### Conditional Registration of the Insecticide, Metaflumizone, on Citrus Fruits, Tree Nuts, and Grapes

Regulatory Rationale

EPA is conditionally granting the first food registra tions of the insecticide, metaflumizone. This registration action establishes uses of metaflumizone , formulated as a granul ar bait for control of fire ants, on citrus fruits, tree nuts, and grapes in bear ing orchards and vineyards.



### I. Chemical Information

Chemical Name : Metaflumizone (2-[2-(4-cyanophenyl)-1-[3 -(trifluoromethyl) phenyl] ethylidene] - N -[4- (trifluoromethoxy) phenyl] hydrazin ecarboxamide; E and Z isomers)

EPA PC Code : 281250 (E Isomer); 281251 (Z isomer)

CAS Number : 139968-49-3

Mode of Action : Metaflumizone is a semicarbazone insecticide that blocks the sodium channels of the nervous system in susceptible insects (Lepidoptera a nd Coleoptera), leading to inhibited feeding and paralysis. The E and Z isomers are typically present at an E:Z ratio of >9:1.

Registrant : BASF Corporation

Products : Metaflumizone Insecticide (EPA Reg. No. 7969-226)

- Technical product registered for use in the formulation of end-use products.

Altrevin Fire Ant Bait Insecticide (EPA File Symbol 7969-270)

- An end-use product for use in citrus orchards; tree nut orchards; grape vineyards; nonbearing stone and pome fruit orchards; and nurseries containing nonbearing cont ainer- or field-grown stone and pome fruit tree stock.

- Formulated as a solid granule, and contains 0.063% of the active ingredient , metaflumizone.

- The maximum single application rate is 1.5 lbs of formulated product (0.0 01 lb a.i.) per acre, with no more than 4 applications per season, fo r a total seasonal rate of 6 lbs formulated product (0.004 lbs a.i.) per acre.

- May be applied by broadcast, or as an individual mound treatment.

- The minimum reapplication interval is 4 weeks; the preharvest interval is 5 days for citrus, tree nuts, and grapes, and 1 year for nonbearing stone and pome fruit trees.

### II. Human Health Risk

A summary of the human health effects and risk of metaflumizone, as assessed in the Agency document entitled, “ Metaflumizone. Revised Human-Health Ri sk Assessment Associated with a Section 3 Registration for a Fire Ant Bait for Application to Citrus, Tree Nuts, and Grape, and a new Section 3 Registration for a Fly Bait for Application around Industrial, Commercial, Agricultural and Recreational Fa cilities/Structures and Premises ,” is provided below.

A. Summary of Toxicological Effects

Hematotoxicity (toxicity of the blood) was the primary toxic effect of concern following

subchronic or chronic oral exposures to metaflumizone. Splenic extramedullary hematopoiesis, increased hemosiderin, and anemia were the mo st common hematotoxic effects reported after repeated oral dosing with metaflumizone. The postulated pesticidal mode of action of

metaflumizone involves inhibition of sodium cha nnels in target insect species; however, in mammals (rats), there were only clinical signs of neurotoxicity (i .e., piloerection and body temperature variations) with no neuropathology in the presence of systemic toxicity (e.g., recumbency and poor general state) following ac ute or repeated exposures. Similarly, several immune system organs seem to be affected fo llowing metaflumizone administration via the oral, dermal, and inhalation routes (e.g., the presence of macrophage s in the thymus, lymphocyte necrosis in the mesenteric lymph nodes, and di ffuse atrophy of the mandibular); however, there was no evidence of any functional deficits at th e highest dose tested in a recently submitted and reviewed guideline immunotoxicity study. Therefore, the clinical neurotoxicity signs and the effects on the immune system organs following me taflumizone administration are likely to be secondary to the hematotoxic effects.

Metaflumizone induced the increased incidence of an absent subclavian artery at a relatively high dose in the developmental toxicity study in ra bbits. However, this was observed at the same dose as severe maternal toxicity, which included late-term abortions and ot her clinical signs of toxicity. There was no evidence (quantitative or qualitat ive) of increased susceptibility following

in utero exposures to rats or rabbit and following pre-and post natal exposures. There was no evidence that metaflumizone is genotoxic and carc inogenicity studies with mice and rabbits were negative.

