exposure assessment was conducted by Cassi Walls, and the human health risk assessment was conducted by Barry O'Keefe.  



                               Table of Contents

1.0	Executive Summary	5
2.0	HED Recommendations	7
2.1	Data Deficiencies	8
2.2.1	Enforcement Analytical Method	8
2.2.2	Recommended Tolerances	8
2.2.3	Revisions to Petitioned-For Tolerances	11
2.2.4	International Harmonization	11
3.0	Introduction	12
3.1	Chemical Identity	13
3.2	Physical/Chemical Characteristics	14
3.3	Pesticide Use Pattern	14
3.4	Anticipated Exposure Pathways	16
3.5	Consideration of Environmental Justice	17
4.0	Hazard Characterization and Dose-Response Assessment	17
4.1	Toxicology Studies Available for Analysis	17
4.2	Absorption, Distribution, Metabolism and Excretion (ADME)	18
4.2.1	Dermal Absorption	18
4.3	Summary of Toxicological Effects	19
4.4	Safety Factor for Infants and Children (FQPA Safety Factor)	20
4.4.1	Completeness of the Toxicology Database	20
4.4.2	Evidence of Neurotoxicity	21
4.4.3	Evidence of Sensitivity/Susceptibility in the Developing or Young Animal	21
4.4.4	Residual Uncertainty in the Exposure Database	22
4.5.1	Dose-Response Assessment	22
4.5.2	Recommendation for Combining Routes of Exposure for Risk Assessment	24
4.5.3	Cancer Classification and Risk Assessment Recommendation	24
4.5.4	Summary of Points of Departure and Toxicity Endpoints Used in Human Risk Assessment	24
5.0	Dietary Exposure and Risk Assessment	26
5.1	Residues of Concern Summary and Rationale	26
5.2	Food Residue Profile	26
5.3	Water Residue Profile	28
5.4	Dietary Risk Assessment	29
5.4.1	Description of Residue Data Used in Dietary Assessment	29
5.4.2	Percent Crop Treated Used in Dietary Assessment	30
5.4.3	Acute Dietary Risk Assessment	30
5.4.4	Chronic Dietary Risk Assessments	30
5.4.5	Summary Table	31
6.0	Residential (Non-Occupational) Exposure/Risk Characterization	31
6.1	Residential Handler Exposure	31
6.2	Post-Application Exposure	34
6.3	Combined Residential Risk Estimates (Multiple Exposure Scenarios)	34
6.4	Residential Risk Estimates for Use in Aggregate Assessment	35
6.5	Residential Bystander Post-application Inhalation Exposure	35
6.6	Spray Drift	35
7.0	Aggregate Exposure/Risk Characterization	36
7.1	Acute Aggregate Risk	36
7.2	Short-Term Aggregate Risk	36
7.3	Chronic Aggregate Risk	37
8.0	Cumulative Exposure/Risk Characterization	37
9.0	Occupational Exposure/Risk Characterization	37
9.1	Short-/Intermediate-Term Handler Risk	38
9.2	Short-and Intermediate-Term Post-Application Risk	39
9.2.1	Dermal Post-Application Risk	39
9.2.2	Inhalation Post-Application Risk	39
10.0	References	40
Appendix A.  Toxicology Profile and Executive Summaries	41
A.1	Toxicology Data Requirements	41
A.2	Toxicity Profiles	42
Appendix B.  Physicochemical Properties of Boscalid.	47
Appendix C.  Review of Human Research	47
Appendix D.  Summaries of Field Residue Data	48
Appendix E.  Summaries of Occupational Handler and Post-application Exposure and Risk Estimates	49
Appendix F.  International Residue Limits Status Sheet	52

1.0	Executive Summary

Introduction
Boscalid, 3-pyridinecarboxamide, 2-chloro-N-(4'-chloro[1,1'-biphenyl]-2-yl), is a fungicide active ingredient that works inside the mitochondria of fungi and stops fungi from producing the energy that they need to carry on basic functions.  Boscalid prevents energy production by binding to the enzyme succinate ubiquinone reductase.  Boscalid is currently registered on numerous agricultural crops and on golf course turf.

Use Profile
The proposed actions of boscalid are as follows: 1) The Interregional Research Project No. 4 (IR-4) is proposing new agricultural uses (PP# 2F8069) on artichoke, Belgium endive, and persimmon; 2) BASF is proposing a new greenhouse tomato use for commercial production and for tomato transplants grown for the home consumer market; 3) Bonide Products is proposing a new use on residential fruit and nut trees; and 4) BASF is proposing new uses on residential ornamentals and landscape gardens.  Additionally, crop group expansions/revisions were requested for the bulb vegetable group 3-07, fruiting vegetable 8-10, citrus fruit group 10-10, pome fruit group 11-10, berry subgroups 13-07A, B, F, and G, vegetable root subgroup 1B except sugar beet, and oilseed group 20.

The proposed agricultural labels require occupational handlers to wear the following personal protective equipment (PPE): long-sleeved shirts, long pants, chemical resistant gloves, and coveralls in a few cases.  The 12 hour restricted entry interval (REI) listed on the labels is appropriate.  

Exposure Profile
The proposed residential uses result in short-term handler dermal and inhalation exposures for adults, short-term post-application dermal exposures for adults, youths (11 to 16 years old), and children 6 to 11 years old, and short-term post-application dermal and incidental oral exposures for children (1 to <2 years old).  Exposure pathways include dietary (food and drinking water), and residential exposure sources.  Dietary exposures are also expected for acute and chronic durations.  Occupational 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 body weight gains 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 chronic 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. There were no susceptibility concerns and no residual uncertainties regarding developing offspring, and the FQPA Safety Factor was reduced to 1X in the risk assessment.  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 were selected for chronic dietary, incidental oral (short- and intermediate-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.  The level of concern (LOC) for all exposure scenarios is a margin of exposure (MOE) <100, with the exception of inhalation exposures where the LOC is an MOE of <1000 because a subchronic inhalation study is required for this risk assessment but is not available.

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.  Estimated drinking water concentrations (EDWCs) were incorporated directly into the dietary exposure assessments.  

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.

The results of the slightly refined chronic dietary (food and drinking water) analysis are below the Agency's level of concern for all population subgroups.  The dietary exposure for food and drinking water for the general U.S. population is 20% of the chronic Population Adjusted Dose (cPAD) and 56% of the cPAD for children 1-2 years old, the population subgroup with the highest estimated chronic dietary exposure to boscalid.

Residential Exposure
New residential uses were requested in this action.  Additionally, boscalid is currently registered for use on golf course turf.  Residential exposures from the proposed and existing residential uses were assessed using the updated 2012 HED Residential Standard Operating Procedures (SOPs).  Residential exposure is expected to be short-term only.  Because the dermal and inhalation PODs are the same, the dermal and inhalation handler exposure estimates were combined using the aggregated risk index (ARI) approach.  All residential handler dermal and inhalation exposure risk estimates were not of concern to HED, with ARI values ranging from 24 to 330.  All residential post-application dermal exposure risk estimates were also not of concern to HED, with margins of exposure (MOEs) ranging from 690 to 16,000.  

Aggregate Exposure 
There is potential for short-term and chronic exposure to boscalid via dietary (which is considered background exposure) and residential (which is considered primary) exposure pathways.  The aggregate MOEs are 310 for children 6 to 11 years old, 690 for youths 11 to 16 years old, and 290 for adults.  None of these aggregate risk estimates are of concern to HED.

Occupational Exposure
Based on the proposed agricultural uses, there is potential for short- and intermediate-term occupational exposure during mixing, loading, and other handling tasks; and during post-application activities.  The proposed labels require occupational handlers to wear the following personal protective equipment (PPE): long-sleeved shirts, long pants, and chemical resistant gloves.  Because the dermal and inhalation PODs are the same, the dermal and inhalation handler exposure estimates were combined using the ARI approach.  

All of the occupational handler ARIs are greater than 1.0 when assessed using labeled PPE (gloves), and are not a concern to HED.

All post-application scenarios resulted in dermal exposure 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 400 to 21,000.  Dislodgable foliar residue (DFR) studies are not required at this time for boscalid since the lowest dermal MOE (400) is greater than 4 times the LOC based on default input values.

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 the need for a quantitative occupational post-application inhalation exposure assessment for boscalid.  The 12 hour restricted entry interval (REI) listed on the labels is appropriate.  

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 Handler Exposure Task Force (AHETF) database, the Residential SOPs (lawns and turf), and MRID 45773201 are subject to ethics review pursuant to 40 CFR 26, have received that review, and are compliant with applicable ethics requirements.  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 Considerations
Potential areas of environmental justice concerns, to the extent possible, were considered in this human health risk assessment, in accordance with U.S. Executive Order 12898, "Federal Actions to Address Environmental Justice in Minority Populations and Low-Income Populations," (http://www.eh.doe.gov/oepa/guidance/justice/eo12898.pdf.  

2.0	HED Recommendations

HED has examined the toxicology and residue chemistry databases for boscalid.  Pending submission of revised Sections B and 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 are discussed in Section 2.2, and label modifications are discussed in Section 2.3.


2.1	Data Deficiencies

870.3465 Subchronic Inhalation study

   * A subchronic Inhalation 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 is not sufficient to alleviate concern (TXR0056585. K. Rury. 03/04/2013). Therefore, a 10X database uncertainty factor has been added for inhalation exposures.

2.2	Tolerance Considerations

2.2.1	Enforcement Analytical Method

There are adequate residue analytical methods for tolerance enforcement and data collection.

An adequate gas chromatography/mass spectrometry (GC/MS) method (Method D0008) is available for enforcing boscalid tolerances in plant commodities.  The Analytical Chemistry branch/Biological and Economic Analysis Division (ACB/BEAD) concluded that the method is acceptable for enforcement purposes in plants without the need for an EPA validation (DP284510; D. Swineford and E. Kolbe, 8/12/2003, PMV memo).

An enforcement method is available for determining the residues of concern in livestock.  Method DFG S19 is a GC/electron capture detection method that was successfully validated by ACB/BEAD.  For the most recent livestock feeding study, residues of boscalid and its hydroxy metabolite M510F01 (including the glucuronide conjugate M510F02) were determined using a LC/MS/MS  method (BASF Method 471/0, modified) which was previously reviewed in conjunction with earlier feeding studies.

Residues of boscalid and its metabolite M510F01 were not adequately recovered using the multiresidue methods.  Protocol A was not applicable.  Protocol B was not applicable for boscalid and yielded inconsistent recoveries of M510F01.  Residues of boscalid and its hydroxy metabolite M510F01 had good responses with GC/ECD on a DB-1 column under Protocol C.  Neither analyte was recovered at >=30% using Protocols D, E, and F.  The study has been forwarded to FDA for a future updating of PAM, Vol. I.

