Document ID: EPA-HQ-OPP-2009-0268-0005
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2010-05-28T04:00Z

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C.  20460

OFFICE OF PREVENTION, PESTICIDES,

AND TOXIC SUBSTANCES

  SEQ CHAPTER \h \r 1 MEMORANDUM

Date:	05-JAN-2010

SUBJECT:	Boscalid.  Human Health Risk Assessment for Proposed Use on
Alfalfa and Citrus (Crop Group 10), and for Proposed Increase in
Tolerance on Stone Fruits (Crop Group 12).

PC Code:  128008	DP Barcode:  363305

Decision Number:  405556	Registration Number:  NA

Petition Number:  9F7527, 9F9529	Regulatory Action:  Section 3

Risk Assessment Type:  Single Chemical/Aggregate	Case Number:  NA

TXR Number:  NA	CAS Number:  188425-85-6

Chemical Class:  Carboxamide (Anilide) Fungicide	40CFR: §180.589

MRID Numbers: NA	Trade Names: Boscalid Technical, Endura® Fungicide,
Pristine® Fungicide

FROM:  	Nancy J. Tsaur, Risk Assessor

	Amelia Acierto, Chemist

	Barry O’Keefe, ORE Assessor

	Risk Assessment Branch 3 (RAB3) 

	Health Effects Division (HED), 7509P   SEQ CHAPTER \h \r 1 		

		

THROUGH:	Paula Deschamp, Branch Chief

	Registration Action Branch 3 (RAB3)

	Health Effects Division (HED), 7509P

		

TO:		Tony Kish and Bryant Crowe, RM Team 22

		Fungicide Branch (FB)

	Registration Division (RD), 7505P

Introduction

This document addresses three different uses regarding the active
ingredient (ai), boscalid, submitted to the Agency under two petitions
(PP#9F7527 and PP#9F9529): to set a tolerance in/on alfalfa, to set a
tolerance in/on citrus crop group 10, and to increase the current
established tolerance on stone fruit crop group 12.  Concomitant with
setting a tolerance on alfalfa, livestock tolerances must also be set to
account for an updated livestock dietary burden.  BASF Corporation
(BASF) has submitted a petition to register new uses on alfalfa and
citrus fruits for boscalid technical (EPA Reg. No. 7969-198), a new use
on alfalfa for Endura® Fungicide (EPA Reg. No. 7969-197), and new uses
on alfalfa and citrus fruits for Pristine® Fungicide (EPA Reg. No.
7969-199).  Endura® is a water dispersible granular (WDG) formulation
containing 70% boscalid and Pristine® is a WDG formulation containing
25.2% boscalid and 12.8% pyraclostrobin.  Only boscalid is addressed in
this document; pyraclostrobin is being evaluated separately. 

Currently, permanent tolerances are established in the U.S. and Canada
for residues of

boscalid (3-pyridinecarboxamide,
2-chloro-N-(4’-chloro(1,1’-biphenyl)-2-yl)) in/on several crops.
There are no tolerances for residues of boscalid in/on alfalfa and
citrus crops. Boscalid tolerances are established in the U.S. for
residues of boscalid in/on stone fruit crop group 12 at 1.7 parts per
million (ppm) (40 CFR §180.589).

HED has examined the database for boscalid and concludes that pending
submission of a revised Section B for alfalfa, and a revised Section F
for alfalfa, citrus fruit, stone fruit, and livestock as noted below,
there are no deficiencies that would preclude establishing permanent
tolerances for boscalid on alfalfa forage and hay and on the citrus crop
group 10, for increasing the existing tolerance on the stone fruit crop
group 12, and for increasing the existing tolerances on hog fat, poultry
fat, and poultry meat byproducts. However, the deficiencies noted below
must be resolved as a condition of registration.  

Note to PM: HED recommends that the following tolerance definition
entries in 40 CFR §180.589 be revised and that tolerances for the
listed commodities be established, as follows:

(a)	General. 

(1) Tolerances are established for residues of the fungicide boscalid,
including its metabolites and degradates, in or on the commodities
listed below.   Compliance with the tolerance levels specified below is
to be determined by measuring only 

3-pyridinecarboxamide, 2-chloro-N-(4'-chloro[1,1'-biphenyl]-2-yl).

Alfalfa, forage	30.0  ppm

Alfalfa, hay	65.0  ppm

Citrus, dried pulp	4.5 ppm

Citrus, oil	85.0 ppm

Fruit, citrus, group 10	1.6 ppm

Fruit, stone, group 12	3.5 ppm

(2) Tolerances are established for residues of the fungicide boscalid,
including its metabolites and degradates, in or on the food commodities
listed below.  Compliance with the tolerance levels specified below is
to be determined by measuring only the sum of 3-pyridinecarboxamide,
2-chloro-N-(4'-chloro[1,1'-biphenyl]-2-yl) and metabolites
2-chloro-N-(4'-chloro-5-hydroxy-biphenyl-2-yl) nicotinamide and
glucuronic acid conjugate of
2-chloro-N-(4'-chloro-5-hydroxy-biphenyl-2-yl) nicotinamide, calculated
as the stoichiometric equivalent of boscalid.

Hog, fat	0.20 ppm

Poultry, fat	0.20 ppm

Poultry, meat byproducts	0.20 ppm

The established tolerances of the following commodities remain
unchanged. 

Cattle, fat	0.30 ppm

Cattle, meat	0.10 ppm

Cattle, meat byproducts	0.35 ppm

Egg	0.02 ppm

Goat, fat	0.30 ppm

Goat, meat	0.10 ppm

Goat, meat byproducts	0.35 ppm

Hog, meat	0.05 ppm

Hog, meat byproducts	0.10 ppm

Horse, fat	0.30 ppm

Horse, meat	0.10 ppm

Horse, meat byproducts	0.35 ppm

Milk	0.10 ppm

Poultry, meat	0.05 ppm

Sheep, fat	0.30 ppm

Sheep, meat	0.10 ppm

Sheep, meat byproducts	0.35 ppm

(d)	Indirect or inadvertent residues.  

Tolerances are established for residues of the fungicide boscalid,
including its metabolites and degradates, in or on the commodities
listed below.   Compliance with the tolerance levels specified below is
to be determined by measuring only 3-pyridinecarboxamide,
2-chloro-N-(4'-chloro[1,1'-biphenyl]-2-yl). 

Animal feed, nongrass, group 18, forage, excluding alfalfa	1.0 ppm

Animal feed, nongrass, group 18, hay, excluding alfalfa	2.0 ppm

Revision to Petitions for Tolerances

The recommended tolerances in/on alfalfa, citrus, and stone fruits are
based on the crop field trial data.  The appropriate tolerance levels
were determined using the HED Standard Operating Proceedure (SOP)
“Guidelines for Setting Pesticide Tolerances Based on Field Trial
Data.”   

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

860.1200	Direction for Use

A revised Section B for alfalfa is required to amend the label direction
for the 70% WDG formulation since it could not be supported by the field
trial data generated with a maximum seasonal use rate of 0.9 lb ai/A.  
The proposed label rate for the 70% WDG formulation is 1.7X higher; the
label should be revised to match the field trial rate.

860.1550	Tolerances

Boscalid residues concentrate in citrus dried pulp (3.1X) and citrus oil
(59X).  A revised Section F is required to propose separate tolerances
for citrus, dried pulp at 4.5 ppm, citrus, oil at 85 ppm, and fruit,
citrus, group 10 at 1.6 ppm.

The available data for stone fruits will not support a tolerance level
of 5.0 ppm.  A revised Section F should be submitted with a tolerance
for fruit, stone, group 12 at 3.5 ppm.

The available data will not support the proposed tolerances for meat,
meat byproducts, and fat of cattle goat, horse, and sheep at 0.2 ppm,
1.5 ppm, and 1.5 ppm, respectively.  The existing tolerances will be
maintained for meat, meat byproducts, and fat of cattle, goat, horse,
and sheep at 0.10 ppm, 0.35 ppm, and 0.30 ppm, respectively.  The
available data will not support the proposed tolerance of 0.2 ppm for
milk and the proposed tolerance of 1.5 ppm for milk fat.  The existing
tolerance of 0.10 ppm will be maintained for milk, and it is adequate to
cover milk fat.   The proposed tolerances of 0.20 ppm for hog, fat;
poultry, fat; and poultry, meat byproducts are adequate.  For all
remaining livestock commodities, the proposed tolerances must be revised
to reflect the recommended tolerance levels as specified in Table 9.0.

870.7800	Immunotoxicity Study

As part of the new 40CFR §158 Guidelines, an immunotoxicity study in
rats and/or mice is required (see Appendix B).  

Note to PM:   Revisions of the livestock commodities data collection
methods have been included in the registrant’s submissions.  However,
BASF has not indicated whether any of the changes were made in their
attempt to resolve any of the deficiencies noted by HED in the 2003
petition (M. Nelson, DP#278385, 08/15/2003).   If the methods have been
revised and finalized, this should be clarified and the entire final
versions of the enforcement and the data collection methods should be
submitted to the Office of Pesticide Programs (OPP).  Otherwise,
registration for the new or amended use patterns for the boscalid
products should be made conditional until the deficiencies noted above
are fully resolved. 

This document provides a summary of the findings from the data
evaluation and subsequent assessment of human health risk resulting from
these requests.  The residue chemistry data review and dietary exposure
assessment were conducted by Amelia Acierto (RAB3), the occupational
exposure data review was conducted by Barry O’Keefe (RAB3), and the
human health risk assessment was conducted by Nancy J. Tsaur (RAB3);
additionally, the drinking water assessment was conducted by David Lieu
of OPP’s Environmental Fate and Effects Division (EFED).Table of
Contents

  TOC \o "1-6" \h \z \u    HYPERLINK \l "_Toc250451630"  1.0	Executive
Summary	  PAGEREF _Toc250451630 \h  6  

  HYPERLINK \l "_Toc250451631"  2.0	INGREDIENT PROFILE	  PAGEREF
_Toc250451631 \h  10  

  HYPERLINK \l "_Toc250451632"  2.1	Summary of Proposed New Uses	 
PAGEREF _Toc250451632 \h  10  

  HYPERLINK \l "_Toc250451633"  2.2	Structure and Nomenclature/Physical
and Chemical Properties	  PAGEREF _Toc250451633 \h  11  

  HYPERLINK \l "_Toc250451634"  3.0	Hazard Characterization/Assessment	 
PAGEREF _Toc250451634 \h  12  

  HYPERLINK \l "_Toc250451635"  3.1	FQPA Safety Factor	  PAGEREF
_Toc250451635 \h  14  

  HYPERLINK \l "_Toc250451636"  3.2	Summary of Toxicological Doses and
Endpoints	  PAGEREF _Toc250451636 \h  15  

  HYPERLINK \l "_Toc250451637"  3.3	Endocrine disruption	  PAGEREF
_Toc250451637 \h  16  

  HYPERLINK \l "_Toc250451638"  4.0	Dietary Exposure/Risk
Characterization	  PAGEREF _Toc250451638 \h  16  

  HYPERLINK \l "_Toc250451639"  4.1	Nature of the Residue and Residue
Analytical Methods	  PAGEREF _Toc250451639 \h  17  

  HYPERLINK \l "_Toc250451640"  4.2	Pesticide Metabolites and Degradates
of Concern	  PAGEREF _Toc250451640 \h  18  

  HYPERLINK \l "_Toc250451641"  4.3	Drinking Water Residue Profile	 
PAGEREF _Toc250451641 \h  18  

  HYPERLINK \l "_Toc250451642"  4.4	Food Residue Profile	  PAGEREF
_Toc250451642 \h  19  

  HYPERLINK \l "_Toc250451643"  4.5	Dietary Exposure and Risk	  PAGEREF
_Toc250451643 \h  25  

  HYPERLINK \l "_Toc250451644"  4.5.1	Acute Dietary Exposure Results and
Characterization	  PAGEREF _Toc250451644 \h  25  

  HYPERLINK \l "_Toc250451645"  4.5.2	Chronic Dietary Exposure Results
and Characterization	  PAGEREF _Toc250451645 \h  25  

  HYPERLINK \l "_Toc250451646"  4.5.3	Cancer Dietary Exposure Results
and Characterization	  PAGEREF _Toc250451646 \h  26  

  HYPERLINK \l "_Toc250451647"  4.5.4	Results of Chronic Dietary
Exposure Analysis	  PAGEREF _Toc250451647 \h  26  

  HYPERLINK \l "_Toc250451648"  4.6	Anticipated Residues and Percent
Crop Treated	  PAGEREF _Toc250451648 \h  26  

  HYPERLINK \l "_Toc250451649"  5.0	Residential (Non-Occupational)
Exposure and Risk  Characterization	  PAGEREF _Toc250451649 \h  26  

  HYPERLINK \l "_Toc250451650"  5.1	Residential Handler Exposure	 
PAGEREF _Toc250451650 \h  27  

  HYPERLINK \l "_Toc250451651"  5.2.	Residential Postapplication
Exposure	  PAGEREF _Toc250451651 \h  27  

  HYPERLINK \l "_Toc250451652"  6.0	Aggregate Risk Assessments and Risk
Characterization	  PAGEREF _Toc250451652 \h  29  

  HYPERLINK \l "_Toc250451653"  6.1	Acute Aggregate Risk	  PAGEREF
_Toc250451653 \h  29  

  HYPERLINK \l "_Toc250451654"  6.2	Short-Term Aggregate Risk	  PAGEREF
_Toc250451654 \h  29  

  HYPERLINK \l "_Toc250451655"  6.3	Intermediate-Term Aggregate Risk	 
PAGEREF _Toc250451655 \h  29  

  HYPERLINK \l "_Toc250451656"  6.4	Long-Term Aggregate Risk	  PAGEREF
_Toc250451656 \h  29  

  HYPERLINK \l "_Toc250451657"  6.5	Cancer Aggregate Risk	  PAGEREF
_Toc250451657 \h  30  

  HYPERLINK \l "_Toc250451658"  7.0	Cumulative Risk
Characterization/Assessment	  PAGEREF _Toc250451658 \h  30  

