Source: https://www.federalregister.gov/documents/2009/05/27/E9-12292/etoxazole-pesticide-tolerances
Timestamp: 2018-04-22 04:04:28
Document Index: 74983755

Matched Legal Cases: ['art 178', 'art 180', 'art 178', 'art 178', 'art 178', 'art 2']

This regulation is effective May 27, 2009. Objections and requests for hearings must be received on or before July 27, 2009, and must be filed in accordance with the instructions provided in 40 CFR part 178 (see also Unit I.C. of the SUPPLEMENTARY INFORMATION).
25156-25161 (6 pages)
EPA-HQ-OPP-2008-0554
FRL-8413-5
https://www.federalregister.gov/d/E9-12292 https://www.federalregister.gov/d/E9-12292
This regulation establishes tolerances for residues of etoxazole in or on stone fruit; plum; prune; spearmint tops and oil; peppermint tops and oil; tomato; and cucumber. This regulation also deletes the existing cherry tolerance, as it will be superseded by inclusion in the stone fruit crop group. The Interregional Research Project Number 4 (IR-4) requested these tolerances under the Federal Food, Drug, and Cosmetic Act (FFDCA).
EPA has established a docket for this action under docket identification (ID) number EPA-HQ-OPP-2008-0554. 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.
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 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. Start Printed Page 25157
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-2008-0554 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 July 27, 2009.
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-2008-0554, by one of the following methods:
In the Federal Register of August 13, 2008 (73 FR 47186) (FRL-8375-8), 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 8E7347) by IR-4, Rutgers, The State University of New Jersey, 500 College Road East, Suite 201 W., Princeton, NJ 08540. The petition requested that 40 CFR 180.593 be amended by establishing tolerances for residues of the insecticide etoxazole, 2-(2,6-difluorophenyl)-4-[4-(1,1-dimethylethyl)-2-ethoxyphenyl]-4,5-dihydrooxazole, in or on fruit, stone, group 12, except plum at 1.0 parts per million (ppm); plum at 0.12 ppm; plum, prune, dried at 0.4 ppm; cucumber at 0.02 ppm; tomato at 0.25; spearmint, tops at 10 ppm; peppermint, tops at 10 ppm; peppermint, oil at 20 ppm; and spearmint, oil at 20 ppm. The petition additionally requested to delete the tolerance for residues of etoxazole in or on the food commodity cherry at 1.0 ppm. That notice referenced a summary of the petition prepared on behalf of IR-4 by Valent U.S.A. Corporation, the registrant, which is available to the public in the docket, http://www.regulations.gov. Comments were received on the notice of filing. EPA's response to these comments is discussed in Unit IV.C.
Based upon review of the data supporting the petition, EPA has revised the proposed tolerance levels for plum; plum, prune, dried; and tomato. The reason for these changes is explained in Unit IV.D.
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 residues of etoxazole on fruit, stone, group 12, except plum at 1.0 ppm; plum at 0.15 ppm; plum, prune, dried at 0.30 ppm; cucumber at 0.02 ppm; tomato at 0.20; spearmint, tops at 10 ppm; peppermint, tops at 10 ppm; peppermint, oil at 20 ppm; and spearmint, oil at 20 ppm. EPA's assessment of exposures and risks associated with establishing tolerances follows.
The existing etoxazole data indicate that it possess low acute toxicity via all routes of exposure. It is not an eye or dermal irritant or a dermal sensitizer. No toxicity was seen at the limit dose in a 28-day dermal toxicity study in rats.
The liver is the main target organ in mice, rats and dogs. In a 90-day toxicity study in dogs, increased liver weights and centrilobular hepatocellular swelling in the liver were observed. Similar effects were observed in a chronic toxicity study in dogs at similar doses, indicating that systemic effects (mainly liver effects) occur at similar dose levels following short- through long-term exposure without increasing in severity. In a 90-day toxicity study in mice, hepatotoxicity (increased relative liver weight, liver enlargement, and centrilobular hepatocellular swelling) was observed at high doses. Similar effects were observed at the high dose in a mouse carcinogenicity study. Subchronic and chronic toxicity studies in rats produced similar effects (increased liver weights, centrilobular hepatocellular swelling, etc.) to those seen in mice and dogs. In addition, slight increases in thyroid weights and incisors were observed in subchronic and chronic toxicity studies in rats at high doses and at terminal stages of the study. Toxicity was not observed at the highest dose tested (HDT) in another carcinogenicity study in mice. There is no evidence of immunotoxicity or neurotoxicity in any of the submitted studies.
Two studies in mice showed no evidence of carcinogenicity up to the HDT. In a rat carcinogenicity study, which was deemed unacceptable due to inadequate dosing, benign interstitial cell tumors (testis) and pancreas benign islet cell adenomas were observed (in females) at the high dose. These effects were not observed in an acceptable carcinogenicity study in rats at higher doses. In special mechanistic male rat studies there were no observable Start Printed Page 25158changes in serum hormone levels (estradiol, luteinizing hormone (LH), prolactin and testosterone) or reproductive effects (interstitial cell proliferation or spermatogenesis) noted. EPA classified etoxazole as “not likely to be carcinogenic to humans.” Etoxazole is not mutagenic.
