UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C.  20460

     OFFICE OF

PREVENTION, PESTICIDES

AND TOXIC SUBSTANCES

Date: June 30, 2009

MEMORANDUM

SUBJECT:      Halosulfuron-methyl:  Human Health Risk Assessment for
Proposed Uses on Soybean.

PC Code:  128721	DP Barcode:  358031

Decision No.:  399589	Registration No.:  81880-2

Petition No.:  8F7424	Regulatory Action:  Section 3 Registration

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 Dodd, Chemist

		Barry O’Keefe, Senior Biologist

		Risk Assessment Branch 3

Health Effects Division (7509P)

THRU:	Paula A. Deschamp, Branch Chief

		Risk Assessment Branch 3

		Health Effects Division (7509P)

TO:		Vickie Walters/James Tompkins (RM Team 25)

		Herbicide Branch

		Registration Division (7505P)

Canyon Group LLC 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:

Soybean …………………………… 0.05 ppm

In conjunction with the subject tolerance petition, Canyon Group LLS is
also proposing to amend the use pattern for the 75% water-dispersible
granule (WG) formulation of halosulfuron-methyl (GWN-3061 Herbicide, EPA
Reg. No. 81880-2) to add uses on soybeans.  Postharvest (fall burndown)
application to soybean, and preplant/preemergence and early
postemergence foliar application to sulfonylurea-tolerant soybean
varieties are proposed at a maximum application rate of 0.062 lb ai/A.
A 30-day pregrazing/preharvest (PGI/PHI) interval is proposed for
soybean forage and silage.

The most recent human health risk assessment was conducted for uses on
alfalfa (D331643, M. Clock-Rust, 09/21/2006). Since then, no new
toxicology data have been submitted. The hazard characterization and
toxicity endpoints for risk assessment remain unchanged relative to the
2006 risk assessment. 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 the 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 Nancy Dodd, who also
conducted the dietary assessment.  The occupational/residential
assessment was performed by Barry O’Keefe. The drinking water
assessment was conducted by Michael Barrett of 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 soybean and
establishment of the following tolerance:

Soybean, seed……………………….0.05 ppm

Table of Contents

  TOC \o "1-3" \h \z \u    HYPERLINK \l "_Toc234215039"  Table of
Contents	  PAGEREF _Toc234215039 \h  3

  HYPERLINK \l "_Toc234215040"  1.0 	EXECUTIVE SUMMARY	  PAGEREF
_Toc234215040 \h  4

  HYPERLINK \l "_Toc234215041"  2.0	INGREDIENT PROFILE	  PAGEREF
_Toc234215041 \h  9

  HYPERLINK \l "_Toc234215042"  2.1 	Summary of Proposed Uses	  PAGEREF
_Toc234215042 \h  9

  HYPERLINK \l "_Toc234215043"  2.2 	Physical/Chemical Properties
Characterization	  PAGEREF _Toc234215043 \h  11

  HYPERLINK \l "_Toc234215044"  3.0	HAZARD CHARACTERIZATION	  PAGEREF
_Toc234215044 \h  12

  HYPERLINK \l "_Toc234215045"  3.1 	FQPA Safety Factor for Infants and
Children	  PAGEREF _Toc234215045 \h  15

  HYPERLINK \l "_Toc234215046"  3.2	Endocrine Disruption	  PAGEREF
_Toc234215046 \h  16

  HYPERLINK \l "_Toc234215047"  4.0 	DIETARY EXPOSURE/RISK
CHARACTERIZATION	  PAGEREF _Toc234215047 \h  16

  HYPERLINK \l "_Toc234215048"  4.1	Pesticide Metabolism and
Environmental Degradation	  PAGEREF _Toc234215048 \h  16

  HYPERLINK \l "_Toc234215049"  4.2	Dietary Exposure and Risk	  PAGEREF
_Toc234215049 \h  21

  HYPERLINK \l "_Toc234215050"  5.0	RESIDENTIAL (Non-Occupational)
EXPOSURE/RISK CHARACTERIZATION	  PAGEREF _Toc234215050 \h  23

  HYPERLINK \l "_Toc234215052"  5.1       Residential Handler Exposure
PAGEREF _Toc234215052 \h  23

  HYPERLINK \l "_Toc234215053"  5.2	Residential Postapplication Exposure
  PAGEREF _Toc234215053 \h  24

  HYPERLINK \l "_Toc234215054"  5.3	Other (Spray Drift, etc.)	  PAGEREF
_Toc234215054 \h  25

  HYPERLINK \l "_Toc234215055"  6.0	Aggregate Risk Assessments and Risk
Characterization	  PAGEREF _Toc234215055 \h  25

  HYPERLINK \l "_Toc234215056"  6.1	Acute Aggregate Risk	  PAGEREF
_Toc234215056 \h  25

  HYPERLINK \l "_Toc234215057"  6.2	Short-Term Aggregate Risk	  PAGEREF
_Toc234215057 \h  26

  HYPERLINK \l "_Toc234215058"  6.3	Intermediate-Term Aggregate Risk
PAGEREF _Toc234215058 \h  27