B. Toxicological End Points and Doses Us ed in the Human Heal th Risk Assessment

Route-specific toxicity studies were selected for assessment of short-/intermediate-term dermal, inhalation, and oral exposures. Short/intermediate-term dermal and inhalation exposures can be aggregated based on the immunotoxi c effects seen at the lowest- observed adverse-effect level (LOAEL) in the selected studies. Short/intermediate-term oral, dermal, and inhalation exposures can be aggregated based on the decreased body we ight or decreased body- weight gain effects

seen at the LOAEL in the selected oral and derm al studies and at doses above the LOAEL in the selected inhalation study.

1. Acute Dietary Endpoint (General popula tion including infants and children) : An acute dietary endpoint was not established for this population group since an endpoint of concern(effect) attributable to a single dose was not identif ied in the database. Studies considered for this endpoint included the acute neurotoxicity study in which no toxicity was observed at any dose including the highest dose tested, whic h is the limit dose (1000 mg/kg/day).

2. Acute Dietary Endpoint (F emales 13-49 years old) : This endpoint was established based on a developmental effect observed in the rabbi t developmental toxicity study that can be potentially due to a single dose of metaflumiz one. This effect consisted of an absent subclavian artery in the offspring at th e LOAEL of 300 mg/kg bw/day metaflumizone (NOAEL = 100 mg/kg bw/day). The rat developmen tal toxicity study was also considered for this endpoint; however, no developmental effects were observed in this study at the highest dose tested of 120 mg/kg bw/day metaflumizone. A combined uncertainty factor (UF) of 300 was applied to account for interspecies (10x) and intraspecies (10x) extrapolation and a Food Quality Protection Act (FQPA) safety fact or of 3x. Thus, the acute population adjusted dose (aPAD) for females 13-49 years old is estimated to be 0.33 mg/kg bw/day.

3. Chronic Dietary Endpoint : This endpoint was establishe d based on the systemic toxicity observed in the chronic toxicity study w ith dogs. At the LOAEL of 30 mg/kg bw/day (NOAEL = 12 mg/kg bw/day), the effects consiste d of consisted of reduced general health condition, slight to severe ataxia , recumbency, and severe saliva tion, slight decreases in mean corpuscular hemoglobin concentration and tota l hemoglobin, leading to increased plasma bilirubin, increased urin ary urobilinogen, and increased hemosi derin in the liver. A combined uncertainty factor (UF) of 300 was applied to account for interspecies (10x) and intraspecies (10x) extrapolation and an FQPA safety factor of 3x. Thus, th e chronic population adjusted dose (cPAD) is estimated to be 0.040 mg/kg bw/day.

4. Dermal (Short- and Intermediate-Term) : This endpoint was base d on a rat 90-day dermal toxicity study in which deficits in body wei ght, body-weight gain a nd food consumption (in males and females); anogenital smearing; incr eased macrophages in the thymus; lymphocyte necrosis in the mesenteric lymph nodes; di ffuse atrophy of the mandibular lymph node; and

increased hemosiderin in the li ver (females only) were obser ved at the LOAEL of 300 mg/kg bw/day (NOAEL = 100 mg/kg bw/day)

. The Agency’s level of concern (LOC) for this

scenario is 100 based on a 10X interspecies factor, and a 10X intraspecies factor.

5. Inhalation (Short- and Intermediate-Term) : There is a 28-day inhalation study for this exposure scenario. There was no NOAEL identifie d for female rats. At the LOAEL of 0.10 mg/L metaflumizone (NOAEL = 0.03 mg/L), hi stopathology of the nasal tissues, lungs, thymus, prostate, and adrenal cortex was obs erved in males. The LOAEL identified in females resulted in lymphocyte necrosis in th e mesenteric lymph node. The Agency’s level of concern (LOC) for this scenario is 1000 based on a 10X interspecies factor, a 10X intraspecies factor, and an FQPA safety factor of 10X. Route-specific toxicity studies were

selected for assessment of short-/intermediate- term dermal, inhalation, and oral exposures. Short/intermediate-term dermal and inhalation exposures can be aggregated based on the

immunotoxic effects seen at the LOAEL in the selected studies. Short/intermediate-term oral, dermal, and inhalation exposures can be aggregated based on the decreased body weight or decreased body-weight gain effects seen at the LOAEL in the selected oral and dermal

studies and at doses above the LOA EL in the selected inhalation study.6. Incidental Oral (Short - and Intermediate-Term) : This endpoint was se lected on the basis of

