Environmental Protection Agency (EPA).
Final rule.
This regulation establishes tolerances for combined residues of indoxacarb and its R-enantiomer in or on cranberry; fruit, pome, except pear, group 11; fruit, stone, group 12; grape; grape, raisin; okra; pea, southern, seed; pear, oriental; peppermint, tops; spearmint, tops; turnip greens; vegetable,
This regulation is effective July 11, 2007. Objections and requests for hearings must be received on or before September 10, 2007, and must be filed in accordance with the instructions provided in 40 CFR part 178 (see also Unit I.C. of the
EPA has established a docket for this action under docket identification (ID) number EPA–HQ–OPP–2005–0149. To access the electronic docket, go to
Barbara Madden, Registration Division (7505P), Office of Pesticide Programs, Environmental Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460–0001; telephone number: (703) 305–6463; e-mail address:
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), e.g., agricultural workers; greenhouse, nursery, and floriculture workers; farmers.
• Animal production (NAICS code 112), e.g., cattle ranchers and farmers, dairy cattle farmers, livestock farmers.
• Food manufacturing (NAICS code 311), e.g., agricultural workers; farmers; greenhouse, nursery, and floriculture workers; ranchers; pesticide applicators.
• Pesticide manufacturing (NAICS code 32532), e.g., agricultural workers; commercial applicators; farmers; greenhouse, nursery, and floriculture workers; residential users.
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
In addition to accessing an electronic copy of this
Under section 408(g) of the FFDCA, 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–2005–0149 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 September 10, 2007.
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
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Based upon review of the data supporting the petitions, EPA has modified the proposed tolerances. The reasons for these changes are explained in Unit V.
Section 408(b)(2)(A)(i) of the 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 the 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 the 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....” These provisions were added to the FFDCA by the Food Quality Protection Act (FQPA) of 1996.
Consistent with FFDCA section 408(b)(2)(D), and the factors specified in 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 the petitioned-for tolerances for combined residues of indoxacarb, (
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 indoxacarb 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
Indoxacarb is an isomeric compound containing two enantiomers, the
DPX-KN128, DPX-MP062 and DPX-JW062 appear to be of similar toxicity acutely. DPX-KN128 and DPX-MP062 were moderately acutely toxic by the oral route (toxicity category II) while DPX-JW062 was practically non-toxic (toxicity category IV) due to its poor solubility in the corn oil vehicle. However, it was equally toxic orally, when tested using a solvent where it had a higher solubility, such as polyethylene glycol (PEG). By the dermal route, they had low toxicity (toxicity category III and IV). DPX-MP062 and DPX-JW062 had low acute inhalation toxicity (IV). DPX-MP062 and DPX-JW062 had moderate to low ocular irritant properties (III and IV), while DPX-KN128 was practically non-irritating to the rabbit's eyes. By the maximization test, DPX-KN128 and DPX-MP062 were considered dermal sensitizers, while DPX-JW062 was not a sensitizer.
There was possible evidence of lung damage in the acute inhalation studies with both DPX-MP062 and DPX-JW062. “Lung noise,” observed with JW062 may indicate the development of acute lung injury and high permeability pulmonary edema. This was not unexpected since an oxidant was generated during indoxacarb metabolism. “Hunched over back and gasping” were also present and suggested arterial hypoxemia that accompanies alveolar flooding. The acute inhalation study report with indoxacarb 70% manufacturing use product, noted that a “red nasal discharge” was detected for 2 days after exposure. This may be indicative of a lung exudate, a sign of lung injury. Subchronic (28 days) inhalation toxicity on indoxacarb in rats was characterized by increased spleen weights, increased pigmentation and hematopoiesis in the spleen, and hematological changes.
