美国修订四聚乙醛（Metaldehyde）在蔬菜、谷物中的残留限量要求

Environmental Protection Agency (EPA).

Final rule.

This regulation establishes tolerances with regional registration for residues of metaldehyde in or on multiple commodities which are identified and discussed later in this document. Interregional Research Project Number 4 (IR-4) requested these tolerances under the Federal Food, Drug, and Cosmetic Act (FFDCA).

This regulation is effective October 18, 2016. Objections and requests for hearings must be received on or before December 19, 2016, and must be filed in accordance with the instructions provided in40 CFR part 178(see also Unit I.C. of theSUPPLEMENTARY INFORMATION).

The docket for this action, identified by docket identification (ID) number EPA-HQ-OPP-2015-0558, is available athttp://www.regulations.govor 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 athttp://www.epa.gov/dockets.

Michael Goodis, Acting Director, 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:RDFRNotices@epa.gov.

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

You may access a frequently updated electronic version of EPA's tolerance regulations at40 CFR part 180through the Government Printing Office's e-CFR site athttp://www.ecfr.gov/cgi-bin/text-idx?&c=ecfr&tpl=/ecfrbrowse/Title40/40tab_02.tpl.Start Printed Page 71634

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 in40 CFR part 178. To ensure proper receipt by EPA, you must identify docket ID number EPA-HQ-OPP-2015-0558 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 19, 2016. Addresses for mail and hand delivery of objections and hearing requests are provided in40 CFR 178.25(b).

In addition to filing an objection or hearing request with the Hearing Clerk as described in40 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 to40 CFR part 2may 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-2015-0558, by one of the following methods:

Additional instructions on commenting or visiting the docket, along with more information about dockets generally, is available athttp://www.epa.gov/dockets.

In theFederal Registerof Wednesday, September 9, 2015 (80 FR 54257) (FRL-9933-26), 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 5E8377) by Interregional Research Project Number 4 (IR-4), IR-4 Headquarters, 500 College Road East, Suite 201 W., Princeton, NJ 08540. The petition requested that40 CFR 180.523be amended by establishing tolerances for residues of the molluscicide metaldehyde, 2,4,6,8-tetramethyl-1,3,5,7-tetroxocane, in or on beet, garden, roots at 0.05 parts per million (ppm); beet, garden, tops at 0.08 ppm; hop, dried cones at 0.05 ppm; rutabaga, roots at 0.05 ppm; turnip, greens (tops) at 0.08 ppm; turnip, roots at 0.05 ppm; wheat, forage at 0.05 ppm; wheat, grain at 0.05 ppm; wheat, hay at 0.05 ppm and wheat, straw at 0.05 ppm. That document referenced a summary of the petition prepared by Lonza, Inc., the registrant, which is available in the docket,http://www.regulations.gov.There were no comments received in response to the notice of filing.

based upon review of the data supporting the petition, EPA has made certain modifications to the petitioned-for crop tolerances. The reason for these changes are explained in Unit IV.C.

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 metaldehyde including exposure resulting from the tolerances established by this action. EPA's assessment of exposures and risks associated with metaldehyde follows.

EPA has evaluated the available toxicity 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 variability of the sensitivities of major identifiable subgroups of consumers, including infants and children.

The toxicity profile of metaldehyde shows that the principal toxic effects are clinical signs of neurotoxicity. The dog is the most sensitive species for the neurotoxic effects. The nervous system effects observed in subchronic and chronic oral toxicity studies include: (1) Neurotoxic signs,i.e.,ataxia; tremor; twitching; salivation; emesis; and rapid respiration in dogs and maternal rats; and (2) neuropathology,i.e.,limb paralysis, spinal cord necrosis, and hemorrhage in maternal rats.

The liver is a target organ following subchronic and chronic oral exposure to metaldehyde as evidenced by increased liver weight, increased incidence of liver lesions,i.e.,hepatocellular necrosis, hepatocellular hypertrophy, inflammation, and an increased incidence of hepatocellular adenomas/carcinomas in female rats and hepatocellular adenomas in both sexes of mice. The testes and prostate are also target organs following subchronic and chronic exposure as evidenced by atrophy of both organs in dogs.

Developmental toxicity was not observed in the rat or rabbit developmental toxicity studies. Maternal toxicity was not observed in the rabbit, although maternal toxicity was observed in the rat, as evidenced by clinical signs including ataxia, tremors, and twitching at the highest dose tested (HDT). In the rat reproductive toxicity study, mortality and clinical signs,i.e.,limb paralysis, spinal cord necrosis and hemorrhage were observed in the maternal animals, and the effects on the offspring consisted of decreased pup body weight and body weight gains. Reproductive toxicity was not observed.