the maternal effects observed in the rat 2- generation reproductive toxicity study at the LOAEL of 50 mg/kg bw/day metaflumizone (NOAEL = 20 mg/kg bw/day). Maternal toxicity consisted of poor general health and bod y weight deficits which were also associated with improper nursing behavior. Similar effects were also noted in a developmental neurotoxicity study (gavage, range finding) also considered for this endpoint. In this study, poor maternal health was also observed at th e LOAEL of 120 mg/kg bw/day metaflumizone (NOAEL = 80 mg/kg bw/day). Both studies cons idered for this endpo int achieved a clear NOAEL for the offspring effects, but the NOA EL of 20 mg/kg bw/day for the 2-generation reproductive toxicity study is considered more protective. The Agency’s level of concern for

this scenario is 300 based on a 10X intraspecies factor, a 10X interspecies factor, and an FQPA safety factor of 3x.

7. Cancer : Metaflumizone is classified as “not lik ely to be carcinogenic to humans,” based on the lack of evidence of carcinogenicity in accep table carcinogenicity stud ies in rats and mice.

C. FQPA Safety Factor (SF)

EPA has determined that reliable data show the safety of infants and children would be adequately protected if the FQPA SF were: (a) reduced from 10x to 3x for all oral exposure scenarios; (b) retained at 10x for inhalation exposure scenarios; and (c) reduced from 10x to 1x for dermal exposure scenarios. That decision is based on the following findings:

1. Although metaflumizone shows evidence of poten tial immunotoxicity inthe form of doserelated effects in the organs of the immune system across multiple studies with either the parent compound (composed of both E and Z isom ers) or the Z-isomer of metaflumizone, evaluation of a recently submitted immunotoxicity study did not result in a point of departure lower than those from a previous risk assessment.

2. Retaining the FQPA SF at 3x for a database uncertainty for all oral exposure scenarios is justified to protect against any toxicity that might occur at 2-fold lower doses in dietary exposures (absorption was noted to be 2-fold greater in dietary versus oral gavage studies).

3. The FQPA SF of 10x is being re tained for inhalation exposure scenarios for the use of a LOAEL in the absence of a NOAEL and extrapol ation of a 28-day i nhalation study to longer durations of exposure (up to 6 months for intermediate-term).

4. The FQPA SF for dermal exposure scenarios is be ing reduced from 10x to 1x since there is a route-specific study with a clear NOAEL.

5. There are no residual concerns or uncertainties for pre- and/or postnatal toxicity. In the rat prenatal development toxicity study, there was no offspring toxicity reported at any dose

tested whereas in the rabbit st udy a maltransformation based on an absent subclavian artery was noted to occur only in the presence of severe maternal toxicity. Similarly, offspring mortality in the 2-generation re productive toxicity occurred on ly in the presence of a poormaternal health state. Thus, there is no evidence for increased susceptibility.

6. There is no clear evidence that metaflumizone di rectly affects the nervous system. Clinical signs consisting of piloerecti on and body temperature variatio ns were observed only in the absence of neuropathology and in the presence of a poor general state. There is no need for a developmental neurotoxicity study or addi tional UFs to account for neurotoxicity.

7. The dietary analysis is conserva tive in that it assumes tolera nce-level residues and 100% crop treated. Fire ants are only found throughout the southeastern United States from Texas through Florida, extending as far north as Ok lahoma and Virginia, and in New Mexico, California, and Puerto Rico; therefore, it is un likely that 100% of crops would be treated.

D. Aggregate Risk Assessment

In accordance with FQPA, EPA must consider and aggregate pesticide exposures and risks from dietary (food and water) and resi dential (dermal, inhalation, inci dental oral) sources. When aggregating exposures and risks from these s ources, EPA considers the route and duration of exposure as well as the toxicological effects fo r each route. Short-/intermediate-term dermal, oral, and inhalation exposures can be aggregated based on a common toxic effect (e.g., decreased body weight or decreased body-weight gain). Ba sed on this and the proposed/registered uses, aggregate acute, short-/interm ediate-term, and chronic assessments were conducted.

