Document ID: EPA-HQ-OPP-2009-0797-0005
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2010-08-04T04:00Z

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C.  20460

     OFFICE OF	

PREVENTION, PESTICIDES

AND TOXIC SUBSTANCES

Date: April 5, 2010   

MEMORANDUM

SUBJECT:      Halosulfuron-Methyl:  Human Health Risk Assessment for
IR-4 Proposed Uses on Crop Group 6B Succulent Shelled Pea and Bean
Subgroup, Crop Group 1C Tuberous and Corn Vegetables Subgroup, Crop
Group 6C Dried Shelled Pea and Bean (Except Soybean), Subgroup 13-07B
Bushberry, Okra, Apples, and Rhubarb.

PC Code:  128721	DP Barcode:  D366410

Decision No.:  414896	Registration No.:  81880-18

Petition No.:  9E7577	Regulatory Action:  Section 3   

Risk Assessment Type:  Single  Chemical/Aggregate	Case No.:  NA

TXR No.:  NA	CAS No.:  100784-20-1

MRID No.:  NA	40 CFR:  180.479

FROM:	Whang Phang, Toxicologist, Risk Assessor

		Nancy Tsaur, Chemist, ORE Assessor

		Risk Assessment Branch 3

Health Effects Division (7509P)

Debra Rate, Biologist, Residue Chemistry and Dietary Assessor

		RIMUERB/RD (7505P)

THRU:	Paula A. Deschamp, Branch Chief

		Risk Assessment Branch 3

		Health Effects Division (7509P)

TO:		Sidney Jackson/Barbara Madden, RM 05

	RIMUERB/Registration Division (7505P)

IR-4 has proposed the establishment of a permanent tolerance for
residues of the herbicide halosulfuron-methyl [methyl
5-[(4,6-dimethoxy-2-pyrimidinyl)amino]
carbonylaminosulfonyl-3-chloro-1-methyl-1H-pyrazole-4-carboxylate] in/on
the following agricultural commodity:

Pea and bean, succulent shelled, Subgroup 6B 	0.05 ppm

Vegetable, tuberous and corm, Subgroup 1C 	0.05 ppm

Pea and bean, dried shelled, except soybean, Subgroup 6C 	0.05 ppm

Bushberry, Subgroup 13-07B 	0.05 ppm

Rhubarb 	0.05 ppm

Apple 	0.05 ppm

Okra 	0.05 ppm

The most recent human health risk assessment was conducted for uses on
soybean (D358031, W. Phang, 6/30/2009). Since then, no new toxicology
data have been submitted. The hazard characterization and toxicity
endpoints for risk assessment remain unchanged since the 2006 risk
assessment for uses on alfalfa (D331643, M. Rust, 9/21/2006). The
details of hazard characterization and the rationale for toxicity
endpoint selection will not be repeated in this risk assessment.
However, the salient features will be summarized for these two topics
and for the Food Quality Protection Act (FQPA) safety factor discussion.

A summary of the findings and an assessment of human risk resulting from
the proposed and registered uses of halosulfuron-methyl are provided in
this document and its attachments.  The residue chemistry data submitted
in support of this petition were reviewed by Debra Rate, who also
conducted the dietary assessment.  The occupational/residential
assessment was performed by Nancy Tsaur.  The drinking water assessment
was conducted by Michael Barrett of the Environmental Fates and Effects
Division (EFED).  The toxicology evaluation and risk assessment were
performed by Whang Phang.

Recommendations for Tolerance

Pending submission of a revised Section B, a revised Section F, and
reference standards, HED concludes that the toxicology and residue
chemistry databases, the dietary, residential, aggregate, and
occupational risk assessments support the requested uses on the
following crops and establishment of the following tolerances: 

Pea and bean, succulent shelled, Subgroup 6B 	0.05 ppm

Vegetable, tuberous and corm, Subgroup 1C 	0.05 ppm

Bushberry, Subgroup 13-07B 	0.05 ppm

Rhubarb 	0.05 ppm

Apple 	0.05 ppm

Okra 	0.05 ppm

	

At this time, HED is unable to recommend establishment of the proposed
tolerance for dried shelled bean (except soybean) and pea, Crop Subgroup
6C because data are required for dried pea including the forages and hay
of field pea cultivars. In addition, concomitant with the establishment
of a tolerance for Subgroup 6B, the individual tolerance for ‘bean,
snap, succulent’ should be revoked.



Table of Contents

  TOC \o "1-3" \h \z \u    HYPERLINK \l "_Toc257814908"  1.0 	EXECUTIVE
SUMMARY	  PAGEREF _Toc257814908 \h  4  

  HYPERLINK \l "_Toc257814909"  2.0	INGREDIENT PROFILE	  PAGEREF
_Toc257814909 \h  8  

  HYPERLINK \l "_Toc257814910"  2.1 	Summary of Proposed Uses	  PAGEREF
_Toc257814910 \h  8  

  HYPERLINK \l "_Toc257814911"  2.3 	Physical/Chemical Properties
Characterization	  PAGEREF _Toc257814911 \h  11  

  HYPERLINK \l "_Toc257814912"  3.0	HAZARD CHARACTERIZATION	  PAGEREF
_Toc257814912 \h  13  

  HYPERLINK \l "_Toc257814913"  3.1 	FQPA Safety Factor for Infants and
Children	  PAGEREF _Toc257814913 \h  16  

  HYPERLINK \l "_Toc257814914"  3.2	Endocrine Disruption	  PAGEREF
_Toc257814914 \h  17  

  HYPERLINK \l "_Toc257814915"  4.0 	DIETARY EXPOSURE/RISK
CHARACTERIZATION	  PAGEREF _Toc257814915 \h  18  

  HYPERLINK \l "_Toc257814916"  4.1	Pesticide Metabolism and
Environmental Degradation	  PAGEREF _Toc257814916 \h  18  

  HYPERLINK \l "_Toc257814917"  4.2	Dietary Exposure and Risk	  PAGEREF
_Toc257814917 \h  26  

  HYPERLINK \l "_Toc257814918"  5.0	RESIDENTIAL (Non-Occupational)
EXPOSURE/RISK CHARACTERIZATION	  PAGEREF _Toc257814918 \h  27  

  HYPERLINK \l "_Toc257814919"  5.1	Residential Handler Exposure	 
PAGEREF _Toc257814919 \h  28  

  HYPERLINK \l "_Toc257814920"  5.2	Residential Postapplication Exposure
  PAGEREF _Toc257814920 \h  28  

  HYPERLINK \l "_Toc257814921"  5.3	Other (Spray Drift, etc.)	  PAGEREF
_Toc257814921 \h  29  

  HYPERLINK \l "_Toc257814922"  6.0	Aggregate Risk Assessments and Risk
Characterization	  PAGEREF _Toc257814922 \h  29  

  HYPERLINK \l "_Toc257814923"  6.1	Acute Aggregate Risk	  PAGEREF
_Toc257814923 \h  29  

  HYPERLINK \l "_Toc257814924"  6.2	Short-Term Aggregate Risk	  PAGEREF
_Toc257814924 \h  30  

  HYPERLINK \l "_Toc257814925"  6.3	Intermediate-Term Aggregate Risk	 
PAGEREF _Toc257814925 \h  30  

  HYPERLINK \l "_Toc257814927"  7.0	Cumulative Risk
Characterization/Assessment	  PAGEREF _Toc257814927 \h  31  

  HYPERLINK \l "_Toc257814928"  8.0	Occupational Exposure/Risk Pathway	 
PAGEREF _Toc257814928 \h  32  

  HYPERLINK \l "_Toc257814929"  8.1	Short- and Intermediate-Term Handler
Exposure and Risk	  PAGEREF _Toc257814929 \h  32  

  HYPERLINK \l "_Toc257814930"  8.2 	Postapplication Exposure/Risk	 
PAGEREF _Toc257814930 \h  38  

  HYPERLINK \l "_Toc257814931"  8.2.1	Data and Assumptions for
Postapplication Exposure Scenarios	  PAGEREF _Toc257814931 \h  38  

  HYPERLINK \l "_Toc257814932"  8.2.2	Agricultural Post-application
Exposure and Risk	  PAGEREF _Toc257814932 \h  39  

  HYPERLINK \l "_Toc257814933"  9.0	Data Needs/Label ReCOMMENDATIONS	 
PAGEREF _Toc257814933 \h  40  

  HYPERLINK \l "_Toc257814934"  9.1	Toxicology	  PAGEREF _Toc257814934
\h  40  

  HYPERLINK \l "_Toc257814935"  9.2	Residue Chemistry	  PAGEREF
_Toc257814935 \h  40  

  HYPERLINK \l "_Toc257814936"  REFERENCES	  PAGEREF _Toc257814936 \h 
41  

  HYPERLINK \l "_Toc257814937"  Attachment A: Toxicology Profile	 
PAGEREF _Toc257814937 \h  43  

  HYPERLINK \l "_Toc257814938"  Attachment B: Rationale for Requiring
the Studies	  PAGEREF _Toc257814938 \h  46  

 1.0 	EXECUTIVE SUMMARY  TC \l1 ".1.0	Executive Summary 

Halosulfuron-methyl is a selective herbicide belonging to the
sulfonylurea group of herbicides, which inhibits the action of
acetolacetate synthase enzyme, a specific plant enzyme. 
Halosulfuron-methyl is used for the pre- and postemergence control of
annual broadleaf weeds and nutsedges in selected crops, as well as
residential turf grass and ornamentals.  It is formulated as a water
dispersible granule (WDG).    

The petitioner, Interregional Research Project No. 4 (IR-4), has
proposed new uses of halosulfuron-methyl on apple; bushberry Subgroup
13-07B; okra; succulent-shelled pea and bean Subgroup 6B; dried shelled
pea and bean, except soybean, Subgroup 6C; rhubarb; and tuberous and
corm vegetable Subgroup 1C.  In conjunction with the requested amended
use, IR-4 has submitted a petition, PP#9E7577, to propose the
establishment of permanent tolerances for residues of the herbicide
halosulfuron-methyl (methyl
3-chloro-5-[[[[(4,6-dimethoxy-2-pyrimidinyl)amino]carbonyl]amino]sulfony
l]-1-methyl-1H-pyrazole-4-carboxylate) in/on the following raw
agricultural commodities:

Pea and bean, succulent shelled, Subgroup 6B 	0.05 ppm

Vegetable, tuberous and corm, Subgroup 1C 	0.05 ppm

Pea and bean, dried shelled, except soybean, Subgroup 6C 	0.05 ppm

Bushberry, Subgroup 13-07B 	0.05 ppm

Rhubarb 	0.05 ppm

Apple 	0.05 ppm

Okra 	0.05 ppm

HED has conducted a human health risk assessment for halosulfuron-methyl
for the purpose of establishing the proposed tolerances for uses in or
on the above agricultural commodities. In addition, concomitant with the
establishment of a tolerance for Subgroup 6B, the individual tolerance
for ‘bean, snap, succulent’ should be revoked.

  SEQ CHAPTER \h \r 1 There are currently no established Codex or
Canadian maximum residues limits (MRLs) for halosulfuron-methyl.

Hazard Assessment and Dose-Response Assessment

The toxicology database is adequate to support the current petition for
establishing the proposed tolerances for uses in/on the above raw
agricultural commodities, with the exception of an immunotoxicity study
required under the new rule in 40 CFR Part 158.  This study is required
as a condition of registration for this action.  However, an additional
safety factor is not needed to account for lack of this study because
the current data suggest halosulfuron-methyl does not directly target
the immune system.

Halosulfuron-methyl has low acute toxicity via the oral, dermal, and
inhalation routes.  It is a non-irritant for skin and eyes and is not a
dermal sensitizer.  With repeated dosing, halosulfuron produces
non-specific effects, which are frequently characterized by reduced body
weight and body weight gains in the test animals.  Carcinogenicity
studies in rats and mice show no increase in treatment-related tumor
incidence, and it is classified as “not likely to be carcinogenic to
humans.”  Halosulfuron-methyl is negative for mutagenicity in a
battery of genotoxicity studies. 

Although the data indicated an increase in qualitative susceptibility in
fetuses following prenatal exposure in rats and rabbits, the
developmental effects were seen in the presence of maternal effects and
clear NOAELs and LOAELs were established for both maternal and
developmental effects.  In addition, the developmental effects in rats
were seen at doses approaching the limit dose (1000 mg/kg).  It was
concluded that the degree of concern was low and there was no residual
uncertainty in either the rat or rabbit developmental toxicity study. 
The FQPA safety factor was reduced to 1X.

The toxicity endpoints and points of departure (POD) for risk assessment
were selected for the following exposure scenarios: acute and chronic
dietary, short- and intermediate-term incidental oral, dermal and
inhalation. A summary of toxicity endpoints and points of depart is
presented in Table 3.1.  Because of a common effect (i.e., body weight
gain changes) seen in the studies selected for the endpoints for all
three routes of exposure, MOEs and exposures can be aggregated where
appropriate. The POD and toxicity endpoints for current risk assessment
are summarized in Table 1.  The level of concern (LOC) for residential
and occupational exposures via dermal and inhalation routes is for an
MOE < 100. 

Acute Dietary Exposure Estimates

An acute dietary exposure analysis for halosulfuron-methyl was conducted
using tolerance-level residues and 100 % crop treated (CT) for all
existing and recommended uses.  Estimated drinking surface water
concentrations (EDWCs) from EFED (59.2 ppb based on modeled use on rice)
were incorporated directly into the exposure analysis.  The only
population with a toxicological endpoint attributable to a single dose
of halosulfuron-methyl was females 13-49 years old.  The results of the
analysis indicate that acute risk from the dietary exposure to
halosulfuron-methyl is less than 1% of the acute population adjusted
dose (aPAD) for females 13-49 years old, and therefore does not exceed
HED’s LOC.

Chronic Dietary Exposure Estimates

A chronic dietary analysis for halosulfuron-methyl was conducted using
tolerance levels and 100% CT for all existing and recommended uses.  The
EDWC for surface water from EFED (59.2 ppb based on modeled use on rice)
was incorporated directly into the exposure analysis.  The drinking
water estimate should be considered highly conservative.  The results of
the analysis indicate that chronic risk from the dietary exposure to
halosulfuron-methyl does not exceed HED’s LOC for the general U.S.
population or any population subgroup.  The estimated risk for the
general U.S. population is 2% of the chronic PAD (cPAD), and the highest
exposure is to all infants (<1 year old) at 5% of the cPAD.

Drinking Water Assessment

Halosulfuron-methyl is a mobile and persistent compound which may reach
ground and surface waters, including those used as drinking water
sources.  The EDWCs for halosulfuron-methyl are based on a maximum
annual application rate of 0.125 lb ai/A for rice.  The two screening
models, FIRST and SCI-GROW, were used for estimating EDWCs of
halosulfuron-methyl. Estimates for halosulfuron-methyl in surface water
based on the FIRST model results for rice are 59.2 ppb for acute and
chronic concentrations.  It should be noted that the drinking water
estimate based on rice application is an upper bound estimate.  The
estimate for halosulfuron-methyl in ground water based on the SCI-GROW
model result is 0.065 ppb.

