Document ID: EPA-HQ-OPP-2006-1026-0006
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2007-08-15T04:00Z

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C.  20460

OFFICE OF           

PREVENTION, PESTICIDES

AND TOXIC SUBSTANCES

MEMORANDUM  

Date:		May 1, 2007

	

Subject:	Pyrasulfotole: Occupational and Residential Exposure/Risk
Assessment for the New Use on Cereal Grains

PC Code: 000692        	DP Barcode: 333434

To:		Joanne Miller, RM 23

		Registration Division/Herbicide Branch (7505P)

			

From:		Kelly M. Lowe, Environmental Scientist

		Health Effects Division/Registration Action Branch 1 (7509P)

Thru:		PV Shah, Acting Branch Chief

Health Effects Division/Registration Action Branch 1 (7509P)

INTRODUCTION

Under Section 3 of the Federal Insecticide, Fungicide and Rodenticide
Act, as amended, Bayer Crop Science has requested registration of the
herbicide pyrasulfotole for use on cereal grains.  This memorandum
serves as HED’s assessment of nondietary exposure and risk that might
result from the proposed use.

USE PATTERN SUMMARY

Table 1 summarizes the proposed use pattern and formulations specified
in the end-use products containing pyrasulfotole.

	

Table 1.   Proposed Use Patterns and Formulations

Product	Formulation	Use Sites	Application Rates	Application Equipment
Area Treated	Timing of Application and Restrictions

AE0317309 +  Bromo	liquid	wheat, barley, oat, triticale	0.037 lb ai/A
aerial	wheat: 1200 acres; 

all other crops: 350 acres	Apply between 1 leaf and up to flag leaf
emergence; PHI: 25 days for forage and 60 days for grain and straw; REI:
12 hours; multiple active ingredients

groundboom 	wheat: 200 acres; 

all other crops: 80 acres

	chemigation	all crops: 350 acres

	AE0317309 SE06 Herbicide

	0.045 lb ai/A	aerial	wheat: 1200 acres; 

all other crops: 350 acres	Apply between 1 leaf and up to flag leaf
emergence; PHI: 25 days for forage/hay; 50 days for wheat/triticale; 45
days for barley/oats; REI: 12 hours

groundboom	wheat: 200 acres; 

all other crops: 80 acres

	

HAZARD INFORMATION tc  \l 1 "2.0  Hazard Information" 

RAB1 toxicologists met to determine appropriate toxicological endpoints
of concern for pyrasulfotole.  Adverse effects were identified at
durations of exposure ranging from short-term (up to 30 days) to
intermediate-term durations (1 to 6 months) to long-term (chronic)
durations (more than 6 months).

The acute toxicity categories for pyrasulfotole are summarized in Table
2.  The doses selected by RAB1 toxicologists are summarized in Table 3.
Short- and intermediate-term dermal risks were assessed using a No
Observable Adverse Effect Level (NOAEL) of 10 mg/kg/day from a 28-day
toxicity study in the rat in which focal degeneration of pancreas (both
sexes) and alteration of thyroid colloid (males) was observed.  Short-
and intermediate-term inhalation risks were assessed using a NOAEL of
1.0 mg/kg/day from a combined chronic toxicity/ carcinogenicity study in
the rat in which corneal opacity, neovascularization of the cornea,
inflammation of the cornea, regenerative corneal hyperplasia, corneal
atrophy, and/or retinal atrophy (both sexes), and hepatocellular
hypertrophy along with increased serum cholesterol (males) was observed.
A body weight of 70 kg was used since the endpoints were not
sex-specific.   The dermal absorption factor was estimated to be 2.5%. 
A 100% oral equivalent inhalation absorption factor is assumed.

Table 2. Acute Toxicity of Pyrasulfotole

Guideline Number	Study Type	MRID #	Results	Tox Cat.

81-1	Acute Oral	46801836	Oral LD50  > 2000 mg/kg females	III

81-2	Acute Dermal	46801837	Dermal LD50 >2000 mg/kg	III

81-3	Acute Inhalation	46801838	LC50> 5.03 mg/L	IV

81-4	Primary Eye Irritation	46801839	Moderate irritant	III

81-5	Primary Skin Irritation	46801840	Not an irritant	IV

81-6	Dermal Sensitization	46801841	Not dermal sensitizer	-



Table 3.  Summary of Toxicological Doses and Endpoints for Pyrasulfotole
for Use in Occupational Human Health Risk Assessments