  HYPERLINK \l "_Toc250451659"  8.0	Occupational Exposure/Risk
Assessment Pathway	  PAGEREF _Toc250451659 \h  30  

  HYPERLINK \l "_Toc250451660"  8.1	Occupational Pesticide Handler
Exposure and Risk	  PAGEREF _Toc250451660 \h  30  

  HYPERLINK \l "_Toc250451661"  8.2	Occupational Postapplication Worker
Exposure and Risk	  PAGEREF _Toc250451661 \h  32  

  HYPERLINK \l "_Toc250451662"  9.0	Tolerance Harmonization and
Recommended Tolerance	  PAGEREF _Toc250451662 \h  33  

  HYPERLINK \l "_Toc250451663"  10.0	Data Needs	  PAGEREF _Toc250451663
\h  38  

  HYPERLINK \l "_Toc250451664"  10.1	Toxicology Data Requirements	 
PAGEREF _Toc250451664 \h  38  

  HYPERLINK \l "_Toc250451665"  10.2	Residue Chemistry Data Requirements
  PAGEREF _Toc250451665 \h  38  

  HYPERLINK \l "_Toc250451666"  10.3	Occupational/Residential Exposure
Data Requirements	  PAGEREF _Toc250451666 \h  39  

  HYPERLINK \l "_Toc250451667"  References		  PAGEREF _Toc250451667 \h 
39  

  HYPERLINK \l "_Toc250451668"  AppendIX A:  Toxicity Profiles for
Boscalid Technical	  PAGEREF _Toc250451668 \h  41  

  HYPERLINK \l "_Toc250451669"  AppendIX B:  Rationale for Toxicity Data
Requirements	  PAGEREF _Toc250451669 \h  45  

  HYPERLINK \l "_Toc250451670"  APPENDIX C: INTERNATIONAL RESIDUE LIMIT
STATUS	  PAGEREF _Toc250451670 \h  46  

 1.0	Executive Summary

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

Background

  SEQ CHAPTER \h \r 1 Boscalid,
2-chloro-N-(4´-chloro[1,1´-biphenyl]-2-yl)-3-pyridinecarboxamide, is a
carboxamide (anilide) class fungicide that inhibits mitochondrial
respiration, thereby inhibiting spore germination, germ tube elongation,
mycelial growth, and sporulation in all major stages of fungal
development and reproduction necessary for disease development in a
variety of vegetable, fruit and row crops.  There are currently two WDG
boscalid end-use products (EPs) registered to BASF in the U.S. for use
on food/feed crops, one containing only boscalid and one which is a
mixture of two active ingredients.  The single ai formulation is a 70%
WDG (Endura® Fungicide; EPA Reg. No. 7969-197) and the mixture
formulation is a WDG containing 25.2% boscalid and 12.8% pyraclostrobin
(Pristine® Fungicide; EPA Reg. No. 7969-199).  Only boscalid is
addressed in this document; pyraclostrobin is being evaluated
separately. 

BASF has submitted several volumes of data in support of two petitions,
PP#9F7527 and PP#9F9529, to establish permanent tolerances for the
combined residues of the fungicide boscalid [3-pyridinecarboxamide,
2-chloro-N-(4’-chloro(1,1’-biphenyl)-2-yl)] in/on the following
crops:  

Alfalfa Forage	35 ppm

Alfalfa Hay	85 ppm

Citrus Crop Group 10	2.0 ppm

Stonefruit Crop Group 12	5.0 ppm

Use Profile

The fungicide boscalid has been proposed for use on alfalfa and citrus
crop group 10.  Broadcast foliar applications of boscalid may be applied
to alfalfa (including alfalfa grown for seed) at a rate of 0.48 lb ai/A
(Endura®) and 0.28 lb ai/A (Pristine®) and to citrus at a rate of 0.29
lb ai/A (Pristine®).  For alfalfa, up to three applications can be made
per season at retreatment intervals (RTI) of 14 to 21 days.  The
pre-harvest interval (PHI) is 14 days.  For citrus, up to four
applications can be made per season at RTIs of 10 to 21 days.  The PHI
is zero days.  Handlers may apply boscalid to alfalfa using aerial,
chemigation, or groundboom equipment.  To citrus, handlers may apply
boscalid using aerial, chemigation, airblast, or handgun equipment. 

  

Toxicity/Hazard

The toxicity database for boscalid is complete and provides sufficient
information to determine whether boscalid poses a human health hazard. 
Boscalid has a low acute toxicity and is not an eye or skin irritant. 
The target organs for boscalid are the liver and thyroid.  An acute
endpoint was not selected because no adverse effects attributable to a
single exposure to boscalid were seen in the database, including the
developmental toxicity studies.  The chronic dietary, incidental oral,
dermal, and inhalation endpoints were all selected from combined results
of the three studies: chronic rat, carcinogenicity rat, and chronic dog.
 The dose selected for regulation of oral, dermal and inhalation risk at
all durations, for all populations is the NOAEL of 21.8 mg/kg/day based
on thyroid and hepatic toxicity seen in rats and dogs at higher dose
levels.  A dermal absorption factor of 15% was derived from an in vivo
dermal penetration study in the rat.  An inhalation absorption factor of
100% was assumed for the inhalation risk assessments.  

The standard UF of 100X to account for inter- and intra-species
variability was applied to all risk assessments.  The Food Quality
Protection Act (FQPA) safety factor (SF) for boscalid was reduced to 1X.
 With the exception of an immunotoxicity study, the boscalid toxicity
database is complete; there are no reproductive, developmental or
developmental neurotoxic concerns.  While the data did show increased
quantitative and qualitative sensitivity, the effects noted were either
transient or inconsistent, or occurred at the limit dose in the presence
of maternal toxicity.  There are clear NOAELs for these effects and EPA
is regulating based on a point of departure (PoD) below where these
effects are seen.  Additionally, the estimates of exposure are unlikely
to underestimate risk.  Therefore, EPA has concluded that the
application of an additional SF to protect infants and children is not
needed.  Boscalid is classified as "suggestive evidence of
carcinogenicity" and the chronic PoD is protective of any tumor response
seen in the boscalid cancer studies.

Recent changes to 40CFR §158 make immunotoxicity testing (OPPTS
Guideline 870.7800) required for pesticide registration.  The available
data for boscalid do not show potential for immunotoxic effects. 
However, the 870.7800 immunotoxicity study is required, and should be
considered confirmatory (see Appendix B).  

Dietary Exposure (food/drinking water)

Residues of Concern:  For purposes of both the tolerance expression and
dietary risk assessment, HED has concluded that the residues of concern
in plant commodities include only boscalid, and the residues of concern
in livestock commodities include boscalid, its 5-hydroxy metabolite, and
the glucuronide conjugate of the 5-hydroxy metabolite.

Acute Dietary Exposure/Risk:  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. 

Chronic Dietary Exposure/Risk:  The chronic dietary analysis was
performed using tolerance level residues and 100% crop treated
assumptions.  Dietary risk estimates were determined considering
exposures from food plus drinking water.  Boscalid exposure from the
existing uses, the proposed new uses on citrus and alfalfa, the
recommended tolerance increase for stone fruits, and the established and
recommenced tolerances on livestock results in estimated risks that are
below the Agency’s LOC for food plus drinking water.  The highest
exposure and risk estimates for food plus drinking water are 11% of the
chronic population adjusted dose (cPAD) for the U.S. population and 37%
for children 1-2 years old, the most highly exposed population subgroup.

Cancer Dietary Risk: A cancer dietary assessment was not conducted since
boscalid was classified by HED as “suggestive evidence of
carcinogenicity” and quantification of human cancer risk is not
recommended. 

Residential Exposure

Residential Handler Exposure:  There are no residential uses associated
with this action and application of boscalid by homeowners is not
anticipated.  Therefore, residential handler exposure was not evaluated.
 

Residential Postapplication Exposure:  For existing uses on registered
labels, there is potential for exposure to homeowners in residential
settings from “pick-your own” (PYO) operations and from  entering
areas previously treated with boscalid, such as lawns where children
might play, or golf courses that could lead to exposures for adults. 
Given the 1-day duration for PYO activities, a exposure/risk assessment
was not conducted since there are no toxic effects anticipated from a
single exposure to boscalid.  The margins of exposure (MOEs) for
residential postapplication exposure to boscalid are all above 100, and
therefore, do not exceed HED's LOC. There are no risks of concern from
residential postapplication exposure during golfing.

Aggregate Risk

Acute Aggregate Risk: Acute exposures were not considered because an
adverse effect attributable to a single dose was not identified. 

Short-Term and Intermediate-Term Aggregate Risk:  There is potential
short- and intermediate-term exposure to boscalid via the dietary (which
is considered background exposure) and residential (which is considered
primary) pathways.  For adults, these pathways lead to exposure via the
oral (background) and dermal (primary) routes.  For children, these
pathways lead to exposure via the oral (background), and incidental oral
and dermal (primary) routes.  All MOEs are greater than 100, which
indicates that exposure and risk do not exceed HED’s LOC.

Long-Term Aggregate Risk:  There is potential chronic exposure via
dietary (food and drinking water) exposure.  Refer to Chronic Dietary
Exposure/Risk. 

Cancer Risk:  Boscalid is classified as “suggestive evidence of
carcinogenicity” and therefore, an aggregate cancer assessment was not
conducted.

Occupational Exposure/Risk

Dermal:  The results of the occupational handler exposure and risk
assessment indicate that short- and intermediate-term dermal MOEs were
greater than the LOC (MOEs ≥ 100) at the baseline clothing level, when
baseline data are available.  The short- and intermediate-term dermal
risks do not exceed HED’s LOC for mixing/loading/applying with handgun
equipment when baseline attire plus chemical-resistant gloves are used. 
The short- and intermediate-term dermal risks do not exceed HED’s LOC
for pilots using enclosed cockpits and wearing baseline attire.

Inhalation:  The short- and intermediate-term inhalation risks to
handlers do not exceed HED’s LOC at baseline (no respirator) for any
of the handler scenarios.  Only engineering control (enclosed cockpit)
data are available to assess short- and intermediate-term inhalation
risks to handlers operating aircraft.  The short- and intermediate-term
inhalation risks do not exceed HED’s LOC for pilots using enclosed
cockpits and wearing no respirator.

Combined:  Combined dermal plus inhalation risks do not exceed HED’s
LOC, provided personal protective equipment (PPE) listed under the
short- and intermediate-term dermal risks are worn. 

Postapplication:  Short- and intermediate-term dermal postapplication
exposures and risks to occupational workers were estimated using
standard values established by HED since no chemical-specific data were
submitted.  Using HED default assumptions and surrogate dislodgeable
foliar residue (DFR) data, all scenarios resulted in MOEs greater than
100 on day 0 (12 hours after application), and therefore risks do not
exceed HED’s LOC.  

Restricted Entry Interval (REI):  Since postapplication risks were not a
concern on day 0 (12 hours following application), the REI is based on
the acute toxicity of boscalid technical material.  Boscalid is
classified as toxicity category III by the dermal route of exposure and
category IV for eye irritation and skin irritation potential.  Under the
Worker Protection Standard (WPS) for Agricultural Pesticides, active
ingredients classified as acute toxicity categories III or IV for these
routes are assigned a 12-hour REI.  Therefore, the 12-hour REI that
appears on the proposed label is adequate.

International Harmonization

The Codex Alimentarius Commission, Canada, and Mexico have not
established any maximum residue limits (MRLs) for residues of boscalid
in/on alfalfa forage and hay or citrus fruits (Appendix I).  However,
there is an existing Codex MRL for stone fruits at 3 mg/kg, and Canada
has established MRLs at 1.7 mg/kg for the various member of the stone
fruits crop group.  Canada also has also established MRLs for various
livestock commodities.  The Canadian MRLs for stone fruits and livestock
commodities are currently harmonized with the respective U.S.
tolerances; however, once the recommended increases are made to U.S.
tolerances, the U.S. tolerances on stone fruits, poultry fat and meat
byproducts, and hog fat will no longer be harmonized with the Canadian
MRLs. 

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,"   HYPERLINK
"http://www.eh.doe.gov/oepa/guidance/justice/eo12898.pdf" 
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 USDA under the Continuing
Survey of Food Intake by Individuals (CSFII) and are used in pesticide
risk assessments for all registered food uses of a pesticide.  These
data are analyzed and categorized by subgroups based on age, season of
the year, ethnic group, and region of the country.  Additionally, OPP is
able to assess dietary exposure to smaller, specialized 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
postapplication 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.

Review of Human Research

This risk assessment relies in part on data from studies in which adult
human subjects were intentionally exposed to a pesticide or other
chemical. These studies, which comprise the Pesticide Handlers Exposure
Database (PHED), have been determined to require a review of their
ethical conduct and have received that review. 

2.0	INGREDIENT PROFILE

Reference:  

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

	

Boscalid is a carboxamide (an anilide) fungicide that inhibits
mitochondrial respiration, thereby inhibiting spore germination, germ
tube elongation, mycelial growth, and sporulation of pathogenic fungi on
the leaf surface.  Boscalid is currently registered to BASF as WDG
formulations for use on a wide variety of food/feed crops.  

2.1	Summary of Proposed New Uses

BASF is proposing new uses for the 70% WDG (Endura®) formulation on
alfalfa and for the 25% WDG (Pristine®) on alfalfa and citrus fruits. 
Supplemental labels were provided. The use directions for alfalfa and
citrus, including the directions for stone fruits, are summarized below
in Table 2.1.  

Table 2.1.`	Summary of Directions for Use of Boscalid.

Application Timing, Type, and Equipment1	Trade Name

Formulation

[EPA Reg. No.]	Application Rate 

(lb ai/A)	Max. No. Application per Season	Max. Seasonal Application Rate

(lb ai/A)	PHI

(days)	Use Directions and Limitations 2

Alfalfa 3

Broadcast foliar applications when conditions are favorable to disease
development; ground, aerial, or chemigation equipment. 	Endura®

70% WDG

[7969-197]	0.09-0.48	3 

(2 per cutting)

	1.44	14	The minimum RTI is 14 days.  For aerial applications, use a
minimum of 10 gal/A

Do not make more than 2 applications per cutting or 3 applications per
season.