1. Dietary (Food and Drinking Water) Risk : Acute and chronic metaflumizone dietary risk assessments were conducted using the DEEM-FCID  (ver. 2.03) model. DEEM-FCIDTM (ver 2.03) incorporates consum ption data from the USDA Con tinuing Survey of Food Intakes by Individuals (CSFII) (1994-1996 and 1998). Th e acute and chronic dietary analyses assumed tolerance-level residues, 100% crop treated, and modeled drinking water estimates

from the Pesticide Root Zone Model-E xposure Analysis Modeling System (PRZMEXAMS). The drinking water estimates were ba sed on the application of metaflumizone as a fly bait on use sites such as recreational faci lities and outdoor recreat ional areas including parks, picnic grounds, and camp grounds repres ented by the turf mode ling scenario [this scenario resulted in the highest estimated dr inking water concentra tion (EDWC)]. DEEMTM (ver 7.81) default processing factors were assumed for all commodities excluding grape raisin, grape juice, and citrus juice which we re reduced to 1 based on empirical data. The acute dietary exposure estimate for fema les 13-49 years old was <1% the aPAD and, therefore, does not exceed EPA’s LOC. An e ndpoint attributable to a single dose was not identified for the remaining population subgroups . The chronic dietary exposure estimates

were  1% the cPAD and, therefore, do not exceed EPA’s LOC (children 1-2 years old were the most highly expos ed population subgroup).

2. Residential Risk : The proposed fire ant bait product (c itrus fruit, grapes and tree nuts) is not expected to result in residen tial exposure since the proposed us e sites are agricultural sites. There are other registered fire ant bait uses (lawns, landscapes, golf courses, and other noncropland) and pet uses (spot-on products) that would result in residential handler and postapplication exposure, which have been assesse d. The pet-use products are in the process of being voluntarily cancelled, and the registrations will not be maintained past 2012; however,the pet products have been included in this assessment because they may continue to be available until stocks are depleted. Since the LO Cs for the dermal, inhalation and incidental oral routes are not the same (dermal LOC = 100, inhalation LOC = 1000, and incidental oral LOC = 300), these routes were combined usi ng the aggregate risk index approach. The combined residential handler and post-applic ation exposures result in aggregate risk estimates of 1600 for the registered fire ant bait uses; 1.5 for the pet care uses; and 120 for the proposed fly bait product, for children 3 to <6 years old. Because EPA’s LOC is an aggregate risk index of less than 1, th e aggregate risks are not of concern

3. Short-/Intermediate- Term Aggregate Risk : The short-term aggregate assessment combines food and drinking water exposure with the highest potential resi dential exposure. Intermediate-term exposures are possible for th e pet care products; how ever, since the points of departure for the short- and intermediate-t erm durations are the same for metaflumizone, the short-term aggregate assessment is protect ive of longer-term exposures for the pet care products. For adults and the general U.S. population, the short- and intermediate-term aggregate assessments combine chronic dietar y with residential pos t-application dermal exposure. For young children, the short-and intermediate-term aggregate assessments combine chronic dietary exposure with incidental oral and dermal post-application exposure. EPA uses chronic dietary exposure when conduc ting short- and intermediate-term aggregate

assessments since it has been determined that these will more accurately reflect exposure

from food over the EPA-defined short- and intermediate-term interval than will acute exposure. Since the LOCs for the dermal, inha lation and incidental oral routes are not the same (dermal LOC = 100, inhalation LOC = 100 0, and incidental oral LOC = 300), these routes were combined using the aggregate risk index approach. The combined short-term food, water, and residential exposures result in aggregate risk indice s of 3 for the general population, and 2 for children 1-2 years old. Be cause EPA’s LOC is an aggregate risk index of less than 1, the aggregate risks are not of concern

4. Chronic Aggregate Risk : Since there are no registered/pro posed uses which result in chronic residential exposure, the chronic aggregate e xposure assessment consis ts of exposure from

food and water. The chronic dietary exposure estimate was ≤ 1% of the cPAD and, therefore,

does not exceed EPA’s LOC.

5. Cancer Aggregate Risk : An aggregate cancer risk asse ssment was not performed because metaflumizone is not considered to be a carcinogen.

E. Occupational Risk Assessment

The proposed use of Altrevin Fire Ant Bait Insecticide for broadcast and individual mound applications to control fire ants may resu lt in occupational handler and post-application

exposure.