Exposure Scenario	Point of Departure	Uncertainty/FQPA Safety Factors
RfD, PAD, Level of Concern for Risk Assessment	Study and Toxicological
Effects

Dermal

Short- and Intermediate- Term (1-30 days and 1-6 months)	NOAEL = 10

mg/kg/day

Estimated dermal absorption factor = 2.5%	UFA = 10X

UFH = 10X

	Occupational LOC for MOE < 100	28-day dermal toxicity (rat) LOAEL = 100
mg/kg bw/day [M/F] based on focal degeneration of pancreas (both sexes)
and alteration of thyroid colloid (males)

Dermal

Long-Term (>6 months)	NOAEL = 1.0

mg/kg/day

Estimated dermal absorption factor = 2.5%	UFA = 10X

UFH = 10X	Occupational LOC for MOE < 100	Combined chronic
toxicity/carcinogenicity (rat; dietary) LOAEL = 10/14 mg/kg/day (M/F)
based on corneal opacity, neovascularization of the cornea, inflammation
of the cornea, regenerative corneal hyperplasia, corneal atrophy, and/or
retinal atrophy (both sexes), and hepatocellular hypertrophy along with
increased serum cholesterol (males).

Inhalation

(All durations)	NOAEL = 1.0

mg/kg/day

100% inhalation assumed	UFA = 10X

UFH = 10X	Occupational LOC for MOE < 100	Combined chronic
toxicity/carcinogenicity (rat; dietary) LOAEL = 10/14 mg/kg/day (M/F)
based on corneal opacity, neovascularization of the cornea, inflammation
of the cornea, regenerative corneal hyperplasia, corneal atrophy, and/or
retinal atrophy (both sexes), and hepatocellular hypertrophy along with
increased serum cholesterol (males).

Cancer (oral, dermal, inhalation)	Classification:  “Suggestive
Evidence of Carcinogenic Potential” based on increased incidences of
corneal tumors in male rats (oral carcinogenicity study) and urinary
bladder tumors in male and female mice (oral carcinogenicity study).

Abbreviations: UF = uncertainty factor, UFA = extrapolation from animal
to human (interspecies), UFH = potential variation in sensitivity among
members of the human population (intraspecies), UFFQPA = FQPA Safety
Factor, UFL = use of a LOAEL to extrapolate a NOAEL, UFDB = to account
for the absence of key data, NOAEL = no observed adverse effect level,
LOAEL = lowest observed adverse effect level, RfD = reference dose (a =
acute, c = chronic), PAD = population adjusted dose, MOE = margin of
exposure, LOC = level of concern, N/A = Not Applicable

HED’s level of concern (LOC) for pyrasulfotole occupational and
residential dermal and inhalation exposures is 100 (i.e., a margin of
exposure (MOE) less than 100 is considered a risk of concern by HED). 
The level of concern is based on 10X to account for interspecies
extrapolation to humans from the animal test species and 10X to account
for intraspecies sensitivity.  

	

NON-OCCUPATIONAL/RESIDENTIAL EXPOSURE

The proposed new use is on agricultural crops (e.g., wheat, oats, barley
and triticale); therefore, residential exposures are not expected and
were not assessed.

 tc "

" OCCUPATIONAL EXPOSURE

Based upon the proposed use pattern, the most likely exposure scenarios
include mixing/loading liquids for aerial, chemigation and groundboom
applications, applying liquids via aerial and groundboom equipment, and
flagging for aerial applications.  HED expects the most highly exposed
occupational pesticide handlers are likely to be:

	Mixer/Loader:

(1) Mixing/Loading Liquids for Aerial Applications (PHED); and

Applicators:

(2) Applying Sprays via Aerial Equipment (PHED).

				

	No chemical specific data were available with which to assess potential
exposure to pesticide handlers.  The estimates of exposure to pesticide
handlers are based upon surrogate study data available in the PHED
Surrogate Guide (August, 1998).   For pesticide handlers, it is HED
standard practice to present estimates of dermal exposure for
“baseline” that is, for workers wearing a single layer of work
clothing consisting of a long sleeved shirt, long pants, shoes plus
socks and no protective gloves, as well as for “baseline” and the
use of protective gloves or other Personal Protective Equipment (PPE) as
might be necessary.  The proposed product labels involved in this
assessment direct applicators and other handlers to wear a long sleeved
shirt and long pants, socks, shoes, chemical resistant gloves and
protective eyewear.  

HED classifies exposures up to 30 days as short-term and exposures
greater than 30 days up to several months as intermediate-term.  Since
only one application is allowed per season for this product, HED expects
most exposures will be short-term in duration, therefore, only
short-term exposures were assessed.  