	Pristine®

25.2% WDG

[7969-199]	0.19-0.28

	3 

(2 per cutting)

	0.85	14

	Citrus Fruits

Broadcast foliar applications prior to infection; ground, aerial, or
chemigation equipment.	Pristine®

25.2% WDG

[7969-199]	0.25-0.29	4	1.17	0	The minimum RTI is 10 days.  For aerial
applications, use a minimum of 10 gal/A.

Stone Fruits

Broadcast foliar applications from pink bud through fruit development;
ground, aerial, or chemigation equipment.	Pristine®

25.2% WDG

[7969-199]	0.17-0.23	5	1.14	0	The minimum RTI is 7 days.

For aerial applications, use a minimum of 10 gal/A.

1	Chemigation may be made through the following types of irrigation
systems: center pivot, lateral move, end tow, side wheel roll, traveler,
big gun, solid set, or hand move. 

2	Use directions allow for the use of spray adjuvants and specify a
14-day plant-back interval for rotational crops without registered uses
for boscalid.

3	For stand establishment of fall seeded alfalfa, begin applications in
fall through early winter prior to first snowfall or extended cool, wet
conditions.  For seed pod protection, begin applications at 10% to 30%
bloom.

2.2	Structure and Nomenclature  TC \l2 "2.2	Structure and Nomenclature
/Physical and Chemical Properties

  TC \l2 "2.3	Physical and Chemical Properties 

The chemical structure and nomenclature of boscalid and its hydroxyl
metabolite and physicochemical properties of the technical grade of
boscalid are presented in Tables 2.2.1 and 2.2.2.

Table 2.2.1.	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	3-pyridinecorboxamide,2-chloro-N-(4'-chloro[1,1'-biphenyl]-2-yl

Molecular weight	343.2

CAS registry number	188425-85-6

End-use product (EPs)	25.2% WDG (Pristine® Fungicide; EPA Reg. No.
7969-199, also contains 12.8% pyraclostrobin)

70% WDG (Endura® Fungicide; EPA Reg. No. 7969-197)

Hydroxy-metabolite	

Common name	Boscalid hydroxy metabolite

Company experimental name	M510F01 (glucuronide conjugate – M510F02)

CAS name	2-chloro-N-(4'-chloro-5-hydroxy-biphenyl-2-yl)nicotinamide

Molecular weight	359.2

Table 2.2.2.	Physicochemical Properties of Boscalid.

Parameter	Value	References

Melting point/range	142.8-143.8°C	MRIDs 45404802 and 45404804-45404809

pH	NA (does not dissociate in water) 

	Relative Density (20ºC)	1.381g/cm3

	Water solubility (20ºC)	4.64 mg/L at pH 6

	Solvent solubility (g/100 mL at 20ºC)	acetone	16-20	ethyl acetate
6.7-8.0 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

UV molecular extinction (ε[Lmol-1cm-1]):  3.15 x104 at 228 nm; 1.53
x103 at 290 nm

	

3.0	Hazard Characterization/Assessment

References: 

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

BAS 510 F: Report of the Cancer Assessment Review Committee. J. Kidwell,
TXR#0051289, 11/14/2002.

Boscalid. Human Health Risk Assessment for a Section 3 Tolerance on
Endive, an Amendment to the Tolerances for Strawberries and Berries,
Crop Group 13, and an Increase in Tolerances in/on Cucumber and
Vegetable, Root, Subgroup 1A, except Sugar Beet, Garden Beet, Radish,
and Turnip. B. Hanson, DP#327906, 07/10/2007.  TC \l1 "3.0  HAZARD
CHARACTERIZATION 

PP# 1F06313 --Human Health Risk Assessment for New Fungicide BAS 510 F
(Common Name: Boscalid) -- Proposal for Tolerances for Residues in/on
Numerous Crops and Livestock Commodities. Y. Donovan, DP#290022,
09/08/2003.

The toxicity database for boscalid is adequate for risk assessment
purposes.  However, as part of the new 40 CFR §158 Guidelines, an
immunotoxicity study (OPPTS Guideline 870.7800) in rats and/or mice is
required (see Appendix B).  No indication of immunotoxicity was observed
in the toxicity database; therefore, an additional 10X database UF is
not warranted.  

Boscalid appeared to have effects on the liver and/or thyroid of several
species. In a 90-day mouse study, there were increased liver weights and
increased incidences in marked fatty change in the liver. These liver
changes were not noted in the 18-month mouse study. In 90-day as well as
in 2-year rat studies, there were thyroid changes (increase in weights
and incidence of follicular cell hyperplasia and hypertrophy). The
thyroid changes were considered to have been the result of liver
adaptive responses. The 90-day and one-year dog studies showed increases
in the levels of alkaline phosphatase as well as hepatic weights. In
three mechanistic rat studies, the following were observed: increase in
liver microsomal activity, induction of total cytochrome P450 activity,
disruption of thyroid homeostasis by decreasing circulating T3 and T4
and increasing TSH (likely the result of hepatic microsomal
glucuronyltransferase), and reversal of liver and thyroid effects with
the cessation of test article administration (it was concluded that the
induction of liver microsomal enzyme system resulted 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).  There were
little or no effects on body weights or body weight gains.

In the developmental toxicity studies, no effects were noted in rats;
whereas, in the rabbit study, abortions or early delivery were observed
at the highest dose tested (1000 mg/kg/day).  Regarding the 2-generation
reproduction study in rats, decreased body weights and/or body weight
gains and hepatocyte degeneration were noted in males only. No
reproductive effects were observed. The only effects noted in pups of
both generations were decreases in body weights (both sexes of both
generations) at the highest dose tested (>1000 mg/kg/day). There was no
evidence of neurotoxicity based on an acute neurotoxicity study, a
90-day neurotoxicity study, and a developmental neurotoxicity study (all
in rats). There was no evidence of increased susceptibility in the
developmental rat study (Limit Dose). Qualitative, but not quantitative,
increased susceptibility was noted in the developmental rabbit study as
characterized by an increased incidence of abortions or early delivery
at the highest dose tested (1000 mg/kg/day). There was quantitative
evidence of increased susceptibility in the two-generation reproduction
rat study where decreases in body weights and body weight gains in male
offspring were seen in the F2 generation and in females from both
generations at a dose that was lower than the dose that induced
parental/systemic toxicity. Quantitative evidence of increased
susceptibility was noted in the developmental neurotoxicity study in
rats where decreases in pup body weights (PND 4) and body weight gains
(PND 1-4) were seen in the absence of any maternal toxicity. The degree
of concern is low for the qualitative evidence of susceptibility seen in
the rabbit developmental study as the increased abortions or early
delivery was seen only at the Limit Dose and the abortions may have been
due to maternal stress. The degree of concern is low for the
quantitative evidence of susceptibility seen in the two-generation
reproduction study in rats because the decreases in body weight and body
weight gains were seen only in the F2 generation in males and in females
in both generations. The degree of concern is low for the quantitative
evidence of susceptibility in the developmental neurotoxicity study
because the decreases in pup body weights seen on post natal days 1
through 4 (at no other time periods) were most likely due to maternal
toxicity.

Boscalid has low acute toxicity via the oral, dermal, and inhalation
routes of exposure, and is not an eye or skin irritant (see Appendix A,
Table A.1).  Dermal sensitization could not be determined because the
skin sensitization study was inadequate.  The target organs for boscalid
are the liver and thyroid.  

An acute dietary endpoint was not selected because no adverse effects
attributable to a single exposure to boscalid were seen in the database,
including the developmental toxicity studies.  The chronic dietary,
incidental oral, dermal, and inhalation endpoints were all selected from
combined results of the three studies: chronic rat, carcinogenicity rat,
and chronic dog.  The dose selected for regulation of oral, dermal, and
inhalation risk at all durations, for all populations, is the no
observed adverse effect level (NOAEL) of 21.8 mg/kg/day, based on
thyroid and hepatic toxicity seen in rats and dogs at higher dose
levels.  A dermal absorption factor of 15% was derived from an in vivo
dermal penetration study in the rat.  An inhalation absorption factor of
100% was assumed for the inhalation risk assessments.  

Boscalid is classified as exhibiting “suggestive evidence of
carcinogenicity, but not sufficient to assess human carcinogenic
potential,” and, therefore, the quantification of human cancer risk is
not recommended. The classification was based on data which were
combined from two 2-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. 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 MOE calculation) was not needed.

Thus, evidence of carcinogenicity was seen in males (significant trend
and pair-wise at the high dose) and in females (trend only); however, no
malignancies were seen in either sex.  Only benign tumors were observed,
and these occurred at dose levels above the dose level used to establish
the cPAD.  Additionally, there is no concern for mutagencity.  The PoD
for chronic risk assessment is protective of any tumor response seen in
the boscalid cancer studies.  

The toxicological profiles for boscalid are outlined in Appendix A of
this document.  

3.1	FQPA Safety Factor

The standard UF of 100X to account for inter- and intra-species
variability was applied to all risk assessments.  The FQPA SF for
boscalid was reduced to 1X for the reasons listed below.  

The toxicity database for boscalid is adequate for risk assessment,
however an immunotoxicity study (OPPTS Guideline 870.7800) in rats
and/or mice is required under the new 40 CFR part 158 data regulations.
No indication of immunotoxicity was observed in the toxicity database;
therefore, an additional 10X database UF is not warranted.

There is no indication that boscalid is a neurotoxic chemical and there
is no need for additional UFs to account for neurotoxicity. There is no
evidence of neurotoxicity in the acute subchronic, or developmental
neurotoxicity studies. The toxicity studies for boscalid demonstrate
that, in general, the chemical has low mammalian toxicity, and the
database reveals no reproductive, developmental, or developmental
neurotoxicity concerns.

Data involving the testing of young animals did show increased
quantitative sensitivity in the young with regard to body weight
effects, and qualitative sensitivity was seen in one developmental
study. However, clear NOAELs were identified for all of these effects.
Moreover, the body weight effects at the LOAELs in these studies were
either transient or inconsistent, and qualitative sensitivity occurred
at the limit dose in the presence of maternal toxicity. Additionally,
EPA is regulating based on a PoD below where these effects are seen. EPA
concludes that there are no residual uncertainties for pre- and/or
post-natal toxicity.

There are no residual uncertainties identified in the exposure
databases. EPA has conservatively estimated human exposure to boscalid,
relying on worst case exposures in food (assuming all registered crops
contain residues at the tolerance level), and conservative models, as
well as pesticide-specific data, in estimating exposure from residues in
drinking water, and from residential uses. These assessments will not
underestimate the exposure and risks posed by boscalid.

Based on consideration of all of these data, HED has concluded that it
has reliable evidence to show that infants and children would be
adequately protected without application of an additional 10X SF.  

3.2	Summary of Toxicological Doses and Endpoints

The endpoints and doses selected for risk assessment purposes are
summarized in Table 3.2.  

Table 3.2.  Summary of Toxicological Doses and Endpoints for Boscalid.  

Exposure

[Scenario]	PoD	Uncertainty and FQPA Safety Factors	RfD/PAD/

LOC	Study and Toxicological Effects

Acute Dietary

[All Populations]	No appropriate endpoint attributable to a single dose
was available in the current database, including the developmental
toxicity studies.  Therefore, an acute RfD and acute PAD were not
established for any population.

Chronic Dietary

[All Populations]	NOAEL = 21.8 mg/kg/day

	UFA = 10X

UFH = 10X

FQPA SF = 1X

	Chronic RfD =  0.218 mg/kg/day

Chronic PAD = 0.218 mg/kg/day	Combined results of chronic rat,
carcinogenicity rat, and 1-year dog studies.  

LOAEL = 57 mg/kg/day, based on liver and thyroid effects.  

Incidental Oral, 

Short- and Intermediate-Term	NOAEL = 21.8 mg/kg/day

	UFA = 10X

UFH = 10X

FQPA SF = 1X

	Residential 

LOC = 

MOE < 100	Combined results of chronic rat, carcinogenicity rat, and
1-year dog studies.

LOAEL = 57 mg/kg/day, based on liver and thyroid effects.  

Dermal

[All Durations]	Oral study NOAEL = 21.8 mg/kg/day

Dermal absorption = 15%	UFA = 10X

UFH = 10X

FQPA SF = 1X

	Residential and Occupational

LOC = 

MOE < 100	Combined results of chronic rat, carcinogenicity rat, and
1-year dog studies.  

LOAEL = 57 mg/kg/day, based on liver and thyroid effects.  

Inhalation

[All Durations]	Oral study NOAEL = 21.8 mg/kg/day

Inhalation absorption = 100%	UFA = 10X

UFH = 10X

FQPA SF = 1X

	Residential and Occupational

LOC = 

MOE < 100	Combined results of chronic rat, carcinogenicity rat, and
1-year dog studies.  

LOAEL = 57 mg/kg/day, based on liver and thyroid effects.  

Cancer

	Classified as exhibiting “suggestive evidence of carcinogenicity.” 
Quantification of human cancer risk is not recommended.

PoD = Point of Departure, a data point (or estimated point) that is
derived from observed dose-response data, and used to mark the beginning
of extrapolation to determine risk associated with lower 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).  FQPA SF = FQPA Safety Factor.  PAD = Population
Adjusted Dose.  RfD = Reference Dose.  LOC = Level Of Concern.  MOE =
Margin Of Exposure.  

3.3	Endocrine disruption  TC \l2 "3.8	Endocrine disruption 	

EPA is required under the FFDCA, as amended by FQPA, to develop a
screening program to determine whether certain substances (including all
pesticide active and other ingredients) “may have an effect in humans
that is similar to an effect produced by a naturally occurring estrogen,
or other such endocrine effects as the Administrator may designate.” 
Following recommendations of its Endocrine Disruptor and Testing
Advisory Committee (EDSTAC), EPA determined that there was a scientific
basis for including, as part of the program, the androgen and thyroid
hormone systems, in addition to the estrogen hormone system.  EPA also
adopted EDSTAC’s recommendation that the Program include evaluations
of potential effects in wildlife.  For pesticide chemicals, EPA will use
FIFRA and, to the extent that effects in wildlife may help

determine whether a substance may have an effect in humans, FFDCA
authority to require the wildlife evaluations.  As the science develops
and resources allow, screening of additional hormone systems may be
added to the Endocrine Disruptor Screening Program (EDSP). 

