Pesticide Tolerance; Exemptions, Petitions, Revocations, etc.: Amicarbazone

Amicarbazone; Pesticide Tolerances

SUPPLEMENTARY INFORMATION:

I. Executive Summary

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. The following list of North American Industrial Classification System (NAICS) codes is not intended to be exhaustive but rather provides a guide to help readers determine whether this document applies to them. Potentially affected entities may include:

• Crop production (NAICS code 111).
• Animal production (NAICS code 112).
• Food manufacturing (NAICS code 311).
• Pesticide manufacturing (NAICS code 32532).

B. What is EPA's authority for taking this action?

EPA is issuing this rulemaking under section 408 of the Federal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 346a. FFDCA section 408(b)(2)(A)(i) 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." FFDCA section 408(b)(2)(A)(ii) 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. FFDCA section 408(b)(2)(C) 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 . . ."

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-2024-0330 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 December 1, 2025. Addresses for mail and hand delivery of objections and hearing requests are provided in 40 CFR 178.25(b).

The EPA's Office of Administrative Law Judges (OALJ), in which the Hearing Clerk is housed, urges parties to file and serve documents by electronic means only, notwithstanding any other particular requirements set forth in other procedural rules governing those proceedings. See "Revised Order Urging Electronic Filing and Service," dated June 22, 2023, which can be found at https://www.epa.gov/system/files/documents/2023-06/2023-06-22%20-%20revised%20order%20urging%20electronic%20filing%20and%20service.pdf. Although the EPA's regulations require submission via U.S. Mail or hand delivery, the EPA intends to treat submissions filed via electronic means as properly filed submissions; therefore, the EPA believes the preference for submission via electronic means will not be prejudicial. When submitting documents to the OALJ electronically, a person should utilize the OALJ e-filing system at https://yosemite.epa.gov/oa/eab/eab-alj_upload.nsf.

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 (excluding any Confidential Business Information (CBI)) for inclusion in the public docket at https://www.regulations.gov. Follow the online instructions for submitting comments. Do not submit electronically any information you consider to be CBI or other information whose disclosure is restricted by statute. If you wish to include CBI in your request, please follow the applicable instructions at https://www.epa.gov/dockets/commenting-epa-dockets#rules and clearly mark the information that you claim to be CBI. Information not marked confidential pursuant to 40 CFR part 2 may be disclosed publicly by EPA without prior notice.

II. Petitioned-For Tolerance

In the Federal Register of July 3, 2025 (90 FR 29515) (FRL-12474-05-OCSPP), EPA issued a document pursuant to FFDCA section 408(d)(3), 21 U.S.C. 346a(d)(3), announcing the filing of a pesticide petition (PP 4E9122) by UPL Delaware, Inc., 630 Freedom Business Center, Suite 402, King of Prussia, PA 19406. The petition requested that 40 CFR 180.615 be amended by establishing tolerances for residues of amicarbazone, [4-amino-N-tert-butyl-4,5-dihydro-3-isopropyl-5-oxo-1H-1,2,4-triazole-1-carboxamide], including its metabolites and degradates, in or on imported sugarcane, cane at 0.2 parts per million (ppm) and imported sugarcane, molasses at 0.5 ppm. That document referenced a summary of the petition prepared by UPL Delaware, Inc., the registrant, which is available in the docket, https://www.regulations.gov. There were no comments received in response to the notice of filing.

III. Final Tolerance Action

A. Aggregate Risk Assessment and Determination of Safety

Consistent with FFDCA section 408(b)(2)(D), and the factors specified therein, EPA has reviewed the available scientific data and other relevant information in support of this action. EPA has sufficient data to assess the hazards of and to make a determination on aggregate exposure for Amicarbazone including exposure resulting from the tolerances established by this action. EPA's assessment of exposures and risks associated with Amicarbazone is summarized in this unit.

B. 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.

In subchronic/chronic animal studies, amicarbazone caused decreased body weight and liver effects. Changes in thyroid hormones and thyroid vacuolization were also seen, although mechanistic studies indicated that these changes were secondary to liver effects. Mice were more sensitive to the effects of amicarbazone than dogs and rats, which were equally sensitive. Minimal progression of toxicity was observed between subchronic and chronic exposure to amicarbazone, which is consistent with the rapid metabolism seen in the absorption, distribution, metabolism, and elimination (ADME) studies. Clinical signs of neurotoxicity (eyelid ptosis, decreased approach response, and red staining of the nasal area) were seen following acute exposure. Evidence of neurotoxicity was not seen in the subchronic or developmental neurotoxicity studies or any other study in the database. There was no evidence of quantitative or qualitative susceptibility in the rat and rabbit developmental, rat developmental neurotoxicity, and rat reproductive toxicity studies. There was no evidence of systemic toxicity following dermal exposure. Amicarbazone is classified as "Not likely to be carcinogenic to humans" based on the lack of evidence for carcinogenicity in mice and rats and the lack of concern for mutagenicity. Evidence of immunotoxicity (decreased number of spleen cells per spleen, suppressed antibody response, and decreased spleen weight) was observed in the immunotoxicity study, but at doses higher than those that caused decreased body weight or liver effects in other studies.

