Document ID: EPA-HQ-OPP-2008-0624-0013
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2009-09-16T04:00Z

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C.  20460

OFFICE OF           

PREVENTION, PESTICIDES

AND TOXIC SUBSTANCES

MEMORANDUM  

Date:		November 2, 2007 

Subject:	Occupational and Residential Exposure/Risk Assessment of
Boscalid for Crop Protection Uses on Tropical Fruits, Herbs, & Cotton;
and for Seed Treatment Use on Cotton 

PC Code: 128008         	DP Barcode: D336634

    To:		Daniel Rosenblatt , RM 05

Registration Division/Fungicide Branch (7509P)

From:		Shih-Chi Wang, Biologist 

Health Effects Division/Registration Action Branch 2 (7509P)

Thru:		Richard Loranger, Branch Senior Scientist

Health Effects Division/Registration Action Branch 2 (7509P)

The enclosed document is an assessment of potential occupational and
residential exposures/risks to support the proposed Section 3
registration for new crop protection uses of boscalid on tropical
fruits, herbs, & cotton; and for new seed treatment use on cotton.  

	Table of Contents

 TOC \f 

1.0  Executive Summary	3

2.0  Hazard Information	4

3.0  Product Use information	5

4.0  Non-Occupational/Residential Exposure 	6

5.0  Occupational Exposure	8

            5.1  For Crop Protection Uses 	8

              5.1.1  Handlers 	8

              5.1.2  Post-application 	11

5.2  For Seed Treatment Uses 	15

              5.2.1  Handlers 	15

              5.2.2  Secondary Handler 	16

 	

1.0  Executive Summary

A Section 3 registration is being requested for the end-use products
containing boscalid as active ingredient.  The proposed uses include:
(1) Pristine( fungicide (boscalid 25.2%, water dispersable granule) on
tropical fruits/herbs (0.29 lb ai/A) and cotton (0.4 lb ai/A) by ground
or aerial equipment, and (2) BAS 510 ST( seed treatment fungicide
(boscalid 70.0%, water dispersable granule) on  cotton (0.12 lb ai/100
lb seed) .

An oral NOAEL (21.8 mg/kg/day, all durations) was used to assess dermal
and inhalation risks.  The NOAEL is based on the liver/thyroid effects
observed from the chronic toxicity rat, carcinogenicity rat and 1-year
dog studies.  The dermal and inhalation absorption rates used were 15
and 100%, respectively.  Daily dermal and inhalation doses were combined
and then compared to the NOAEL to determine the level of risks.  The
level of concern for the margin of exposure (MOE) is 100.  Boscalid is
classified as “suggestive evidence of carcinogenicity, but not
sufficient to assess human carcinogenic potential”, and, therefore,
the human cancer risk was not evaluated.  

The number of exposure days per year was not provided.  Based on the
frequency/interval of applications on the crops and the seasonal nature
of seed treatment operation, EPA assumes that all exposures would be
less than 6 months per year (short- and intermediate-term exposures).  

Since no chemical-specific data for assessing human exposures during 
pesticide handling activities were submitted to the Agency in support of
the registration of boscalid, HED used surrogate data from the PHED
Version 1.1 (PHED Surrogate Exposure Guide, 8/98) to assess exposures
for crop protection uses.  Defaults established by the HED Science
Advisory Council for Exposure were used for acres treated per day and
body weight.  For seed treatment uses, 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).
  

No MOEs for handlers performing crop protection uses exceed the level of
concern at the baseline or engineering control level (300 ~ 23,000).  No
MOEs for handlers performing seed treatment use exceed the level of
concern at the single layer level (1,000 ~ 6,800).  The HED level of
concern is an MOE of <100.  The MOE for secondary handler (seed planter)
is also greater than 100 (8,700) and does not exceed HED’s  level of
concern.  

All post-application MOEs for crop protection uses are greater than 100
on the day of application (650~20,000).  These MOEs do not exceed
HED’s level of concern (MOE<100).  

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.

The non-occupational/residential exposure/risk assessment is based on
the previous HED’s assessment for BAS 510F (D290072).  No MOEs exceed
HED’s level of concern (<100).

2.0  Hazard Information   

 

On September 5, 2002 and January 23, 2003, the Health Effects Division
(HED) Hazard Identification Assessment Review Committee (HIARC) selected
endpoints for chronic dietary exposure (all populations), incidental
oral short- and intermediate-term residential only, dermal (all
durations) and inhalation (all durations) exposures to boscalid (also
called as BAS 510F).  A dermal toxicity study was submitted and no
endpoint was selected at the limit dose (1000 mg/kg/day).  For all of
the endpoints selected, liver and thyroid effects were chosen from the
chronic toxicity study in rats, the carcinogenicity study in rats and
the 1-year study in dogs.  The NOAEL was 21.8 mg/kg/day.  For the dermal
route, the absorption rate was 15%.  For the inhalation route, the
absorption rate was assumed to be 100%.   