1. Short- and Intermediate-Term Handler Risk : Dermal and inhalati on exposures/risks were estimated for handlers involved in mixing/loadin g activities for granular formulations for tractor-drawn spreader equipment, applying gran ulars via tractor-drawn spreader or by hand, and mixing/loading/applying activities for handheld equipment, such as push-type spreaders,belly grinders and spoons. The metaflumizone product labels require lo ng-sleeved shirt and long pants and chemical-resistant gloves as de rmal personal protective equipment (PPE) for all applicators and other handlers. Based on use data and label instructions, EPA believes that occupational exposures may occur over a sing le day or up to weeks at a time for many use-patterns and that intermittent exposure over several weeks may also occur. Some applicators may apply these products over a pe riod of weeks because they are commercial applicators who are completing multiple applic ations for multiple clients. Long-term exposures are not expected, therefore, a l ong-term assessment was not conducted. Dermal

and inhalation risks were combined in this a ssessment, since the toxicological effects for these exposure routes were similar. A total ag gregated risk index a pproach was used since the LOCs for dermal exposure (100) and inhala tion exposure (1000) are different. The target aggregate risk index is 1; therefore, aggregate ri sk indices of less than 1 are risks of concern. The dermal and inhalation exposure risk s for mixer/loaders, applicators and mixer/loader/applicators are not of concern (i.e., MOEs >100 for dermal and >1000 for inhalation; aggregate risk index > 1) at baseline and with the addition of gloves.

2. Post-Application Dermal Risk : EPA believes the presence of commercial workers in treated areas is minimal after application, and dermal c ontact with treated surf aces is not expected, since all applications are dire cted towards the soil surface. In addition, workers are not expected to frequent areas infested with activ e fire ants. For these reasons, a quantitative dermal post-application assessm ent has not been conducted.

3. Post-Application Inhalation Risk : Based on the Agency's current practices, a quantitative occupational post-application i nhalation exposure assessment wa s not performed. However, there are multiple potential sources of post-ap plication inhalation exposure to individuals performing post-applicati on activities in previously treated fields. These potential sources

include volatilization of pesticides and resuspension of dusts and/or particulat es that contain pesticides. The Agency is in the process of evaluating current polic ies and procedures to identify the need for and, subsequently, the wa y to incorporate occupational post-application inhalation exposure into the Agency 's risk assessments. If new policies or procedures are put into place, the Agency may revisit the need fo r a quantitative occupational post-application inhalation exposure assessmen t for metaflumizone.

4. Restricted Entry Interval (REI) : Metaflumizone is classified in Acute Toxicity Category IV for acute dermal toxicity, acute inhalation to xicity, primary eye irritation, primary dermal

irritation and it is not a dermal sensitizer. B ecause the product is formulated as a bait, postapplication exposure to workers is expected to be low. Therefore, an interim worker protection standard (WPS) REI of 12 hours is ad equate to protect agri cultural workers from post-application exposures.



### III. Environmental Risk

A summary of the environmental fate and ecologi cal effects and risks of metaflumizone, as assessed in the Agency document entitled “ Environmental Fate and Ecological Risk Assessmentfor the Proposed New Use Registration of Metaflum izone for Control of Fire Ants in Citrus/Nut Orchards, Grape Vineyards, Nurseries , and Agricultural/Residential Areas, ” is provided below.

A. Environmental Fate

Based on the available environmental fate data, it can be concluded that metaflumizone is highly stable to biodegradation and there is the pot ential for bioconcentration/bioaccumulation in aquatic and terrestrial systems. Due to the rela tively low mobility of metaflumizone, it is not expected to leach substantially into groundwater, but it may reach adjacent bodies of water via runoff events accompanied by erosion. Once there, metaflumizone may be expected to remain adsorbed to suspended solids in the water colu mn, and eventually transported to the bottom sediment, where it would accumulate.

Available data indicate that metaflumizone has th e potential to bioaccumulate substantially in aquatic food webs, with a relativ ely high octanol/water partition coefficient and bioconcentration factor (BCF), and a relatively slow rate of de puration. In addition, it should be noted that a steady-state was not achieved in the bioconcentration study, even after a 42-day exposure period, and therefore, these BCF values could underestimate the potential for bioconcentration.

To address concerns about the potential for meta flumizone to bioaccumulate in the environment, product labels will be required to contain mandatory buffer zones and other statements that are intended to keep the product in the treatment area and limit runoff to bodies of water. Further details regarding label requirements are describe d in the Proposed Regulatory Decision section.

B. Ecological Risk

Ecological risk characterization in tegrates the results of the e xposure and ecotoxicity data to

evaluate the likelihood of adverse ecological effects. The means of integrating the results of exposure and ecotoxicity data is called the quo tient method. For this method, risk quotients (RQs) are calculated by dividing exposure es timates by ecotoxicity values, both acute and chronic (RQ = Exposure/Toxicity). RQs are then compared to EPA's levels of concern (LOCs). The LOCs are criteria used by the Agency to indicat e potential risk to non-target organisms. The criteria indicate whether a pesticide, when used as directed, has the potential to cause adverse effects to non-target organisms.