The toxicity profiles for DPX-KN128, DPX-MP062 and DPX-JW062 in rats, mice and dogs with both subchronic and chronic oral exposures were similar. Dermal subchronic exposure in the rat also resulted in a similar profile. The toxic signs occurred at similar doses and with a similar magnitude of response, with females generally being more sensitive than males. The endpoints that most frequently defined the LOAEL were non-specific, and included decreased body weight, weight gain, food consumption and food efficiency. These compounds also affected the hematopoietic system by decreasing the red blood cell count, hemoglobin and hematocrit in rats, dogs and mice. It was frequently accompanied by an increase in reticulocytes in all three species and an increase in Heinz bodies (dogs and mice only). None of these signs of toxicity appeared to get worse over time. In one subchronic rat study, the parameters appeared to return to normal levels following a four-week recovery period. High doses in the rats and mice also sometimes caused mortality.
There was no evidence of susceptibility from either
Neurotoxicity was present in both rats and mice; however, it did not occur in the absence of other signs of toxicity. Neurotoxicity was characterized by one or more of the following symptoms in both male and female rats and mice: Weakness, head tilting, and abnormal gait or mobility with inability to stand, ataxia. Acute and subchronic neurotoxicity screening batteries were performed using DPX-MP062 in rats. Neurotoxicity was characterized by clinical signs (depression, abnormal gait, head shake, salivation) and functional-observation battery (FOB) (circling behavior, incoordination, slow righting reflex, decreased forelimb grip strength, decreased foot splay, decreased motor activity). However, there was no evidence of neurohistopathology in any study. Learning and memory parameters were affected in the pups in the developmental neurotoxicity study in rats with DPX-KN128.
There was no evidence of carcinogenicity in either the rat or mouse in acceptable studies using DPX-JW062. DPX-JW062 was not mutagenic in a complete battery of mutagenicity studies. There was also no evidence of mutagenicity with either DPX-KN128, or DPX-MP062.
Both DPX-JW062 and DPX-MP062 were rapidly absorbed and eliminated following oral administration. The absorption of DPX-JW062 was dose dependent and appeared to be saturated at the high dose. Both urine and feces represented major routes of excretion (35–45% and 33–47%, respectively). The distribution pattern did not vary with dosing regimen and overall tissue burden was limited to only 3.4–12.9% of the administered dose. The red blood cells of rats dosed with the trifluoromethoxyphenyl label consistently contained much greater levels of radioactivity than did plasma. Fat tissue contained the greatest level of radioactivity (1.76–8.76% of the administered dose) and, for both compounds, was greater in female rats. The finding also demonstrates a greater propensity for accumulation by female rats than by male rats. Both DPX-MP062 and DPX-JW062 were extensively metabolized and the metabolites were eliminated in the urine, feces, and bile. With the exception of parent compound (DPX-JW062, which accounted for 19.2% of a single low dose in the feces of female rats), none of the metabolites from any source represented more than 12.3% of the administered dose. The metabolite profile for DPX-JW062 was dose dependent and varied quantitatively between males and females. Differences in metabolite profiles were also observed for the different label positions. All of the biliary metabolites appear to undergo further biotransformation in the gut.
For hazards that have a threshold below which there is no appreciable risk, the toxicological level of concern (LOC) is derived from the highest dose at which 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) is sometimes used for risk assessment. Uncertainty/safety factors (UF) are used in conjunction with the LOC 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 risks by comparing aggregate exposure to the pesticide to the acute population adjusted dose
For non-threshold risks, the Agency assumes that any amount of exposure will lead to some degree of risk and estimates risk in terms of the probability of occurrence of additional adverse cases. Generally, cancer risks are considered non-threshold. For more information on the general principles EPA uses in risk characterization and a complete description of the risk assessment process, see
A summary of the toxicological endpoints for indoxacarb used for human risk assessment can be found at
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Section 408(b)(2)(F) of the FFDCA states that the Agency may use data on the actual percent of food treated for assessing chronic dietary risk only if:
a. The data used are reliable and provide a valid basis to show what percentage of the food derived from such crop is likely to contain such pesticide residue;
b. The exposure estimate does not underestimate exposure for any significant subpopulation group; and
c. Data are available on pesticide use and food consumption in a particular area, the exposure estimate does not understate exposure for the population in such area. In addition, the Agency must provide for periodic evaluation of any estimates used. To provide for the periodic evaluation of the estimate of PCT as required by section 408(b)(2)(F) of FFDCA, EPA may require registrants to submit data on PCT.
