Page 2 of 18

Executive Summary

The HED Registration Review Team has evaluated the most recent human health assessments

and database for the herbicide rimsulfuron to determine whether sufficient data are available and whether any updates are needed to support Registration Review. HED has considered the most

recent human

- health risk assessments for rimsulfuron , updates to the toxicity, exposure, and usage databases , and current Agency science policy and risk assessment methodologies to determine the scope of work necessary to support Registration Review. In addition, HED conducted an open literature search to look for new literature relevant to the human health ris k

assessment. The results of the literature search showed that no new information relevant to the human health risk assessment has been published.

Rimsulfuron is a sulfonylurea herbicide (Group 2) used to control certain broad

- leaf weeds and grasses, and acts by inhibiting the acetolactate synthase (ALS) biochemical process, a process not present in humans. Rimsulfuron has low acute toxicity but is a moderate eye irritant . With repeated dosing, the kidney and liver were the primary target organs of rims ulfuron toxicity.

Subchronic studies indicate that target organs for rimsulfuron are the liver and kidney in the rat and dog, along with the testis and blood in the mouse and dog. In the mouse, the stomach was also a target organ. Adverse changes in body weight and food consumption were observed in rats, mice and dogs. Rimsulfuron is classified as “ Not Likely to be Carcinogenic to Humans.” It is negative for mutagenicity in a battery of genotoxicity studies. The toxicity and exposure database supported the reduction of the FQPA Safety Factor to 1X.

Sufficient data are available to assess the toxicity of rimsulfuron. All the requirements of the new Part 158 guidelines have now been submitted or waived. The recently submitted immunotoxicity, acute neu rotoxicity and subchronic neurotoxicity studies are currently under

review. Once these new studies have been completely reviewed, the rimsulfuron Registration Review Team recommends that the points of departure and safety factors used for risk assessment purposes for rimsulfuron be re

- examined.

Rimsulfuron is currently registered for use on non

- residential turf such as golf courses, sod farms

athl etic fields, industrial and commercial lawns and similar nonresidential areas

. Additionally

, it is registered on agricultural food crops including bushberries, caneberries, soybeans, potatoes, field corn, tomatoes, grapes, various tree fruits, and tree nu ts. There is currently a pending use on chicory.

The residue chemistry database is sufficient to support current and pending registrations of

rimsulfuron

. The nature of the residue in plants and livestock has been defined. Adequate f ield trial, rotati onal crop , and storage stability data are available.

A new risk assessment may be needed depending on the results of the toxicology studies that are currently in review and the reevaluation of databases using current policies. O ccupational

exposure assessments may need to be reassessed based on current Occupational and Residential Exposure ( ORE ) polic ies and exposure data and to consider the exposures that were not previously assessed due to the lack of the endpoints at the time the risk assessment was beingPage 3 of 18

conducted

. In addition, the Agency may need to consider off

- target movement of pesticides into residential settings.

Introduction

HED has evaluated the existing human health risk assessments for rimsulfuron to determine

whe ther sufficient data are available and whether a new human health risk assessment is needed to support Registration Review. HED has considered the most recent risk assessments for

rimsulfuron

, updates to its toxicity, exposure and usage databases, and cur rent Agency science policies and risk assessment methods. The most recent risk assessment for rimsulfuron was conducted in 2012 (D391083, C. Walls, 5/04/12 ).

Hazard Identification/ Toxicology

Rimsulfuron belongs to the pyrimidinylsulfonylurea class of herbicides and controls weeds by inhibiting the acetolactate synthase (ALS) biochemical process. Since ALS is a component in

the synthesis of some essential amino acids, weed survival and growth are inhibited. A direct

correlation of this mode of action in plants to a mode of action in mammals is not clear because ALS is not present in mammals.

The toxicity database indicates that target organs for rimsulfuron are the liver and kidney in the rat and dog, along with the testis and blood in the m ouse and dog. In the mouse, the stomach was also a target organ. Adverse changes in body weight and food consumption were observed in rats, mice and dogs.

Effects seen in the subchronic and/or chronic toxicity studies in one or more species included decreased body weight and body weight gain, increased relative and/or absolute liver and kidney weights, diuresis (increased urine volume), decreased liver enzym es and bilirubin and increased serum cholesterol, fatty change, hepatocellular hypertrophy, increased red blood cell (RBC), hemoglobin and platelet concentration, increased incidences of dilation and cysts in the glandular stomach, degeneration of the test icular artery and tunica albuginea, increased incidence of seminiferous tubule degeneration and increased numbers of spermatid giant cells present in epididymides in males.