When additional appropriate screening and/or testing protocols being
considered under the Agency’s EDSP have been developed, boscalid may
be subjected to further screening and/or testing to better characterize
effects related to endocrine disruption.

4.0	Dietary Exposure/Risk Characterization

A residue chemistry summary document has been prepared for the proposed
uses on alfalfa, citrus fruits, and increased tolerance on stone fruits
(A. Acierto, DP#364447, 10/16/2009).  Reference may be made to this
document for details concerning residue chemistry considerations
associated with the current use request, such as a summary of registered
uses, boscalid nomenclature, physical and chemical properties, use
directions, metabolism in plants and animals, analytical methods,
storage stability, field trial results, etc.  

4.1	Nature of the Residue and Residue Analytical Methods

Boscalid residues in all samples associated with the current field
trials and livestock studies were determined using the methods described
below.  For purposes of both the tolerance expression and dietary risk
assessment, HED has concluded that the ROC in plant commodities include
only boscalid, and the ROC in livestock commodities include boscalid,
its 5-hydroxy metabolite, and the glucuronide conjugate of the 5-hydroxy
metabolite.

860.1300 Nature of the Residue and 860.1340 Residue Analytical Methods
– Plants

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

860.1300 Nature of the Residue and 860.1340 Residue Analytical Methods
– Livestock

The nature of boscalid residues in livestock is adequately understood,
based upon acceptable 14C metabolism studies conducted on lactating
goats and laying hens.  An enforcement method (BASF Method DFG S19) is
available for determining the residues of concern in livestock and has
been successfully validated by ACB/BEAD.  For the current livestock
feeding study, residues of boscalid and its hydroxyl metabolite M510F01
(including the glucoronide 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.

For calculating combined residues, Metabolite M510F01 residues are
converted into parent equivalents using a conversion factor of 0.96. 
The above method was adequately validated prior to and in conjunction
with the analysis of feeding study samples, using control samples
fortified with boscalid and M510F01 at 0.01 ppm – 2.5 ppm for milk,
skim milk, and cream, and 0.025 ppm – 2.5 ppm for liver, kidmey,
muscle, and fat samples.

860.1360 Multiresidue Methods

Residues of boscalid and its metabolite M510F01 were not adequately
recovered using the Multiresidue methods.

860.1380 Storage Stability

re available indicating that boscalid is relatively stable at ≤20°C
in fortified samples of cabbage (leafy vegetables), canola seed (oil
seed), peach (fruit/fruiting vegetable), sugar beet roots (root crop),
peas (legume vegetable, wheat grain (non-oily grain), wheat forage
(foliage), and wheat straw (dry feed) for up to 24 months.  In addition
to the above date, a concurrent storage stability study was conducted in
conjunction with the orange processing study (MRID 47584402.der).  The
available storage stability data are adequate and support the storage
conditions and durations for samples of alfalfa, citrus fruits, and
stone fruits from the current field trials and the acceptable citrus
processing study.

4.2	Pesticide Metabolites and Degradates of Concern

Boscalid is a persistent compound with low mobility in most soils.  The
primary degradation pathway is aerobic soil metabolism, which proceeds
slowly and results in the formation of intermediates which are
relatively rapidly transformed into CO2 or bound soil residues. 
Boscalid is stable to hydrolysis and to photolysis on soil and in water.
 The compound is also not transformed to any significant extent in
either aerobic or anaerobic aquatic systems. TC \l3 "5.1.5	Environmental
Degradation   The residues of concern to be included in the tolerance
expression and for risk assessment purposes are summarized below in
Table 4.2.

Table 4.2.	Summary of Metabolites and Degradates to be included in the
Risk Assessment and Tolerance Expression.

Matrix	Residues included in Risk Assessment	Residues included in
Tolerance Expression

Plants

	Primary Crop	Parent only	Parent only

	Rotational Crop	Parent only	Parent only

Livestock

	Ruminant	Parent and  hydroxy and glucuronic acid metabolites	Parent and
 hydroxy and glucuronic acid metabolites

	Poultry	Parent and  hydroxy and glucuronic acid metabolites	Parent and 
hydroxy and glucuronic acid metabolites

Drinking Water	Parent only	Not Applicable

4.3	Drinking Water Residue Profile

References:  

Drinking Water Exposure Assessment for New Uses of Boscalid on Alfalfa
Forage and Hay, Citrus group 10, and an Increase in Tolerance on Stone
Fruit group 12.  D. Lieu, DP#367184, 09/24/2009.

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

EFED completed a drinking water assessment (DWA) for boscalid (D. Lieu,
DP#367184, 09/24/2009), indicating that the previous assessment
conducted by C. Sutton (DP#336183, 08/08/2007) yields higher EDWCs.  The
highest EDWCs were based on the turf use.  The current requests for new
uses on alfalfa and citrus and the increase of tolerances for stone
fruit crop group 12 do not affect the EDWCs.  As a result, the EDWCs
used in the previous assessment were used in this assessment as well. 
The EDWCs were incorporated directly into the dietary assessment via the
food categories “water, direct, all sources” and “water, indirect,
all sources.”

The EDWCs for boscalid in surface water and ground water were calculated
using the screening model FIRST (FQPA Index Reservoir Screening Tool,
Version 1.1.0, dated 12/12/2005), and the regression model SCI-GROW
(Screening Concentration in Ground Water, Version 2.3, dated
07/29/2003), respectively.  An acute dietary risk assessment was not
conducted.  The maximum estimated chronic ground water EDWC was 0.63
ppb.  The maximum estimated chronic surface water EDWC was 29.6 ppb. 
The surface water value is higher than the ground water value and was,
therefore, used in the dietary assessment.  

4.4	Food Residue Profile

References:  

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

BASF is proposing new uses for boscalid on alfalfa using the 25% WDG and
70% WDG formulations and on citrus fruits using the 25% WDG formulation.
 The proposed uses on alfalfa are for repeated broadcast foliar
applications at up to 0.28 lb ai/A for the 25% WDG and 0.48 lb ai/A for
the 70% WDG, with a minimum RTI of 14 days, for a maximum of 0.85 lb
ai/A/season and 1.44 lb ai/A/season for the 25% WDG and 70% WDG,
respectively.  A maximum of 3 applications to alfalfa are allowed per
season with no more than 2 applications per cutting.  The proposed use
on citrus fruits is for up to four broadcast foliar applications during
fruit development at rates up to 0.29 lb ai/A with a minimum RTI of 10
days, for a maximum of 1.17 lb ai/A/season.  All applications can be
made using ground, aerial, or chemigation equipment, and the proposed
PHIs are 14 days for alfalfa and 0 days for citrus fruits.  

860.1480 Meat, Milk, Poultry, and Eggs

Adequate cattle and poultry feeding studies are available.  The maximum
dietary burden for poultry was originally calculated to be 1.85 ppm (M.
Nelson, DP#278385, 8/15/2003), and the maximum dietary burdens for other
livestock were most recently calculated to be 16.4 ppm for beef  cattle,
13.2 ppm for dairy cattle, and 1.79 ppm for swine (D. Dotson, DP#322235,
11/03/2005).  A summary of the combined residue data from the 2008 dairy
cattle feeding study and the poultry feeding studies are summarized in
DP#364447 (A. Acierto, 10/16/2009).

 

Cattle Feeding Studies.  BASF submitted a new cattle feeding study
conducted in 2008 in which two groups of lactating dairy cows were
administered with encapsulated boscalid via balling gun for 29
consecutive days at the target doses of 35 ppm (Group 2; 3 cows) or 105
ppm (Group 3; 7 cows).  These dose levels are intended to represent 1X
and 3X the anticipated European Union (EU) dietary burden of 35 ppm in
the feed on a dry weight basis.  

Poultry Feeding Study.  In the poultry feeding study, three groups of
laying hens were dosed orally once a day for 29 consecutive days with
boscalid at levels equivalent to 1.02 ppm, 5.31 ppm, and 19.6 ppm in the
diet, which are respectively equivalent to 0.25X, 1.3X, and 4.8X of the
maximum dietary burden of poultry to boscalid.

Livestock Dietary Burdens.  As alfalfa forage and hay are major
livestock feedstuffs, the dietary burdens for livestock were
recalculated for this petition.  Based on the recent changes in
calculating residues in reasonably balanced livestock diets (Table 1,
Feedstuffs, June 2008), the dietary burden for livestock from boscalid
residues were recalculated to be 10.8 ppm for beef cattle, 22.5 ppm for
dairy cattle, 4.0 ppm for poultry, and 5.3 ppm for swine (Table 4.4.3).

TABLE 4.4.3.	Calculation of Dietary Burdens of Boscalid Residues to
Livestock.

Feedstuff	Type1	% Dry Matter2	% Diet2	Recommended Tolerance (ppm)
Dietary Contribution (ppm)3

Beef Cattle

Alfalfa, hay	R	89	10	65	7.3

Cotton, gin byproducts	R	90	5	55	3.06

Field corn, grain	CC	88	80	0.2	0.18

Canola, meal	PC	88	5	3.5 4	0.2

TOTAL BURDEN	--	--	100	--	10.8

Dairy Cattle

Alfalfa, forage	R	35	20	30	17.2

Grass, hay	R	88	25	8.0	2.27

Apple, wet pomace	CC	40	10	10	2.50

Field corn, grain	CC	88	35	0.2	0.08

Canola, meal	P	88	10	3.5 4	0.4

TOTAL BURDEN	--	--	100	--	22.5

Poultry

Field corn, grain	CC	88	75	0.2	0.15

Alfalfa, meal	PC	90	5	65 4	3.25

Canola, meal	PC	89	15	3.5 4	0.53

Peanut, meal	PC	85	5	0.15	0.0075

TOTAL BURDEN	--	--	100	--	4.0

Swine

Field corn, grain	CC	88	85	0.2	1.70

Alfalfa, meal	PC	90	5	65 4	3.25

Canola, meal	PC	89	10	3.5 4	0.35

TOTAL BURDEN	--	--	100	--	5.3

1	R:  Roughage; CC:  Carbohydrate concentrate; PC:  Protein concentrate.

2	OPPTS 860.1000 Table 1 Feedstuffs (June 2008).  

3	Contribution = ([tolerance /% DM] X % diet) for beef and dairy cattle;
contribution = ([tolerance] X % diet) for poultry and swine.

4	The tolerance for canola seed (3.5 ppm) was used for meal, and the
tolerance for alfalfa hay (65 ppm) was used for alfalfa meal.

Conclusions.  The available cattle and poultry feeding studies are
adequate and cover the potential levels of dietary exposure of livestock
to boscalid residues.  The magnitude of the residues of boscalid and
M510F01 was adequately determined in the new (2008) feeding study.  

For hogs, the adequacy of the existing tolerances were assessed using
residue data from the 5.9 ppm dose group in the cattle feeding studies;
this group represents 1.1X the calculated dietary burden for swine.  The
data indicate that the existing tolerances for meat (0.05 ppm) and meat
byproducts (0.10 ppm) of hogs are adequate; however, the tolerance for
hog fat should be increased to 0.20 ppm.

For poultry, the adequacy of the existing tolerances were assessed using
residue data from the 5.31 ppm dose group in the poultry feeding
studies; this group represents 1.3X the calculated dietary burden for
poultry.  These data indicate that the existing tolerances for eggs
(0.02 ppm) and poultry meat (0.05 ppm) are adequate; however, the
tolerances for poultry fat and meat byproducts should each be increased
to 0.20 ppm.

860.1500 Crop Field Trials

References: 

Boscalid. Petition for a Tolerance for Belgian Endive; Petition for
Increased Tolerances on Strawberry and the Berries Crop Group;
Submission of Requested Field Trial Data on Cucumber, Mustard Greens,
and Sunflower; and Supplemental Field Trial Data on Fruiting Vegetables,
Radishes, Spearmint, Peppermint, Grapes, and Stone Fruits; and
Submission of Field Trials and a Processing Study for Cotton. Summary of
Analytical and Residue Data. D. Soderberg, DP#323288, 06/14/2007.

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

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

BASF submitted field trial data on alfalfa, oranges, lemons, and
grapefruits in support of new uses for boscalid (WDG formulations) on
alfalfa and the citrus fruits crop group.  BASF also submitted new stone
fruit field trial data supporting an amended tolerance for stone fruits.
 The results from the new field trials and the previously submitted
stone fruit field trails are summarized in Table 4.4.4 and discussed
below.  Adequate storage stability studies and acceptable analytical
methods are available.

TABLE 4.4.4.	Summary of Residue Data from Crop Field Trials with
Boscalid (WDG).

Crop Matrix

(DER)	Treatment Info.	Total Applic. Rate (lb ai/A)	PHI (days) 1	Residue
Levels (ppm) 2

n	Min.	Max.	HAFT 3	Median	Mean	Std. Dev.