Specific information on the studies received and the nature of the adverse effects caused by amicarbazone 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 https://www.regulations.gov in the document titled " Amicarbazone. Human Health Risk Assessment for the Proposed Tolerance on Sugarcane Without a U.S. Registration" (hereafter referred to as the " Amicarbazone Human Health Assessment" ) on pages 24-30 in docket ID number EPA-HQ-OPP-2024-0330.

C. 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 NOAEL and 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 https://www.epa.gov/pesticides/factsheets/riskassess.htm.

A summary of the toxicological endpoints for amicarbazone used for human risk assessment is discussed in section 4.3 (Toxicity Endpoint and Point of Departure Selections) of the Amicarbazone Human Health Assessment.

D. Exposure Assessment

1. Dietary exposure from food and feed uses. In evaluating dietary exposure to amicarbazone, EPA considered exposure under the petitioned-for tolerances as well as all existing amicarbazone tolerances in 40 CFR 180.615. EPA assessed dietary exposures from amicarbazone 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 amicarbazone.

In estimating acute dietary exposure, EPA used the Dietary Exposure Evaluation Model software with the Food Commodity Intake Database (DEEM-FCID) Version 4.02. This software uses 2005-2010 food consumption data from the U.S. Department of Agriculture's (USDA's) National Health and Nutrition Examination Survey, What We Eat in America, (NHANES/WWEIA). As to residue levels in food, EPA assumed 100 percent crop treated and used tolerance-level residues adjusted for metabolite factors. Processing factors were reduced to 1X for several processed commodities based on processing data showing that the raw agricultural commodity tolerances are adequate to cover residues in processed commodities.

ii. Chronic exposure. In conducting the chronic dietary exposure assessment EPA used the food consumption data from the USDA 2005-2010 CSFII. As to residue levels in food, assumed 100 percent crop treated and used tolerance-level residues adjusted for metabolite factors. Processing factors were reduced to 1X for several processed commodities based on processing data showing that the raw agricultural commodity tolerances are adequate to cover residues in processed commodities.

iii. Cancer. Based on the data summarized in Unit III.A., EPA has concluded that amicarbazone does not pose a cancer risk to humans. Therefore, a dietary exposure assessment for the purpose of assessing cancer risk is unnecessary.

iv. Anticipated residue and PCT information. EPA did not use anticipated residue and/or PCT information in the dietary assessment for amicarbazone. Tolerance level residues adjusted for metabolite factors and 100 PCT were assumed for all food commodities.

2. Dietary exposure from drinking water. The Agency used screening level water exposure models in the dietary exposure analysis and risk assessment for amicarbazone in drinking water. These simulation models take into account data on the physical, chemical, and fate/transport characteristics of amicarbazone. Further information regarding EPA drinking water models used in pesticide exposure assessment can be found at https://www.epa.gov/oppefed1/models/water/index.htm.

Based on the Pesticide in Water Calculator (PWC), the estimated drinking water concentrations (EDWCs) of amicarbazone for acute exposures are estimated to be 223 parts per billion (ppb) for ground water. The chronic exposures are estimated to be 149 ppb for ground water. The groundwater numbers were used because they are higher than the surface water numbers. Modeled estimates of drinking water concentrations were directly entered into the dietary exposure model.

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).

While there are no proposed residential uses for these tolerances, Amicarbazone is currently registered for the following uses that could result in residential exposures: residential lawns, golf courses, sod farms, commercial turf sites, parks, recreation areas, and school grounds. EPA assessed residential exposure using the following assumptions: Residential handler exposure is not expected. There is expected to be residential post-application exposure. There is no POD for the dermal route of exposure; therefore, dermal exposures have not been estimated. The post application exposure to children 1 to less than 2 years old, reflecting hand-to-mouth exposures resulting from outdoor (turf) applications, was used in the aggregate assessment. Food is the only route of exposure resulting from the petitioned-for tolerances. However, EPA's risk assessment considers all relevant exposure pathways. Further information regarding EPA standard assumptions and generic inputs for residential exposures may be found at https://www.epa.gov/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."