2.2.2	Recommended Tolerances

For the use of boscalid on globe artichoke, Belgium endive, and persimmon, tolerances are required.  Based on evaluation of the field trial data with the Organization of Economic Cooperation and Development (OECD) tolerance calculation procedure (Appendix II), the tolerances listed in Table 2.2.2.1 are appropriate.  With the establishment of the tolerance for Belgium endive, the existing tolerance for Section 18 emergency exemption for Belgium endive should be removed.

Several crop group conversions were requested.  Most were crop group or subgroup updates.  The request to replace vegetable, root subgroup 1A, except sugar beet, garden beet, radish, and turnip at 1.0 ppm with vegetable, root, except sugar beet, subgroup 1B at 1.0 ppm is not acceptable.  The original tolerance was established based on data for carrot only (DP287829, M. Nelson, MRID 45405113).  No field trial data were submitted for radish, the other representative commodity.  Therefore the request must be amended to vegetable, root, except sugar beet, subgroup 1B, except garden beet, radish, and turnip at 1.0 ppm.  The proposed changes and their evaluation are summarized in Table 2.2.2.1.

Table 2.2.2.1.	Tolerance Summary for Boscalid.
Commodity
                       Proposed/Existing Tolerance (ppm)
                    Recommended/ Harmonized Tolerance (ppm)
Comments; Correct Commodity Definition
40 CFR 180.589(a) General.  It is recommended that tolerances be established for residues of the fungicide boscalid, including its metabolites and degradates, in or on the commodities listed below.  Compliance with the tolerance levels specified below is to be determined by measuring only boscalid, 3-pyridinecarboxamide, 2-chloro- N -(4′-chloro[1,1'-biphenyl]-2-yl), in or on the following raw agricultural commodities:
Artichoke, globe
                                      6.0
                                      6.0

Endive, belgium
                                      5.0
                                      6.0
OECD statistical calculation estimates  6.0 ppm
Persimmon
                                      7.0
                                      8.0
OECD statistical calculation estimates  8.0 ppm 
Vegetable, bulb, group 3-07
                                      3.0
                                      5.0
Group update.  Harmonization with Codex (VA 0035 Bulb vegetables:  5 mg/kg)
Vegetable, bulb, group 3
                                      3.0
                                    Remove
Group update.
Vegetable, fruiting, group 8-10
                                      1.2
                                      3.0
Group update. Harmonization with Codex (Fruiting vegetables other than cucurbits VO 0050: 3 mg/kg)
Vegetable, fruiting, group 8
                                      1.2
                                    Remove
Group update.
Fruit, citrus, group 10-10
                                      1.6
                                      2.0
Group update. Harmonization with Codex (Citrus fruits FC 0001: 2 mg/kg)
Fruit, citrus, group 10
                                      1.6
                                    Remove
Group update.
Fruit, pome, group 11-10
                                      3.0
                                      3.0
Group update.
Fruit, pome, group 11
                                      3.0
                                    Remove
Group update.
Caneberry subgroup 13-07A
                                      6.0
                                     10.0
Subgroup update.  Harmonization with Codex (Berries and other small fruits, FB 0018: 10 mg/kg)
Caneberry subgroup 13A
                                      6.0
                                    Remove
Subgroup update.
Bushberry subgroup 13-07B
                                     13.0
                                     13.0
Subgroup update.
Bushberry subgroup 13B
                                     13.0
                                    Remove
Subgroup update.
Fruit, small, vine climbing, except fuzzy kiwifruit, subgroup 13-07F
                                      3.5
                                     5.0 
Subgroup update.  Harmonization with Codex (Grapes FB 0269: 5 mg/kg)
Grape
                                      3.5
                                    Remove
Group update. See subgroup 13-07F.
Berry, low growing, subgroup 13-07G except cranberry
                                      4.5
                                      4.5
Subgroup update.
Strawberry
                                      4.5
                                    Remove
Group update. See subgroup 13-07G.
Oilseed group 20
                                      3.5
                                      5.0
Group update.  Harmonization with Canada (canola oil and mustard seed oil, 5.0 ppm)
Canola, seed
                                      3.5
                                    Remove
Group update.  See group 20.
Sunflower, seed
                                     0.60
                                    Remove
Group update.  See group 20.
Cotton, undelinted seed
                                      1.0
                                    Remove
Group update.  See group 20.
Vegetable, root, except sugar beet, subgroup 1B
                                      1.0
                                      2.0
Vegetable, root, except sugar beet, subgroup 1B, except garden beet, radish, and turnip.
Subgroup update.  Harmonization with Codex (Root and tuber vegetables, VR 0075: 2 mg/kg)
Vegetable, root subgroup 1A, except sugar beet, garden beet, radish, and  turnip
                                      1.0
                                    Remove
Group update.
Turnip, greens
                                     18.0
                                     40.0
Turnip, greens
Translation of data from mustard greens, for which a tolerance of 18.0 ppm exists (Brassica leafy greens). Harmonization with Codex (Leafy vegetables VL 0053: 40 mg/kg)
40 CFR 180.589(b) Section 18 emergency exemptions  
Endive, belgium
                                      16
                                    Remove
Replaced by tolerance under 40 CFR 180.589(a)
40 CFR 180.589(d) Indirect or inadvertent residues
Flax, seed
                                      3.5
                                    Remove
Group update.  See group 20.
Cotton, gin byproducts
                                     0.30
                                    Remove
Duplicate of existing 40 CFR 180.589(a) entry.

No new tolerances are proposed for boscalid based on the proposed residential use on pome fruit, stone fruit, and tree nuts using the proposed label for the Bonide Products, Inc FT09 (EPA File Symbol 4-UII).  The existing tolerances based on the BASF Pristine[(R)] label cover these residential uses on pome fruit, stone fruit, and tree nuts.  The Bonide Products, Inc FT09 label compares favorably with the BASF Pristine[(R)] label.  Therefore, the existing tolerances for pome fruit, stone fruit, and tree nuts will also cover the proposed new residential uses.


2.2.3	Revisions to Petitioned-For Tolerances

860.1550 Proposed Tolerances
   * The available data for Belgium endive will not support a tolerance level of 5.0 ppm.  A revised Section F should be submitted with a tolerance for Belgium endive at 6.0 ppm.

   * The available data for persimmon will not support a tolerance level of 7.0 ppm.  A revised Section F should be submitted with a tolerance for persimmon at 8.0 ppm.

Several crop group conversions were requested.  Most were crop group or subgroup updates.  The request to replace vegetable, root subgroup 1A, except sugar beet, garden beet, radish, and turnip at 1.0 ppm with vegetable, root, except sugar beet, subgroup 1B at 1.0 ppm is not acceptable.  The original tolerance was established based on data for carrot only (D287829, M. Nelson, MRID 45405113).  No field trial data were submitted for radish, the other representative commodity.  Therefore the request must be amended to vegetable, root, except sugar beet, subgroup 1B, except garden beet, radish, and turnip.  Moreover, the tolerance should be revised to 2.0 ppm in order to harmonize with Codex. 

The request to create a tolerance for turnip greens is acceptable.  Turnip greens may be covered by translation of field trial residue data for mustard greens.  Data for the latter were used in establishing the Brassica leafy greens subgroup 5B tolerance at 18.0 ppm.  However, the proposed value of 18 ppm is not acceptable.  A value of 40.0 ppm is recommended in order to harmonize with Codex. 

The proposed conversions of certain existing crop groups (including the removal of certain commodity or commodity group/subgroup tolerances), with the exception of the conversion of vegetable, root, subgroup 1A except sugar beet, garden beet, radish, and turnip at 1.0 ppm to vegetable, root subgroup 1B, except sugar beet, at 1.0 ppm are acceptable.  The exceptions of garden beet, radish, and turnip must be maintained.

2.2.4	International Harmonization

Codex MRLs and/or Canadian MRLs have not been established for boscalid in/on globe artichoke, Belgium endive, or persimmon.  Therefore, there is no issue of harmonization with Codex or Canada for these commodities (see Appendix F).

Some harmonizations with Codex were not possible because the corresponding commodity group/subgroup tolerance in the US is higher than the Codex MRL.  Decreasing the tolerance value has the potential to create apparent violation of the label use instructions when boscalid is used according to the label.  Subgroup 13.07G could not be changed from 4.5 ppm to harmonize with Codex (strawberry, 3 mg/kg).  Pome fruit group 11-10 could not be changed from 3.0 to harmonize with Codex (apple, 2 mg/kg).  Bushberry subgroup 13-07B could not be changed from 13.0 ppm to harmonize with Codex (small berry, 10 mg/kg).

Many of the group crop updates include changes in the tolerances in order to harmonize with Codex.  These are bulb vegetable group 3-07 (3.0 to 5.0 ppm); fruiting vegetables group 8-10 (1.2 to 3.0 ppm); citrus fruit group 8-10 (1.6 to 2.0 ppm); caneberry subgroup 13-07A (6.0 to 10.0 ppm); small vine fruit subgroup 13-07F (3.5 to 5.0 ppm); root vegetable subgroup 1B (1.0 to 2.0 ppm).  The update from canola, sunflower, and cotton seeds to oilseed group 20 includes a revision in the tolerance from 3.5 ppm to 5.0 ppm in order to harmonize with Canada.

Also, the proposed turnip greens tolerance (18 ppm) is based on the proposed addition of turnip greens (turnip tops) to crop subgroup 5B, for which adequate data were previously presented for the representative commodity mustard greens.  The tolerance proposal of 18.0 ppm is changed to 40.0 ppm in order to harmonize with Codex.

2.3	Label Recommendations

860.1200 Directions for Use
   * The proposed Pristine[(R)] label (EPA Reg. No. 7969-199) and the proposed Endura[(R)] label (EPA Reg. No. 7969-197) provide directions for use on "root vegetables, 1B (except sugar beet)."  This must be modified to use on "vegetable, root, except sugar beet, subgroup 1B, except garden beet, radish, and turnip".  The specific crops garden beet, radish, and turnip must be removed from the description of root vegetables for treatment with Pristine[(R)].

   * The proposed Pristine(R) label (Reg. No. 7969-199) and the proposed Endura (R) label (EPA Reg. No. 7969-197) provide directions for use on the low growing berry subgroup 13-07G.  Cranberry must be removed from the list of crops.  The title "low growing berry subgroup" should be changed to "berry, low growing, subgroup 13-07G, except cranberry."

