Document ID: EPA-HQ-OPP-2005-0145-0046
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2008-03-28T04:00Z

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C.  20460

     OFFICE OF	

PREVENTION, PESTICIDES

AND TOXIC SUBSTANCES

Date:  2/13/08

							

MEMORANDUM

SUBJECT:	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.
 PC Code: 128008; Petition Nos: 6E7164, 7F7169; DP Barcodes:  336182,
337369

		Regulatory Action: Section 3 Registration Action

		Risk Assessment Type:   Single Chemical Aggregate

					

FROM:	Donna S. Davis, Chemist/Risk Assessor	

		Reregistration Branch 1

		Health Effects Division (7509P)

		Christine L. Olinger, Chemist, RRB1

Shih-Chi Wang, Biologist, RAB2

		Health Effects Division (7509C)

THROUGH:	Kit Farwell, D.V.M

		Matthew Lloyd, Industrial Hygienist

		Michael S. Metzger, Chief	

		Reregistration Branch 1

		Health Effects Division (7509P)

TO:		Shaja Brothers/Barbara Madden/Dan Rosenblatt

RIMUERB/Registration Division (7505P)

	and

Bryant Crowe/Tony Kish/Cynthia Giles-Parker

Fungicide Branch/Registration Division (7505P)

Attached please find the Human Health Risk Assessment for the active
ingredient, boscalid, to support requested new uses on the herbs crop
subgroup 19A, various tropical fruits and cotton.

Table of Contents

  TOC \o "1-3" \h \z \u    HYPERLINK \l "_Toc185647174"  1.0	Executive
Summary	  PAGEREF _Toc185647174 \h  4  

  HYPERLINK \l "_Toc185647175"  Regulatory Recommendation	  PAGEREF
_Toc185647175 \h  7  

  HYPERLINK \l "_Toc185647176"  2.0	Ingredient Profile	  PAGEREF
_Toc185647176 \h  7  

  HYPERLINK \l "_Toc185647177"  2.1	Summary of Proposed New Uses	 
PAGEREF _Toc185647177 \h  7  

  HYPERLINK \l "_Toc185647178"  2.2	Structure and Nomenclature	  PAGEREF
_Toc185647178 \h  8  

  HYPERLINK \l "_Toc185647179"  2.3	Physical and Chemical Properties	 
PAGEREF _Toc185647179 \h  8  

  HYPERLINK \l "_Toc185647180"  3.0	Hazard Characterization	  PAGEREF
_Toc185647180 \h  9  

  HYPERLINK \l "_Toc185647181"  3.1	Hazard Characterization/ Endpoint
Selection	  PAGEREF _Toc185647181 \h  9  

  HYPERLINK \l "_Toc185647182"  3.2	FQPA Uncertainty Factors	  PAGEREF
_Toc185647182 \h  11  

  HYPERLINK \l "_Toc185647183"  3.3	Endocrine Disruption	  PAGEREF
_Toc185647183 \h  11  

  HYPERLINK \l "_Toc185647184"  4.0	Public Health and Pesticide
Epidemiology Data	  PAGEREF _Toc185647184 \h  12  

  HYPERLINK \l "_Toc185647185"  5.0	Dietary Exposure/Risk
Characterization	  PAGEREF _Toc185647185 \h  12  

  HYPERLINK \l "_Toc185647186"  5.1	Pesticide Metabolism and
Environmental Degradation	  PAGEREF _Toc185647186 \h  12  

  HYPERLINK \l "_Toc185647187"  5.2	Dietary Exposure and Risk	  PAGEREF
_Toc185647187 \h  17  

  HYPERLINK \l "_Toc185647188"  6.0	Residential (Non-Occupational)
Exposure/Risk Characterization	  PAGEREF _Toc185647188 \h  18  

  HYPERLINK \l "_Toc185647189"  6.1	Residential Handler Exposure	 
PAGEREF _Toc185647189 \h  18  

  HYPERLINK \l "_Toc185647190"  6.2.	Residential Postapplication
Exposure	  PAGEREF _Toc185647190 \h  19  

  HYPERLINK \l "_Toc185647191"  6.3	Other (Spray Drift, etc.)	  PAGEREF
_Toc185647191 \h  20  

  HYPERLINK \l "_Toc185647192"  7.0	Aggregate Risk Assessments and Risk
Characterization	  PAGEREF _Toc185647192 \h  21  

  HYPERLINK \l "_Toc185647193"  7.1	Acute Aggregate Risk	  PAGEREF
_Toc185647193 \h  21  

  HYPERLINK \l "_Toc185647194"  7.2	Short-Term Aggregate Risk	  PAGEREF
_Toc185647194 \h  21  

  HYPERLINK \l "_Toc185647195"  7.3	Intermediate-Term Aggregate Risk	 
PAGEREF _Toc185647195 \h  21  

  HYPERLINK \l "_Toc185647196"  7.4	Long-Term Aggregate Risk	  PAGEREF
_Toc185647196 \h  22  

  HYPERLINK \l "_Toc185647197"  7.5	Cancer Aggregate Risk	  PAGEREF
_Toc185647197 \h  22  

  HYPERLINK \l "_Toc185647198"  8.0	Cumulative Risk
Characterization/Assessment	  PAGEREF _Toc185647198 \h  22  

  HYPERLINK \l "_Toc185647199"  9.0	Occupational Exposure/Risk Pathway	 
PAGEREF _Toc185647199 \h  22  

  HYPERLINK \l "_Toc185647200"  9.1	Short-/Intermediate-Term Handler
Risk	  PAGEREF _Toc185647200 \h  23  

  HYPERLINK \l "_Toc185647201"  9.2	Short-Term Postapplication Risks	 
PAGEREF _Toc185647201 \h  26  

  HYPERLINK \l "_Toc185647202"  9.3	Worker Protection Standard	  PAGEREF
_Toc185647202 \h  27  

  HYPERLINK \l "_Toc185647203"  10.0	Data Needs and Label
Recommendations	  PAGEREF _Toc185647203 \h  27  

  HYPERLINK \l "_Toc185647204"  10.1	Toxicology	  PAGEREF _Toc185647204
\h  27  

  HYPERLINK \l "_Toc185647205"  10.2	Residue Chemistry	  PAGEREF
_Toc185647205 \h  28  

  HYPERLINK \l "_Toc185647206"  10.3	Occupational and Residential
Exposure	  PAGEREF _Toc185647206 \h  28  

  HYPERLINK \l "_Toc185647207"  11.0 	Environmental Justice	  PAGEREF
_Toc185647207 \h  28  

  HYPERLINK \l "_Toc185647208"  12.0	Review of Human Research	  PAGEREF
_Toc185647208 \h  29  

  HYPERLINK \l "_Toc185647209"  References	  PAGEREF _Toc185647209 \h 
29  

 

1.0	Executive Summary

The Interregional Research Project No. 4 (IR-4) has requested the
establishment of tolerances for residues of the fungicide, boscalid
in/on the herb subgroup 19A, and various tropical fruits to support
foliar application to those crops in-field.  Concurrently, IR-4 proposes
to amend the product label for Pristine® Fungicide (EPA Reg. No.
7969-199) to add the new uses.  BASF has requested the establishment of
boscalid tolerances in/on cotton resulting from foliar and seed
treatment uses.  Concurrently, BASF wishes to amend the product label
for Pristine® Fungicide to add a foliar use on cotton.  In addition the
registrant wishes to register BAS 516 ST Seed Treatment Fungicide (EPA
File Symbol 7969-EUI) to add a seed treatment use on cotton.