Residential Exposure Estimates

No residential uses are being requested in this petition; however,
halosulfuron-methyl is currently registered for use on residential turf
grass and ornamentals.  Short-term exposures may occur during adult
residential handling activities.  Short- and intermediate-term exposures
may occur during postapplication activities for adults and children. 
Combined MOEs for adult and children’s dermal exposure and toddler’s
incidental oral exposure from all residential activities are greater
than the LOC of 100, and therefore are not of concern.

Acute Aggregate Risk

For acute aggregate risk, drinking water estimates were incorporated
directly into the dietary analysis for female 13-49 years old. Exposure
through food and drinking water sources occupies less than 1% of the
aPAD; thus, estimated risk does not exceed HED’s level of concern.  

Short-Term Aggregate Risk

The short-term aggregate risk assessment estimates risks likely to
result from exposure to halosulfuron-methyl residues from food, drinking
water, and residential pesticide uses.  High-end estimates of
residential exposure are used, while average values are used for food
and drinking water exposure (i.e., chronic exposures).  Short-term
aggregate MOEs range from 2,800 to 4,800.  The MOE for the U.S.
Population is 4,700.  The most highly exposed subgroup is All Infants
(less than 1 year old), with a MOE of 2,800.  These estimates of
short-term aggregate risk do not exceed HED’s level of concern.

Intermediate-Term Aggregate Risk

The intermediate-term aggregate risk assessment estimates risks likely
to result from exposure to halosulfuron-methyl residues from food,
drinking water, and residential pesticide uses.  Although unlikely due
to the use pattern (no more than 4 applications to turf per season),
residential exposure was included in the intermediate-term aggregate
risk assessment.  High-end estimates of residential exposure are used,
while average values are used for food and drinking water exposure
(i.e., chronic exposures).  Intermediate-term aggregate MOEs ranged from
500 to 680.  The MOE for the U.S. Population is 500.  The most highly
exposed children’s subgroup was All Infants (less than 1 year old),
with a MOE of 680.  These estimates of aggregate risk do not exceed
HED’s level of concern.

Occupational Exposure and Risk

For occupational handlers, short- and intermediate-term exposure may
occur during mixing, loading and application.  For occupational
postapplication activities, exposure may occur over short- and
intermediate-term periods.  Chronic exposure ((6 months of continuous
exposure) is not expected.  

Agricultural Handler Risk

No chemical-specific handler exposure data were submitted in support of
this registration.  It is the policy of the HED to use data from the
Pesticide Handlers Exposure Database (PHED), Version 1.1 as presented in
PHED Surrogate Exposure Guide (8/98) to assess handler exposures for
regulatory actions when chemical-specific monitoring data are not
available (HED ExpoSAC Standard Operating Procedure (SOP) No. 7, dated
1/28/99).  Data from the Outdoor Residential Exposure Task Force (ORETF)
are also used when appropriate.

 (MOEs ≥ 100) at some level of risk mitigation.  The inhalation risk
estimates to handlers do not exceed HED’s LOC at baseline (no
respirator) for any of the handler scenarios where baseline data are
available.  The combined dermal and inhalation risks to handlers do not
exceed HED’s LOC with baseline attire (i.e., long-sleeved shirt, long
pants, shoes, and socks) where baseline data are available.  There are
no data to assess the mixing/loading/applying handgun scenario at
baseline attire.  The short- and intermediate-term combined dermal and
inhalation risks do not exceed HED’s LOC for mixing/loading/applying
with handgun equipment when baseline attire plus chemical-resistant
gloves are used. 

Agricultural Postapplication Risk

No chemical-specific dislodgeable foliar residue (DFR) data are
available for halosulfuron-methyl to assess postapplication dermal
risks.  Using the default assumption that 20% of the application rate is
retained on foliage on day 0 yields the dermal MOEs for occupational
postapplication workers on the day of application greater than 100,
demonstrating that there are minimal potential risks to workers
re-entering fields treated with postemergent applications of
halosulfuron-methyl.  Based on the use pattern, as well as the acute
toxicity of halosulfuron-methyl, the 12-hour restricted entry interval
(REI) appearing on the label is adequate. 

Recommendations for Tolerance

Pending submission of a revised Section B, a revised Section F, and 
analytical reference standards, there are no additional residue
chemistry issues that would preclude granting a Section 3 registration
for the requested uses or the establishment of a tolerance for residues
of the herbicide  halosulfuron-methyl, methyl
3-chloro-5-[[[[(4,6-dimethoxy-2-pyrimidinyl)
amino]carbonyl]amino]sulfonyl]-1-methyl-1H-pyrazole-4-carboxylate, as
follows:

Pea and bean, succulent shelled, Subgroup 6B 	0.05 ppm

Vegetable, tuberous and corm, Subgroup 1C 	0.05 ppm

Bushberry, Subgroup 13-07B 	0.05 ppm

Rhubarb 	0.05 ppm

Apple 	0.05 ppm

Okra 	0.05 ppm

At this time, HED is unable to recommend for a registration and
tolerance for dried shelled bean (except soybean) and pea, Crop Subgroup
6C because data are required for dried pea including the forages and hay
of field pea cultivars. In addition, concomitant with the establishment
of a tolerance for Subgroup 6B, the individual tolerance for ‘bean,
snap, succulent’ should be revoked.

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 PHED, the Outdoor
Residential Exposure Task Force (ORETF), and the Agricultural Reentry
Task Force (ARTF) have been determined to require a review of their
ethical conduct, and have received that review.

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 Intake by Individuals (CSFII) and are used in pesticide
risk assessments for all registered food uses of a pesticide.  These
data are analyzed and categorized by subgroups based on age, season of
the year, ethnic group, and region of the country.  Additionally, OPP is
able to assess dietary exposure to smaller, specialized subgroups and
exposure assessments are performed when conditions or circumstances
warrant.  Whenever appropriate, non-dietary exposures based on home use
of pesticide products and associated risks for adult applicators and for
toddlers, youths, and adults entering or playing on treated areas
postapplication are evaluated.  Further considerations are currently in
development as OPP has committed resources and expertise to the
development of specialized software and models that consider exposure to
bystanders and farm workers as well as lifestyle and traditional dietary
patterns among specific subgroups.

2.0	INGREDIENT PROFILE

  TC \l1 "2.0	Ingredient Profile 

2.1 	Summary of Proposed Uses

 TC \l2 "2.1	Summary of Proposed Uses 

Halosulfuron-methyl is a sulfonylurea herbicide proposed for pre- and
post-emergence control of broadleaf weeds and nutsedge. The end-use
products (EPs) relevant to this registration action are Sandea®
Herbicide (EPA Reg. No. 81880-18) and GWN-3061 Herbicide (EPA Reg. No.
81880-2).  Both products are currently registered to Gowan Company and
are classified as WDG formulations containing 75% halosulfuron-methyl.  

The petitioner, IR-4, is proposing to add the following crops to the
Sandea® Herbicide label:  apple, bushberry Subgroup 13-07B, okra,
succulent shelled pea and bean Subgroup 6B, dried shelled pea and bean
(except soybean) Subgroup 6C, rhubarb, and tuberous and corm vegetables
Subgroup 1C and also to amend the product label for GWN-3061 Herbicide
include uses on dried shelled pea and bean (except soybean) Subgroup 6C.
The proposed use patterns are presented in Table 2.1.



Table 2.1.  Proposed Use Pattern for Halosulfuron-Methyl.

Crop	Treatment Type/Target of Application	Application  Equipment	Maximum
Application Rate

(lb ai/A)	Treatment Interval	Preharvest Interval

Sandea® Herbicide, EPA Reg. No. 81880-18, WDG 75% ai

Succulent shelled peas and beans (subgroup 6B)	Ground	Groundboom	0.023
lb ai/acre	Not applicable	Not provided

Tuberous and corm vegetables (subgroup 1C)	Ground & Foliage	Groundboom
0.047 lb ai/acre	Not provided	45 days

Rhubarb	Ground	Groundboom, Handgun	0.047 lb ai/acre	Not applicable	60
days

Bushberry (subgroup 13-07B)	Ground & Foliage	Groundboom, Handgun	0.047
lb ai/acre	45 days	14 days

Dried shelled peas and beans (except soybean, subgroup 6C)

(West of Rockies)	Ground & Foliage	Groundboom, Handgun	0.047 lb ai/acre
Not applicable	30 days

Dried shelled peas and beans (except soybean, subgroup 6C)

(East of Rockies)	Ground & Foliage	Groundboom, Handgun	0.031 lb ai/acre
Not applicable	30 days

Apples

(West of Rockies)	Ground	Groundboom, Handgun	0.094 lb ai/acre	Not
provided	14 days

Apples

(East of Rockies)	Ground	Groundboom, Handgun	0.047 lb ai/acre	Not
provided	14 days

Okra	Ground	Groundboom, Handgun	0.047 lb ai/acre	Not applicable	30 days

	2.2	Directions for Use

The directions for use of halosulfuron-methyl are summarized in Table
2.2. The submitted labels for Sandea® Herbicide (EPA Reg. No. 81880-18)
and GWN-3061 Herbicide (EPA Reg. No. 81880-2) are adequate to allow
evaluation of the residue data relative to the proposed uses.  However,
the petitioner is required to	: (1) amend the proposed use directions of
Sandea® Herbicide (EPA Reg. No. 81880-18) on Crop Subgroup 6B to
prohibit applications to legumes grown for livestock feeds because no
residue data are available for cowpea forage and hay; (2) amend the
proposed use directions of Sandea® Herbicide (EPA Reg. No. 81880-18) on
Crop Subgroup 13-07B (bushberry) to remove the instructions pertaining
to the use of a non-ionic surfactant; and (3) remove the use directions
from both labels for Crop Subgroup 6C (dried pea and bean (except
soybean)).  

Table 2.2.  Summary of Directions for Use of Halosulfuron-Methyl.

Applic. Timing, Type, and Equip.	Formulation

[EPA Reg. No.]	Applic. Rate 

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

(lb ai/A)	PHI

(days)	Use Directions and Limitations

Apple; East of the Rocky Mts.

Broadcast to orchard floor; Ground

(≥15 gal/A)	75% WDG

[81880-18]	0.023-0.047	Not specified

(NS)	0.094	14	Single or sequential applications may be made on each side
of the tree row.  Use of a non-ionic surfactant (NIS) is recommended. 
Application to trees established less than one year is
prohibitedܮ䄇灰敬※敗瑳漠⁦桴⁥潒正⁹瑍⹳܇牂慯捤獡
⁴潴漠捲慨摲映潬牯※片畯摮

(≥15 gal/A)	75% WDG

[81880-18]	0.035-0.094	NS	0.094	14	Single or sequential applications may
be made on each side of the tree row.  Use of an NIS or a penetrating
type surfactant is recommended.  Application to trees established less
than one year is prohibited.

Bushberry Subgroup 13-07B

Soil broadcast; Ground

(≥15 gal/A)	75% WDG

[81880-18]	0.023-0.047	NS	0.094	14	Single or sequential applications may
be made on each side of the row with a minimum retreatment interval
(RTI) of 45 days for sequential applications.  Use of an NIS is
recommended.  Application to plants established less than one year is
prohibited.

Fruiting Vegetables Group Including But Not Limited to Eggplant, Okra,
Pepper, and Tomato

Row middle/furrow applications; Ground

(≥15 gal/A; ≥20 gal/A for okra from Section B)	75% WDG

[81880-18]	0.023-0.047	NS	0.094	30	Applications are to be made between
rows of direct-seeded or transplanted fruiting vegetables.

Pea and Bean, Succulent Shelled, Subgroup 6B 1

[Any succulent shelled cultivar of bean (Phaseolus, spp.), or immature
soybean seed (Glycine max), or any Vigna spp., and garden pea (Pisum,
spp.)] 

Preemergence; Soil broadcast; Ground

(≥15 gal/A)	75% WDG

[81880-18]	0.023	1	0.023	30	Timing is after planting but before crop
emergence.

Pea and Bean (Except Soybean), Dried Shelled, Subgroup 6C 1; East of the
Rocky Mts.

Postemergence; Broadcast or directed; Ground

(≥15 gal/A)	75% WDG

[81880-2]

[81880-18]	0.023-0.031	1	0.047 (per crop cycle)

0.094 (per year)	30	Application is to be made when plants have 2 to 4
trifoliate leaves, but before flowering.  An NIS is to be used. 
Directed sprays are recommended.

Pea and Bean (Except Soybean), Dried Shelled, Subgroup 6C; West of the
Rocky Mts.

Postemergence; Broadcast; Ground

(≥15 gal/A)	75% WDG

[81880-2]

[81880-18]	0.023-0.047	1	0.047 (per crop cycle)

0.094 (per year)	30	Application is to be made when plants have 2 to 4
trifoliate leaves, but before flowering.  An NIS is to be used. 
Directed sprays are recommended.

Rhubarb

Dormant;

Broadcast;  Ground

(≥15 gal/A)	75% WDG

[81880-18]	0.023-0.047	1	0.047	60	Application is to be made as close as
possible to breaking of dormancy.  An NIS is to be used if labeled weeds
have emerged.

Tuberous and Corm Vegetables, Subgroup 1C

[Arracacha; arrowroot; artichoke, Chinese; artichoke, Jerusalem; canna,
edible; cassava, bitter and sweet; chayote (root); chufa; dasheen
(taro); ginger; leren; potato; sweet potato; tanier; turmeric; yam bean;
yam, true]

Preemergence; Soil broadcast;  Ground

≥15 gal/A)	75% WDG

[81880-18]	0.023-0.047	2	0.047	45	First application is to be made after
planting but prior to crop emergence; if necessary, a second application
may be made 45 days before harvest.  If a second application is made, an
NIS should be used in the second application.

Postemergence

Foliar broadcast

Ground

(≥15 gal/A)

1  Individual crop uses of Sandea® Herbicide (EPA Reg. No. 81880-18)
are currently registered on succulent beans and dry beans; the
petitioner now requests uses on Subgroups 6B and 6C.  The EP, GWN-3061
Herbicide (EPA Reg. No. 81880-2), is also currently registered on
soybeans.

2.3 	Ph TC \l2 "2.2	Physical/Chemical Properites Characteriztion
ysical/Chemical Properties Characterization 

The chemical structure and nomenclature of halosulfuron-methyl and the
3-chlorosulfonamide moiety (3-CSA) are presented in Table 2.3.1.  The
physicochemical properties of the technical grade of halosulfuron-methyl
are presented in Table 2.3.2.  



Table 2.3.1.  Halosulfuron-Methyl Nomenclature.                        
                                   

Chemical structure	

Common name	halosulfuron-methyl

Company experimental name	MON 12000, NC-319

IUPAC name	methyl
3-chloro-5-(4,6-dimethoxypyrimidin-2-ylcarbamoylsulfamoyl)-1-methylpyraz
ole-4-carboxylate

CAS name	methyl
3-chloro-5-[[[[(4,6-dimethoxy-2-pyrimidinyl)amino]carbonyl]amino]sulfony
l]-1-methyl-1H-pyrazole-4-carboxylate

CAS registry number	100784-20-1

End-use product (EP)	75% WDG (GWN-3061 Herbicide; EPA Reg. No. 81880-2)

Chemical structure of

3-chlorosulfonamide moiety (3-CSA)	

3-chloro-1-methyl-5-sulfamoyl-1H-pyrazole-4-carboxylic acid

Rearrangement ester (RRE) of halosulfuron-methyl

	

Table 2.3.2.  Physicochemical Properties of Halosulfuron-Methyl.