3.0	Introduction

Boscalid, 3-pyridinecarboxamide, 2-chloro-N-(4'-chloro[1,1'-biphenyl]-2-yl), is a fungicide active ingredient that works inside the mitochondria of fungi and stops fungi from producing the energy that they need to carry on the basic functions in life like obtaining food, growing and reproducing.  Boscalid prevents energy production by binding to the enzyme succinate ubiquinone reductase.  

Boscalid is currently registered on alfalfa, beans, 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, pistachios, pome fruits, potatoes, soybeans, spinach, stone fruits, strawberries, tree nuts, tropical fruits (avocado, black sapote, canistel, 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.

The proposed actions of boscalid are as follows: 1) The Interregional Research Project No. 4 (IR-4) is proposing new agricultural uses (PP# 2F8069) on artichoke, Belgium endive, and persimmon; 2) BASF is proposing a new greenhouse tomato use for commercial production and for tomato transplants grown for the home consumer market; 3) Bonide Products is proposing a new use on residential fruit and nut trees; and 4) BASF is proposing new uses on residential ornamentals and landscape gardens.  Additionally, crop group expansions/revisions were requested for the bulb vegetable group 3-07, fruiting vegetable 8-10, citrus fruit group 10-10, pome fruit group 11-10, berry subgroups 13-07A, B, F, and G, vegetable root subgroup 1B except sugar beet, and oilseed group 20.

3.1	Chemical Identity

The chemical structure and nomenclature of boscalid and its hydroxyl metabolite are presented in Tables 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[(R)] Fungicide; EPA Reg. No. 7969-199, also contains 12.8% pyraclostrobin)
70% WDG (Endura[(R)] Fungicide; EPA Reg. No. 7969-197)
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
359.2

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 volatilize 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.  Volatilization from moist soil surfaces or water surfaces is not expected to be an important fate process based upon a Henry's Law constant of 5.1 x 10[-10] atm-cu m/mole.  A biodegradation half-life in soil ranging from 96 to 578 days and a dissipation half-life range of 27 to 372 days indicate that biodegradation is not an important environmental fate process.  If released into water, boscalid is expected to adsorb to suspended solids and sediment based upon the estimated Koc.  An estimated bioconcentration factor (BCF) of 38 suggests the potential for bioconcentration in aquatic organisms is moderate.  Boscalid is stable to hydrolysis.  The physiochemical properties of boscalid are summarized in Appendix B.  

3.3	Pesticide Use Pattern

Globe artichoke, Belgium endive, and persimmon
IR-4 is proposing the use of Pristine Fungicide on globe artichokes, Belgium endive, and persimmons. Pristine Fungicide (EPA Reg. No. 7969-199) is a MAI WDG fungicide containing 12.8% pyraclostrobin and 25.2% boscalid.  Belgium endive may be treated at a maximum rate of 0.025 lb ai/1000 lb roots prior to cold storage and 0.028 lb ai/70 ft[2] prior to forcing, each at one application per season.  The maximum single application rate for artichoke and persimmon is 0.36 lb ai/A using aerial, ground, or chemigation equipment.  Pristine may be applied 3 times per crop cycle at a maximum crop-cycle application rate of 1.08 lb ai/A/yr.  

Greenhouse tomato use for commercial production and for tomato transplants grown for the home consumer market
BASF is proposing the use of Pagent(R) Fungicide on greenhouse grown tomatoes.  Pagent(R) Fungicide label (EPA Reg. No.7969-251) is a MAI WDG fungicide containing 12.8% pyraclostrobin and 25.2% boscalid.  Pagent may be applied at a maximum single application rate of 0.36 lb ai/A (or 0.0036 lb ai/gal).  Pagent may be applied 3 times per crop cycle at a maximum crop-cycle application rate of 1.08 lb ai/A (or 0.0108 lb ai/gal).  Handlers may apply Pagent using high or low pressure sprayer, or a backpack sprayer.  

Residential fruit and nut trees
Bonide Products is proposing a new product, Bonide(R) Fruit Tree Spray Concentrate (FT09), for use on home orchard fruit and nut trees via a homeowner applicator.  Bonide(R) Fruit Tree Spray Concentrate (EPA Reg No.4-UII) is a MAI SC fungicide containing 0.500% lambda-cyhalothrin, 3.06% pyraclostrobin, and 5.622% boscalid.  The maximum single application rate is 0.22 lb ai/A with no more than 4 or 5 applications per year, depending on the tree type.  The retreatment interval ranges from 7 to 10 days.  Residential handlers may apply FT 09 using handheld spray equipment.


Residential ornamentals and landscape gardens
BASF is proposing a new product, Homeowner Garden Spray Fungicide, for use on residential ornamentals and landscape gardens via a residential applicator.  Homeowner Garden Spray Fungicide (EPA Reg No. 7969-GLG) is a MAI SC fungicide containing 9.0% pyraclostrobin and 18.0% boscalid.  The maximum single application rate for this product is 0.0033 lb ai/gal via residential handheld spray equipment or hose-end sprayers.

The proposed uses of boscalid are summarized in Table 3.3.

Table 3.3.  Use Profile for Proposed Boscalid Uses
                                   Proposed
                                      Use
                              Product Formulation
                                [EPA Reg. No.]
                             Application Equipment
                          Max. Single 
Applic. Rate 
                                   (lb ai/A)
                          Max. No. Applic. Per Season
                          Max. Seasonal Applic. Rate 
                                 (lb ai/A/yr)
                                     PHI 
                                    (days)
                        Use Directions and Limitations
Globe Artichoke

Persimmon
                              Pristine Fungicide 
                            [EPA Reg. No.7969-199]
                                       
                              WDG 25.2% boscalid
                        Ground, Aerial, or Chemigation
                                     0.36
                                       3
                                      1.1
                                       0
Continue treatment on a 7 to 14 day interval.
Belgium endive
                                       
Make one app as a spray to roots when brought into cold storage prior to forcing.  Apply again at the beginning of forcing after the roots have been packed in forcing trays.
                            Prior to cold storage:
                           0.028 lb ai/1000 lb roots
                                       1
                                      NA
                                      19
Prior to Cold Storage: make one app as a spray to the roots as they move along a conveyor belt used to bring the roots from field transportation into cold storage bins.

                                       
                                       
                              Prior to forcing: 
                      0.028 lb ai/70ft[2] of forcing tray
                                       1
                                       
                                       
Prior to Forcing: make one app as a spray to roots at the beginning of forcing, after they have been packed into forcing trays.
Greenhouse tomatoes
                              Pagent(R) Fungicide
                             [EPA Reg. No.7969-251]
                                       
                              WDG 25.2% boscalid
                                       
                                 Chemigation,
                                  Ground, or
                           Handheld spray equipment
                                 0.36 lb ai/A
                                      or
                              0.0036 lb ai/gal  
                                       3
                                     1.1 
                                       0
For commercial production:

Apply as a foliar spray in a minimum of 100 gal/A water volume.  

Allow at least 7 days between applications.

Do not make more than one application before alternations to a fungicide with a different mode of action for at least on application.

                                       
                                       
                                 0.28 lb ai/A
                                      or
                              0.0028 lb ai/gal  
                                       
                                     0.85
                                        
                                      NA
For tomato transplants grown for the home consumer market:

Do not exceed 100 gal/A spray volume.

Allow at least 7 days between applications.

Do not use in transplant production for commercial field-grown tomatoes.

Do not apply more than 2 consecutive applications in any crop production cycle.
Residential fruit and nut trees

                 Bonide(R) Fruit Tree Spray Concentrate (FT09)
                             [EPA Reg. No. 4-UII]
                                       
                                       
                               SC 5.62% boscalid
                           Handheld spray equipment
                               0.0076 lb ai/gal
                                       
                             0.000051 lb ai/ft[2]
                                       
                                 0.22 lb ai/A
Pome Fruit and Tree nuts: 4

Stone Fruit: 5

                                       
                                       
                                 Pome Fuit: 21
                                       
                                Stone Fruit: 14
                                       
                                  Almonds: 25
                                       
                                 Tree Nuts: 14
Apply thoroughly as a foliar cover spray to both sides of plant leaves and surfaces.  Spray leaf surfaces to the point of drip but do not exceed 2 fl oz of product per 1,500 ft[2]
Residential ornamentals
                       Homeowner Garden Spray Fungicide 
                            [EPA Reg. No. 7969-GLG]
                                       
                               SC 18.0% boscalid
                                       
                           Handheld spray equipment
                               0.0033 lb ai/gal
                                       
                                0.33 lb ai/A[1]
                                       6

                                      NA
For manual spray applications: spray until foliage is wet.

For hose-end sprayers: typically hose-end applicators are designed to deliver the desired dial setting per gallon of water in 30 seconds.

Retreatment interval is 14 days.
1 Assumed 100 gallons treats 1 acre based on other similar labels; HED recommends that the Homeowner Garden Spray Fungicide (EPA Reg. No. 7969-GLG) label should be clarified by including the spray volume (i.e., number of gallons of spray treated per acre).  This information is needed so that the application rate can be presented in terms of lbs ai/A as well as, lbs ai/gal (which is currently on the label).  
3.4	Anticipated Exposure Pathways

The Registration Division has requested an assessment of human health risk to support proposed new uses of boscalid on the following: 1) agricultural crops globe artichoke, Belgium endive, and persimmon; 2) greenhouse tomato use for commercial production and for tomato transplants grown for the home consumer market; 3) residential fruit and nut trees; and 4) residential ornamentals and landscape gardens.  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 residential uses of boscalid so there is exposure to residential 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 residents 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 existing uses of boscalid, particularly in the dietary and residential exposure assessments.  

3.5	Consideration of Environmental Justice

Potential areas of environmental justice concerns, to the extent possible, were considered in this human health risk assessment, in accordance with U.S. Executive Order 12898, "Federal Actions to Address Environmental Justice in Minority Populations and 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 pesticide exposures that are based on patterns of that subgroup's food and water consumption, and activities in and around the home that involve pesticide use in a residential setting.  Extensive data on food consumption patterns are compiled by the U.S. Department 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 based 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 resources 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.

4.0	Hazard Characterization and Dose-Response Assessment

4.1	Toxicology Studies Available for Analysis

The available toxicity database includes: 
   * acute toxicity battery,
   * oral subchronic studies (rat, mouse and dog),
   * dermal subchronic study (rat),
   * oral developmental (rat, rabbit), reproductive (rat), neurotoxicity (rat, acute and subchronic) and immunotoxicity (rat) studies,
   * oral chronic (rat, dog) and carcinogenicity (rat, mouse) studies,
   * mutagenicity battery,
   * metabolism  and pharmacokinetics studies (rat), and
   * special oral subchronic (rat) studies on hepatic enzyme induction, thyroid hormone induction and reversibility of these inductions.

