Pesticide Tolerances: Spiromesifen

Federal Register: February 3, 2010 (Volume 75, Number 22)

Rules and Regulations

Page 5522-5526

From the Federal Register Online via GPO Access [wais.access.gpo.gov]

DOCID:fr03fe10-12

ENVIRONMENTAL PROTECTION AGENCY 40 CFR Part 180

EPA-HQ-OPP-2008-0262; FRL-8436-9

Spiromesifen; Pesticide Tolerances

AGENCY: Environmental Protection Agency (EPA).

ACTION: Final rule.

SUMMARY: This regulation establishes tolerances for the inadvertent or indirect combined residues of spiromesifen (2-oxo-3-(2,4,6- trimethylphenyl)-1-oxaspiro[4.4]non-3-en-4-yl 3,3-dimethylbutanoate) its enol metabolite (4-hydroxy-3-(2,4,6-trimethylphenyl)-1- oxaspiro[4.4]non-3-en-2-one), and its metabolites containing the 4- hydroxymethyl moiety (4-hydroxy-3-[4-(hydroxymethyl)-2,6- dimethylphenyl]-1-oxaspiro[4.4]non-3-en-2-one), calculated as the parent compound equivalents, in or on the following commodities from crops grown as rotational crops: bulb vegetables. Bayer CropScience requested these tolerances under the Federal Food, Drug, and Cosmetic

Act (FFDCA).

DATES: This regulation is effective February 3, 2010. Objections and requests for hearings must be received on or before April 5, 2010, 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-2008-0262. 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: Jennifer Gaines, Registration Division

(7505P), Office of Pesticide Programs, Environmental Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460-0001; telephone number: (703) 305-5967; e-mail address: gaines.jennifer@epa.gov.

SUPPLEMENTARY INFORMATION:

1. General Information

   1. 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.

   2. How Can I Access Electronic Copies of this Document?

      In addition to accessing electronically available documents at http://www.regulations.gov, you may access this Federal Register document electronically through the EPA Internet under the ``Federal

      Register'' listings at

      Page 5523

      http://www.epa.gov/fedrgstr. You may also access a frequently updated electronic version of EPA's tolerance regulations at 40 CFR part 180 through the Government Printing Office's e-CFR cite at http:// www.gpoaccess.gov/ecfr.

   3. Can I File an Objection or Hearing Request?

      Under section 408(g) of FFDCA, 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-2008-0262 in the subject line on the first page of your submission. All requests must be in writing, and must be mailed or delivered to the Hearing Clerk as required by 40 CFR part 178 on or before April 5, 2010.

      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 that is described in ADDRESSES. Information not marked confidential pursuant to 40 CFR part 2 may be disclosed publicly by EPA without prior notice. Submit this copy, identified by docket ID number

      EPA-HQ-OPP-2008-0262, 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.

2. Petition for Tolerance

   In the Federal Register of November 5, 2008 (73 FR 65851) (FRL- 8385-1), 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 8F7398) by Bayer CropScience, P.O. Box 12014, 2 T. W. Alexander Dr.,

   Research Triangle Park, NC 27709. The petition requested that 40 CFR 180.607 be amended by establishing tolerances for the inadvertent or indirect combined residues of the insecticide spiromesifen (2-oxo-3-

   (2,4,6-trimethylphenyl)-1-oxaspiro[4.4]non-3-en-4-yl 3,3- dimethylbutanoate), its enol metabolite (4-hydroxy-3-(2,4,6- trimethylphenyl)-1-oxaspiro[4.4]non-3-en-2-one), and its metabolites containing the 4-hydroxymethyl moiety (4-hydroxy-3-[4-(hydroxymethyl)- 2,6-dimethylphenyl]-1-oxaspiro[4.4]non-3-en-2-one), calculated as the parent compound equivalents, in or on the following commodities from crops grown as rotational crops: vegetable, bulb, group 3-07 at 0.07 parts per million (ppm). That notice is available to the public in the docket, http://www.regulations.gov. One comment was received on the notice of filing. EPA's response to this comment is discussed in Unit

   IV.C.

3. 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 the petitioned-for tolerances for inadvertent or indirect combined residues of spiromesifen, (2-oxo-3-(2,4,6- trimethylphenyl)-1-oxaspiro[4.4]non-3- en-4-yl 3,3-dimethylbutanoate), its enol metabolite (4-hydroxy-3-

   (2,4,6-trimethylphenyl)-1-oxaspiro[4.4]non-3-en-2-one), and its metabolites containing the 4-hydroxymethyl moiety (4-hydroxy-3-[4-

   (hydroxymethyl)-2,6-dimethylphenyl]-1-oxaspiro[4.4]non-3-en-2-one), calculated as the parent compound equivalents, on the following commodities from crops grown as rotational crops: vegetable, bulb, group 3-07. EPA's assessment of exposures and risks associated with establishing tolerances follows.