The potential for increased susceptibility of infants and children from
exposure to boscalid was also evaluated as required by the Food Quality
Protection Act (FQPA) of 1996.  The FQPA safety factor was reduced to 1X
because the existing data indicate that there are no/low concerns and no
residual uncertainties with regard to pre- and/or post-natal toxicity. 
The Cancer Assessment Review Committee (CARC) classified boscalid as,
“suggestive evidence of carcinogenicity, but not sufficient to assess
human carcinogenic potential”, and, therefore, the quantification of
human cancer risk is not recommended. 

 The acute toxicity categories for the technical material are summarized
in Table 1.  The HIARC’s conclusions, the doses and toxicological
endpoints for various exposure scenarios are summarized and presented in
Table 2 (from the HIARC document on BAS 510F 03/07/03). 

Table 1.  Acute Toxicity Profile - Boscalid Technical.

Test Material	

GDLN

	

Study Type	

MRID	

Results	

Tox

Category

Technical

	

870.1100	

Acute Oral - rat	

45404814

	

LD50 > 5000 mg/kg

	

IV

Technical	

870.1200	

Acute Dermal - rat	

45404815	

LD50 > 2000 mg/kg	

III

Technical	

870.1300	

Acute Inhalation	

45404816	

LC50 (M & F): > 6.7 mg/L	

IV

Technical	

870.2400	

Primary Eye Irritation	

45404817	

Not irritating to the eye	

IV

Technical

	

870.2500	

Primary Dermal Irritation	

45404818

	

Not irritating to the skin

	

IV

Technical

	

870.2600	

Dermal Sensitization	

45404819

	

Study unacceptable as challenge dose was inadequate

	

N/A



Table 2.  Summary of Toxicological Dose and Endpoints for Boscalid. 

Exposure

Scenario	

Dose Used in Risk Assessment, UF 	

 FQPA SF and Level of Concern for Risk Assessment	

Study and Toxicological Effects

Acute Dietary

	

No appropriate endpoint identified	

NA	

NA

Chronic Dietary

(All populations)	

 NOAEL= 21.8

UF = 100

Chronic RfD = 0.218 mg/kg/day	

FQPA SF = 1

cPAD = 

chronic RfD

 FQPA SF

= 0.218 mg/kg/day	

Chronic rat, carcinogenicity rat and 1-year dog studies

LOAEL = 57-58 mg/kg/day based on liver and thyroid effects

Incidental Oral (Short and intermediate term residential only)

	

NOAEL= 21.8  mg/kg/day	

Residential LOC for MOE = 100

Occupational LOC for MOE = 100	

Chronic rat, carcinogenicity rat and 1-year dog studies

LOAEL = 57-58 mg/kg/day based on liver and thyroid effects

Dermal (All Durations)	

Oral study NOAEL=21.8 mg/kg/day

(dermal absorption rate = 15%)	

Residential LOC for MOE = 100

Occupational LOC for MOE = 100 	

Chronic rat, carcinogenicity rat and 1-year dog studies

LOAEL = 57-58 mg/kg/day based on liver and thyroid effects

Inhalation (All Durations)

	

Oral study NOAEL= 21.8 mg/kg/day

(inhalation absorption rate = 100%)	

Residential LOC for MOE = 100 

Occupational LOC for MOE = 100	

Chronic rat, carcinogenicity rat and 1-year dog studies

LOAEL = 57-58 mg/kg/day based on liver and thyroid effects 

Cancer (oral, dermal, inhalation)	

Classification: “Suggestive evidence of carcinogenicity, but not
sufficient to assess human carcinogenic potential.”

UF = uncertainty factor, FQPA SF = FQPA safety factor, NOAEL = no
observed adverse effect level, LOAEL = lowest observed adverse effect
level, PAD = population adjusted dose (a = acute, c = chronic) RfD =
reference dose, MOE = margin of exposure, LOC = level of concern, NA =
Not Applicable

For the purpose of conducting risk assessments for occupational workers,
dermal and inhalation exposures may be combined because the same studies
(with the same endpoints) were used for each route of exposure for each
of the respective exposure scenarios.

3.0  Product Use information tc \l1 "3.0  Product Use information 

Proposed use patterns for boscalid are summarized in Table 3.

Table 3.  Proposed Use Patterns for Boscalid.

