Pesticide Tolerances:


Federal Register: December 29, 2010 (Volume 75, Number 249)

Rules and Regulations

Page 81878-81885

From the Federal Register Online via GPO Access []



EPA-HQ-OPP-2009-0205; FRL-8857-4

Imazosulfuron; Pesticide Tolerances

AGENCY: Environmental Protection Agency (EPA).

ACTION: Final rule.

SUMMARY: This regulation establishes tolerances for residues of imazosulfuron in or on pepper, bell; pepper, non-bell; rice, grain; and tomato. Valent USA Corporation requested these tolerances under the

Federal Food, Drug, and Cosmetic Act (FFDCA).

DATES: This regulation is effective December 29, 2010. Objections and requests for hearings must be received on or before February 28, 2011, and must be filed in accordance with the instructions provided in 40

CFR part 178 (see also Unit I.C. of the SUPPLEMENTARY INFORMATION).

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ADDRESSES: EPA has established a docket for this action under docket identification (ID) number EPA-HQ-OPP-2009-0205. All documents in the docket are listed in the docket index available at http:// Although listed in the index, some information is not publicly available, e.g., Confidential Business Information (CBI) or other information whose disclosure is restricted by statute. Certain other material, such as copyrighted material, is not placed on the

Internet and will be publicly available only in hard copy form.

Publicly available docket materials are available in the electronic docket at, or, if only available in hard copy, at the OPP Regulatory Public Docket in Rm. S-4400, One Potomac

Yard (South Bldg.), 2777 S. Crystal Dr., Arlington, VA. The Docket

Facility is open from 8:30 a.m. to 4 p.m., Monday through Friday, excluding legal holidays. The Docket Facility telephone number is (703) 305-5805.

FOR FURTHER INFORMATION CONTACT: Susan Stanton, Registration Division

(7505P), Office of Pesticide Programs, Environmental Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460-0001; telephone number: (703) 305-5218; e-mail address:


I. General Information

A. Does this action apply to me?

You may be potentially affected by this action if you are an agricultural producer, food manufacturer, or pesticide manufacturer.

Potentially affected entities may include, but are not limited to those engaged in the following activities:

Crop production (NAICS code 111).

Animal production (NAICS code 112).

Food manufacturing (NAICS code 311).

Pesticide manufacturing (NAICS code 32532).

This listing is not intended to be exhaustive, but rather to provide a guide for readers regarding entities likely to be affected by this action. Other types of entities not listed in this unit could also be affected. The North American Industrial Classification System

(NAICS) codes have been provided to assist you and others in determining whether this action might apply to certain entities. If you have any questions regarding the applicability of this action to a particular entity, consult the person listed under FOR FURTHER


B. How can I get electronic access to other related information?

You may access a frequently updated electronic version of EPA's tolerance regulations at 40 CFR part 180 through the Government

Printing Office's e-CFR site at To access the harmonized test guidelines referenced in this document electronically, please go and select ``Test

Methods and Guidelines.''

C. How can I file an objection or hearing request?

Under FFDCA section 408(g), 21 U.S.C. 346a, any person may file an objection to any aspect of this regulation and may also request a hearing on those objections. You must file your objection or request a hearing on this regulation in accordance with the instructions provided in 40 CFR part 178. To ensure proper receipt by EPA, you must identify docket ID number EPA-HQ-OPP-2009-0205 in the subject line on the first page of your submission. All objections and requests for a hearing must be in writing, and must be received by the Hearing Clerk on or before

February 28, 2011. Addresses for mail and hand delivery of objections and hearing requests are provided in 40 CFR 178.25(b).

In addition to filing an objection or hearing request with the

Hearing Clerk as described in 40 CFR part 178, please submit a copy of the filing that does not contain any CBI for inclusion in the public docket. Information not marked confidential pursuant to 40 CFR part 2 may be disclosed publicly by EPA without prior notice. Submit a copy of your non-CBI objection or hearing request, identified by docket ID number EPA-HQ-OPP-2009-0205, by one of the following methods:

Federal eRulemaking Portal:

Follow the online instructions for submitting comments.