HED classified rimsulfuron as “Not Likely to be Carcinogenic to Humans ” based on t he lack of evidence for carcinogenicity in rats and mice in the long term carcinogenicity studies. Rimsulfuron is not considered to be a mutagen or clastogen. It has low acute oral, dermal and

inhalation toxicity, but is a moderate eye irritant. It is n ot a dermal sensitizer.

In the developmental toxicity study in rats, no developmental toxicity was seen at the highest

dose tested. In the developmental toxicity study in rabbits, and in the two generation study in rats, developmental/offspring toxicity was seen in the presence of maternal/systemic toxicity of comparable severity, and at similar dose levels. Consequently, there is no quantitative or qualitative evidence of increased susceptibility following pre

- and/or postnatal exposures, and

there are no concerns or residual uncertainties. There was no evidence of neurotoxicity or immunotoxicity in the recently submitted studies which have undergone preliminary evaluationPage 4 of 18

and are currently under detailed review. Therefore, HED has concluded that the F QPA Safety

Factor should be reduced to 1X.

All the requirements of the revised 40 CFR Part 158 guidelines have now been submitted or

waived. The recently submitted immunotoxicity, acute neurotoxicity and subchronic neurotoxicity studies are currently und er review. Once these new studies have been completely reviewed, the rimsulfuron Registration Review Team recommends that the points of departure and safety factors used for risk assessment purposes for rimsulfuron be re

- examined.

Toxicity endpoints, points of departure, and safety factors for rimsulfuron risk assessment were initially se lected by HED in 1998 ( HED Document No. 012501 , J Rowland, 19/FEB/1998) and updated in 2006 ( TXR # 0054356, E. Rinde, 27/SEP/ 2006) and in 2011 (D384623, E. Holman, 11/04/11) for the following exposure scenarios: chronic dietar y; short

- and intermediate

- term dermal, and short

- and intermediate

- term inhalation

. Long

- term dermal and inhalation endpoints

were not identified because exposure is not anticipated for these scenarios. An endpoint for acute dietary risk was not selected because no adverse effects were observed which could be attributed to a single dose exposure. The endpoint for chronic dietary risk assessment was

chose n from the rat chronic/carcinogenicity study, and was based on liver and body weight

effects. Incidental oral endpoints were not selected because residential exposures are not anticipated. The endpoint for dermal and inhalation risk assessments for occupa tional workers

was chosen from the 90

- day oral study in the dog, and was based on kidney effects. The toxicity endpoints are presented in Attachment 3

.

Conclusions : No new toxicity data are required to support the registration review of rimsulfuron

. Once all data have been reviewed, the rimsulfuron Registration Review Team recommends that the points of departure and safety factors used for risk assessment purposes for rimsulfuron be

re

- examined. However, a preliminary screen of the recently submitted studies indicate that the PODs will not change.

Dietary Exposure

The residue chemistry data and drinking water data are adequate to assess dietary exposure. The most recent dietary (food and drinking water) exposure assessment was conducted in 2011 (D 39 4389

, E. Holman, 10/28 /11) using the Dietary Exposure Evaluation Model DEEM

- FCID TM

, Version 2.03. This assessment was conducted to support the pending 2012 PRIA action for an additional food use on chicory

. The dietary exposure assessment relies on cons ervative inputs (tolerance level residues, 100% crop treated, DEEMTM default processing factors) to model

exposure to rimsulfuron through food and drinking water.

The e stimated drinking water concentration (EDWC) of rimsulfuron was provided by the

Enviro nmental Fate and Effects Division (EFED) and incorporated directly into the chronic

assessment

. EFED estimated residues of rimsulfuron in surface water and groundwater using the FIRST and SCIGROW (Screening Concentrations in Groundwater) models, respectiv ely. The

chronic surface water EDWC (0.120 ppb) was higher than the groundwater EDWC (0.016 ppb) ; therefore, the surface water value of 0.120 ppb was used in the chronic dietary assessment. The

assessments are based on reliable data and will not underest imate exposure/risk.Page 5 of 18

The chronic dietary exposure estimates for food and drinking water are below HED’s level of concern for the general U.S. population and all population subgroups ( <1 % of the cPAD for the general U.S. population and <1 % of the cPAD for children 1 to 2 years old

, the most highly exposed population subgroup).

HED classified rimsulfuron as “ no evidence of carcinogenicity to humans ;” therefore, quantification of human cancer risk was not conducted.

The residue chemistry database is sufficient to support current and pending registrations. The nature of the residue in plants and livestock has been defined. The residue of concern in plant

and livestock commodities for risk assessment and tolerance setting purposes is rimsulfuron. N o tolerances have been established for livestock commodities. Acceptable high performance liquid chromatography with tandem mass spectros copy detection (LC/MS/MS) and HPLC/UV (ultra

violet) methods are available to enforce the established tolerances . Rim sulfuron is not recovered by FDA Multiresidue Methods.

