Federal Register: December 1, 2010 (Volume 75, Number 230)
Rules and Regulations
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
ENVIRONMENTAL PROTECTION AGENCY 40 CFR Part 180
Spiroxamine; Pesticide Tolerances
AGENCY: Environmental Protection Agency (EPA).
ACTION: Final rule.
SUMMARY: This regulation establishes tolerances for residues of spiroxamine, [(8-(1,1-dimethylethyl)-N-ethyl-N-propyl-1, 4- dioxaspiro[4,5]decane-2-methanamine)], including its metabolites and degradates in or on artichoke, globe, import at 0.7 parts per million
(ppm) asparagus, import at 0.05 ppm; and vegetables, fruiting, crop group 8, import at 1.2 ppm. Bayer CropScience requested these tolerances under the Federal Food, Drug, and Cosmetic Act (FFDCA).
DATES: This regulation is effective December 1, 2010. Objections and requests for hearings must be received on or before January 31, 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).
ADDRESSES: EPA has established a docket for this action under docket identification (ID) number EPA-HQ-OPP-2010-0136. 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: Tamue L. Gibson, Registration Division
(7505P), Office of Pesticide Programs, Environmental Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460-0001; telephone number: (703) 305-9096; e-mail address: email@example.com.
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 INFORMATION CONTACT.
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://www.gpoaccess.gov/ecfr.
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-2010-0136 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
January 31, 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-2010-0136, by one of the following methods:
Federal eRulemaking Portal: http://www.regulations.gov.
Follow the on-line 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.
Summary of Petitioned-For Tolerance
In the Federal Register of March 24, 2010 (75 FR 14154) (FRL-8815- 6), 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 9E7564) by Bayer CropScience, 2 T.W. Alexander Drive, P.O. Box 12014,
Research Triangle Park, North Carolina 27709. The petition requested that 40 CFR part 180 be amended by establishing tolerances for residues of the fungicide spiroxamine, (8-(1,1-dimethylethyl)-N-ethyl-N-propyl- 1,4-dioxaspiro[4,5]decane-2-methanamine) and its metabolites containing the N-ethyl-N-propyl-1,2-dihydroxy-3-aminopropane moiety, calculated as parent equivalent, in or on artichoke, globe at 0.7 parts per million
(ppm); asparagus at 0.05 ppm and vegetable, fruiting, group 8 at 1.2 ppm. That notice referenced a summary of the petition prepared by Bayer
CropScience, the registrant, which is available in the docket, http:// www.regulations.gov. There were no comments received in response to the notice of filing.
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 sufficient data to assess the hazards of and to make a determination on aggregate exposure for spiroxamine including exposure resulting from the tolerances established by this action.
EPA's assessment of exposures and risks associated with spiroxamine follows.
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. Specific information on the studies received and the nature of the adverse effects caused by spiroxamine 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 ``Spiroxamine: Human Health Risk
Assessment for Spiroxamine on Imported Artichoke, Asparagus and
Fruiting Vegetables (Corp Group 8),'' pp. 33-36 in docket ID number
Spiroxamine has low acute oral and inhalation toxicity and is not irritating to the eye. However, spiroxamine is a skin sensitizer when tested in guinea pigs and is a severe dermal irritant. Spiroxamine subchronic studies show the target organ of toxicity is the liver.
These studies were characterized by slight to mild hepatotoxicity, with associated elevation in liver enzymes. Mucous membranes of the esophagus and forestomach were keratinized and hyperplastic as a result of the strong irritant properties of spiroxamine. Administration of spiroxamine in long-term studies in the dog resulted in hepatocytomegaly, cataracts, and liver discoloration. In the rat, it resulted in an increased mortality in females, decreased body weights and body weight gains in both sexes, and increased esophageal hyperkeratosis in both sexes, while in the mouse, chronic administration resulted in uterine nodules, hyperplasia in the adrenal gland of males, hyperkeratosis in the esophagus, forestomach, and tongue of females, and acanthosis in the pinnae and tails of females.
Developmental effects in rats entailed delayed ossification which may be considered secondary to decreased body weight. Treatment-related developmental effects
were not seen in rabbits. There was no evidence of increased susceptibility of the young animals following exposure to spiroxamine in any developmental toxicity studies in the data base. There was evidence of mild spiroxamine-induced neurotoxicity characterized by piloerection and slight to moderate gait incoordination, and functional observational battery (FOB) effects of decreased forelimb grip strength and foot splay in males in the acute neurotoxicity study. No neuropathology was seen in either the acute or subchronic toxicity studies in rats and no neurotoxicity was detected in the subchronic study. Spiroxamine has no carcinogenic potential, as indicated in both the rat and the mouse carcinogenicity studies. In addition, spiroxamine has no mutagenicity potential, based on several in vivo and in vitro studies.
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 spiroxamine used for human risk assessment is shown in Table 1 of this unit.
Table 1--Summary of Toxicological Doses and Endpoints for Spiroxamine for Use in Human Health Risk Assessment
RfD, PAD, level
Uncertainty/FQPA of concern for
Study and departure
safety factors risk assessment toxicological effects
Acute Dietary (General
NOAEL = 10 mg/kg/ UFA = 10X........ aRfD = 0.1 mg/kg/ Acute Neurotoxicity in population, including infants day.
UFH = 10X........ day.
Rats. LOAEL = 30 mg/ and children.
FQPA = 1X........ aPAD = 0.1 mg/kg/ kg based on clinical day.
signs (piloerection and slight to moderate gait in coordination) and FOB effects (decreased forelimb grip strength and foot splay) in males on
Acute Dietary (females 13-49
No hazard identified. years old).
NOAEL = 2.5 mg/kg/ UFA = 10X........ cRfD = 0.025 mg/ Chronic Oral Toxicity population, including infants day.
UFH = 10X........ kg/day.
Study in Dogs. LOAEL and children.
FQPA = 1X........ cPAD = 0.025 mg/
= 28.03/25.84 mg/kg/ kg/day.
day M/F based on hepatocytomegaly, cataracts and decreased albumin in males and females; liver discoloration and decreased triglycerides in females; and increased alanine aminotransferase in males.
Short-term (1-30 days)
No residential uses are proposed.
Intermediate Term (1-6 months)
No residential uses are proposed.
Short-term (1-30 days) Dermal.. NOAEL 5 mg/kg/day UFA = 10X........ LOC =............ Prenatal Toxicity
UFH = 10X........ MOE