The toxicology data for etoxazole provides no indication of increased susceptibility, as compared to adults, of rat and rabbit fetuses to in utero exposure in developmental studies. The rabbit developmental toxicity study included maternal toxic effects (liver enlargement, decreased weight gain, and decreased food consumption) at the same dose as developmental effects (increased incidences of 27 presacral vertebrae and 27 presacral vertebrae with 13th ribs). In the two-generation reproduction study conducted with rats, offspring toxicity was more severe (pup mortality) than parental toxicity (increased liver and adrenal weights) at the same dose, indicating increased qualitative susceptibility.
Specific information on the studies received and the nature of the adverse effects caused by etoxazole as well as the no-observed-adverse-effect-level (NOAEL) and the lowest-observed-adverse-effect-level (LOAEL) from the toxicity studiescan be found at http://www.regulations.gov in document “Etoxazole; Human Health Risk Assessment for Proposed Uses on Stone Fruits, Cucumber, Tomato, and Mint,” pages 29-31 in docket ID number EPA-HQ-OPP-2008-0554.
A summary of the toxicological endpoints for etoxazole used for human risk assessment can be found at http://www.regulations.gov in document “Etoxazole; Human Health Risk Assessment for Proposed Uses on Stone Fruits, Cucumber, Tomato, and Mint,” page 15 in docket ID number EPA-HQ-OPP-2008-0554.
1. Dietary exposure from food and feed uses. In evaluating dietary exposure to etoxazole, EPA considered exposure under the petitioned-for tolerances as well as all existing etoxazole tolerances in (40 CFR 180.593). EPA assessed dietary exposures from etoxazole in food as follows:
ii. Chronic exposure. In conducting the chronic dietary exposure assessment EPA used the food consumption data from the USDA 1994-1996 and 1998 CSFII. As to residue levels in food, EPA used tolerance-level residues and empirically determined (when available) or DEEM default processing factors. Additionally, EPA assumed 100 percent crop treated (PCT) for all commodities covered by proposed or existing tolerances.
iii. Cancer. Two mouse studies showed no evidence of carcinogenicity at the high dose. While benign interstitial cell tumors in the testis and pancreas benign islet cell adenomas were observed in an unacceptable rat carcinogenicity study, these effects were not seen in a repeat study at higher doses. Furthermore, special mechanistic male rat studies resulted in no observable changes in serum hormone levels (estradiol, luteinizing hormone, prolactin and testosterone) or reproductive effects (interstitial cell proliferation or spermatogenesis). EPA determined that cancer risk concerns due to long-term consumption of etoxazole residues are adequately addressed by the chronic dietary exposure analysis; therefore, etoxazole was classified as “not likely to be carcinogenic to humans,” and a quantitative exposure assessment to evaluate cancer risk is unnecessary.
iv. Anticipated residue and PCT information. EPA did not use anticipated residue or PCT information in the dietary assessment for etoxazole. Tolerance level residues and 100 PCT were assumed for all food commodities.
2. Dietary exposure from drinking water. The Agency used screening level water exposure models in the dietary exposure analysis and risk assessment for etoxazole in drinking water. These simulation models take into account data on the physical, chemical, and fate/transport characteristics of etoxazole. 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.
Based on the First Index Reservoir Screening Tool (FIRST) model for surface water, and Screening Concentration in Ground Water (SCI-GROW) model for ground water, the estimated drinking water concentrations (EDWCs) of etoxazole and its major metabolites (R-8 and R-13) for surface water are estimated to be 15.73 parts per billion (ppb) for acute exposures and 4.761 ppb for chronic exposures. For ground water, the estimated drinking water concentration is estimated to be 0.746 ppb.
Modeled estimates of drinking water concentrations were directly entered into the dietary exposure model. For chronic dietary risk assessment, the water concentration of value 4.761 ppb was used to assess the contribution to drinking water.
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). Etoxazole Start Printed Page 25159is not registered for any specific use patterns that would result in residential exposure.
EPA has not found etoxazole to share a common mechanism of toxicity with any other substances, and etoxazole does not appear to produce a toxic metabolite produced by other substances. For the purposes of this tolerance action, therefore, EPA has assumed that etoxazole 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.