1. Risk to Terrestrial Organisms : Given the apparent low sensiti vity of earthworms and plants to metaflumizone, the low likeli hood of significant exposure of flying non-target insects to granular metaflumizone, and the low application rate of metaflumizone fire ant bait (0.001 lbs a.i./A), the focus of the terrestrial organi sm risk assessment is on birds and mammals.

Risks from chronic exposure of mammals to metaflumizone from direct consumption of granules appear relatively low, based on a re fined risk analysis. Risks from acute and chronic exposure of birds to metaflumizone cannot be precluded, and depend largely on the availability on the granules to fo raging birds in treated areas.Some information suggests that wildlife may avoi d areas of fire ant infestation while other information indicates that gran ulated pesticide products used for fire ant control may be available to animals. Based on refined analys es with the most sensitive toxicity endpoints available, acute exposure resulti ng from direct ingestion of fire ant bait granules appears to be a reasonable possibility, and there is evidence that suggests that the use of metaflumizone ant bait poses an acute risk to avian species.

Other information suggests that, due to the aggre ssive nature of fire ants, it may be unlikely that any wildlife would feed on or near fire an t mounds, and the presence of fire ants alone may result in reduced exposure of non-target wildlife to metaflumizone fire ant bait. Furthermore, it is possible that the aggressive foraging behavior of fire ants would result in most of the fire ant bait being picked up within an hour of a pplication, making it less

available to mammals and birds.

The potential for significant acute and chronic exposure of terrestrial wildlife to ant bait granules may be reduced under certain applicatio n practices. For example, if metaflumizone fire ant bait application is applie d only when fire ants are actively foraging, then there is the potential for a significant reduc tion in acute and chronic exposu res to birds and mammals. The potential for exposure will remain for both transport to water a nd direct ingestion by birds and mammals from the broadcast use because some bait may be overlooked during foraging by fire ants. However, the presence of active fire ants on the field should help to decrease exposure of non- target wildlife.

Other sources of uncertainty surrounding the ex posure and risk of non-target wildlife to

metaflumizone ant bait include : (1) lack of knowledge rega rding aggregate exposure (e.g., direct consumption of granules , ingestion of granul es that adhere to soil invertebrates, partitioning of dissolved metaflumizone to on-s ite sources of wildlife drinking water, and dermal exposure of granules released to surrounding soil and on-si te puddles) and (2) temperature dependence of fire ant bait retrieval which may lead to prolonged availability of

fire ant bait.

In order to address concerns rega rding the availability of metafl umizone fire ant bait granules to non-target wildlife, product labels will be required to contain single application and seasonal rate restrictions, directions for ma king applications only dur ing observed fire ant activity, as well as other statements about how to clean up spilled product. Further details regarding label requirements are described in the Proposed Regulatory Decision section.

2. Risk to Aquatic Organisms : The maximum acute RQ for all aquatic organisms exposed to metaflumizone solely through the water column is less than the acute endangered species LOC, even if all acute toxic effects to water column-dwelling invertebrates, water column dwelling and benthic fish, and aquatic vascular plants are assumed to occur at the limit of solubility. In addition, chronic tests that were submitted with estuarine/marine fish and

freshwater invertebrates did not show any signs of toxicity at or below the maximum 1-in-10 year peak concentration from PRZM/EXAMS, an d therefore, risk to these taxonomic groups due solely to exposure from metaflumizone freel y-dissolved in water is not expected. Thetoxicity data upon which these risks were quant ified do not account for exposure via the diet, due to the very low concentrations predicted in aquatic ecosystems.

3. Bioaccumulation Risks : To address the bioaccumulative characteristics of metaflumizone and potential secondary exposure to piscivorous wildlife, con centrations in representative organisms of an aquatic food web were pred icted using a bioaccumu lation model. Results from this analysis indicate that acute and chronic risks to avian species are unlikely via consumption of contaminated aquatic prey. Sim ilarly, results indicate that chronic risks to mammalian species are unlikely via this exposur e pathway. Finally, an analysis of the potential metaflumizone bioconcentration in ear thworms indicates that exposure and risks to

insectivorous birds and mammals are substantially below the Agen cy’s levels of concern for endangered species.