Ad equate storage stability data are available to support storage durations for rimsulfuron. Adequate confined rotational crop data are available to support minimum plant

- back intervals up

to 18 month s, depending on the end

- use product.

Conclusions: Provided that EFED drinking water estimates do not need revision , a new diet ary assessment for rimsulfuron may not be required for the purpose of registration review. Furthermore, a lthough a new version of DEEM (Version 3.04) will be released, a new dietary

risk assessment may not be needed since it is anticipated that the changes in the model will not

affect the risk conclusion.

Residential Exposure

Residential Handlers

A r eside ntial handler exposure assessment is not required because rimsulfuron is only applied to

use sites that are not treated by residential handlers (e.g., golf courses and other non

- residential turf areas such as industrial parks, tank farms, sod farms, seed f arms, and professionally managed sports fields ).

Residential Post

- A pplication

Based on the current use patterns, t here is only potential for post

- application dermal exposure for recreational golfers. Dermal exposure was not assessed at the time of registration because n o dermal endpoint was selected based on the lack of dermal toxicity. However, the endpoints have

been re

- evaluated since the golf course turf registration and a dermal endpoint has now been selected. Therefore, a new risk assessment is needed for the existing golf course turf use

.Page 6 of 18

Conclusions: A new risk assessment is needed include the short

- term dermal exposure for the recreational golfer.

Aggregate Risk Assessment

A ggregate assessments consider exposures from food, drinking water, and residential uses. In

the most recent human heal th risk assessment (D391083, C. Walls, 5/04/12 ), aggregate risks were estimated for the chronic (food and dr inking water) exposure duration . As previously mentioned, these aggregate dieta ry risks were below HED’s level of concern. As previously stated, a dermal end point was not selected when the golf turf was first registered. However, the endpoints have been re

- evaluated since the golf turf registration and a dermal endpoint has now

b een selected. Therefore, short

- term aggregate risk assessments are now required since a short

or intermediate

- term dermal tox icity endpoint has been identified

.

Conclusions: Currently, t he a ggregate risk assessment include s only food and drinking water

. However

, it will need to be reassessed to include the short

- term dermal exposure for the recreational golfer

.

Occupational E xpos ure

Rimsulfuron is currently registered for use on several agricultural crops as well as on g olf course and other professionally managed turf areas . There is potential for short

- and intermediate

- term occupational exposure to rimsulfuron during handling (mixing, loading, and applying) and post

application activities.

Occupational Handlers

O ccupational handler exposure and risk assessments have been conducted on caneberries, bushberries, and the pending use on chicory

. The resulting risk estimates are not of concern (MOEs ranging from 370 to 11 ,000). Occupational exposure and risk assessmen ts were not conducted for uses on golf course

, sod farms athletic fields, industrial and commercial lawns and similar nonresidential areas or the agricultural food crops including soybeans, potatoes, field corn, tomatoes, grapes, various tree fruits, and t ree nuts. Dermal and inhalation end points were not selected due to lack of observed toxic effects when these uses were registered. However, the endpoints have been re

- evaluated and dermal and inhalation endpoints have now been selected. Therefore, a n ew occupational handler risk assessment is needed

.

Occupational Post

- A pplication

There is a possibility for agricultural workers to have post

- application dermal exposure to

rimsulfuron following its uses. Based on the use pattern for bushberries and caneberries, it was determined that post

- application dermal exposure would be negligible and therefore not quantitatively assessed

. Additionally, t he resulting post

- application risk estimates for chicory are also not of concern (MOEs ranging from 1,300 to 12 ,000).Page 7 of 18

Occupational post

- application exposure and risk assessments were not conducted for the following uses : soybeans, potatoes, field corn, tomatoes, grapes, vari ous tree fruits, tree nuts , and golf course turf because when these uses were reg istered a d ermal end point was not selected due to lack of observed toxic effects. However, the endpoints have been re

- evaluated and a dermal endpoint has now been selected. Therefore, a new occupational post

- application risk assessment

is needed.

Bas ed on the Agency's current practices, a quantitative occupational post

- application inhalation

exposure assessment has not been performed for rimsulfuron at this time. However, there are multiple potential sources of post

- application inhalation exposure to individuals performing post

application activities in previously treated fields. These potential sources include volatilization of pesticides and resuspension of dusts and/or particulates that contain pesticides. The Agency sought expert advice and inpu t on issues related to volatilization of pesticides from its Federal Insecticide, Fungicide, and Rodenticide Act Scientific Advisory Panel (SAP) in December 2009. The Agency received the SAP’s final report on March 2, 2010 ( http://www.epa.gov/scipoly/SAP/ meetings/2009/120109meeting.html ). The Agency is in the process of evaluating the SAP report as well as available post

- application inhalation exposure data generated by the Agricultural Reentry Task Force and may, as appropriate, develop policies and proc edures to identify the need for and, subsequently, the way to incorporate occupational

post

- application inhalation exposure into the Agency's risk assessments. If new policies or procedures are put into place, the Agency may revisit the need for a quantit ative occupational

post

- application inhalation exposure assessment for rimsulfuron

.