HED notes that, in addition to boscalid, Pristine® Fungicide also
contains the active ingredient, pyraclostrobin.  This risk assessment
addresses only hazards, exposures and risks from the active ingredient,
boscalid.

Boscalid is a carboxamide (anilide) fungicide that inhibits
mitochondrial respiration, thereby inhibiting spore germination, germ
tube elongation, mycelial growth, and sporulation of pathogenic fungi on
the leaf surface.  Tolerances for residues of boscalid are established
under 40CFR §180.589.  

Hazard Characterization/Endpoint Selection

The toxicity database for boscalid is complete.  Boscalid has a low
acute toxicity and is not an eye or skin irritant.  The target organs
for boscalid are the thyroid and liver.

An acute endpoint was not selected since there were no adverse effects
seen in the database, including the developmental toxicity studies,
attributable to a single exposure of boscalid.  The chronic dietary
endpoint, incidental oral endpoint, dermal, and inhalation endpoints
were all selected from three co-critical studies, the chronic rat study,
the rat carcinogenicity study and a one-year feeding study in dogs.  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 uncertainty factor of 100 to account for inter- and
intra-species variability was applied to all risk assessments.  The FQPA
safety factor for boscalid was reduced to 1.  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 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 safety factor to protect infants and children is not
required.  

Boscalid is classified as "suggestive evidence of carcinogenicity". 
Quantification of human cancer risk is not required.

Residue Chemistry Considerations

The nature of the residue in plants, animals and rotational crops is
adequately understood for the purposes of this action.  Submitted field
trial and processing data are adequately supported by storage stability
data and were generated using appropriately validated analytical
methodology.  With the exception of the need for confirmatory data on
avocado residues at a 1X rate, adequate field trial and processing
studies have been submitted to support the requested uses.  An adequate
GC/MS method is available to enforce the proposed tolerances.

There are no Codex maximum residue limits (MRLs) established for
boscalid.  Canada has established MRLs for boscalid, but not for the
crops which are the subject of this risk assessment.  Therefore there
are no issues of international harmonization raised by this action.

Drinking Water Consideration

The proposed new uses have lower total maximum rates than the currently
registered turf use.  Estimated surface and ground drinking water
concentrations (EDWCs) were modeled based on the turf scenario using the
screening model FIRST (FQPA Index Reservoir Screening Tool; v.1.10;
dated 12/12/2005) and the regression model SCI-GROW (Screening
Concentration in Ground Water, v.2.3; dated 7/29/2003), respectively. 
The chronic, maximum Tier 1 estimated EDWC from surface water was used
in the dietary and aggregate risk assessments. 

Dietary Exposure and Risk Assessment

A Tier 1 chronic dietary (food and water) risk assessment was conducted
which incorporated tolerance level residues, the assumption that all
crops were treated, and either data-based or DEEM default processing
factors.  Boscalid exposure from the existing and newly proposed uses
resulted in an estimated risk equivalent to 9.9% of the chronic
population adjusted dose (cPAD) for the U.S. population.  The most
highly exposed subgroup was children 1 – 2 years of age with an
exposure which results in an estimated risk equivalent to 33% of the
cPAD.  Since HED has no concern for risks below 100% of the PAD, there
are no chronic dietary concerns based on exposure to the existing and
newly proposed uses of boscalid.

Non-Occupational (Residential) Exposure and Risk Assessments

There are no new residential uses associated with this action.  Existing
residential uses were previously assessed.  Application of boscalid by
homeowners is not anticipated, so a residential handler assessment was
not required.  “U-pick” operations and golfing were the two
post-application scenarios identified for boscalid.  Given the 1-day
duration for “U-pick activities, a risk assessment was not required
since there are no toxic effects anticipated from a single exposure to
boscalid.  There are no risks of concern from residential
post-application exposure during golfing.

Aggregate Risk Assessments

Short- and Intermediate-Term aggregate risk assessments were conducted
for boscalid.  The assessments combined average food and water residues
with residential exposures.  MOEs ranged from 1000 to 1400.  The level
of concern (LOC) for this assessment is for MOEs that are below 100;
therefore, there are no short- and intermediate-term aggregate risks of
concern raised by this action.  

Since there are no long-term residential exposures for boscalid, the
long-term (chronic) aggregate risk assessment includes only average food
and water residues and is identical to the chronic dietary risk
assessment.  There are no long-term aggregate risks of concern for the
existing and newly proposed uses of boscalid.

Occupational Exposure and Risk Assessments

Handler and postapplication occupational exposure and risk assessments
were conducted for the in-field and seed treatment uses that are the
subject of this petition.  All occupational handler and post-application
MOEs were significantly above the LOC of 100 for these assessments.  

The 12-hour REI (reentry interval) appearing on the label is in
compliance with the Worker Protection Standard.

Environmental Justice

Potential areas of environmental justice concerns, to the extent
possible, were considered in this human health risk assessment, in
accordance with U.S. Executive Order 12898, "Federal Actions to Address
Environmental Justice in Minority Populations and Low-Income
Populations,"   HYPERLINK
"http://www.eh.doe.gov/oepa/guidance/justice/eo12898.pdf" 
http://www.eh.doe.gov/oepa/guidance/justice/eo12898.pdf 

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. 

Regulatory Recommendation

Provided that the confirmatory data on the magnitude of the residue in
avocado are required as a condition of registration, and further
provided the petitioner submits a revised Section F as specified in the
Residue Chemistry Summary Document cited in this memorandum, this Human
Health Risk Assessment supports the registration of the requested new
uses and establishment of the following tolerances:

Herbs subgroup 19A, fresh leaves	40 ppm

Herbs subgroup 19 A, dried…………………..	……190 ppm

Dill seed	140 ppm

Avocado	1.5 ppm

Sapote, black	1.5 ppm

Canistel	1.5 ppm

Sapote, mamey	1.5 ppm

Mango	1.5 ppm

Papaya	1.5 ppm

Sapodilla	1.5 ppm

Star Apple	1.5 ppm

Cotton, undelinted seed	1.0 ppm

Cotton, gin byproducts	55 ppm

2.0	Ingredient Profile

Residue Chemistry Summary Chapter, DP 336632, C. Olinger, 11/27/2007

	

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 Corporation
as water dispersible granule (WDG) formulations for use on a wide
variety of food/feed crops.  

2.1	Summary of Proposed New Uses

Table 2.1.   Summary of Directions for Use of Boscalid.

Applic. Timing, Type, and Equip. 	Formulation

[EPA Reg. No.]	Max. Single Applic. Rate 

(lb ai/A) 1	Max. No. Applic. per Season	Max. Seasonal Applic. Rate

(lb ai/A)	PHI

(days)	Use Directions and Limitations

Fresh Herbs (including Angelica, Balm, Basil, Borage, Burnet, Chamomile,
Catnip, Chervil, Chive, Chinese Chive, Clary, Coriander (leaf),
Costmary, Cilantro (leaf), Curry (leaf), Dillweed (fresh and for
processing into oil), Horehound, Hyssop, Lavender, Lemongrass, Lovage
(leaf), Marigold, Marjoram (Origanum spp.), Nasturtium, Parsley,
Pennyroyal, Rosemary, Rue, Sage, Summer Savory, Winter Savory, Sweet
Bay, Tansy, Tarragon, Thyme, Wintergreen, Woodruff, and Wormwood)

Foliar

Ground, aerial or through sprinkler irrigation	25.2% WDG

[7969-199]	0.29	2	0.58	0	Begin applications prior to the onset of
disease development and repeat applications 7 days later as needed, or
alternate with another registered fungicide having a different mode of
action.