  HYPERLINK \l "_Toc234215059"  6.4	Cancer Risk	  PAGEREF _Toc234215059
\h  28

  HYPERLINK \l "_Toc234215060"  7.0	Cumulative Risk
Characterization/Assessment	  PAGEREF _Toc234215060 \h  28

  HYPERLINK \l "_Toc234215061"  8.0	Occupational Exposure/Risk Pathway
PAGEREF _Toc234215061 \h  28

  HYPERLINK \l "_Toc234215062"  8.1	Short- and Intermediate-Term Handler
Exposure and Risk	  PAGEREF _Toc234215062 \h  28

  HYPERLINK \l "_Toc234215063"  8.2 	Postapplication Exposure/Risk
PAGEREF _Toc234215063 \h  32

  HYPERLINK \l "_Toc234215064"  8.2.1	Data and Assumptions for
Postapplication Exposure Scenarios	  PAGEREF _Toc234215064 \h  32

  HYPERLINK \l "_Toc234215065"  8.2.2 	Short- and Intermediate-Term
Postapplication Risk Estimates	  PAGEREF _Toc234215065 \h  33

  HYPERLINK \l "_Toc234215066"  9.0	Data Needs/Label ReCOMMENDATIONS
PAGEREF _Toc234215066 \h  33

  HYPERLINK \l "_Toc234215067"  9.1	Toxicology	  PAGEREF _Toc234215067
\h  33

  HYPERLINK \l "_Toc234215068"  9.2	Residue Chemistry	  PAGEREF
_Toc234215068 \h  34

  HYPERLINK \l "_Toc234215069"  9.3	Occupational and Residential
Exposure	  PAGEREF _Toc234215069 \h  34

  HYPERLINK \l "_Toc234215070"  References:	  PAGEREF _Toc234215070 \h
35

  HYPERLINK \l "_Toc234215071"  Attachment A: Toxicology Profile
PAGEREF _Toc234215071 \h  36

 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, and is formulated as
water-dispersible granule formulation (WG).

The Canyon Group LLC, a joint venture formed by Gowan Company and Nissan
Chemical Industries (NCI), is proposing to amend the use pattern for the
75% water-dispersible granule (WG) formulation of halosulfuron-methyl
(GWN-3061 Herbicide, EPA Reg. No. 81880-2) to add uses on soybeans.
Postharvest (fall burndown) application to soybean, and
preplant/preemergence and early postemergence foliar application to
sulfonylurea-tolerant soybean varieties are proposed at a maximum
application rate of 0.062 lb ai/A.  A 30-day pregrazing/preharvest
(PGI/PHI) interval is proposed for soybean forage and silage.

In conjunction with the requested amended use, the Canyon Group also
proposes the establishment of a permanent tolerance for residues of the
herbicide halosulfuron-methyl [methyl
3-chloro-5-(4,6-dimethoxypyrimidin-2-ylcarbamoylsulfamoyl)-1-methylpyraz
ole-4-carboxylic acid], expressed as parent equivalents, in/on the
following raw agricultural commodity:

Soybean 	0.05 ppm

HED has conducted a human health risk assessment for halosulfuron-methyl
for the purpose of establishing the proposed tolerance for uses in or on
soybean.

  SEQ CHAPTER \h \r 1 There are currently no established Codex,
Canadian, or Mexican 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 a tolerance for uses in/on soybean, 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 mutagenicity tests.

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 pathways: acute and chronic
dietary, short- and intermediate-term incidental oral, dermal and
inhalation.  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 MOE < 100.

Table 1.  Summary of Toxicological Doses used in the Current Risk
Assessment

Exposure Scenario	Point of departure for Risk Assessment	Toxicity
Endpoints

Acute dietary

(females 13-49 yrs only)	Oral NOAEL = 50 mg/kg/day

aPAD = 0.5 mg/kg/day	Deveolopmental tox-rabbits: decreased mean litter
size, increased incidence of resorption and increased post implantation
loss.

Chronic dietary	Oral NOAEL = 10 mg/kg/day

cPAD = 0.1 mg/kg/day	Chronic tox –dogs: decrease in body weight gains.

Short-term incidental oral	Oral NOAEL = 50 mg/kg/day	Developmental
tox-rabbits: decrease in  body weight gains, food consumption, and food
efficiency  (Maternal effects)

Intermediate-term incidental oral	Oral NOAEL = 10 mg/kg/day	13-week
tox-dogs: decreased body weight gains and food efficiency.

Short-term dermal	Dermal  NOAEL = 100 mg/kg/day	21-day dermal tox-rats:
decreased body weight gains

Intermediate-term dermal	Oral NOAEL = 10 mg/kg/day	13 –week tox-dogs
decreased body weight gains and food efficiency.

Short-term inhalation	Oral NOAEL = 50 mg/kg/day	Developmental
tox-rabbits: decrease in  body weight gains, food consumption, and food
efficiency  (maternal effects)

Intermediate-term inhalation	Oral NOAEL = 10 mg/kg/day	13 –week
tox-dogs decreased body weight gains and food efficiency

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 proposed 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.