Mail: Office of Pesticide Programs (OPP) Regulatory Public

Docket (7502P), Environmental Protection Agency, 1200 Pennsylvania

Ave., NW., Washington, DC 20460-0001.

Delivery: OPP Regulatory Public Docket (7502P),

Environmental Protection Agency, Rm. S-4400, One Potomac Yard (South

Bldg.), 2777 S. Crystal Dr., Arlington, VA. Deliveries are only accepted during the Docket Facility's normal hours of operation (8:30 a.m. to 4 p.m., Monday through Friday, excluding legal holidays).

Special arrangements should be made for deliveries of boxed information. The Docket Facility telephone number is (703) 305-5805.

II. Summary of Petitioned-For Tolerance

In the Federal Register of May 6, 2009 (74 FR 20947) (FRL-8412-7),

EPA issued a notice pursuant to section 408(d)(3) of FFDCA, 21 U.S.C. 346a(d)(3), announcing the filing of a pesticide petition (PP 9F7535) by Valent USA Corporation, 1600 Riviera Ave., Suite 200, Walnut Creek,

CA 94596. The petition requested that 40 CFR part 180 be amended by adding a section for the herbicide imazosulfuron and establishing tolerances therein for residues of imazosulfuron, 2-chloro-N-[(4,6- dimethoxy-2-pyrimidinyl)amino]carbonyl] imidazo-[1,2-a]pyridine-3- sulfonamide, in or on pepper, bell, fruit; pepper, non-bell, fruit; rice, grain; and tomato, fruit; each at 0.02 parts per million (ppm).

That notice referenced a summary of the petition prepared by Valent USA

Corporation, the registrant, which is available in the docket, http:// There were no comments received in response to the notice of filing.

EPA has modified the proposed commodity terms for pepper and tomato commodities and revised the requested tolerance expression in accordance with current policy. The reasons for these changes are explained in Unit IV.C.

III. Aggregate Risk Assessment and Determination of Safety

Section 408(b)(2)(A)(i) of FFDCA allows EPA to establish a tolerance (the legal limit for a pesticide chemical residue in or on a food) only if EPA determines that the tolerance is ``safe.'' Section 408(b)(2)(A)(ii) of FFDCA defines ``safe'' to mean that ``there is a reasonable certainty that no harm will result from aggregate exposure to the pesticide chemical residue, including all anticipated dietary exposures and all other exposures for which there is reliable information.'' This includes exposure through drinking water and in residential settings, but does not include occupational exposure.

Section 408(b)(2)(C) of FFDCA requires EPA to give special consideration to exposure of infants and children to the pesticide chemical residue in establishing a tolerance and to ``ensure that there is a reasonable certainty that no harm will result to infants and children from aggregate exposure to the pesticide chemical residue. * *


Consistent with section 408(b)(2)(D) of FFDCA, and the factors specified in section 408(b)(2)(D) of FFDCA, EPA has reviewed the available scientific data and other relevant information in support of this action. EPA has

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sufficient data to assess the hazards of and to make a determination on aggregate exposure for imazosulfuron including exposure resulting from the tolerances established by this action. EPA's assessment of exposures and risks associated with imazosulfuron follows.

A. Toxicological Profile

EPA has evaluated the available toxicity data and considered its validity, completeness, and reliability as well as the relationship of the results of the studies to human risk. EPA has also considered available information concerning the variability of the sensitivities of major identifiable subgroups of consumers, including infants and children.

The toxicology data for imazosulfuron suggest that this herbicide possesses relatively low toxicity. Many of the effects of single or repeated dosing were observed near or beyond the respective limit doses.

Imazosulfuron is of low acute toxicity by the oral, dermal, and inhalation routes of exposure; it is not a skin or eye irritant or a dermal sensitizer. The primary target organ of imazosulfuron in repeated-dose studies was the liver in all species tested. Mild to moderate thyroid effects were apparent only in the chronic toxicity study in dogs. Dramatic eye effects (retinal degeneration, lens vascularization, cataracts and corneal scarring) were observed in rats fed > 1,000 mg/kg/day beginning at 3 months in the chronic toxicity/ carcinogenicity study. Ocular effects (increased incidence of eye opacity, corneal edema, inflammation and neovascularization) were also observed in the high-dose males (4,577 mg/kg/day) in the 90-day feeding toxicity study in rats. Decreased body weight and body weight gain compared to control were frequent findings throughout the toxicology database for imazosulfuron.

