Document ID: EPA-HQ-OPP-2010-0637-0002
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2010-10-27T04:00Z

EPA REGISTRATION DIVISION COMPANY NOTICE OF FILING FOR PESTICIDE PETITIONS PUBLISHED IN THE FEDERAL REGISTER 

EPA Registration Division contact: Andrew Ertman 703-308 - 9367

Interregional Research Project #4.

PP #0E7748

	EPA has received a pesticide petition (PP #0E7748) from IR-4 Project Headquarters, Rutgers, The State University of New Jersey, 500 College Road East, Suite 201 W, Princeton, NJ 08540 proposing, pursuant to section 408(d) of the Federal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 346a(d), to amend 40 CFR part 180.205 by establishing a tolerance for residues of paraquat dichloride in or on the raw agricultural commodities for the following perennial tropical and sub-tropical fruit trees: sugar apple, cherimoya, atemoya, custard apple, ilama, soursop, biriba, lychee, longan, Spanish lime, rambutan, pulasan, star apple, black sapote, mango, sapodilla, canistel, mamey sapote, feijoa, jaboticaba, wax jambu, starfruit (carambola), pawpaw, pomegranate, and white sapote at 0.05 parts per million (ppm).  EPA has determined that the petition contains data or information regarding the elements set forth in section 408 (d)(2) of FDDCA; however, EPA has not fully evaluated the sufficiency of the submitted data at this time or whether the data supports granting of the petition. Additional data may be needed before EPA rules on the petition.

A. Residue Chemistry

	1. Plant metabolism. The qualitative nature of the residue in plants is adequately understood based on studies depicting the metabolism of paraquat dichloride in carrots and lettuce following preemergence treatments and in potatoes and soybeans following desiccant treatment. The residue of concern in plants is the parent, paraquat dichloride; the current tolerance expression for plant commodities, as defined in 40 CFR 180.205(a) and (b). 

	2. Analytical method. An adequate analytical method (spectrometric method) has been accepted and published in The Pesticide Analytical Manual (PAM Vol. II) for the enforcement of tolerances in plant commodities.

	3. Magnitude of residues. The proposed use pattern for the perennial tropical fruit crops is based upon the use pattern for the following currently labeled perennial crops: avocado, acerola, banana, papaya, guava,  coffee, tree nuts, fig, citrus fruit, pome fruit, olive, persimmon, and stone fruit, which all have a tolerance of 0.05 ppm.  As such, IR-4 is requesting tolerances and registrations be established on all perennial tropical fruit crops based on surrogate data and current registrations. Specifically, IR-4 requests 0.05 ppm tolerances and registrations for the following perennial tropical and semi-tropical fruit trees: sugar apple, cherimoya, atemoya, custard apple, ilama, soursop, birba, lychee, longan, Spanish lime, rambutan, pulasan, star apple, black sapote, mango, sapodilla, canistel, mamey sapote, feijoa, jaboticaba, wax jambu, starfruit (carambola), pawpaw, pomegranate, and white sapote. 

B. Toxicological Profile
The United States Environmental Protection Agency (EPA) has evaluated the available paraquat dichloride toxicological database 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 reliability of the sensitivities of major identifiable subgroups of consumers, including infants and children. The nature of the toxicity profile of paraquat dichloride is discussed in the September 6, 2006 Federal Register publication of the Final Rule for establishing tolerances for residues of paraquat dichloride in or on various food and feed commodities [EPA - HQ - OPP - 2006 - 0664; FRL - 8089 - 3]. 

C. Aggregate Exposure

	1. Dietary exposure. Tier II acute and chronic risk assessments were performed for the herbicide paraquat (1,1′-dimethyl-4,4′-bipyridinium-ion) derived from application of either the bis(methyl sulfate) or the dichloride salt (both calculated as the cation) using the Dietary Exposure Evaluation Model (DEEM-FCIDTM, version 2.16) from Exponent.  In addition to the established tolerances for residues of paraquat listed in 40CFR180.205, these exposure assessments also included revised crop tolerances for a proposed new post-emergent use on tropical fruits (0.05 ppm) including sugar apple, cherimoya, atemoya, custard apple, ilama, soursop, birba, lychee, longan, Spanish lime, rambutan, pulasan, star apple, black sapote, mango, sapodilla, canistel, mamey sapote, feijoa, jaboticaba, wax jambu, starfruit (carambola), pawpaw, pomegranate and white sapote.  Tolerance-level residues were assumed for all meat, milk, and egg commodities.  The EPA's Biological and Economic Analysis Division (BEAD) maximum and average percent crop treated (%CT) estimates described in the most recent EPA exposure assessment for paraquat (DP Barcode D327805, July 31, 2006) were utilized in the acute and chronic exposure assessments, respectively.  For all crops where BEAD %CT estimates were unavailable, 100%CT was conservatively assumed.  Syngenta exposure assessors believe that a value of 0.1 ppb, the Limit of Quantitation (LOQ) of the analytical screening method is appropriate for use as the EDWC for both acute and chronic assessments.  All consumption data for these assessments was taken from the USDA's Continuing Survey of Food Intake by individuals (CSFII) with the 1994-96 consumption database and the Supplemental CSFII children's survey (1998) consumption database.