Chronic Dietary Exposure Estimates

A chronic dietary analysis for halosulfuron-methyl was conducted using
tolerance levels and 100% CT for all existing and proposed 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 level of concern for the
U.S. population or any population subgroup.  The exposure to the general
U.S. population is 1.6% of the cPAD and the highest exposure is to all
infants (<1 year old) at 4.6% 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 groundwater 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 the population of concern, females 13-49 years old, the acute
dietary risk assessment reported in the Acute Dietary Exposure Estimates
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; thus,
estimated acute aggregate 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
700.  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 700.  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.

No chemical-specific exposure data for handlers or postapplication
activities are available to support the proposed uses of
halosulfuron-methyl.  In accordance with HED policy, occupational
handler exposures were estimated using the Pesticide Handlers Exposure
Database (PHED) Surrogate Exposure Guide (revised August, 1998).  MOEs
for occupational handlers reach or exceed the LOC of 100, and therefore,
are not of concern.

Most of the current proposed uses for halosulfuron-methyl are
soil-directed preplant or preemergent uses where no crop foliage is
present except for a postemergent application when soybeans are in the
V2-V4 growth stage.  Postapplication exposure and risk were assessed for
scouting and irrigation activities for short- and intermediate term
dermal exposure.  This assessment is considered to be a Tier I,
screening level estimate. The results demonstrate the dermal MOEs for
occupational postapplication workers on the day of application are
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 on soybean, 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]sulfony
l]-1-methyl-1H-pyrazole-4-carboxylate, as follows:

Soybean, seed	0.05 ppm

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

The propose use patterns and the directions for use are summarized in
Tables 2.1.1 and 2.1.2, respectively.

Table 2.1.1  Proposed Use Pattern for Halosulfuron-methyl

Crop	Product, Formulation	Treatment Type/Target of Application

	Application  Equipment	Maximum Application Rate

(lb ai/A)	Treatment Interval	Preharvest Interval (PHI)

Soybeans	GWN-3061

EPA Reg. No. 81880-2

Water-dispersible granules 75% ai	Broadcast to soil and foliage	Aerial,
Groundboom	0.062

lb ai/acre	Not provided	30 days

Table 2.1.2. Summary of Directions for Use of Halosufuron-Methyl

Applic. Timming, Type,  & Equip.	Applic. Rate

(lb ai/A)	Max. No.

Applic. per

Season	Max. Seasonal

Applic. Rate

(lb ai/A)	PHI	Use Directions and Limitations1

Soybean

Postharvest burndown (fall), broadcast, ground, or air	0.031-0.062	Not
specified (NS)	NS	NS	Application is to be made in the fall after
harvest, prior to ground freeze.  For control of broadleaf weeds, a COC
(1-2% v/v) and granular AMS (2-4 lb/A) or UAN (1-2% v/v) should always
be added.  Tank-mix partners include 2,4-D amine, 2,4-D LV  ester,
tribenuron-methyl, thifensulfuron-methyl, glyphosate (for emerged grass
weeds), or any other herbicide with registration for fall application.

Preemergence or preplant (spring); broadcast, ground or air	0.031-0.062
NS	NS	NS	Application is to be made to soybean varieties tolerant to
sulfonyl-urea herbicides only, 21 days prior to planting up to
preemergence (cracking) of soybeans.  For control of broadleaf weeds, a
COC (1% v/v) and granular AMS (2-4 lb/A) or UAN (1-2% v/v) should always
be added.  Tank-mix partners include glyphosate, 2,4-D LV ester, and
thifensulfuron-methyl (7-21 days preplant).

Postemergence; broadcast,  ground or air	0.031-0.062	NS2	NS	30 days
before grazing or harvest of forage or silage	Application is to be made
to soybean varieties tolerant to sulfonyl-urea herbicides only, at the
V2 to V4 growth stage.  An NIS or COC and granular AMS (2-4 lb/A) or UAN
(1-2% v/v) should always be added.  Tank-mix partners include glyphosate
(if soybean variety is also glyphosate tolerant), thifensulfuron-methyl,
and other registered postemergence soybean herbicides unless
specifically restricted by those product labels.

1  The supplemental label includes the following statements for all
application types:  “All applicable directions, restrictions and
precautions on the EPA registered [master] label are to be followed.
Refer to “TIME INTERVAL BEFORE PLANTING” table on the EPA-registered
label.”  COC = crop oil concentrate; NIS = nonionic surfactant; AMS =
ammonium sulfate fertilizer; and UAN = urea ammonium nitrate solution
(fertilizer).

2  The label states that for heavy infestations of nutsedge, sequential
applications may be required.

2.2 	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 2.2.1.  The
physicochemical properties of the technical grade of halosulfuron-methyl
are presented in Table 2.2.2.

Table 2.2.1	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% WG (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 2.2.2	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 the most recent risk assessment (Memo, M. Clock-Rust, et al.,
9/21/06; DP331643).  Briefly, 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.

