Carfentrazone-ethyl; Pesticide Tolerances
Federal Register, Volume 77 Issue 87 (Friday, May 4, 2012)
Federal Register Volume 77, Number 87 (Friday, May 4, 2012)
Rules and Regulations
Pages 26456-26462
From the Federal Register Online via the Government Printing Office www.gpo.gov
FR Doc No: 2012-10688
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ENVIRONMENTAL PROTECTION AGENCY
EPA-HQ-OPP-2011-0428; FRL-9346-5
Carfentrazone-ethyl; Pesticide Tolerances
AGENCY: Environmental Protection Agency (EPA).
ACTION: Final rule.
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SUMMARY: This regulation establishes tolerances for residues of carfentrazone-ethyl in or on crop group 18, non-grass animal feed (forage, hay, and seed). FMC Corporation requested these tolerances under the Federal Food, Drug, and Cosmetic Act (FFDCA).
DATES: This regulation is effective May 4, 2012. Objections and requests for hearings must be received on or before July 3, 2012, 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: EPA has established a docket for this action under docket identification (ID) number EPA-HQ-OPP-2011-0428. All documents in the docket are listed in the docket index available at http://www.regulations.gov. 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 http://www.regulations.gov, 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: Bethany Benbow, Registration Division (7505P), Office of Pesticide Programs, Environmental Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460-0001; telephone number: (703) 347-8072; email address: benbow.bethany@epa.gov.
SUPPLEMENTARY INFORMATION:
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General Information
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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
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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 INFORMATION CONTACT.
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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 http://ecfr.gpoaccess.gov/cgi/t/text/text-idx?&c=ecfr&tpl=/ecfrbrowse/Title40/40tab_02.tpl.
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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-2011-0428 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 July 3, 2012. 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-2011-0428, by one of the following methods:
Federal eRulemaking Portal: http://www.regulations.gov. 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.
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Summary of Petitioned-For Tolerance
In the Federal Register of July 6, 2011 (76 FR 39360) (FRL-8875-6), EPA issued a notice pursuant to FFDCA section 408(d)(3), 21 U.S.C. 346a(d)(3), announcing the filing of a pesticide petition (PP 1F7839) by FMC Corporation, 1735 Market St., Philadelphia, PA 19103. The petition requested that 40 CFR 180.515 be amended by establishing tolerances for residues of the herbicide, carfentrazone-ethyl and its metabolite, carfentrazone-ethyl chloropropionic acid, in or on alfalfa, forage at 5 parts per million (ppm); alfalfa, hay at 18 ppm; alfalfa, seed at 10 ppm; clover, forage at 5 ppm; clover, hay at 18 ppm; and clover, seed at 10 ppm. That notice referenced a summary of the petition prepared by FMC Corporation, the registrant, which is available in the docket, http://www.regulations.gov. There were no comments received in response to the notice of filing.
Based upon review of the data supporting the petition, EPA has revised the proposed individual alfalfa and clover tolerances to crop group 18 tolerances. The reason for this change is explained in Unit IV.C.
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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 FFDCA section 408(b)(2)(D), and the factors specified in FFDCA section 408(b)(2)(D), 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 carfentrazone-ethyl including exposure resulting from the tolerances established by this action. EPA's assessment of exposures and risks associated with carfentrazone-
ethyl follows.
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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.
Carfentrazone-ethyl was ranked low in acute oral toxicity in rats via the oral, dermal, and inhalation routes of exposure. It was minimally irritating to eyes, non-irritating to skin, and not a skin sensitizer.
The proposed mode of action of carfentrazone-ethyl in target plants is through inhibition of the enzyme protoporphyrinogen oxidase (PPO) which is involved in chlorophyll biosynthesis. In mammals, PPO is also an important enzyme in heme biosynthesis and its inhibition can lead toxic effects where heme is utilized (e.g., red blood cells). Some of the toxicities reported for carfentrazone-ethyl are consistent with this mode of action. The target tissues/organs identified are the blood and liver and the most sensitive species was the rat. Subchronic toxicity studies in rats, mice, and dogs demonstrated that the primary effects were on hematological parameters (decreased mean corpuscular hemoglobin (MCH) and mean corpuscular volume (MCV)). There was also increased urinary porphyrin excretion, increased liver weights, and liver histopathology findings consisting of hepatic pigment deposition, hepatocytomegaly, single cell necrosis, and cell mitosis. Similarly, chronic toxicity studies in rats and dogs demonstrated increased urinary porphyrin excretion and liver histopathology findings in rats and mice consisting of liver pigmentation and increases in red fluorescence. Fluorescence microscopy on liver sections also revealed red fluorescent granules consistent with porphyrin deposits in rats and mice.