2. Prenatal and postnatal sensitivity. The toxicology data for etoxazole provides no indication of increased susceptibility, as compared to adults, of rat and rabbit fetuses to in utero exposure in developmental studies. In a rat reproduction study, offspring toxicity was more severe (pup mortality) than parental toxicity (increased liver and adrenal weights) at the same dose; thereby indicating increased qualitative susceptibility. Based on the above concerns, a Degree of Concern Analysis was performed by EPA, which concluded that concern is low since:
ii. The pup effects occur at the same dose as parental toxicity; and
iii. The doses selected for various risk assessment scenarios are lower than the doses that caused offspring toxicity.
i. The toxicity database for etoxazole is complete except for acute and subchronic neurotoxicity and immunotoxicity studies. Recent changes to 40 CFR 180.158 make acute and subchronic neurotoxicity testing (OPPTS Guideline 870.6200), and immunotoxicity testing (OPPTS Guideline 870.7800) required for pesticide registration. Because these testing requirements went into effect shortly before the tolerance petition was submitted, these studies are not yet available for etoxazole. However, the available data for etoxazole do not show potential for immunotoxicity. Further, there is no evidence of neurotoxicity in any study in the toxicity database for etoxazole. Therefore, EPA does not believe that conducting neurotoxicity and immunotoxicity studies will result in a NOAEL lower than the NOAEL of 4.62 milligrams/kilograms/day already established for etoxazole. Consequently, an additional database uncertainty factor does not need to be applied.
ii. There is no indication that etoxazole is a neurotoxic chemical and there is no need for a developmental neurotoxicity study or additional Uncertainity Factors (UFs) to account for neurotoxicity.
iii. Although there is qualitative evidence of increased susceptibility of offspring (pup mortality) compared to less severe parental effects (increased liver and adrenal weights) at the same dose in the rat multi-generation reproduction study, the Agency did not identify any residual uncertainties after establishing toxicity endpoints and traditional UFs (10X for interspecies variation and 10X for intraspecies variation) to be used in the risk assessment. Therefore, there are no residual concerns regarding developmental effects in the young.
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, etoxazole 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 etoxazole from food and water will utilize 10% of the cPAD for children 1-2 years old, the population group receiving the greatest exposure. There are no residential uses for etoxazole to consider.
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).
Etoxazole is not registered for any use patterns that would result in residential exposure. Therefore, the short-, and intermediate-term aggregate risk is the sum of the risk from exposure to etoxazole through food and water and will not be greater than the chronic aggregate risk.
4. Aggregate cancer risk for U.S. population. As discussed in Unit III.C.1.iii., EPA has classified etoxazole as “not likely to be carcinogenic to humans,” and it 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 etoxazole residues.Start Printed Page 25160
Adequate enforcement methodologies (gas chromatography/nitrogen-phosphorus detection (GC/NPD) and gas chromatography/mass selective detection (GC/MSD) methods) are available to enforce the tolerance expression. The 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: residuemethods@epa.gov.
Currently, there are no Codex, Canadian, or Mexican maximum residue limits (MRLs) established for residues of etoxazole in or on the subject commodities.
EPA received one comment to the Notice of Filing that made a general objection to the presence of any pesticide residues on crops and stated that EPA should set no pesticide tolerance greater than zero. The Agency understands the commenter's concerns and recognizes that some individuals believe that pesticides should be banned completely. However, the existing legal framework provided by section 408 of FFDCA states that tolerances greater than zero may be set when persons seeking such tolerances or exemptions have demonstrated that the pesticide meets the safety standard imposed by that statute. This citizen's comment appears to be directed at the underlying statute and not EPA's implementation of it; the citizen has made no contention that EPA has acted in violation of the statutory framework.
Based upon review of the data supporting the petition, EPA revised tolerances for certain proposed commodities, as follows: Plum from 0.12 ppm to 0.15 ppm; plum, prune, dried from 0.40 ppm to 0.30 ppm; and tomato from 0.25 ppm to 0.20 ppm. EPA revised the tolerance levels based on analysis of the residue field trial data using the Agency's Tolerance Spreadsheet in accordance with the Agency's Guidance for Setting Pesticide Tolerances Based on Field Trial Data.
Therefore, tolerances are established for residues of etoxazole, 2-(2,6-difluorophenyl)-4-[4-(1,1-dimethylethyl)-2-ethoxyphenyl]-4,5-dihydrooxazole, in or on fruit, stone, group 12, except plum at 1.0 ppm; plum at 0.15 ppm; plum, prune, dried at 0.30 ppm; cucumber at 0.02 ppm; tomato at 0.20 ppm; spearmint, tops at 10 ppm; peppermint, tops at 10 ppm; spearmint, oil at 20 ppm; and peppermint, oil at 20 ppm. This regulation also deletes the existing tolerance in or on cherry at 1.0 ppm, as it is superseded by inclusion in fruit, stone, group 12.
2. Section 180.593 is amended in paragraph (a), by removing the commodity “Cherry” and by alphabetically adding the following commodities to the table to read as follows:
(a) General. * * *Start Printed Page 25161
Fruit, stone, group 12, except plum 1.0
Peppermint, oil 20
Peppermint, tops 10
Plum 0.15
Plum, prune, dried 0.30
Spearmint, oil 20
Spearmint, tops 10
[FR Doc. E9-12292 Filed 5-26-09; 8:45 am]