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 non-specific decrease in body
weight gains at high dose levels in short- and long-term oral and dermal
studies. 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).  The
degree of concern is low and there are no residual uncertainties for
prenatal toxicity in both rats and rabbits. In both studies, there are
clear NOAELs/LOAELs for developmental and maternal toxicities,
developmental effects were seen in the presence of maternal toxicity,
and effects were only seen at the high dose. Additionally, in rats
developmental effects were seen at a dose which is approaching the
limit-dose. 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.
Halosulfuron-methyl is negative for mutagenicity in a battery of
mutagenicity studies.

The database for halosulfuron-methyl is sufficient to support a
tolerance petition for use in soybean. However, new data requirements as
presented in the 40 CFR Part 158 requires an immunotoxicity study for
halosulfuron-methyl. The toxicology database of this chemical does not
show any evidence of biologically relevant effects on the immune system
that relate to this chemical. The overall weight of evidence suggests
that this chemical does not directly target the immune system. HED does
not believe that conducting a functional immunotoxicity study will
result in a lower NOAEL than the regulatory dose for risk assessment,
and an additional factor (UFDB) for database uncertainty is not needed
to account for lack of this study.

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.

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.

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 the previous risk assessment (Memo, M. Clock-Rust, et al.,
9/21/06; D331643). 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 toxicity database for halosulfuron-methyl is complete for FQPA
safety evaluation with the exception of an immunotoxicity study, which
is required based on the new rule.  The halosulfuron-methyl toxicology
database 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 conducting a functional immunotoxicity study will result in
a lower NOAEL than the regulatory dose for risk assessment, and an
additional factor (UFDB) for database uncertainty is not needed to
account for the lack of this study.

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 Uncertainity Factors (UFs) to account
for neurotoxicity.

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.  EFED has provided conservative
ground and surface water modeling estimates.  The HED Residential SOPs
are used to assess post-application exposure to 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

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

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

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 with corn, sugarcane, and soybean; all
studies investigated pre- and postemergence uses.  The metabolism of
halosulfuron-methyl was similar in the three tested crops but dependent
on the mode of application (pre- or postemergence).  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.

HED has concluded that tolerances for halosulfuron-methyl residues in
poultry commodities are not required due to low use rates, low residues
of halosulfuron-methyl in poultry feed items, and the low transfer rate
of residues to poultry tissues (D173627 & D180565, 7/30/92, G.J.
Herndon; PP#2G4073).  The inclusion of poultry feed items from soybeans
(seed and meal) will not increase the dietary burdens expected from the
currently registered uses on alfalfa, corn, and sorghum; therefore, HED
continues to conclude that tolerances for poultry commodities are not
required.

Residue Analytical Methods

Plants:  The residue analytical methods data are adequate to satisfy
data requirements for the subject action.  For tolerance enforcement
purposes, residues in/on crop commodities, and residues of
halosulfuron-methyl in/on soybean commodities from the crop field trial
and processing studies were determined using acceptable enforcement
methodology. The GC method quantifies halosulfuron-methyl as its RRE
(1-H-pyrazole-4-carboxylic acid,
3-chloro-5-[(4,6-dimethoxy-2-pyrimidinyl)amino]-1-methyl, methyl ester)
using thermionic-specific detection (TSD, nitrogen specific).  Monsanto
Analytical Method RES-109-97-4 (MRID 44495801) has been validated as an
enforcement method by the Analytical Chemistry Branch (ACB)/BEAD.  The
limit of quantification on rice straw, sugarcane, milo grain, field corn
grain, cotton gin byproducts, and almond nutmeats was estimated to be
0.05 ppm (D250584, G. Jeffrey Herndon, 10/28/98).

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, 3/8/94,
G.J. Herndon).  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

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

The available storage stability data for soybeans are adequate to
support storage conditions and durations of seed samples from the
soybean field trial and processing studies.  Processed soybean samples
were stored <30 days from collection to analysis; therefore, supporting
storage stability data are not required for these matrices.

Meat, Milk, Poultry, and Eggs

Provided the petitioner amends the proposed label to prohibit the
grazing or feeding of treated soybean forage/silage and hay, the
inclusion of the applicable livestock feed items from soybeans (seed,
meal, and hulls) would not increase the dietary burden expected from the
currently registered uses on alfalfa, corn, and sorghum.  Therefore, HED
continues to conclude that tolerances for poultry commodities are not
required and the existing livestock tolerances (0.1 ppm for meat
byproducts of cattle, goat, hog, horse and sheep) are adequate. If the
petitioner intends to support a 30-day PGI/PHI for soybean forage and
hay, the dietary burdens for livestock will be re-evaluated when the
additional field trial data become available.

Crop Field Trials

The petitioner has submitted field trial data for halosulfuron-methyl
with sulfonylurea-tolerant soybeans (MRID 47527401).  Twenty soybean
field trials were conducted in Zones 2 (NC, SC; 2 trials), 4 (AR, LA; 3
trials) and 5 (IA, IL, IN, MN, MO, NE, OH; 15 trials) during the 2007
growing season. The results of the soybean seed field trials are
summarized in Table 4.1.1  Residues of halosulfuron-methyl were
nonquantifiable (<0.01 ppm) in/on all samples of sulfonylurea-tolerant
soybean seed harvested 88-133 days following a single foliar broadcast
application of the 75% WG formulation of halosulfuron-methyl, made early
postemergence (BBCH 12-14) at 0.0603-0.0639 lb ai/A.