Crop 

 	

Product, Formulation	

Treatment Type	

Applications Per Season 1	

Maximum Application Rate2

(lb ai/acre) or (lb ai/100 lb seed)	

PHI3 

(days)

Per Application	

Per Season

	

Tropical 

Herbs 	

Pristine, 

water-dispersable granule	

Ground or Aerial

equipment	2	0.29	0.58	0

Tropical

Fruits	

Pristine, 

water-dispersable granule	

Ground or Aerial

equipment	2	0.29	0.58	0

       Cotton	Pristine, 

water-dispersable granule	Ground or Aerial

     equipment	            2	            0.4          	          0.8	   
     30

Cotton	

BAS 510 ST, water-dispersable granule	

Treating seeds with commercial equipment	                               
  NA                             	0.12	          NA

	         NA

1 Maximum number of applications allowed on label.

2 Rate = Maximum application rates specified on proposed labels.

3 PHI = Pre-harvest Interval

4 NA= Not Applicable

4.0  Non-Occupational/Residential Exposure

The non-occupational/residential exposure/risk assessment is based on
the previous HED’s assessment for BAS 510F (D290072, by S. Wang, M.
Collantes, G. Bangs 6/18/03; Boscalid is also called as BAS 510F).  

Potential non-occupational exposure scenarios were identified for
golfers and persons harvesting fruit at "U-pick" farms and orchards. 
Residues may be contacted from treated golf course turf or while picking
strawberries, caneberries, and tree fruit.  Based on low vapor pressure,
outdoor uses and the weight of evidence from many residue studies, no
post-application inhalation exposures are anticipated for boscalid. 
Because “U-pick” is a “one-time” event (duration<1-day) and the
HIARC found that the oral studies used to select endpoints were not
appropriate to quantitate acute risk,   “U-pick” exposure/risk was
not evaluated.  Only golfing scenario is evaluated in this assessment.

The Boscalid label specifies that this product is intended for golf
course use only, and not for use on residential turfgrass or turfgrass
being grown for sale or other commercial use such as sod production. 
Although the label does not indicate that the product is applied by
licensed or commercial applicators, it is acknowledged that the
homeowner will not be applying the product to golf courses and
therefore, a risk assessment for handler exposure is not required.  
Boscalid is not packaged or marketed for home orchard use, and therefore
that use is not assessed.  

It has been determined that there is a potential for exposure from
entering areas previously treated with boscalid that could lead to
exposures for adults and children.  Based on the discussion presented in
the Exposure SAC document (Child Golfer Exposure Characterization
9/29/03) the child golfer’s exposure is likely to be similar to that
of the adult golfer.  Hence, there is only one potential
non-occupational post-application scenario associated with boscalid:
adults golfing (Table 4).  Duration of exposure is anticipated to be
short-term.

Table  4.  Non-Occupational Post-application Exposure Scenario for
Boscalid

Scenario, Product,

Formulation	

Method of Application	

Use Sites	

Application Rate

BAS 510 02F Turf Fungicide, EPA Reg No. 7969-Pending	

ground equipment only	

golf course use only	

0.5 lb ai/A

 

Turf Transferable Residue Data:

The Registrant, BASF Corporation submitted a turf transferable residue
(TTR) study using boscalid in support of previous registration action
(D290072).  Since the TTR study was performed using the modified
California roller, the collected TTR values from this study are not
compatible with the HED’s transfer coefficient of 500 cm2/hr for
golfer (HED SOP 3.1).  Hence, the TTR values collected from the study
were not used to estimate dermal post-application exposure.  

Assumptions:

adult transfer coefficient is 500 cm2/hr (based on HED SOP 3.1)

duration of exposure is estimated to be 4 hours (assuming chemical is
used on all parts of a course [greens, tees and fairways] and an adult
plays 18 holes of golf)

Equations and Calculations:

PDRo = TTRo x CF1 x Tc x ET x % DA

where

PDRo	=	potential dose rate on day 0 (mg/day)

TTRo	=	turf transferable residue on day 0 (ug/cm2)

CF1	=	unit conversion factor to convert ug units in the DFR to mg for
daily exposure (0.001 mg/ug)

Tc	=	transfer coefficient (500 cm2/hr)

ET	=	exposure time (4 hr/day)

%DA	=	percent dermal absorption (15%)

Table 5 provides a summary of dermal post-application exposure for
golfing.  The MOE was greater than 100 and therefore did not exceed
HED’s level of concern.

	Table  5.  Dermal  Post-application Exposure for Adults and Youth

Scenario & Product	

DFR/TTR 1 (ug/cm2)	

CF1 (mg/ug)	

Tc (cm2/hr)	

ET (hr/day)	

% DA	

BW (kg)	

Daily Dose 2

(mg/kg/day)	

Dermal MOE 3

Golfing

BAS 510 02F Turf Fungicide

TTR Study MRID# 45405301	

0.05	

0.001

	

500	

4	

15	

70	

0.000214	

100,000

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)

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.  