Conclusions: There is sufficient information available to assess occup ational handler and post

application exposure s . However, not all of the occupati onal exposure scenarios were assessed based on current ORE policies and current toxicological endpoints

. An up

- to

- d at e handler and

post

- application occupational assessment is needed , accounting for the changes in policies and endpoints

.

Public Health and Pesticide Ep idemiology Data

The evaluation of the OPP Inciden t Data System (IDS) indicated nine incidents identified in the

United States for rimsulfuron in either Main or Agg regate IDS, from January 1, 2007 to February 22, 2012 (D402251

, S. Recore, 05/08 /12 ). Base d on the low frequency and severity of incident cases, there does not appear to be a concern at this time that would warrant further investigation. The Agency will continue to monitor the incident information and if a concern is triggered, additional analy sis will be included in the risk assessment.

Tolerance Assessment and International Harmonization

The US tolerances for field corn grain, potatoes, and tomatoes are harmonized with Canada. The US tolerance for bushberry subgroup 13

- 07B is not in harmony with Canada ; the US tolerance of 0.01 ppm is established based on field trial data on blueberries . The Can adian MRL was not established for subgroup 13

- 07B but was established at 0.05 ppm on blueberries. There are no

Codex MRLs established for rims ulfuron (See Attachment 2).Page 8 of 18

Environmental Justice

Potential areas of environmental justice concerns, to the extent possible, were considered in this human health risk assessment, in accordance with US Executive Order 12898, "Federal Actions to Address Environmental Justice in Minority Populations and Low

- Income Populations," 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 accordin g 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

pe sticide 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 pesti cide. 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 perf ormed when conditions or circumstances warrant. Whenever appropriate, non

- dietary exposures based on home use of pesticide products and associated risks for adult applicators and for toddlers, youths, and adults entering or playing on treated areas

post

- a pplication 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

.

Endocrine Disruptor Screening Program

As required by FIFRA and FFDCA, EPA reviews numerous studies to assess potential adverse outcomes from exposure to chemicals. Collectively, these studies inclu de acute, subchronic and chronic toxicity, including assessments of carcinogenicity, neurotoxicity, developmental, reproductive, and general or systemic toxicity. These studies include endpoints which may be susceptible to endocrine influence, including e ffects on endocrine target organ histopathology, organ weights, estrus cyclicity, sexual maturation, fertility, pregnancy rates, reproductive loss, and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests and

chronic studi es that assess growth, developmental and reproductive effects in different taxonomic groups. As part of the most recent registration decision , EPA reviewed these data and selected the most sensitive endpoints for the relevant risk assessment scenarios fro m the existing

hazard database. However, as required by FFDCA section 408(p), flazasulfuron is subject to the endocrine screening part of the Endocrine Disruptor Screening Program (EDSP).

EPA has developed the EDSP to determine whether certain substances (including pesticide active and other ingredients) may have an effect in humans or wildlife similar to an effect produced by a “naturally occurring estrogen, or other such endocrine effects as the Administrator may designate.” The EDSP employs a two

- tiered approach to making the statutorily required

determinations. Tier 1 consists of a battery of 11 screening assays to identify the potential of a

chemical substance to interact with the est rogen, androgen, or thyroid (E, A, or T) hormonal systems. Chemicals that go through Tier 1 screening and are found to have the potential toPage 9 of 18

interact with E, A, or T hormonal systems will proceed to the next stage of the EDSP where EPA

will determine whic h, if any, of the Tier 2 tests are necessary based on the available data. Tier 2 testing is designed to identify any adverse endocrine

- related effects caused by the substance, and

establish a dose

- response relationship between the dose and the E, A, or T effect.

Under FFDCA section 408(p), the Agency must screen all pesticide chemicals. Between October 2009 and February 2010, EPA issued test orders/data call

- ins for the first group of 67 chemicals, which contains 58 pesticide active ingredients and 9 in ert ingredients. Rimsulfuron is not among the group of 58 pesticide active ingredients on the initial list to be screened under the EDSP. Accordingly, as part of registration review, EPA will issue future EDSP orders/data call

ins, requiring the submissi on of EDSP screening assays for rimsulfuron

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

.