Table 4.1.1.	Summary of Residue Data from Crop Field Trials with
Halosulfuron-methyl.

Crop matrix	Total Applic. Rate

 (lb ai/A)	PHI (days)	Residue Levels (ppm)

	n	Min.	Max.	HAFT1	Median	Mean	Std. Dev.2

SOYBEAN (proposed use = fall burndown, preplant/preemergence, or
postemergance at 0.062 lb ai/A application rate, 30-day PHI/PGI for
forage and silage)

Soybean seed	0.0603-0.0639	88-133	40	<0.01	<0.01	<0.01	0.01	0.01	NA

1  HAFT = Highest Average Field Trial.

2  Standard deviation is not applicable (NA) when all residues are below
the method LOQ.

HED concludes that, provided the petitioner revises the proposed use
pattern as stated below, the submitted field trial data will support the
proposed tolerance for residues of halosulfuron-methyl in/on soybean
seed at 0.05 ppm.  The submitted field trial data reflect a single
postemergence foliar broadcast application at 0.0603-0.0639 lb ai/A,
with soybean seed harvested at PHIs of 88-133 days. The number and
locations of the field trials are in accordance with 860.1500 for
soybean.  An acceptable method was used for the quantitation of residues
of halosulfuron-methyl, and the study is supported by adequate storage
stability data.  No residue data were provided for soybean forage and
hay; however, feeding and grazing of soybean forage/silage and hay can
be prohibited since they are considered to be under grower control.
Residue data for aspirated grain fractions were not provided but are not
required because application is to be made to soybean plants early in
the season.

The petitioner must revise the proposed Section B/label as indicated
below and in Section 860.1200 of this review since the available residue
data do not support the proposed use:

The proposed Section B/label must be revised to specify a maximum of one
application per year at the maximum application rate of 0.062 lb
ai/A/year since the field trial residue data reflect one application at
approximately 0.062 lb ai/A/year.

Although the postemergence application is restricted to the vegetative
V4 stage (4th trifoliate), prior to flowering/pod formation, a
preharvest interval for soybean seed must be stated.  Based on the
available field trial data, the proposed Section B/label must be revised
to establish a preharvest interval for soybean seed of 88 days.

The petitioner must revise the proposed Section B/label to prohibit the
grazing or feeding of treated soybean forage/silage and hay since no
residue data were provided for soybean forage and hay.

If the petitioner wishes to support a 30-day PGI/PHI for soybean
forage/silage and hay, residue data will be required for soybean forage
and hay harvested at a 30-day preharvest interval.

Processed Food and Feed

The petitioner has submitted a processing study conducted in IL for
halosulfuron-methyl with sulfonylurea-tolerant soybeans. The processing
data for soybean are acceptable. The results indicate that residues of
halosulfuron-methyl in soybean processed commodities (meal, hulls, and
refined oil) are unlikely to exceed the tolerance on soybeans;
therefore, separate tolerances for the processed commodities are not
needed (MRID 47527401).

Confined/Field Accumulation in Rotational Crops

Acceptable confined rotational and limited field rotational crop studies
were previously submitted and review (Memoranda: 3/11/93, G.J. Herndon,
D188144; D192510, G.F. Kramer, D192510).  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, 10/29/98, G.J. Herndon).  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.

At this time, the proposed use on soybeans is not expected to alter the
potential for inadvertent residues in rotated crops from currently
registered uses.  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 petitioner has proposed the
following tolerance expression: halosulfuron-methyl [methyl
3-chloro-5-(4,6-dimethoxypyrimidin-2-ylcarbamoylsulfamoyl)-1-methylpyraz
ole-4-carboxylic acid and expressed as parent equivalents.

Table 4.1.2 presents the proposed/recommended tolerance level and the
corrected commodity definition.  The submitted soybean processing study
is adequate and indicates that no separate tolerances are required for
the processed commodities of soybean meal, hulls, and refined oil.

Table 4.1.2. 	Tolerance Summary for Halosulfuron-methyl

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

soybean	0.05	0.05	Soybean, seed

The petitioner must submit a revised Section F to: 1) revise the
proposed tolerance expression for halosulfuron-methyl to be the same as
the Chemical Abstracts Service (CAS) nomenclature (i.e., methyl
3-chloro-5-[[[[(4,6-dimethoxy-2-pyrimidinyl)amino]carbonyl]amino]sulfony
l]-1-methyl-1H-pyrazole-4-carboxylate) and to remove the phrase “and
expressed as parent equivalents” which is not needed for a tolerance
for the parent only; and 2) propose a tolerance for soybean, seed
instead of soybean.

Provided the use pattern is amended as requested, adequate field trial
data are available to support the proposed tolerance of 0.05 ppm on
soybean, seed.  Because all residue values for soybean seed were below
the LOQ, the Agency’s Guidance for Setting Pesticide Tolerances Based
on Field Trial Data was not utilized for determining an appropriate
tolerance level.

International Residue Limits

There are no Codex, Canadian, or Mexican MRLs established for residues
of halosulfuron-methyl in/on soybean matrices.