	i. Food. Acute Exposure. The acute dietary (food only) risk assessment for females 13 to 49 years old was performed using an acute reference dose (aRfD) of 0.0042 mg/kg-bw/day, based upon a multigenerational study in rats with a no observable adverse effect level (NOAEL) of 1.25 mg/kg/day and an uncertainty factor (UF) of 100X for intra- and inter-species variations; an additional FQPA safety factor of 3X was applied for females between the ages of 13 and 49 years due to a data gap for a prenatal developmental study (UF=300X).  The acute dietary risk assessment for the general population and all other subgroups was performed using an aRfD of 0.0125 mg/kg-bw/day based upon the same NOAEL of 1.25 mg/kg/day and a UF of 100X for intra- and inter-species variations.  No additional FQPA safety factor was applied.  For the purpose of aggregate risk assessment, the exposure values were expressed in terms of margin of exposure (MOE), which was calculated by dividing the NOAEL by the exposure.  In addition, exposure was also expressed as a percent of the acute reference dose (% aRfD).  It should be noted that the most recent EPA acute exposure assessment for paraquat dichloride was based on a probabilistic Monte Carlo analysis using tolerance residue values. The current Syngenta acute assessment that is the subject of this petition was performed deterministically using tolerance residue values.  At the 99.9th percentile, acute (food only) exposure to the U.S. population resulted in a MOE of 393 (25.4% of the aRfD of 0.0125 mg/kg-bw/day).  The most exposed sub-population was children 1-2 years old, with a MOE of 261 (38.2% of the aRfD of 0.0125 mg/kg-bw/day).  

Chronic Exposure. The paraquat chronic dietary (food only) risk assessment was performed for all population subgroups using a chronic reference dose (cRfD) of 0.0045 mg/kg-bw/day, based upon a chronic toxicity study in dogs with a no observable adverse effect level (NOAEL) of 0.45 mg/kg/day and an uncertainty factor of 100X.  The 100X safety factor includes intra- and inter-species variations; no additional FQPA safety factor was applied.  For the purpose of aggregate risk assessment, the exposure values were expressed in terms of margin of exposure (MOE), which was calculated by dividing the NOAEL by the exposure for each population subgroup.  In addition, exposure was expressed as a percent of the chronic reference dose (% cRfD).  Chronic (food only) exposure to the U.S. population resulted in a MOE of 1,510 (6.6% of the cRfD of 0.0045 mg/kg-bw/day).  The most exposed sub-population was children 1-2 years old with a MOE of 428 (23.3% of the cRfD of 0.0045 mg/kg-bw/day).  

Cancer. Paraquat has been classified as a Group E chemical (no evidence of human carcinogenic potential).  Therefore, no cancer risk assessment was performed.

	ii. Drinking water. Syngenta exposure assessors believe that a value of 0.1 ppb, the Limit of Quantitation (LOQ) in the screening analytical method for paraquat in water, is appropriate for use as the estimated drinking water concentration (EDWCs) for paraquat dichloride.  Paraquat dichloride exhibits strong cation-exchange sorption to soils, thus current screening models are not appropriate for use in predicting EDWCs of the herbicide.  In most circumstances the levels of paraquat dichloride in surface or ground water are expected to be insignificant.  In the unlikely event that paraquat dichloride residues reached surface water bodies, they would be expected to be removed by sedimentation, coagulation, and flocculation processes in water treatment plants.  Therefore, residues of paraquat dichloride in drinking water derived from surface supplies can be assumed to be negligible.  Due to its extremely low mobility and strong tendency to bind tightly to soils, paraquat dichloride contamination of drinking water supplies derived from groundwater is expected to be highly unlikely.  Given these rationale, and since the proposed use parameters of paraquat dichloride on the perennial tropical fruit crops (sugar apple, cherimoya, atemoya, custard apple, ilama, soursop, birba, lychee, longan, Spanish lime, rambutan, pulasan, star apple, black sapote, mango, sapodilla, canistel, mamey sapote, feijoa, jaboticaba, wax jambu, starfruit (carambola), pawpaw, pomegranate, and white sapote) does not exceed currently labeled application and use parameters, Syngenta exposure assessors believe that the 0.1 ppb LOQ value is appropriate for use as the EDWC for both acute and chronic exposure assessments, and is protective for any surface or ground water concentration concerns.