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 amicarbazone and any other substances and amicarbazone does not appear to produce a toxic metabolite produced by other substances. For the purposes of this action, therefore, EPA has not assumed that amicarbazone has a common mechanism of toxicity with other substances. In 2016, EPA's Office of Pesticide Programs released a guidance document titled, Pesticide Cumulative Risk Assessment: Framework for Screening Analysis https://www.epa.gov/pesticide-science-and-assessing-pesticide-risks/pesticide-cumulative-risk-assessment-framework. This document provides guidance on how to screen groups of pesticides for cumulative evaluation using a two-step approach beginning with the evaluation of available toxicological information and if necessary, followed by a risk-based screening approach. This framework supplements the existing guidance documents for establishing common mechanism groups (CMGs) and conducting cumulative risk assessments. During registration review, the Agency will utilize this framework to determine if the available toxicological data for amicarbazone suggests a candidate CMG may be established with other pesticides. If a CMG is established, a screening-level toxicology and exposure analysis may be conducted to provide an initial screen for multiple pesticide exposure.

E. 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. There was no evidence of quantitative or qualitative susceptibility in the rat and rabbit developmental, rat developmental neurotoxicity, and rat reproductive toxicity studies. There was no evidence of systemic toxicity following dermal exposure. Evidence of immunotoxicity (decreased number of spleen cells per spleen, suppressed antibody response, and decreased spleen weight) was observed in the immunotoxicity study, but at doses higher than those that caused decreased body weight or liver effects in other studies.

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 amicarbazone is complete.

ii. Acute neurotoxicity was observed in the database. A clear NOAEL was established for the acute neurotoxic effects, and the endpoints and PODs selected for risk assessment are protective of the clinical signs observed in the acute neurotoxicity study.

iii. No evidence of increased quantitative or qualitative susceptibility was seen in rat and rabbit developmental toxicity, rat reproduction, or rat developmental neurotoxicity studies. All effects in the young were observed in the presence of comparable maternal toxicity. Delayed skeletal development and incomplete ossification were observed in the rat and rabbit developmental studies, respectively, at doses where dams had decreased body weight. In the reproduction study, decreased pup weight was seen at the same doses as decreased body weight in the dams. The endpoints selected for risk assessment are protective of all effects observed in these studies.

iv. There is no residual uncertainty with respect to the exposure assessments conducted for amicarbazone. The dietary exposure estimates in this assessment rely on conservative estimates of all residues of concern from both the food and drinking water exposure pathways. The aggregate assessment, which includes children's exposures to residues on treated turf, is expected to be conservative due to the use of default turf transferable residue (TTR) data, whereas the greatest herbicidal effectiveness is achieved when it is watered in.

F. Aggregate Risks and Determination of Safety

EPA determines whether acute and chronic dietary pesticide exposures are safe by comparing aggregate exposure estimates to the acute PAD (aPAD) and chronic PAD (cPAD). For linear cancer risks, EPA calculates the lifetime probability of acquiring cancer given the estimated aggregate exposure. Short-, intermediate-, and chronic-term risks are evaluated by comparing the estimated aggregate food, water, and residential exposure to the appropriate PODs to ensure that an adequate MOE exists.

1. Acute risk. Using the exposure assumptions discussed in this unit for acute exposure, the acute dietary exposure from food and water to amicarbazone will occupy 45% of the aPAD for all infants less than 1 year old, the population group receiving the greatest exposure.

2. Chronic risk. Using the exposure assumptions described in this unit for chronic exposure, EPA has concluded that chronic exposure to amicarbazone from food and water will utilize 61% of the cPAD for all infants less than 1 year old, the population group receiving the greatest exposure. Based on the explanation in Unit III.C.3., regarding residential use patterns, chronic residential exposure to residues of amicarbazone is not expected.

3. Short-term risk. Short-term aggregate exposure takes into account short-term residential exposure plus chronic exposure to food and water (considered to be a background exposure level). Amicarbazone is currently registered for uses that could result in short-term residential exposure, and the Agency has determined that it is appropriate to aggregate chronic exposure through food and water with short-term residential exposures to amicarbazone.

Using the exposure assumptions described in this unit for short-term exposures, EPA has concluded the combined short-term food, water, and residential exposures result in aggregate MOEs of 400 for children 1-2 years old, the only population group of concern. Because EPA's level of concern for amicarbazone is an MOE of 100 or below, this MOE is not of concern.

4. Intermediate-term risk. Intermediate-term aggregate exposure takes into account intermediate-term residential exposure plus chronic exposure to food and water (considered to be a background exposure level).

An intermediate-term adverse effect was identified; however, amicarbazone is not registered for any use patterns that would result in intermediate-term residential exposure. Intermediate-term risk is assessed based on intermediate-term residential exposure plus chronic dietary exposure. Because there is no intermediate-term residential exposure and chronic dietary exposure has already been assessed under the appropriately protective cPAD (which is at least as protective as the POD used to assess intermediate-term risk), no further assessment of intermediate-term risk is necessary, and EPA relies on the chronic dietary risk assessment for evaluating intermediate-term risk for amicarbazone.