The Agency used PCT information as follows:
For the acute assessment, maximum PCT estimates were used for the following commodities: apple (5%), broccoli (50%), cabbage (25%), cauliflower and the remaining
For the chronic assessment, average weighted PCT estimates were used for the following commodities: apple (1%), broccoli (40%), cabbage (15%), cauliflower and the remaining
EPA uses an average PCT for chronic dietary risk analysis. The average PCT figure for each existing use is derived by combining available federal, state, and private market survey data for that use, averaging by year, averaging across all years, and rounding up to the nearest multiple of five percent except for those situations in which the average PCT is less than one. In those cases <1% is used as the average and <2.5% is used as the maximum. EPA uses a maximum PCT for acute dietary risk analysis. The maximum PCT figure is the single maximum value reported overall from available federal, state, and private market survey data on the existing use, across all years, and rounded up to the nearest multiple of five percent. In most cases, EPA uses available data from United States Department of Agriculture/National Agricultural Statistics Service (USDA/NASS), Proprietary Market Surveys, and the National Center for Food and Agriculture Policy (NCFAP) for the most recent six years.
The Agency believes that the three conditions listed above have been met. With respect to Condition 1, PCT estimates are derived from Federal and private market survey data, which are reliable and have a valid basis. The Agency is reasonably certain that the percentage of the food treated is not likely to be an underestimation. As to Conditions 2 and 3, regional consumption information and consumption information for significant subpopulations is taken into account through EPA's computer-based model for evaluating the exposure of significant subpopulations including several regional groups. Use of this consumption information in EPA's risk assessment process ensures that EPA's
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Based on the EPA's Pesticide Root Zone Model/Exposure Analysis Modeling System (PRZM/EXAMS) and Screening Concentration in Ground Water (SCI-GROW) models, the estimated environmental concentrations (EECs) of indoxacarb for acute exposures are estimated to be 25.1 parts per billion (ppb) for surface water and 0.21 ppb for ground water. The EECs for chronic exposures are estimated to be 5.37 ppb for surface water and 0.21 ppb for ground water.
Modeled estimates of drinking water concentrations were directly entered into the dietary exposure model. For acute dietary risk assessment, the water concentration value of 25.1 ppb was used to assess the contribution to drinking water. For chronic dietary risk assessment, the water concentration of value 5.37 ppb was used to assess the contribution to drinking water.
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Indoxacarb is currently registered for the following residential non-dietary sites: as a fire ant bait for turf, which may be applied as a mound treatment or as a broadcast application by “residential” (i.e., private persons) applicators as well as by commercial handlers.
EPA assessed residential exposure using the following assumptions: EPA has determined that residential handlers are likely to be exposed to indoxacarb residues via dermal and inhalation routes during handling and applying activities. Based on the current use pattern, EPA expects duration of exposure to be short-term (1–30 days). The broadcast treatment results in a higher handler exposure than the mound treatment and is, therefore, the scenario assessed by EPA. EPA assessed exposure of residential handlers applying indoxacarb with a push-type spreader using SOPs for Residential Exposure Assessments (DEC-1997) in conjunction with unit exposures developed by the Outdoor Residential Exposure Task Force (ORETF).
There is also the potential for short-term and intermediate-term post-application exposure of adults and children from entering areas previously treated with indoxacarb (i.e., turf treated for fire ants). The post-application scenarios assessed from exposure to treated turf include: Dermal exposure from treated lawns due to high contact lawn activities (adult and toddler); Dermal exposure from treated turf due to golfing (adults and youths); Hand-to-mouth transfer of pesticide residues on lawns (toddler); Incidental ingestion of granules from pesticide-treated residential areas (toddler); and Incidental ingestion of soil from pesticide-treated residential areas (toddler).