Avocado, Black Sapote, Canistel, Mamey Sapote, Mango, Papaya, Sapodilla,
and Star Apple

Foliar

Ground, aerial or through sprinkler irrigation	25.2% WDG

[7969-199]	0.29	2	0.58	0	Begin application prior to the onset of disease
development and repeat applications 7 days later as needed, or alternate
with another registered fungicide having a different mode of action.

Cotton

Foliar

Ground/aerial	25.2% WDG

[7969-199]	0.39	2	0.79	30	Begin applications prior to the onset of
disease development and continue on a 7-14 day interval.

Seed treatment

Slurry or mist type seed treatment equipment	70% WDG

[7969-EUI]	0.12 lb ai/

100 lb seed	1	0.12 lb ai/

100 lb seed	NA	Apply only in conjunction with labeled rates of
mefenoxam-or metalaxyl-containing seed treatment products.

2.2	Structure and Nomenclature  TC \l2 "2.2	Structure and Nomenclature 

2.3	Physical and Chemical Properties  TC \l2 "2.3	Physical and Chemical
Properties 

Table 2.2.  Test Compound Nomenclature

Compound	

Common name	Boscalid

Company experimental name	BAS 510 F

IUPAC name	2-chloro-N-(4'-chlorobiphenyl-2-yl)-nicotinamide

CAS name	3-pyridinecarboxamide,2-chloro-N-(4'-chloro[1,1'-biphenyl]-2-yl

CAS registry number	188425-85-6

End-use product (EPs) requested for registration	Pristine® Fungicide
(EPA Reg. No. 7969-199, a WDG formulation containing 12.8%
pyraclostrobin + 25.2% boscalid)

BAS 516 ST Seed Treatment Fungicide (EPA File Symbol 7969-EUI), a 70%
WDG formulation

TABLE 2.3	Physicochemical Properties of Boscalid.

Parameter	Value	References

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

pH	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

N,N-DMF >25

	Vapor pressure	7 x 10-9 hPa 

	Dissociation constant, pKa	None

	Octanol/water partition coefficient, Log(KOW)	2.96 

	UV/visible absorption spectrum	UV molecular extinction (e[lmol-1cm-1]):
 3.15 x104 at 228 nm; 1.53 x103 at 290 nm

	

3.0	Hazard Characterization

Boscalid HED HIARC Report, TXR No. 0051613, A. Levy, 3/7/2003

Boscalid Report of the CARC, TXR No. 0051289, J. Kidwell, 11/14/2002

Boscalid Human Health Risk Assessment, DP 290022, Y. Donovan, 9/8/2003

Boscalid Human Health Risk Assessment, DP 327906, L. Hanson, 7/10/2007 
TC \l1 "3.0  HAZARD CHARACTERIZATION 

The hazard characterization, dose-response and regulatory endpoint
selection for boscalid has been discussed in detail in the documents
cited above and remain unchanged for this assessment with the exception
of the discussion of the FQPA safety factor.  Toxicity endpoints are
briefly summarized here.  Further details on endpoint selection can be
found in the documents referenced above.  A complete discussion of the
FQPA safety factor is contained in Section 3.2 below.  This discussion
supersedes previous discussion of the FQPA safety factor for boscalid.

3.1	Hazard Characterization/ Endpoint Selection

The toxicity database for boscalid is complete for the purpose of
endpoint selection.  Boscalid has a low acute toxicity and is not an eye
or skin irritant.  The target organs for boscalid are the thyroid and
liver.

An acute endpoint was not selected for all populations since there were
no adverse effects seen in the database, including the developmental
toxicity studies, attributable to a single exposure of boscalid.

The chronic dietary endpoint, incidental oral endpoint, dermal, and
inhalation endpoints were selected from three co-critical studies, the
chronic rat study, the carcinogenicity in rats study and a one-year
feeding study in dogs.  The dose selected for regulation 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.  100% inhalation absorption is assumed for
risk assessment purposes. 

Boscalid is classified as "suggestive evidence of carcinogenicity". 
Evidence of carcinogenicity was seen in males (significant trend and
pair-wise at the high dose) and in females (trend only), however in both
sexes no malignancies were seen.  Only benign tumors were observed and
these occurred at dose levels above the dose level used to establish the
chronic PAD.  Additionally, there is no concern for mutagencity. 
Quantification of human cancer risk is not required.

The endpoints and doses selected for risk assessment purposes are
summarized below.  

Table 3.1.  Summary of Toxicological Doses and Endpoints for Boscalid 

Exposure/

Scenario	Point of Departure	Uncertainty/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/acute PAD was 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	Chronic rat, carcinogenicity rat and
1-year dog studies

LOAEL = ~58 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 = 100	Chronic rat, carcinogenicity rat and 1-year dog
studies

LOAEL =  ~58 mg/kg/day based on liver and thyroid effects

Dermal

(All Durations)	Oral study NOAEL = 21.8 mg/kg/day

DA = 15%	UFA = 10X

UFH = 10X

FQPA SF = 1X

	Residential LOC = 100

Occupational LOC = 100	Chronic rat, carcinogenicity rat and 1-year dog
studies

LOAEL =  ~58 mg/kg/day based on liver and thyroid effects

Inhalation

(All Durations)	Oral study NOAEL = 21.8 mg/kg/day

IA = 100%	UFA = 10X

UFH = 10X

FQPA SF = 1X

	Residential LOC = 100

Occupational LOC = 100	Chronic rat, carcinogenicity rat and 1-year dog
studies

LOAEL =  ~58 mg/kg/day based on liver and thyroid effects

Cancer

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

Point of Departure (POD) = A data point or an estimated point that is
derived from observed dose-response data and  used to mark the beginning
of extrapolation to determine risk associated with lower environmentally
relevant human exposures.  NOAEL = no observed adverse effect level. 
LOAEL = lowest observed adverse effect level.  UF = uncertainty factor. 
UFA = extrapolation from animal to human (intraspecies).  UFH =
potential variation in sensitivity among members of the human population
(interspecies).  FQPA SF = FQPA Safety Factor.  PAD = population
adjusted dose.  RfD = reference dose.  LOC = Level of Concern.  DA =
dermal absorption.  IA = inhalation absorption

3.2	FQPA Uncertainty Factors

The FQPA safety factor has been reduced to 1X for this assessment for
the following reasons:

EPA has a complete toxicity database for boscalid. 

The toxicity studies for boscalid show it generally to have low
mammalian toxicity and the database reveals no reproductive,
developmental concerns, 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 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. 

EPA concludes that there are no residual uncertainties for pre and/or
post-natal toxicity.  The NOAEL used for various risk assessments would
address the body weight effects seen at higher doses in the
developmental and reproductive studies.

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.

Based on consideration of all of these data, EPA has concluded that is
has reliable data showing that infants and children would be safe
without application of an additional 10X safety factor.