	

Daily dermal or inhalation handler exposures are estimated for each
applicable handler task with the application rate, the area treated in a
day, and the applicable dermal or inhalation unit exposure using the
following formula:

Daily Exposure (mg ai/day) = UE (mg ai/lb ai handled) x AR (lbs ai/area)
x AT (area/day)

Where:  

Daily Exposure		=	Amount (mg ai/day) deposited on the surface of the
skin that is available for dermal absorption or amount inhaled that is
available for inhalation absorption;

UE	 		=	Unit exposure value (mg ai/lb ai) derived from August 1998 PHED
Surrogate Guide;

AR			=	Application rate (lb ai/A or lb ai/gal); and

	AT		 	=	Application area based on a logical unit treatment such as
acres (A/day) or gallons per day (gal/day). 

	The daily dermal or inhalation dose is calculated by normalizing the
daily exposure by body weight and adjusting, if necessary, with an
appropriate dermal or inhalation absorption factor using the following
formula:

Average Daily Dose (mg/kg/day) = Daily Exposure (mg ai/day) x
(Absorption Factor (%/100) / Body Weight (kg)

Where:

Average Daily Dose 		= 	Absorbed dose received from exposure to a
pesticide in a given scenario (mg pesticide active ingredient/kg body
weight/day);

Daily Exposure 			=	Amount (mg ai/day) deposited on the surface of the
skin that is available for dermal absorption or amount inhaled that is
available for inhalation absorption;

Absorption Factor 		= 	A measure of the amount of chemical that crosses
a biological boundary such as the skin or lungs (% of the total
available absorbed); and

Body Weight 			= 	Body weight determined to represent the population of
interest in a risk assessment (kg).

	Non-cancer dermal and inhalation risks for each applicable handler
scenario are calculated using a MOE, which is a ratio of the NOAEL to
the daily dose.  All MOE values were calculated using the formula below:

MOE= NOAEL or LOAEL (mg/kg/day) / Average Daily Dose (mg/kg/day)

A total MOE was calculated because the dermal and inhalation
toxicological endpoints of concern are based on the same adverse
effects.  The total MOE values were calculated using the formula below:

  SEQ CHAPTER \h \r 1  Total MOE = NOAEL / (dermal + inhalation daily
dose (mg/kg/day))

Occupational Handler Non-cancer Risk Summary  tc "2.1.3.2	CAMA
Non-cancer Risk Summary (using PHED and ORETF data) " \l 4 

Table 4 presents the exposure/risks for short and intermediate-term
dermal and inhalation exposures at baseline.  HED has no data to assess
exposures to pilots using open cockpits.  The only data available is
for exposure to pilots in enclosed cockpits.  Therefore, risks to
pilots are assessed using the engineering control (enclosed cockpits)
and baseline attire (long-sleeve shirt, long pants, shoes, and socks). A
MOE of 100 is adequate to protect occupational pesticide handlers.  All
MOEs are >100 with baseline attire; and, therefore, are not of concern
to HED.

Table 4.  Pyrasulfotole Occupational Noncancer Dermal and Inhalation
Exposures and Risks from Application to Cereal Grains

Application Rate 

(lb ai/acre)a	Area Treated Daily (acres)b	Unit Exposures --

Dermal and Inhalation 

(mg/lb ai)	Doses (mg/kg/day)f	MOEsg	Combined MOEsh

Mixer/Loader for Aerial Applications

0.045	1200	Dermal

Baselinec: 2.9	Dermal

Baseline:  0.056	Dermal

Baseline: 180	Baseline Dermal + Inhalation: 150

Inhalation

Baselined: 0.0012	Inhalation

Baseline: 0.00093	Inhalation

Baseline: 1,100

	Applicator for Aerial Equipment

0.045	1200	Dermal

Engineering controle: 0.005	Dermal

Engineering control: 0.000096	Dermal

Engineering control: 100,000	Engineering control Dermal + Inhalation:
16,000                                                                  
                                                                        
                                                                        
                                                                        
                                                                        
                                                                        
                                                                        
                                                                        
                                                                        
                                                                        
                                                                        
              

Inhalation

Engineering control: 0.000068	Inhalation

Engineering control: 0.000052	Inhalation

Engineering control: 19,000

	a	Application rates are the maximum application rates determined from
proposed labels for pyrasulfotole

b	Amount handled per day values are HED estimates of acres treated per
day based on Exposure SAC SOP #9 “Standard Values for Daily Acres
Treated in Agriculture,” industry sources, and HED estimates.	