Clinical signs (decreased motor activity, abnormal gait, upward curvature of the spine and piloerection) were observed in males at the limit dose of the acute neurotoxicity study; however, these effects can be attributed to generalized toxicity and were resolved by Day 2 of the study. No neurotoxic effects were observed during the subchronic screening battery or noted as clinical signs in any other repeated-dose study.

No developmental effects were observed at the highest dose tested

(HDT) (125 mg/kg/day) in the rabbit developmental toxicity study. No developmental or reproductive toxicity was observed in the 1-generation rat study. Decreased pup viability was observed in the rat 2-generation reproduction study at a dose approaching the limit dose (LOAEL = 892 mg/kg/day) in both the F1 and F2 offspring generations. Mortality was also observed in the parental generation at this dose. No increased qualitative or quantitative offspring susceptibility was apparent in any of the submitted studies for imazosulfuron.

There was no evidence of carcinogenicity in rats and mice up to the limit dose at 24 and 18 months, respectively. Imazosulfuron was determined to be non-mutagenic in bacteria and negative in an in vivo mammalian cytogenetics assay. Overall, there was no evidence that imazosulfuron was either mutagenic or clastogenic in either in vivo or in vitro assays. The cancer classification is ``not likely to be carcinogenic to humans,'' based on the absence of significant tumor increases in the carcinogenicity studies.

Specific information on the studies received and the nature of the adverse effects caused by imazosulfuron as well as the no-observed- adverse-effect-level (NOAEL) and the lowest-observed-adverse-effect- level (LOAEL) from the toxicity studies can be found at http:// in the document ``Imazosulfuron: Human Health Risk

Assessment for Proposed Uses on Rice, Peppers and Tomatoes,'' p. 45 in docket ID number EPA-HQ-OPP-2009-0205.

B. Toxicological Points of Departure/Levels of Concern

Once a pesticide's toxicological profile is determined, EPA identifies toxicological points of departure (POD) and levels of concern to use in evaluating the risk posed by human exposure to the pesticide. For hazards that have a threshold below which there is no appreciable risk, the toxicological POD is used as the basis for derivation of reference values for risk assessment. PODs are developed based on a careful analysis of the doses in each toxicological study to determine the dose at which no adverse effects are observed (the NOAEL) and the lowest dose at which adverse effects of concern are identified

(the LOAEL). Uncertainty/safety factors are used in conjunction with the POD to calculate a safe exposure level--generally referred to as a population-adjusted dose (PAD) or a reference dose (RfD)--and a safe margin of exposure (MOE). For non-threshold risks, the Agency assumes that any amount of exposure will lead to some degree of risk. Thus, the

Agency estimates risk in terms of the probability of an occurrence of the adverse effect expected in a lifetime. For more information on the general principles EPA uses in risk characterization and a complete description of the risk assessment process, see pesticides/factsheets/riskassess.htm. A summary of the toxicological endpoints for imazosulfuron used for human risk assessment is shown in the Table of this unit.

Table--Summary of Toxicological Doses and Endpoints for Imazosulfuron for Use in Human Health Risk Assessment

Point of departure and



RfD, PAD, LOC for risk

Study and toxicological factors



Acute dietary (Females 13-49 years

An acute reference dose specific to females age 13-49 was not identified, of age).

because there was no prenatal or fetal toxicity observed in developmental or reproductive animal studies following a single oral dose.

Acute dietary (General population

NOAEL = 400 mg/kg/day

Acute RfD = 4 mg/kg/

Acute neurotoxicity including females 13-49 years of

UFA = 10x.


screening battery. age and infants and children).

LOAEL = 2,000 mg/kg/day based on the following clinical signs: Abnormal gait, decreased activity, piloerection and upward curvature of the spine; and incidents of irregular breathing, reduced righting reflex, tremors, decreased visual placement response in males and increased response to sound in one female.