Drinking Water Residue Profile

The drinking water residues profile was provided by the Environmental
Fate and Effects Division (EFED) (M. Barrett, D358032, 5/27/09).
Halosulfuron-methyl is a mobile and persistent compound which may reach
ground or surface waters, including those used as drinking water
sources.  Its persistence in soil and water appears to be variable.

 The Tier I estimated drinking water concentrations (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
groundwater based on the SCI-GROW model result is 0.065 ppb. The results
are summarized in Table 4.1.3.

The estimated drinking water concentrations shown in Table 4.1.3 are
incorporated directly into this dietary assessment.  Water residues are
incorporated in the DEEM-FCID into the food categories “water, direct,
all sources” and “water, indirect, all sources.”

Table 4.1.3.  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

Halosulfuron-methyl acute and chronic dietary exposure assessments were
conducted using the Dietary Exposure Evaluation Model software with the
Food Commodity Intake 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.

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.  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
exposure estimates are 1.6% of the cPAD for the general U.S. population
and 4.6% of the cPAD for all infants (<1 year old), the most highly
exposed population subgroup.

Table 4.2 Summary of Dietary (Food & Drinking Water) Exposure/Risk

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	0.001584	1.6

All Infants (< 1 year old)

	0.004592	4.6

Children 1-2 years old

	0.002498	2.5

Children 3-5 years old

	0.002405	2.4

Children 6-12 years old

	0.001689	1.7

Youth 13-19 years old

	0.001239	1.2

Adults 20-49 years old

	0.001446	1.4

Adults 50+ years old

	0.001488	1.5

Females 13-49 years old	0.003305	<1	0.001436	1.4

Cancer Dietary Risk

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.   Therefore,
halosulfuron-methyl is not expected to pose a cancer risk for humans.

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 soybeans, and 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, 09/21/2006). 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 (K. O’Rourke,
D278588, 8/28/02) and is summarized in the following sections.

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
total MOE (dermal + inhalation exposure) for residential handlers is
2,000,000 is well above the LOC of 100 and is not of risk concern.  The
upper-bound risk estimate for residential handlers and postapplication
exposure is a MOE of 5,200.

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

21,000	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
postapplication 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 toddler postapplication dermal
exposure, (2) toddlers’ 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)
toddlers’ incidental ingestion of soil from pesticide-treated
residential areas.  Postapplication 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 toddlers 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 toddlers 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
Postapplication 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 4.2.1 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

0.003305

<1 (0.66)

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 (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.

 TC \l2 "7.2	Short-Term Aggregate Risk 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	32,000	N/A	5,500	7,000,000	4,700

Females, 13-49 years old

35,000	N/A	5,500	7,000,000	4,800

All Infants

(<1 year old)

11,000	43,000	4,200	N/A	2,800

Adults 50+ years

34,000	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)].

 	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.

 [(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).

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

As an additional protective measure, residential handler exposures were
included in the intermediate-term aggregate risk assessment, although
residential exposure over the intermediate-term (more than 30 days) 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 700.  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 700.  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	0.001584	N/A

0.0183	0.0000071	500

Females, 13-49 years old

0.001436	N/A

0.0183	0.0000071	500

All Infants

(<1 year old)

0.004592	0.0006731

0.0090	N/A	700

Adults 50+ years old

0.001488	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)

6.4	Cancer Risk TC \l2 "6.5	Cancer Risk

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.   Therefore,
halosulfuron-methyl is not expected to pose a cancer risk for humans.

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, flagging, 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 to soybeans using aerial and
groundboom equipment at a maximum application rate of 0.062 lb ai/acre,
which is used for estimating exposure and risk for handlers. No
chemical-specific handler exposure data were submitted in support of
this registration.  It is the policy of the HED to use data from the
Pesticide Handlers Exposure Database (PHED), Version 1.1 as presented in
PHED Surrogate Exposure Guide (8/98) to assess handler exposures for
regulatory actions when chemical-specific monitoring data are not
available (HED Science Advisory Council for Exposure (ExpoSAC) Standard
Operating Procedure (SOP) No. 7, dated 1/28/99).

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 level of concern (LOC) for occupational
exposure is for margins of exposure (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 8.2.1
(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

Aerial Applications (PHED)	Soybeans	0.062	1200	0.066	0.066	0.77	0.07
0.07	0.00082	1,400	1,400	61,000	1,400	1,400

Mixing/Loading Dry Flowables for

Groundboom Applications (PHED)	Soybeans	0.062	200	0.066	0.066	0.77	0.012
0.012	0.00014	8,600	8,600	370,000	8,400	8,400

Applicator

Applying Sprays via

Aerial Equipment (PHED)	Soybeans	0.062	1200	0.005

(eng. control)	No Data	0.068

(eng. control)	0.0053

(eng. control)	No Data	0.000072

(eng. control)	19,000

(eng. control)	No Data	690,000

(eng. control)	18,000

(eng. control)	No Data

Applying Sprays via

Groundboom Equipment (PHED)	Soybeans	0.062	200	0.014	0.014	0.74	0.0025
0.0025	0.00013	40,000	40,000	380,000	36,000	36,000

Flagger

Flagging for

Aerial Sprays Applications (PHED)	Soybeans	0.062	350	0.011	Not
applicable	0.35	0.0034	Not applicable	0.00011	29,000	Not applicable
460,000	28,000	Not applicable

a.  Application Rates based on proposed uses on label for
halosulfuron-methyl product GWN-3061 (EPA Reg. No. 81880-2).

b.  Science Advisory Council Policy  No.  9.1

c.  Unit Exposures based on PHED Version 1.1.  Engineering control unit
exposure for applying sprays via aerial equipment = enclosed cockpit.