5.0  Occupational Exposure

                                                                        
                                                                        
              

5.1   For Crop Protection Uses   

5.1.1.  Handlers  tc \l2 "5.1   For Crop Protection Uses   5.1.1. 
Handlers  

Equations/Calculations

The following equations were used to calculate handler exposure and
risk:

Dermal Dose (mg/kg/day) 	=	Rate (lb ai/A) x UE (mg/lb ai) x DA x Acres
Treated (A/day)

BW (kg)

Inhalation Dose (mg/kg/day)	=	 Rate (lb ai/acre) x UE (mg/lb ai) x Acres
Treated (A/day)

        BW (kg)

Where:

Rate (Application Rate)		=	Maximum application rate on product label (lb
ai/acre)

UE (Unit Exposure)		=	Exposure value derived from August 1998 PHED
Surrogate Exposure Table (mg/lb ai handled)

DA (dermal absorption factor)	=	Factor to account for dermal absorption
(15%) when endpoint is selected from an oral study.

Acres Treated			=	Maximum number of acres treated per day (acres/day)

             BW				=	Body weight (kg)

Combined Daily Dose (mg/kg/day) 	=	Dermal Dose (mg/kg/day) + Inhalation
Dose (mg/kg/day)

Total MOE		                             =	NOAEL (21.8 mg/kg/day)        
      

                                                                        
             Combined Daily Dose (mg/kg/day)

Exposure Scenarios

There are 7 handler scenarios that are expected to result in the highest
exposure for the proposed uses:

Mixing/Loading Dry Flowable for Ground-boom Applications (Scenario 1)

Mixing/Loading Dry Flowable for Airblast Applications (Scenario 2)

Mixing/Loading Dry Flowable for Aerial Applications (Scenario 3)

Applying Sprays with Ground-boom Equipment (Scenario 4)

Applying Sprays with Airblast Equipment (Scenario 5)

Applying Sprays with Aerial Equipment (Scenario 6)

Flagging during Aerial Application (Scenario 7)

Application Rate

The maximum application rates listed on the proposed labels provided by
the Registration Division were used for all exposure assessments.  The
maximum rates were 0.29 lb ai/A for tropical fruits and herbs and 0.4 lb
ai/A for cotton.

Area or the Amount Treated

Based on HED’s Exposure Science Advisory Council Policy Number 9.1, 80
acres/day for applications on tropical herbs using ground-boom
equipment, 40 acres/day for applications on tropical fruits using
airblast equipment, and 350 acres/day for applications using fix-wing
aerial equipment on tropical fruits and herbs were assumed.  For cotton,
200 acres/day for applications using ground-boom equipment, and 1200
acres/day for applications using fix-wing aerial equipment, were
assumed.

Body Weight									

The average body weight for general population (70 kg) was used for all
assessments.

Exposure Frequency

No data on the number of exposure days per year was provided   For this
risk assessment,  it was assumed that handlers would be exposed for less
than 6 months per year (short- and intermediate-term exposures). 
Long-term exposure is not expected.  

Unit Exposures

The unit exposures are based on the PHED Version 1.1 as presented in the
August 1998 PHED Surrogate Exposure Guide.  PHED was designed by a task
force of representatives from the U.S. EPA, Health Canada, the
California Department of Pesticide Regulation, and member companies of
the American Crop Protection Association.  PHED is a software system
consisting of two parts–a database of measured exposure values for
workers involved in the handling of pesticides under actual field
conditions and a set of computer algorithms used to subset and
statistically summarize the selected data.  Currently, the database
contains values for over 1,700 monitored individuals (i.e., replicates).

Users select criteria to subset the PHED database to reflect the
exposure scenario being evaluated.  The subsetting algorithms in PHED
are based on the central assumption that the magnitude of handler
exposures to pesticides is primarily a function of activity (e.g.,
mixing/loading, applying), formulation type (e.g., wettable powders,
granulars), application method (e.g., aerial, groundboom), and clothing
scenarios (e.g., gloves, double layer clothing).

Once the data for a given exposure scenario have been selected, the data
are normalized (i.e., divided by) by the amount of pesticide handled
resulting in standard unit exposures (milligrams of exposure per pound
of active ingredient handled).  Following normalization, the data are
statistically summarized.  The distribution of exposure values for each
body part (e.g., chest, upper arm) is categorized as normal, lognormal,
or “other” (i.e., neither normal nor lognormal).  A central tendency
value is then selected from the distribution of the exposure values for
each body part.  These values are the arithmetic mean for normal
distributions, the geometric mean for lognormal distributions, and the
median for all “other” distributions.  Once selected, the central
tendency values for each body part are composited into a “best fit”
exposure” value representing the entire body.