Cumulative

Unlike other pesticides for which EPA has followed a cumulative risk approach based on a common mechanism of toxicity, EPA has not made a common mechanism of toxicity finding as

to rims ulfuron and any other substances and rimsulfuron does not appear to produce a toxic

metabolite produced by other substances. For the purposes of this action, therefore, EPA has not

assumed that rimsulfuron has a common mechanism of toxicity with other sub stances. For information regarding EPA’s efforts to determine which chemicals have a common mechanism of toxicity and to evaluate the cumulative effects of such chemicals, see the policy statements released by EPA’s Office of Pesticide Programs concerning common mechanism determinations and procedures for cumulating effects from substances found to have a common mechanism on

EPA’s website at http://www.epa.gov/pesticides/cumulative/.

Human Studies

The previous risk assessment s rely 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.

Data Requirements / Outstanding Deficiencies

None

References

As shown in Reference s below, only four human health risk assessment s have been conducted

for rimsulfuron

.Page 10 of 18

Memoranda Relevant to Registration Review of Rimsulfuron

Author Barcode

(DP#) Date Title

S. Recore 402251 05/08/12 Rimsulfuron : Review of Human Incidents

C. Walls 391083 05/04/12 Rimsulfuron. Human Health Risk Assessment for Proposed Section 3 Use on Chicory

M. Barrett 391086 3/15/12 Tier I Estimated Drinking Water Concentrations of

Rimsulfuron , for the Use in the Human Health Risk

Assessment: New Use Request for the Use of Rimsulfuron on
“Chr yosolite” Variety of Sulfonylurea Tolerant Chicory

E. Holman 384623 11/04/11 Rimsulfuron. Human Health Risk Assessment for Proposed Section 3 Uses on Caneberry and Bushberry.

E. Holman 394389 10/28/11 Rimsulfuron: Chronic Aggregate Dietary (Food and Drinking Water) Exposure and Risk Assessment for the Section 3 Registration on Caneberry, Bushberry, and Chicory

D. Rate 358866 09/08/09 Rimsulfuron. Human Health Risk Assessment for Proposed

Section 3 Use s on Genetically Modified Field Corn and Soybean

D. Rate 333256 05/16/07 Rimsulfuron: Human Health Risk Assessment for Proposed Uses on Almonds; Citrus Fruit; Grapes; Pistachio; Pome Fruit; Stone Fruit; and Tree Nuts.

E

. Rinde 09/27/06 Rimsulfuron

- Updated Executive Summaries and Section 4.0 of Risk Assessment Document for Registration Action

Branch 2

J Rowland 02/19/98 RIMSULFURON :

- Report of the Hazard Identification

Assessment Review Committee.

Attachment s 1. Chemical Identity Table

2. International Residue Limits

3. Endpoint Selection Table and Toxicity ProfilesPage 11 of 18 Attachment 1

Chemical Identity Table

Table 1.1 . Chemical Identity of Rimsulfuron

Chemical Structure

Common name Rimsulfuron

Company experimental name DPX

- E9636

IUPAC name 1

- (4,6

- dimethoxypyrimidin

- 2

- yl)

- 3

- (3

- ethylsulfonyl

- 2

- pyridylsulfonyl)urea

CAS name N

- [[(4,6

- dimethoxy

- 2

- pyrimidinyl)amino]carbonyl]

- 3

- (ethylsulfonyl)

- 2

- pyridinesulfonamide

CAS registry number 122931

- 48

- 0

PC Code 129009

Chemical Class Sulfonylurea herbicide

Table 1.2 . Chemical Names and Structures for Rimsulfuron Metabolites/Degradates

Company code; Chemical name Chemical structure

IN

— 70941

N

- (4 ,6

- Dimetho x y
- 2

- pyrimidinyl)

- N

- ((3

- ethylsulfonyl)

- 2

- pyridinyl)

urea

IN

- 70942

N

- ((3

- ethylsulfonyl)

- 2

- pyridinyl)

- 4,6

- dimethoxy

- 2

- pyrimidinamine

IN

- E9260

3

- (Ethylsulfonyl )

- 2

- pyridinesulfonamide.Page 12 of 18

Table 1.2 . Chemical Names and Structures for Rimsulfuron Metabolites/Degradates

Company code; Chemical name Chemical structure

IN

- T5831

N

- (4,6

- dimethoxy

- 2

- pyrimidinyl)urea

IN

- 69190

2

- amino

- 4,6

- dimethoxy

- 5

- pyrimidinol

IN

- J290

2

- Amino

- 4,6

- dimethoxypyrimidine

IN

- H1043

2

- Amino

- 4,6

- dihydroxypyrimidine

IN

- JF999

N

- [((3

- Ethylsulfonyl)

- 2

- pyridinyl)]