Citrus Fruits (proposed use = 1.17 lb ai/A total application rate, 0-day
PHI) 4

Orange

(45903601.de1)	Concentrated 	1.19-1.22	0	12	0.179	1.425	1.393	0.388
0.610	0.467

	Dilute	1.20-1.21	0	14	0.238	0.676	0.588	0.353	0.418	0.146

Grapefruit

(45903601.de1)	Concentrated 	1.20	0	6	0.115	0.847	0.836	0.143	0.365
0.364

	Dilute	1.20	0	6	0.064	0.272	0.261	0.125	0.155	0.086

Lemon

(45903601.de1)	Concentrated 	1.18-1.23	0	6	0.522	1.51	1.239	0.671	0.822
0.370

	Dilute	1.18-1.20	0	4	0.600	0.936	0.872	0.775	0.771	0.140

Stone Fruits (proposed use = 1.15 lb ai/A total application rate, 0-day
PHI) 5

Cherry  

(47470201.de2)	NA	1.15	0	14	<0.05	2.98	1.63	1.47	1.57	0.89

	1	14	<0.05	2.69	1.95	1.09	1.28	0.81

Peach

(47470201.de2)

1.15	0	12	0.56	3.79	1.94	0.76	1.15	1.03

	1	12	0.46	3.87	2.74	0.75	1.19	1.15

Plum

(47470201.de2)

1.15	0	10	<0.05	0.79	0.67	0.14	0.34	0.31

	1	10	<0.05	0.57	0.71	0.11	0.26	0.24

Cherry

(45405121.der)	NA	1.35	0	2	1.28	1.70	1.49	1.49	1.49	NA

Peach

(45405121.der)

1.14-1.17

8	0.47	1.20	1.19	0.74	0.77	0.29

Plum

(45405121.der)

1.15-1.17

8	0.09	0.85	0.70	0.50	0.47	0.23

Cherry

(46665505.der)	Concentrated 	1.15-1.16	0	6	0.641	1.635	1.635	0.999	1.056
0.370

	Dilute	1.15	0	6	0.736	1.505	1.505	1.313	1.229	0.309

Peach

(46665505.der)	Concentrated 	1.14-1.16	0	9	0.157	0.663	0.663	0.479	0.450
0.157

	Dilute	1.14-1.17	0	9	0.193	0.746	0.746	0.422	0.434	0.203

Plum

(46665505.der)	Concentrated 	1.14-1.15	0	6	0.081	0.566	0.566	0.154	0.214
0.182

	Dilute	1.14-1.15	0	6	0.103	0.344	0.344	0.198	0.211	0.105

Alfalfa (proposed use = 0.85 lb ai/A total application rate, 14-day PHI)
6

Alfalfa Forage

(47584401.der) 	 Trt #2 7	0.88-0.92	12-15	24	1.10	20.30	17.67	5.04	7.05
5.20

	12-16	24	0.81	19.40	17.23	4.98	6.25	5.09

	43-73	22	<0.05	0.53	0.37	0.12	0.17	0.14

	 Trt #3	0.86-0.93	19-23	24	0.11	6.16	6.10	1.94	2.05	1.66

	20-23	24	0.32	5.59	5.06	2.12	2.29	1.62

	49-76	22	<0.05	0.50	0.50	0.11	0.16	0.13

	 Trt #4	0.59-0.62	12-15	24	0.97	15.68	14.47	3.95	4.94	3.78

	12-16	24	0.85	15.32	15.07	3.59	5.56	4.51

	43-70	22	<0.05	0.38	0.32	0.08	0.12	0.09

	 Trt #5	0.57-0.62	19-23	24	0.05	5.44	5.38	1.21	1.75	1.58

	20-23	24	0.29	3.64	3.46	2.12	2.03	1.07

	49-76	22	<0.05	0.44	0.44	0.07	0.14	0.14

Alfalfa Hay

(47584401.der)	Trt #2 7	0.88-0.92	12-15	24	3.36	43.02	42.62	14.00	17.37
11.19

	12-16	24	5.22	51.12	48.91	16.10	20.93	13.64

	43-73	22	0.07	3.63	2.38	0.37	0.62	0.78

	 (Trt #3	0.86-0.93	19-23	24	0.14	20.84	19.84	6.37	6.97	5.93

	20-23	24	1.52	15.26	14.72	6.72	7.24	4.44

	49-76	22	<0.05	1.36	1.17	0.24	0.49	0.45

	Trt #4	0.59-0.62	12-15	24	3.11	33.78	31.34	10.80	15.30	9.21

	12-16	24	4.48	40.06	39.33	16.89	18.23	11.40

	43-70	22	<0.05	0.72	0.70	0.27	0.31	0.19

	Trt #5	0.57-0.62	19-23	24	0.42	12.46	12.23	3.80	5.29	4.45

	20-23	24	1.88	21.60	18.31	7.44	7.50	4.76

	49-76	22	<0.05	1.12	1.10	0.25	0.45	0.40

1	For the alfalfa field trials, the three separate harvest intervals are
the PHIs for the 1st, 2nd and 3rd cuttings.

2	The validated LOQ for boscalid is 0.05 ppm in plant commodities.  For
all calculations, the LOQ (0.05 ppm) was used for all values reported as
<LOQ.

3	HAFT = Highest average field trial result.

4	The citrus field trials were conducted using either concentrate or
dilute spray volumes.

5	For stone fruits, the data are reported separately for the three MRIDs
(47470201, 46665505, and 45405121).  In MRID 45405121, applications to
stone fruits were made using either concentrate or dilute spray volumes.

6	For the alfalfa field trials, Treatments #2 and #3 included three
boscalid applications at ~0.3 lb ai/A/application with the first and
second applications made prior to the 1st cutting and the final
application made prior to the 2nd cutting.  Treatments #4 and #5
included two applications at ~0.3 lb ai/A/application, with the first
application made prior to the 1st cutting and the second application
made prior to the 2nd cutting.

7	Treatment #2 represents the worse case use on alfalfa and reflects the
proposed use pattern.  As residues (bolded) from the 1st and 2nd cutting
were similar in magnitude and both reflected the proposed 14-day PHI,
all values from these two cutting were used to access tolerances for
forage and hay.

Citrus Fruits, Crop Group 10.  BASF submitted field trial data for
boscalid on citrus fruits.  The submitted field trial data are adequate
and support the use of boscalid (WDG) on citrus fruits as either dilute
or concentrated broadcast foliar applications during fruit development
and maturation at rates of up to 0.29 lb ai/A.   The highest residues
which were found were 1.43 ppm in oranges,  0.85 ppm in grapefruit, and
1.51 ppm in lemons.  The data support a maximum of 4 applications per
season and a maximum seasonal use rate of 1.16 lb ai/A, a minimum RTI of
10 days, and a minimum PHI of 0 days.

Some of the oranges were separated into wet peel and pulp.  As compared
to the whole fruit, boscalid residues were lower in orange pulp and
higher in peel.

  

Stone Fruits, Crop Group 12.  Adequate field trial data supporting the
use of boscalid (WDG) on stone fruits were previously submitted (M.
Nelson, DP#278385, 8/15/2003; and D. Soderberg, DP#323288, 6/14/2007). 
BASF has submitted additional field trial data for boscalid on stone
fruits and the available stone fruit field trial data are adequate to
support a tolerance increase from 1.7 ppm to 3.5 ppm for the stone fruit
crop group 12.   The recommended tolerance is based on the tolerance
spreadsheet using the pooled data from field trials for representative
crops of cherries, peaches, and plum treated at 1X rate with the PHI of
0 day. When residue data from all the adequate stone fruit field trials
(1X rate with 0-day PHI) are pooled by crop, the data support the use of
boscalid (WDG) on stone fruits for up to five broadcast foliar
applications during fruit development at 0.23 lb ai/A/application, for a
total application rate of 1.15 lb ai/A.  The data support a minimum RTI
of 7 days and a minimum PHI of 0 days.  

Alfalfa.  BASF submitted field trial data for boscalid and the submitted
alfalfa field trial data are adequate and would support the use of two
or three broadcast foliar applications of  boscalid  (25.2%, WDG
formulation) to alfalfa at up to ~0.30 lb ai/A/application, with no more
than two applications per cutting, for maximum seasonal use rates 0.6 or
0.9 lb ai/A.  The data also support a minimum RTI of 14 days and minimum
PHIs of either 14 or 21 days.    However, the alfalfa field trial data
will not support the proposed use rates of the 70% WDG as the proposed
maximum single (0.48 lb ai/A) and seasonal (1.44 lb ai/A) application
rates for the 70% WDG are approximately 1.6X higher than the rates used
in the alfalfa field trials.

860.1520 Processed Food and Feed

BASF submitted residue data from an orange processing study conducted in
FL (Zone 3) during 2008.  A 70% WDG formulation of boscalid was applied
to Valencia orange trees during fruit maturation as two broadcast foliar
applications at rates of 0.30 lb ai/A/application at a RTI of 10 days,
for a total rate of 0.60 lb ai/A.  

The data collection LC/MS/MS method (BASF Method D9908, Version II) used
to analyze boscalid residues in/on orange fruit and processed
commodities was adequately validated prior to and in conjunction with
the analysis of processing samples.

The average boscalid residues in the processed commodities were 0.694
ppm in dried pulp, <0.05 ppm in juice, and 13.1 ppm in oil.  These data
indicate that boscalid residues were reduced in juice by 0.23X, but
concentrated 3.1X in dried pulp and 59X in oil. The theoretical
processing factors for citrus are 2X for juice, 3.3X for dried pulp, and
1000X for oil (OPPTS 860.1520, Table 3).

For the storage stability study, whole orange fruits, dried pulp, and
oil were stored at <-5°C for up to 3.6 months prior to analysis. After
3.6 months of frozen storage, the corrected recoveries of boscalid were
109-126% from all four citrus matrices. 

Table 4.4.5.	Residue Data from Orange Processing Study with Boscalid
(WDG).

RAC	Processed

Commodity	Total Rate

(lb ai/A)	PHI

(days)	Residues (ppm) 1	Processing Factor3

Orange	Fruit (RAC)	0.602	1	0.2210, 0.2209 (0.2210)	--

	Dried Pulp

	0.5884, 0.8002 (0.694)2	2.7X, 3.6X (3.1X)

	Juice

	<0.05, <0.05 (<0.05)	<0.23X, <0.23X (<0.23X)

	Oil

	13.6, 12.49 (13.05)2	61X, 57X (59X)

1	The LOQ is 0.05 ppm for all commodities.  

2	Residues are averages of 3 replicates each.  Means of multiple
processing study analyses are in parenthesis.  

3	The processing factor was calculated by dividing the residue in the
processed commodity by the residue in the associated RAC sample.  The
LOQ was used to calculate the processing factor for the value below the
LOQ.  Mean processing factors are in parenthesis.

Conclusions.  The orange processing study is adequate.  As boscalid
residues were reduced in juice (<0.2X), a separate tolerance is not
required for citrus juice.  However, separate tolerances are required
for citrus dried pulp and oil.  Based on the processing factors for
dried pulp (3.1X) and oil (59X) and the HAFT residues (see Table 4.4.5)
for citrus fruits (orange – 1.39 ppm), the maximum expected boscalid
residues would be 4.31 ppm in dried pulp and 82 ppm in oil.  These data
support tolerances of 4.5 ppm for dried citrus pulp and 85 ppm for
citrus oil.

860.1850 and 860.1900 Rotational Crops

The nature of the residue in rotational crops is adequately understood
and was summarized in a previous residue chemistry summary document. 
HED has concluded that the residue of concern in rotated crops for
purposes of risk assessment and the tolerance expression is parent
compound.

Adequate limited and extensive field rotational crop 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. 

4.5	Dietary Exposure and Risk

References:  

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

Boscalid. Chronic Aggregate Dietary (Food and Drinking Water) Exposure
and Risk Assessment for the Section 3 Registration on the Citrus Crop
Group 10 and Alfalfa, and an Increase in the Tolerance on the Stone
Fruit Crop Group 12.  A. Acierto, DP#365262, 11/19/2009.

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

HED MARC Decision Memo, DP#286786, 01/09/2003.

A dietary exposure memorandum has been prepared for the proposed new
uses on alfalfa and citrus and subsequent amendment of Section 3
registrations of BAS 510F (EPA Reg. No. 7969-198), Endura® (EPA Reg.
No. 7969-197), and Pristine® (EPA Reg. No. 7969-199), and the proposed
increase of tolerances for the stone fruit crop group 12 (A. Acierto,
DP#365262, 11/19/2009).  Reference may be made to this document for
details concerning the dietary exposure analysis that was performed in
support of the new proposed tolerances in alfalfa and citrus, and the
increased tolerance in stone fruits.  

 DEEM-FCID™ (Version 2.03) which uses food consumption data from the
U.S. Department of Agriculture’s Continuing Surveys of Food Intakes by
Individuals (CSFII) from 1994 to 1996, and 1998.  The analysis was
performed to support the establishment of tolerances for residues of
boscalid in alfalfa and citrus, and the increased tolerance in stone
fruits.  

4.5.1	Acute Dietary Exposure Results and Characterization

No toxic effects attributable to a single dose of boscalid have been
identified.  As a result, an acute reference dose (RfD) was not
established for this chemical; therefore, acute dietary risk is not of
concern.  Thus, an acute dietary exposure assessment was not conducted. 

4.5.2	Chronic Dietary Exposure Results and Characterization

A chronic dietary (food and drinking water) exposure and risk assessment
was conducted for boscalid using tolerance level residues and 100% crop
treated (%CT) assumptions.  Boscalid exposure from the existing uses,
the proposed new uses on citrus and alfalfa, the recommended tolerance
increase for stone fruits, and the established and recommended
tolerances on livestock results in estimated risks that are below
HED’s LOC for food plus drinking water.  The highest exposure and risk
estimates for food plus drinking water are 11% of the cPAD for the
general U.S. population and 37% of the cPAD for children 1-2 years old,
the most highly exposed population subgroup.   

4.5.3	Cancer Dietary Exposure Results and Characterization

HED has classified boscalid as demonstrating “suggestive evidence of
carcinogenicity” and has recommended against the quantification of
human cancer risk (J. Kidwell, TXR#0051289, 11/14/2002).  No change has
been made to the cancer classification.  Quantification of human cancer
risk is not required.  As a result, dietary cancer risk is not of
concern; thus, a dietary cancer assessment was not conducted.  

4.5.4	Results of Chronic Dietary Exposure Analysis

The results of the dietary exposure analysis (food and drinking water)
for the general U.S. population, and all regulated population subgroups
are listed below in Table 4.5.4.

Table 4.5.4.	Summary of Dietary (Food and Drinking Water) Exposure and
Risk for Boscalid.