   1. 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.

      Spiromesifen shows low acute toxicity via the oral, dermal and inhalation routes of exposure. It was neither an eye nor dermal irritant, but showed moderate potential as a contact sensitizer. In short- and long-term animal toxicity tests, the critical effects observed were loss of body weight, adrenal effects (discoloration, decrease in fine vesiculation, and the presence of cytoplasmic eosinophilia in zona fasciculata cells), thyroid effects (increased thyroid stimulating hormone, increased thyroxine binding capacity, decreased T3and T4levels, colloidal alteration and thyroid follicular cell hypertrophy), liver effects (increased alkaline phosphatase, ALT and decreased cholesterol, triglycerides), and spleen effects (atrophy, decreased spleen cell count, and increased macrophages). Spiromesifen shows no significant developmental or reproductive effects, is not likely to be carcinogenic based on bioassays in rats and mice, and lacks in vivo and in vitro mutagenic effects. Spiromesifen is not considered a neurotoxic chemical based on the chemical's mode of action and the available data from multiple studies, including acute and subchronic neurotoxicity studies.

      Specific information on the studies received and the nature of the adverse effects caused by spiromesifen 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 the document ``Spiromesifen: Human-Health Risk

      Assessment for Request to Reduce Rotational Crop Plantback Interval

      (PBI) for Bulb Vegetables (Crop Group 3),'' at pages 11-16 in docket ID number EPA-HQ-OPP-2008-0262 and memo, D363706, June 11, 2009.

      Page 5524

   2. Toxicological Endpoints

      For hazards that have a threshold below which there is no appreciable risk, a toxicological point of departure (POD) is identified as the basis for derivation of reference values for risk assessment. The POD may be defined as the highest dose at which no adverse effects are observed (the NOAEL) in the toxicology study identified as appropriate for use in risk assessment. However, if a

      NOAEL cannot be determined, the lowest dose at which adverse effects of concern are identified (the LOAEL) or a Benchmark Dose (BMD) approach is sometimes used for risk assessment. Uncertainty/safety factors (UFs) are used in conjunction with the POD to take into account uncertainties inherent in the extrapolation from laboratory animal data to humans and in the variations in sensitivity among members of the human population as well as other unknowns. Safety is assessed for acute and chronic dietary risks by comparing aggregate food and water exposure to the pesticide to the acute population adjusted dose (aPAD) and chronic population adjusted dose (cPAD). The aPAD and cPAD are calculated by dividing the POD by all applicable UFs. Aggregate short-, intermediate-

      , and chronic-term risks are evaluated by comparing food, water, and residential exposure to the POD to ensure that the margin of exposure

      (MOE) called for by the product of all applicable UFs is not exceeded.

      This latter value is referred to as the Level of Concern (LOC).

      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 greater than that 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 spiromesifen used for human risk assessment can be found at http://www.regulations.gov in the document ``Spiromesifen: Human-Health Risk Assessment for Request to

      Reduce Rotational Crop Plantback Interval (PBI) for Bulb Vegetables

      (Crop Group 3),'' at page 17 in docket ID number EPA-HQ-OPP-2008-0262.

   3. Exposure Assessment 1. Dietary exposure from food and feed uses. In evaluating dietary exposure to spiromesifen, EPA considered exposure under the petitioned- for tolerances as well as all existing spiromesifen tolerances in (40

      CFR 180.607). EPA assessed dietary exposures from spiromesifen 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. No such effects were identified in the toxicological studies for spiromesifen; therefore, a quantitative acute dietary exposure assessment is unnecessary. ii. Chronic exposure. In conducting the chronic dietary exposure assessment EPA used the food consumption data from the USDA 1994-1996 and 1998 Cummulative Survey of Food Intake by Individuals. As to residue levels in food, EPA assumed tolerance-level residues for all commodities except for the leafy-greens and leafy Brassica greens subgroups (4A and 5B). The tolerance values for leafy vegetables were adjusted upward to account for the metabolite BSN 2060-4-hydroxymethyl

      (free and conjugated), which is a residue of concern in leafy vegetables for risk assessment purposes only. EPA used data from the metabolism studies to create a tolerance-equivalent value for the parent spiromesifen and the BSN 2060-4-hydroxymethyl metabolite to estimate residues in leafy vegetables. Dietary Exposure Evaluation

      Model (DEEM) 7.81 default processing factors and 100% crop treated (CT) were assumed for all commodities. iii. Cancer. Due to no evidence of carcinogenic effects in the submitted rat and mouse cancer studies, spiromesifen has been classified as ``not likely to be carcinogenic to humans.'' Therefore, an exposure assessment to evaluate cancer risk was not performed. iv. Anticipated residue and percent crop treated (PCT) information.