- 4

- hydroxy

- 6

- methoxy

- 2

- pyrimidineaminePage 13 of 18 Attachment 2

International Residue Limits

Rimsulfuron (PC Code

- 129009; 03/21/2012)

Table 2. Summary of US and International Tolerances and Maximum Residue Limits Residue Definition :
US Canada Mexico 1 Codex

40 CFR 180. 478 : (a) General: rimsulfuron, N

- ((4,6

- dimethoxypyrimidin

- 2

- yl)aminocarbonyl)

- 3

- (ethylsulfonyl)

- 2

- pyridinesulfonamide) N

- [[(4,6

- dimethoxy

- 2

- pyrimidinyl)amino]carbonyl]

- 3

- (ethylsulfonyl)

- 2

- pyridinesulfonamide None

Commodity Tolerance (ppm) /Maximum Residue Limit (mg/kg)

US Canada Mexico 1 Codex
Almond, hulls 0.09 Bushberry, subgroup 13

– 07B 0.01 0.05 blueberries Caneberry, subgroup 13

– 07A 0.01 Corn, field, forage 0.4 Corn, field, grain 0.1 0.1 field corn
Corn, field, stover 2.5 Fruit, citrus, group 10 0.01 Fruit, pome, group 11 0.01 Fruit, stone, group 12 0.01 Grain, aspirated fractions 4.5 Grape 0.01 Nut, tree, group 14 0.01

Pistachio 0.01

Potato 0.1 0.1 potatoes Soybean, forage 0.25 Soybean, hay 1.2 Soybean, hulls 0.04 Soybean, seed 0.01

Tomato 0.05 0.05 tomatoes

Completed: M. Negussie; 03/21/2012

1 Mexico adopts US tolerances and/or Codex MRLs for its export purposes.Page 14 of 18 Attachment 3

Summary of Rimsulfuron Endpoints Selected for Risk Assessment

Table 3.1. Summary of Toxicological Doses and Endpoints for Rimsulfuron for Use in Dietary, Non

Occupational , and 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 ( All Populations ) An appropriate endpoint attributable to a single dose was not identified

.

Chronic Dietary (All Populations) NOAEL=

11.8 mg/kg bw/day UF A =10x

UF H =10x FQPA SF=1x Chronic RfD

= 0.118 mg/kg/day

cPAD = 0.118 mg/kg/day Combined Chronic/Carcinogenicity

- Rat

LOAEL= 121 mg/kg/day in males; 568mg/kg/day in females (NOAEL=163 mg/kg/day), based on decreased body weight gains and liver effects.

Incidental Oral

Short

- Term (1

- 30 days);

intermediate

Term (1

- 6 months) Use pattern does not indicate a need for this risk assessment.

Dermal Short

Term (1

- 30 days);

intermediate

Term (1

- 6 months) NOAEL=

6

. 25 mg/kg /day UF A =1 0 x

UF H =10x

DAF=10 0% Occupational

LOC for

MOE = 100 90 Day Toxicity

- Dog

LOAEL=125 mg/kg/day, based on increased urinary volume, kidney weights, and decreased osmolality.

Inhalation Term (1

- 30 days);

intermediate

Term (1

- 6 months) NOAEL=

6

. 25 mg/kg /day UF A =1 0 x

UF H =10x Occupational

LOC for

MOE = 100 90 Day Toxicity

- Dog

LOAEL=125 mg/kg/day, based on increased urinary volume, kidney weights, and decreased osmolality.

Cancer (oral, dermal, inhalation) Rimsulfuron is considered “not likely to be carcinogenic to humans” due to the absence of tumors

in rat and mouse carcinogenicity studies.

Point of Departure (POD) = A data point or an estimated point that is derived from observed dose

- response data and used to mark the beginning of extrapolation to determine risk associated with lower environmentally relevant human exposures. NOAEL = no observed adverse effect level. LOAEL = lowest observed adverse effect level. UF = uncertainty factor. UF A = extrapolation from animal to human (intraspecies). UF H = potent ial variation in sensitivity among members of the human population (interspecies). FQPA SF = FQPA Safety Factor. PAD = popu lation adjusted dose (a = acute, c = chronic). RfD = reference dose. DAF=Dermal absorption factor.Page 15 of 18