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UFH = 10x.............. aPAD = 4 mg/kg/day

FQPA SF = 1x...........

Chronic dietary (All populations).. NOAEL= 75 mg/kg/day UFA Chronic RfD = 0.75 mg/ Chronic toxicity in the

= 10x.



LOAEL = 150 mg/kg/day based on moderate thyroid hypertrophy (males at mid- and high-dose; mild hypertrophy in females at high-dose).

UFH = 10x.............. cPAD = 0.75 mg/kg/day.

FQPA SF = 1x...........

Incidental oral short-term (1 to 30 NOAEL= 235 mg/kg/day

LOC for MOE = 100..... Reproduction, 2-generation days) and intermediate-term (1 to

UFA = 10x.

(rat). 6 months).

LOAEL = 892 mg/kg/day based on mortality, clinical signs, decreased body weights, body weight gains and food consumption in parents. 90-day oral toxicity


LOAEL = 956 mg/kg/day based on decreased body weight gains and food efficiency.

UFH = 10x..............

FQPA SF = 1x...........

Dermal short-term (1 to 30 days)

No systemic toxicity occurred at the limit dose and the primary toxic and intermediate-term (1 to 6

effects of concern (liver, eye) were adequately assessed in a 21-day months).

dermal toxicity study. It is concluded that this compound is not or is poorly absorbed through the skin and, therefore, a quantitative risk assessment for this route and duration of exposure is not necessary.

Inhalation short-term (1 to 30

Inhalation (or oral)

LOC for MOE = 100..... Reproduction, 2-generation days) and intermediate-term (1 to study NOAEL = 235 mg/

(rat). 6 months).

kg/day (inhalation

LOAEL = 892 mg/kg/day absorption rate =

based on mortality, 100%).

clinical signs, decreased body weights, body weight gains and food consumption in parents.

UFA = 10x..............

UFH = 10x..............

FQPA SF = 1x........... ...................... 90-day oral toxicity

(rat). LOAEL = 956 mg/kg/ day based on decreased body weight gains and food efficiency.

Cancer (Oral, dermal, inhalation)..

Classification: ``Not likely to be Carcinogenic to Humans'' based on the absence of significant tumor increases in two adequate rodent carcinogenicity studies.

UFA = extrapolation from animal to human (interspecies). UFH = potential variation in sensitivity among members of the human population (intraspecies). UFL = use of a LOAEL to extrapolate a NOAEL. UFS = use of a short-term study for long-term risk assessment. UFDB = to account for the absence of data or other data deficiency. FQPA

SF = Food Quality Protection Act Safety Factor. PAD = population adjusted dose (a = acute, c = chronic). RfD = reference dose. MOE = margin of exposure. LOC = level of concern.

C. Exposure Assessment 1. Dietary exposure from food and feed uses. In evaluating dietary exposure to imazosulfuron, EPA considered exposure under the petitioned-for tolerances. There are no tolerances currently established for imazosulfuron. EPA assessed dietary exposures from imazosulfuron in food as follows: i. Acute exposure. Quantitative acute dietary exposure and risk assessments are performed for a food-use pesticide, if a toxicological study has indicated the possibility of an effect of concern occurring as a result of a 1-day or single exposure. Such effects were identified for imazosulfuron. In estimating acute dietary exposure, EPA used food consumption information from the United States Department of

Agriculture (USDA) 1994-1996 and 1998 Nationwide Continuing Surveys of

Food Intakes by Individuals (CSFII). As to residue levels in food, EPA assumed that residues are present in all commodities at the tolerance level and that 100% of commodities are treated with imazosulfuron.