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).

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).  Those risks specified as engineering
control represent enclosed cockpit application.

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

Aerial Applications (PHED)	Soybeans	0.062	1200	0.066	0.066	0.77	0.053
0.053	0.00082	190	190	12,000	190	190

Mixing/Loading Dry Flowables for

Groundboom Applications (PHED)	Soybeans	0.062	200	0.066	0.066	0.77
0.0088	0.0088	0.00014	1100	1,100	73,000	1,100	1,100

Applicator

Applying Sprays via

Aerial Equipment (PHED)	Soybeans	0.062	1200	0.005

(eng. control)	No Data	0.068

(eng. control)	0.004

(eng. control)	No Data	0.000072

(eng. control)	2,500

(eng. control)	No Data	140,000

(eng. control)	2,500

(eng. control)	No Data

Applying Sprays via

Groundboom Equipment (PHED)	Soybeans	0.062	200	0.014	0.014	0.74	0.0019
0.0019	0.00013	5,400	5,400	76,000	5,000	5,000

Flagger

Flagging for

Aerial Sprays Applications (PHED)	Soybeans	0.062	350	0.011	Not
applicable	0.35	0.0026	Not applicable	0.00011	3,900	Not applicable
92,000	3,800	Not applicable

a.  Application Rates based on proposed uses on label for
halosulfuron-methyl product GWN-3061 (EPA Reg. No. 81880-2).

b.  Science Advisory Council Policy # 9.1

c.  Unit Exposures based on PHED Version 1.1 Engineering control unit
exposure for applying sprays via aerial equipment = enclosed cockpit.

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).

ily 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).  Those risks specified as engineering
control represent enclosed cockpit application.

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:  HED assumes that inhalation exposures are minimal following
outdoor applications of an a.i. with a low vapor pressure.  Since the
proposed use of halosulfuron-methyl include only outdoor applications
and halosulfuron-methyl has a low vapor pressure, postapplication
inhalation exposures and risks are not assessed.

Dermal:  Most of the proposed uses for halosulfuron-methyl are
soil-directed preplant or preemergent uses where no crop foliage is
present.  Currently, HED has no transfer coefficients 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 assessed.   One proposed use is for a
postemergent application when soybeans are in BBCH 12-14 stage.
Postapplication exposure and risk were assessed for this proposed use.
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 were submitted in support of this
registration action, dermal exposures during postapplication activities
were estimated using dermal transfer coefficients from the Science
Advisory Council for Exposure Policy Number 003.1: Agricultural Transfer
Coefficients, August 2000, summarized in Table 6 below and the following
assumptions:

Application Rate	= 	0.062 lb ai/A

Exposure Duration	=	8 hours per day

Body Weight		=	70 kg for adult male

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

Fraction of a.i. 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’s Science Advisory Council (SAC) for
Exposure.

Table 8.2.1. Anticipated Postapplication Activities and Dermal Transfer
Coefficients

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

Soybean	Field/row crop low/medium	Medium	1500	Scouting, Irrigation

Low	100	Hand weeding

	8.2.2 	Short- and Intermediate-Term Postapplication Risk Estimates

The postapplication exposures and risks associated with agricultural
crops are summarized in Table 8.2.1.  All scenarios resulted in MOEs
greater than 100 on day 0 (12 hours after
application)愠摮琠敨敲潦敲愠敲渠瑯漠潣据牥潴䠠䑅
ഠ名扡敬㠠㈮㈮倠獯慴灰楬慣楴湯䔠灸獯牵湡
楒歳映牯䠠污獯汵畦潲⵮敭桴汹܇牃灯䄇瑣癩瑩ݹ牔湡
晳牥䌍敯晦捩敩瑮ൡ挨㉭栯⥲䐇呁ݢ䙄捒

(μg/cm2)	Short-Term	Intermediate-Term

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

Soybean	Scouting, Irrigation	1,500	0

(12 hours)	0.14	0.024	4,200	0.018	560

	Hand weeding	100	0

(12 hours)	0.14	0.0016	63,000	0.0012	8,400

a	Transfer coefficients and associated activities from ExpoSAC Policy
Memo 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

The petitioner must revise the proposed Section B/label to specify a
maximum of one application per year at the maximum application rate of
0.062 lb ai/A/year since the field trial residue data reflect one
application at approximately 0.062 lb ai/A/year.

Although the postemergence application is restricted to the vegetative
V4 stage (4th trifoliate), prior to flowering/pod formation, a
preharvest interval for soybean seed must be stated.  Based on the
available field trial data, the petitioner must revise the proposed
Section B/label to establish a preharvest interval for soybean seed of
88 days.