3.3	Endocrine Disruption

EPA is required under the Federal Food Drug and Cosmetic Act (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 the
recommendations of its Endocrine Disruptor Screening and Testing
Advisory Committee (EDSTAC), EPA determined that there was 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 has 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 the appropriate screening and/or testing protocols being considered
under the Agency’s EDSP have been developed, boscalid may be subjected
to additional screening and/or testing to better characterize effects
related to endocrine disruption.

4.0	Public Health and Pesticide Epidemiology Data

No public health/epidemiology data were used in developing this risk
assessment.

5.0	Dietary Exposure/Risk Characterization

5.1	Pesticide Metabolism and Environmental Degradation  TC \l2 "5.1 
Pesticide Metabolism and Environmental Degradation 

5.1.1	Metabolism in Primary Crops

Boscalid Residue Chemistry Summary Chapter, DP 336632, C. Olinger,
11/27/2007

Residue Chemistry Memo DP# 278385, 8/15/03, M. Nelson, (PP# 1F06313)

HED MARC Decision Memo DP# 286786, 1/9/03

  SEQ CHAPTER \h \r 1 The nature of boscalid residues in target
(primary) crops is adequately understood, based upon acceptable 14C
metabolism studies conducted on grapes, lettuce, and beans.  No
significant metabolism of boscalid occurred in grapes or lettuce;
unchanged parent was the only component identified, accounting for
92-98% and 99% TRR (total radioactive residues), respectively.  In bean
plants, boscalid metabolized slowly; unchanged parent was the major
component identified, accounting for up to 72% TRR in/on bean dry seeds
and 99% TRR in/on bean plants; cleavage products
1-(chlorophenyl)-2-aminobenzene and 2-chloronicotinic acid were present
in small amounts, accounting for <1% and <10% TRR, respectively.  

The HED MARC has concluded that parent boscalid is the sole residue of
concern for risk assessment and the tolerance expression for primary
(target) crops; the cleavage products were not included based on the
limited cleavage which occurred and the low levels of their ingestion
expected from dietary and environmental sources.

5.1.2	Metabolism in Rotational Crops  TC \l3 "5.1.2	Metabolism in
Rotational Crops 

Boscalid Residue Chemistry Summary Chapter, DP 336632, C. Olinger,
11/27/2007

Residue Chemistry Memo DP# 278385, 8/15/03, M. Nelson, (PP# 1F06313)

HED MARC Decision Memo DP# 286786, 1/9/03

  SEQ CHAPTER \h \r 1 The nature of boscalid residues in rotational
crops is adequately understood, based upon a 14C confined rotational
crop study conducted with three representative crops (radish, head
lettuce, and wheat).  In lettuce, radish (roots, tops), and wheat
(forage,), parent boscalid was the major residue identified (50-96%
TRR), with the glucoside metabolite, M510F61, accounting for 1-21% TRR;
only parent was identified in wheat grain.  

The HED MARC concluded that parent boscalid is the sole residue of
concern for risk assessment and the tolerance expression for rotational
(inadvertent or indirect residue) crops; M510F61 was not included based
on its being found mainly in feed items and at a relatively low
percentage compared to the parent.

5.1.3	Metabolism in Livestock

Boscalid Residue Chemistry Summary Chapter, DP 336632, C. Olinger,
11/27/2007

Residue Chemistry Memo DP# 278385, 8/15/03, M. Nelson, (PP# 1F06313)

HED MARC Decision Memo DP# 286786, 1/9/03

  SEQ CHAPTER \h \r 1 The nature of boscalid residues in livestock is
adequately understood based upon acceptable 14C metabolism studies
conducted on lactating goat and laying hens.  In both the goat and the
hen, parent boscalid, M510F 01 (hydroxy metabolite), and M510F 02
(M510F01 glucuronide) were identified as the major residues, with
radioactivities >10% TRR; no amide bridge cleavage products were
identified.  

Based on the structural similarity of boscalid and M510F 01, and the
fact that the enzymatic hydrolysis step in the proposed enforcement
method will release M510F 02 back to free M510F 01, the MARC concluded
that the combined residues of parent BAS 510 F, M510F 01, and M510F02
are the residues of concern for risk assessment and the tolerance
expression in livestock matrices.

5.1.4	Analytical Methodology

Boscalid Residue Chemistry Summary Chapter, DP 336632, C. Olinger,
11/27/2007

An adequate GC/MS   SEQ CHAPTER \h \r 1 method (Method D0008) is
available for enforcing existing and new tolerances in plant
commodities, and an adequate GC/ECD method (Method DFG S19) is available
for enforcing existing tolerances in animal commodities.  

Residues in/on plant commodities from the field and processing studies
associated with these petitions were determined using an LC/MS/MS data
collection method (BASF Method D9908).  This method was adequately
validated in conjunction with the field trial analyses, and the
validated limit of quantitation (LOQ) was 0.05 ppm for boscalid in all
commodities tested.

The requirements for multiresidue methods (MRM) testing data are
fulfilled.  Residues of boscalid and its hydroxy metabolite were not
adequately recovered using the MRMs.

5.1.5	Environmental Degradation

EFED Drinking Water Assessment, DP 336183, 341459, C. Sutton, 8/8/2007

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 

5.1.6	Comparative Metabolic Profile

Boscalid Residue Chemistry Summary Chapter, DP 336632, C. Olinger,
11/27/2007

Boscalid HED HIARC Report, TXR No. 0051613, A. Levy, 3/7/2003

In the rat metabolism study, boscalid was readily absorbed orally and
was primarily excreted in the feces, with most of the dose being
excreted within 24 hours for low doses and 48 hrs for higher doses. 
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.

Metabolism of boscalid in other animals (poultry and ruminant) appears
to be similar to its metabolism in rats.  In both the goat and the hen,
parent boscalid, the hydroxy metabolite and the glucuronide were
identified as the major residues. 

The major residues found in plants were unchanged parent.  Cleavage
products 1-(chlorophenyl)-2-aminobenzene and 2-chloronicotinic acid were
present in small amounts.  In rotational corps, the major residue was
parent, boscalid with a minor amount of the glucoside metabolite found. 

The HED MARC has concluded that parent boscalid is the sole residue of
concern for risk assessment and the tolerance expression for primary
(target) crops; the cleavage products were not included based on the
limited cleavage which occurred and the low levels of their ingestion
expected from dietary and environmental sources.

5.1.7	Pesticide Metabolites and Degradates of Concern TC \l3 "5.1.8
Pesticide Metabolites and Degradates of Concern 

Boscalid Residue Chemistry Summary Chapter, DP 336632, C. Olinger,
11/27/2007

The residues of concern to be included in the tolerance expression and
for risk assessment purposes are summarized in the table, below.

Table 5.1.7  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

5.1.8	Drinking Water Residue Profile

EFED Drinking Water Assessment, DP 336183, 341459, C. Sutton, 8/8/2007

The estimated drinking water concentrations (EDWC) for boscalid in
surface water and groundwater were calculated using the screening model
FIRST (FQPA Index Reservoir Screening Tool; v.1.10; dated 12/12/2005)
and the regression model SCI-GROW (Screening Concentration in Ground
Water, v.2.3; dated 7/29/2003), respectively.  

