ACTION
Final Rule.
SUMMARY
This regulation establishes an exemption from the requirement of a tolerance for residues of di-n-butyl carbonate (CAS Reg. No. 542-52-9) when used as an inert ingredient (solvent) in pesticide formulations applied to growing crops, raw agricultural commodities after harvest, and animals, and when used as an inert ingredient in antimicrobial pesticide formulations in food-contact surfaces sanitizer products at a maximum levelin the end-use concentration of 15,000 ppm (1.5%). Exponent Inc., on behalf of Huntsman Corp., submitted a petition to EPA under the Federal Food, Drug, and Cosmetic Act (FFDCA), requesting establishment of an exemption from the requirement of a tolerance. This regulation eliminates the need to establish a maximum permissible level for residues of di-n-butyl carbonate.
TABLE OF CONTENTS
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DATES:
ADDRESSES:
FOR FURTHER INFORMATION CONTACT:
SUPPLEMENTARY INFORMATION:
I. General Information
A. Does this action apply to me?
B. How can I get electronic access to other related information?
C. How can I file an objection or hearing request?
II. Petition for Exemption
III. Inert Ingredient Definition
IV. Aggregate Risk Assessment and Determination of Safety
A. Toxicological Profile
B. Toxicological Points of Departure/Levels of Concern
C. Exposure Assessment
D. Safety Factor for Infants and Children
E. Aggregate Risks and Determination of Safety
V. Other Considerations
A. Analytical Enforcement Methodology
VI. Conclusions
VII. Statutory and Executive Order Reviews
VIII. Congressional Review Act
List of Subjects in 40 CFR Part 180
PART 180—[AMENDED]
DATES:
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This regulation is effective June 15, 2015. Objections and requests for hearings must be received on or before August 14, 2015, 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:
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The docket for this action, identified by docket identification (ID) number EPA-HQ-OPP-2014-0176, 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:
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Susan Lewis, Director, 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.
SUPPLEMENTARY INFORMATION:
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I. General Information
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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. 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 Publishing Office's e-CFR site at http://www.ecfr.gov/cgi-bin/text-idx?&c=ecfr&tpl=/ecfrbrowse/Title40/40tab_02.tpl. To access the OCSPP test guidelines referenced in this document electronically, please go to http://www.epa.gov/ocspp 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-2014-0176 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 August 14, 2015. 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-2014-0176, 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.
II. Petition for Exemption
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In the Federal Register of January 28, 2015 (80 FR 4525) (FRL-9921-55), EPA issued a document pursuant to FFDCA section 408, 21 U.S.C. 346a, announcing the filing of a pesticide petition (PP IN-10683) by Exponent Inc., 1150 Connecticut Ave. NW., Suite 1100, Washington, DC 20036, on behalf of Huntsman Corporation, 8600 Gosling Road, The Woodlands, TX 77381. The petition requested that 40 CFR 180.910, 180.930, and 180.940 be amended by establishing an exemption from the requirement of a tolerance for residues of di-n-butyl carbonate (CAS Reg. No. 542-52-9) when used as an inert ingredient (solvent) in pesticide formulations applied to growing crops, raw agricultural commodities after harvest, and animals, and when used as an inert ingredient in antimicrobial formulations in food-contact surface sanitizer products. That document referenced a summary of the petition prepared by Exponent Inc., on behalf of Huntsman Corp., the petitioner, which is available in the docket, http://www.regulations.gov. There were no comments received in response to the notice of filing.
based on a review of the data submitted in support of this petition, EPA has modified the exemption requested by limiting the amount of di-n-butyl carbonoate allowed in food contact sanitizing solutions to a maximum 15,000 ppm (1.5%). This limitation is based on the Agency's risk assessment which can be found at http://www.regulations.gov in document “Di-n-Butyl Carbonate; Human Health Risk Assessment and Ecological Effects Assessment to Support Proposed Exemption from the Requirement of a Tolerance When Used as an Inert Ingredient in Pesticide Formulations,” in docket ID number EPA-HQ-OPP-2014-0176.
III. Inert Ingredient Definition
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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.