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Unlike other pesticides for which EPA has followed a cumulative risk approach based on a common mechanism of toxicity, EPA has not made a common mechanism of toxicity finding as to indoxacarb and any other substances and indoxacarb does not appear to produce a toxic metabolite produced by other substances. For the purposes of this tolerance action, therefore, EPA has not assumed that indoxacarb has 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
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i. The toxicity database for indoxacarb is complete.
ii. Neurotoxicity was seen in animal studies in rats and mice but at higher doses than the hematologic effects on which EPA's risk assessments are based. To evaluate the potential for increased sensitivity of infants and children to neurotoxic effects, EPA required a rat developmental neurotoxicity (DNT) study. The study has been submitted and reviewed. There was no evidence of increased sensitivity of offspring in the submitted study. Clinical observations, motor activity, acoustic startle habituation, and learning and memory testing were all comparable between the control and treated groups. Mean brain weight, gross and microscopic examinations and morphometric measurements of the brain were also
iii. There is no evidence that indoxacarb results in increased susceptibility in
iv. There are no residual uncertainties identified in the exposure databases. The acute and chronic dietary food exposure assessments utilize anticipated residues for most commodities that are based on reliable field trial data. They also utilize PCT data that have been verified by the Agency for most existing uses. For all new uses, 100 PCT is assumed. The acute and chronic assessments are somewhat refined and based on reliable data and will not underestimate exposure/risk. Conservative ground and surface water modeling estimates were used. Similarly conservative Residential SOPs were used to assess post-application exposure to children as well as incidental oral exposure of toddlers. These assessments will not underestimate the exposure and risks posed by indoxacarb.
Safety is assessed for acute and chronic risks by comparing aggregate 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 LOC by all applicable uncertainty/safety factors. For linear cancer risks, EPA calculates the probability of additional cancer cases given aggregate exposure. Short-term, intermediate-term, and long-term risks are evaluated by comparing aggregate exposure to the LOC to ensure that the margin of exposure (“MOE”) called for by the product of all applicable uncertainty/safety factors is not exceeded.
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Indoxacarb is currently registered for use that could result in short-term residential exposure and the Agency has determined that it is appropriate to aggregate chronic food and water and short-term exposures for indoxacarb.
Using the exposure assumptions described in this unit for short-term exposures, EPA has concluded that food, water, and residential exposures aggregated result in aggregate MOEs of 620 for the general U.S. population and 190 for children, 1 to 2 years old. The aggregate MOE for the general U.S. population is based on the residential turf (fire ant control) scenario and includes combined residential applicator and post-application dermal exposures. EPA determined that it is not appropriate to include applicator inhalation exposure in the aggregate exposure assessment, since toxicological endpoints of concern for dermal and inhalation exposures are different. The aggregate MOE for children includes post-application dermal and incidental oral exposures from entering turf areas previously treated with indoxacarb for fire ants.
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Indoxacarb is currently registered for use(s) that could result in intermediate-term residential exposure and the Agency has determined that it is appropriate to aggregate chronic food and water and intermediate-term exposures for indoxacarb.
Using the exposure assumptions described in this unit for intermediate-term exposures, EPA has concluded that food, water, and residential exposures aggregated result in aggregate MOEs of 620 for the general U.S. population and 190 for children, 1 to 2 years old. The aggregate MOE for the general U.S. population is based on the residential turf (fire ant control) scenario and includes combined residential applicator and post-application dermal exposures. EPA determined that it is not appropriate to include applicator inhalation exposure in the aggregate exposure assessment, since toxicological endpoints of concern for dermal and inhalation exposures are different. The aggregate MOE for children includes post-application dermal and incidental oral exposures from entering turf areas previously treated with indoxacarb for fire ants.
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Adequate enforcement methodology is available to enforce the tolerance expression (high-performance liquid chromatography (HPLC)/column switching/ultraviolet (UV) methods AMR 2712-93 and Du Pont 11978 with confirmation/specificity provided by gas chromatography (GC)/mass-selective detector method AMR 3493-95, Supplement No. 4). These methods may be requested from: Chief, Analytical Chemistry Branch, Environmental Science Center, 701 Mapes Rd., Ft. Meade, MD 20755–5350; telephone number: (410) 305–2905; e-mail address:
There are no established or proposed Codex maximum residue limits (MRLs) for indoxacarb.