DEEMTM7.81 default concentration factors were used to estimate residues of imazosulfuron in processed commodities. ii. Chronic exposure. In conducting the chronic dietary exposure assessment EPA used the food consumption data from the USDA 1994-1996 and 1998 CSFII. As to residue levels in food, EPA assumed that residues are present in all commodities at the tolerance level and that 100% of commodities are treated with imazosulfuron. DEEMTM7.81 default concentration factors were used to estimate residues of imazosulfuron in processed commodities. iii. Cancer. Based on the results of carcinogenicity studies in rats and mice, EPA classified imazosulfuron as ``Not likely to be

Carcinogenic to Humans''; therefore, a dietary exposure assessment for the purpose of assessing cancer risk is unnecessary. iv. Anticipated residue and percent crop treated (PCT) information.

EPA did not use anticipated residue or PCT information in the dietary assessment for imazosulfuron. Tolerance level residues and 100 PCT were assumed for all food commodities. 2. Dietary exposure from drinking water. The residues of concern in drinking water include imazosulfuron and its degradates HMS, IPSN,

UDPM, ADPM, and SDPM. The Agency used screening level water exposure models in the dietary exposure analysis and risk assessment for imazosulfuron and its degradates in drinking water. These simulation models take into account data on the physical, chemical, and fate/ transport characteristics of imazosulfuron and its degradates. Further information regarding EPA

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drinking water models used in pesticide exposure assessment can be found at

Based on the First Index Reservoir Screening Tool (FIRST), Tier 1

Rice Model, and Screening Concentration in Ground Water (SCI-GROW) models, the estimated drinking water concentrations (EDWCs) of imazosulfuron and its degradates for both acute exposures and chronic exposures for non-cancer assessments are estimated to be 278.9 parts per billion (ppb) for surface water (based on the Tier 1 Rice Model results) and 4.8 ppb for ground water (based on the SCI-GROW model results).

Modeled estimates of drinking water concentrations were directly entered into the dietary exposure model. For acute and chronic dietary risk assessment, the water concentration value of 278.9 ppb was used to assess the contribution to drinking water. 3. From non-dietary exposure. The term ``residential exposure'' is used in this document to refer to non-occupational, non-dietary exposure (e.g., for lawn and garden pest control, indoor pest control, termiticides, and flea and tick control on pets). Imazosulfuron is currently registered for the following uses that could result in residential exposures: Residential turfgrass and recreational areas.

EPA assessed residential exposure using the following assumptions:

There is a potential for exposure of homeowners applying products containing imazosulfuron on home lawns. There is also a potential for post-application exposure of adults and children entering turf areas that have been treated with imazosulfuron and for bystander exposure of adults and children in areas adjacent to pesticide applications.

Residential handlers may receive short-term dermal and inhalation exposure to imazosulfuron when mixing, loading and applying the pesticide on home lawns. Since a dermal endpoint of concern was not identified for imazosulfuron, only short-term inhalation exposure of residential handlers was assessed.

Adults and children may receive short-term inhalation and dermal exposures from entering turf areas treated with imazosulfuron.

Volatilization of imazosulfuron may also be a source of short-term post-application inhalation exposure of bystanders nearby application sites. Finally, children may receive short-term incidental oral exposure (i.e., hand-to-mouth, object-to-mouth and soil ingestion exposure) during post-application activities on treated turf. EPA did not identify any dermal endpoints of concern for imazosulfuron; and a quantitative post-application inhalation exposure assessment was not performed for imazosulfuron due to its low acute inhalation toxicity, low vapor pressure (-6Pa), low proposed use rate

(0.3 lb ai/A), and the soil-directed application method (i.e., it is not applied using equipment, such as air blast sprayers, that would result in higher post-application inhalation exposures). Therefore, EPA assessed only short-term post-application incidental oral exposure of children (toddlers).

Further information regarding EPA standard assumptions and generic inputs for residential exposures may be found at pesticides/trac/science/trac6a05.pdf. 4. Cumulative effects from substances with a common mechanism of toxicity. Section 408(b)(2)(D)(v) of FFDCA requires that, when considering whether to establish, modify, or revoke a tolerance, the

Agency consider ``available information'' concerning the cumulative effects of a particular pesticide's residues and ``other substances that have a common mechanism of toxicity.''