Anticipated exposure routes include oral, dermal and inhalation.  While acute and subchronic oral and dermal studies are available, a subchronic inhalation study was not included in the submitted toxicity database.

4.2	Absorption, Distribution, Metabolism and Excretion (ADME)

In metabolism and kinetics studies, boscalid was absorbed to some degree, 17% in the low dose (50 mg/kg/day) and 3.5% at 500 mg/kg/day.  These values were increased approximately three-fold when biliary excretion data were incorporated.  The lower percentages of high-dose absorption were considered to be due to saturation, which was supported by the decreased urinary and biliary excretion, and greater fecal excretion observed in the high-dose group. There did not appear to be any biologically relevant differences in the total absorption between the single dose and the 15-day repeated dose regimens nor were there any remarkable gender-related differences. Maximum plasma concentration (Tmax) was achieved in 8 hours regardless of dose.  Elimination of radioactivity from the plasma appeared to be biphasic with a rapid decline from Tmax to 24 hours (t1/2~8.1 hr) followed by a slower elimination phase (t1/2~29.9 hr).  There did not appear to be biologically significant gender-related differences in pharmacokinetic parameters.  The AUC values and maximum plasma concentrations did not reflect the 10-fold difference in administered dose.

Tissue distribution data showed that radioactivity was most prevalent in organs/tissues associated with absorption, metabolism and elimination processes such as liver, kidneys, gut, and adipose tissue. Tissue burdens for the low- and high-dose groups did not, however, reflect the 10-fold difference in dose.  Radioactivity in the thyroid and bone marrow appeared to be greatest at the 168 - hour time point.  The metabolite characterization findings were consistent with Phase I oxidation followed by Phase II conjugation processes.  The most prominent metabolites in the urine, bile, and liver were M510F01 (a hydroxylation product) and M510F02 (a glucuronide conjugate).  In the feces, parent compound (representing unabsorbed material) was the most prevalent component.

Excretion of administered radioactivity was primarily via the feces (~80-98%) for all treatment groups regardless of dose level or label position.  Urinary excretion accounted for the majority of the remainder of the radiolabel.  Although excretion profiles were similar for the single high-dose and repeat high-dose groups, somewhat greater urinary excretion of radioactivity was observed for the low-dose group. Biliary excretion represented approximately 40 to 50% of the fecal radioactivity in the low-dose group but only about 10% in high-dose group.  This was also confirmed by the plasma kinetics and AUC data.  Excretory patterns did not significantly differ by gender or position of the radiolabel.

4.2.1	Dermal Absorption

Based on the results of an available dermal absorption study in rats, the dermal absorption factor (DAF) of boscalid was determined to be 15% in the previous risk assessment, as represented by 11% being absorbed plus 4% found as bound residue on the skin following a 24 hr exposure and 24 hr sacrifice.  The 10 hr exposure and 10 hr sacrifice DAF is 11%, based on 8% being absorbed and 3% found as bound residue on the skin.

4.3	Summary 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 chronic feeding studies in rats, mice and dogs, boscalid generally caused decreased body weights and body weight gains (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 in 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 (limit dose).  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 limit dose.  There was quantitative evidence of increased susceptibility in the two-generation reproduction study in rats, where decreases in body weights and body weight gains 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 (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 increased 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 was negative in the mutagenicity battery.

There was not 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 (toxicity categories III or IV for oral, dermal, inhalation, primary eye irritation and primary skin irritation).


4.4	Safety Factor for Infants and Children (FQPA Safety Factor)

A database of acceptable developmental, reproduction, and neurotoxicity (acute, subchronic and developmental) studies is available.  Based on the weight-of-evidence considerations, it is determined that there is a low concern for increased susceptibility and pre- or post-natal toxicity resulting from exposure to boscalid.

There was no evidence of increased susceptibility in the rat developmental study as no developmental toxicity was seen at the highest dose tested (limit dose).

There was evidence of increased qualitative susceptibility in the rabbit developmental study as characterized by an increased incidence of abortions or early delivery at the limit dose.  It could not be ascertained if the abortions were the result of a treatment-related effect on the dams, the fetuses or both. It was concluded that the 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.

There was evidence of increased quantitative susceptibility seen in the rabbit developmental study and the developmental neurotoxicity study, in that reduced body weights were seen in the offspring at dose levels where no parental toxicity was observed.  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, and the effect was shown to be reversible in the developmental neurotoxicity study.

Therefore, it was determined that the FQPA Safety Factor can be reduced to 1X because there 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 study after establishing toxicity endpoints and traditional uncertainty factors to be used in the risk assessment.

4.4.1	Completeness of the Toxicology Database

The toxicity database is considered complete and adequate for risk 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, acute and subchronic neurotoxicity studies and an immunotoxicity study are also available.  The subchronic inhalation study is required because the use of an oral point of departure (POD) results in MOEs as low as 370 for occupational exposure, which the Hazard and Science Policy Council has determined is not sufficient to alleviate concern (TXR0056585. K.Rury. 03/04/2013).  Therefore, a 10x database uncertainty factor has been added for inhalation exposure.


4.4.2	Evidence of Neurotoxicity

There was no evidence of neurotoxicity based on an acute neurotoxicity study, a 90-day neurotoxicity study and a developmental neurotoxicity study (all in rats).  There was no evidence of neurotoxicity in the other subchronic and chronic studies in the database.

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

There 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 study 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 tested (limit dose).

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 limit dose.  It could not be ascertained if the abortions were the result of a treatment-related effect on either the dams, the fetuses, or both. The 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.

There was quantitative evidence of increased susceptibility in the two-generation reproduction study in rats, where decreases in body weights and body weight gains in male offspring were seen in the F2 generation at a dose that was lower than the dose that induced 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 that 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 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 durations (subchronic and chronic exposures) which were not observed at the LOAELs in either the two-generation reproduction or the developmental 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)

4.4.4	Residual Uncertainty in the Exposure Database

There are no residual uncertainties identified in the exposure databases.  The chronic dietary food exposure assessments were performed using tolerance level residues, average percent crop treated estimates and 100% crop treated assumptions (for new 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 employing surrogate study data, including conservative exposure assumptions based on Day 0 contact to turf and surfaces treated at the maximum application rate.  These 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 dietary exposure assessment were slightly refined, these assessments will not underestimate the exposure and risks posed by boscalid. 

4.5	Toxicity Endpoint and Point of Departure Selections

4.5.1	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 endpoints:  As there were no toxic effects attributable to a single dose, including the developmental toxicity studies, an endpoint of concern was not identified to quantify 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 limit dose (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, carcinogenicity 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)
                                  LOAEL: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 and body weight gains 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 durations (subchronic and chronic exposures) 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. Neither dermal nor systemic toxicity was seen at the limit dose (1000 mg/kg/day) in the 28-day dermal toxicity study in rats.  The oral NOAEL of 21.8 mg/kg/day was selected because of the concerns for the decreases in the body weight and body weight gains seen in the offspring in the two-generation reproduction and the developmental neurotoxicity studies.  Additionally, this dose would be protective of the thyroid and hepatotoxicity 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 to 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 and body weight gain as well as hepatocyte degeneration in males only.  No such effects were observed in the 28-day dermal study.

The use of an oral point of departure (POD) for inhalation exposure results in MOEs as low as 370 for occupational exposure, which is not sufficient to alleviate concern (TXR0056585. K. Rury. 03/04/2013).  Therefore a 10X database uncertainty factor has been added for inhalation exposures.

4.5.2	Recommendation for Combining Routes of Exposure for Risk Assessment

As per FQPA, 1996, when there are potential residential exposures to a pesticide, aggregate risk assessment must consider exposures from three major sources: oral, dermal and inhalation exposures.  Since all endpoints are from the same study, exposures from oral, dermal and inhalation exposure routes can be aggregated.

4.5.3	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 (TXR0051289. 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 mutagenic studies were negative with or without activation.  Based on the overall weak evidence of carcinogenic effects, the CARC indicated that a dose-response assessment for cancer (either linear low-dose extrapolation or margin of exposure calculation) was not needed.

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

Table 4.5.4.1. Summary of Toxicological Doses and Endpoints for Boscalid for Use in Dietary and Non-Occupational Human Health Risk Assessments.
Exposure/ Scenario
Point of Departure
Uncertainty/FQPA 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
UFA= 10x
UFH=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
UFA= 10x
UFH=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
UFA= 10x
UFH=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 Short- Term (1-30 days) & Intermediate-Term (1-6 months)
NOAEL= 21.8 mg/kg/day
UFA = 10x
UFH = 10x
UFDB = 10x
FQPA SF= 1x
Residential LOC for MOE = 1000
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 from 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.  UFA = extrapolation from animal to human (interspecies).  UFH = potential variation in sensitivity among members of the human population (intraspecies).  UFDB = 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.

Table 4.5.4.2. 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)
NOAEL= 21.8 mg/kg/day
UFA = 10x
UFH =10x
FQPA SF= 1x
Occupational 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 Intermediate-Term (1-6 months)
NOAEL= 21.8 mg/kg/day
UFA = 10x
UFH = 10x
FQPA SF= 1x
Occupational 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 Short-Term (1-30 days)
NOAEL= 21.8 mg/kg/day
UFA = 10x
UFH=10x
UFDB = 10x
FQPA SF= 1x
Occupational LOC for MOE = 1000
Co-critical chronic rat, carcinogenicity rat, and 1-year dog studies
LOAEL = 57-58 mg/kg/day based on liver and thyroid effects
Inhalation Intermediate-term (1-6 months)
NOAEL= 21.8 mg/kg/day
UFA = 10x
UFH =10x
UFDB = 10x
FQPA SF = 1x
Occupational LOC for MOE = 1000
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 from 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.  UFA = extrapolation from animal to human (interspecies).  UFH = potential variation in sensitivity among members of the human population (intraspecies).  UFDB = 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.

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, DP286786, M. Nelson, 1/9/03).  HED has concluded that the residue of concern in plants is boscalid for purposes of tolerance enforcement and risk assessment.  The nature of boscalid residues in livestock is adequately understood, based upon acceptable [14]C metabolism studies conducted on lactating goats and laying hens.  In both goats and hens, parent boscalid, M510F01 (hydroxy metabolite), and M510F 02 (M510F01 glucuronide) were identified as the major residues, each with >=10% TRR.  No amide bridge cleavage products were identified.  Based on the structural similarity of boscalid and M510F 01, and the fact that the enzymatic hydrolysis 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 residue of concern for boscalid is the parent only.