Based upon review of the data supporting the petitions, EPA has modified the proposed tolerances as follows:
(1) PP 3F6576: Revised the commodity term and tolerance for “raisin” to read “grape, raisin” at 5.0 ppm;
(2) PP 5E6911: Replaced the proposed tolerances for “leafy greens, except spinach, subgroup 4A”, “leaf petioles subgroup 4B” and “spinach” with a single tolerance in or on “vegetable, leafy, except
(3) PP 5E 6926: Revised the commodity term “pea (southern”) to read “pea, southern, seed”; and revised the commodity term and tolerance level for “mint” to read “peppermint, tops” at 11 ppm and “spearmint, tops” at 11 ppm; and
(4) PP 5E6991: Revised the tolerances for “vegetable, cucurbit, group 9”, “fruit, stone, group 12” and “cranberry” to 0.60 ppm, 0.90 ppm and 0.90 ppm, respectively. The reasons for these changes are discussed below.
EPA revised the commodity terms “raisin”, mint” and “pea (southern)” to agree with recommended commodity terms in the Office of Pesticide Program's Food and Feed Commodity Vocabulary. Based on data submitted with PP 5E6911 and data previously submitted to support the existing tolerances on leaf and head lettuce, EPA determined that it was appropriate to establish a tolerance for the crop group “vegetable, leafy, except
Therefore, tolerances are established for combined residues of indoxacarb, (S)-methyl 7-chloro-2,5-dihydro-2-[[(methoxycarbonyl)[4-(trifluoromethoxy)phenyl]amino]carbonyl]indeno[1,2-
Time-limited tolerances were established for combined residues of indoxacarb and its R-enantiomer in or on cherry, sweet; cherry, tart; and peach in connection with a FIFRA section 5 experimental use permit granted by EPA. Time-limited tolerances were established for combined residues of indoxacarb and its R-enantiomer in or on collards and cranberry in connection with FIFRA section 18 emergency exemptions granted by EPA. All of these time-limited tolerances have expired, except the time-limited tolerance on cranberry, which is set to expire on December 31, 2007. Because EPA is establishing tolerances on stone fruit,
Finally, the word “enantiomer” is incorrectly spelled (“enantimomer”) in the tolerance expression for indoxacarb in 40 CFR 180.564(a)(1) and is being corrected in this regulation.
This final rule establishes a tolerance under section 408(d) of FFDCA in response to a petition submitted to the Agency. The Office of Management and Budget (OMB) has exempted these types of actions from review under Executive Order 12866, entitled
Since tolerances and exemptions that are established on the basis of a petition under section 408(d) of FFDCA, such as the tolerance in this final rule, do not require the issuance of a proposed rule, the requirements of the Regulatory Flexibility Act (RFA) (5 U.S.C. 601
This final rule directly regulates growers, food processors, food handlers and food retailers, not States or tribes, nor does this action alter the relationships or distribution of power and responsibilities established by Congress in the preemption provisions of section 408(n)(4) of FFDCA. As such, the Agency has determined that this action will not have a substantial direct effect on States or tribal governments, on the relationship between the national government and the States or tribal governments, or on the distribution of power and responsibilities among the various levels of government or between the Federal Government and Indian tribes. Thus, the Agency has determined that Executive Order 13132, entitled
This action does not involve any technical standards that would require Agency consideration of voluntary consensus standards pursuant to section 12(d) of the National Technology Transfer and Advancement Act of 1995 (NTTAA), Public Law 104–113, section 12(d) (15 U.S.C. 272 note).
The Congressional Review Act, 5 U.S.C. 801
Environmental protection, Administrative practice and procedure, Agricultural commodities, Pesticides and pests, Reporting and recordkeeping requirements.
21 U.S.C. 321(q), 346a and 371.
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