The proposed new uses on tropical fruit and herbs have a lower total
maximum use rate than the use rate for the previously approved use on
turf.  Additionally, modeling conducted on cotton indicated that EDWCs
from cotton would be well below those determined for turf.  Therefore,
the EDWCs for turf represent the maximum exposures.  EFED has provided
updated numbers for turf incorporating a percentage crop area factor. 
The maximum Tier 1 estimated EDWCs are summarized in the table, below. 
The surface water value of 0.0296 ppm, which is the highest chronic
EDWC, was incorporated into the chronic dietary exposure and risk
assessment.  

Table 5.1.8	Summary of Estimated Surface Water and Groundwater
Concentrations for Boscalid

	Boscalid

	Surface Water Conc., ppb a	Groundwater Conc., ppb b

Acute	100.6	0.63

Chronic (non-cancer)	29.6	0.63

Chronic (cancer)	Not reported	0.63

a From the FIRST (FQPA Index Reservoir Screening Tool; v.1.10; dated
12/12/2005) Tier 1 model.  Input parameters are based on application to
turf.

b From the SCI-GROW (Screening Concentration in Ground Water, v.2.3;
dated 7/29/2003)model based on turf application.

5.1.9	Food Residue Profile

Boscalid Residue Chemistry Summary Chapter, DP 336632, C. Olinger,
11/27/2007

The field trial and processing data which serve as the basis for the
recommended tolerances and residue levels for the dietary risk
assessment are supported by adequate storage stability data and were
generated using appropriately validated data collection methods.  

The submitted field trial data for basil (fresh) and chives, the
representative commodities of Herbs subgroup 19A, along with the data
submitted for fresh dill are adequate to support a tolerance of 40 ppm
for the Herbs subgroup 19A, fresh leaves.  Data submitted for dill seed
are adequate to support the required dill seed tolerance of 140 ppm.

The submitted residue data for avocado are inadequate to fulfill data
requirements because the field trials were conducted at exaggerated
rates.  While the submitted data represent an overestimate of the
residues expected from the proposed use, the degree of exaggeration can
not be determined. Given that the proposed use is for late season foliar
application, and includes a 0-day preharvest interval, HED will use the
submitted data to support a tolerance for avocado at 1.5 ppm. The
avocado data may be translated to other tropical fruits for which uses
are proposed.  However, since HED believes that the tropical fruit
tolerances may need to be reduced since they will be based on
exaggerated rate data; and further, since the avocado data are being
translated to support a wide number of tropical/subtropical fruits, HED
requests that the petitioner provide additional bridging data.  HED
recommends the conduct of two or three avocado field trials at the label
rates as a condition of registration.

The submitted field trial data for cotton reflecting foliar treatments
are adequate and support a tolerance of 1.0 ppm on undelinted seed. 
However, the cotton field trial data reflecting seed treatment are
inadequate because the application rate used was ~0.2x the maximum
proposed seed treatment rate.  Although the seed treatment study was
conducted at <1x, no additional seed treatment data will be required
since the bulk of residues are expected to result from foliar uses.

Acceptable processing studies on basil and cotton were submitted.  The
processing of fresh basil to dried basil resulted in an increase of
boscalid residues with an observed average processing factor of 6.3x for
dried basil leaves.  Based on the highest average field trial value and
the average processing factor, the data support a tolerance for the
Herbs subgroup 19 A, dried leaves at 190 ppm.  The cotton processing
study indicates that residues did not concentrate in meal, hulls, crude
oil, and refined oil processed from cottonseed bearing detectable
residues.  The submitted data support a tolerance of 55 ppm in cotton
gin byproducts.

Animal tolerances were not reassessed as a result of the proposed new
uses as the only feedstuffs associated with proposed uses are undelinted
cottonseed, cotton gin byproducts, meal, and hulls.  Based on the number
of animal feedstuffs with higher tolerances and higher exposure rates,
boscalid residues in/on cotton commodities are not expected to
contribute substantially to the dietary exposure of livestock.  

Adequate confined and limited field rotational crops studies are
available, and tolerances for indirect or inadvertent residues have been
established based on extensive rotational crop field trials on legume
vegetables, cereal grains, grasses, alfalfa, clover, cotton, and root
crops.  The available data support the 14-day plant-back interval (PBI)
on the labels for rotated crops without primary uses of boscalid.  There
are currently no deficiencies pertaining to rotational crops.

5.1.10	International Residue Limits

There are no Codex maximum residue limits (MRLs) established for
boscalid.  Canada has established MRLs for boscalid, with identical
residue definition as the U.S., but not for the crop commodities
discussed in this action review.  Therefore, there are no issues of
international harmonization raised by these petitions.  

5.2	Dietary Exposure and Risk TC \l2 "5.2  Dietary Exposure and Risk 

5.2.1	Acute Dietary Exposure/Risk

Boscalid Chronic Aggregate Exposure and Risk Assessment, DP 336633, D.
Davis, 12/13/2007

No toxic effects attributable to a single (i.e., acute) exposure to
boscalid have been identified; therefore, an acute reference dose (RfD)
has not been established for boscalid and an acute dietary exposure
assessment has not been conducted.  

5.2.2	Chronic Dietary Exposure/Risk

Boscalid Chronic Aggregate Exposure and Risk Assessment, DP 336633, D.
Davis, 12/13/2007 

A Tier 1 chronic dietary exposure and risk assessment (food and drinking
water) was conducted for boscalid.  For food residues, the analysis
included tolerance level residues and assumed 100% crop treated.  Where
data were available, actual processing factors were used in the
assessment.  In the absence of processing data, DEEM (version 7.81)
default factors were used for processed commodities.  For drinking
water, the highest modeled chronic EDWC was input into the assessment.  

Boscalid exposure from the existing and newly proposed uses resulted in
an estimated risk equivalent to 9.9% of the chronic population adjusted
dose (cPAD) for the U.S. population.  The most highly exposed subgroup
was children 1 – 2 years of age with an exposure which results in an
estimated risk equivalent to 33% of the cPAD.  Since HED has no concern
for risks below 100% of the PAD, there are no chronic dietary risks of
concern as a result of exposure to the established and new uses of
boscalid.   The results of the chronic dietary risk assessment for all
populations are summarized in the table below.



Table 5.2.2  Summary of Dietary (Food and Drinking Water) Exposure and
Risk for Boscalid

Population Subgroup	Chronic Dietary

	Dietary Exposure

(mg/kg/day)	% cPAD*

U. S. Population	0.021623	9.9

All Infants (< 1 year old)	0.049087	22

Children 1-2 years old	0.071939	33

Children 3-5 years old	0.050548	23

Children 6-12 years old	0.026387	12

Youth 13-19 years old	0.015048	6.9

Adults 20-49 years old	0.016462	7.6

Adults 50+ years old	0.018228	8.4

Females 13-49 years old	0.016662	7.6

5.2.3	Cancer Dietary Risk

Boscalid Chronic Aggregate Exposure and Risk Assessment, DP 336633, D.
Davis, 12/13/2007

Boscalid has been classified as “suggestive evidence of
carcinogenicity” by the Cancer Assessment Review Committee (CARC) and
the CARC has noted that quantification of human cancer risk is not
recommended; therefore, a dietary cancer assessment is not required.