Population Subgroup 1	Acute Dietary	Chronic Dietary	Cancer

	Exposure (mg/kg/day)	% aPAD	Exposure

(mg/kg/day)	% cPAD	Exposure

(mg/kg/day)	Risk

General U.S. population	NA 2	NA	0.024694	11	NA	NA

All infants (< 1 year old)

	0.052987	24

Children 1-2 years old

	0.081585	37

Children 3-5 years old

	0.057899	27

Children 6-12 years old

	0.030924	14

Youth 13-19 years old

	0.017901	8

Adults 20-49 years old

	0.018608	8

Adults 50+ years old

	0.020774	10

Females 13-49 years old

	0.019007	9

1	Values for the population subgroup with the highest estimated chronic
exposure and risk are in bold type.  

2	NA = Not Applicable.  

4.6	Anticipated Residues and Percent Crop Treated

The chronic dietary exposure analysis was based on tolerance level
residues and 100%CT assumptions for all commodities.  As there were no
risks of concern, the generation of anticipated residues was not needed,
and %CT data were not incorporated into the assessment.  

5.0	Residential (Non-Occupational) Exposure and Risk 	Characterization 
TC \l1 "6.0	Residential (Non-Occupational) Exposure/Risk
Characterization 

For a discussion of the residential exposures and risks associated with
the use of boscalid, reference may be made to the previous risk
assessment on coffee (W. Drew, DP#354689, 03/25/2009), or to the
occupational and residential exposure (ORE) memo prepared in support of
this risk assessment (B. O’Keefe, DP#364449, 10/23/2009).  

5.1	Residential Handler Exposure

There are no new residential (non-occupational) uses proposed for
boscalid as a result of the requested uses on alfalfa forage, citrus
fruits, and increased tolerance on stone fruits.  Current labels specify
that boscalid is to be applied to golf courses only, and is not for use
on residential turfgrass or turfgrass being grown for sale or other
commercial use such as sod production.  Additionally, boscalid is
neither packaged nor marketed for home orchard use.  As the product is
not intended for homeowner use, residential handler exposure and risk
assessments are not required (B. O’Keefe, DP#364449, 10/23/2009).  

5.2.	Residential Postapplication Exposure

Reference: 

-	Boscalid:  Human Health Risk Assessment to Support Proposed New Uses
on Fresh Herbs (Herbs Subgroup 19A), Avocado, Black Sapote, Canistel,
Mamey Sapote, Mango, Papaya, Sapodilla, Star Apple and Cotton. D. Davis,
DP#336182, 02/13/2008.

There are no new residential postapplication exposure scenarios
resulting from the proposed uses on alfalfa forage, citrus fruits, or
increased tolerance on stone fruits.  Potential non-occupational
postapplication exposure scenarios identified for boscalid, based on the
established uses, include postapplication exposure to golfers and
persons harvesting fruit at “pick-your-own” (PYO) farms and
orchards.  Exposure can occur during contact with treated golf course
turf, or while picking strawberries, caneberries, and tree fruit at a
PYO facility.  

Based on the low vapor pressure of boscalid (7 x 10-9 hPa), the outdoor
nature of the uses, and the weight of evidence from available residue
studies, HED does not anticipate postapplication inhalation exposures
from the currently approved uses of boscalid.  

PYO activities are considered to be one-time (<1 day) events.  As no
adverse effects were seen in the boscalid toxicity database resulting
from a single exposure to the chemical, a postapplication exposure and
risk assessment is not required for this scenario.  

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

The postapplication dermal MOE for golfers exposed to boscalid is
18,000.  This value exceeds 100, and thus does not exceed HED’s LOC
(i.e., the LOC is an MOE = 100).  Table 5.2 summarizes the inputs for
the assessment and the exposure and risk results to golfers.  

Table 5.2.	Dermal Postapplication Exposure and Risk from Boscalid for
Adults and Youth Golfers.  

Scenario	TTR 1 (ug/cm2)	CF1 (mg/ug)	TC 2 (cm2/hr)	ET (hr/day)	%DA	BW
(kg)	Daily Dose 3

(mg/kg/day)	Dermal MOE 4

Golf course turf	0.28	0.001	500	4	15	70	0.0012	18,000

TTR = Turf Transferable Residue on day 0 (mg/day).  CF1 = unit
Conversion Factor to convert μg units in the TTR to mg for daily
exposure (0.001 mg/ug).  TC = Transfer Coefficient.  ET = Exposure Time.
 DA = Dermal Absorption.  BW = Body Weight.  

1	TTR = use rate (0.5 lb ai/A) x [4.54E+8 (g/lb] x [24.7E-9 A/cm2] x
0.05.  

2	Based on ExpoSAC SOP# 3.1.     

3	Daily dose (mg/kg/day) = [TTR x CF1 x TC x ET x %DA] ÷ BW.  

4	Dermal MOE = NOAEL (21.8 mg/kg/day) ÷ daily dose (mg/kg/day).  

Golfing is considered to be a lifetime sport.  As a result, individuals
of all ages, excluding very small children, are assumed to play
routinely.  Children who are 12 years of age or older are likely to
represent the vast majority of the youth who play golf on a routine
basis.  However, the popularity of golf as a recreational pastime has
increased steadily over the last several years, which has resulted in
more young children (less than 12 years old) becoming involved in the
sport.  Risk assessments for these children are more difficult to
complete because of the increased uncertainties associated with
extrapolation of adult dermal exposure data, and because of the
increased likelihood of other behaviors that might contribute to
exposure, such as mouthing contaminated hands or golf balls.  Therefore,
the risk associated with children in a golfing scenario is addressed
qualitatively in the following discussion.

Five-year-old children were selected as the target group for this
exercise because younger children are not believed to be a viable
population for the purposes of assessing risk from a golfing scenario. 
The surface area to body weight ratio (SA/BW) for male children 5 years
of age (i.e., the difference is larger for males compared to female
making the value more protective) was calculated by using the 95th
percentile body surface area and the 50th percentile for body weight. 
The ratio was intentionally skewed to account for the uncertainties that
would be expected with calculating dose levels for children if more
definitive data were available, and for potential additional exposure
that may occur from mouthing behaviors.  This skewed SA/BW for children
was compared to that of the average adult, and found to be approximately
70% greater.  Based on this parameter alone, the child’s exposure
could be almost twice that of the adult golfer, however, it should be
noted that a child is not expected to use the golf course for the same
length of time as an adult.  While an adult is likely to play a full
round of golf (i.e., 18 holes), which takes approximately 4 hours, a
child would probably only spend about 2 hours (i.e., the 75th percentile
for time spent playing on grass by children aged 1-4 years and 5-11
years) on the course.  Thus, the child’s shorter duration on the golf
course offsets the higher SA/BW, and therefore, the child golfer’s
exposure is likely to be similar to that of the adult golfer.  [Note:
The values used to calculate SW/BW and estimate time spent playing on
grass were obtained from the EPA Exposure Factors Handbook (1997)].

6.0	Aggregate Risk Assessments and Risk Characterization  TC \l1 "7.0
Aggregate Risk Assessments and Risk Characterization 

Reference:  

Boscalid. Chronic Aggregate Dietary (Food and Drinking Water) Exposure
and Risk Assessment for the Section 3 Registration on the Citrus Crop
Group 10 and Alfalfa, and an Increase in the Tolerance on the Stone
Fruit Crop Group 12.  A. Acierto, DP#365262, 11/19/2009.

6.1	Acute Aggregate Risk

No toxic effects attributable to a single dose of boscalid have been
identified.  Therefore, an acute RfD has not been established for
boscalid and acute aggregate risk is not of concern.  

6.2	Short-Term Aggregate Risk

The boscalid short-term aggregate exposure and risk assessments combine
average dietary (food and drinking water) exposures with short-term
postapplication exposures of adult and youth golfers.  MOEs ranged from
840 to 1140.  The LOC for this assessment is for MOEs that are below
100.  Therefore, there are no short-term aggregate risks of concern. 
Short-term aggregate risks are summarized below in Table 6.2.

 TC \l2 "7.2	Short-Term Aggregate Risk Table 6.2.	Short-Term Aggregate
Risk Calculations for Boscalid.  

Population	Short-Term Scenario

	NOAEL

(mg/kg/day)	LOC 1	Maximum Allowable

Exposure 2

(mg/kg/day)	Average

Dietary

Exposure

(mg/kg/day)	Residential Exposure 3

(mg/kg/day)	Aggregate (Dietary and Rresidential) MOE 4

U.S. Population	21.8	100	0.218	0.024694	0.0012	840

Females (13-49 years)	21.8	100	0.218	0.019007	0.0012	1080

Adults  (50+ years)	21.8	100	0.218	0.020774	0.0012	1000

Youth  (13-19 years)	21.8	100	0.218	0.017901	0.0012	1140

1	The LOC includes the standard inter- and intraspecies UFs totaling
100; the FQPA SF = 1.  

2	Maximum allowable exposure (mg/kg/day) = NOAEL ÷ LOC.  

3	Residential exposure = dermal exposure; the residential exposure value
was taken from Table 5.2, above.  

4	Aggregate MOE = NOAEL ÷ [average dietary exposure + residential
exposure].  

6.3	Intermediate-Term Aggregate Risk

There are no intermediate-term residential scenarios; therefore,
intermediate-term aggregate exposure and risk are not of concern.  

6.4	Long-Term Aggregate Risk

There are no long-term residential scenarios for boscalid; therefore the
long-term aggregate risk assessment would incorporate only dietary (food
and drinking water) residues.  The long-term aggregate risk assessment
is identical to the chronic dietary risk assessment for which there are
no concerns, as shown in Section 4.5.2 of this memorandum. TC \l2 "7.4
Long-Term Aggregate Risk   

6.5	Cancer Aggregate Risk TC \l2 "7.5	Cancer Risk 

HED classified boscalid as demonstrating “suggestive evidence of
carcinogenicity” and noted that quantification of human cancer risk
was not recommended.  As a result, aggregate cancer exposure and risk
are not of concern.

7.0	Cumulative Risk Characterization/Assessment  TC \l1 "7.0	Cumulative
Risk Characterization/Assessment 

Unlike other pesticides for which EPA has followed a cumulative risk
approach based on a common mechanism of toxicity, EPA has not made a
common mechanism of toxicity finding as to boscalid and any other
substances and boscalid does not appear to produce a toxic metabolite
produced 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/.

8.0	Occupational Exposure/Risk Assessment Pathway

Reference:  

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

8.1	Occupational Pesticide Handler Exposure and Risk

Broadcast foliar applications of boscalid may be applied to alfalfa
(including alfalfa grown for seed) at a rate of 0.48 lb ai/A (Endura®)
and 0.28 lb ai/A (Pristine®) and to citrus at a rate of 0.29 lb ai/A
(Pristine®).  For alfalfa, up to three applications can be made per
season at RTI of 14 to 21 days.  The PHI is 14 days.  For citrus, up to
four applications can be made per season at RTIs of 10 to 21 days.  The
PHI is zero days.  Handlers may apply boscalid to alfalfa using aerial,
chemigation, or groundboom equipment.  To citrus, handlers may apply
boscalid using aerial, chemigation, airblast, or handgun equipment. 

Agricultural Handlers

No chemical-specific handler exposure data were submitted in support of
this registration.  It is the policy of the HED to use data from the
Pesticide Handlers Exposure Database (PHED) Version 1.1 as presented in
PHED Surrogate Exposure Guide (8/98) to assess handler exposures for
regulatory actions when chemical-specific monitoring data are not
available (HED ExpoSAC SOP #7, dated 1/28/99).  Additionally, data from
Outdoor Residential Exposure Task Force (ORETF) were used to assess some
scenarios.  Handler exposure is expected to be short- or
intermediate-term based on information provided on proposed labels.

Dermal.  The results of the occupational handler exposure and risk
assessment indicate that short- and intermediate-term dermal MOEs were
greater than the LOC (MOEs ≥ 100) at the baseline clothing level, when
baseline data are available.  There are no data to assess the
mixing/loading/applying handgun scenario at baseline attire.  The short-
and intermediate-term dermal risks do not exceed HED’s LOC for
mixing/loading/applying with handgun equipment when baseline attire plus
chemical-resistant gloves are used.  Additionally, only engineering
control (enclosed cockpit) data are available to assess dermal risks to
handlers operating aircraft.  The short- and intermediate-term dermal
risks do not exceed HED’s LOC for pilots using enclosed cockpits and
wearing baseline attire.

 

Inhalation.  The short- and intermediate-term inhalation risks to
handlers do not exceed HED’s LOC at baseline (no respirator) for any
of the handler scenarios.  Only engineering control (enclosed cockpit)
data are available to assess short- and intermediate-term inhalation
risks to handlers operating aircraft.  The short- and intermediate-term
inhalation risks do not exceed HED’s LOC for pilots using enclosed
cockpits and wearing no respirator.

Combined.  Combined dermal plus inhalation risks do not exceed HED’s
LOC, provided personal protective equipment (PPE) listed under the
short- and intermediate-term dermal risks are worn. 

 (MOEs ≥ 100) at some level of risk mitigation.  

TABLE 8.1.	Short- and Intermediate-Term Agricultural Handler Exposure
and Risk for Boscalid.