There are three basic risk mitigation approaches considered appropriate
for controlling occupational exposures.  These include administrative
controls, the use of personal protective equipment or PPE, and the use
of engineering controls.  Occupational handler exposure assessments were
completed by HED using baseline, PPE, and engineering controls. [Note:
Administrative controls available generally involve altering application
rates for handler exposure scenarios.  These are typically not utilized
for completing handler exposure assessments.] The baseline clothing
level scenario for occupational exposure scenarios is generally an
individual wearing long pants, a long-sleeved shirt, no chemical
resistant gloves, and no respirator.  The first level of mitigation
generally applied is PPE.  As reflected in the calculations included
herein, PPE may involve the use of an additional layer of clothing,
chemical-resistant gloves, and a respirator.  The next level of
mitigation considered in the risk assessment process is the use of
appropriate engineering controls which, by design, attempt to eliminate
the possibility of human exposure.  Examples of commonly used
engineering controls include enclosed tractor cabs and cockpits, closed
mixing/loading/transfer systems, and water-soluble packets.

Handlers’ Exposure and Risk

No MOEs for handlers performing crop protection uses exceed the level of
concern at the baseline or engineering control level (300 ~ 23,000). 
The HED level of concern is an MOE of <100.  Summaries of the
exposures/risks for handlers are presented in Table 6.  

The handler exposure estimates in this assessment are based on a central
tendency estimate of unit exposure and an upper-percentile assumption
for the application rate, and are assumed to be representative of
high-end exposures.  The uncertainties associated with this assessment
stem from the use of surrogate exposure data (e.g., differences in use
scenario and data confidence), and assumptions regarding that amount of
chemical handled.  The estimated exposures are believed to be reasonable
high-end estimates based on observations from field studies and
professional judgement.

5.1.2  Post-application 

Equations/Calculations

The following equations were used to calculate post-application exposure
and risk:

Daily dermal dose t	=	DFRt (µg/cm2) x 1E-3 mg/µg x Tc (cm2/hr) x DA x
ET (hrs)

  BW (kg)

Where:

t	=	number of days after application day (days)

DFRt	=	dislodgeable foliage residue on day “t” (µg/cm2)

Tc	=	transfer coefficient (cm2/hr)

DA	=	dermal absorption factor (unitless)

ET	=	exposure time (hr/day)

BW	=	body weight (kg)

DFRt (µg/cm2)		= AR (lb ai/acre) x F x (1-D)t x 4.54E8 µg/lb x 24.7E-9
acre/cm2

Where:

Rate	=	application rate (lb ai/acre)

F	=	fraction of ai retained on foliage or 20% (unitless)

D	=	fraction of residue that dissipates daily or 10% (unitless)

MOE		=	NOAEL (21.8 mg/kg/day)               

                                           Daily dermal dose t
(mg/kg/day)

Post-application Activities and Transfer Coefficients

Anticipated post-application activities and their respective dermal
transfer coefficients (TCs) are summarized in Table 7.  The information
in the table is based on the Science Advisory Council for Exposure
Policy Number 3.1 and is based on proprietary and non-proprietary data.

Application Rate

The maximum application rates listed on the proposed label provided by
the Registration Division were used for all assessments.  The maximum
rates were 0.29 lb ai/A for herbs/tropical fruits and 0.4 lb ai/A for
cotton.

Exposure Frequency

No data on the number of exposure days per year was provided   For this
risk assessment,  it was assumed that post-application workers would be
exposed for less than 30 days per year.  

Exposure Duration

Workers were assumed to be exposed 8 hours per day.

Body Weight

The average body weight of an adult (70 kg) was assumed.

Table 7.  Anticipated Post-application Activities and Dermal Transfer
Coefficients.

Proposed Crops	

Policy Crop Group Category	

Exposure Potential	

Transfer Coefficients (cm2/hour)	

Activities

       Herbs	Vegetable, leafy	

Low	

500	

irrigation, scouting, thinning, weeding immature plants

Medium	

1500	

irrigation, and scouting mature plants

High	

2500	

hand harvesting, pruning, thinning mature plants

Tropical Fruits	   Tree, fruit,           evergreen	

Very Low	

100	

propping

        Low 	         1000	irrigation, scouting, hand weeding

Medium	

1500	

harvesting

High	

3000	

thinning

       Cotton

	Field/row crop,

  Low/medium	

Low	

100	

irrigation, scouting

Medium	

1500	

irrigation, and scouting thinning, weeding immature/low plants

      Post-application Exposure and Risk

All post-application MOEs on the day of application are greater than 100
(650~20,000), and do not exceed HED’s level of concern (MOE<100).  A
summary of the post-application exposures/risks is presented in Table 8.
 

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.

           Table 6.  Non-Cancer Risks for Boscalid Handlers.