				

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

6.1	Residential Handler Exposure

Boscalid Occupational/Residential Exposure Memorandum, D290072, S. Wang,
6/23/03

Occupational and Residential Exposure/Risk Assessment for Boscalid,
D336634, S. Wang, 11/2/07

There are no new residential (non-occupational) uses proposed for
boscalid as a result of the two petitions that are the subject of this
risk assessment.  The current label specifies 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 not packaged or marketed
for home orchard use.  Since the product is not intended for homeowner
use, a residential handler exposure and risk assessment is not required.

6.2.	Residential Postapplication Exposure

Boscalid Occupational/Residential Exposure Memorandum, D290072, S. Wang,
6/23/03

Occupational and Residential Exposure/Risk Assessment for Boscalid,
D336634, S. Wang, 11/2/07

There are no new residential post application exposure scenarios
resulting from the uses proposed in these petitions.  Potential
non-occupational post application exposure scenarios identified for
boscalid based on the established uses include post-application exposure
to golfers and persons harvesting fruit at "U-pick" (pick your own)
farms and orchards.  Exposure can occur during contact with treated golf
course turf or while picking strawberries, caneberries, and tree fruit
at a “U-pick” facility. 

Based on the low vapor pressure of boscalid, the outdoor nature of the
uses and the weight of evidence from available residue studies, HED does
not anticipate post-application inhalation exposures from the currently
approved uses of boscalid.  

“U-pick” activities are considered to be “one-time” (<1 day)
event.  Since no adverse effects were seen in the boscalid toxicity
database resulting from a single exposure to the chemical, a
post-application exposure and risk assessment is not required for this
scenario.  

HED conducted a post-application exposure and risk assessment for
golfers exposed to treated turf.  Duration of exposure is anticipated to
be short-term.  While BASF did submit a TTR study, due to the
methodology used in the study, HED considered it more appropriate to use
the standard transfer coefficient of 500 cm2/hr for golfers. 
Additionally, the assessment assumed that boscalid would be present on
all of the turf through out the course and that the duration of exposure
was estimated to be 4 hours.   Details of the assessment can be found in
the ORE memorandum cited above. 

The postapplication dermal MOE for golfers exposed to boscalid is
100,000, which greatly exceeds the level of concern of 100 for this risk
assessment.   Table 6.2, below summarizes the inputs into the assessment
and the exposure and risk to golfers. 

	Table 6.2  Dermal  Post-application Exposure and Risk for Adults and
Youth Golfers

Scenario & Product	

TTR 1 (ug/cm2)	

CF1 (mg/ug)	

Tc1

(cm2/hr)	

ET (hr/day)	

% DA	

BW (kg)	

Daily Dose 2

(mg/kg/day)	

Dermal MOE 3

Golfing

BAS 510 02F Turf Fungicide	

0.05	

0.001	

500	

4	

15	

70	

0.000214	

100,000

TTR is turf transferable residue on day 0 (mg/day).  CF1 is unit
conversion factor to convert ug units in the TTR to mg for daily
exposure (0.001 mg/ug).  ET is the exposure time.  DA is dermal
absorption.  BW is body weight.  MOE is margin of exposure

1     Based on HED SOP 3.1     

2.    DD (mg/kg/day)  = DFR x CF1 x Tc x ET x %DA/BW

3.    Dermal MOE = NOAEL (21.8 mg/kg/day)/ Daily Dose (mg/kg/day)

Golfing is considered a lifetime sport, so individuals of all ages,
excluding very small children, routinely play.  Children who are 12
years of age or older are likely to represent the vast majority of the
youth that play golf on a routine basis.  However, the popularity of
golf as a recreational pastime has increased steadily over the last few
years which has resulted in more young children (i.e., 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 percent 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)]. 	

6.3	Other (Spray Drift, etc.) TC \l2 "6.3	Other (Spray Drift, etc.) 

Spray drift is always a potential source of exposure to residents nearby
to spraying operations.  This is particularly the case with aerial
application, but, to a lesser extent, could also be a potential source
of exposure from the ground application method employed for boscalid. 
The Agency has been working with the Spray Drift Task Force, EPA
Regional Offices and State Lead Agencies for pesticide regulation and
other parties to develop the best spray drift management practices.  The
Agency is now requiring interim mitigation measures for aerial
applications that must be placed on product labels/labeling.  The Agency
has completed its evaluation of the new data base submitted by the Spray
Drift Task Force, a membership of U.S. pesticide registrants, and is
developing a policy on how to appropriately apply the data and the
AgDRIFT computer model to its risk assessments for pesticides applied by
air, orchard airblast and ground hydraulic methods.  After the policy is
in place, the Agency may impose further refinements in spray drift
management practices to reduce off-target drift and risks associated
with aerial as well as other application types where appropriate.  

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

7.1	Acute Aggregate Risk

 TC \l2 "7.1	Acute Aggregate Risk 

No toxic effects attributable to a single (i.e., acute) exposure to
boscalid have been identified; therefore, an acute reference dose (RfD)
has not been established for boscalid and an acute aggregate risk
assessment is not required.   

7.2	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 to adult and youth golfers.  MOEs ranged from
1000 to 1400.   The level of concern (LOC) for this assessment is for
MOEs that are below 100; therefore, there are no short- and
intermediate-term aggregate risks of concern.   Short-term aggregate
risks are summarized in Table 7.2, below.

 TC \l2 "7.2	Short-Term Aggregate Risk 

Table 7.2  Short-Term Aggregate Risk Calculations for Boscalid

Population	Short-Term Scenario

	NOAEL

mg/kg/day	LOC1	Max Allowable

Exposure2

mg/kg/day	Average

Food & Water

Exposure

mg/kg/day	Residential Exposure3

mg/kg/day	Aggregate MOE

(food and

residential)4

U.S. Population	21.8	100	0.218	0.021622	0.000214	1000

Females

(13 – 49 yrs)	21.8	100	0.218	0.016661	0.000214	1300

Adults

 (50+ yrs)	21.8	100	0.218	0.018227	0.000214	1200

Youth

 (13 – 19yrs)	21.8	100	0.218	0.01504	0.000214	1400

1 The LOC includes the standard inter- and intra- species uncertainty
factors totaling 100. 

2 Maximum Allowable Exposure (mg/kg/day) = NOAEL/LOC

3 Residential Exposure = Dermal exposure.  Residential exposure value
taken from Table 6.2.

4 Aggregate MOE = [NOAEL/ (avg Food & Water Exposure + residential
Exposure)]

7.3	Intermediate-Term Aggregate Risk

There are no intermediate-term residential scenarios; therefore, an
intermediate-term aggregate exposure and risk assessment is not
required.   TC \l2 "7.3	Intermediate-Term Aggregate Risk 

7.4	Long-Term Aggregate Risk

There are no long-term residential scenarios for boscalid; therefore the
long-term aggregate risk assessment would incorporate only 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 5.2.2 of this memorandum. TC \l2 "7.4
Long-Term Aggregate Risk 

7.5	Cancer Aggregate Risk TC \l2 "7.5	Cancer Risk 

Boscalid has been classified as “suggestive evidence of
carcinogenicity” by the Cancer Assessment Review Committee (CARC) and
the CARC has noted that quantification of human cancer risk is not
recommended; therefore, an aggregate cancer exposure and risk assessment
is not required.

8.0	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   HYPERLINK
http://www.epa.gov/pesticides/cumulative/.
http://www.epa.gov/pesticides/cumulative/. 