      EPA did not use anticipated residue and/or PCT information in the dietary assessment for spiromesifen. Tolerance level residues were used for all food commodities except for the leafy-greens and leafy Brassica greens subgroups (4A and 5B). For these subgroups, the residue values were adjusted to account for the metabolite BSN 2060-4-hydroxymethyl

      (free and conjugated), which is a residue of concern in leafy vegetables for risk assessment purposes only. The Agency assumed 100%

      CT for all food commodities. 2. Dietary exposure from drinking water. The Agency lacks sufficient monitoring data to complete a comprehensive dietary exposure analysis and risk assessment for spiromesifen in drinking water.

      Because the Agency does not have comprehensive monitoring data, the

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

      Parent spiromesifen is not likely to persist in the environment as it readily undergoes both biotic and abiotic degradation; however, its primary degradate, BSN2060-enol, is expected to persist. While parent spiromesifen strongly sorbs to sediment and is not likely to be mobile, its major degradates, BSN2060-enol and BSN2060-carboxy, do not sorb to sediment and are expected to leach into groundwater. Spiromesifen has limited solubility in water (130 micrograms/Liter ([micro]g/L) at 25[deg] C) and in some cases has been reported to have a practical solubility of 40 to 50 [micro]g/L. The pesticide degrades primarily through aerobic soil metabolism and hydrolysis; however, in clear shallow water it will readily undergo photolysis. Field studies indicate that spiromesifen readily dissipates with field dissipation half-lives ranging from 2 to 10 days.

      Based on the Pesticide Root Zone Model/Exposure Analysis Modeling

      System (PRZM/EXAMS) and Screening Concentration in Ground Water (SCI-

      GROW) models, the estimated drinking water concentrations (EDWCs) of spiromesifen for chronic exposure are 188 parts per billion (ppb) for surface water and 86 ppb for ground water. For chronic dietary risk assessment, the water concentration of value 188 ppb was used to assess the contribution to drinking water. 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).

      Spiromesifen is not registered for any specific use patterns that would result in residential exposure. 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

      Page 5525

      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 spiromesifen to share a common mechanism of toxicity with any other substances, and spiromesifen does not appear to produce a toxic metabolite produced by other substances. For the purposes of this tolerance action, therefore, EPA has assumed that spiromesifen 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 website at http:// www.epa.gov/pesticides/cumulative.

   4. 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 no evidence of increased susceptibility of rats or rabbits to in utero and/or postnatal exposure to spiromesifen. In the prenatal developmental toxicity studies in rats and rabbits and in the two-generation reproduction study in rats, developmental toxicity to the offspring occurred at equivalent or higher doses than parental toxicity. 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: 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 spiromesifen is complete and no additional immunotoxicity or neurotoxicty testing is required. The rationale is described below: a. Because spleen effects were seen in several toxicity studies, the registrant pursued specialized immunotoxicity studies in rats and mice that were both negative. These studies satisfy the revised 40 CFR part 158 requirement for immunotoxicity testing. In addition, the endpoints selected for the risk assessment are considered protective of any possible immunotoxic effects. b. There is no concern for neurotoxicity resulting from exposure to spiromesifen. Neurotoxic effects such as reduced motility, spastic gait, increased reactivity, tremors, clonic-tonic convulsions, reduced activity, labored breathing, vocalization, avoidance reaction, piloerection, limp, cyanosis, squatted posture, and salivation were observed in two studies (5-day inhalation and subchronic oral rat) at high doses (134 and 536 milligrams/kilogram/day (mg/kg/day), respectively). These effects were neither reflected in neurohistopathology nor in other studies. Because these effects were not observed in the acute and subchronic neurotoxicity studies, they were not considered reproducible. Thus, based on the chemical's mode of action and the available data from multiple studies, the chemical is not considered neurotoxic. ii. There is no evidence that spiromesifen results in increased susceptibility in in utero rats or rabbits in the prenatal developmental studies or in young rats in the 2-generation reproduction study. A developmental neurotoxicity study is not required. iii. 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. EPA made conservative

      (protective) assumptions in the ground and surface water modeling used to assess exposure to spiromesifen in drinking water. These assessments will not underestimate the exposure and risks posed by spiromesifen.

   5. Aggregate Risks and Determination of Safety

      EPA determines whether acute and chronic pesticide exposures are safe by comparing aggregate exposure estimates to the aPAD and cPAD.

      The aPAD and cPAD represent the highest safe exposures, taking into account all appropriate SFs. EPA calculates the aPAD and cPAD by dividing the POD by all applicable UFs. For linear cancer risks, EPA calculates the probability of additional cancer cases 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 POD to ensure that the MOE called for by the product of all applicable UFs is not exceeded. 1. Acute risk. An acute aggregate risk assessment takes into account exposure estimates from acute 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, spiromesifen 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 spiromesifen from food and water will utilize 77% of the cPAD for infants (