Document ID: EPA-HQ-OPP-2014-0769-0002
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2015-02-11T05:00Z

EPA REGISTRATION DIVISION - COMPANY NOTICE OF FILING FOR PESTICIDE PETITION

Docket ID Number: EPA-HQ-OPP-2014-0769

EPA Registration Division contact: Sidney Jackson (703) 305-7610

Interregional Research Project Number 4 
Pesticide Petition Number: 4E8310
EPA has received a pesticide petition number (PP#) 4E8310 from the Interregional Research Project Number 4 (IR-4), IR-4 Project Headquarters, Rutgers, The State University of New Jersey, 500 College Road East, Suite 201 W, Princeton, NJ 08450 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 by establishing a tolerance for residues of 1-naphthaleneacetic acid, including its metabolites and degradates, determined by measuring only 1-naphthaleneacetic acid and its conjugates, calculated as the Stoichiometric equivalent of 1-naphthaleneacetic acid,  in or on the raw agricultural commodity pomegranate 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 support granting of the petition. Additional data may be needed before EPA rules on the petition.

A. Residue Chemistry

	1. Plant metabolism. EPA has now determined that the terminal residues of concern in plants are the parent compounds, 1-naphthaleneacetic acid (NAA) and its conjugates, based on the nature of residues identified from apple and olive studies [MRID 43948501 and 44190501].1

	2. Analytical method. The nature of the residues of NAA is adequately understood and an acceptable analytical method is available for enforcement purposes.2

	3. Magnitude of residues. . Pomegranates  -  All total NAA residues from four pomegranate field trials were <0.050 ppm at a 45 day preharvest interval (PHI) after each application.

B. Toxicological Profile

	1. Acute toxicity.  NAA and all its conjugates show low acute toxicity.3

	2. Genotoxicty. NAA and all its conjugates are not mutagenic.3

	3. Reproductive and developmental toxicity. There was no evidence of developmental toxicity at highest doses tested of 250 mg/kg/day in the rat or 150 mg/kg/day of NAA in the rabbit administered by gavage during the critical gestation period of pregnancy.  Reproductive effects of NAA sodium salt occurred at 210 mg/kg/day and were limited to reduced litter survival and pup weight throughout lactation in both generations of offspring in a two generation reproduction study. Parental effects (reduced body weight gain and reduced food consumption) occurred at the same dose level.4

	4. Subchronic toxicity.  The most common short term effect from high exposures to NAA and all its conjugates is reduced body weight gain, seen at dose levels of 200 mg/kg/day and higher. 3

	5. Chronic toxicity. Repeated exposure in the oral toxicity studies primarily resulted in decreased body weight and body weight gain accompanied by decreased food consumption.  Other chronic effects included vomiting, stomach lesions and slight sinusoidal histiocytosis in the livers of males (dogs).  Studies in the rat and mouse have shown no evidence of carcinogenicity.4

	6. Animal metabolism. The metabolism studies of the acid and its acetamide and the ethyl ester in animals provide supporting evidence that the toxicity of these various forms of NAA would be expected to be similar since all are metabolized to the acid form and eliminated from the body within 36 to 48 hours after exposure as glycine and glucuronic acid conjugates.4

	7. Metabolite toxicology. EPA has not identified any metabolites of toxicological concern.3

	8. Endocrine disruption. As the appropriate screening and/or testing protocols under the Agency's (EDSP) have now been developed and vetted, the naphthalene acetates may be subjected to additional screening and/or testing to better characterize effects related to endocrine disruption.

C. Aggregate Exposure

	1. Dietary exposure. The acute and chronic aggregate risk assessments for naphthalene acetates include exposure from food and drinking water only.  Both acute and chronic aggregate risks are not of concern.3

	i. Food. Based on analyses of estimated dietary risks for the general U.S. population and various population subgroups, the acute and chronic dietary exposure estimates for naphthalene acetates are significantly below EPA's level of concern for all supported commodities and not a risk of concern.3

	ii. Drinking water. Based on screening level computer models that provide high-end estimates of pesticide concentrations for surface and ground water sources, all estimates of drinking water concentrations (EDWCs) are low and do not pose risks of concern.3

	2. Non-dietary exposure. Residential  -  Estimated dermal and inhalation margin of exposures (MOEs) for the most highly exposed scenario of residential exposure to the naphthalene acetates are well above the target MOE of 100 and do not pose risks of concern.  Occupational Handler  -  The Agency believes all naphthalene acetate handler risks are not of concern and all handlers will only be required to wear baseline personal protection equipment (PPE).  Post-Application Exposure  -  The MOEs for the two post-application exposure scenarios are well above the target MOE of 100 on the day of application and, therefore, not of risk concern.3

D. Cumulative Effects

	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 for the naphthalene acetates.  They do not appear to produce a toxic metabolite produced by other substances.  Therefore, for the purpose of risk assessments, EPA has not assumed that the naphthalene acetates have a common mechanism of toxicity with other substances.3

E. Safety Determination.  
Acute and chronic risk estimates for all commodities are less than 100% of the acute population adjusted dose (aPAD) (0.5 mg/kg/day) and chronic population adjusted dose (cPAD) (0.15 mg/kg/day).2  The % aPAD and % cPAD utilized by the proposed tolerances are for small use minor crops and are not expected to add to the existing percentages.

	1. U.S. population. 2% of the aPAD and 1% of the cPAD.3

	2. Infants and children. Infants  -  8% of the aPAD and 6% of the cPAD.  
Children  -  10% of the aPAD and 8% of the cPAD.3

F. International Tolerances

	No maximum residue limits (MRLs) for NAA, its salts, ester, and acetamide have been established in the Codex Alimentarius, the food code established by the UN's World Health Organization and the Food and Agriculture Organization;  therefore, issues of compatibility between Codex MRLs and U.S. tolerances do not exist.  Moreover, no Canadian or Mexican MRLs have been established for naphthalene acetates.3

FOOTNOTES:
1.  1-Naphthaleneacetic Acid (NAA), its Salts, Ester, and Acetamide.  Residue Chemistry Considerations for Reregistration Eligibility Decision. Case No. 0379.
2.  Enclosed Petition Proposing Tolerances for NAA Use in Avocado, Mango, Mamey Sapote and Rambutan
3.  Amended Reregistration Eligibility Decision.  October 2007.
4.  1-Naphthaleneacetic Acid  -  Toxicology Disciplinary Chapter for the Reassessment Eligibility Decision (RED) (or Registration Support) Document (Revised).  March 8, 2004