Parameter	Value	Reference

Melting point/range	175.5-177.2 ºC	MRID 42139403; D173627 & D180565,
7/30/92, G.J. Herndon

pH	4.11 at 25 ºC (1% w/v slurry)

	Density	1.618 g/mL at 25 ºC

	Water solubility at 20 ºC	pH 5	0.0015 g/100 mL

pH 7	0.165 g/100 mL

pH 9	0.747 g/100 mL

	Solvent solubility at 20 ºC	methanol	0.1616 g/100 mL

n-hexane	0.001278 g/100 mL

	Vapor pressure	<1 x 10-7 mm Hg at 25 ºC

	Dissociation constant, Ka	3.61 x 10-4 at 22.4 ºC

	Octanol/water partition coefficient, Log(KOW) at 23 ºC	1.67 at pH 5

-0.0186 at pH 7

-0.542 at pH 9

	UV/visible absorption spectrum	Not available

	

3.0	HAZARD CHARACTERIZATION  TC \l1 "3.0 Hazard Characterization 

A detailed hazard characterization for halosulfuron-methyl is presented
in a risk assessment conducted in 2006 (DP331643, M. Rust, et al.,
9/21/06).  Briefly, the toxicology database for halosulfuron-methyl is
sufficient and of good quality.  However, recent changes to 40 CFR §158
make the immunotoxicity study (OPPTS Guideline 870.7800) required for
pesticide registration. In the absence of specific immunotoxicity
studies, HED has evaluated the available toxicity database to determine
whether an additional database uncertainty factor is needed to account
for potential immunotoxicity.  The toxicology database of this chemical
does not show any evidence of biologically relevant effects on the
immune system.  The overall weight of evidence suggests that this
chemical does not directly target the immune system.  HED does not
believe that immunotoxicity testing will result in a NOAEL less than
that (10 mg/kg/day) used to derive the current cRfD of 0.1 mg/kg/day. 
Consequently, HED believes the existing data are sufficient for endpoint
selection for exposure/risk assessment scenarios and for evaluation of
the requirements under the FQPA, and an additional database uncertainty
factor (UFDB) does not need to be applied at this time.

Halosulfuron-methyl is a member of the sulfonylurea herbicides, and it
inhibits acetolactate synthase, a specific plant enzyme not found in
mammals.  The mode of action in mammals for halosulfuron-methyl is
undetermined.  

The metabolism data indicated that with oral administration,
halosulfuron-methyl was absorbed rapidly with incomplete absorption from
the GI tracts.  Within 72 hours, the absorbed halosulfuron-methyl was
eliminated in the urine and feces.  Desmethyl NC-319 and the 5-hydroxy
derivative were the major urinary and fecal metabolites.  No tissue
retention was demonstrated.  The absorption, elimination, and metabolism
showed no sex dependence.  

Halosulfuron-methyl has low acute toxicity (Toxicity Category III-IV) by
oral, dermal, and inhalation routes of exposure.  It is not a dermal
sensitizer.  With repeated dosing, the available data show that the dog
is the most sensitive mammalian species.  In the dog, decreased body
weight was seen in the chronic oral toxicity study and decreased body
weight gain was observed in females in the subchronic oral toxicity
study.  In the rat and mouse, there was a decrease in body weight gains
at high dose levels in short- and long-term oral and dermal studies. 
The results of both acute and subchronic neurotoxicity studies showed no
neurotoxic effects.  There was no quantitative evidence for increased
susceptibility following pre- and/or post-natal exposure.  However,
there was qualitative evidence for increased susceptibility.  In the rat
study, increases in resorptions, soft tissue (dilation of the lateral
ventricles) and skeletal variations, and decreases in body weights were
seen in the fetuses compared to clinical signs and decreases in body
weights and food consumption in the maternal animals.  In the rabbit
study, increases in resorptions and post-implantation losses and
decrease in mean litter size was seen in the presence of decreases in
body weight and food consumption in maternal animals.  Thus, in both
species, the developmental effect was considered to be qualitatively
more severe than maternal effects (i.e., qualitative evidence for
susceptibility).  In both studies, there are clear NOAELs/LOAELs for
developmental and maternal toxicities, developmental effects were seen
in the presence of maternal toxicity, and the effects were only seen at
the high dose.  Additionally, in rats developmental effects were seen at
a dose which is approaching the limit-dose. The degree of concern is low
and there are no residual uncertainties for prenatal toxicity in both
rats and rabbits.  Halosulfuron-methyl is negative for mutagenicity in a
battery of genotoxicity studies. Halosulfuron-methyl is classified as
“not likely to be carcinogenic to humans” based on lack of evidence
for carcinogenicity in mice and rats following long-term dietary
administration. Cancer risk assessment will not be conducted for
halosulfuron methyl..  

The PODs and toxicity endpoints selected for various exposure scenarios
applicable to this risk assessment are summarized in Tables 3.1
(Non-Occupational) and 3.2 (Occupational). 

Table 3.1.	Toxicological Doses and Endpoints for Halosulfuron-Methyl
for Non-Occupational Human Health Risk Assessments.

Exposure/

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

Acute Dietary

(Females 13-49 years of age)	NOAEL= 50 mg/kg/day	UFA= 10x

UFH= 10x

FQPA SF= 1x	Acute RfD = 0.5 mg/kg/day

aPAD =0.5 mg/kg/day	Developmental Toxicity - Rabbit

LOAEL = 150 mg/kg/day based on decreased mean litter size, increased
number of resorptions (total and per dam) and increased postimplantation
loss (developmental toxicity).

Acute Dietary (General Population including Infants and Children)	N/A
N/A	N/A	No adverse effect attributable to a single dose was identified;
therefore, no dose/endpoint was selected for this exposure scenario.

Chronic Dietary (All Populations)	NOAEL= 10 mg/kg/day	UFA= 10x

UFH= 10x

FQPA SF= 1x 	Chronic RfD = 0.1

mg/kg/day

cPAD = 0.1 mg/kg/day	Chronic Toxicity - Dog

LOAEL = 40 mg/kg/day based on decreased body weight gains in females.

Incidental Oral Short-Term (1-30 days)	NOAEL= 50 mg/kg/day	UFA= 10x

UFH= 10x

FQPA SF= 1x 	Residential LOC for MOE = 100	Developmental Toxicity -
Rabbit

LOAEL = 150 mg/kg/day based on decreased body weight gain, food
consumption, and food efficiency  (maternal toxicity). 

Incidental Oral Intermediate-Term (1-6 months)	NOAEL= 10 mg/kg/day	UFA=
10x

UFH= 10x

FQPA SF= 1x 	Residential LOC for MOE = 100	13 Week Subchronic Toxicity -
Dog

LOAEL = 40 mg/kg/day based on decreased body weight gains and food
efficiency along with hematological and clinical chemistry changes.

Dermal Short-Term (1-30 days)	NOAEL= 100 mg/kg/day	UFA= 10x

UFH= 10x

FQPA SF= 1x 	Residential LOC for MOE = 100

	21-Day Dermal Toxicity Study - Rat

LOAEL = 1000 mg/kg/day based on decreased body weight gain in males.

Dermal Intermediate-Term (1-6 months)+	NOAEL=10 mg/kg/day	UFA= 10x

UFH= 10x

FQPA SF= 1x 	Residential LOC for MOE = 100

	13 Week Subchronic Toxicity - Dog

LOAEL = 40 mg/kg/day based on decreased body weight gains and food
efficiency along with hematological and clinical chemistry changes.

Inhalation Short- Term (1-30 days)	NOAEL = 50 mg/kg/day	UFA= 10x

UFH= 10x

FQPA SF= 1x 	Residential LOC for MOE = 100	Developmental Toxicity -
Rabbit

LOAEL = 150 mg/kg/day based on decreased body weight gain, food
consumption, and food efficiency (maternal toxicity).

Inhalation Intermediate-Term (1-6 months)	NOAEL= 10 mg/kg/day	UFA= 10x

UFH= 10x

FQPA SF= 1x 	Residential LOC for MOE = 100

	13 Week Subchronic Toxicity - Dog

LOAEL = 40 mg/kg/day based on decreased body weight gains and food
efficiency along with hematological and clinical chemistry changes.

Cancer (oral, dermal, inhalation)	Classification: "not likely to be
carcinogenic to humans" by the oral route, based on no evidence of
carcinogenicity from studies in rats and mice.

+: A 75% dermal absorption factor should be used in route-to-route
extrapolation for the intermediate term dermal exposure risk. 
Absorption via the inhalation route is presumed to be equivalent to oral
absorption.

NOAEL = no observed adverse effect level.  LOAEL = lowest observed
adverse effect level.  UF = uncertainty factor.  UFA = extrapolation
from animal to human (inter-species).  UFH = potential variation in
sensitivity among members of the human population (intra-species).  FQPA
SF = FQPA Safety Factor.  PAD = population adjusted dose (a = acute, c =
chronic).  RfD = reference dose.  MOE = margin of exposure.  LOC = level
of concern.  N/A = not applicable.

Table 3.2.	Summary of Toxicological Doses and Endpoints for
Halosulfuron-Methyl for Occupational Human Health Risk Assessments.

Exposure/

Scenario	Point of Departure

(mg/kg/day)	Uncertainty Factors	Level of Concern for Risk Assessment
Study and Toxicological Effects

Dermal Short-Term (1-30 days)	NOAEL= 100 	UFA= 10x

UFH= 10x

	Occupational LOC for MOE = 100	21-Day Dermal Toxicity Study - Rat

LOAEL = 1000 mg/kg/day based on decreased body weight gain in males.

Dermal Intermediate-Term (1-6 months)+	NOAEL=10 	UFA= 10x

UFH= 10x

 	Occupational LOC for MOE = 100	13 Week Subchronic Toxicity - Dog

LOAEL = 40 mg/kg/day based on decreased body weight gains and food
efficiency along with hematological and clinical chemistry changes.

Inhalation Short-Term (1-30 days)	NOAEL=50 	UFA= 10x

UFH= 10x

 	Occupational LOC for MOE = 100	Developmental Toxicity – Rabbit

LOAEL = 150 mg/kg/day based on decreased body weight gain, food
consumption, and food efficiency   (maternal toxicity).

Inhalation Intermediate-term (1-6 months)	NOAEL= 10 	UFA= 10x

UFH= 10x

 	Occupational LOC for MOE = 100	13 Week Subchronic Toxicity - Dog

LOAEL = 40 mg/kg/day based on decreased body weight gains and food
efficiency along with hematological and clinical chemistry changes.

Cancer (oral, dermal, inhalation)	Classification: "not likely to be
carcinogenic to humans" by the oral route, based on no evidence of
carcinogenicity from studies in rats and mice.

+: A 75% dermal absorption factor should be used in route-to-route
extrapolation for the intermediate term dermal exposure risk. 
Absorption via the inhalation route is presumed to be equivalent to oral
absorption.

NOAEL = no observed adverse effect level.  LOAEL = lowest observed
adverse effect level.  UF = uncertainty factor.  UFA = extrapolation
from animal to human (intra-species).  UFH = potential variation in
sensitivity among members of the human population (inter-species).  MOE
= margin of exposure.  LOC = level of concern.  

3.1 	FQPA Safety Factor TC \l2 "3.1	FQPA Considerations and FQPA Safety
Factor  for Infants and Children

A detailed analysis of the data supporting HED’s FQPA evaluation is
presented in a previous risk assessment (D331643, M. Rust, 9/21/06).  No
additional data have been submitted and no new policy changes have been
implemented that would change the conclusions of the 2006 risk
assessment.  With the exception of a new data requirement for an
immunotoxicity study, the conclusions regarding the FQPA Safety Factor
in the previous risk assessment are applicable to the current action and
are summarized below.

HED has determined that reliable data show it would be safe for infants
and children to reduce the FQPA safety factor to 1X.  The decision is
based on the following findings:

The adequacy of the halosulfuron-methyl data has been described in
Section 3.0.  To reiterate, the toxicity database for
halosulfuron-methyl is complete for FQPA safety evaluation and toxicity
endpoint and points of departure evaluation.  However, under the new
rule for registration an immunotoxicity study is required.  After
analysis of the database, an additional factor (UFDB) for database
uncertainty is not needed to account for the lack of this study because
the available data do not suggest that this chemical affects the immune
system.

There is no evidence of increased susceptibility of young rats in the
reproduction study with halosulfuron-methyl.  Although there is
qualitative evidence of increased susceptibility in the prenatal
developmental studies in rats and rabbits, the risk assessment team did
not identify any residual uncertainties after establishing toxicity
endpoints and uncertainty factors to be used in the risk assessment of
halosulfuron-methyl.  The degree of concern for pre-and/or post-natal
toxicity is low and there are no residual uncertainties.

There is no indication in the toxicity data which include acute and
subchronic neurotoxicity studies that halosulfuron-methyl is a
neurotoxic chemical, and there is no need for a developmental
neurotoxicity study or additional factors (UFs) to account for
neurotoxicity.

4.	There are no residual uncertainties identified in the exposure
databases.  The dietary food exposure assessments were performed based
on 100% CT  and  tolerance-level residues, and conservative (protective)
assumptions in the ground water and surface water modeling were used to
assess exposure to halosulfuron-methyl in drinking water. Similarly
conservative assumptions were also used to assess post-application
exposure of children as well as incidental oral exposure of toddlers.
These assessments will not underestimate the exposure and risks posed by
halosulfuron-methyl.

3.2	Endocrine Disruption

As required under FFDCA section 408(p), EPA has developed the Endocrine
Disruptor Screening Program (EDSP) to determine whether certain
substances (including pesticide active and other ingredients) may have
an effect in humans or wildlife similar to an effect produced by a
“naturally occurring estrogen, or other such endocrine effects as the
Administrator may designate.”  The EDSP employs a two-tiered approach
to making the statutorily required determinations. Tier 1 consists of a
battery of 11 screening assays to identify the potential of a chemical
substance to interact with the estrogen, androgen, or thyroid (E, A, or
T) hormonal systems.  Chemicals that go through Tier 1 screening and are
found to have the potential to interact with E, A, or T hormonal systems
will proceed to the next stage of the EDSP where EPA will determine
which, if any, of the Tier 2 tests are necessary based on the available
data. Tier 2 testing is designed to identify any adverse endocrine
related effects caused by the substance, and establish a quantitative
relationship between the dose and the E, A, or T effect.

Between October 2009 and February 2010, EPA issued test orders/data
call-ins for the first group of 67 chemicals, which contains 58
pesticide active ingredients and 9 inert ingredients.  This list of
chemicals was selected based on the potential for human exposure through
pathways such as food and water, residential activity, and certain
post-application agricultural scenarios.  This list should not be
construed as a list of known or likely endocrine disruptors.

Halosulfuron-methyl is not among the group of 58 pesticide active
ingredients on the initial list to be screened under the EDSP.  Under
FFDCA sec. 408(p) the Agency must screen all pesticide chemicals. 
Accordingly, EPA anticipates issuing future EDSP orders/data call-ins
for all Registration Review cases, including those for which EPA has
already opened a Registration Review docket for a pesticide active
ingredient. 

For further information on the status of the EDSP, the policies and
procedures, the list of 67 chemicals, the test guidelines and the Tier 1
screening battery, please visit our website:  http://www.epa.gov/endo/.