Exposure Scenario (Scenario #)	

Mitigation Levela	

Dermal Unit Exposureb (mg/lb ai)	

Inhalation Unit Exposurec   (Ug/lb ai)	

Application Rate

(lb ai/A)	

Amount Treatedd

(A/day)	

Daily

Dermal

Dosee (mg/kg/day)	

Daily

Inhalation

Dosef (mg/kg/day)	

Combined

Daily Doseg (mg/kg/day)	

Total

MOEh    

Mixer/Loader

Dry Flowables for 

Ground application (1)	Baseline	0.066	0.77	0.29

0.4 (Cotton)	80

200 (Cotton)	0.0033

0.0113 (Cotton)	0.00026

0.00088 (Cotton) 	0.0036

0.0122 (Cotton)	6,100

1,800 (Cotton) 

Dry Flowables for 

Airblast application (2)      

	Baseline	0.066	0.77	0.29	40	0.0016	0.00013	0.0017	13,000

Dry Flowables for 

Aerial application (3)	Baseline	0.066	0.77	0.29

0.4 (Cotton)	350

1200 (Cotton)	0.014

0.0678 (Cotton) 	0.0011

0.0053 (Cotton)	0.015

0.073 (Cotton)	1,500

300 (Cotton)

Applicator

Sprays with       Groundboom (4)	

Baseline	0.014	0.74	0.29

0.4 (Cotton)	80

200 (Cotton)	0.00070

0.0024 (Cotton)	0.00025

0.00084 (Cotton)	0.00095

0.0032 (Cotton)	23,000

6,800 (Cotton)

Sprays with               Airblast (5)  

	Baseline                      	0.36	4.5	0.29	40	0.0089	0.00075	0.0097
2,200



Sprays with 

Fix-Wing aircraft (6)	

Eng. Cont.	0.0050	0.068	0.29

0.4 (Cotton)	350

1200 (Cotton)	0.0011

0.0051 (Cotton)	0.000099

0.00046 (Cotton)	0.0012

0.0056 (Cotton)	18,000

3,900 (Cotton)

Flagger

Flagging during                  aerial applications (7)	

Baseline	0.011	0.35	0.29

0.4 (Cotton)	350	0.0024

0.0033 (Cotton)	0.00051

0.0007 (Cotton)	0.0029

0.004 (Cotton)	7,500

5,500 (Cotton)

a	Baseline consists of long-sleeve shirt, long pants, shoes, and socks
and no respirator.  Eng. Cont. consists of enclosed cockpit.

b	Baseline Dermal Unit Exposure represents long pants, long sleeved
shirt, no gloves, open mixing/loading, and open cab tractors, as
appropriate.  Eng. Cont. Dermal Unit Exposure represents enclosed
cockpit. 

c	Baseline Inhalation Unit Exposure represents no respiratory
protection, open mixing/loading, and open cab tractors, as appropriate. 
Eng. Cont. Inhalation Unit Exposure represents enclosed cockpit. 

d	Daily acres treated values are from EPA estimates of acreage that
could be treated in a single day for each exposure scenario of concern. 
Exposure SAC Policy 9, 7/5/2000.  

e	Daily dermal dose (mg/kg/d) =  [unit dermal exposure (mg/lb ai) *
dermal absorption (0.15) * application rate (lb ai/acre) * daily acres
treated /  body weight (70kg).

f	Daily inhalation dose (mg/kg/d) = (unit exposure (µg/lb ai) *
(1mg/1000 µg) conversion * appl. rate (lb ai/acre) * daily acres
treated / body weight (70kg).

g	Combined daily dose = daily dermal dose + daily inhalation dose.

h	Short-term MOE = NOAEL (21.8 mg/kg/d) / combined daily dose.  UF =
100.



Table  8.  Post-application Exposure and Risk for Crop Protection 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).

5.2   For Seed Treatment Uses   

5.2.1  Handlers 

Equations/Calculations

The following equations were used to calculate handler exposure and
risk:

Dermal Dose (mg/kg/day) 	=	Rate (lb ai/lb seed) x UE (mg/lb ai) x DA x
lb. Treated (lb/day)

BW (kg)

Inhalation Dose (mg/kg/day)	=	 Rate (lb ai/lb seed) x UE (mg/lb ai) x
lb. Treated (lb/day)

        BW (kg)

Where:

Rate (Application Rate)		=	Maximum application rate on product label (lb
ai/lb seed)

UE (Unit Exposure)		=	Exposure value derived from Exposure SAC Policy #
14; May 1, 2003

DA (dermal absorption factor)	=	Factor to account for dermal absorption
(15%) when endpoint is selected from an oral study.

lb. Treated			=	Maximum number of pounds (of seeds) treated per day     
                                                                        
                             (lb/day)

BW				=	Body weight (kg)

Combined Daily Dose (mg/kg/day) 	=	Dermal Dose (mg/kg/day) + Inhalation
Dose (mg/kg/day)

MOE	                                                         =          
 NOAEL (21.8 mg/kg/day)              

                                                                        
             Combined Daily Dose (mg/kg/day)

Exposure Scenarios

There are four commercial seed handler scenarios that are expected to
result in the highest exposure for the  proposed uses:

Loading (Open)/Applying Liquid for Seed Treatment (Scenario 1) 

Sewing Seeds after Seed Treatment (Scenario 2)

Bagging Seeds after Seed Treatment (Scenario 3)

Multiple Activities Worker for Seed Treatment (Scenario 4)

Application Rate

The maximum application rate listed on the proposed labels provided by
the Registration Division was used for all exposure assessments.  The
maximum rate is 0.12 lb ai/100 lbs seed.