IV. Aggregate Risk Assessment and Determination of Safety
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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 di-n-butyl carbonate including exposure resulting from the exemption established by this action. EPA's assessment of exposures and risks associated with di-n-butyl carbonate follows.
A. Toxicological Profile
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 di-n-butyl carbonate 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.
Di-n-butyl carbonate acute toxicity testing indicate that it has low acute oral, dermal and inhalation toxicity (acute oral and dermal LD 50> 2,000 milligrams/kilogram (mg/kg); acute inhalation LC 50>8 mg/Liter (mg/L) and is non-irritating to the eyes and negative for dermal sensitization. Di-n-butyl carbonate is irritating to the skin. In a combined repeated dose toxicity study with the reproductive and developmental toxicity screening test, di-n-butyl carbonate was administered daily to rats by gavage. The di-n-butyl carbonate test material did not result in any test material related mortality or clinical observations in the parental animals. No effects were observed in the functional observational battery, hematology and clotting parameters, clinical chemistry parameters, or organ weights. No macroscopic findings related to the test item were observed. No histopathological effects were reported in neurological tissues (cerebrum, cerebellum, pons, peripheral nerve, spinal cord) (cervical, midthoracic and lumbar sections) or any immunological tissues (bone marrow, thymus, spleen, lymph nodes).
The NOAEL of di-n-butyl carbonate in rats is 500 mg/kg bw/day for parental animals (males and females) and 500 mg/kg bw/day for embryo-fetal toxicity. The LOAEL is 750 mg/kg bw/day based on decreased body weight gain in male and female paternal animals and embryo-fetal toxicity at 750 mg/kg bw/day as evidenced by increased pre- and post-implantation losses and decreased total number of pups.
If ingested di-n-butyl carbonate would be readily hydrolyzed by esterases in the gut to generate two molar equivalents of n-butanol and one molar equivalent of carbonic acid. EPA has stated for the n-butanol tolerance reassessment that once absorbed, n-butanol disappears rapidly from the blood. The carbonic acid rapidly dissociates into CO 2 and water.
Di-n-butyl carbonate was negative in an OCSPP Harmonized Test Guideline Bacterial Reverse Mutation Assay (at concentrations ranging from 1.5 to 5,000 ug per plate); no positive mutagenic response was observed.
There are no carcinogenicity studies available for di-n-butyl carbonate. based on predicted rapid metabolism and excretion, the lack of specific target organ toxicity in the OCSPP Harmonized Test Guideline 870.3650 study, the results of genotoxicity testing being negative, and a Quantitative Structure Activity Relationship (QSAR) expert model, DEREK Nexus, that indicates no structural alerts for carcinogenicity, di-n-butyl carbonate is not expected to be carcinogenic.
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 http://www.epa.gov/pesticides/factsheets/riskassess.htm.
No acute toxicological endpoints have been identified for di-n-butyl carbonate; therefore no acute exposure assessments are warranted.
The overall NOAEL for di-n-butyl carbonate was established at 500 mg/kg/day. The chronic risk assessment for di-n-butyl carbonate is based on this endpoint and the chronic reference dose (cRfD) is therefore 5.0 mg/kg/day. The cRfD incorporates a 10X interspecies factor and a 10X intraspecies factor. Since the FQPA SF has been reduced to 1X, the cPAD is also 5.0 mg/kg/day.