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

d	Baseline Inhalation: no respirator.

e	Engineering control:  enclosed cockpit and baseline attire
(long-sleeve shirt, long pants, shoes, and socks).

f	Dose (mg/kg/day) = Unit exposure(mg/lb ai) x App Rate (lb ai/acre) x
Area Treated (acres/day) x  %Absorption (2.5% dermal and 100%
inhalation) / Body weight (70 kg).  

g	MOE = NOAEL/Dose; where the short-term dermal NOAEL = 10 mg/kg/day and
the short-term inhalation NOAEL = 1.0 mg/kg/day

h	Combined MOE = NOAEL / (dermal + inhalation daily dose (mg/kg/day))

	

Postapplication 

Since no postapplication data was submitted in support of this
registration action, exposures during postapplication activities were
estimated using dermal transfer coefficients from the Science Advisory
Council For Exposure Policy Number 3.1: Agricultural Transfer
Coefficients, August 2000, summarized in Table 6 below and the following
assumptions:

					

Assumptions:

Application Rate	= 	0.045 lb ai/A 

Exposure Duration	=	8 hours per day

Body Weight		=	70 kg			

Dermal Absorption	= 	2.5%

Fraction of a.i. retained on foliage is assumed to be 20% (0.2) on day
zero (= % dislodgeable foliar residue, DFR, after initial treatment). 
This fraction is assumed to further dissipate at the rate of 10% (0.1)
per day on following days.  These are default values established by
HED’s Science Advisory Council (SAC) for Exposure.

Table 6: Anticipated Postapplication Activities and Dermal Transfer
Coefficients

Proposed Crops	Policy Crop Group Category	Transfer Coefficients (cm2/hr)
Activities

Cereal grains	Field / row crop, low / medium	100 	Scouting, irrigation
of crops at low height

1,500 	Scouting, irrigation of crops at medium height

The information in the table is based on  proprietary and
non-proprietary data.

	Daily dermal doses were calculated on each postapplication day after
application using the following equations:

Dermal Dose (mg/kg/day) = [DFR(t) (µg/cm2) x TC (cm2/hr) x ET (hr/day)
* CF1 * Abs (%)] / BW (kg)

Where:

	DFR(t)	=	Dislodgeable foliar residues at time “t” (0.1 µg/cm2 on
day 0);

	TC	=	Transfer Coefficient (cm2/hour); 

ET	=	Exposure time meant to represent a typical workday (8 hours);

CF1	=	Conversion factor (0.001 mg/ug); 

Abs	=	Dermal absorption (2.5%); and

BW	=	Body weight (70 kg).

And

DFR(t) (µg/cm2) =  [AR (lb ai/A) * (CF2/CF3)] * TR

Where:

	DFR(t)	=	Dislodgeable foliar residues at time “t” (0.1 µg/cm2 on
day 0);

	AR	=	Application rate (lb ai/A); 

CF2	=	Conversion factor (4.54E+08 ug/lb)

CF1	=	Conversion factor (4.05E+07 cm2/A); and

TR	=	Transferable residue that can be dislodgeable foliar residue at
time (t) (20% on day 0).

Occupational Postapplication Noncancer Risk Summary  tc "2.2.3	Noncancer
Risk Summary " \l 3  

Table 6 presents a summary of occupational postapplication risks
associated with use of pyrasulfotole.  For cereal grains, risks are not
of concern for irrigation and scouting activities on day 0 (REI = 12
hours).  

	Table 6.  Summary of Occupational Postapplication Risks for
Pyrasulfotole

Crop Grouping	Application rate

(lb ai/acre)	Transfer Coefficient (cm2/hr)	Days after Application	MOE at
Day 0

(Level of Concern = 100)

Cereal grains	0.045	100 

(Scouting, irrigation crops at low height)	0 (12 hours)	350,000

1,500 

(Scouting, irrigation crops at medium height)	0 (12 hours)	23,000

		

	

RESTRICTED ENTRY INTERVAL (REI)

Pyrasulfotole is classified in Acute Toxicity Category II for acute oral
toxicity, acute dermal toxicity, and primary eye irritation.  It
classified in Category IV for acute inhalation toxicity and primary skin
irritation.  It is not a dermal sensitizer.  Therefore, the interim
worker protection standard (WPS) restricted entry interval of 12 hours
is adequate to protect agricultural workers from post-application
exposures.  The two end-use product labels list a REI of 12 hours.  

		  

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