n-Butyl 3-hydroxybutyrate and Isopropyl 3-hydroxybutyrate; Exemption From the Requirement of a Tolerance
Federal Register, Volume 81 Issue 157 (Monday, August 15, 2016)
Federal Register Volume 81, Number 157 (Monday, August 15, 2016)
Rules and Regulations
From the Federal Register Online via the Government Publishing Office www.gpo.gov
FR Doc No: 2016-19115
ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180
n-Butyl 3-hydroxybutyrate and Isopropyl 3-hydroxybutyrate; Exemption From the Requirement of a Tolerance
AGENCY: Environmental Protection Agency (EPA).
ACTION: Final rule.
SUMMARY: This regulation establishes exemptions from the requirement of a tolerance for residues of n-butyl 3-hydroxybutyrate (CAS Reg. No. 53605-94-0) and isopropyl 3-hydroxybutyrate (CAS Reg. No. 54074-94-1) when used as inert ingredients (solvents) in pesticide formulations applied to growing crops or raw agricultural commodities after harvest; to animals; and to food contact surfaces in public eating places, dairy-processing equipment, and food-processing equipment and utensils. Steptoe and Johnson, on behalf of Eastman Chemical Company, submitted a petition to EPA under the Federal Food, Drug, and Cosmetic Act (FFDCA), requesting establishment of these exemptions from the requirement of a tolerance. This regulation eliminates the need to establish a maximum permissible level for residues of n-butyl 3-hydroxybutyrate and isopropyl 3-hydroxybutyrate when applied or used under these conditions.
DATES: This regulation is effective August 15, 2016. Objections and requests for hearings must be received on or before October 14, 2016, and must be filed in accordance with the instructions provided in 40 CFR part 178 (see also Unit I.C. of the SUPPLEMENTARY INFORMATION).
ADDRESSES: The docket for this action, identified by docket identification (ID) number EPA-HQ-OPP-2015-0719, is available at http://www.regulations.gov or at the Office of Pesticide Programs Regulatory Public Docket (OPP Docket) in the Environmental Protection Agency Docket Center (EPA/DC), West William Jefferson Clinton Bldg., Rm. 3334, 1301 Constitution Ave. NW., Washington, DC 20460-0001. The Public Reading Room is open from 8:30 a.m. to 4:30 p.m., Monday through Friday, excluding legal holidays. The telephone number for the Public Reading Room is (202) 566-1744, and the telephone number for the OPP Docket is (703) 305-5805. Please review the visitor instructions and additional information about the docket available at http://www.epa.gov/dockets.
FOR FURTHER INFORMATION CONTACT: Susan Lewis, Registration Division (7505P), Office of Pesticide Programs, Environmental Protection Agency, 1200 Pennsylvania Ave. NW., Washington, DC 20460-0001; main telephone number: (703) 305-7090; email address: RDFRNotices@epa.gov.
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).
How can I get electronic access to other related information?
You may access a frequently updated electronic version of 40 CFR part 180 through the Government Printing Office's e-CFR site at http://www.ecfr.gov/cgi-bin/text-idx?&c=ecfr&tpl=/ecfrbrowse/Title40/40tab_02.tpl.
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-2015-0719 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 October 14, 2016. 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 (excluding any Confidential Business Information (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 the non-CBI copy of your objection or hearing request, identified by docket ID number EPA-HQ-OPP-2015-0719, by one of the following methods:
Federal eRulemaking Portal: http://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.
Mail: OPP Docket, Environmental Protection Agency Docket Center (EPA/DC), (28221T), 1200 Pennsylvania Ave. NW., Washington, DC 20460-0001.
Hand Delivery: To make special arrangements for hand delivery or delivery of boxed information, please follow the instructions at http://www.epa.gov/dockets/contacts.html. Additional instructions on commenting or visiting the docket, along with more information about dockets generally, is available at http://www.epa.gov/dockets.
Petition for Exemption
In the Federal Register of November 23, 2015 (80 FR 72941) (FRL-
9936-73), EPA issued a document pursuant to FFDCA section 408, 21 U.S.C. 346a, announcing the filing of a pesticide petition (PP IN-
10841) by Steptoe and Johnson LLP (1330 Connecticut Avenue NW., Washington, DC 20036-1795) on behalf of the Eastman Chemical Company (200 South Wilcox Drive, Kingsport, TN 37660-5280). The petition requested that 40 CFR 180.910, 180.930, and 180.940 be amended to establish exemptions from the requirement of a tolerance for residues of n-butyl 3-hydroxybutyrate (CAS Reg. No. 53605-94-0); and isopropyl 3-hydroxybutyrate (CAS Reg. No. 54074-94-1) when used as inert ingredients (solvents) in pesticide formulations applied to pre- and post-harvest crops under 40 CFR 180.910; to animals under 40 CFR 180.930; and to food contact surface sanitizing solutions under 40 CFR 180.940(a). That document referenced a summary of the petition prepared by Steptoe and Johnson on behalf of Eastman Chemical Company, the petitioner, which is available in the docket, http://www.regulations.gov.
Comments were received on the notice of filing. EPA's response to these comments is discussed in Unit V.B.