C. Exposure Assessment
1. Dietary exposure from food and feed uses. In evaluating dietary exposure to di-n-butyl carbonate, EPA considered exposure under the proposed exemption from the requirement of a tolerance. EPA assessed dietary exposures from di-n-butyl carbonate in food as follows:
The Agency assessed the dietary exposures to di-n-butyl carbonate as an inert ingredient for use in pesticide formulations applied to growing crops, raw agricultural commodities, and livestock, as well as an inert ingredient for use in food-contact surface sanitizing solutions. In the case of dietary exposures to di-n-butyl carbonate as an inert ingredient used in pesticide formulations applied to growing crops, raw agricultural commodities, and livestock, a chronic dietary exposure assessment was conducted using the Dietary Exposure evaluation Model/Food Commodity Intake Database (DEEM-FCID) TM, Version 3.16. EPA used food consumption information from the U.S. Department of Agriculture's National Health and Nutrition Examination Survey, What We Eat in America, (NHANES/WWEIA). This dietary survey was conducted from 2003 to 2008. As to residue levels in food, no residue data were submitted for di-n-butyl carbonate. In the absence of specific residue data, EPA has developed an approach which uses surrogate information to derive upper bound exposure estimates for the subject inert ingredient. Upper bound exposure estimates are based on the highest tolerance for a given commodity from a list of high-use insecticides, herbicides, and fungicides. A complete description of the general approach taken to assess inert ingredient risks in the absence of residue data is contained in the memorandum entitled “Alkyl Amines Polyalkoxylates (Cluster 4): Acute and Chronic Aggregate (Food and Drinking Water) Dietary Exposure and Risk Assessments for the Inerts.” (D361707, S. Piper, 2/25/09) and can be found at http://www.regulations.gov in docket ID number EPA-HQ-OPP-2008-0738.
In the case of the proposed use of di-n-butyl carbonate as an inert ingredient in food-contact sanitizing pesticide products, EPA has utilized a conservative, health-protective method of estimating dietary intake that is based upon conservative assumptions related to the amount of residues that can be transferred to foods as a result of the proposed use. This same methodology has been utilized by EPA in estimating dietary exposures to antimicrobial pesticides used in food-handling settings. A complete description of the approach used to assess dietary exposures resulting from food contact sanitizing solution uses of di-n-butyl carbonate can be found at http://www.regulations.gov in document “Di-n-Butyl Carbonate; Human Health Risk Assessment and Ecological Effects Assessment to Support Proposed Exemption from the Requirement of a Tolerance When Used as an Inert Ingredient in Pesticide Formulations,” pp. 12-23 in docket ID number EPA-HQ-OPP-2014-0176.
The exposures from food and food contact sanitizing are then added together for the final dietary exposure assessment.
2. Dietary exposure from drinking water. For the purpose of the screening level dietary risk assessment to support this request for an exemption from the requirement of a tolerance for di-n-butyl carbonate, a conservative drinking water concentration value of 100 parts per billions (ppb) based on screening level modeling was used to assess the contribution to drinking water for the chronic dietary risk assessments for parent compound. These values 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., textiles (clothing and diapers), carpets, swimming pools, and hard surface disinfection on walls, floors, tables).
There are no current or proposed residential uses for di-n-butyl carbonate; however, it is possible that di-n-butyl carbonate may be used as an inert ingredient in pesticide products. A highly conservative residential exposure assessment was performed in which it was assumed that all residential use pesticide products would contain di-n-butyl carbonate as an inert ingredient. A complete description of the approach used to assess possible residential exposures from di-n-butyl carbonate can be found in http://www.regulations.gov in document “Di-n-Butyl Carbonate; Human Health Risk Assessment and Ecological Effects Assessment to Support Proposed Exemption from the Requirement of a Tolerance When Used as an Inert Ingredient in Pesticide Formulations,” pp. 16 in docket ID number EPA-HQ-OPP-2014-0176.
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 di-n-butyl carbonate to share a common mechanism of toxicity with any other substances, and di-n-butyl carbonate does not appear to produce a toxic metabolite produced by other substances. For the purposes of this tolerance action, therefore, EPA has assumed that di-n-butyl carbonate 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://www.epa.gov/pesticides/cumulative.
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. There is evidence for qualitative susceptibility in the OECD 422 study. In this study, embryo-fetal toxicity was manifested as evidenced by increased pre- and post-implantation losses and decreased total number of pups in the presence of maternal toxicity (decreased in body weights). However, considering the overall toxicity profile and the toxicity endpoints and doses selected for di-n-butyl carbonate, the degree of concern for the effects observed in the di-n-butyl carbonate reproductive and developmental toxicity screening studyis low. There is a clear NOAEL for the offspring effects, and endpoints and regulatory doses were selected for use in the dietary risk assessment to be protective of these effects.
