Mandestrobin; Pesticide Tolerances


Federal Register, Volume 81 Issue 196 (Tuesday, October 11, 2016)

Federal Register Volume 81, Number 196 (Tuesday, October 11, 2016)

Rules and Regulations

Pages 70038-70043

From the Federal Register Online via the Government Publishing Office

FR Doc No: 2016-24492



40 CFR Part 180

EPA-HQ-OPP-2014-0285; FRL-9945-37

Mandestrobin; Pesticide Tolerances

AGENCY: Environmental Protection Agency (EPA).

ACTION: Final rule.


SUMMARY: This regulation establishes tolerances for residues of S-2200 (here after referred to within this document as mandestrobin) in or on multiple commodities which are identified and discussed later in this document. Valent U.S.A., Corporation requested these tolerances under the Federal Food, Drug, and Cosmetic Act (FFDCA).

DATES: This regulation is effective October 11, 2016. Objections and requests for hearings must be received on or before December 12, 2016, 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: The docket for this action, identified by docket identification (ID) number EPA-HQ-OPP-2014-0285, is available at or at the Office of Pesticide Programs Regulatory Public Docket (OPP Docket) in the Environmental Protection Agency Docket Center (EPA/DC), West William Jefferson Clinton Bldg., Rm. 3334, 1301 Constitution Ave. NW., Washington, DC 20460-0001. The Public Reading Room is open from 8:30 a.m. to 4:30 p.m., Monday through Friday, excluding legal holidays. The telephone number for the Public Reading Room is (202) 566-1744, and the telephone number for the OPP Docket is (703) 305-5805. Please review the visitor instructions and additional information about the docket available at

FOR FURTHER INFORMATION CONTACT: Susan Lewis, Registration Division (7505P), Office of Pesticide Programs, Environmental Protection Agency, 1200 Pennsylvania Ave. NW., Washington, DC 20460-0001; main telephone number: (703) 305-7090; email address:


  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. The following list of North American Industrial Classification System (NAICS) codes is not intended to be exhaustive, but rather

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      provides a guide to help readers determine whether this document applies to them. Potentially affected entities may include:

      Crop production (NAICS code 111).

      Animal production (NAICS code 112).

      Food manufacturing (NAICS code 311).

      Pesticide manufacturing (NAICS code 32532).

    2. How can I get electronic access to other related information?

      You may access a frequently updated electronic version of 40 CFR part 180 through the Government Printing Office's e-CFR site at

    3. How can I file an objection or hearing request?

      Under FFDCA section 408(g), 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-2014-0285 in the subject line on the first page of your submission. All objections and requests for a hearing must be in writing, and must be received by the Hearing Clerk on or before December 12, 2016. Addresses for mail and hand delivery of objections and hearing requests are provided in 40 CFR 178.25(b).

      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 (excluding any Confidential Business Information (CBI)) for inclusion in the public docket. Information not marked confidential pursuant to 40 CFR part 2 may be disclosed publicly by EPA without prior notice. Submit the non-CBI copy of your objection or hearing request, identified by docket ID number EPA-HQ-OPP-2014-0285, by one of the following methods:

      Federal eRulemaking Portal: Follow the online instructions for submitting comments. Do not submit electronically any information you consider to be CBI or other information whose disclosure is restricted by statute.

      Mail: OPP Docket, Environmental Protection Agency Docket Center (EPA/DC), (28221T), 1200 Pennsylvania Ave. NW., Washington, DC 20460-0001.

      Hand Delivery: To make special arrangements for hand delivery or delivery of boxed information, please follow the instructions at Additional instructions on commenting or visiting the docket, along with more information about dockets generally, is available at

  2. Summary of Petitioned-for Tolerances

    In the Federal Register of December 17, 2014 (79 FR 75107) (FRL-

    9918-90), EPA issued a document pursuant to FFDCA section 408(d)(3), 21 U.S.C. 346a(d)(3), announcing the filing of a pesticide petition (PP 3F8224) by Valent U.S.A., Corporation,1600 Riviera Ave., Suite 200, Walnut Creek, California, 94596. The petition requested that 40 CFR 180 be amended by establishing tolerances for residues of the fungicide mandestrobin, (2-(2,5-dimethylphenoxy)methyl-alpha-methoxy-N-

    methyl-benzeneacetamide), in or on small fruit vine climbing except fuzzy kiwifruit crop subgroup 13-07F, fruit at 5 parts per million (ppm), juice at 7 ppm, and dried fruit at 10 ppm; low growing berry subgroup 13-07G, fruit at 3 ppm; and rapeseed crop subgroup 20A, seed at 0.6 ppm. That document referenced a summary of the petition prepared by Valent U.S.A. Corporation, the registrant, which is available to the public in the docket, There were no comments received in response to the notice of filing.