9.0	Occupational Exposure/Risk Pathway

The occupational handler exposure and risk assessment is limited to the
new uses on herbs, tropical fruit and cotton (foliar and seed treatment)
that are the subject of this risk assessment.  

Based on the frequency/interval of applications on the agricultural
crops and the seasonal nature of seed treatment operation, HED has
assumed that handler exposures will be short- or intermediate-term in
duration.  Since exposure is not expected to be long-term in duration, a
long-term handler exposure and risk assessment is not required.

Boscalid has been classified as “suggestive evidence of
carcinogenicity” by the Cancer Assessment Review Committee (CARC) and
the CARC has noted that quantification of human cancer risk is not
recommended; therefore, an occupational handler cancer exposure and risk
assessment is not required.  

9.1	Short-/Intermediate-Term Handler Risk

Occupational and Residential Exposure/Risk Assessment for Boscalid,
D336634, S. Wang, 11/2/07

The maximum application rates listed on the proposed labels were used
for all handler assessments.  The average body weight for the general
population (70 kg) was used for all assessments.  

The handler exposure estimates are based on a central tendency estimate
of unit exposure and an upper-percentile assumption for the application
rate.  The uncertainties in the assessment stem from the use of
surrogate exposure data, and assumptions regarding that amount of
chemical handled.  The estimated exposures are not likely to
underestimate risk to occupational handlers.  

9.1.1	Handler Exposures and Risks for Crop In-Field Uses

Occupational and Residential Exposure/Risk Assessment for Boscalid,
D336634, S. Wang, 11/2/07

HED identified the seven occupational handler scenarios that would be
expected to yield the highest exposure based on the newly requested
in-field uses of boscalid.  The exposure scenarios assessed are
summarized in Table 9.1.1, below. 

 

In the absence of chemical-specific data on human exposure during
pesticide handling activities for boscalid, HED used surrogate data from
the PHED Version 1.1 to assess exposures.  Defaults established by the
HED Science Advisory Council for Exposure were used for acres treated
per day.  

Details of the occupational handler exposure and risk for in-field uses
are contained in the memorandum cited above.  Occupational handler risks
from in-field uses ranged from 300 to 23,000, which exceeds the level of
concern (LOC) of 100 for this assessment.  Exposures and risks for each
scenario are summarized in the table below.

 



Table 9.1.1  Short-/Intermediate-Term Occupational Exposure and Risk
Estimates for In-Field Uses of Boscalid.1  

Exposure Scenario	Crop	Daily

Dermal

Dose

( mg/kg/day)	Daily

Inhalation

Dose

(mg/kg/day)	Combined Daily Dose

(mg/kg/day)	Total MOE

Mixer/Loader

Dry Flowables for Ground Application	Tropical Fruit & Herbs	0.0033
0.00026	0.0036	6,100

	Cotton (Foliar)	0.0113	0.00088	0.0122	1800

Dry Flowables for 

Airblast application	Tropical Fruit & Herbs	0.0016	0.00013	0.0017	13,000

Dry Flowables for 

Aerial application	Tropical Fruit & Herbs	0.014	0.0011	0.015	1,500

	Cotton (Foliar)	0.0678	0.0053	0.073	300

Applicator

Sprays with Groundboom	Tropical Fruit & Herbs	0.00070	0.00025	0.00095
23,000

	Cotton (Foliar)	0.0024	0.00084	0.0032	6,800

Sprays with Airblast	Tropical Fruit & Herbs	0.0089	0.00075	0.0097	2,200

Sprays with Fix-Wing Aircraft	Tropical Fruit & Herbs	0.0011	0.000099
0.0012	18,000

	Cotton (Foliar)	0.0051	0.00046	0.0056	3,900

Flagger

Flagging during Aerial Application	Tropical Fruit & Herbs	0.0024	0.00051
0.0029	7,500

	Cotton (Foliar)	0.0033	0.0007	0.004	5,500

1All estimates assume no additional PPE beyond the baseline (long-sleeve
shirt, long pants, shoes and socks, no respirator) with the exception of
the application by fixed wing aircraft where a closed cockpit is
typically employed and reflected in the exposure estimate. The short-
and intermediate- dermal NOAEL is 21.8 mg/kg/day from an oral study with
15% dermal absorption.  The short- and intermediate- term inhalation
NOAEL is 21.8 mg/kg/day with 100% inhalation absorption.

It is understood that human flagging is an uncommon because Global
Positioning Satellite (GPS) technology is now predominantly used as
indicated by the 2003 National Agricultural Aviation Association (NAAA)
survey of their membership.  This survey did indicate, however, that
human flaggers are still used in approximately 4 percent of aerial
application operations.  The Agency will continue to evaluate risks for
human flaggers until the potential for exposure is eliminated.

9.1.2	Handler Exposures and Risks for Seed Treatment Use

Occupational and Residential Exposure/Risk Assessment for Boscalid,
D336634, S. Wang, 11/2/07

Four commercial seed treatment handler scenarios were identified that
were expected to result in the highest exposures for the proposed seed
treatment use on cotton.  A complete listing of the exposure scenarios
assessed is shown in Table 9.1.2, below.  

Handler assessments were based on the unit exposure data from the
Science Advisory Council for Exposure (Exposure SAC) Policy #14 (May 1,
2003) and based on the treating/planting data from the Exposure SAC
Policy #15 (March 2, 2004). 

Details of the occupational handler exposure and risk assessment for the
seed treatment use on cotton are contained in the memorandum cited
above.  Occupational handler risks from the seed treatment application
ranged from 1,000 to 6,800 and are above the level of concern of 100 for
this risk assessment.  Occupational handler exposures and risks for all
scenarios assessed for the seed treatment use are summarized in the
table below.

Table 9.1.2  Short-/Intermediate-Term Occupational Exposure and Risk
Estimates for Seed Treatment Uses of Boscalid.1  

Exposure Scenario	Crop	Daily

Dermal

Dose

( mg/kg/day)	Daily

Inhalation

Dose

(mg/kg/day)	Combined Daily Dose

(mg/kg/day)	Total MOE

Loader/Applicator

Loading/Applying

Liquids for 

Seed Treatment	Cotton	0.0095	0.00093	0.010	2,200

Sewer

Sewing Seeds after Seed Treatment	Cotton	0.0026	0.00063	0.0032	6,800

Bagger

Bagging Seeds after Seed Treatment 	Cotton	0.0037	0.00044	0.0041	5,300

Multiple Activities Worker

Multiple Activities for Seed Treatment	Cotton	0.017	0.0044	0.021	1,000

1Loader/Applicator and Multiple Activities Worker assessments assume
single layer of clothing and gloves. Sewer and Bagger assessments assume
single layer of clothing, no gloves.   The short- and intermediate-
dermal NOAEL is 21.8 mg/kg/day from an oral study with 15% dermal
absorption.  The short- and intermediate- term inhalation NOAEL is 21.8
mg/kg/day with 100% inhalation absorption.

9.1.3	Secondary Handler Risks from Seed Treatment Uses

Occupational and Residential Exposure/Risk Assessment for Boscalid,
D336634, S. Wang, 11/2/07

A “secondary handler” assessment was conducted for the seed
treatment use of boscalid.  The scenario consists of the farmer
purchasing bags of treated seed, placing the seed in the hopper, and
applying seed to fields.  Secondary handler’s exposure associated with
seed treatment was calculated using unit exposures given from the
Science Advisory Council for Exposure Policy #14 (May 1, 2003).  For
cotton, it was assumed that 3,600 lbs of seed per day could be planted. 
The details of the assessment are contained the memorandum cited above. 
The MOE for the scenario is 8,700 as shown in table 9.1.3 and is not of
concern.  