Treating Capacity

The treating capacity, amount of seeds treated per day in a commercial
seed treatment facility, were based on the data shown in the Science
Advisory Council for Exposure (Exposure SAC) Policy #15. The treating
capacity is 160,000 lbs/day for treating cotton seeds.

Body Weight

The average body weight for general population (70 kg) was used for all
assessments. 

Exposure Frequency

No data on the number of exposure days per year were provided.  Due to
the seasonal nature of seed treatment operation, it was assumed that
handlers would be exposed for less than 6 months per year (i.e.
short-/intermediate- term in duration).  

Unit Exposures

The unit exposures used for assessing seed treatment exposures were
based on the exposure data (Table 5) obtained from the Exposure SAC
Policy #14: Standard Operating Procedures (SOP) for Seed Treatment (May
1, 2003).



Table 9.  Unit Exposure Values from Exposure SAC Policy #14

Scenario	

Dermal (mg/lb ai)	

Inhalation (mg/lb ai)	

PPE Level

Loader/Operator	

0.023	

0.00034	

single layer, glove

Sewer	

0.0062	

0.00023	

single layer, no glove 

Bagger	

0.0091	

0.00016	

single layer, no glove

Multiple Activities	

0.042	

0.0016	

single layer, glove

The engineering controls level assessment for the loader/applicator to
support seed treatment use is based on the unit exposure values (for
closed mixing liquids) given in the PHED Version 1.1 as presented in the
August 1998 PHED Surrogate Exposure Guide.

Handlers’ Exposure and Risk

No MOEs for handlers performing seed treatment use exceed the level of
concern at the single layer level (1,000 ~ 6,800).  The HED level of
concern is an MOE of <100.  A summary of the risks for handlers is
presented in Table 10.  

The handler exposure estimates in this assessment are based on a central
tendency estimate of unit exposure and an upper-percentile assumption
for the application rate, and are assumed to be representative of
high-end exposures.  The uncertainties associated with this assessment
stem from the assumptions regarding that amount of chemical handled and
the amount of seed treated per day.  The estimated exposures are
believed to be reasonable high-end estimates based on observations from
field studies and professional judgement.

5.2.2  Secondary Handler  tc \l2 "5.2.2  Post-application  

Scenario and Unit Exposure

The secondary handler exposure scenario for seed treatment 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)

Assumptions and Factors									

Policy #14 HED dermal unit exposure = 0.25 mg/lb ai; inhalation unit
exposure  = 0.0034 mg/lb ai 

amount of seed planted per day (lb seed/day) is based on the data shown
in Exposure SAC Policy # 15 (3,600 lb seed/day for cotton).

exposure frequency - 60 days/year and 8 hour/day exposure

body weight  = 70 kg

dermal absorption = 15%, inhalation absorption = 100%



Equations and Calculations

Daily Dermal Dose 	= Dermal UE x Amount of Seed Planted/day x
Application Rate x DA

Body Weight (kg)

Daily Inhalation Dose      = Inhalation UE x Amount of Seed Planted/day
x Application Rate x IA

Body Weight (kg)

              Combined Daily Dose Dose (mg/kg/day) = Daily Dermal Dose +
Daily Inhalation Dose		

MOE		 =	 NOAEL (21.8 mg/kg/day)              

                                                          Combined Daily
Dose (mg/kg/day)

Secondary Handler’s Exposure and Risk

The secondary handler’s MOE for seed planters does not exceed the
level of concern at the single layer level (8,700). The HED level of
concern is an MOE of <100.  These exposure/risk values are presented in
Table 11.

The secondary handler exposure estimates in this assessment are based on
a central tendency estimate of unit exposure, an upper-percentile
assumption for the application rate, and a conservative estimate of
exposure frequency; and are assumed to be representative of high-end
exposures.  The uncertainties associated with this assessment stem from
the use of surrogate exposure data (e.g., differences in use scenario
and data confidence) and assumptions regarding that amount of chemical
handled.  The estimated exposures are believed to be reasonable high-end
estimates based on observations from field studies and professional
judgement.