4.0 	DIETARY EXPOSURE/RISK CHARACTERIZATION  TC \l1 "4.0	Dietary
Exposure/Risk Characterization 

4.1	Pesticide Metabolism and Environmental Degradation

Nature of the Residue - Plants

The nature of the residue in plants is adequately understood based on
acceptable metabolism studies reflecting pre- and postemergence modes of
applications on corn, sugarcane, and soybean.  The metabolism of
halosulfuron-methyl was similar in the three tested crops but dependent
on the mode of application.  When halosulfuron-methyl was applied
preemergence, initial breakdown of the herbicide in the soil and
preferential uptake of the pyrazole moieties resulted in the primary
residue being 3-chlorosulfonamide (3-CSA), which has been determined to
be less toxic than the parent.  With a postemergence application, the
major residue was the parent compound with minimal translocation of the
herbicide in the plant, except in grain where the major residue was
3-CSA. 

  SEQ CHAPTER \h \r 1 Based on the very low toxicity of the metabolite
3-CSA, relatively low toxicity of the parent compound, and low residue
levels of both parent compound and the 3-CSA metabolite, HED has
concluded that the residue of concern in plants is the parent compound,
halosulfuron-methyl.

 

Nature of the Residue - Livestock

Acceptable livestock metabolism studies conducted on goats and hens were
previously submitted in conjunction with petitions for uses on corn and
sorghum.  In goat milk and tissues, the major extractable residue was
the parent; acid hydrolysis released bound or conjugated residues of
aminopyrimidine and 3-CSA.  HED has concluded that the residue of
concern in ruminants is halosulfuron-methyl; however, because the
approved enforcement method for livestock commodities quantifies the
parent compound and metabolites containing the 3-CSA moiety by
converting residues to 3-CSA, tolerances for residues in livestock
commodities are expressed in terms of halosulfuron-methyl and its
metabolites determined as 3-CSA, expressed as halosulfuron-methyl
equivalents.  

There are no poultry feedstuffs associated with the recommended
tolerances and crop uses addressed in this action.  In addition, Due to
low use rates, low residue levels of halosulfuron-methyl in poultry feed
items, and the low transfer rate of residues to poultry tissues,
tolerances for halosulfuron-methyl residues in poultry commodities are
not required (PP# 2G4073, G. J. Herndon, 3/8/94). Therefore, a
discussion of the metabolism of halosulfuron-methyl in poultry is not
needed in this action.  

Residue Analytical Methods

Plants: The residue analytical methods data are adequate to satisfy data
requirements for the subject action.  An acceptable residue analytical
method (GC) is available for tolerance enforcement purposes for residues
in/on crop commodities (i.e., Monsanto Analytical Method RES-109-97-4
(MRID 44495801)).  Residues of halosulfuron-methyl in/on the crop
commodities from the magnitude of the residue studies were determined
using an acceptable data collection method. Residue in plants were
analyzed as the RRE of halosulfuron-methyl (structure is shown in Table
2.3.1).

Livestock: An adequate analytical method is available for enforcement of
tolerances for secondary residues of halosulfuron-methyl in livestock
commodities.  The method (GC) has been validated as an enforcement
method by the Analytical Chemistry Branch (ACB)/BEAD at a limit of
quantification of 0.01 ppm in milk and liver (D. Swineford, 4/28/95).

Multiresidue Methods

Adequate multiresidue method data for halosulfuron-methyl and 3-CSA were
submitted previously in conjunction with PP#3F4193 (D189198, G.J.
Herndon, 3/8/94).  Residues of halosulfuron-methyl and 3-CSA are not
recoverable by the FDA Multiresidue Protocols A through E.  The results
have been forwarded to FDA.  

Additional Reference Standards

As indicated in the most recent risk assessment (D358031, W. Phang,
6/30/09), the registrant must submit analytical reference standards for
the 3-CSA (3-chlorosulfonamide acid) metabolite and the rearrangement
ester (RRE) of halosulfuron-methyl to the EPA National Pesticide
Standards Repository.

Storage Stability

Adequate storage stability data are available to support the storage
conditions and durations of samples collected from the magnitude of the
residue and processing studies on apples, blueberry, dry bean seed,
succulent pea seed, potato tuber, potato processed commodities, and
rhubarb.  As residues of halosulfuron-methyl have been found to be
stable in tested crop matrices, which are representative of the
currently proposed crops proposed crops, storage stability corrections
need not be applied to the recommended tolerances for
halosulfuron-methyl residues in this action. 

Meat, Milk, Poultry, and Eggs

The livestock feedstuffs derived from registered and proposed uses would
not significantly increase the dietary burdens of halosulfuron-methyl to
beef and dairy cattle provided the petitioner amends the proposed use
directions of Sandea® Herbicide on Crop Subgroup 6B to prohibit
applications to legumes grown for livestock feeds.  The available dairy
cattle feeding study is adequate, and HED concludes that tolerances for
halosulfuron-methyl residues of concern need not be established for the
milk, meat, and fat of cattle, goat, hog, horse, and sheep.  The
established tolerances of 0.1 ppm for the meat byproducts of cattle,
goat, hog, horse, and sheep remain adequate.  There are no poultry and
swine feedstuffs associated with the recommended tolerances and crop
uses.  The petitioner should note that if additional uses are proposed
in the future which would result in an increase in the dietary burdens,
HED will re-assess the adequacy of established animal tolerances.

Crop Field Trials

IR-4 has submitted magnitude of the residue studies on apples,
blueberry, dry bean, succulent pea, potato, and rhubarb.    SEQ CHAPTER
\h \r 1 The results from these field trials are discussed below and the
residue data are summarized in Table 4.1.2.

Table 4.1.2.   Summary of Residue Data from Crop Field Trials with
Halosulfuron-Methyl. 

Crop Matrix	Total Applic. Rate

(lb ai/A)	PHI (days)	Residues of Halosulfuron-methyl (ppm)

	n	Min.	Max.	HAFT1	Median	Mean	Std. Dev.

Apple

(proposed use = 0.094 lb ai/A total application rate, 14-day PHI)

Apple (fruit)	0.092-0.104	13-14	26	<0.05a	<0.05	<0.05	0.05	0.05	--

Bushberry Subgroup 13-07B

(proposed use = 0.094 lb ai/A total application rate, 14-day PHI)

Blueberry (fruit)	0.093-0.099	13-14	12	<0.05	<0.05	<0.05	0.05	0.05	--

Okra

(proposed use = 0.094 lb ai/A total application rate, 30-day PHI)

Okra 	No okra data were submitted.

Pea and Bean, Succulent Shelled, Subgroup 6B

(proposed use = 0.023 lb ai/A total application rate, 30-day PHI)

Pea seed	0.032	55-68	4	<0.05	<0.05	<0.05	0.05	0.05	--

	0.060-0.070	55-72; 1662	18	<0.05	<0.05	<0.05	0.05	0.05	--

Pea seed in pods	0.065-0.066	69-77	6	<0.05	<0.05	<0.05	0.05	0.05	--

Pea and Bean (Except Soybean), Dried Shelled, Subgroup 6C

(proposed use = 0.047 lb ai/A total application rate per crop cycle and
0.094 lb ai/A total application rate per year, 30-day PHI)

Dry bean seed	0.061-0.075	27-31	24	<0.05	<0.05	<0.05	0.05	0.05	--

Rhubarb

(proposed use = 0.047 lb ai/A total application rate, 60-day PHI)

Rhubarb petiole	0.093-0.101	61-78	8	<0.05	<0.05	<0.05	0.05	0.05	--

Tuberous and Corm Vegetables, Subgroup 1C

(proposed use = 0.047 lb ai/A total application rate, 45-day PHI)

Potato tuber	0.094-0.103	42-46	28	<0.05	<0.05	<0.05	0.05	0.05	--

a LOQ = 0.05 ppm

Apple

The submitted field trial data for halosulfuron-methyl on apples are
adequate with regard to the number (13) and locations (6 regions) of
field trials.  The application rate and PHI reflect the proposed use
pattern, and the data are supported by concurrent storage stability
data.  Although the apple data did not reflect the use of a nonionic
surfactant as recommended on the proposed label, this is not an issue as
the application is directed to the orchard floor and presence/absence of
surfactant is not expected to change the residue level on the apple
fruit.  The available data will support the proposed tolerance of 0.05
ppm for apple.  

Bushberry Subgroup 13-07B

The submitted field trial data for halosulfuron-methyl on blueberries
and the representative commodity of Crop Subgroup 13-07B are adequate
with regards to the number and location of field trials.  The number of
field trials is a 25% reduction of the OPPTS 860.1500 guidance; this
number is considered sufficient to support the Subgroup 13-07B tolerance
based on the lack of quantifiable residues. The application rate and PHI
reflect the proposed use pattern, and the data are supported by
concurrent storage stability data.  However, the blueberry data did not
reflect the use of a nonionic surfactant as recommended on the proposed
label.  The blueberry data support the proposed tolerance of 0.05 ppm
for the bushberry Subgroup 13-07B provided the label for Sandea®
Herbicide is amended to remove the instructions pertaining to the use of
a non-ionic surfactant on crops belonging to the Subgroup 13-07B.  If it
is IR-4’s intention to add a nonionic surfactant when Sandea®
Herbicide is applied on Subgroup 13-07B, then additional field trial
data are required.  Although the spray is directed to the rows between
blueberry bushes, there is a finite possibility of the spray contacting
the bushes, and the presence/absence of surfactant might impact the
residue on the blueberries.

  

Okra

No residue data were submitted to support the proposed use on okra. 
Okra was listed by the petitioner in its proposed labels as part of the
fruiting vegetables crop group.  The ChemSAC meeting of 10/18/2006 has
recommended the inclusion of okra in Crop Group 8 (fruiting vegetables).
 The ChemSAC has also determined that a separate tolerance for okra
should be listed in the appropriate section of the CFR entry until the
new crop group regulation is published.

A tolerance of 0.05 ppm for residues of halosulfuron-methyl has been
established on the fruiting vegetable Crop Group 8 based on field trial
data for tomato and pepper (D267423, A. Acierto, 4/25/2002).  The
available field trial data for fruiting vegetables will be translated to
okra.  HED recommends for the establishment of a tolerance of 0.05 ppm
for residues of halosulfuron-methyl in/on okra.  This recommendation is
identical to the level proposed by the petitioner.

Pea and Bean, Succulent Shelled, Subgroup 6B

The representative crops of Subgroup 6B are any succulent shelled
cultivar of bean (Phaseolus spp.) and garden pea (Pisum spp.).  IR-4 has
submitted field trial data for halosulfuron-methyl on succulent shelled
and edible podded peas from 12 field trials conducted in the United
States during the 2003-2004 growing seasons.  The field trial data for
succulent peas do not fully support the proposed use pattern because the
trials were conducted at exaggerated rates (1.4X or 2.8X) and the
collected samples did not reflect the proposed 30-day PHI (the earliest
PHI tested was 55 days).  The available data for succulent beans,
previously submitted under PP#1E06322 (D278587, A. Acierto, 6/15/2002)
to support the established individual tolerance of 0.05 ppm, also do not
reflect the proposed use on Subgroup 6B because these data represent
foliar application whereas the new proposed use pattern is for
preemergence soil application.  

HED will not require additional data on succulent peas since treatment
at 1X will likely result in residues below 0.05 ppm, even when harvested
at a PHI of 30-days.  HED also will not require additional data on
succulent beans since soil treatment will likely result in residues
below 0.05 ppm.  HED recommends for the proposed tolerance of 0.05 ppm
for the Subgroup 6B (pea and bean, succulent shelled).  Concomitant with
the establishment of a tolerance for Subgroup 6B, the individual
tolerance for ‘bean, snap, succulent’ should be revoked.

Pea and Bean (Except Soybean), Dried Shelled, Subgroup 6C

The representative commodities of Subgroup 6C are any one dried cultivar
of bean (Phaseolus spp.) and any one dried cultivar of pea (Pisum spp.) 
The submitted residue data for dry bean are adequate with regard to
geographic representation of data; the data are supported by concurrent
storage stability data.  The dry bean data from the current submission
reflect a single foliar broadcast application conducted at ~1.6X the
proposed application rate per crop cycle (or ~0.8X the proposed total
application rate per year), the use of a nonionic surfactant, and an
approximate       30-day PHI.  Additional data for dry beans were
submitted under PP#1E06322 (DP#278587, A. Acierto, 6/15/2002) to support
the established individual tolerance of 0.05 ppm.  These data represent
a single application of Permit 75 WDG Herbicide at 0.032 lb ai/A made 0
to 6 days after planting and a 86- to 113-day PHI.

HED is unable to recommend for the proposed tolerance of 0.05 ppm for
Crop Subgroup 6C (Dried Shelled Bean (Except Soybean) and Pea) at this
time because residue data on dried pea including the forages and hay of
field pea cultivars are required.  When adequate residue data for dried
peas become available, the petitioner may again request a tolerance for
Subgroup 6C.  A revised Section F should be submitted removing the
request for Crop Subgroup 6C (dried shelled pea and bean (except
soybean)).

Rhubarb

The submitted field trial data for halosulfuron-methyl on rhubarb are
adequate with regard to the number and location of field trials.  The
data also reflected the use of nonionic surfactant as recommended on the
proposed label, samples were collected at appropriate PHI, and were
supported by concurrent storage stability data.  However, the rhubarb
data were generated using slightly exaggerated rates of ~2.0-2.1X.  At
this time, HED does not require additional data on rhubarb since
treatment at 1X is likely to yield residues below 0.05 ppm.  The
available data are supportive of the proposed tolerance of 0.05 ppm for
rhubarb.

Tuberous and Corm Vegetables, Subgroup 1C

The submitted field trial data for halosulfuron-methyl on potato, the
representative commodity of Crop Subgroup 1C, reflect the use of a
nonionic surfactant as recommended on the proposed label and approximate
the proposed PHI.  The data are also supported by concurrent storage
stability data.  The number and location of field trials do not fully
conform to the OPPTS 860.1500 guideline; however, all the residue level
were below the LOQ when conducted at the exaggerated use rates.
Therefore, HED is not requesting additional field trials. The available
data support the proposed use pattern, and HED recommends for a
tolerance of 0.05 ppm for Crop Subgroup 1C.

Processed Food and Feed

Apple

An additional plot was established at the NJ site using a total seasonal
rate of 0.484 lb ai/A (~5.1X the proposed maximum seasonal rate), to
generate samples for processing; however, residues were not detectable
in any apple fruit sample. An apple processing study and tolerances for
apple processed commodities are not required for this action.

Potato

The submitted processing data for potato are acceptable.  Residues of
halosulfuron-methyl were nonquantifiable (<0.05 ppm) in/on potato tubers
following treatments at 2X the proposed seasonal rate.  Residues were
also nonquantifiable in processed potato granules/flakes, chips, and wet
peel.  The Agency would have preferred that a trial with an exaggerated
rate equal to or higher than the maximum theoretical concentration
factor of 5X for potato have been conducted.  However, because of
phytotoxicity limitations as reported in the magnitude of the residue
trials, a new potato processing study will not be required.  Based on
these data, tolerances for potato processed commodities are not needed.