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
                                    parent
                                    parent

Rotational Crop
                                    parent
                                    parent
Livestock
Ruminant
                        parent, M510F 01 & M510F02
                        parent, M510F 01 & M510F02

Poultry
                        parent, M510F 01 & M510F02
                        parent, M510F 01 & M510F02
Drinking Water
                                  parent only
                                Not Applicable

5.2	Food Residue Profile

Field trial data on artichoke (MRID 48897401), Belgium endive (MRID 48897402), and persimmon (MRID 48897403) have been submitted to support the proposed tolerances.  These data are adequate to support dietary risk assessment as well as the proposed tolerances of boscalid on artichoke, Belgium endive, and persimmon.  The number and geographic distribution of the field trials are adequate.  The analytical method was demonstrated to be acceptable via concurrent recoveries of fortified control samples.  The intervals of frozen storage of samples are covered by previous storage stability studies, and no corrections for loss of residue are needed.  The trials were conducted according to the proposed labels (single and seasonal application rates, PHI).  Summaries of the residue data from the crop field trials are presented in Appendix D, Table D-1 through D-3.

Greenhouse Grown Tomato Transplants Grown for Home Consumer Market
BASF Corporation has requested the addition of greenhouse tomato use for commercial production and for tomato transplants grown for the home consumer market to the Pageant(TM) Fungicide label (EPA Reg. No. 7969-251).  This product is identical to Pristine(TM) Fungicide (EPA Reg. No. 7969-199), which includes use on greenhouse tomatoes, but does not cover tomato transplants for consumers or use of lathe type structures.  No residue chemistry data were submitted with this request.

Residues on tomato fruits from such use of Pristine(TM) Fungicide (EPA Reg. No. 7969-199) for tomato transplants in green house, lath house, and other production structures would be expected to be less than those found in the greenhouse trials supporting the approved greenhouse use.  The existing tolerance for fruiting vegetables will cover the requested new uses of the Pageant(TM) Fungicide (EPA Reg. No. 7969-251) formulation.

Residential Use of FT09 (EPA File Symbol 4-UII) on Pome Fruit, Stone Fruit, and Tree Nuts
The submitted use directions are sufficient to allow for evaluation of the proposed residential use of FT09 based on comparison to the existing BASF Pristine[(R)] label for agricultural uses.  The BASF formulation is a water dispersible granule.  It is a solid material that forms a dispersion when mixed with water.  The Bonide formulation is a suspension concentrate or suspension of solid materials in water.  It also will form a dispersion when mixed with water.  The formulations are expected to behave similarly when applied in the same manner (same rate) to crops.  The Organization of Economic Cooperation and Development (OECD) Crop Field Trial Guidance recognizes such formulations as yielding the same residues at PHIs greater than 7 days.  All relevant Bonide PHIs exceed 7 days, and therefore the resulting residues based on formulation will not be greater than residues from the BASF formulation.

The PHIs for the Bonide formulation are equal to or longer/greater than the BASF Pristine(R) formulation PHIs.  Therefore, residues from use on the Bonide formulation are anticipated to be no more than or less than residues from the BASF formulation, based on comparison of the PHIs.  

The application rates (lbs ai/A) for the Bonide formulation, both per application and per season, are approximately equal to or less than the corresponding application rates for the BASF Pristine(R) formulation.  Therefore, residues from the use of the Bonide formulation are anticipated to be no more than or less than residues from the BASF formulation, based on comparison of the application rates.

Residential use of the Bonide FT09 per the proposed label will not yield residues in excess of those from agricultural use of the BASF formulation Pristine[(R)] per the approved label.  

Processed Food and Feed
There are no proposed uses that are relevant to this guideline topic.  There are no processed commodities on artichoke, Belgium endive, or persimmon of regulatory interest.

Livestock
There are no proposed uses that are relevant to this guideline topic.  There are no feed items associated with artichoke, Belgium endive, or persimmons.  Therefore, the previous livestock dietary intake calculations and resulting tolerance recommendations are not changed.

Rotational Crops
The nature of the residue in rotational crops is adequately understood and was summarized in a previous residue chemistry summary document (DP278385, M. Nelson, 8/15/03).  HED has concluded that the residue of concern in rotated crops for purposes of risk assessment and the tolerance expression is parent compound.  Adequate limited and extensive field rotational crop 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

The drinking water residues used in the dietary risk assessment were provided by EFED (D409880, K. White, 04/17/2013) and incorporated directly into the dietary assessment.  Water residues were incorporated in the DEEM-FCID into the food categories "water, direct, all sources" and "water, indirect, all sources."

The drinking water assessment considered new uses on Belgium endive, globe artichoke, and persimmon and new uses on tomatoes in greenhouses and lath houses, and homeowner garden spray and ornamental applications.  All existing uses were also considered.

Surface water estimated 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, D405064) 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 Concentration 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 water, 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 concentrations 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 purposes.

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 used 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 Based on Boscalid Use on Turf.[1]
Source of Drinking Water
                                     Acute
                                    (ug/L)
                  Annual Average or Post Breakthrough Average
                                    (ug/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.  

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.

A partially refined chronic dietary analysis was conducted.  The chronic dietary exposure and risk assessment is based on tolerance-level residues for all commodities.  The data used in the 2009 dietary assessments were also used in this current analysis except for the addition of tolerances for globe artichoke, Belgium endive, and persimmon.  The Biological Economic Analysis Division (BEAD) has provided percent crop treated information for boscalid (J. Alsadek, BEAD, 03/08/2013).  The EDWC for boscalid (697 ug/L) was calculated based on a turf scenario for ground water.

The analysis includes HED-recommended tolerance level residue values for the herb subgroup 19A, although these tolerances were never finalized.  The tolerances were recommended in connection with PP# 6E7164 and PP#7F7169 (DP 336632, C. Olinger, 11/27/2007).  At the request of the Registration Division, 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 processing 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 data were not available, DEEM (version 7.81) processing factors were used (DP# 336633, D. Davis, 12/17/2007).

Boscalid is classified as "not likely to be carcinogenic to humans".  Therefore, a cancer dietary exposure assessment was not conducted.

5.4.2	Percent Crop Treated Used in Dietary Assessment

BEAD has provided percent crop treated information for boscalid (J. Alsadek, BEAD, 03/08/2013).  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 <2.5%; cherries 45%; cucumbers 5%; dry beans/dry peas <2.5%; garlic 5%; grapes 30%; hazelnuts 5%; lettuce 25%; nectarines 15%; onions 20%; peaches 20%;  peanuts <1%; pears 15%; green peas <1%; peppers <2.5%; pistachios 30%; plums/prunes 5%; potatoes 20%; pumpkins 10%; squash 5%; strawberries 55%; tomatoes 5%; walnuts <1%; watermelons 25%.

5.4.3	Acute Dietary Risk Assessment

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.

5.4.4	Chronic Dietary Risk Assessments

The chronic dietary analysis was performed using tolerance level residues, average percent crop treated estimates, and 100% crop treated assumptions for new proposed uses.  Dietary risk estimates were determined considering exposures from food plus drinking water.  Boscalid exposure from the existing uses, including tolerance modifications to harmonize with Codex, and the proposed new uses on persimmon, Belgium endive, and globe artichoke results in estimated risks 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 20% of the chronic population adjusted dose (cPAD) for the U.S. population and 56% for children 1-2 years 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
                                     Cancer
                                        
                          Dietary Exposure (mg/kg/day)
                                     % aPAD
                          Dietary Exposure (mg/kg/day)
                                     % cPAD
                          Dietary Exposure (mg/kg/day)
                                      Risk
 General U.S. Population
                                      N/A
                                      N/A
                                    0.042751
                                       20
                                      N/A
                                      N/A
 All Infants (< 1 year old)
                                        
                                        
                                    0.091079
                                       42
                                        
                                        
 Children 1-2 years old
                                        
                                        
                                    0.121118
                                       56
                                        
                                        
 Children 3-5 years old
                                        
                                        
                                    0.088299
                                       41
                                        
                                        
 Children 6-12 years old
                                        
                                        
                                    0.047744
                                       22
                                        
                                        
 Youth 13-19 years old
                                        
                                        
                                    0.029796
                                       14
                                        
                                        
 Adults 20-49 years old
                                        
                                        
                                    0.036670
                                       17
                                        
                                        
 Adults 50+ years old
                                        
                                        
                                    0.038128
                                       18
                                        
                                        
 Females 13-49 years old
                                        
                                        
                                    0.036893
                                       17
                                        
                                        
[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 proposed residential uses for boscalid will result in residential handler and post-application exposures.  In addition, the existing use on golf course turf (Emerald Fungicide label; EPA Reg. No. 7969-1964) was reassessed in this document to reflect updates to HED's 2012 Residential SOPs along with policy changes for body weight assumptions, since the revisions to these exposures could impact the human health aggregate risk assessment for boscalid.  Registered and proposed products do not lead to any residential handler or post-application risk estimates of concern.

6.1	Residential Handler Exposure

The residential handler assessment includes short-term exposures via the dermal and inhalation routes from treating gardens, trees, and turf.  

HED's LOC for the MOE is defined by the uncertainty factors that are applied to the assessment.  HED applies a 10X factor 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 non-cancer dermal assessment of boscalid is 100X for residential exposure.  Residential dermal exposure and risk resulting in MOEs greater than or equal to 100 will not be of concern to HED (LOC = 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 non-cancer inhalation assessments of boscalid is 1000X for residential handler exposure.  Residential 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 combined in this assessment because the PODs are based on the same toxicological study, thus the effects for these 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) are different.  The LOC ARI is 1; therefore, ARIs of less than 1 are risk estimates of concern.  

Summaries of the inhalation and dermal risk estimates for residential handlers are included in Table 6.1.  The maximum application rate for each exposure scenario is presented as the worst case scenario.  The residential handler ARIs range from 24 to 330.  Therefore, the dermal and inhalation risk estimates to residential handlers are not of concern to HED for any of the residential handler scenarios.