The petitioner must revise the proposed Section B/label to prohibit the
grazing or feeding of treated soybean forage/silage and hay since no
residue data were provided for soybean forage and hay.

860.1500 Crop Field Trials

If the petitioner wishes to support a 30-day PGI/PHI for soybean
forage/silage and hay,  residue data will be required for soybean forage
and hay harvested at a 30-day preharvest interval.

  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 rearrangement ester (RRE) of halosulfuron-methyl must
be submitted to the EPA National Pesticide Standards Repository.

860.1550 Proposed Tolerances

The petitioner must submit a revised Section F to revise the proposed
tolerance expression for halosulfuron-methyl to be the same as the
Chemical Abstracts Service (CAS) nomenclature (i.e., methyl
3-chloro-5-[[[[(4,6-dimethoxy-2-pyrimidinyl)amino]carbonyl]amino]sulfony
l]-1-methyl-1H-pyrazole-4-carboxylate) and to remove the phrase “and
expressed as parent equivalents” which is not needed for a tolerance
for the parent only.

The petitioner must submit a revised Section F to propose a tolerance
for soybean, seed instead of soybean.

9.3	Occupational and Residential Exposure

None.

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, 09/21/2009.

Residue Chemistry Assessment

  SEQ CHAPTER \h \r 1 Halosulfuron-methyl.  Application for Amended
Section 3 Registration to Add Uses on Soybeans.  Summary of Analytical
Chemistry and Residue Data.  PP#8F7424, D358029, N. Dodd, 04/23/2009.

Dietary Exposure Analysis

  SEQ CHAPTER \h \r 1 Halosulfuron-methyl: Acute and Chronic Aggregate
Dietary (Food and Drinking Water) Exposure and Risk Assessment for the
Section 3 Registration Action on Soybeans. D359457, N. Dodd, 05/27/2009.

Occupational and Residential Exposure Assessment

HALOSULFURON-METHYL: Occupational and Residential Risk Assessment for
Proposed Field use of Halosulfuron-methyl on Soybeans.  D3359456, Barry.
O’Keefe, 04/27/2009.

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
捡摩琭敨瀠楲据灩污猠楯敭慴潢楬整漠慨潬畳晬牵
湯洭瑥票⹬܇㠍〷㔮〳‰⠠㐸㈭ܩ䴍瑵条湥捩ⴠ䜠湥
畍慴楴湯ⴠ䠠浡瑳牥⠠桃湩獥⥥ഇ㌴ㄶ㌶㌰⠠㤱㔹

敍慴潢楬整 捁散瑰扡敬ഠ⬨⴯㥓
潃据㨮㌠〵㌭〱‰
業牣杯⽭䱭ܠ

㄀$摧座'

⸀⼀㄀$摧座'

.

4

C

S

T

r

‘

“

¨

Æ

È

.

/

_

r

’

“

Î

è

5

j

jÝ

j`

jÑ

jT

␃ഃ׆Āᭈ༊ꂄ帅ꂄ愅̤摧䦉ë

h

h%

h¸V

kd

@

@

 h´

>

 h

 hØ

hØ

$

hØ

  hØ

 hØ

hØ

hØ

 hØ

hØ

耀㬆

耀㬆

耀㬆

耀㬆

攃昀Ĵ瑹缵ø

hØ

愀Ĥ摧缵ø

혈Fᴃἀ⼍괛$Ȇ

혈Fᴃἀ⼍괛$Ȇ

혈Fᴃἀ⼍괛$Ȇ

혈Fᴃἀ⼍괛$Ȇ

혈Fᴃἀ⼍괛$Ȇ

혈Fᴃἀ⼍괛$Ȇ

혈Fᴃἀ⼍괛$Ȇ

혈Fᴃἀ⼍괛$Ȇ

혈Fᴃἀ⼍괛$Ȇ

hd

h¸V

$

$

$

hÐ

hÐ

 h¬K

 hX

$

 h

&

@

@

@

&

&

&

&

&

&

&

&

&

&

&

&

&

&

&

&

&

&

@

$

@

{

ù

û

ü

þ

B

C

D

O

e

f

g

w

x

y

‚

ƒ

„

Ž

ž

Ÿ

Å

Æ

Ç

È

Ý

ß

ã

ø

ý

þ

ÿ

+g

k

y

}

„

ˆ

®

Ç

Ø

Ù

Ý

ä

è

î

ø

þ

 h›

@

kd9

„@

„0ý^„@

  ha

&

hó

 hó

 hó

hó

hó

  ha

 ha

&

½

&

@

hó

"̀Ĥ옍)

  ha

 ha

 hX

 h

㄀$摧וC

摧✈

摧✈

摧✈

摧✈

摧✈

摧✈

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

870.5300  (84-2)

Mutagenic - (HGPRT) - Hamster (Chinese).

42139431 (1991) - Metabolite/ 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.

Halosulfuron-methyl Human Health Risk Assessment	 D358031

 PAGE

Page   PAGE  1  of   NUMPAGES  39