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There was no evidence of increased susceptibility in prenatal developmental toxicity studies (rats and rabbits) or the multigenerational reproductive toxicity study in rats. Carfentrazone-
ethyl induced a significant increase in litter incidences of wavy and thickened ribs in rats at a dose (1,250 mg/kg/day) much higher than the dose (600 mg/kg/day) that caused maternal toxicity consistent with interference with porphyrin metabolism (i.e., staining of the abdominogenital area and of the cage pan liner). The rabbit prenatal developmental toxicity study did not yield any evidence of treatment-
related prenatal developmental toxicity even at the highest dose tested (HDT) (300 mg/kg/day). The offspring effects from the 2-generation reproduction study consisted of decreased pup body weight in both sexes of the F2 generation at the HDT (343 mg/kg/day) and at which maternal toxicity was observed in the form of decreased body-weight gains, increased liver weights, liver and bile duct histopathology, and reductions in the mean cell volume (F0 and F1 males, F1 females), mean cell hemoglobin (F0 and F1 males, F1 females), hematocrit (F1 males), and hemoglobin (F1 males).
There is no concern for neurotoxicity. The results of the acute neurotoxicity study indicate clinical signs (i.e., salivation) and mild decreases in motor activity only on the treatment day and the subchronic neurotoxicity showed no signs of neurotoxicity up to the limit dose (1,178 mg/kg/day for males and 1,434 mg/kg/day for females).
In a 21-day dermal toxicity study, carfentrazone-ethyl did not induce any type of dermal or systemic toxicity up to the limit dose of 1,000 mg/kg/day. There are no toxicity studies based on repeated inhalation exposures to carfentrazone-ethyl. A waiver of a 28-day inhalation toxicity study was previously accepted based on its relatively low volatility, low acute inhalation lethality, and the large inhalation MOEs associated with the requested applications.
The mutagenic test battery demonstrated that carfentrazone-ethyl is not mutagenic. In accordance with the Draft Proposed Guidelines for Carcinogen Risk Assessment (April, 1999), carfentrazone-ethyl is classified as a ``not likely human carcinogen,'' based on the lack of evidence for carcinogenicity in the mouse and rat.
Specific information on the studies received and the nature of the adverse effects caused by carfentrazone-ethyl 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://www.regulations.gov in document: ``Carfentrazone-ethyl. Section 3 Registration for Application to the Non-grass Animal Feed Crop Group 18. Human-Health Risk Assessment'' pp. 30-32 in docket ID number EPA-
HQ-OPP-2011-0428.
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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.
A summary of the toxicological endpoints for carfentrazone-ethyl used for human risk assessment is shown in the Table of this unit.
Table--Summary of Toxicological Doses and Endpoints for Carfentrazone-ethyl for Use in Human Health Risk
Assessment
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Point of departure
Exposure/scenario and uncertainty/ RfD, PAD, LOC for Study and toxicological effects
safety factors risk assessment
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Acute dietary (General population NOAEL = 500 mg/kg/ Acute RfD = 5 mg/kg/ Acute neurotoxicity--rat.
including infants and children). day. day. LOAEL = 1000 mg/kg/day based on
UFA = 10x........... aPAD = 5 mg/kg/day. clinical observations
UFH = 10x........... (salivation) and decreased motor
FQPA SF = 1x........ activity.
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Chronic dietary (All populations) NOAEL = 3 mg/kg/day. Chronic RfD = 0.03 Chronic toxicity--rat.
UFA = 10x........... mg/kg/day. LOAEL = 12 mg/kg/day based on
UFH = 10x........... cPAD = 0.03 mg/kg/ liver histopath-ology (increases
FQPA SF = 1x........ day. in microscopic red fluor-escence
and pigmentation) and increased
urinary porphyrin levels in both
sexes.
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Incidental oral short-term (1 to NOAEL = 50 mg/kg/day LOC for MOE
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