Table 6.1.  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/Loader/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 = Dermal Unit Exposure (mg/lb ai) x Application Rate (lb ai/acre or gal) x Area Treated or Amount Handled (A/day or gallons/day) x Dermal 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) x Application Rate (lb ai/acre or gal) x Area Treated or Amount Handled (A/day or gallons/day) / BW (80 kg).
6	Inhalation MOE = Inhalation NOAEL (mg/kg/day) / Inhalation Dose (mg/kg/day).
7 Aggregate Risk Index (ARI) = 1/ (1 / RIdermal) + (1 / RIinhalation) 
   Risk Index (RI) = MOE / LOC; Inhalation LOC = 1,000 and Dermal LOC = 100



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.  Incidental oral exposure to children 1 to <2 years old is not expected from treated turf because boscalid is only registered for use on golf course turf only and proposed for use on residential gardens and trees.  Short-term dermal exposures were assessed for adults, youth 11 to 16 years old, and children 6 to 11 years old.  A series of assumptions and exposure factors served as the basis for completing the residential post-application risk assessment.  Each assumption and factor is detailed in the 2012 Residential SOPs6.

Summary of Residential Post-application Non-Cancer Exposure and Risk Estimates
All the short-term MOEs for each scenario are greater than the LOC of 100, and therefore, are not of concern.  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.  Additionally, DFR studies are not required at this time for boscalid since the lowest dermal MOE (690) is greater than 4 times the LOC based on default input values.

Table 6.2.  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
                                      690
                               Child (6-11 yrs)
                                       
                                       
                                       
                                     0.022
                                     1000
                                     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
                                 0.35 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(R) Fungicide (EPA Reg. No.7969-251); and the registered golf turf use on Emerald(R) Fungicide label (EPA Reg. No. 7969-196).
2	Dermal MOE = Dermal NOAEL (21.8 mg/kg/day) / Dermal Dose (mg/kg/day).

6.3	Combined Residential Risk Estimates (Multiple Exposure Scenarios)

Because dermal post-application exposures to treated gardens, fruit or nut trees, and turf could conceivably co-occur within the same day for adults and children 6 to 11 year olds, combined exposures from these scenarios were considered.  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 Tables 6.1 and 6.2 reflect the residential risk estimates that are recommended for use in the aggregate assessment for boscalid.  Table 6.4 presents the residential risk estimates that are recommended for use in the aggregate assessment for boscalid.

   * The recommended residential dermal 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 treated 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
                                      690
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
                                    10,000
[1] Daily Dose = See table 6.1 for adult handler scenarios and Table 6.2 for post-application scenarios.
2 MOE = NOAEL/Daily Dose

6.5	Residential Bystander Post-application Inhalation Exposure

Based on the Agency's current practices, a quantitative post-application inhalation exposure assessment was not performed for boscalid at this time primarily because of the low acute inhalation toxicity (Toxicity Category IV), low vapor pressure (5.3 x 10[-9] mm Hg at 20[0] C), and the low proposed use rates (0.22 to 0.36 lb ai/A).  However, 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, Fungicide, and Rodenticide Act Scientific Advisory Panel (SAP) in December 2009, and received the SAP's final report on March 2, 2010.  The Agency is in the process of evaluating the SAP report and may, as appropriate, develop policies and procedures to identify the need for and, subsequently, the way to incorporate post-application inhalation exposure into the Agency's risk assessments.  If new policies or procedures are developed, the Agency may revisit the need for a quantitative post-application inhalation exposure assessment for boscalid.

6.6	Spray Drift

Spray drift is always a potential source of exposure to residents nearby to spraying operations.  This is particularly the case with aerial application, but, to a lesser extent, could also be a potential source of exposure from the ground application method employed for boscalid.  The Agency has been working with the Spray Drift Task Force, 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 Spray Drift website for more information).  The Agency has completed its evaluation of the new database submitted by the Spray Drift Task Force, a membership of U.S. pesticide registrants, and is developing a policy on how to appropriately apply the data and the AgDRIFT computer model to its risk assessments for pesticides applied by air, orchard airblast and ground hydraulic methods.  After the policy is in place, the Agency may impose further refinements in spray drift management practices to reduce off-target drift with specific products with significant risk estimates associated with drift.

Although a quantitative residential post-application inhalation exposure assessment was not performed as a result of pesticide drift from neighboring treated agricultural fields, an inhalation exposure assessment was performed for flaggers.  This exposure scenario is representative of a worst case inhalation (drift) exposure and may be considered protective of most outdoor agricultural and commercial post-application inhalation exposure scenarios.

7.0 Aggregate Exposure/Risk Characterization

In accordance with FQPA, HED must consider and aggregate (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 NOAEL 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.  

This assessment considers the changes in the 2012 Residential SOPs implemented in January 2012.  HED confirms that there are no exposure risks of concern resulting from boscalid on globe artichoke, Belgium endive, or persimmon, nor from utilizing the 2012 Residential SOPs to estimate residential exposure and risk.  

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.

74.2 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 conservative scenarios were chosen for each.  For a description of the residential exposure scenarios considered in the aggregate assessment, see Section 6.4.  

The non-cancer aggregate MOEs are 490 for children 6 to 11 years old, 1,300 for youths 11 to 16 years old, and 410 for adults.  None of these aggregate risk estimates are of concern to HED.

Table 7.2.1.  Short-Term Aggregate Risk Calculations 
                                   Lifestage
                                   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
                                   0.047744
                                      460
                                      310
                                Youth 11-16 yrs
                   Post-application golfing on treated turf
                                     21.8
                                    0.0018
                                    12,000
                                     21.8
                                   0.029796
                                      730
                                      690
                                     Adult
                Post-application activities in treated gardens
                                     21.8
                                     0.032
                                      680
                                     21.8
                                   0.042751
                                      510
                                      290
[1] The Level of Concern MOE is 100.
[2] Total Combined MOE = 1/ [(1/MOEDermal) + (1/MOEOral)]

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. population and all population subgroups).  The dietary exposure is estimated at 0.042751 mg/kg/day for the general U.S. population (20% of the cPAD) and 0.121118 mg/kg/day (56% of the cPAD) for children 1-2 years old, the population subgroup with the highest estimated chronic dietary exposure to boscalid.  See Section 5.4.4 for details.

6.0 Cumulative Exposure/Risk Characterization

Unlike other pesticides for which EPA has followed a cumulative risk approach based on a common mechanism of toxicity, EPA has not made a common mechanism of toxicity finding as to boscalid and any other substances and boscalid does not appear to produce a toxic metabolite produced by other substances.  For the purposes of this tolerance 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 effects 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://www.epa.gov/pesticides/cumulative/.

7.0 Occupational Exposure/Risk Characterization

Boscalid is proposed for new occupational uses on globe artichoke, Belgium endive, persimmon, and greenhouse grown tomatoes.  Application methods, maximum application rates, and use sites are summarized in Section 3.3 and Table 3.3.  Based on the proposed use patterns, there is a potential for short- and intermediate-term occupational exposure to boscalid during handling (mixing, loading, and applying) and post-application activities.  Boscalid uses are proposed for multiple applications, with the retreatment intervals ranging from 7 to 28 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 labels require occupational handlers to wear the following personal protective equipment (PPE): long-sleeved shirts, long pants, chemical resistant gloves, and coveralls in a few cases.  The 12 hour restricted entry interval (REI) listed on the labels 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 functions or tasks related to applications and exposures can vary depending on the specifics of each task.  Job requirements (amount of chemical used in each application), the kinds of equipment used, the target being treated, and the level of protection used by a handler can cause exposure levels to differ in a manner specific to each application event.  

Based on the anticipated use patterns from the proposed labels, 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 factor 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 uncertainty 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 combined in this assessment because the PODs are based on the same toxicological study, thus the effects for these 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) are different.  The LOC ARI is 1; therefore, ARIs of less than 1 are risk estimates of concern.  

Summaries of the short- and intermediate-term non-cancer risk estimates for occupational handlers applying boscalid are provided in Appendix E, Table E-1.  The dermal MOEs range from 410 (mixing/loading of WDG formulation to support aerial and chemigation applications to artichoke and persimmon) to 1800 (applying with aerial equipment to typical artichoke) 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 1500 (mixing/loading of WDG formulation to support aerial and chemigation applications to artichoke and persimmon) to 400,000 (applying with manually pressurized equipment to greenhouse tomatoes) at baseline PPE (no respirator).  All of the inhalation MOEs are greater than the LOC of 1,000 when assessed at baseline PPE and are not a concern to HED.  Furthermore, all of the ARIs are greater than 1.0 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 exposures 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 the potential for post-application exposure. 

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-application risk assessment for dermal exposures is needed.  It should be noted that there is no post-application dermal exposure anticipated for the proposed Belgium endive use, because the roots are treated with pyraclostrobin prior to forcing in the trays.  Thus there would be negligible exposure to the residue when the crop is harvested or maintained.

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 400 to 21,000.  DFR studies are not required at this time for boscalid since the lowest dermal MOE (400) is greater than 4 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.  

Restricted Entry Interval
The REI specified on the proposed label is based on the acute toxicity of boscalid. Boscalid is classified as Toxicity Category III via the dermal route 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 40 CFR 156.208 (c) (2) (iii), ai'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 protect agricultural workers from post-application exposures to boscalid.

9.2.2	Inhalation Post-Application Risk

Based on the Agency's current practices, a quantitative post-application inhalation exposure assessment was not performed for boscalid at this time primarily because of the low acute inhalation toxicity (Toxicity Category IV), low vapor pressure (5.3 x 10[-9] mm Hg at 20[o] C) and the low proposed use rate (0.22 to 0.36 lb ai/A).  However, 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 Federal Insecticide, Fungicide, and Rodenticide Act Scientific Advisory Panel (SAP) in December 2009, and received the SAP's final report on March 2, 2010. The Agency is in the process of evaluating the SAP report as well as available post-application inhalation exposure data generated by the ARTF and may, as appropriate, develop policies and procedures, to identify the need for and, subsequently, the way to incorporate occupational post-application inhalation exposure into the Agency's risk assessments.  If new policies or procedures are put into place, the Agency may revisit the need for a quantitative occupational post-application inhalation exposure assessment for boscalid.

Although a quantitative occupational post-application inhalation exposure assessment was not performed, an inhalation exposure assessment was performed for occupational/commercial handlers.  Handler exposure 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-application inhalation exposure scenarios.

The Worker Protection Standard for Agricultural Pesticides contains requirements for protecting workers from inhalation exposures during and after greenhouse applications through the use of ventilation requirements [40 CFR 170.110, (3) (Restrictions associated with pesticide applications)].

10.0	References

S. Funk, 4/30/13, DP398877.  Boscalid and Pyraclostrobin:  Application by Bonide Products, Inc. to Register an End Use Product Containing Pyraclostrobin, Boscalid, and Lambda Cyhalothrin for Homeowner Use on Pome Fruit, Stone Fruit, and Tree Nuts.  