EPA has not found imazosulfuron to share a common mechanism of toxicity with any other substances, and imazosulfuron does not appear to produce a toxic metabolite produced by other substances. For the purposes of this tolerance action, therefore, EPA has assumed that imazosulfuron does not have 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 EPA's Web site at http://

D. Safety Factor for Infants and Children 1. In general. Section 408(b)(2)(C) of FFDCA provides that EPA shall apply an additional tenfold (10X) margin of safety for infants and children in the case of threshold effects to account for prenatal and postnatal toxicity and the completeness of the database on toxicity and exposure unless EPA determines based on reliable data that a different margin of safety will be safe for infants and children. This additional margin of safety is commonly referred to as the FQPA Safety

Factor (SF). In applying this provision, EPA either retains the default value of 10X, or uses a different additional safety factor when reliable data available to EPA support the choice of a different factor. 2. Prenatal and postnatal sensitivity. The pre- and postnatal toxicity database for imazosulfuron includes guideline rat and rabbit developmental toxicity studies and a 2-generation reproduction toxicity study in rats. No developmental effects were observed at the HDT in the rabbit developmental toxicity study, and no developmental or reproductive toxicity was observed in the developmental (1-generation) rat study. In the 2-generation rat reproduction study, both decreased pup viability and parental mortality were observed, but only at a dose approaching the limit dose. 3. Conclusion. EPA has determined that reliable data show the safety of infants and children would be adequately protected if the

FQPA SF were reduced to 1X. That decision is based on the following findings: i. The toxicity database for imazosulfuron is largely complete, lacking only an immunotoxicity study. EPA has evaluated the available toxicity data for imazosulfuron and determined that an additional database uncertainty factor is not needed to account for potential immunotoxicity. The most sensitive endpoint in the database is moderate thyroid hypertrophy. Liver toxicity accompanied by body weight and food consumption effects is seen throughout the toxicology database. No treatment-related changes indicative of potential immunotoxicity were seen in hematology parameters, organ weights (thymus, spleen), gross necropsy (enlarged lymph nodes) or histopathology (spleen, thymus, lymph nodes) when tested up to the limit dose in mice and rats.

Therefore, EPA does not believe that conducting a special series 870.7800 immunotoxicity study will result in a NOAEL less than 75 mg/ kg/day, which is presently used as the point of departure for chronic risk assessment. ii. No neurotoxic effects were observed during the subchronic screening battery or noted as clinical signs in any other repeated-dose study. Although untoward clinical signs were observed in the acute neurotoxicity study, these effects can be attributed to generalized toxicity and were resolved by Day 2 of the study. Based on these considerations, there is no need for a developmental neurotoxicity study or additional UFs to account for neurotoxicity. iii. There is no evidence that imazosulfuron results in increased susceptibility in in utero rats or rabbits in the prenatal developmental studies or in young rats in the 2-generation reproduction study.

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iv. There are no significant residual uncertainties in the exposure databases. Data have been requested to confirm the stability of imazosulfuron during frozen storage and the metabolic profile of pyrimidine-labeled imazosulfuron in rice grain in the confined rotational crop trial. A field rotational crop study is also required for grain (wheat); however, as explained in Unit III.D.3.iv.c., EPA does not expect these studies to have a measurable impact on exposure estimates for imazosulfuron. a. Storage stability. The final reports of the storage stability studies must be submitted, reflecting frozen storage intervals of up to 11.8 months for peppers, up to 34.5 months for rice grain, and up to 17.3 months for tomatoes. Interim data suggest that imazosulfuron is stable in frozen storage, and similar sulfonylurea chemicals are known to be stable. Therefore, EPA expects imazosulfuron to be stable in frozen storage but is requiring the final study reports as confirmation. b. Metabolic profile. The HPLC profile for the pyrimidinyl (Py)- label grain storage stability analysis must be submitted to confirm that the metabolite profile was stable in Py-label grain. Grain samples from the confined rotational crop study were stored for a relatively long interval (9 months) prior to completion of the analyses. Analysis of an imidozolyl (Im)-label sample after the 9-month period yielded a metabolic profile similar to that of a sample analyzed at the start of the period. A similar comparison must be made for the Py-label sample of grain. This is of no practical consequence for risk assessment because total residue levels on grain were small (