5. Aggregate cancer risk for U.S. population. Based on the lack of evidence of carcinogenicity in two adequate rodent carcinogenicity studies, amicarbazone is not expected to pose a cancer risk to humans.

6. Determination of safety. Based on these risk assessments, EPA concludes that there is a reasonable certainty that no harm will result to the general population, or to infants and children from aggregate exposure to amicarbazone residues.

IV. Other Considerations

A. Analytical Enforcement Methodology

Adequate enforcement methodology (LC-MS/MS) is available to enforce the tolerance expression.

B. International Residue Limits

In making its tolerance decisions, EPA seeks to harmonize U.S. tolerances with international standards whenever possible, consistent with U.S. food safety standards and agricultural practices. EPA considers the international maximum residue limits (MRLs) established by the Codex Alimentarius Commission (Codex), as required by FFDCA section 408(b)(4).

The Codex has not established a MRL for amicarbazone in or on sugarcane.

V. Conclusion

Therefore, tolerances are established for residues of amicarbazone in or on sugarcane, cane at 0.2 ppm; and sugarcane, molasses at 0.5 ppm.

VI. Statutory and Executive Order Reviews

Additional information about these statutes and Executive orders can be found at https://www.epa.gov/regulations/and-executive-orders.

A. Executive Order 12866: Regulatory Planning and Review

This action is exempt from review under Executive Order 12866 (58 FR 51735, October 4, 1993), because it establishes or modifies a pesticide tolerance or a tolerance exemption under FFDCA section 408 in response to a petition submitted to the Agency. The Office of Management and Budget (OMB) has exempted these types of actions from review under Executive Order 12866.

B. Executive Order 14192: Unleashing Prosperity Through Deregulation

Executive Order 14192 (90 FR 9065, February 6, 2025) does not apply because actions that establish a tolerance under FFDCA section 408 are exempted from review under Executive Order 12866.

C. Paperwork Reduction Act (PRA)

This action does not impose an information collection burden under the PRA 44 U.S.C. 3501 et seq., because it does not contain any information collection activities.

D. Regulatory Flexibility Act (RFA)

Since tolerance actions that are established on the basis of a petition under FFDCA section 408(d), such as the tolerance in this final rule, do not require the issuance of a proposed rule, the requirements of the RFA, 5 U.S.C. 601 et seq., do not apply to this action.

E. Unfunded Mandates Reform Act (UMRA)

This action does not contain an unfunded mandate of $100 million or more (in 1995 dollars and adjusted annually for inflation) as described in UMRA, 2 U.S.C. 1531-1538, and does not significantly or uniquely affect small governments. The action imposes no enforceable duty on any State, local, or Tribal governments or on the private sector.

F. Executive Order 13132: Federalism

This action does not have federalism implications as specified in Executive Order 13132 (64 FR 43255, August 10, 1999), because it will not have substantial direct effects on the States, on the relationship between the National Government and the States, or on the distribution of power and responsibilities among the various levels of government.

G. Executive Order 13175: Consultation and Coordination With Indian Tribal Governments

This action does not have Tribal implications as specified in Executive Order 13175 (65 FR 67249, November 9, 2000), because it will not have substantial direct effects on Tribal governments, on the relationship between the Federal Government and the Indian Tribes, or on the distribution of power and responsibilities between the Federal Government and Indian Tribes.

H. Executive Order 13045: Protection of Children From Environmental Health Risks and Safety Risks

This action is not subject to Executive Order 13045 (62 FR 19885, April 23, 1997) because tolerance actions like this one are exempt from review under Executive Order 12866. However, EPA's 2021 Policy on Children's Health applies to this action.

This rule finalizes tolerance actions under the FFDCA, which 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 . . ." (FFDCA 408(b)(2)(C)). The Agency's consideration is documented in the pesticide-specific registration review documents, located in each chemical docket at https://www.regulations.gov.

I. Executive Order 13211: Actions Concerning Regulations That Significantly Affect Energy Supply, Distribution or Use

This action is not subject to Executive Order 13211 (66 FR 28355) (May 22, 2001) because it is not a significant regulatory action under Executive Order 12866.

J. National Technology Transfer Advancement Act (NTTAA)

This action does not involve technical standards that would require Agency consideration under NTTAA section 12(d), 15 U.S.C. 272.

K. Congressional Review Act (CRA)

This action is subject to the CRA, 5 U.S.C. 801 et seq., and EPA will submit a rule report to each House of the Congress and to the Comptroller General of the United States. This action is not a "major rule" as defined by 5 U.S.C. 804(2).

Therefore, 40 CFR chapter I is amended as follows:

PART 180-TOLERANCES AND EXEMPTIONS FOR PESTICIDE CHEMICAL RESIDUES IN FOOD

[FR Doc. 2025-19144 Filed 9-30-25; 8:45 am]

BILLING CODE 6560-50-P