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 di-n-butyl carbonate summarize the studies included in the database. EPA concludes that these data are sufficient for assessing the effects of di-n-butyl carbonate on infants and children.
ii. There is no indication that di-n-butyl carbonate is a neurotoxic chemical and there is no need for a developmental neurotoxicity study or additional UFs to account for neurotoxicity.
iii. Although there is some evidence that di-n-butyl carbonate results in increased susceptibility in rats, the degree of concern for these effects is low for the reasons explained in Unit IV.D.2.
iv. There are no residual uncertainties identified in the exposure databases. The dietary food exposure assessments were performed based on 100% CT and tolerance-level residues as well as conservative assumptions regarding exposures from food-contact sanitizer uses. EPA made conservative (protective) assumptions in the ground and surface water modeling used to assess exposure to di-n-butyl carbonate in drinking water. These assessments will not underestimate the exposure and risks posed by di-n-butyl carbonate.
E. Aggregate Risks and Determination of Safety
1. Acute risk. An acute aggregate risk assessment takes into account acute exposure estimates from dietary consumption of food and drinking water. No adverse effect resulting from a single oral exposure was identified and no acute dietary endpoint was selected. Therefore, di-n-butyl carbonate is not expected to pose an acute risk.
2. Chronic risk. Using the exposure assumptions described in this unit for chronic exposure, EPA has concluded that chronic exposure to di-n-butyl carbonate from food and water will utilize 21% of the cPAD for the U.S. population and 94% of the cPAD for children 1-2 years old, the population group receiving the greatest exposure.
3. Short- and Intermediate-term risk. Short- and intermediate-term aggregate exposure takes into account short- and intermediate-term residential exposure plus chronic exposure to food and water (considered to be a background exposure level). While di-n-butyl carbonate is not currently used as an inert ingredient in pesticide products that are registered for uses that could result in short- or intermediate-term residential exposure, it is possible that di-n-butyl carbonate could be used in such products and the Agency has determined that it is appropriate to aggregate chronic exposure through food and water with potential short-and intermediate-term residential exposures to n-butyl benzoate.
Using the exposure assumptions described in this unit for short-and intermediate-term exposures, EPA has concluded the combined food, water, and residential exposures result in aggregate short- and intermediate-term MOEs of 320 for adults and 100 for children (1-2 years old). EPA's level of concern for n-butyl benzoate is a MOE of 100 or below; however, these MOEs are not of concern based on the highly conservative assumptions made regarding residential and dietary exposures to n-butyl benzoate.
4. Aggregate cancer risk for U.S. population. As discussed in Unit IV.A., di-n-butyl carbonate is not expected to pose a cancer risk to humans.
5. 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 di-n-butyl carbonate residues.
V. Other Considerations
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A. Analytical Enforcement Methodology
An analytical method for enforcement purposes is not required for di-n-butyl carbonate in pesticide formulations which include uses on crops for pre- and post-harvest, and on animals, since the Agency is establishing an exemption from the requirement of a tolerance without any numerical limitation.
An analytical method is also not required for enforcement purposes for di-n-butyl carbonate on food-contact surfaces in antimicrobial applications since the Agency is not establishing a numerical tolerance for residues of di-n-butyl carbonate in or on any food commodities. EPA is establishing a limitation on the amount of di-n-butyl carbonate that may be used in food-contact surface antimicrobial applications. That limitation will be enforced through the pesticide registration process under the Federal Insecticide, Fungicide, and Rodenticide Act (“FIFRA”), 7 U.S.C. 136 et seq. EPA will not register any food-contact surface antimicrobial applications for sale or distribution that contains greater than 15,000 ppm (1.5%) of di-n-butyl carbonate by weight.
VI. Conclusions
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Therefore, exemptions from the requirement of a tolerance is established under 40 CFR 180.910, 180.930, and 180.940(a) for di-n-butyl carbonate (CAS Reg. No. 542-52-9) when used as an inert ingredient (solvent) in pesticide formulations applied to growing crops, raw agricultural commodities after harvest, and animals, and when used as an inert ingredient in antimicrobial formulations in food-contact surface sanitizer products at a maximum level in the end-use concentration of 15,000 ppm.