In chronic feeding studies in mice and rats, benign liver tumors were seen in both sexes of mice and in female rats. The Agency has determined that quantification of risk using a non-linear Reference Dose (RfD) approach for metaldehyde will adequately account for all chronic toxicity, including carcinogenicity, that could result from exposure to metaldehyde. That conclusion is based on the following considerations: (1) The tumors found are commonly seen in the mouse; (2) the liver tumors (adenomas) in both species were benign; (3) metaldehyde is not mutagenic; (4) no carcinogenic response was seen in the male rat; (5) incidence of adenomas at the high-dose in theStart Printed Page 71635female rat was within the historical control range of the testing lab; and (6) both the no-observed-adverse-effect-level (NOAEL) and the lowest-observed-adverse-effect-level (LOAEL) from the chronic rat study on which the chronic RfD/population-adjusted dose (PAD) was based are well below the dose at which adenomas were seen.

Specific information on the studies received and the nature of the adverse effects caused by metaldehyde as well as the NOAEL and the LOAEL from the toxicity studies can be found athttp://www.regulations.govin document “metaldehyde; Human Health Risk Assessment for Proposed New Uses on Garden Beets, Hops, Rutabaga, Turnips and Wheat with Regional Registration in the Pacific Northwest,” in docket ID number EPA- HQ-OPP-2015-0558.

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 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 PAD or a 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, seehttp://www2.epa.gov/pesticide-science-and-assessing-pesticide-risks/assessing-human-health-risk-pesticides.

A summary of the toxicological endpoints for metaldehyde used for human risk assessment is discussed in Unit III.B. of the final rule published in theFederal Registerof November 27, 2013 (78 FR 70864) (FRL-9388-8).

1.Dietary exposure from food and feed uses.In evaluating dietary exposure to metaldehyde, EPA considered exposure under the petitioned-for tolerances as well as all existing metaldehyde tolerances in40 CFR 180.523. EPA assessed dietary exposures from metaldehyde in food as follows:

i.Acute exposure.Quantitative acute dietary exposure and risk assessments are performed for a food-use pesticide, if a toxicological study has indicated the possibility of an effect of concern occurring as a result of a 1-day or single exposure.

Such effects were identified for metaldehyde. In estimating acute dietary exposure, EPA used the Dietary Exposure evaluation Model software with the Food Commodity Intake Database (DEEM-FCID), Version 3.16, which incorporates 2003-2008 food consumption data from the U.S. Department of Agriculture's (USDA's) National Health and Nutrition Examination Survey, What We Eat in America, (NHANES/WWEIA). As to residue levels in food, EPA assumed tolerance-level residues for all commodities and 100 percent crop treated (PCT). In addition, the Agency assumed processing factors to be 1.0 for all commodities except for tomato, dried; tomato, juice; cranberry, juice; and high fructose corn syrup; for these commodities, DEEM default processing factors were used.

ii.Chronic exposure.In conducting the chronic dietary exposure assessment EPA used the DEEM-FCID, Version 3.16, which incorporates 2003-2008 food consumption data from the USDA's, NHANES/WWEIA. As to residue levels in food, EPA assumed tolerance-level residues for all commodities and 100 PCT. Processing factors were assumed to be 1.0 for all commodities except for tomato, dried; tomato, juice; cranberry, juice; and high fructose corn syrup; for these commodities, DEEM default processing factors were used.

iii.Cancer.based on the data summarized in Unit III.A., EPA concluded that quantification of risk using a non-linear RfD approach will adequately account for all chronic toxicity, including carcinogenicity. Therefore, a dietary exposure assessment for the purpose of assessing cancer risk was not conducted.

iv.Anticipated residue and PCT information.EPA did not use anticipated residue or PCT information in the dietary assessment for metaldehyde. 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 metaldehyde in drinking water. These simulation models take into account data on the physical, chemical, and fate/transport characteristics of metaldehyde. Further information regarding EPA drinking water models used in pesticide exposure assessment can be found athttp://www2.epa.gov/pesticide-science-and-assessing-pesticide-risks/about-water-exposure-models-used-pesticide.

based on the Pesticide Root Zone Model/Exposure Analysis Modeling System (PRZM/EXAMS) and Pesticide Root Zone Model Ground Water (PRZM GW), the estimated drinking water concentrations (EDWCs) of metaldehyde for acute exposures are estimated to be 205 parts per billion (ppb) for surface water and 1880 ppb for ground water. Chronic exposures for non-cancer assessments are estimated to be 136 ppb for surface water and 915 ppb for ground water.