S. Funk, 4/30/13, DP406471.  Pyraclostrobin and Boscalid:   Request to Add Indoor Use on Greenhouse Tomato for Commercial Production and on Greenhouse/Lathhouse Transplants for Consumer Home Market. Pagent(TM) Fungicide Reg. No. 7969-251.

S. Funk, 4/30/13, DP405063.  Boscalid: Petition for the Establishment of Permanent Tolerances and Registration for Use on Belgium Endive, Persimmon, and Globe Artichoke. Request for Crop Group Expansions/Revisions for Bulb Vegetable Group 3-07, Fruiting Vegetable 8-10,  Citrus Fruit Group 10-10, Pome Fruit Group 11-10, Berry Subgroups 13-07A, B, F, and G, and Oilseed Group 20. Summary of Analytical Chemistry and Residue Data. 

S. Funk, 6/24/13, DP410743.  Revised: Boscalid. Chronic Aggregate Dietary (Food and Drinking Water) Exposure and Risk Assessments to Support New Uses on Globe Artichoke, Belgium Endive, and Persimmon.

C. Walls, 4/30/13, DP405533.  Boscalid.  Occupational and Residential Exposure Assessment for proposed new uses of boscalid on globe artichoke, Belgium endive, persimmon, greenhouse grown tomato transplants grown for home consumer market, and residential ornamentals, landscape gardens, fruit trees and nut trees.

K. White, 4/17/13, DP409880.  Tier I Drinking Water Exposure Assessment for the Section 3 New Uses of Boscalid on Various Agricultural Crops and Homeowner Uses.

Appendix A.  Toxicology Profile and Executive Summaries

A.1	Toxicology Data Requirements

The requirements (40 CFR 158.500) for food uses 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
                                      yes
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	in vitro Mammalian Cell Gene Mutation Test	
870.5375	in 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
                                      ---
                                      ---
                                      ---
CR: Conditionally Required



A.2	Toxicity Profiles
 Table A.2.1.  Acute Toxicity of Boscalid


Table A.2.1.  Acute Toxicity Profile  -  Boscalid (BAS 510 F) Technical

                                 Test Material

                                       
                                     GDLN
                                       

                                       
                                  Study Type

                                       
                                     MRID

                                       
                                    Results

                                      Tox
                                   Category

                                   Technical
                                       

                                   870.1100

                               Acute Oral - rat

                                   45404814
                                       

                             LD50 > 5000 mg/kg
                                       

                                      IV
                                       

                                   Technical

                                   870.1200

                              Acute Dermal - rat

                                   45404815

                             LD50 > 2000 mg/kg

                                      III

                                   Technical

                                   870.1300

                               Acute Inhalation

                                   45404816

                        LC50 (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

                                   45404819
                                       
                                       

              Study unacceptable as challenge dose was inadequate
                                       

                                      N/A


 
 Table A.2.2.  Non-acute Toxicity Profile for Boscalid
 

  Table A.2 Repeated Dose Toxicity Profile of Boscalid (BAS 510 F) Technical.

                                 Guideline No.

                                  Study Type

                                    Results

870.3100

90-Day oral toxicity rodents (rats)

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

870.3100

90-Day oral toxicity rodents (mice)

NOAEL: 197/2209 mg/kg/day (M/F)
LOAEL: 788/2209 mg/kg/day (M/F): M = increased liver weights and increased incidence of marked fatty change in the liver; F = not attained

870.3150

90-Day oral toxicity in nonrodents (dogs)

NOAEL: 7.6/8.1 mg/kg/day (M/F)
LOAEL: 78.1/81.7 mg/kg/day (M/F): M = increased alkaline phosphatase activity and hepatic weights; F = increased alkaline phosphatase activity and hepatic weights.

870.3200

21/28-Day dermal toxicity
(rats)

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

870.3700

Prenatal developmental in rodents (rats)

Maternal NOAEL: 1000 mg/kg/day
Maternal LOAEL: cannot be established
Developmental NOAEL: 1000 mg/kg/day
Developmental LOAEL: cannot be established

870.3700

Prenatal developmental in nonrodents (rabbit)

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

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 and body weight gain (F1) as well as hepatocyte degeneration F0 and F1) 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 F2 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)

NOAEL: 21.9/30.0 mg/kg/day (M/F)
LOAEL: 110.0/150.3 mg/kg/day (M/F): M = thyroid toxicity (weights and microscopic changes); F = thyroid toxicity (weights and microscopic changes). Thyroid follicular cell adenomas: M = 0/20, 0/20, 2/20,1/20; F = 0/20, 0/20, 1/20,0/20.

870.4100

Chronic toxicity dogs

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 rats

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 body weight gain and increased incidence of thyroid follicular cell hyperplasia and hypertrophy.  Thyroid follicular cell adenomas: M = 0/50, 0/50, 1/50, 4/50; F = 0/50, 1/50, 0/50, 3/50.

870.4200

Carcinogenicity mice

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

870.4300

Chronic feeding/Carcinogenicity rat

See 870.4100a and 870.4200.

870.5100

Gene Mutation bacterial reverse mutation assay

Negative without and with S-9 activation up to limit dose of 5000 ug/plate.

870.5300

In vitro mammalian cell forward gene mutation assay (CHO cells/HGPRT locus)

Negative without and with S-9 activation up to the limit of solubility of 25 ug/mL.

870.5375

In vitro mammalian cytogenetics assay in Chinese hamster V79 cells

Negative without and with S-9 activation up to 3500 ug/mL with precipitation showing at concentrations of 100 ug/mL and higher.

870.5395


Cytogenetics - mammalian erythrocyte micronucleus test in the mouse

Negative at doses up to 2000 mg/kg.

870.5500


In vitro unscheduled DNA synthesis (primary rat hepatocytes)

Negative response up to 50 ug/mL.  Cytotoxicity at 100-500 ug/mL.

870.6200

Acute neurotoxicity screening battery (rat)

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

870.6200

Subchronic neurotoxicity screening battery (rat)

NOAEL:1050.0/1272.5  mg/kg/day (M/F)
LOAEL: >1050.0/1272.5 mg/kg/day (M/F)

870.6300

Developmental neurotoxicity (rat)

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

870.7485

Metabolism and pharmacokinetics (rat)

BAS 510 F was readily absorbed and excreted following single oral 50 mg/kg; at single 500 mg/kg or 15 doses of 500 mg/kg, absorption was saturated.  Excretion mainly by feces (80-98%).  Biliary excretion 40-50% of fecal activity at 50 mg/kg, 10% at 500 mg/kg.  Urine, about 16% at 50 mg/kg, 3-5% at 500 mg/kg.  Absorption about 56% at 50 mg/kg and 13-17% at 500 mg/kg.  Excretory patterns similar by gender or radiolabel position.  Metabolites (hydroxylation and conjugation products) were consistent with Phase I oxidation reactions followed by Phase II conjugation with glucuronic acid or sulfate, or by conjugation of the parent with glutathione with cleavage to sulfate metabolites.

870.7800
Immunotoxicity

MRID 48203801 (2003)

0, 100, 1000, or 10000 ppm 0, 7.45, 73.1, or 736.2 m/k/d 

Acceptable / Guideline

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

870.7600

Dermal Penetration (rat)

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)

none

SPECIAL STUDY: Hepatic enzyme induction  (rat)

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

none

SPECIAL STUDY: Hormone and enzyme induction (rat)

1. slight (statistically significant) decrease in circulating T3 and T4 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 T3 and T4 and increasing TSH; likely the result of hepatic microsomal glucuronyltransferase induction

none

SPECIAL STUDY: Reversibility study (dietary): 4-week administration followed by 4 weeks recovery or 13 weeks recovery (rat)

4 weeks dosing: at 2500 and 15000 ppm: increase in TSH (68% and 87%); 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 weeks recovery: no increases in TSH; increase in absolute and relative thyroid weights; thyroid hypertrophy and hyperplasia decreased to control values; all liver effects reversed to control.

CONCLUSION: induction of liver microsomal enzyme system resulting in increased glucuronidation of thyroxine, resulting in an increase in TSH secretion as a compensatory response of the physiological negative feedback system; increased TSH resulted in increased thyroid weight.

 
 

 
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, pKa
None (does not dissociate in water)

Octanol/water partition coefficient, Log(KOW)
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).  



Appendix D.  Summaries of Field Residue Data


Table D-1.  Summary of Residue Data from Globe Artichoke Crop Field Trials with Boscalid.
                                   Commodity
                              Total Applic. Rate
                                   (lb ai/A)
                                  [kg ai/ha]
                                  PHI (days)
                                    Analyte
                               Residue Levels[1]
                                     (ppm)
                                       
                                       
                                       
                                       
                                       n
                                  SampleMin.
                                    Sample
                                     Max.
                                    LAFT[2]
                                    HAFT[2]
                                    Median
                                     Mean
                                   Std. Dev.
                             Artichoke Flower Head
                                  1.081-1.105
                                  (1.21-1.24)
                                       0
                                   Boscalid
                                       3
                                     1.159
                                     2.596
                                     1.446
                                     2.563
                                     1.722
                                     1.910
                                     0.582
[1]  Except for sample min/max, values reflect per trial averages; n = no. of field trials. Statistics were calculated by the study reviewer. 
[2]  LAFT = lowest average field trial; HAFT = highest average field trial.

Table D-2.  Summary of Residue Data from Belgium Endive Crop Field Trials with Boscalid.
                                   Commodity
                                    Rate[1]
                                  PHI (days)
                                    Analyte
                               Residue Levels[2]
                                     (ppm)
                                       
                                       
                                       
                                       
                                       n
                                  SampleMin.
                                    Sample
                                     Max.
                                    LAFT[3]
                                    HAFT[3]
                                    Median
                                     Mean
                                   Std. Dev.
            Treatment 02: One pre-cold-storage application to roots
Belgium endive heads
                        1.14-1.18 g ai/100 lb of roots
                                     25-27
                                   Boscalid
                                       3
                                   <0.05
                                     0.15
                                   <0.05
                                     0.13
                                   <0.075
                                   <0.085
                                     0.041
      Treatment 03: One pre-forcing application to roots in packing tray
Belgium endive heads
                            0.177-0.192 g ai/ft[2]
                                     17-19
                                   Boscalid
                                       3
                                     0.25
                                     2.97
                                     0.28
                                     2.26
                                     1.75
                                     1.43
                                     1.028
Treatment 04: One pre-cold-storage application to roots + One pre-forcing application to roots in packing tray
Belgium endive heads
                      1.16-1.17 g ai/100 lb of roots and
                            0.182-0.199 g ai/ft[2]
                                     17-19
                                   Boscalid
                                       3
                                     0.43
                                     1.41
                                     0.455
                                     1.255
                                     1.05
                                     0.92
                                     0.416
[1]  Rate for boscalid, as calculated by the study reviewer based on the certificate of analysis of applied product in the study report.
[2]  Except for sample min/max, values reflect per trial averages; n = no. of field trials.  For calculation of median, mean, and standard deviation, the LLMV (0.05 ppm) was used for any results reported as <LLMV 
[3]  LAFT = lowest average field trial; HAFT = highest average field trial.