Confined/Field Accumulation in Rotational Crops

Acceptable confined rotational and limited field rotational crop studies
were previously submitted and reviewed (D188144 & 188814, G.J. Herndon,
3/11/93; D192510,G.F. Kramer, 8/30/93).  The results of these studies
indicate that metabolites containing the pyrazole moiety may accumulate
in harvested crops planted at intervals greater than one year.  The
confined rotational crop study, conducted at 0.19 lb ai/A, indicated
that no measurable residues of halosulfuron-methyl were detected in any
rotational crop commodities of wheat, soybean, radish and lettuce at any
plantback interval (30, 120, and 360 days after treatment).  The limited
field rotational crop study, conducted at 0.22 lb ai/A in a split
(preplant + postemergence) application, with rotated crops of winter
wheat, spring wheat, soybean, sugar beet, and leaf lettuce indicated
that no measurable residues of halosulfuron-methyl were detected in any
field rotational crop samples, except in one spring wheat forage sample
at 0.090 ppm (364-day plantback interval).  

HED previously concluded that the residue of concern in rotational crops
is halosulfuron-methyl (D225273, G.J. Herndon, 10/29/98).  Based on the
absence of the parent compound in the confined studies and in the
limited field rotational crop studies, with the exception of one forage
sample, HED also concluded that rotational crop tolerances and
restrictions are not required for halosulfuron-methyl.  

The proposed uses on okra, pea and bean (succulent shelled and dried),
tuberous and corm vegetables, and rhubarb are not expected to alter
HED’s earlier assessment regarding the potential for inadvertent
residues in rotatable crops addressed in this registration action.  No
additional data are required.  

Proposed Tolerances

Halosulfuron-methyl tolerances for plant commodities have been
established in 40 CFR §180.479(a)(2) and are expressed in terms of
halosulfuron-methyl, methyl
5-[(4,6-dimethoxy-2-pyrimidinyl)amino]carbonylaminosulfonyl-3-chloro-1-m
ethyl-1H-pyrazole-4-carboxylate.  The proposed tolerance expression is
consistent with the halosulfuron-methyl tolerances established in 40 CFR
§180.479(a)(2) and reflect the residues of concern as previously
determined by HED.

Halosulfuron-methyl tolerances for livestock commodities are listed in
40 CFR §180.479(a)(1) and are expressed in terms of   SEQ CHAPTER \h \r
1 halosulfuron-methyl and its metabolites determined as
3-chloro-1-methyl-5-sulfamoylpyrazole-4-carboxylic acid (also referred
to as 3-CSA, expressed as parent equivalents). Residues of
halosulfuron-methyl were below the LOQ of 0.05 ppm, when the test
formulation was applied to the proposed crops according to the
conditions and parameters used in the field trials.  

Table 4.1.4 presents the proposed/recommended tolerance levels and
corrected commodity definition.  HED is currently unable to recommend
for a registration and tolerance for Crop Subgroup 6C (dried shelled
bean (except soybean) and pea) because data are required for dried pea
including the forages and hay of field pea cultivars.  When adequate
residue data for dried peas become available, the petitioner may again
request a tolerance for Subgroup 6C.

Table 4.1.4.    Tolerance Summary for Halosulfuron-Methyl.

Commodity (as Defined in Section F)	Proposed Tolerance (ppm)	Recommended
Tolerance (ppm)	Comments; Correct Commodity Definition

PEA AND BEAN, SUCCULENT SHELLED, SUBGROUP 6B	0.05	0.05	HED recommends a
label revision to prohibit applications to legumes grown for livestock
feeds because no residue data are available for cowpea forage and hay.

Pea and bean, succulent shelled, subgroup 6B

VEGETABLE TUBEROUS AND CORM, SUBGROUP 1C	0.05	0.05	Vegetable, tuberous
and corm, subgroup 1C

RHUBARB	0.05	0.05	Rhubarb

PEA AND BEAN, DRIED SHELLED, EXCEPT SOYBEAN, SUBGROUP 6C	0.05	None
Revised Section F.  When adequate residue data for dried peas become
available, the petitioner may again request a tolerance for Subgroup 6C.

Pea and bean, dried shelled, except soybean, subgroup 6C

APPLE	0.05	0.05	The proposed label should be amended to remove the
instructions pertaining to the use of a non-ionic surfactant.

Apple

OKRA	0.05	0.05	The recommended tolerance is based on translation of data
from fruiting vegetables.

Okra

BUSHBERRY SUBGROUP 13-07B	0.05	0.05	The proposed label should be amended
to remove the instructions pertaining to the use of a non-ionic
surfactant.

Bushberry subgroup 13-07B

International Residue Limits

There are no Codex or Canadian maximum residue limits (MRLs )
established for residues of halosulfuron-methyl in/on crop or livestock
commodities Table 4.1.5.



Table 4.1.5. INTERNATIONAL RESIDUE LIMIT STATUS

Chemical Name:  methyl
5-[(4,6-dimethoxy-2-pyrimidinyl)amino]carbonylaminosulfonyl-3-chloro-1-m
ethyl-1H-pyrazole-4-carboxylate	Common Name:

Halosulfuron-methyl

	X   Proposed tolerance

□    Reevaluated tolerance

□    Other	Date:  10/2009

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

X No Codex proposal step 6 or above

□ No Codex proposal step 6 or above for the crops requested	Petition
Number:  PP#9E7577

DP#:  367058

Other Identifier:  

Residue definition (step 8/CXL): N/A	Reviewer/Branch:  P. Deschamp, N.
Dodd/RAB3

	Residue definition:  halosulfuron-methyl

Crop (s)	MRL (mg/kg)	Crop(s) 	Tolerance (ppm)

Pea and bean, succulent shelled, Subgroup 6B	0.05

Vegetable, tuberous and corm, Subgroup 1C	0.05

Rhubarb	0.05

Pea and bean, dried shelled, except soybean, Subgroup 6C	0.05

Apple	0.05

Okra	0.05

Bushberry, Subgroup 13-07B	0.05

Limits for Canada	Limits for Mexico

X No Limits

□ No Limits for the crops requested	X No Limits

□ No Limits for the crops requested

Residue definition:  N/A

	Residue definition:  N/A

Mexico defers to Codex MRLs or US tolerances for its export purposes.

Crop(s)	MRL (mg/kg)	Crop(s)	MRL (mg/kg)

	Notes/Special Instructions:  S. Funk, 10/15/2009.

Drinking Water Residue Profile  

The drinking water residues used in the dietary risk assessment were
provided by EFED in the following memorandum: “Halosulfuron-methyl
Drinking Water Assessment for Additional Food Uses (including Proposed
Use on Soybean)” (D358032, M. Barrett, 5/27/2009) and incorporated
directly into this dietary assessment.  Water residues were incorporated
in the DEEM-FCID into the food categories “water, direct, all
sources” and “water, indirect, all sources.”  Since the
application rates associated with the proposed new uses did not exceed
the application rate on rice (0.125 lb ai/A), a new drinking water
assessment was not required for this dietary analysis.         

The Tier I EDWCs for halosulfuron-methyl are based on a maximum annual
application rate of 0.125 lb ai/A for rice.  The two screening models,
FQPA Index Reservoir Screening Tool (FIRST)  and Screening Concentration
in Ground Water (SCI-GROW), were used for estimating EDWCs of
halosulfuron-methyl.  Estimates for halosulfuron-methyl in surface water
based on the FIRST model results for rice are 59.2 ppb for acute and
chronic concentrations.  It should be noted that the drinking water
estimate based on rice application is an upper bound estimate.  The
estimate for halosulfuron-methyl in groundwater based on the SCI-GROW
model result is 0.065 ppb. The results are summarized in Table 4.1.6.

Table 4.1.6. 	Summary of Estimated Surface Water and Groundwater
Concentrations for Halosulfuron-Methyl.

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

Acute	59.2	0.065

Chronic (non-cancer)	59.2	0.065

a From the FIRST model.  

b From the SCI-GROW model.

4.2	Dietary Exposure and Risk

 

Database DEEM-FCID™, Version 2.03, which incorporates consumption data
from USDA’s Continuing Surveys of Food Intakes by Individuals (CSFII),
1994-1996 and 1998.  

Acute Dietary Exposure/Risk

For acute dietary analysis, exposure assessment was conducted using
tolerance levels and 100 %CT for all existing and proposed uses.  EDWCs
from EFED were incorporated directly into the exposure analysis.  The
only population with a toxicological endpoint attributable to a single
dose of halosulfuron-methyl is identified to be females 13-49 yrs old. 
The results of the analysis indicate that acute risk from the dietary
exposure to halosulfuron-methyl did not exceed HED’s level of concern
for females 13-49 yrs old at less than 1% of the aPAD (Table 4.2.1).

Chronic Dietary Exposure/Risk

For chronic dietary exposure assessment, an estimate of the residue
level in each food or food-form (e.g., orange or orange juice) on the
food commodity residue list is multiplied by the average daily
consumption estimate for that food/food form to produce a residue intake
estimate.  The resulting residue intake estimate for each food/food form
is summed with the residue intake estimates for all other food/food
forms on the commodity residue list to arrive at the total average
estimated exposure.  Exposure is expressed in mg/kg body weight/day and
as a percent of the cPAD.  This procedure is performed for each
population subgroup. The results are summarized in Table 4.2.1.  The
results show that the chronic dietary (food and drinking water) exposure
to halosulfuron-methyl is below HED’s level of concern for the general
U.S. population and all population subgroups.  The chronic dietary risk
estimates are 2% of the cPAD for the general U.S. population and 5% of
the cPAD for all infants (<1 year old), the most highly exposed
population subgroup.

Table 4.2.1.  Summary of Dietary Exposure and Risk for
Halosulfuron-Methyl.  

Population Subgroup	Acute Dietary 

(95th Percentile)	Chronic Dietary

	Dietary Exposure (mg/kg/day)	% aPAD	Dietary Exposure

(mg/kg/day)	% cPAD

General U.S. Population	N/A	N/A	0.001705	2

All Infants (< 1 year old)

	0.005059	5

Children 1-2 years old

	0.003157	3

Children 3-5 years old

	0.002823	3

Children 6-12 years old

	0.001859	2

Youth 13-19 years old

	0.001327	1

Adults 20-49 years old

	0.001511	2

Adults 50+ years old

	0.001558	2

Females 13-49 years old	0.003401	<1	0.001503	2

The population subgroup with the highest estimated exposure/risk is
bolded.

5.0	RESIDENTIAL (Non-Occupational) EXPOSURE/RISK CHARACTERIZATION  TC
\l1 "5.0	Residential (Non-Occupational) Exposure/Risk Characterization 

The current petition focuses on the proposed agricultural use of
halosulfuron-methyl on succulent shelled pea and bean, tuberous and corn
vegetables subgroup dried shelled pea and bean (except soybean),
bushberry, okra, apples, and rhubarb; no residential uses are being
requested.  However, some halosulfuron-methyl labels permit application
to commercial and residential turf and on other non-crop sites including
airports, cemeteries, fallow areas, golf courses, landscaped areas,
public recreation areas, residential property, road sides, school
grounds, sod or turf seed farms, sports fields, landscaped areas with
established woody ornamentals and other similar use sites.  Such
residential handler and postapplication exposures were previously
assessed (D331643, M. Rust, 9/21/2006).  A major portion of that
residential assessment is reproduced in this document for the purposes
of conducting the aggregate exposure and risk assessment.

A product containing halosulfuron-methyl, Manage® (EPA Reg No.
524-465), which contains 75% halosulfuron-methyl, is currently
registered for application to commercial and residential turf and other
non-crop sites including airports, cemeteries, fallow areas, golf
courses, landscaped areas, public recreation areas, residential
property, road sides, school grounds, sod or turf seed farms, sports
fields, landscaped areas with established woody ornamentals and other
similar use sites.  Manage® may be applied by homeowners or commercial
applicators at a rate of 0.031 to 0.062 lb ai/acre.  No more than 4
applications may be made per use season, for a maximum total use rate of
0.125 lb ai/A per season.

Residential handlers may receive short-term dermal and inhalation
exposure to halosulfuron-methyl when mixing, loading and applying the
formulations.  Adults and children may be exposed to halosulfuron-methyl
residues through dermal contact with turf during postapplication
activities.  In addition, toddlers may receive short- and
intermediate-term oral exposure from incidental ingestion during
postapplication activities.  A residential exposure and risk assessment
was previously conducted for these exposure scenarios (D278588, K.
O’Rourke, 8/28/02) and is summarized in the following sections	 TC \l2
"5.1.	Residential  Handler Exposure 

5.1	Residential Handler Exposure

No chemical-specific exposure data for handler activities were submitted
to HED in support of the registered lawn uses.  HED’s Draft Standard
Operating Procedures (SOPs) for Residential Exposure Assessments, and
Recommended Revisions (HED Policy Number 11, revised 22 Feb 2001), were
used as the basis for the residential handler exposure calculations. 
The handler exposure data used in this assessment are from the Outdoor
Residential Exposure Task Force (ORETF) (MRID 44972201).  The ORETF data
were used in this assessment in place of PHED data for the garden
hose-end sprayer scenario.  The ORETF data were designed to replace the
present PHED data with higher-confidence, higher quality data that
contain more replicates than the PHED data for those scenarios.  The
upper-bound risk estimate for residential handlers and post-application
exposure is a MOE of 5,200 (Table 5.1), and it is not of risk concern. 

Table 5.1.  Adult’s Combined Exposure and Risk Estimates from
Residential Lawns.

Adult’s

Scenario

	

Exposure

Route	

 Rate

(lb ai/

acre) 	

Acres Treated

(acres/

day)	

PHED 

Unit Exposure

(mg/lb ai) 	

Short-term Daily

Dose 

(mg/kg/day)	

Short-term

 MOE1	

Total

 MOE2

1.  Mix/load and broadcast application of liquid formulation (garden
hose-end sprayer)	

dermal	

0.062	

0.5	

30	

0.0043	

23,000	5,200

	

inhalation

	

0.016	

0.0000071	

7,000,000

	

2.  Postapplication exposure	

dermal	

0.062	

N/A	

N/A	

0.014	

7,000

	1. Short-term dermal NOAEL = 100 mg/kg/day; Short-term inhalation NOAEL
= 50 mg/kg/day.

2. Total MOE = dermal + inhalation exposure from both handler and
post-application activities; Total MOE=1/(1/dermal MOE+1/inhalation MOE)

5.2	Residential Postapplication Exposure TC \l2 "5.2.	Residential 
Postapplication Exposure 

The following postapplication exposure scenarios resulting from lawn
treatment were assessed: (1) adult and children 3 to <6 years old
post-application dermal exposure, (2) child 3 to <6 years old incidental
ingestion of pesticide residues on lawns from hand-to-mouth transfer,
(3) toddlers’ object-to-mouth transfer from mouthing of
pesticide-treated turf grass, and (4) children 3 to <6 years old
incidental ingestion of soil from pesticide-treated residential areas. 
Post-application exposures from various activities following lawn
treatment are considered to be the most common and significant in
residential settings.  The exposure via incidental ingestion of other
plant material may occur but is considered negligible. 

The exposure and risk estimates for the residential exposure scenarios
are assessed for the day of application (day “0") because it is
assumed that adults and child 3 to <6 years old could contact the lawn
immediately after application.  Both short- and intermediate-term
exposure is expected.  Dermal postapplication risk was assessed by
comparing the dermal exposure values to the NOAELs of 100 mg/kg/day and
10 mg/kg/day, respectively.  Risk from short-and intermediate-term
incidental ingestion by child 3 to <6 years old is assessed by comparing
these exposures to the NOAELs of 50 mg/kg/day and 10 mg/kg/day,
respectively.  