### IV. Regulatory Decision

The Agency is granting the first food uses of meta flumizone on citrus fruits, tree nuts, and grapes in bearing orchards and vineyards, formul ated as a bait for control of fire ants.

As required by FIFRA, the Agency published a Notice of Receipt (NOR) of the registration application in the Federal Register on October 26, 2009 (Vol. 74, No. 205). No comments were received in response to the NOR.

On January 3, 2012, the Agency posted the propo sed decision document for metaflumizone entitled “Proposed Conditional Regi stration of the Insecticide, Me taflumizone, on Citrus Fruits, Tree Nuts, and Grapes,” the associated risk asse ssments, and the proposed end-use product label in docket ID number EPA-HQ-OPP-2008-0168. No co mments were received in response to

these documents.

A. Data Requirements

The human health risk assessment concluded that the database is largely complete and adequate for a dietary, residential, a nd occupational risk assessment. The following data are being requested for confirmatory purposes:

1. Storage stability data - To support the subject field trial and processing studies, the following storage stability data are required which demons trate the stability of metaflumizone (E and Z isomers) and M320I04: grapes - 4.8 months; citrus fruit - 5.6 months; almond hulls - 6.5 months; and almond nutmeat - 5.8 months.

The environmental fate and effects review concl uded that the database is adequate for a risk assessment of the proposed uses. No additional studies ar e being requested.

B. Labeling RequirementsIn order to mitigate risks to humans and the environment, label language is required for Altrevin

Fire Ant Bait Insecticide that is intended to: 1. Keep the pesticide on the treatment area, thereby reducing the potential for runoff to bodies of water; 2. Limit the amount of product available to foraging wildlife, thereby limiting exposure to no n-target plants and animals; and 3. Limit human exposure (dietary and occupationa l) to metaflumizone residues.

1. Buffers :

 “Do not make broadcast applications within 15 feet of fresh water environments.”

 “Do not make broadcast applications within 60 feet of estuarine/marine environments.”

2. Application Restrictions :

 “Do not apply more than 6.0 lbs of Altrevin per acre per season.”

 “Do not apply more than 1.5 lbs of A ltrevin per acre per application.”

 “Do not make more than 4 applications per year.”

 “Do not apply when the ground is saturated with water, heavy dew, or when heavy rains are expected within 48 hours.”

3. Spills and Disposal :

 “Cover, incorporate, or clean up granules that are spilled.”

 “Keep spills out of all sewers and open bodies of water.”

4. Preharvest Intervals :

 Citrus Trees, Nut Trees, and Grapes: 5 days

 Non-Bearing Stone and Po me Fruit Trees: 1 year

5. Restricted Entry Interval :

 “Do not enter or allow worker entry into treated areas during the restricted-entry interval (REI) of 12 hours.”

C. Public Interest

This registration action establishe s the first food uses of metaflumizone, formulated as a bait for

the control of fire ants. Fire ants can be found throughout the s outheastern United States from Texas through Florida, extending as far north as Oklahoma and Virginia, and have been transported to New Mexico, Califor nia, and Puerto Rico. Fire ants are considered public health pests; their sting is extremely painful and can result in allergic reactions or even death to humans, livestock, and wildlife. The Agency cons iders products that cont rol public health pests to be in the public’s interest.

Fire ants pose a serious public health risk to agricultural work ers, particularly those who are involved in the production and harvest of labor-i ntensive crops such as grapes. Therefore, metaflumizone will provide a new tool for the protection of growers and workers involved in U.S. production and harvest of grapes, nuts, and citrus.

Metaflumizone belongs to a new semicarbazone in secticide class, design ated by the Insecticide Resistance Action Committee (IRAC) as Category 22B. Metaflumizone is a voltage-dependentsodium channel blocker that does not exhibit cro ss resistance to conventional chemistries. The only other existing sodium channel blocker is an oxadiazine that is classified in Category 22A by

IRAC.

D. Registration Decision

Based on these considerations, cons istent with the requirements of FIFRA section 3(c)(7)(B), EPA concludes that (i) it has satisfactory data pe rtaining to the proposed uses of metaflumizone in/on citrus fruit, tree nuts, and grapes; (ii) a pproving this application as set forth above will not cause any unreasonable adverse effect on the environment; and (iii) the registration of metaflumizone is in the public interest. Acco rdingly, the Agency is granting these conditional registrations.