Toxicity Profiles

Table 3.2 Acute Toxicity Profile

– Rimsulfuron

Guideline No. Study Type MRID(s) Results Toxicity Category

870.1100 Acute oral Rat

Acute oral Mouse 41356311, 41356310,

41931634

41931623 LD 50 = > 5000

mg/kg

LD 50 = > 5000 mg/kg IV

IV

870.1200 Acute dermal Rabbit 41356312, 41356313, 41931624,41

931635 LD 50 = > 2000

mg/kg IV

870.1300 Acute inhalation Rat 41356314; 41931625; 41931637; 41931636; LC 50 = >5.4; > 5.0;

> 7.5; > 5.4 mg/L IV

870.2400 Acute eye irritation Rabbit 41931626, 41356315, 41356316,

41931638 Moderate eye

irritant III

870.2500 Acute dermal irritation Rabbit 41931627

, 41356318, 41931639,

41356317 No irritation IV

870.2600 Skin sensitization Guinea Pig 41931628, 41356320, 41931641, 41931640,

41356319 Not a sensitizer IV

Table 3.3 Subchronic, Chronic and Other Toxicity Profile

- Rimsulfuron

Guideline No./ Study Type MRID No. (year)/ Classification /Doses Results

870.3100

90

- Day oral toxicity (rat) 41356321 (1989)/ ACCEPTABLE

GUIDELINE 0, 50, 1500, 7500, 2000 ppm (0, 2.5, 75, 375, 1000 mg/kg bw/day) NOAEL = 75 mg/kg bw/day LOAEL = 375 mg/kg bw/day based on reduced body wt. gains.

870.3100

90

- Day oral toxicity (mouse) 41356323 ((1989)/ ACCEPTABLE

NONGUIDELINE (90

- day oral toxicity in the mouse is not required under the 1884 Subdivision F guideline requirements.) 0, 50, 375, 1500, 7500 ppm (0, 7.5, 56.25, 225, 1125 mg/kg bw/day) NOAEL = M: 56.25 ; F: > 1125 mg/kg bw/day LOAEL = M: 225 mg/kg bw/day based on increased RBC and hemoglob in and decreased body weight gain and food efficiency. F: LOAEL not established.

870.3150

90

- Day oral toxicity (dog) 41356322 (1989)/ ACCEPTABLE

GUIDELINE 0, 250, 5000, 20000 ppm (0, 6.25, 125, or 500 mg/kg bw/day). NOAEL = 6. 25 mg/kg bw/day

LOAEL = 125 mg/kg/day based on urinary volume and osmolarityPage 16 of 18

Table 3.3 Subchronic, Chronic and Other Toxicity Profile

- Rimsulfuron

Guideline No./ Study Type MRID No. (year)/ Classification /Doses Results

870.3700a

Prenatal developmental in (Rat) 41356324 (1989)/ ACCEPTABLE

GUIDELINE 0, 200, 700, 2000, 6000 mg/kg bw/day Maternal NOAEL ≥ 6000 mg/kg bw/day

LOAEL = not established Developmental NOAEL ≥ 6000 mg/kg bw/day

LOAEL = not established

870.3700b

Prenatal developmental in (rabbit) 41356325 (1989)/ ACCEPTABLE

GUIDELINE 0, 25, 170, 500, 1500 mg/kg bw/day Maternal NOAEL = 170 mg/kg bw/day LOAEL = 500 mg/kg bw/day based on death and reduced weight gain. Developmental NOAEL = 500 mg/kg bw/day Developmental LOAEL = 1500 mg/kg bw/day based on production of only two

viable fetuses.

870.3800 Reproduction and fertility effects (rat) 41931644 (1990)/ ACCEPTABLE

GUIDELINE 0, 50, 3000, 15000 ppm ( 0, 2.76, 165, 830 mg/kg bw/day (F 0 males);

0, 3.38, 204, 1021 mg/kg bw/day (F 0 females); 0, 3.66, 217, 1316 mg/kg bw/day (F 1 males); and 0, 4.29, 264, 1316 mg/kg bw/day (F 1 females) respectively). Parental/Systemic NOAEL = 165 mg/kg bw/day in males, 204 mg/kg bw/day in

females Parental/Systemic LOAEL = M: 830; F: 1021mg/kg bw/day based on decreased body weight gain in males and females Reproductive NOAEL =1316 mg/kg bw/day (HDT) Reproductive LOAEL = Not Established.

Offspring NOAEL = M: 217; F; 264 mg/kg bw/day LOAEL = 1316 mg/kg bw/day based on decreased mean body weight in F 1 males, decreased body weight gain in F 1 females and decreased daily food consumption in

F 1 males.

870.4100b

Chronic toxicity (dog) 41931643(1991)/ ACCEPTABLE

GUIDELINE 0, 50, 2500, 10,000 ppm (0, 1.6, 81.8, 342.4 mg/kg bw/day (males); 0,1.6, 86.5, 358.5 mg/kg bw/day (females) respectively) Following re

- evaluation (HED DOC. NO. 012501, HIARC, 19/FEB/1998):

NOAEL = in males 81.8 mg/kg/day and in females 86.5 mg/kg bw/day. LOAEL = 342.4 mg/kg/day) based on increased absolute liver and kidney weights and increased incidence of seminiferous tubule degeneration and increased numbers of spermatid giant cells present in epidi dymides in males.