Exposure Scenario	Crop or Target	App Ratea

(lb ai/A)	Acres Treated Dailyb	Mitigation Levelc	Unit Exposured	Dose
(mg/kg/day)	MOE (Target MOE = 100)

	Dermal

(mg/lb ai)	Inhalation

(µg/lb ai)	Dermale	Inhalationf	Dermalg	Inhalationh	Combined Dermal +
Inhalationi

Mixing/Loading Dry Flowables for Aerial Applications	Alfalfa	0.48	1200
Baseline	0.066	0.77	0.081	0.0063	270	3,400	250

0.28	1200

0.066	0.77	0.048	0.0037	460	5,900	430

	Citrus	0.29	350

0.066	0.77	0.014	0.0011	1,500	20,000	1,400

Mixing/Loading Dry Flowables for Chemigation Applications	Alfalfa	0.48
350	Baseline	0.066	0.77	0.024	0.0018	920	12,000	850

0.28	350

0.066	0.77	0.014	0.0011	1,600	20,000	1,500

	Citrus	0.29	350

0.066	0.77	0.014	0.0011	1,500	20,000	1,400

Mixing/Loading Dry Flowables for Groundboom Applications	Alfalfa	0.48
200	Baseline	0.066	0.77	0.014	0.0011	1,600	21,000	1,500

0.28	200

0.066	0.77	0.0079	0.00062	2,800	35,000	2,600

Mixing/Loading Dry Flowables for Airblast Applications	Citrus	0.29	40
Baseline	0.066	0.77	0.0016	0.00013	13,000	170,000	12,000

Applying Sprays via Aerial Equipment	Alfalfa	0.48	1200	Engineering
Controls	0.005	0.068	0.0062	0.00056	3,500	39,000	3,200

0.29	1200

0.005	0.068	0.0037	0.00034	5,800	64,000	5,400

	Citrus	0.29	350

0.005	0.068	0.0011	0.000099	20,000	220,000	18,000

Applying Sprays via Groundboom Equipment	Alfalfa	0.48	200	Baseline	0.014
0.74	0.0029	0.001	7,600	21,000	5,600

0.28	200

0.014	0.74	0.0017	0.00059	13,000	37,000	9,600

Applying Sprays via Airblast Equipment	Citrus	0.29	40	Baseline	0.36	4.5
0.0089	0.00075	2,400	29,000	2,200

Flagging for Aerial Sprays Applications	Alfalfa	0.48	350	Baseline	0.011
0.35	0.004	0.00084	5,500	26,000	4,500

0.28	350

0.011	0.35	0.0023	0.00049	9,400	44,000	7,800

	Citrus	0.29	350

0.011	0.35	0.0024	0.00051	9,100	43,000	7,500

Mixing/Loading/Applying Dry Flowables Concentrates with a Handgun
Sprayer	Citrus	0.29	5	Dermal: Baseline Plus Gloves

Inhalation: Baseline	0.58	22	0.0018	0.00046	12,000	48,000	9,600

a	Application Rates based on proposed uses on boscalid labels for
Endura® (EPA Reg. No. 7969-197) and Pristine® (EPA Reg. No. 7969-198).

b	Science Advisory Council Policy # 9.1

c	Baseline Dermal:  Long-sleeve shirt, long pants, and no gloves.

Baseline Inhalation: no respirator.

Engineering control unit exposure for applying sprays via aerial
equipment = enclosed cockpit.  

Baseline plus Gloves Dermal: Baseline plus chemical-resistant gloves.

d	Unit Exposures based on PHED Version 1.1 or ORETF data. 

e	Dermal Dose  (mg/kg/day)  = daily unit exposure (mg/lb ai)  x
application rate (lb ai/acre) x acres treated x dermal absorption factor
(15%) / body weight (70 kg adult).

f	Inhalation Dose (mg/kg/day) = daily unit exposure (μg/lb ai)  x
application rate (lb ai/acre) x acres treated x inhalation absorption
(100%) / body weight (70 kg adult).  

g	Dermal MOE = NOAEL (21.8 mg/kg/day) / dermal daily dose (mg/kg/day). 
Level of concern = 100.

h	Inhalation MOE = NOAEL (21.8 mg/kg/day) / inhalation daily dose
(mg/kg/day). Level of concern = 100.

i	Combined Baseline Dermal + Inhalation MOE = 1 / (1/Baseline Dermal
MOE) + (1/Baseline Inhalation MOE).

8.2	Occupational Postapplication Worker Exposure and Risk

HED assumes that inhalation exposures are minimal following outdoor
applications of an ai with low vapor pressure.  Since the proposed uses
of boscalid are applied only in outdoor settings and boscalid has a low
vapor pressure, postapplication inhalation exposures and risks were not
assessed. 

Short- and intermediate-term dermal postapplication exposures and risks
to occupational workers were estimated using standard values established
by HED since no chemical-specific data were submitted.  The TCs used for
all postapplication activities were established by ExpoSAC SOP #3.1. 
The DFR levels were estimated using HED standard values where it is
assumed that the initial residue on treated foliage is 20% of the
application rate and the residues degrade at a rate of 10% per day. 
Using HED default assumptions and surrogate DFR data, all scenarios
resulted in MOEs greater than 100 on day 0 (12 hours after application),
and therefore risks do not exceed HED’s LOC.  Table 8.2.1 presents the
default DFR values on day 0 (12 hours after application) that were used
for this postapplication exposure and risk assessment. 

TABLE 8.2.1.  Summary of DFRs by Crop Grouping Based on HED Default
Assumptions.1

Crop	Application rate

(lb ai/acre)	Fraction of ai retained on the foliage	Conversion 

Factor 1

(µg/lb)	Conversion 

Factor 2

(A/cm2)	Day after Application	Default DFR

(µg/cm2)

Alfalfa	0.48	20% (Default)	4.54E+8	2.47E-8	0

(12 hours)	1.077

	0.28

	0.628

Citrus	0.29

	0.651

1	Default DFR (µg/cm2) = application rate (lb ai/A) x (1- daily
dissipation rate) t x 4.54E8 µg/lb x  24.7E-9 A/cm2  x   20% DFR after
initial treatment.

The postapplication exposure associated with agricultural crops is
summarized in Table 8.2.2.  Using HED default assumptions and surrogate
DFR data, all scenarios resulted in MOEs greater than 100 on day 0 (12
hours after application) and, therefore, risks do not exceed HED’s
LOC.  

TABLE 8.2.2.	Summary of Occupational Postapplication Risks (Short- and
Intermediate-Term) with HED Default Assumptions.

Crop Grouping	Application rate

(lb ai/acre)	Default DFR 

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

(LOC = 100)

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

	0.28	0.628

0 (12 hours)	1,300

Citrus	0.29	0.651	3,000 (Pruning)	0 (12 hours)	650

Notes: Crops were assessed using the highest transfer coefficient
available.

Since postapplication risks were not a concern on day 0 (12 hours
following application), the restricted entry interval (REI) is based on
the acute toxicity of boscalid technical material.  Boscalid is
classified as toxicity category III by the dermal route of exposure and
category IV for eye irritation and skin irritation potential.  Under the
Worker Protection Standard (WPS) for Agricultural Pesticides, active
ingredients classified as acute toxicity categories III or IV for these
routes are assigned a 12-hour REI.  Therefore, the 12-hour REI that
appears on the proposed label is adequate.

9.0	Tolerance Harmonization and Recommended Tolerance

For purposes of both the tolerance expression and dietary risk
assessment, HED has concluded that the ROC in plant commodities include
only boscalid, and the residues of concern in livestock commodities
include boscalid, its 5-hydroxy metabolite, and the glucuronide
conjugate of the 5-hydroxy metabolite.

According to the memo Interim Guidance on Tolerance Expressions by S.
Knizner, the tolerances should be expressed as follows:

(a)	General. 

(1) Tolerances are established for residues of the fungicide boscalid,
including its metabolites and degradates, in or on the commodities
listed below.   Compliance with the tolerance levels specified below is
to be determined by measuring only 

3-pyridinecarboxamide, 2-chloro-N-(4'-chloro[1,1'-biphenyl]-2-yl).

Alfalfa, forage	30.0  ppm

Alfalfa, hay	65.0  ppm

Citrus, dried pulp	4.5 ppm

Citrus, oil	85.0 ppm

Fruit, citrus, group 10	1.6 ppm

Fruit, stone, group 12	3.5 ppm

(2) Tolerances are established for residues of the fungicide boscalid,
including its metabolites and degradates, in or on the food commodities
listed below.  Compliance with the tolerance levels specified below is
to be determined by measuring only the sum of 3-pyridinecarboxamide,
2-chloro-N-(4'-chloro[1,1'-biphenyl]-2-yl) and metabolites
2-chloro-N-(4'-chloro-5-hydroxy-biphenyl-2-yl) nicotinamide and
glucuronic acid conjugate of
2-chloro-N-(4'-chloro-5-hydroxy-biphenyl-2-yl) nicotinamide, calculated
as the stoichiometric equivalent of boscalid.

Hog, fat	0.20 ppm

Poultry, fat	0.20 ppm

Poultry, meat byproducts	0.20 ppm

The established tolerances of the following commodities remain
unchanged. 

Cattle, fat	0.30 ppm

Cattle, meat	0.10 ppm

Cattle, meat byproducts	0.35 ppm

Egg	0.02 ppm

Goat, fat	0.30 ppm

Goat, meat	0.10 ppm

Goat, meat byproducts	0.35 ppm

Hog, meat	0.05 ppm

Hog, meat byproducts	0.10 ppm

Horse, fat	0.30 ppm

Horse, meat	0.10 ppm

Horse, meat byproducts	0.35 ppm

Milk	0.10 ppm

Poultry, meat	0.05 ppm

Sheep, fat	0.30 ppm

Sheep, meat	0.10 ppm

Sheep, meat byproducts	0.35 ppm

(d)	Indirect or inadvertent residues.  

Tolerances are established for residues of the fungicide boscalid,
including its metabolites and degradates, in or on the commodities
listed below.   Compliance with the tolerance levels specified below is
to be determined by measuring only 3-pyridinecarboxamide,
2-chloro-N-(4'-chloro[1,1'-biphenyl]-2-yl). 

Animal feed, nongrass, group 18, forage, excluding alfalfa	1.0 ppm

Animal feed, nongrass, group 18, hay, excluding alfalfa	2.0 ppm

Permanent tolerances are established for residues of boscalid in/on
various plant commodities at levels ranging from 0.05 to 60 ppm [40 CFR
§180.589(a)(1)].  Separate tolerances are also established for indirect
or inadvertent residues of boscalid in rotational crops at levels
ranging from 0.05 to 8.0 ppm [40 CFR §180.589(d)].  Tolerances are also
established for the combined residues of boscalid, its 5-hydroxy
metabolite, and the glucuronic acid conjugate of the 5-hydroxy
metabolite, at levels ranging from 0.02 ppm to 0.35 ppm [40 CFR
§180.589(a)(2)].  The proposed and recommended tolerances for boscalid
are presented in Table 9.0.

An adequate number of field trials conducted at ~1X the existing or
proposed use rates are available on alfalfa, citrus fruits (orange,
lemon, grapefruit), and stone fruits (cherry, peach, plum) to support
permanent tolerances.  The Agency’s SOP “Guidelines for Setting
Pesticide Tolerances Based on Field Trial Data” was utilized for
determining the appropriate tolerance level for each commodity.  For
alfalfa forage and hay, residue data from both the 1st and 2nd cuttings
of Treatment #2 (1X rate) were used to assess tolerances as both
cuttings were collected around the proposed 14-day PHI, and residue
levels were similar for the two cuttings.  The recommended tolerances
for alfalfa forage and hay are 30 and 65 ppm, respectively.

For the citrus fruits, the residue data were pooled by crop, and
separate possible tolerances were calculated for oranges (1.6 ppm),
lemons (1.6 ppm), and grapefruits (1.1 ppm) using the tolerance
spreadsheet.  As the minimum and maximum recommended tolerances differ
by less than 5X, a crop group tolerance is appropriate for citrus, and
the recommended tolerance is 1.6 ppm.

For stone fruits, all the adequate residue data were pooled by crop
(including previously reviewed studies), and separate possible
tolerances were calculated for cherry (3.5 ppm), peach (3.0 ppm), and
plum (1.6 ppm) using the tolerance spreadsheet.  As the minimum and
maximum recommended tolerances differ by less than 5X, a crop group
tolerance is appropriate for stone fruits, and the recommended tolerance
is 3.5 ppm.

As boscalid residues were reduced in orange juice (<0.2X), a separate
tolerance is not required for citrus juice.  However, boscalid residues
were shown to concentrate in dried pulp (3.1X) and oil (59X).  Based on
these processing factors and the HAFT residues for citrus fruits (1.39
ppm), the maximum expected boscalid residues would be 4.31 ppm in dried
pulp and 82 ppm in oil.  These data support tolerances of 4.5 ppm for
dried citrus pulp and 85 ppm for citrus oil.

were <0.03 ppm in milk, <0.08 ppm in cream, ≤0.11 ppm in liver and
kidneys, <0.05 ppm in muscle, and <0.24 ppm in fat.  These data indicate
that the existing tolerances for milk and fat, meat, and meat byproducts
of cattle, goats, horses, and sheep are more than adequate.  Separate
tolerances for liver and kidney are not required.

For hogs, the adequacy of the existing tolerances were assessed using
residue data from the 5.9 ppm dose group (1.1X dietary burden for swine)
in the cattle feeding studies.  Maximum combined residues for this dose
group were <0.064 ppm in liver, <0.090 ppm in kidney, <0.05 ppm in
muscle, and <0.12 ppm in fat.  These data indicate that the existing
tolerances for meat (0.05 ppm) and meat byproducts (0.10 ppm) of hogs
are adequate; however, the tolerance for hog fat should be increased to
0.20 ppm. Separate tolerances of hog liver and kidney are not necessary.

For poultry, the adequacy of the existing tolerances were assessed using
residue data from the 5.31 ppm dose group in the poultry feeding
studies; this group represents 1.3X the calculated dietary burden for
poultry.  Maximum combined residues for this dose group were <0.02 ppm
in eggs, <0.175 ppm in liver, <0.05 ppm in muscle, and <0.124 ppm in
fat.  These data indicate that the existing tolerances for eggs (0.02
ppm) and poultry meat (0.05 ppm) are adequate; however, the tolerances
for poultry fat and meat byproducts should each be increased to 0.20
ppm.  A separate tolerance for liver is not necessary.

 

The Codex Alimentarius Commission, Canada, and Mexico have not
established any maximum residue limits (MRLs) for residues of boscalid
in/on alfalfa forage and hay or citrus fruits (Appendix C).  However,
there is an existing Codex MRL for stone fruits at 3 mg/kg, and Canada
has established MRLs at 1.7 mg/kg for the various member of the stone
fruits crop group.  Canada also has also established MRLs for various
livestock commodities.  The Canadian MRLs for stone fruits and livestock
commodities are currently harmonized with the respective U.S.
tolerances; however, once the recommended increases are made to U.S.
tolerances, the U.S. tolerances on stone fruits, poultry fat and meat
byproducts, and hog fat will no longer be harmonized with the Canadian
MRLs. 