Acute Exposure from Drinking Water:  The full method LOQ of 0.1 ppb (0.0001 ppm) was used as the acute EDWC and was incorporated with food residues as "water, direct and indirect, all sources" directly into the DEEM-FCID(TM) software to obtain acute dietary (food and water) exposures.  At the 99.9th percentile, acute (food and water) exposure to paraquat for the U.S. population resulted in a MOE of >1,000,000 (0.0% of the aRfD of 0.0125 mg/kg-bw/day).  The most exposed sub-population was children 3-5 years old, with a MOE of 62,500 (0.2% of the aRfD of 0.0125 mg/kg-bw/day).  

Chronic Exposure from Drinking Water.  The full method LOQ of 0.1 ppb (0.0001 ppm) was used as the chronic EDWC and was incorporated with food residues as "water, direct and indirect, all sources" directly into the DEEM-FCID(TM) software to obtain chronic dietary (food and water) exposures.  Chronic exposure (food and water) to the U.S. population resulted in a MOE of 213,497 (0.0% of the cRfD of 0.0045 mg/kg-bw/day).  The most exposed sub-population was all infants (<1 year old), with a MOE of 65,120 (0.2% of the cRfD of 0.0045 mg/kg-bw/day).  

Cancer.  Paraquat has been classified as a Group E chemical (no evidence of human carcinogenic potential).  Therefore, no cancer risk assessment was performed.

2.  Non-Dietary Exposure:  Paraquat dichloride is not registered for use on any sites that would result in residential exposure.

D. Cumulative Effects

	Cumulative Exposure to 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 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."  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 paraquat and any other substances and paraquat does not appear to produce a toxic metabolite produced by other substances.  For the purposes of this tolerance action, the EPA has not assumed that paraquat has a common mechanism of toxicity with other substances.

E. Safety Determination

	1. U.S. population. The acute dietary exposure analysis (food plus water) showed that exposure from all established and proposed paraquat tolerances would result in a MOE of 394 (25.3 % of the aRfD of 0.0125 mg/kg-bw/day) for the U.S. population, which exceeds the Benchmark MOE of 100.  The chronic dietary exposure analysis (food plus water) showed that exposure from all established and proposed paraquat tolerances resulted in a MOE of 1,510 (6.6% of the cRfD of 0.0045 mg/kg-bw/day) for the U.S. population, which exceeds the Benchmark MOE of 100.  A chronic cancer exposure analysis was not performed, since there is no evidence of human carcinogenic potential for paraquat.  Short-term aggregate and intermediate-term aggregate risk was not assessed because there are no current, pending, or proposed residential uses for paraquat.  

	2. Infants and children. The acute dietary exposure analysis (food plus water) showed that exposure from all established and proposed paraquat tolerances would result in a MOE of 261 (38.3 % of the aRfD of 0.0125 mg/kg-bw/day) for children 1-2 years old, which exceeds the Benchmark MOE of 100.  The chronic dietary exposure analysis (food plus water) showed that exposure from all established and proposed paraquat tolerances resulted in a MOE of 428 (23.4% of the cRfD of 0.0045 mg/kg-bw/day) for children 1-2 years old, which exceeds the Benchmark MOE of 100.  A chronic cancer exposure analysis was not performed, since there is no evidence of human carcinogenic potential for paraquat.  Short-term aggregate and intermediate-term aggregate risk was not assessed because there are no current, pending, or proposed residential uses for paraquat. 

      3. Females 13-49 years of age.  The acute dietary exposure analysis (food plus water) showed that exposure from all established and proposed paraquat tolerances would result in a MOE of 867 (34.3% of the aRfD of 0.0042 mg/kg-bw/day) for females 13-49 years old, which exceeds the Benchmark MOE of 300.  The chronic dietary exposure analysis (food plus water) showed that exposure from all established and proposed paraquat tolerances resulted in a MOE of 2,232 (4.5% of the cRfD of 0.0045 mg/kg-bw/day) for females 13-49 years old, which exceeds the Benchmark MOE of 100.  A chronic cancer exposure analysis was not performed, since there is no evidence of human carcinogenic potential for paraquat.  Short-term aggregate and intermediate-term aggregate risk was not assessed because there are no current, pending, or proposed residential uses for paraquat.  

F. International Tolerances

	Compatibility between U.S. tolerances and Codex Maximum Residue Levels (MRLs) exist for eggs, milk, ruminant tissues, passion fruit, sunflower seed and vegetables including beans (succulent), Brassica (cole) leafy vegetables group, carrots, cassava, corn (sweet), cucurbits, fruiting vegetables, lettuce, onions (dry bulb and green), peas (succulent), pigeon peas, turnips (roots and tops), and yams. Incompatibilities of U.S. tolerances and Codex MRLs on the following raw plant commodities remain because of differences in agricultural practices: Cottonseed, dry hops, dry peas/beans, maize, olives, potatoes, rice, sorghum, soybeans and wheat. No questions of compatibility exist with respect to commodities where no Codex MRLs have been established but United States tolerances exist or where Codex MRLs have been established but U.S. tolerances do not exist.