For acute dietary risk assessment, the full distribution of ground water concentrations from the PRZM-GW model was used to assess the contribution from drinking water.

For chronic dietary risk assessment, the water concentration of value 915 ppb was used to assess the contribution from 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).

metaldehyde is currently registered for the following uses that could result in residential exposures: Residential ornamentals and lawn/turf applications. EPA assessed residential exposure using the following assumptions and exposure factors: For adult residential handlers, EPA conducted a short-term exposure assessment of metaldehyde for adults based on the inhalation route, incorporating the maximum labeled application rate, and unit exposure values and estimates for area treated/amount handled taken from the 2012 Residential Standard Operating Procedures (SOPs). The scenario resulting in the highest adult exposure in a residential setting was hand dispersal of granules, which was used in the short-term aggregate assessment. Additional scenarios assessed included; loading and applying distinct metaldehyde product types,i.e.,liquid ready-to-use products applied manually via pressurized hand wands, hose-end sprayers, and sprinkler cans, as well asStart Printed Page 71636applying granular products via push-type rotary spreaders, belly grinders, spoons, cups, hands, and shaker cans.

For children, the highest estimated metaldehyde exposure resulted from post-application incidental oral exposures of short-term duration from hand-to-mouth and object-to-mouth contact with treated turf, and short- and intermediate-term exposures from treated soil. Further information regarding EPA standard assumptions and generic inputs for residential exposures may be found athttp://www2.epa.gov/pesticide-science-and-assessing-pesticide-risks/standard-operating-procedures-residential-pesticide.

4.Cumulative effects from 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.”

EPA has not found metaldehyde to share a common mechanism of toxicity with any other substances, and metaldehyde does not appear to produce a toxic metabolite produced by other substances. For the purposes of this tolerance action, therefore, EPA has assumed that metaldehyde 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 Web site athttp://www2.epa.gov/pesticide-science-and-assessing-pesticide-risks/cumulative-assessment-risk-pesticides.

1.In general.Section 408(b)(2)(C) of FFDCA provides that EPA shall apply an additional tenfold (10X) margin of safety for infants and children in the case of threshold effects to account for prenatal and postnatal toxicity and the completeness of the database on toxicity and exposure unless EPA determines based on reliable data that a different margin of safety will be safe for infants and children. This additional margin of safety is commonly referred to as the FQPA Safety Factor (SF). In applying this provision, EPA either retains the default value of 10X, or uses a different additional safety factor when reliable data available to EPA support the choice of a different factor.

2.Prenatal and postnatal sensitivity.Developmental toxicity was not observed in the rat or rabbit developmental toxicity studies and no maternal toxicity observed in the rabbit. Maternal toxicity was observed in the rat, as evidenced by clinical signs,i.e.,ataxia, tremors, and twitching, however these effects were observed only at the highest dose tested. In the rat reproductive toxicity study, mortality and clinical signs,i.e.,limb paralysis, spinal cord necrosis and hemorrhage were observed in the maternal animals, and the effects on the offspring consisted of decreased pup body weight and body weight gains. Reproductive toxicity was not observed.

3.Conclusion.EPA has determined that reliable data show the safety of infants and children would be adequately protected if the FQPA SF were reduced to 1x. That decision is based on the following findings:

i. The toxicity database for metaldehyde is complete;

ii. Although there are indications of neurotoxicity from exposure to metaldehyde, there are clear NOAELs/LOAELS for these effects, and Points of Departure selected for risk assessment are protective for these effects. EPA has determined that the acute and developmental neurotoxicity studies are not needed, nor are additional uncertainty factors (UFs) necessary to account for neurotoxicity. There were no indications of neurotoxic effects in developing rats or rabbits in either the developmental or reproductive studies. Although there were some effects in adult rats, those effects occurred at doses much higher than in the dog study. The dog is the more sensitive species for neurotoxic effects and points of departure (30 mg/kg/day and 10 mg/kg/day) are based on the chronic dog oral toxicity study, which EPA considers to be protective of any neurotoxicity at higher dose levels.

iii. There is no evidence that metaldehyde results in increased susceptibility followingin uteroexposure to metaldehyde in either the rat or rabbit developmental toxicity study, and there is no evidence of increased susceptibility followingin uteroand/or pre-/post-natal exposure in the 2-generation reproduction study in rats.

iv. There are no residual uncertainties identified in the exposure databases. The dietary food exposure assessments were performed based on established and proposed tolerance-level residues, 100 PCT, default processing factors, and EDWCs from chronic ground water (worst case) models to assess exposure to metaldehyde in drinking water. EPA used similarly conservative assumptions to assess exposure to adult handlers, and post application exposure of children (including incidental oral exposure of toddlers). These assessments will not underestimate the exposure and risks posed by metaldehyde based on the current and proposed use patterns.