While not officially part of the Codex Alimentarius Commission
structure, the Joint FAO/WHO Meetings on Pesticide Residues (JMPR)
provide independent scientific expert advice to the Commission and its
specialist Committee on Pesticide Residues.  To determine MRLs for the
stone fruit crop group, both the U.S. and JMPR used the same database of
field trial studies in 2006.  The resulting values are not in harmony
because the U.S. uses the averages of duplicate samples for a given
trial, whereas JMPR uses the highest value from each trial site.  

Additionally, the U.S. used the NAFTA statistical calculation method
whereas the JMPR did not routinely use statistical calculation methods
in 2006.

TABLE 9.0.	Tolerance Summary for Boscalid.

Commodity	Proposed  Tolerance (ppm)	Existing Tolerance (ppm)	Recommended
Tolerance (ppm)	Comments; Correct Commodity Definition

40 CFR 180.589(a)(1)

Alfalfa, forage	35	--	30	Adequate alfalfa forage and hay residue data
are available.

Alfalfa, hay	85	--	65

	Citrus, dried pulp	None	--	4.5	An adequate orange processing study is
available indicating that boscalid residues can concentrate in dried
pulp (3.1X) and oil (59X).

Citrus, oil	None	--	85

	Fruit, citrus, group 10	2.0	--	1.6	Adequate orange, grapefruit, and
lemon residue data are available.

Fruit, stone, group 12	5.0	1.7	3.5	An increase in the established
tolerance is required based on adequate cherry, peach, and plum residue
data.

40 CFR 180.589(a)(2)

Cattle, fat	1.5	0.30	0.30	Based on the residue data from the 35.8 ppm
dose group in the cattle feeding studies and the calculated dietary
burden for dairy cattle (35.2 ppm), the existing tolerances are
adequate.  Separate tolerances for liver and kidney are not necessary.

Cattle, kidney	1.0	--	None

	Cattle, liver	1.0	--	None

	Cattle, meat	0.2	0.10	0.10

	Cattle, meat byproducts	1.5	0.35	0.35

	Egg	0.02	0.02	0.02	The existing tolerance on eggs is adequate.

Goat, fat	1.5	0.30	0.30	See Cattle above.

Goat, kidney	1.0	--	None

	Goat, liver	1.0	--	None

	Goat, meat	0.2	0.10	0.10

	Goat, meat byproducts	1.5	0.35	0.35

	Hog, fat	0.2	0.10	0.20	Based on the residue data from the 5.9 ppm dose
group in the cattle feeding studies and the calculated dietary burden
for swine (5.30 ppm), the existing tolerances on hog meat and meat
byproducts are adequate.  However, the tolerance for hog fat should be
increased to 0.20 ppm.

Hog, meat	0.05	0.05	0.05

	Hog, meat byproducts	0.2	0.10	0.10

	Hog, kidney	0.2	--	None

	Hog, liver	0.2	--	None

	Horse, fat	1.5	0.30	0.30	See Cattle above.

Horse, kidney	1.0	--	None

	Horse, liver	1.0	--	None

	Horse, meat	0.2	0.10	0.10

	Horse, meat byproducts	1.5	0.35	0.35

	Milk	0.2	0.10	0.10	The existing tolerance for milk will adequately
cover residues in both whole milk and milk fat

Milk, fat (cream)	1.5	--	None

	Poultry, liver	0.2	--	None	Based on the residue data from the 5.31 ppm
dose group in the poultry feeding study and the calculated dietary
burden for poultry (4.10 ppm), the existing tolerance for meat is
adequate and the tolerances of fat and meat byproducts should be
increased to 0.20 ppm.  A separate tolerance for liver is not necessary.

Poultry, fat	0.2	0.05	0.20

	Poultry, meat	0.05	0.05	0.05

	Poultry, meat byproducts	0.2	0.10	0.20

	Sheep, fat	1.5	0.30	0.30	See Cattle above.

Sheep, kidney	1.0	--	None

	Sheep, liver	1.0	--	None

	Sheep, meat	0.2	0.10	0.10

	Sheep, meat byproducts	1.5	0.35	0.35

	

10.0	Data Needs

10.1	Toxicology Data Requirements

870.7800	Immunotoxicity Study

As part of the new 40CFR §158 Guidelines, an immunotoxicity study in
rats and/or mice is required (see Appendix B).  

10.2	Residue Chemistry Data Requirements

860.1200	Direction for Use

A revised Section B for alfalfa is required to amend the label direction
for the 70% WDG formulation since it could not be supported by the field
trial data generated with a maximum seasonal use rate of 0.9 lb ai/A.  
The proposed label rate for the 70% WDG formulation is 1.7X higher; the
label should be revised to match the field trial rate.

860.1550	Proposed Tolerances

Boscalid residues concentrate in citrus dried pulp (3.1X) and citrus oil
(59X).  A revised Section F is required to propose separate tolerances
for citrus, dried pulp at 4.5 ppm, citrus, oil at 85 ppm, and fruit,
citrus, group 10 at 1.6 ppm.

The available data for stone fruits will not support a tolerance level
of 5.0 ppm.  A revised Section F should be submitted with a tolerance
for fruit, stone, group 12 at 3.5 ppm.

The available data will not support the proposed tolerances for meat,
meat byproducts, and fat of cattle goat, horse, and sheep at 0.2 ppm,
1.5 ppm, and 1.5 ppm, respectively.  The existing tolerances will be
maintained for meat, meat byproducts, and fat of cattle, goat, horse,
and sheep at 0.10 ppm, 0.35 ppm, and 0.30 ppm, respectively.  The
available data will not support the proposed tolerance of 0.2 ppm for
milk and the proposed tolerance of 1.5 ppm for milk fat.  The existing
tolerance of 0.10 ppm will be maintained for milk, and it is adequate to
cover milk fat.  The proposed tolerances of 0.20 ppm for hog, fat;
poultry, fat; and poultry, meat byproducts are adequate.  For all
remaining livestock commodities, the proposed tolerances must be revised
to reflect the recommended tolerance levels as specified in Table 9.0.

10.3	Occupational/Residential Exposure Data Requirements

None.

References

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

BAS 510 F: Report of the Cancer Assessment Review Committee. J. Kidwell,
TXR#0051289, 11/14/2002.

Boscalid. Human Health Risk Assessment for a Section 3 Tolerance on
Endive, an Amendment to the Tolerances for Strawberries and Berries,
Crop Group 13, and an Increase in Tolerances in/on Cucumber and
Vegetable, Root, Subgroup 1A, except Sugar Beet, Garden Beet, Radish,
and Turnip. B. Hanson, DP#327906, 07/10/2007.  TC \l1 "3.0  HAZARD
CHARACTERIZATION 

Boscalid:  Human Health Risk Assessment to Support Proposed New Uses on
Fresh Herbs (Herbs Subgroup 19A), Avocado, Black Sapote, Canistel, Mamey
Sapote, Mango, Papaya, Sapodilla, Star Apple and Cotton. D. Davis,
DP#336182, 02/13/2008.

Boscalid Occupational/Residential Exposure Memorandum. S. Wang,
DP#290072, 06/23/2003.

Boscalid. Petition for a Tolerance for Belgian Endive; Petition for
Increased Tolerances on Strawberry and the Berries Crop Group;
Submission of Requested Field Trial Data on Cucumber, Mustard Greens,
and Sunflower; and Supplemental Field Trial Data on Fruiting Vegetables,
Radishes, Spearmint, Peppermint, Grapes, and Stone Fruits; and
Submission of Field Trials and a Processing Study for Cotton. Summary of
Analytical and Residue Data. D. Soderberg, DP#323288, 06/14/2007.

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

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

Drinking Water Exposure Assessment for New Uses of Boscalid on Alfalfa
Forage and Hay, Citrus group 10, and an Increase in Tolerance on Stone
Fruit group 12.  D. Lieu, DP#367184, 09/24/2009.

PP# 1F06313 --Human Health Risk Assessment for New Fungicide BAS 510 F
(Common Name: Boscalid) -- Proposal for Tolerances for Residues in/on
Numerous Crops and Livestock Commodities. Y. Donovan, DP#290022,
09/08/2003.

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

Table A.1.	Acute Toxicity Profile for Boscalid.  

Guideline Number	Study Type	MRID Number	Results	Toxicity Category

870.1100	Acute Oral	45404814	LD50 =>5,000 mg/kg	IV

870.1200	Acute Dermal	45404815	LD50 =>2000 mg/kg	III

870.1300	Acute Inhalation 	45404816	LC50 =>6.7 mg/L	IV

870.2400	Primary Eye  Irritation	45404817	Not irritating	IV

870.2500	Primary Skin Irritation	45404818	Not irritating	IV

870.2600	Dermal Sensitization	45404819 1	Could not be determined	NA 2

1. Unacceptable because the 5% concentration used for the challenge was
inadequate.  

2. NA = Not Applicable.  

Table A.2.	Subchronic, Chronic and Other Toxicity Profile of Boscalid
Technical

Guideline Number	Study Type	Results

870.3100	90-Day oral toxicity rodents (rats)	NOAEL: 34/159 mg/kg/day
(M/F)

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

870.3100	90-Day oral toxicity rodents (mice)	NOAEL: 197/2209 mg/kg/day
(M/F)

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

870.3150	90-Day oral toxicity in nonrodents (dogs)

	NOAEL: 7.6/8.1 mg/kg/day (M/F)

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

F = increased alkaline phosphatase activity and hepatic weights.

870.3200	21/28-Day dermal toxicity

(rats)	NOAEL: 1000 mg/kg/day (HDT)

LOAEL: >1000 mg/kg/day

870.3700	Prenatal developmental in rodents (rats)	Maternal NOAEL: 1000
mg/kg/day

Maternal LOAEL: cannot be established

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
µg/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 µg/mL.

870.5375	In vitro mammalian cytogenetics assay in Chinese hamster V79
cells

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

870.5395	Cytogenetics - mammalian erythrocyte micronucleus test in the
mouse

	Negative at doses up to 2000 mg/kg.

870.5500	In vitro unscheduled DNA synthesis (primary rat hepatocytes)

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

870.6200	Acute neurotoxicity screening battery (rat)

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

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

870.6200	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.

870.7600	Dermal Penetration (rat)	Maximum % absorption:

0.01 mg/cm2 = 10.93 (24 hour exposure, 24 hour sacrifice)

0.10 mg/cm2 = 3.76 (24 hour exposure, 24 hour sacrifice)

1.00 mg/cm2 = 1.48 (10 hour exposure, 72 hour sacrifice)

None	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:  Rationale for Toxicity Data Requirements

OPPTS Guideline Number:  870.7800

Study Title:  Immunotoxicity

Rationale for Requiring the Data

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

	The Immunotoxicity Test Guideline (OPPTS 870.7800) prescribes
functional immunotoxicity testing, and is designed to evaluate the
potential of a repeated chemical exposure to produce adverse effects
(such as suppression) on the immune system.  Immunosuppression is a
deficit in the ability of the immune system to respond to a challenge of
bacterial or viral infections, such as tuberculosis (TB), Severe
Acquired Respiratory Syndrome (SARS), or neoplasia.  Because the immune
system is highly complex, studies not specifically conducted to assess
immunotoxic endpoints are inadequate to characterize a pesticide’s
potential immunotoxicity.  While data from hematology, lymphoid organ
weights, and histopathology in routine chronic or subchronic toxicity
studies may offer useful information on potential immunotoxic effects,
these endpoints alone are insufficient to predict immunotoxicity.  

Practical Utility of the Data

How will the data be used?

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瑹暈<܀ and are inadequate to characterize a pesticide’s potential
immunotoxicity in humans, animal studies are used as the most sensitive
endpoint for risk assessment.  These animal studies can be used to
select endpoints and doses for use in risk assessment of all exposure
scenarios, and are considered a primary data source for reliable
reference dose calculation.  For example, animal studies have
demonstrated that immunotoxicity in rodents is one of the more sensitive
manifestations of TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) among
developmental, reproductive and endocrinologic toxicities. 
Additionally, the EPA has established an oral reference dose (RfD) for
tributyltin oxide (TBTO), based on observed immunotoxicity in animal
studies (IRIS, 1997).  

How could the data impact the Agency's future decision-making? 

	If the immunotoxicity study shows that the test material poses either a
greater or a diminished risk than that given in the interim decision’s
conclusion, the risk assessments for the test material may need to be
revised to reflect the magnitude of potential risk derived from the new
data.  

 	If the Agency does not have these data, a 10X database UF may be
applied for conducting a risk assessment from the available studies.  

APPENDIX C: INTERNATIONAL RESIDUE LIMIT STATUS

INTERNATIONAL RESIDUE LIMIT STATUS

Chemical Name:  

3-pyridinecarboxamide, 2-chloro-N-(4'-chloro[1,1'-biphenyl]-2-yl	Common
Name:

Boscalid	X  Proposed tolerances

X  Reevaluated tolerance

□  Other	Date: 8/05/09

Codex Status (Maximum Residue Limits)	U. S. Tolerances

□No Codex proposal step 6 or above

□No Codex proposal step 6 or above for the crops requested 
Petition Numbers:  PP#9F7527 and PP#9F9529

DP#: 364447 

□ No Limits

□  No Limits for the crops requested	X  No Limits

nition: NA.  Mexico defers to U.S. tolerances or Codex MRLs for its
export purposes.

Crops/Commodities	MRL (mg/kg)	Crops/Commodities	MRL (ppm)

apricot, plumcot, plum, peach, sweet cherry, and tart cherry	1.7

Eggs	0.02

Fat of cattle, goats, hogs, horses, and sheep	0.3

Fat of poultry	0.05

Meat of cattle, goats, hogs, horses, and sheep	0.1

Meat of poultry 	0.05

Meat byproducts of cattle, goats, hogs, horses, and sheep	0.35

Meat byproducts of poultry	0.1

Milk	0.1

	Notes/Special Instructions: S.Funk, 10/14/2009.

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