    Based upon review of the data supporting the petition, EPA lowered the requested tolerance levels for grape, raisin. Tolerances for juice and dried fruit are not required. At this time, EPA is not granting a tolerance for rapeseed crop group 20A. The reason for these changes is explained 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 FFDCA section 408(b)(2)(D), and the factors specified in FFDCA 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 mandestrobin including exposure resulting from the tolerances established by this action. EPA's assessment of exposures and risks associated with mandestrobin as 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.

      The main target organs for mandestrobin toxicity in all mammalian species tested are the liver and gall bladder with effects ranging from hepatocyte hypertrophy and increased liver weight (usually considered not adverse in the absence of corroborative hepatic enzyme changes or histopathology) to centrilobular degeneration, hepatocyte and bile duct pigmentation, periductular inflammation and gall stones. Dogs were more sensitive to the adverse liver effects than rats; mice showed only non-

      adverse liver effects.

      Thyroid effects were observed in rats (increased weight, follicular cell hypertrophy, decreased serum hormone levels) at higher doses than early signs of liver effects suggesting that effects in the thyroid may be secondary to liver effects.

      Gonadal effects were observed at higher doses than the liver effects, and were more evident in dogs (immature prostate and/or testes, low sperm count, immature ovaries, decrease uterus weight) but equivocal and/or not adverse in rats. Gonadal effects did not affect the reproductive capacity of rats.

      No developmental effects were observed in rats or rabbits, and no adverse reproductive, immunotoxic, or neurotoxic effects were observed in any of the studies. No adverse effects were

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      seen in a route-specific dermal toxicity study. Mutagenicity studies were negative. There is no evidence of carcinogenicity because there was no increase in tumor incidence in rat and mouse long-term studies. The Agency classified mandestrobin as ``not likely to be a human carcinogen''.

      Specific information on the studies received and the nature of the toxic effects caused by mandestrobin 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 in: Mandestrobin. Human Health Risk Assessment for Proposed Foliar Uses on Small Fruit Vine Climbing (Except Fuzzy Kiwifruit) (Subgroup 13-07F), Low Growing Berry (Subgroup 13-07G) (Except Cranberry), Turf, and Seed Treatment Uses on Corn (Field, Pop, Sweet), Sorghum Grain (Milo), and Legume Vegetables (Crop Group 6C) (Except Cowpea and Field Pea) at page 18 in docket ID number EPA-HQ-


    2. Toxicological Points of Departure/Levels of Concern

      Once a pesticide's toxicological profile is determined, EPA identifies toxicological points of departure (POD) and levels of concern to use in evaluating the risk posed by human exposure to the pesticide. For hazards that have a threshold below which there is no appreciable risk, the toxicological POD is used as the basis for derivation of reference values for risk assessment. PODs are developed based on a careful analysis of the doses in each toxicological study to determine the dose at which no adverse effects are observed (the NOAEL) and the lowest dose at which adverse effects of concern are identified (the LOAEL). Uncertainty/safety factors are used in conjunction with the POD to calculate a safe exposure level--generally referred to as a population-adjusted dose (PAD) or a reference dose (RfD)--and a safe margin of exposure (MOE). 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 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

      A summary of the toxicological endpoints for mandestrobin used for human risk assessment is shown in Table 1.

      Table 1--Summary of Toxicological Doses and Endpoints for Mandestrobin for Use in Human Health Risk Assessment


      Point of departure

      Exposure/scenario and uncertainty/ RfD, PAD, LOC for Study and toxicological effects

      safety factors risk assessment


      Acute dietary (General population No toxicity was observed that could be attributed to a single exposure.

      including infants and children).


      Chronic dietary (All populations) NOAEL = 92 mg/kg/day Chronic RfD = 0.92 Chronic Toxicity--Dog LOAEL = 181

      mg/kg/day. mg/kg/day based on incidence of

      cPAD = 0.92 mg/kg/ liver centrilobular degeneration,

      day. hepatocytehypertrophy, hepatocyte

      pigment, and elevated serum ALP

      and ALT.

      Incidental Oral Short-Term (1-30 UFA = 10x........... LOC for MOE