The LOAEL in females is 358.5 mg/kg/day based on decreased mean body weight and body weight gain, increased

serum cholesterol levels and alkaline phosphatase activity, increased absolute liver weight, and increased relative liver

and ki dney weights.Page 17 of 18

Table 3.3 Subchronic, Chronic and Other Toxicity Profile

- Rimsulfuron

Guideline No./ Study Type MRID No. (year)/ Classification /Doses Results

870.4200 Carcinogenicity (rat) 42047701(1991)/ ACCEPTABLE

GUIDELINE 0, 25, 300, 3000, 10,000 ppm [0, 1.0, 11.8, 121, 414 mg/kg bw/day (males); 1.38, 17.1, 163, 568 mg/kg bw/day (females)] NOAEL = 11. 8 mg/kg bw/day for males

and 163 mg/kg/day for females.

LOAEL = 121 mg/kg bw/day for males

and 568 mg/kg bw/day for females, based on decreased body weight gain and liver

effects.

No evidence of carcinogenicity.

870.4300 Carcinogenicity (mouse) 41931642 (1991)/ ACCEPTABLE

GUIDELINE 0, 25, 250, 2500, or 7500 ppm [0, 3.47, 35.5, 351, or 1127 mg/kg bw/day (males) 0, 4.99, 50.5, 488, or 1505 mg/kg bw/day (females)] NOAEL = 351 mg/kg bw/day (males); 488 mg/kg bw/day (females). LOAEL = 1127 mg/kg bw/day for males; and 1505 mg/kg bw/day, females, based

on decreased mean body weight in males and females, increased incidence of dilation and cysts in the glandular stomach and degeneration of the testicular artery and tunica albuginea in males.

No eviden ce of carcinogenicity.

870.5100

In vitro Bacterial Gene Mutation Assay 42471310 (1992)/ ACCEPTABLE

GUIDELINE 5000, 1000, 750, 500, 100, 75, 50, 25, 10, 0 μg/plate and (Trial 2) 5000, 2500, 1000, 750, 500, 100, 0 μg/plate in the presence and

absence of mammalian metabolic activation

with 0.5 ml S

- 9 mix. There was no evidence of induced mutant colonies over background.

870.5300

In Vitro Mammalian

Cells in Culture Gene Mutation assay in

CHO 41356328 (1989)/ ACCEPTABLE

GUIDELINE 0, 10, 100, 250, 750, 1300 μg/mL in the presence and absence of mammalian

metabolic activation with S/9.

41356327 (1989)/ ACCEPTABLE

GUIDELINE 0, 0. 0008, 0.004, 0.008, 0.04, 0.08, 0.4, 0.8, or 1.1 mg /mL There was no evidence of induced mutant colonies over background.

There was no evidence that unscheduled DNA synthesis, as determined by radioactive tracer procedures [nuclear silver grain counts] was induced.Page 18 of 18

Table 3.3 Subchronic, Chronic and Other Toxicity Profile

- Rimsulfuron

Guideline No./ Study Type MRID No. (year)/ Classification /Doses Results

870.6200a Acute Neurotoxicity (rat) 48710302 (2011)

0 , 200, 1000, 2000 mg/kg

NOT YET CLASSIFIED

– study under

review Provisionary NOAEL = 2000 mg/kg Provisionary LOAEL > 2000 mg/kg. No clinical signs, changes in body weight and/or food consumption, gross or microscopic pathology, or

neurobehavioral effects were observed

870.6200b

Subchronic Neurotoxicity (rat) 48710303 (2011) 0, 1000. 3000, 7500 ppm (M/F) 0, 55. 170, 438 mg/kg/day (M) 0, 69, 193, 507 mg/kg/day (F)

NOT YET CLASSIFIED

– study under

review Provisionary NOAEL = 438/507 mg/kg/day (M/F) Provisionary LOAEL > 438/507 mg/kg/day (M/F) No clinical signs, gross or microscopic pathology, or changes in survival, body weight and/or food consumption,

fore/hind

- limb grip strength, footsplay, body temperature, rearing, FOB

measurements or motor activ ity were

observed.

870.7800

28

- day Immuno

toxicity (mouse) 48710305 (2011) 0, 300, 600, 1800, 6500 ppm 0, 45, 93, 288, 1006 mg/kg/day

NOT YET CLASSIFIED

– study under

review Provisionary NOAEL = 1006 mg/kg/day Provisionary LOAEL > 1006 mg/kg/day

No clinical signs, gross or microscopic pathology, or changes in body weight and/or food consumption, brain, spleen or thymus weights, or in humoral immune

response were observed.