Table 9.1.3  Short-Term Occupational “Secondary Handler” Exposure
and Risk Estimates for Seed Treatment Uses of Boscalid.1  

Exposure Scenario	Crop	Daily

Dermal

Dose

( mg/kg/day)	Daily

Inhalation

Dose

(mg/kg/day)	Combined Daily Dose

(mg/kg/day)	Total MOE

Post-application:

planting seeds in the field	Cotton	0.0023	0.00021	0.0025	8,700

1All estimates assume single layer of clothing and gloves.  The short-
and intermediate- dermal NOAEL is 21.8 mg/kg/day from an oral study with
15% dermal absorption.  The short- and intermediate- term inhalation
NOAEL is 21.8 mg/kg/day with 100% inhalation absorption.

9.2	Short-Term Postapplication Risks

Occupational and Residential Exposure/Risk Assessment for Boscalid,
D336634, S. Wang, 11/2/07

Postapplication exposure and risk assessments used the maximum proposed
use rates.  Assessments assumed a body weight of 70 kg and that workers
could be exposed for 8 hrs a day.  For the postapplication risk
assessments, the duration of exposure was assumed to be less than 30
days per year (short-term).

9.2.1	Post Application Exposures and Risks from In-Field Uses

Occupational and Residential Exposure/Risk Assessment for Boscalid,
D336634, S. Wang, 11/2/07

Occupational postapplication exposure scenarios that were assessed for
the in-field uses of boscalid that are the subject of this action are
summarized in Table 9.2.1, below.  Transfer coefficients were taken from
the Science Advisory Council for Exposure Policy Number 3 and the
exposure and risk assessment were conducted for “0-day” exposures.
MOEs ranged from 650 to 20,000 and are not of concern since they exceed
the LOC of 100 for this assessment.  Post application exposures and
risks resulting from the in-field uses of boscalid are summarized in the
table below.



Table  9.2.1   Post-application Exposure and Risk for In-Field Uses

Crop	

Application Rate 

(lb ai/A)	

Work Activity	

Transfer Coefficientsa (cm2/hr)	

Post-application Dayb	

DFRc

(µg/cm2)	

Daily Dosed (mg/kg/day)	     

 MOE e 

Herbs	0.29	irrigation, scouting, thinning, weeding immature plants	500	0
0.651	0.0056	3,900

irrigation, and scouting mature plants	1500	0	0.651	0.0167	1,300

hand harvesting, pruning, thinning mature plants	2500	0	0.651	0.0279	780

Tropical        Fruits	     0.29	 propping	100	0	0.651	0.0011	20,000

irrigation, scouting, hand weeding	1000	0	0.651	0.011	2,000

harvesting	1500	0	0.651	0.017	1,300

thinning 	3000	0	0.651	0.033	650

Cotton	     0.4	

irrigation, scouting	

100	0	0.898	0.0015	14,000

irrigation, and scouting thinning, weeding immature/low plants	

1500	0	0.898	0.0231	940

a	Transfer coefficient from Science Advisory Council for Exposure:
Policy Memo #003 "Agricultural Transfer Coefficients," 05/07/98.

b	Day after treatment represents approximately 12 hours following
application  when sprays have dried.

c	DFR = Application Rate (lb ai/acre) x Fraction of active ingredient
that remains on the foliage when sprays have dried  x 4.54E8 µg/lb x
24.7E-9 acre/cm2.

d	Daily dose = DFR (µg/cm2) x TC (cm2/hr) x conversion factor (1
mg/1,000 µg) x exposure time (8 hrs/day) x dermal absorption (0.15) /
body weight (70 kg).

e	MOE = NOAEL (21.8 mg/kg/day) / daily dose (mg/kg/day).

9.3	Worker Protection Standard

The technical material has a Toxicity Category IV for eye
irritation/skin irritation, and a Category III for acute dermal
Toxicity.  Per the Worker Protection Standard (WPS), a 12-hr restricted
entry interval (REI) is required.  The 12 hour REI appearing on the
labels is appropriate.

10.0	Data Needs and Label Recommendations  TC \l1 "10.0	Data Needs and
Label Recommendations 

10.1	Toxicology

The toxicology database for boscalid is complete.  No new data on the
toxicity of boscalid are required to support the requested new uses.

  TC \l2 "10.1	Toxicology 		

10.2	Residue Chemistry

Boscalid Residue Chemistry Summary Chapter, DP 336632, C. Olinger,
11/27/2007

The following residue chemistry data are required to support the
requested new uses:

Additional avocado field trial studies at the label maximum rate are
required to bridge the submitted exaggerated rate studies.  These data
are considered confirmatory and can be required as a condition of the
registration of boscalid on tropical fruits.

The petitioner should submit a revised Section F to incorporate the
recommended commodity definitions and tolerances specified in the
Residue Chemistry Summary Chapter cited above.  

10.3	Occupational and Residential Exposure

No new occupational or residential exposure information is required to
support the requested new uses.

  TC \l2 "10.3	Occupational and Residential Exposure 

11.0 	Environmental Justice

Potential areas of environmental justice concerns, to the extent
possible, were considered in this human health risk assessment, in
accordance with U.S. Executive Order 12898, "Federal Actions to Address
Environmental Justice in Minority Populations and Low-Income
Populations,"   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 Intakes 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
post-application are evaluated.  Further considerations are currently in
development as OPP has committed resources and expertise to the
development of specialized software and models that consider exposure to
bystanders and farm workers as well as lifestyle and traditional dietary
patterns among specific subgroups.

12.0	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. 

References

BAS 510 F: Report of the Cancer Assessment Review Committee, TXR No.
0051289, J. Kidwell, 11/14/2002.

BAS 510 F- Report of the Hazard Identification Assessment Review
Committee, A. Levy, TXR No. 0051613, 3/7/2003.

Boscalid.  Petitions for the Establishment of Permanent Tolerances on: 
(i) Fresh Herbs (Herbs Subgroup 19A), Avocado, Black Sapote, Canistel,
Mamey Sapote, Mango, Papaya, Sapodilla, and Star Apple - PP#6E7164; and
(ii) Cotton Commodities - PP#7F7169.  Summary of Analytical Chemistry
and Residue Data, DP 336632 and 338785, C. Olinger, 11/27/2007.

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, DP
336183 and 341459, C. Sutton, 8/8/2007.

Boscalid Chronic Aggregate Dietary (Food and Drinking Water) Exposure
and Risk Assessment for the Section 3 Registration Action to Add New
Uses on the Herb Crop Subgroup (19A), Various Tropical Fruits and
Cotton, DP 336633, D. Davis, 12/13/07.

Occupational and Residential Exposure/Risk Assessment of Boscalid for
Crop Protection Uses on Tropical Fruits, Herbs, & Cotton; and for Seed
Treatment Use on Cotton, DP 336634, S. Wang, 11/2/2007.

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, DP 327906, B. Hanson, 7/10/2007.

  TC \l1 "References: 

Boscalid	Human Health Risk Assessment	DP 336182

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