Both short-term and intermediate-term MOEs for each scenario are above
the LOC of 100, and are not of concern.  As mentioned previously, a
common effect (i.e., decreased body weight gain) was observed in the
studies selected for the endpoints for all routes of exposure;
therefore, MOEs are to be combined where appropriate.  The Total MOEs
resulting from the combined MOEs for adults (summarized in Table 5.1
above) and children (summarized in Table 5.2), are also above the LOC of
100, and not of concern. 

	Table 5.2..  Children’s Combined Exposure and Risk Estimates from
Residential Lawns.

Children’s Scenarios	

TTR/GR/SR0 (ug/cm2 or g) 1	

Short-Term

PDR0-norm

(mg/kg/day)	

Int-Term

PDR0-norm

(mg/kg/day)	

Short-Term

 MOE	

Int-term

MOE	

Total

Short-Term

 MOE	

Total

Int-term

MOE

(1) Dermal Contact	

0.035	

0.024	

0.0090	

4,200	

1,100	3,800	1,000

(2) Hand-to-Mouth	

0.035	

0.00093	

0.00044	

54,000	

23,000

(3) Mouthing Grass	

0.14	

0.00023	

0.00023	

220,000	

43,000

(4) Soil Ingestion	

0.47	

3.1E-6	

3.1E-6	

16,000,000	

3,200,000

1. TTR=turf transferable residue on day “0"; GR=grass residue on day
“0"; SR0=soil residue on day “0"; Int=intermediate.

5.3	Other (Spray Drift, etc.) TC \l2 "5.3	Other (Spray Drift, etc.) 

Recreational exposures to turf are expected to be similar to, or in many
cases less than, those evaluated in Section 5.2, Residential
Post-application Exposure; therefore, a separate recreational exposure
assessment was not included.

Spray drift is always a potential source of exposure to residents nearby
to spraying operations.  This is particularly the case with aerial
applications, but, to a lesser extent, could also be a potential source
of exposure from ground application methods.  As indicated in this
assessment, halosulfuron-methyl is directly applied to residential turf
and does not result in exposures of -concern to HED.  Based on this
assessment, HED believes that it is unlikely that there is a higher
potential for risk of exposure to spray drift from agricultural uses of
this chemical.

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

6.1	Acute Aggregate Risk TC \l2 "6.1	Acute Aggregate Risk 

An acute aggregate risk assessment was conducted for the population
subgroup of concern, females 13-49 years old.  An appropriate endpoint
for the general population was not identified; therefore, a
corresponding assessment is not required.  

For the population of concern, the acute dietary risk assessment
reported earlier in Section 4.2

 represents acute aggregate risk since drinking water estimates were
incorporated directly into the analysis.  Exposure through food and
drinking water sources occupies less than 1% of the aPAD for the
population of concern, Females 13-49 years old; thus, estimated acute
aggregate risk does not exceed HED’s level of concern (Table 6.1). 

Table 6.1  Acute Aggregate Risk (Food+Water).

Population Subgroup	

aPAD(mg/kg/day)	

Exposure (mg/kg/day)	

% aPAD

Females 13-50 years old	

0.5	

0.003401	

<1 

6.2	Short-Term Aggregate Risk TC \l2 "6.2	Short-Term Aggregate Risk 

  SEQ CHAPTER \h \r 1 The short-term aggregate risk assessment estimates
risks likely to result from exposure to halosulfuron-methyl residues
from food, drinking water, and residential pesticide uses.  High-end
estimates of residential exposure are used, while average values are
used for food and drinking water exposure (i.e., chronic exposures). 
Since the LOC is the same for all routes of exposure, exposures are
compared to the short-term NOAEL corresponding to the route of exposure
to calculate a route-specific MOE.  Then an aggregate MOE was calculated
by combining MOEs across all relevant routes of exposure (oral, dermal
and inhalation).  

A short-term risk assessment is required for adults because there is a
residential handler exposure scenario.  In addition, a short-term risk
assessment is required for infants and children because there is a
residential post-application exposure scenario for infants and children.
 

Results of the short-term aggregate risk assessment are summarized in
Table 6.2 below.  Short-term aggregate MOEs ranged from 2,800 to 4,800. 
The MOE for the U.S. population is 4,700.  The most highly exposed
subgroup was all infants (< 1 year old), with a MOE of 2,800.  These
estimates of short-term aggregate risk do not exceed HED’s level of
concern.

Table 6.2.	Short-Term Aggregate Risk Calculations. 

Population	LOC for Aggregate

Risk1	MOE

food & water2	MOE

oral3 	MOE

dermal4	MOE inhalation5	Aggregate MOE

 (food and residential)6

U.S. Population	

100	29,000	N/A	5,500	7,000,000	4,700

Females, 13-49 years old

33,000	N/A	5,500	7,000,000	4,800

All Infants 

(<1 year old)

9,900	43,000	4,200	N/A	2,800

Adults 50+ years

32,000	N/A	5,500	7,000,000	4,700

1 HED’s LOC is a MOE of at least 100 (10X for inter-species
variability and 10X for intra-species variability)

2 MOE food = [(short-term oral NOAEL=50 mg/kg/day) / (chronic dietary
exposure)] Dietary exposure from Table 4.4.2.

3 MOE oral = [(short-term oral NOAEL=50 mg/kg/day) / (oral residential
exposure)] Residential exposure from Table 5.2. 

4 MOE dermal = [(short-term dermal NOAEL=100 mg/kg/day) / (high-end
dermal residential exposure (for adult, included

 mix/load plus post-application exposure))]. Residential exposure from
Tables 5.1 and 5.2.

5 MOE inhalation = [(short-term inhalation NOAEL=50 mg/kg/day) /
(high-end inhalation residential exposure)] 

Residential MOEs from Table 5.1.

6 Aggregate MOE (food and residential) = 1 [(1/MOE food) + (1/MOE
oral) + (1/MOE dermal) + (1/MOE inhalation)].

6.3	Intermediate-Term Aggregate Risk TC \l2 "6.3	Intermediate-Term
Aggregate Risk 

  SEQ CHAPTER \h \r 1 The intermediate-term aggregate risk assessment
estimates risks likely to result from exposure to halosulfuron-methyl
residues from food, drinking water, and residential pesticide uses. 
High-end estimates of residential exposure are used, while average
values are used for food and drinking water exposure (i.e., chronic
exposures).  Intermediate-term exposures across all routes of exposure
were summed and compared to the intermediate-term NOAEL (10 mg/kg/day)
from the 13-week subchronic toxicity study in dogs, since this study and
endpoint are to be used for all intermediate-term risk assessments
(LOAEL = 40 mg/kg/day based on decreased body weight gains and food
efficiency along with hematological and clinical chemistry changes).

The aggregate MOEs for adults include intermediate-term dermal and
inhalation exposures for residential handlers and post-application
dermal exposures from activities on turfgrass previously treated with
halosulfuron-methyl. The inclusion of intermediate-term residential
handler exposures in the aggregate MOE is conservative (protective),
since intermediate-term

exposure of handlers is unlikely.

Results of the intermediate-term aggregate risk assessment are
summarized in Table 6.3 below.  Intermediate-term aggregate MOEs ranged
from 500 to 680.  The MOE for the U.S. population is 500.  The most
highly exposed children’s subgroup was all infants (< 1 year old),
with a MOE of 680.  These estimates of aggregate risk do not exceed
HED’s level of concern.

Table 6.3. Intermediate-Term (IT) Aggregate Risk Calculations

Population	LOC for Aggregate Risk1	Exposure Food & Water (mg/kg/day)
Exposure oral

(mg/kg/day)2	Dermal Exposure (mg/kg/day) 3	Exposure inhalation
(mg/kg/day)4	Aggregate MOE (food and residential)5

U.S. Population (total)	100	0.001705	N/A	

0.0183	0.0000071	500

Females, 13-49 years old

0.001503	N/A	

0.0183	0.0000071	500

All Infants 

(<1 year old)

0.005059	0.0006731	

0.0090	N/A	680

Adults 50+ years old

0.001558	N/A	

0.0183	0.0000071	500

1. LOC=100 (10x for inter-species variability*10x for intra-species
variability).

2. Incidental oral exposure applies only to subpopulations consisting of
infants and children. From Table 5.2.

3 Dermal exposure from Table 5.1 (0.0043 + 0.014 mg/kg/day = 0.0183
mg/kg/day).

4. Inhalation exposure from Table 5.1.

5 Aggregate MOE (food, water and residential) = IT NOAEL (10
mg/kg/day)/(food & water exposure + dermal exposure + inhalation
exposure + incidental oral exposure).

7.0	Cumulative Risk Characterization/Assessment  TC \l1 "7.0	Cumulative
Risk Charaterization/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 for halosulfuron-methyl and any
other substances, and halosulfuron-methyl 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
halosulfuron-methyl 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 OPP 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/. 

8.0  SEQ CHAPTER \h \r 1 	Occupational Exposure/Risk Pathway  TC \l1
"8.0	Occupational Exposure/Risk Pathway 

Workers may be exposed to halosulfuron-methyl during mixing, loading,
applying, and postapplication activities.  Based on the proposed
application rates, short- and intermediate-term exposure may occur. 
Chronic exposure ((6 months of continuous exposure) is not expected.

8.1	Short- and Intermediate-Term Handler Exposure and Risk TC \l2 "8.1
Short- and Intermediate-Term Handler Exposure and Risk 

Halosulfuron-methyl may be applied using handgun and groundboom
equipment.  The application methods, maximum application rates, and use
sites are summarized in Tables 2.1 and 2.2. Chemical-specific data for
assessing exposure during pesticide handling activities were not
submitted to the Agency in support of this Section 3 application.  It is
HED policy to use data from PHED Version 1.1 to assess handler exposures
for regulatory actions when chemical-specific data are not available
(HED ExpoSAC, SOP No.7, January 1999) or from the Outdoor Residential
Exposure Task Force (ORETF).  

Standard values established by the ExpoSAC were used for acres treated
per day and body weight.  For short-term dermal occupational exposure,
the toxicity endpoint was decreased body weight gain, and the point of
departure was 100 mg/kg/day (NOAEL) based on the results of a 21-day
dermal toxicity study in rats.  For intermediate-term dermal exposure
assessment, the toxicity endpoint was also decreased body weight gains
and reduced food efficiency along with hematological changes; the point
of departure was 10 mg/kg/day (NOAEL) based on a 13-week oral toxicity
in dogs.  Because this point of departure is derived from an oral study,
intermediate-term dermal doses were adjusted to account for 75% dermal
absorption.

For short-term inhalation occupational exposure, the point of departure
(50 mg/kg/day) was derived from an oral developmental rabbit study in
which decreased body weight gains were observed at the LOAEL of 150
mg/kg/day.  For the intermediate-term inhalation occupational exposure,
the point of departure (10 mg/kg/day) was based on an oral 13-week oral
toxicity study in dogs in which decreased body weight gains and food
efficiency along with hematology and clinical chemistry changes were
observed at the LOAEL of 40 mg/kg/day.  Since no inhalation absorption
data are available, toxicity by the inhalation route is considered to be
equivalent to the estimated toxicity by the oral route of exposure. 

Resulting dermal and inhalation risk estimates were combined into total
risk estimates because of a common effect (i.e., body weight gain
decreases) seen in the studies selected for the endpoints for both
routes of exposure.  The LOC for occupational exposure is for MOEs less
than 100. 

Halosulfuron-methyl is characterized as “not likely to be carcinogenic
to humans” based on lack of evidence from oral studies in rats and
mice.  Therefore, cancer risk was not assessed.

Summaries of the exposure and risk estimates for occupational handlers
are presented in  Table 8.1.1 (Short-Term) and Table 8.1.2
(Intermediate-Term).  All combined MOEs exceed the LOC of 100, and
therefore, are not of concern. 



Table 8.1.1 .	Short-Term Agricultural Handler Exposure and Risk for
Halosulfuron-Methyl.

Exposure Scenario	Crop or Target	App Ratea

(lb ai/A)	Acres Treated Dailyb	Unit Exposurec	Dose

(mg/kg/day)	MOEs

Baseline Dermal

mg/lb ai	PPE-G

Dermal

mg/lb ai	Baseline Inhalation µg/lb ai	Baseline Dermald,h	PPE-G Dermali
Baseline Inhalatione,h	Baseline Dermalf	PPE-G

Dermal	Baseline Inhalationg	Combined Baseline Dermal + Inhalationj
Combined PPE-G + Baseline Inhalationk

Mixer/Loader

Mixing/Loading Dry Flowables for 

Groundboom Applications (PHED)	Succulent shelled peas and bean	0.023	80
0.066	0.066	0.77	0.0017	0.0017	0.00002	58,000	58,000	2,500,000	56,000
56,000

	Tuberous and corm vegetables; 

Rhubarb; 

Bushberry;  

Dried shelled pea and bean (except soybean) (West of the Rockies); 

Okra; 

Apples (East of the Rockies)	0.047	80	0.066	0.066	0.77	0.0035	0.0035
0.000041	28,000	28,000	1,200,000	28,000	28,000

	Dried shelled pea and bean (except soybean) (East of the Rockies)	0.031
80	0.066	0.066	0.77	0.0023	0.0023	0.000027	43,000	43,000	1,800,000
42,000	42,000

	Apples (West of the Rockies)	0.094	80	0.066	0.066	0.77	0.0071	0.0071
0.000083	14,000	14,000	600,000	14,000	14,000

Applicator

Applying Sprays via

Groundboom Equipment (PHED)	Succulent shelled peas and bean	0.023	80
0.014	0.014	0.74	0.00037	0.00037	0.000019	270,000	270,000	2,600,000
250,000	250,000

	Tuberous and corm vegetables;

Rhubarb;

Bushberry;

Dried shelled pea and bean (except soybean) (West of the Rockies);

Okra; Apples

(East of the Rockies)	0.047	80	0.014	0.014	0.74	0.00075	0.00075	0.00004
130,000	130,000	1,300,000	120,000	120,000

	Dried shelled pea and bean (except soybean) (East of the Rockies)	0.031
80	0.014	0.014	0.74	0.0005	0.0005	0.000026	200,000	200,000	1,900,000
180,000	180,000

	Apples (West of the Rockies)	0.094	80	0.014	0.014	0.74	0.0015	0.0015
0.000079	66,000	66,000	630,000	60,000	60,000

Mixer/Loader/Applicator

Mixing/Loading/Applying Dry Flowables Concentrates with a Handgun
Sprayer (LCO ORETF data)	Rhubarb; Bushberry; 

Dried shelled pea and bean (except soybean) (West of the Rockies); 

Apples (East of the Rockies); Okra	0.047	25	No Data	0.58	22	No Data
0.0097	0.00037	No Data	10,000	140,000	No Data	9,300

	Dried shelled pea and bean (except soybean) (East of the Rockies)	0.031
25	No Data	0.58	22	No Data	0.0064	0.00024	No Data	16,000	210,000	No Data
14,000

	Apples (West of the Rockies)	0.094	25	No Data	0.58	22	No Data	0.019
0.00074	No Data	5,100	68,000	No Data	4,800

a	Application Rates based on proposed uses on label for
halosulfuron-methyl product Sandea® Herbicide (EPA Reg. No. 81880-18).

b	Exposure Science Advisory Council Policy No.  9.1

c	Unit Exposures based on PHED Version 1.1.  

d	Dermal Dose  (mg/kg/day)  = daily unit exposure (mg/lb ai)  x
application rate (lb ai/acre) x acres treated / body weight (70 kg).

e	Inhalation Dose (mg/kg/day) = daily unit exposure (μg/lb ai)  x
application rate (lb ai/acre) x acres treated / body weight (70 kg).  