Due to the nature of the use pattern (seed treatment), the REI is based
on the acute toxicity of the active ingredient.  Boscalid is classified
in Acute Toxicity Category III for acute dermal toxicity; and in Acute
Toxicity Category IV for primary eye irritation, acute inhalation
toxicity, and primary skin irritation.  The labels list a 12 hour REI.  

Title 40 of the Code of Federal Regulations, § 156.208 (c) (2) states: 
If a product contains only one active ingredient and it is in Toxicity
Category I by the criteria in paragraph (c) (1) of this section, the
restricted-entry interval shall be 48 hours.”   The Federal Register
Vol. 57, No. 163,  21 August 1992  page 38104 and 38142 (For 40 CFR
Parts 156 and 170) indicates that “...a 48-hour REI is established for
any product containing an active ingredient that is in Acute Toxicity
Category I (most acutely toxic category) because of dermal toxicity or
skin or eye irritation.”  Boscalid is not classified in Acute Toxicity
Category I, but in Category III and IV; hence, the 12 hour REI is
appropriate.

	

Table 10.  Non-Cancer Risk for Seed-Treatment Handlers.

Exposure Scenario (Scenario #)	

Mitigation Level	

Dermal Unit Exposure (mg/lb ai)	

Inhalation Unit Exposure   (mg/lb ai)	

Seed Species	

Application Rate

(lb ai  per 100 lb seed)	

Amount Treateda

(lb seed trt per day)	

Daily

Dermal

Dose b (mg/kg/day)	

Daily

Inhalation

Dosec (mg/kg/day)	

Combined Daily Dosed  (mg/kg/day)	

Total 

MOEe  

Loader/Applicator

Loading/Applying

Liquids for 

Seed Treatment (1)	

Single Layer, Gloves	

0.023	

0.00034	cotton	0.12	160,000	0.0095	0.00093	0.010	2,200

Sewer

Sewing Seeds after Seed treatment (2)	

Single Layer, 

No Gloves	

0.0062	

0.00023	cotton	0.12	160,000	0.0026	0.00063	0.0032	6,800

Bagger

Bagging Seeds after Seed treatment (3)	

Single Layer, 

No Gloves	

0.0091	

0.00016	cotton	0.12	160,000	0.0037	0.00044	0.0041	5,300

Multiple Activities Worker

Multiple Activities for Seed treatment (4)	

Single Layer, Gloves	

0.042	

0.0016	cotton	0.12	160,000	0.017	0.0044	0.021	1,000

a	Daily amounts treated values are based on the information provided by
the Registrant through Registration Division. 

b	Daily dermal dose (mg/kg/d) =  [unit dermal exposure (mg/lb ai) *
dermal absorption (0.15) * application rate (lb ai/lb seed) * daily
amounts treated /  body weight (70 kg).

c	Daily inhalation dose (mg/kg/d) = (unit exposure (mg/lb ai) *
application. rate (lb ai/lb seed) * daily amounts treated / body weight
(70 kg).

d	Combined daily dose (mg/kg/d) =  Daily dermal dose (mg/kg/d) + Daily
inhalation dose (mg/kg/d).

e	MOE = NOAEL (21.8  mg/kg/d) / combined daily dose.  UF = 100.

Table 11.  Non-Cancer Risk for Secondary Handler-Seed Planters.

Exposure Scenario (Scenario #)	

Mitigation Level	

Dermal Unit Exposure (mg/lb ai)	

Inhalation Unit Exposure   (mg/lb ai)	

Seed  Category--Representative

Seed Species	

Application Rate

(lb ai  per 100lb seed)	

Amount Planteda

(lb seed pnted/day)	

Daily

Dermal

Dose b (mg/kg/day)	

Daily

Inhalation

Dosec (mg/kg/day)	

Combined Daily Dosed 

(mg/kg/day) 	

Total

MOEe  

Seed Planters

Post-application:

planting seeds in the field	

Single Layer, Gloves	

0.25	

0.0034	cotton	0.12	3,600	0.0023	0.00021	0.0025	8,700

a	Daily amounts planted values are based on the information provided by
the Registrant through Registration Division. 

b	Daily dermal dose (mg/kg/d) =  [unit dermal exposure (mg/lb ai) *
dermal absorption (0.15) * application rate (lb ai/lb seed) * daily
amounts treated /  body weight (70 kg).

c	Daily inhalation dose (mg/kg/d) = (unit exposure (mg/lb ai) *
application. rate (lb ai/lb seed) * daily amounts treated / body weight
(70 kg).

d	Combined daily dose (mg/kg/d) =  Daily dermal dose (mg/kg/d) + Daily
inhalation dose (mg/kg/d).

e	MOE = NOAEL (21.8 mg/kg/d) / combined daily dose.  UF = 100.			



CC:   RAB2 RF, D. Davis, S. Wang

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