Inert Ingredient Definition
Inert ingredients are all ingredients that are not active ingredients as defined in 40 CFR 153.125 and include, but are not limited to, the following types of ingredients (except when they have a pesticidal efficacy of their own): Solvents such as alcohols and hydrocarbons; surfactants such as polyoxyethylene polymers and fatty acids; carriers such as clay and diatomaceous earth; thickeners such as carrageenan and modified cellulose; wetting, spreading, and dispersing agents; propellants in aerosol dispensers; microencapsulating agents; and emulsifiers. The term ``inert'' is not intended to imply nontoxicity; the ingredient may or may not be chemically active. Generally, EPA has exempted inert ingredients from the requirement of a tolerance based on the low toxicity of the individual inert ingredients.
Aggregate Risk Assessment and Determination of Safety
Section 408(c)(2)(A)(i) of FFDCA allows EPA to establish an exemption from the requirement for 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. . . .''
EPA establishes exemptions from the requirement of a tolerance only in those cases where it can be clearly demonstrated that the risks from aggregate exposure to pesticide chemical residues under reasonably foreseeable circumstances will pose no appreciable risks to human health. In order to determine the risks from aggregate exposure to pesticide inert ingredients, the Agency considers the toxicity of the inert in conjunction with possible exposure to residues of the inert ingredient through food, drinking water, and through other exposures that occur as a result of pesticide use in residential settings. If EPA is able to determine that a finite tolerance is not necessary to ensure that there is a reasonable certainty that no harm will result from aggregate exposure to the inert ingredient, an exemption from the requirement of a tolerance may be established.
Consistent with FFDCA section 408(c)(2)(A), and the factors specified in FFDCA section 408(c)(2)(B), 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 n-butyl 3-hydroxybutyrate and isopropyl 3-hydroxybutyrate including exposure resulting from the exemption established by this action. EPA's assessment of exposures and risks associated with n-butyl 3-hydroxybutyrate and isopropyl 3-
EPA has evaluated the available toxicity data and considered their 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. Specific information on the studies received and the nature of the adverse effects caused by n-butyl 3-hydroxybutyrate and isopropyl 3-hydroxybutyrate as well as the no-observed-adverse-effect-
level (NOAEL) and the lowest-observed-adverse-effect-level (LOAEL) from the toxicity studies are discussed in this unit.
n-Butyl-3-hydroxybutyrate and isopropyl-3-hydroxybutyrate are structurally similar chemical entities differing only in one methyl group (CH3). Therefore the toxicity of these two chemicals is expected to be similar. Since there are no adequate data available for each one individually, the Agency utilizes read-across data to fill data gaps.
n-Butyl-3-hydroxybutyrate and isopropyl-3-hydroxybutyrate both exhibit very low levels of acute oral, dermal and inhalation toxicity each with LD50 values >5,000 mg/kg. n-Butyl-3-
hydroxybutyrate is moderately irritating to the rabbit eye and is slightly irritating to rabbit skin. Isopropyl-3-hydroxybutyrate is not irritating to rabbit skin. n-Butyl-3-hydroxybutyrate and isopropyl-3-
hydroxybutyrate are not dermal sensitizers.
In a 28-day subchronic feeding study in rats which included a reproduction/developmental screening assessment, exposure to isopropyl-
3-hydroxybutyrate resulted in no adverse test item-related toxicological effects on clinical observations, no adverse effects seen in FOB assessments, no adverse effects on motor activity evaluations, no adverse effects seen in gross necropsy observations, male or female reproductive performance, or neurobehavioral parameters. The no-
observed-adverse-effect-level (NOAEL) for reproductive toxicity was 1,000 mg/kg/day. The NOAEL for systemic toxicity was 1,000 mg/kg/day. In the absence of effects on the general physical condition of F1 pups, the NOAEL for neonatal toxicity was 1,000 mg/kg/
n-Butyl-3-hydroxybutyrate and isopropyl-3-hydroxybutyrate were negative in reverse gene mutation assays. Isopropyl-3-hydroxybutyrate was negative in a chromosome aberration assay and a gene mutation assay.
There were no neurotoxicity or immunotoxicity studies available. However, there was no evidence of adverse neurotoxic effects noted during the FOB evaluations and the motor activity evaluations. There was no evidence of immunotoxicity in the available database.
Based on the negative responses seen in the genotoxicity and lack of systemic toxicity in the reproductive and developmental screening study, n-butyl-3-hydroxybutyrate and isopropyl-3-hydroxybutyrate are considered unlikely to be carcinogenic.
n-Butyl-3-hydroxybutyrate and isopropyl-3-hydroxybutyrate both have a low solubility; therefore, it is unlikely that either material will be absorbed by the body and become systemically bioavailable. Both compounds are expected to hydrolyze quickly and completely in vivo, and the resulting hydrolysis products are very close in structure or are the same, depending on the specific hydrolysis product. The available in vitro data suggests that isopropyl-3-hydroxybutyrate can undergo fast hydrolysis by enzymes in the plasma and liver to produce n-butyl-
3-hydroxybutyrate, which is perhaps further metabolized. Isopropyl-3-
hydroxybutyrate concentration decreased from approximately 70 muM to below the limit of detection (