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

g	Inhalation MOE = NOAEL (50 mg/kg/day) / inhalation daily dose
(mg/kg/day).  Level of concern = 100.

h	Baseline Dermal: Long-sleeve shirt, long pants, and no gloves;
Baseline Inhalation: no respirator.

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

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

k	Combined PPE-G + Baseline Inhalation MOE = 1 / (1/PPE-G Dermal MOE +
1/Baseline Inhalation MOE).  

Table 8.1.2.	Intermediate-Term Agricultural Handler Exposure and Risk
for Halosulfuron-Methyl.

Exposure Scenario	Crop or Target	App Ratea

(lb ai/A)	Acres Treated Dailyb	Unit Exposurec	Dose

(mg/kg/day)	MOEs

Baseline Dermal

mg/lb ai	PPE-G

Dermal

mg/lb ai	Baseline Inhalation µg/lb ai	Baseline Dermald,h	PPE-G Dermali
Baseline Inhalatione,h	Baseline Dermalf	PPE-G

Dermal	Baseline Inhalationg	Combined Baseline Dermal + Inhalationj
Combined PPE-G + Baseline Inhalationk

Mixer/Loader

Mixing/Loading Dry Flowables for 

Groundboom Applications (PHED)	Succulent shelled peas and bean	0.023	80
0.066	0.066	0.77	0.0013	0.0013	0.00002	7,700	7,700	490,000	7,600	7,600

	Tuberous and corm vegetables; Rhubarb; Bushberry;  Dried shelled pea
and bean (except soybean) (West of the Rockies); Okra; Apples (East of
the Rockies)	0.047	80	0.066	0.066	0.77	0.0027	0.0027	0.000041	3,800
3,800	240,000	3,700	3,700

	Dried shelled pea and bean (except soybean) (East of the Rockies)

	0.031	80	0.066	0.066	0.77	0.0018	0.0018	0.000027	5,700	5,700	370,000
5,600	5,600

	Apples (West of the Rockies)	0.094	80	0.066	0.066	0.77	0.0053	0.0053
0.000083	1,900	1,900	120,000	1,900	1,900

Applicator

Applying Sprays via

Groundboom Equipment (PHED)	Succulent shelled peas and bean	0.023	80
0.014	0.014	0.74	0.00028	0.00028	0.000019	36,000	36,000	510,000	34,000
34,000

	Tuberous and corm vegetables;Rhubarb;

Bushberry;Dried shelled pea and bean (except soybean) (West of the
Rockies);

Okra;Apples

(East of the Rockies)	0.047	80	0.014	0.014	0.74	0.00056	0.00056	0.00004
18,000	18,000	250,000	17,000	17,000

	Dried shelled pea and bean (except soybean) (East of the Rockies)

	0.031	80	0.014	0.014	0.74	0.00037	0.00037	0.000026	27,000	27,000
380,000	25,000	25,000

	Apples (West of the Rockies)	0.094	80	0.014	0.014	0.74	0.0011	0.0011
0.000079	8,900	8,900	130,000	8,300	8,300

Mixer/Loader/Applicator

Mixing/Loading/Applying Dry Flowables Concentrates with a Handgun
Sprayer (LCO ORETF data)	Rhubarb; Bushberry; 

Dried shelled pea and bean (except soybean) (West of the Rockies); 

Apples (East of the Rockies); Okra	0.047	25	No Data	0.58	22	No Data
0.0073	0.00037	No Data	1,400	27,000	No Data	1,300

	Dried shelled pea and bean (except soybean) (East of the Rockies)	0.031
25	No Data	0.58	22	No Data	0.0048	0.00024	No Data	2,100	41,000	No Data
2,000

	Apples (West of the Rockies)	0.094	25	No Data	0.58	22	No Data	0.015
0.00074	No Data	680	14,000	No Data	650

a	Application Rates based on proposed uses on label for
halosulfuron-methyl product Sandea® Herbicide (EPA Reg. No. 81880-18). 

b	Exposure Science Advisory Council Policy No.  9.1.     

c	Unit Exposures based on PHED Version 1.1.   

d	Dermal Dose  (mg/kg/day)  = daily unit exposure (mg/lb ai)  x
application rate (lb ai/acre) x acres treated x dermal absorption factor
(75%) / body weight (70 kg).

e	Inhalation Dose (mg/kg/day) = daily unit exposure (μg/lb ai)  x
application rate (lb ai/acre) x acres treated / body weight (70 kg).  

f	Dermal MOE = NOAEL (10 mg/kg/day) / dermal daily dose (mg/kg/day). 
Level of concern = 100.

g	Inhalation MOE = NOAEL (10 mg/kg/day) / inhalation daily dose
(mg/kg/day).  Level of concern = 100.

h	Baseline Dermal:  Long-sleeve shirt, long pants, and no gloves;
Baseline Inhalation: no respirator. 

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

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

k	Combined PPE-G + Baseline Inhalation MOE = 1 / (1/PPE-G Dermal MOE +
1/Baseline Inhalation MOE).  

8.2 	  SEQ CHAPTER \h \r 1 Postapplication Exposure/Risk TC \l2 "8.2
Postapplicaiton Exposure/Risk 

8.2.1	Data and Assumptions for Postapplication Exposure Scenarios	 TC
\l3 "8.2.1	Data and Assumptions for Postapplication Exposure Scenarios 

Inhalation: Based on the Agency's current practices, a quantitative
postapplication inhalation exposure assessment was not performed for
halosulfuron-methyl at this time primarily because it 

is not applied using airblast aerial equipment or another method that
could result in higher postapplication inhalation exposure than other
application methods. Further halosulfuron-methyl has low vapor pressure.
However, volatilization of pesticides may be a potential source of
postapplication inhalation exposure to individuals nearby to pesticide
applications.  The Agency sought expert advice and input on issues
related to volatilization of pesticides from its Federal Insecticide,
Fungicide, and Rodenticide Act Scientific Advisory Panel (SAP) in
December 2009.  The Agency received the SAP’s final report on March 2,
2010. (   HYPERLINK "http://www.epa.gov/scipoly/" 
http://www.epa.gov/scipoly/  SAP/meetings/2009/ 120109meeting.html). 
The Agency is in the process of evaluating the SAP report and may, as
appropriate, develop policies and procedures to identify the need for
and, subsequently, the way to incorporate postapplication inhalation
exposure into the Agency's risk assessments.  If new policies or
procedures are put into place, the Agency may revisit the need for a
quantitative postapplication inhalation exposure assessment for
halosulfuron-methyl.

Dermal: Most of the proposed uses for halosulfuron-methyl are
ground-directed uses where no crop foliage is treated.  Currently, HED
has no transfer coefficients (TCs) or other data to assess
postapplication dermal exposures to soil by occupational workers.  In
general, such exposures are considered to be negligible. Therefore, for
the proposed soil-directed uses, postapplication exposures and risks to
occupational workers were not quantitatively assessed.  However, some of
the proposed uses for halosulfuron-methyl are for postemergent
applications when crop foliage is present.  Postapplication exposure and
risk were assessed for these proposed uses.  This assessment is
considered to be a Tier I, screening level estimate, demonstrating that
there are minimal potential risks to workers re-entering fields treated
with postemergent applications of halosulfuron-methyl.

Since no postapplication data was submitted in support of this
registration action, dermal exposures during postapplication activities
were estimated using dermal TCs from the ExpoSAC SOP No. 003.1:
Agricultural Transfer Coefficients, August 2000, and the following
assumptions:

					

Application Rate	= 	0.047 lb ai/A for tuberous and corm vegetables,
bushberries, and dried shelled peas and beans (West of the Rockies); and
0.031 lb ai/A for dried shelled peas and beans (East of the Rockies).   

Exposure Duration	=	8 hours per day

Body Weight	=	70 kg for average adult		

Dermal Absorption	= 	100% for short-term and 75% for intermediate-term

Fraction of ai retained on foliage is assumed to be 20% (0.2) on day
zero for agricultural crops.  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 ExpoSAC.

Foliar residue is expected to be very low during postapplication
activities.  Since halosulfuron-methyl is typically applied early in the
season prior to flowering, the postapplication tasks are unlikely to
encounter foliar residues of concern.  The dermal exposure risk
estimates for postapplication activities are summarized below in Table
8.2.1.1.

Table 8.2.1.1.  Anticipated Postapplication Activities and Dermal
Transfer Coefficients.

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

Tuberous and Corm Vegetables	Vegetable, “Root”	Medium	1,500
Irrigation, Scouting

Low	300	Hand Weeding

Bushberries	Vine/Trellis	Low	500	Hedging, Irrigation, Hand Weeding,
Scouting

Dried Shelled Peas and Beans	Field/Row Crop, Low/Medium	Low	100
Irrigation, Scouting, Hand Weeding

	8.2.2	Agricultural Post-application Exposure and Risk TC \l3 "8.2.2
Agricultural Post-application Exposure and Risk 

The postapplication exposure associated with agricultural crops is
summarized in Table 8.2.1.2.  All scenarios resulted in MOEs greater
than 100 on day 0 (12 hours after application) and, therefore, do not
exceed HED’s LOC.

Table 8.2.1.2.	Postapplication Exposure and Risk for
Halosulfuron-Methyl.

Crop	Activity	Transfer

Coefficienta

(cm2/hr)	DATb	DFRc

(μg/cm2)	Short-Term	Intermediate-Term

	Daily Dermal Dosed (mg/kg/day)	MOEe	Daily Dermal Dosed (mg/kg/day)	MOEe

Tuberous and corm vegetables	Irrigation, scouting	1,500	0

(12 hours)	0.1054	0.018	5,500	0.014	740

	Hand weeding	300	0

(12 hours)	0.1054	0.0036	28,000	0.0027	3,700

Bushberry	Hedging, irrigation, hand weeding, scouting	500	0

(12 hours)	0.1054	0.0060	17,000	0.0045	2,200

Dried shelled peas and beans

(West of Rockies)	Irrigation, Scouting,

Hand weeding	100	0

(12 hours)	0.1054	0.0012	83,000	0.00090	11,000

Dried shelled peas and beans

(East of Rockies)	Irrigation, Scouting,

Hand weeding	100	0

(12 hours)	0.0695	0.00079	130,000	0.00060	17,000

a	Transfer coefficients and associated activities from ExpoSAC SOP No.
003.1 “Agricultural Transfer Coefficients,” 8/17/2000. 

b	DAT = Days after treatment needed to reach the LOC of 100; DAT 0 = the
day of treatment, after sprays have dried; assumed to be approximately
12 hours.  

c	DFR (µg/cm2) = Application rate (lb ai/A) x (1- daily dissipation
rate) t x CF (4.54E+8 µg/lb) x CF (2.47E-8 A/cm2) x 20% DFR after
initial treatment.

d	Daily Dose = [(DFR x TC x Dermal absorption x 8-hr Exposure Time)] /
[(CF: 1000 µg/mg) x (70 kg Body Weight)]    (Short-term dermal
absorption factor = 100%; Intermediate-term dermal absorption factor =
75%). 

e	MOE = NOAEL/Daily Dose   (Short-Term Dermal NOAEL = 100 mg/kg/day;
Intermediate-Term Dermal NOAEL = 10 mg/kg/day).

Restricted-Entry interval  

The halosulfuron-methyl technical material has been classified in
Toxicity Category III for acute dermal toxicity and Toxicity Category IV
for primary eye irritation and primary skin irritation.  Per the Worker
Protection Standard (WPS), a 12-hr restricted entry interval (REI) is
required for chemicals classified under Toxicity Category III or IV. 
The current GWN-3061 label has a 12-hour REI, which complies with the
WPS.  

9.0	Data Needs/Label ReCOMMENDATIONS

9.1	Toxicology

870.3465 28-Day Inhalation – Rat

A 28-day inhalation toxicity study in the rat is required due to concern
for repeated exposure via the inhalation route based on the use pattern.

870.7800 Immunotoxicity

Under the new rule for data requirements as presented in 40 CFR Part
158, an immunotoxicity study is required.

9.2	Residue Chemistry

860.1200 Directions for Use

●	For Crop Subgroup 6B (pea and bean, succulent shelled), the label(s)
should be amended to prohibit applications to legumes grown for
livestock feeds because no residue data are available for cowpea forage
and hay.

●	For Crop Subgroup 13-07B (bushberry), the label(s) should be amended
to remove the instructions pertaining to the use of a non-ionic
surfactant.  If it is IR-4’s intention to add a nonionic surfactant
when Sandea® Herbicide is applied to these crops, then additional field
trial data are required.

For Crop Subgroup 6C (dried pea and bean (except soybean)), the labels
should be amended to remove the use directions for Crop Subgroup 6C.  

860.1500 Crop Field Trials

Prior to granting a registration on Crop Subgroup 6C (dried shelled pea
and bean (except soybean)), data on dried pea including the forages and
hay of field pea cultivars are required from a minimum of five field
trials.  The requested field trials should reflect total application
rates of 0.047 lb ai/A per crop cycle or 0.094 lb ai/A per year, a
minimum 30-day PHI, and the incorporation of a non-ionic surfactant in
the spray mixture.  A revised Section F should be submitted removing the
request for Crop Subgroup 6C (dried shelled pea and bean (except
soybean)).

  SEQ CHAPTER \h \r 1 860.1650 Submittal of Analytical Reference
Standards

	Analytical reference standards for the 3-CSA (3-chlorosulfonamide acid)
metabolite and the RRE of halosulfuron-methyl must be submitted to the
EPA National Pesticide Standards Repository.

REFERENCES

2002 Hazard Assessment 

  SEQ CHAPTER \h \r 1 HALOSULFURON-METHYL: - Report of the Hazard
Identification Assessment Review Committee.  08/23/2002.

2006 Risk Assessment

Halosulfuron-methyl: Human Health Risk Assessment for Propose Uses on
Alfalfa. D331643, M. Clock-Rust, 09/21/2006.