EPA determines whether acute and chronic dietary pesticide exposures are safe by comparing aggregate exposure estimates to the acute PAD (aPAD) and chronic PAD (cPAD). For linear cancer risks, EPA calculates the lifetime probability of acquiring cancer given the estimated aggregate exposure. Short-, intermediate-, and chronic-term risks are evaluated by comparing the estimated aggregate food, water, and residential exposure to the appropriate PODs to ensure that an adequate MOE exists.

1.Acute risk.Using the exposure assumptions discussed in this unit for acute exposure, the acute dietary exposure from food and water to metaldehyde will occupy 18% of the aPAD for the general population, and 55% of the aPAD for all infants less than 1 year old, the population group receiving the greatest exposure.

2.Chronic risk.Using the exposure assumptions described in this unit for chronic exposure, EPA has concluded that chronic exposure to metaldehyde from food and water will utilize 22% of the cPAD for the general population, and 52% of the cPAD for all infants less than 1 year old, the population group receiving the greatest exposure. based on the explanation in Unit III.C.3., regarding residential use patterns, chronic residential exposure to residues of metaldehyde is not expected.

3.Short-term risk:Short-term aggregate exposure takes into account short-term residential exposure plus chronic exposure to food and water (considered to be a background exposure level).

metaldehyde is currently registered for uses that could result in short-term residential exposure, and the Agency has determined that it is appropriate to aggregate chronic exposure through food and water with short-term residential exposures to metaldehyde. Using the exposure assumptions described in this unit for short-term exposures, EPA has concluded the combined short-term food, water, and residential exposures result in aggregate MOEs of 1400 for adults and 580 for children. Because EPA's level of concern for metaldehydeStart Printed Page 71637is an MOE of 100 or below, these MOEs are not of concern.

4.Intermediate-term risk.Intermediate-term aggregate exposure takes into account intermediate-term residential exposure plus chronic exposure to food and water (considered to be a background exposure level). metaldehyde is currently registered for uses that could result in intermediate-term residential exposure, and the Agency has determined that it is appropriate to aggregate chronic exposure through food and water with intermediate-term residential exposures to metaldehyde. Using the exposure assumptions described in this unit for intermediate-term exposures, EPA has concluded that the combined intermediate-term food, water, and residential exposures result in an aggregate MOE of 270 (for children only). Because EPA's level of concern for metaldehyde is a MOE of 100 or below, this MOE is not of concern.

5.Aggregate cancer risk for U.S. population.based on the data summarized in Unit III, EPA believes that quantification of metaldehyde risk using a non-linear RfD approach will adequately account for all related chronic toxicity, including carcinogenicity. based on the chronic risk assessment, EPA concludes that aggregate exposure to metaldehyde will not pose a cancer risk.

6.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 metaldehyde residues.

Adequate enforcement methodology (gas chromatography with mass spectrometry (GC/MS) method (EN-CASTMMethod No. ENC-3/99, Revision 1) is available to enforce the tolerance expression. The limit of quantitation (LOQ) for this method is 0.05 ppm for all plant commodities except hops, for which it is 0.10 ppm.

The method may be requested from: Chief, Analytical Chemistry Branch, Environmental Science Center, 701 Mapes Rd., Ft. Meade, MD 20755-5350; telephone number: (410) 305-2905; email address:residuemethods@epa.gov.

In making its tolerance decisions, EPA seeks to harmonize U.S. tolerances with international standards whenever possible, consistent with U.S. food safety standards and agricultural practices. EPA considers the international maximum residue limits (MRLs) established by the Codex Alimentarius Commission (Codex), as required by FFDCA section 408(b)(4). The Codex Alimentarius is a joint United Nations Food and Agriculture Organization/World Health Organization food standards program, and it is recognized as an international food safety standards-setting organization in trade agreements to which the United States is a party. EPA may establish a tolerance that is different from a Codex MRL; however, FFDCA section 408(b)(4) requires that EPA explain the reasons for departing from the Codex level.

The Codex has not established a MRL for metaldehyde.

For hop, dried cones, the analytical method was not successfully validated at the proposed tolerance level of 0.05 ppm. Therefore, EPA is establishing the tolerance level for this commodity at the lowest validated LOQ for hops of 0.10 ppm. In addition, the commodity definition proposed as “beet, garden, tops” is corrected to read: “beet, garden, leaves”.