Table D-3  Summary of Residue Data from Persimmon Crop Field Trials with Boscalid.
                                   Commodity
                              Total Applic. Rate
                                   (lb ai/A)
                                  [kg ai/ha]
                                  PHI (days)
                                    Analyte
                               Residue Levels[1]
                                     (ppm)
                                       
                                       
                                       
                                       
                                       n
                                  SampleMin.
                                    Sample
                                     Max.
                                    LAFT[2]
                                    HAFT[2]
                                    Median
                                     Mean
                                   Std. Dev.
                                Persimmon Fruit
                                  1.110-1.126
                                  (1.24-1.26)
                                       0
                                   Boscalid
                                       3
                                     0.184
                                     3.285
                                     0.198
                                     3.019
                                     0.862
                                     1.360
                                     1.475
[1]  Except for sample min/max, values reflect per trial averages; n = no. of field trials.  Statistics were calculated by the study reviewer.
[2]  LAFT = lowest average field trial; HAFT = highest average field trial.




Appendix E.  Summaries of Occupational Handler and Post-application Exposure and Risk Estimates

Table E-1.  Occupational Handler Non-Cancer Exposure and Risk Estimates for Boscalid.
                               Exposure Scenario
                                     Crop
                             Dermal Unit Exposure 
                                (μg/lb ai)[1]
                    Inhalation Unit Exposure (μg/lb ai)[1]
                                    Maximum
                              Application 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]
                              Dose (mg/kg/day)[6]
                                    MOE[7]
                                       
                                 Mixer/Loader
                          Aerial applications of WDG
                                      and
                        Chemigation application of WDG
                                   Artichoke
                                   Persimmon
                                      227
                                     8.96
                                     0.18
                                      350
                                     0.054
                                      410
                                     0.014
                                     1,500
                                      1.1
                          Airblast application of WDG
                                   Persimmon
                                      227
                                     8.96
                                     0.18
                                      40
                                    0.0061
                                     3,600
                                    0.0016
                                    14,000
                                      10
                        Chemigation application of WDG
                                      and
                         Groundboom application of WDG
                              Greenhouse tomatoes
                                      227
                                     8.96
                                     0.18
                                      60
                                    0.0092
                                     2,400
                                    0.0024
                                     9,000
                                      6.5
                         Groundboom application of WDG
                                   Artichoke
                                      227
                                     8.96
                                     0.18
                                      80
                                     0.12
                                     1,800
                                    0.0032
                                     6,700
                                      4.9
                                  Applicator
                              Aerial application
                                   Artichoke
                                   Persimmon
                                       5
                                     0.068
                                     0.18
                                      350
                                    0.0012
                                    18,000
                                    0.00011
                                    200,000
                                      95
                             Airblast application
                                   Persimmon
                                     1770
                                     4.71
                                     0.18
                                      40
                                     0.048
                                      460
                                    0.00085
                                    26,000
                                      3.9
                            Groundboom application
                              Greenhouse tomatoes
                                     78.6
                                     0.34
                                     0.18
                                      60
                                    0.0032
                                     6,800
                                   0.000092
                                    240,000
                                      53
                            Groundboom application
                                   Artichoke
                                     78.6
                                     0.34
                                     0.18
                                      80
                                    0.0042
                                     5,100
                                    0.00012
                                    180,000
                                      40
                                    Flagger
                                    Flagger
                                   Artichoke
                                   Persimmon
                                      11
                                     0.35
                                     0.18
                                      350
                                    0.0026
                                     8,400
                                    0.00055
                                    40,000
                                      27
                            Mixer/Loader/Applicator
                          Backpack application of WDG
                              Greenhouse tomatoes
                                    13,200
                                      140
                                    0.0018
                                   lb ai/gal
                                      40
                                      gal
                                    0.0036
                                     6,100
                                    0.00025
                                    86,000
                                      36
                   Manually pressurized handwand app of WDG
                              Greenhouse tomatoes
                                    100,000
                                      30
                                    0.0018
                                   lb ai/gal
                                      40
                                      gal
                                     0.027
                                      810
                                   0.000054
                                    400,000
                                      7.9
                    Mechanically pressurized handgun of WDG
                                   Artichoke
                                   Persimmon
                                     1300
                                      3.9
                                    0.0018
                                   lb ai/gal
                                     1000
                                      gal
                                    0.0088
                                     2,500
                                    0.00018
                                    120,000
                                      21
                    Mechanically pressurized handgun of WDG
                              Greenhouse tomatoes
                                     3500
                                      120
                                    0.0018
                                   lb ai/gal
                                     1000
                                      gal
                                     0.024
                                      920
                                    0.0054
                                     4,000
                                      2.8
                    Mechanically pressurized handgun of WDG
                   Belgium Endive  -  prior to cold storage
                                     1300
                                      3.9
                                   0.000028 
                                lb ai/ lb root
                                    200,000
                                    lb root
                                     0.014
                                     1,600
                                    0.00027
                                    80,000
                                      13
                    Mechanically pressurized handgun of WDG
                      Belgium Endive  -  prior to forcing
                                     1300
                                      3.9
                                    0.0004
                                  lb ai/ft[2]
                                    10,890
                                     ft[2]
                                     0.011
                                     2,100
                                    0.00021
                                    100,000
                                      17
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) x Conversion Factor (0.001 mg/μg) x Application Rate (lb ai/acre or gal) x Area Treated or Amount  Handled Daily (A or gal/day) x 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) x Conversion Factor (0.001 mg/μg) x Application Rate (lb ai/acre or gal) x Area Treated or Amount  Handled Daily (A or gal/day) / BW (kg).
7	Inhalation MOE = Inhalation NOAEL (mg/kg/day) / Inhalation Dose (mg/kg/day).
8  Aggregate Risk Index (ARI) = 1/ (1 / RIdermal) + (1 / RIinhalation) 
     Risk Index (RI) = MOE / LOC; Inhalation LOC = 1,000 and Dermal LOC = 100



Table E-2.  Occupational Post-application Non-Cancer Exposure and Risk Estimates for Boscalid.
                                   Crop/Site
                                  Activities
                        Transfer Coefficient (cm[2]/hr)
                                    DFR[1]
                                  (ug/cm[2])
                                 Dermal Dose 
                                (mg/kg/day)[2]
                                    MOE[3]
                                   Artichoke
                                Hand Harvesting
                                     1,100
                                     1.01
                                    0.0167
                                     1,300
                                       
                        Hand Weeding, Thinning, Pruning
                                      70
                                       
                                    0.0011
                                    21,000
                                       
                                  Irrigation
                                   (Hand Set)
                                     1,900
                                       
                                     0.029
                                      760
                                       
                                   Scouting
                                      210
                                       
                                    0.0032
                                     6,900
                                       
                                 Transplanting
                                      230
                                       
                                    0.0035
                                     6,300
                                   Persimmon
                       Scouting, Hand Pruning, Training
                                      580
                                     1.01
                                    0.0088
                                     2,500
                                       
                  Hand weeding, Propping, Orchard Maintenance
                                      100
                                       
                                    0.0015
                                    14,000
                                       
                                Hand Harvesting
                                     1,400
                                       
                                     0.021
                                     1,000
                                       
                                 Transplanting
                                      230
                                       
                                    0.0035
                                     6,300
                                       
                                   Thinning
                                     3,600
                                       
                                     0.055
                                      400
                              Greenhouse Tomatoes
Hand Harvesting, Pinching, Hand Pruning, Scouting, Turning, Tying, Hand Weeding, 
                                     1200
                                     1.01
                                     0.018
                                     1,200
                                       
                   Irrigation (Hand Watering), Transplanting
                                      230
                                       
                                    0.0035
                                     6,300
1 DFR = Application Rate x F x (1-D)t x 4.54E8 ug/lb x 2.47E-8 acre/cm[2]; where F = 0.25 and D = 0.10 per day  
2	Daily Dermal Dose = [DFR (ug/cm[2]) x Transfer Coefficient x 0.001 mg/ug x 8 hrs/day x dermal absorption (%)]  BW (kg).
3	MOE = POD (mg/kg/day) / Daily Dermal Dose.  Daily Dermal Dose = [DFR (ug/cm[2]) x TC x 0.001 mg/ug x 8 hrs/day x dermal absorption factor (%)]  BW (kg).



Appendix F.  International Residue Limits Status Sheet

                        Boscalid (128008); 02/21/2013)
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.  The residue is fat soluble.
Commodity[1]
Tolerance (ppm) /Maximum Residue Limit (ppm)

                                      US
Canada
Mexi-co[2]
Codex[3]
Artichoke, globe
                                      6.0
None

None
Belgium endive
(witloof chicory)
                                      6.0
None

None
Persimmon
                                      8.0
None

None
Vegetable, bulb, group 3-07
                                      5.0


5.0
Vegetable, fruiting, group 8-10
                                      3.0
1.4

3.0
Fruit, citrus, group 10-10
                                      2.0


2.0
Fruit, pome, group 11-10
                                      3.0
3.0

2 (Apple)
Caneberry, subgroup 13-07A
                                     10.0
6.0

10 (Berries and other small fruits)
Bushberry subgroup 13-07B
                                     13.0


10 (Berries and other small fruits)
Fruit, small, vine climbing, except fuzzy kiwifruit, subgroup 13-07F
                                      5.0
3.5

5 (Grapes)
Berry, low growing, subgroup 13-07G except cranberry
                                      4.5
4.5
Strawberry
11
Low bush blueberry

3 (Strawberry)
Oilseed group 20
                                      5.0
5.0
Canola oil
Mustard seed oil

1
Vegetable, root, except sugar beet, subgroup 1B, except garden beet, radish, and turnip
                                      2.0
0.7
Carrot
0.7
Rutabaga root
0.7
Burdock root
0.7 Ginseng root
0.7 Horseradish
[1 sugar beet
1 turnip root
1 radish root]

2 (Root and tuber vegetables)
Turnip, tops
                                      40
1.0

40 (Leafy vegetables)
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 quantitation; 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 not been finalized by the CCPR and the CAC.