2009 Risk Assessment

Halosulfuron-methyl: Human Health Risk Assessment for Propose Uses on
Soybean. D35803, W. Phang, 06/30/2009

Residue Chemistry Assessment

Halosulfuron-methyl.  Application for Section 3 Registration of Sandea®
Herbicide (EPA Reg. No. 81880-18) and GWN-3061 Herbicide (EPA Reg. No.
81880-2) to Add New Uses on:  Pea and Bean, Succulent Shelled, Subgroup
6B; Vegetable, Tuberous and Corm, Subgroup 1C; Rhubarb; Bushberry
Subgroup 13-07B; Pea and Bean, Dried Shelled, Except Soybean, Subgroup
6C; Apple; and Okra.  Summary of Analytical Chemistry and Residue Data.
D367058, Debra Rate, 03/03/2010

Dietary Exposure Analysis

Halosulfuron-methyl Acute and Chronic Aggregate Dietary (Food and
Drinking Water) Exposure and Risk Assessments for the Section 3
Registration Action on Pea and Bean, Succulent Shelled, Subgroup 6B;
Vegetable, Tuberous and Corm, Subgroup 1C; Rhubarb; Bushberry Subgroup
13-07B; Apple; and Okra. D367059, Debra Rate, 03/04/2010

Occupational and Residential Exposure Assessment

Halosulfuron-Methyl. Occupational and Residential Exposure Assessment
for Proposed Field Use of Halosulfuron-Methyl on Succulent Shelled Peas
and Beans (Subgroup 6B), Tuberous and Corm Vegetables (Subgroup 1C),
Rhubarb, Bushberry (Subgroup 13-07B), Dried Shelled Peas and Beans
(Except Soybean, Subgroup 6C), Apples, and Okra. D367060

Drinking Water Assessment

  SEQ CHAPTER \h \r 1  Halosulfuron-Methyl Drinking Water Assessment for
Additional Food Uses (Including Proposed Use on Soybeans). D358031, M.
Barrett, 05/27/2009.	

Attachment A: Toxicology Profile  

Table 1.  Acute Toxicity of Halosulfuron-Methyl Technical.

OPPTS No.	

Study Type	

MRID	

Results	

Toxicity Category

870.1100	Acute Oral- Rats	42139413	LD50:  Males = 10,435  mg/kg

           Females = 7758 mg/kg

           Combined = 8866 mg/kg	IV

870.1200	Acute Dermal- Rats	42139415	LD50 >2000  mg/kg (limit test)	III

870.1300	Acute Inhalation- Rats	42139417	LC50 >6 mg/L	IV

870.2400	Primary Eye Irritation- Rabbits	42139419	Mild transient (<24
hr) irritation involving the conjunctiva and iris.	IV

870.2500	Primary Skin Irritation- Rabbits	42139421	Non-irritant	IV

870.2600	Dermal Sensitization- Guinea pigs	42139423	Not a skin
sensitizer (maximization test)	N/A



Table 2. Toxicity Profile of Halosulfuron-Methyl Technical (Repeated
dosing and others).

 Guideline  No.	

Study Type 	

MRID No. (Date)/Classification/ Doses	

Results

870.3100 (82-1)	

Subchronic oral toxicity study in rats 	

43616301 (1995)/ Acceptable/Guideline 

Doses: 0, 100, 1000, 10000, or 20000 ppm (diet) (M/F: 6.7/7.6,
66.5/75.8, 682.8/772.8, 1400/1578 mg/kg/day)	

NOAEL = M > 1400, F = 75.8 mg/kg/day

LOAEL = M not determined, F = 772.8 mg/kg/day based on decreased body
weight gains.

870.3100 (82-1)

 	

Subchronic oral toxicity study in rats (28 day range-finder)

	

42171501 (1988)/ Acceptable/Nonguideline  

Doses: 0, 100, 400, 1600, or 6400 ppm (diet)

(M/F: 7.4/8.9, 28.8/37.3, 116/147, 497/640 mg/kg/day)	

NOAEL = M = 116, F =147 mg/kg/day

LOAEL = M = 497, F = 640 mg/kg/day based on decreased body weight gains,
decreased organ weights and changes in clinical chemistry parameters.

870.3150 (82-1)	

Subchronic oral toxicity study in nonrodents - dogs 	

42171502 (1991)/ Acceptable/Nonguideline

 Doses: 0, 2.5, 10, 40, and 160 mg/kg/day (capsule) 	

NOAEL = 10 mg/kg/day

LOAEL = 40 mg/kg/day based on decreased body weight gains and food
efficiency along with hematology and clinical chemistry changes.

870.3200 (82-2)	

21-day dermal toxicity  in rats

	

42661417 (1990)/ Acceptable/Guideline

Doses: 0, 10, 100, or 1000 mg/kg/day	

NOAEL = 100 mg/kg/day

LOAEL = 1000 mg/kg/day based on a dose-related decrease in total body
weight gain in males.  Total body weight gain was also decreased in the
100 mg/kg/day group females, but the 1000 mg/kg/day group females were
comparable to the control group.

870.4100 (83-1b) 	

Chronic oral toxicity study in dogs

	

42396211 (1991)/ Acceptable/Guideline

Doses: 0, 0.25, 1.0, 10.0, or 40 mg/kg/day (capsule).	

NOAEL = 10 mg/kg/day

LOAEL = 40 mg/kg/day based on decreased body weight gains in males and
females, decreased relative food efficiency in females along with
hematological and clinical chemistry changes. 	

870.4300 (83-5)	

Combined Chronic/ Carcinogenicity in rats

	

42661418 (1992)/ 

Acceptable/Guideline

Doses: 0, 10, 100, 1000, or 2500, 5000 (males only) ppm (diet)

(M/F: 0.44/0.56, 4.4/5.6, 43.8/56.3, 108.3/138.6, 225.6 (M) mg/kg/day)	

NOAEL = M=108.3, F=56.3 mg/kg/day

LOAEL = M=225.6, F=138.6 mg/kg/day based on marginal decrease in body
weight gain in both males and females.

No evidence of carcinogenicity.

870.4200 (83-2) 	

Carcinogenicity study in mice  

	

42661419 (1992)/ Acceptable/Guideline

Doses: 0, 30, 300, 3000, or 7000 ppm (diet)

(M/F: 4.0/5.2, 41.1/51.0, 410.0/509.1, or 971.9/1214.6 mg/kg/day)	

NOAEL = M=410.0, F > 1214.6 mg/kg/day

LOAEL = M=971.9, F>1214.6 mg/kg/day based on decreased body weight gains
and necropsy findings (increase incidence of
microconcretion/mineralization in the testis and epididymis). 

No evidence of carcinogenicity.

870.3700 (83-3) 

	

Developmental toxicity in rats

	

42139425 (1990)/ Acceptable/Guideline

Doses: 0, 75, 250, or 750 mg/kg/day (gavage)	

Maternal NOAEL = 250 mg/kg/day.

Maternal LOAEL = 750 mg/kg/day, based on increased incidence of clinical
observations, reduced body weight gains, reduced food consumption and
food efficiency.

Developmental NOAEL = 250 mg/kg/day.  

Developmental LOAEL = 750 mg/kg/day, based on decreased mean fetal body
weight and mean litter size, increased fetal and litter incidences of
soft tissue and skeletal variations.

870.3700 (83-3b)	

Developmental toxicity study in rabbits

	

42139426 (1990)/ Acceptable/Guideline

Doses: 0, 15, 50, or 150 mg/kg/day (gavage)	

Maternal NOAEL = 50 mg/kg/day

Maternal LOAEL = 150 mg/kg/day based on reduced body weight gain, food
consumption and food efficiency.

Developmental NOAEL = 50 mg/kg/day

Developmental LOAEL = 150 mg/kg/day based on group decreased mean litter
size, increased number of resorptions and resorptions per dam, and
increased postimplantation loss.

870.3700 (83-3b)	

Developmental toxicity study in rabbits

	

43621901 (1995) 3-chlorosulfonamide acid

Metabolite/

Acceptable/Guideline

Doses: 0, 30, 300, or 1000 mg/kg/day  	

Maternal Toxicity NOAEL => 1000 mg/kg/day

Maternal Toxicity LOAEL > 1000 mg/kg/day

Developmental Toxicity NOAEL => 1000 mg/kg/day

Developmental Toxicity LOAEL > 1000 mg/kg/day

870.3800 (83-4)	

Two-Generation reproduction study in rats

	

42139427 (1991)/ Acceptable/Guideline

Doses: 0, 100, 800, or 3600 ppm (diet)

( F0 Males: 6.3, 50.4, and 223.2 mg/kg/day; F0 Females: 7.4, 58.7, and
261.4 mg/kg/day)	

Parental/Systemic NOAEL = M=50.5, F=58.7 mg/kg/day 

Parental/Systemic LOAEL = M=223.2, F=261.4 mg/kg/day based on decreased
body weights, body weight gains, and reduced food consumption during the
premating period in both sexes.

Offspring NOAEL = 51/59 mg/kg/day

Offspring LOAEL = 223.2/261.4 mg/kg/day based on decreased body weight
in the F1 pups and marginal decreased body weight in F2 pups.

Reproductive NOAEL > = 223.2/261.4 mg/kg/day.

870.6200a (82-7)	

Acute neurotoxicity in rats.	

45754701 (1994) and 46199501 (1989)[positive control study]/ 
Acceptable/Guideline

Doses: 0, 200, 600, or 2000 mg/kg (limit dose)	NOAEL = 600 mg/kg.  

LOAEL = 2000 mg/kg (limit dose) based on mortality in males. 

870.6200b (82-7)	

Subchronic neurotoxicity study in rats.	

45754702 (1992)/ Acceptable/Guideline

Doses: M: 0, 100, 1000, or 10,000 ppm; F:  0, 100, 1000, or 4000  ppm
(diet) (M/F: 0/0, 6.3/8.1, 62.8/82.6, or 706.0/315.9 mg/kg/day)	

NOAEL = M = F = 1000 ppm (M/F: 62.8/82.6 mg/kg/day). 

LOAEL = M = 10,000 ppm; F =4000 ppm (M: 706.0 mg/kg/day) in males based
on decreased body weight and body weight gain and (F: 315.9 mg/kg/day)
in females based on decreased body weight gain. 

870.6300 (83-6)	

Metabolism	

42139433 (1990)/ Acceptable/Guideline

5 or 250 mg/kg single dose or 5 mg/kg/day repeated doses	

Absorption was rapid, incomplete and similar in both sexes.  Elimination
was mostly by urine and feces within 72 hours, appearing to be
independent of dose and sex.  Desmethyl NC-319 and the 5-hydroxy
derivative were the major urinary and fecal metabolites.

870.5100  

(84-2 a) 	

Mutagenic - Ames

Salmonella typhimurium and E. Coli.	

42139428 (1991)/ Acceptable 

(+/-S9) 5 strains S. typh. Conc.: 1 - 10000 microgm/plate; E. Coli
WpuvrA Conc.: 333 - 10000 microgram/plate	

Negative. Concentrations => 5000 microgm/plate found to be insoluble
and/or cytotoxic.

870.5100  

(84-2 a) 	

Mutagenic - Gene Mutation	

43616302 (1995)/ Acceptable 

(+/-S9) 5 strains S. typh. Conc.: 50 - 5000 microgm/plate	

Negative. Conducted with 3-chlorosulfonamide acid-the principal soil
metabolite of halosulfuron-methyl.

870.5300  (84-2)	

Mutagenic - Gene Mutation - Hamster (Chinese)	

43616303 (1995) - Metabolite/ Acceptable 

(+/-S9) Conc.: 350-3100 microgm/mL 	

Negative. Conducted with 3-chlorosulfonamide acid-the principal soil
metabolite of halosulfuron-methyl.

870.5300  (84-2)	

Mutagenic - (HGPRT) - Hamster (Chinese).	

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/ Unacceptable 

Conc.: 100-1000 microgm/mL 	

Conclusions indefinite due to partly to relatively high negative and low
positive control values, solubility problems with test article.

870.5300  (84-2)	

Mutagenic - (HGPRT) - Hamster (Chinese).	

42661420 (1993)/ Acceptable 

(+/-S9) Conc.: 50-900 microgm/mL	

Negative.  Did not induce forward mutations at the HGPRT locus in
Chinese Hamster ovary cells. Concentrations above 700 ug/mL were
insoluble.

870.5375 (84-2)	

Mutagenic - In vitro Clastogenic - Hamster (Chinese) 	

42139429 (1989)/ Acceptable 

(+/-S9) Conc.: 449-1810 microgm/mL	

Negative.  No chromosomal aberrations.

870.5395  (84-2)	

Mutagenic - Micronucleus Assay - Mouse (CD-1)	

43616304 (1995) - Metabolite/Acceptable

 Doses: 1250, 2500 or 5000 mg/kg	

Negative.  Conducted with 3-chlorosulfonamide acid-the principal soil
metabolite of halosulfuron-methyl.  No overt toxicity for the treated
animals or cytotoxicity for the target organ (bone marrow cells) was
observed.

870.5395  (84-2)	

Mutagenic - Micronucleus Assay - Mouse	

42139430 (1989)/ Acceptable 

Doses: 500, 1667 0r 5000 mg/kg.	

Negative. Did not induce significant elevations in the frequencies of
micronucleated polychromatic erythrocytes.

870.5500 

(84-2)	

Mutagenic - Unscheduled DNA synthesis - Rat	

42139432 (1990)/ Acceptable

(+/-S9) Conc.: 25-1000 microgm/mL	

Negative. Fail to induce unscheduled DNA synthesis in primary rat
hepatocytes.  

Attachment B: Rationale for Requiring the Studies 

Guideline Number: 870.3465

Study Title:   90-Day Inhalation Toxicity 

Rationale for Requiring the Data

The 28-day inhalation toxicity study evaluates the potential hazard of a
pesticide chemical following repeated inhalation exposures.  This study
is critical for pesticides with use pattern in which there is potential
for repeated human exposures (e.g., professional applicators, green
house use etc) exposure.  The study design simulates the route of human
exposure (inhalation).  In this study animals are exposed (nose/whole
body) to aerosol concentrations of the test material for 6 hours/day, 5
day/week for 28 days.  A detailed toxicological examination including
the histopathology of the respiratory system is conducted.  This is
route-specific study would provide data for hazard characterization,
dose response assessment, and a dose and endpoint for assessing
potential risks via the inhalation route.  

Practical Utility of the Data

How did the Agency make its re-registration decision without these data?
 

A subchronic inhalation study provides critical scientific information
needed to characterize potential hazard to human population on the
respiratory system from pesticide exposure.  In the case of
halosufluron-methyl, subchronic inhalation study is not available; an
oral toxicity study is employed for toxicity endpoint and points of
departure selections. Absorption via the inhalation route is presumed to
be equivalent to oral absorption, and the effects seen in the oral
toxicity study are also presumed to be similar to those resulted from
the inhalation study. A 28-day repeated exposure study that follows the
Test Guidelines (870.3465) will characterize hazard and provide data for
a much accurate inhalation risk assessment.

How will the data be used?  

This study will identify hazard (i.e., provide a dose and endpoint)
following longer repeated exposures, this data will be used in risk
assessments, and will result in the removal of the database uncertainty
factor.



Guideline Number: 870.7800

Study Title:  Immunotoxicity

Rationale for Requiring the Data

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

The Immunotoxicity Test Guideline (OPPTS 870.7800) prescribes functional
immunotoxicity testing and is designed to evaluate the potential of a
repeated chemical exposure to produce adverse effects (i.e.,
suppression) on the immune system. Immunosuppression is a deficit in the
ability of the immune system to respond to a challenge of bacterial or
viral infections such as tuberculosis (TB), Severe Acquired Respiratory
Syndrome (SARS), or neoplasia.  Because the immune system is highly
complex, studies assessing functional immunotoxic endpoints are helpful
in fully characterizing a pesticide’s potential immunotoxicity.  These
data will be used in combination with data from hematology, lymphoid
organ weights, and histopathology in routine chronic or subchronic
toxicity studies to characterize potential immunotoxic effects.  

Practical Utility of the Data

How will the data be used?

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

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

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

 

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

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