Conditional Registration of the Insecticide, Metaflumizone, on 

Citrus Fruits, Tree Nuts, and Grapes 

Regulatory Rationale 

EPA is conditionally granting the first food registrations of the insecticide, metaflumizone. This 

registration action establishes uses of metaflumizone, formulated as a granular bait for control of 

fire ants, on citrus fruits, tree nuts, and grapes in bearing orchards and vineyards. 

I. Chemical Information 

Chemical Name: 

Metaflumizone (2-[2-(4-cyanophenyl)-1-[3-(trifluoromethyl) phenyl] ethylidene] -N-[4-

(trifluoromethoxy) phenyl] hydrazinecarboxamide; 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 and 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 container- 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 (0.001 lb a.i.) per acre, 

with no more than 4 applications per season, for 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 Risk 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 Facilities/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 most common hematotoxic effects reported after 

repeated oral dosing with metaflumizone. The postulated pesticidal mode of action of 

metaflumizone involves inhibition of sodium channels 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 acute or repeated exposures. Similarly, several 

immune system organs seem to be affected following metaflumizone administration via the oral, 

dermal, and inhalation routes (e.g., the presence of macrophages in the thymus, lymphocyte 

necrosis in the mesenteric lymph nodes, and diffuse atrophy of the mandibular); however, there 

was no evidence of any functional deficits at the 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 metaflumizone 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 rabbits. However, this was observed at the same 

dose as severe maternal toxicity, which included late-term abortions and other clinical signs of 

toxicity. There was no evidence (quantitative or qualitative) 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 carcinogenicity studies with mice and rabbits were 

negative. 

B. Toxicological End Points and Doses Used in the Human Health 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 immunotoxic 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 weight or decreased body-weight gain effects 

seen at the LOAEL in the selected oral and dermal studies and at doses above the LOAEL in the 

selected inhalation study. 

1. Acute Dietary Endpoint (General population 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 identified 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, which is the limit dose (1000 mg/kg/day). 

2. Acute Dietary Endpoint (Females 13-49 years old): This endpoint was established based on 

a developmental effect observed in the rabbit developmental toxicity study that can be 

potentially due to a single dose of metaflumizone. This effect consisted of an absent 

subclavian artery in the offspring at the LOAEL of 300 mg/kg bw/day metaflumizone 

(NOAEL = 100 mg/kg bw/day). The rat developmental 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 factor 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 established based on the systemic toxicity 

observed in the chronic toxicity study with dogs. At the LOAEL of 30 mg/kg bw/day 

(NOAEL = 12 mg/kg bw/day), the effects consisted of consisted of reduced general health 

condition, slight to severe ataxia, recumbency, and severe salivation, slight decreases in mean 

corpuscular hemoglobin concentration and total hemoglobin, leading to increased plasma 

bilirubin, increased urinary urobilinogen, and increased hemosiderin 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, the chronic population adjusted 

dose (cPAD) is estimated to be 0.040 mg/kg bw/day. 

4. Dermal (Short- and Intermediate-Term): This endpoint was based on a rat 90-day dermal 

toxicity study in which deficits in body weight, body-weight gain and food consumption (in 

males and females); anogenital smearing; increased macrophages in the thymus; lymphocyte 

necrosis in the mesenteric lymph nodes; diffuse atrophy of the mandibular lymph node; and 

increased hemosiderin in the liver (females only) were observed 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 identified for female rats. At the LOAEL of 0.10 

mg/L metaflumizone (NOAEL = 0.03 mg/L), histopathology of the nasal tissues, lungs, 

thymus, prostate, and adrenal cortex was observed in males. The LOAEL identified in 

females resulted in lymphocyte necrosis in the 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 LOAEL in the selected inhalation study. 
6. Incidental Oral (Short- and Intermediate-Term): This endpoint was selected 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 body 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 the LOAEL of 120 mg/kg bw/day metaflumizone 

(NOAEL = 80 mg/kg bw/day). Both studies considered for this endpoint achieved a clear 

NOAEL for the offspring effects, but the NOAEL 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 likely to be carcinogenic to humans,” based on 

the lack of evidence of carcinogenicity in acceptable carcinogenicity studies 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 potential immunotoxicity in the 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 isomers) 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 retained for inhalation exposure scenarios for the use of a 

LOAEL in the absence of a NOAEL and extrapolation of a 28-day inhalation study to longer 

durations of exposure (up to 6 months for intermediate-term). 

4. The FQPA SF for dermal exposure scenarios is being 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 study 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 reproductive toxicity occurred only in the presence of a poor 
maternal health state. Thus, there is no evidence for increased susceptibility. 

6. There is no clear evidence that metaflumizone directly affects the nervous system. Clinical 

signs consisting of piloerection and body temperature variations 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 additional UFs to account for neurotoxicity. 

7. The dietary analysis is conservative in that it assumes tolerance-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 Oklahoma and Virginia, and in New Mexico, 

California, and Puerto Rico; therefore, it is unlikely 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 residential (dermal, inhalation, incidental oral) sources. When 

aggregating exposures and risks from these sources, EPA considers the route and duration of 

exposure as well as the toxicological effects for 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). Based on this and the proposed/registered uses, 

aggregate acute, short-/intermediate-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 consumption data from the USDA Continuing Survey of Food Intakes 

by Individuals (CSFII) (1994-1996 and 1998). The acute and chronic dietary analyses 

assumed tolerance-level residues, 100% crop treated, and modeled drinking water estimates 

from the Pesticide Root Zone Model-Exposure Analysis Modeling System (PRZMEXAMS). The drinking water estimates were based on the application of metaflumizone as a 

fly bait on use sites such as recreational facilities and outdoor recreational areas including 

parks, picnic grounds, and camp grounds represented by the turf modeling scenario [this 

scenario resulted in the highest estimated drinking water concentration (EDWC)]. DEEMTM 

(ver 7.81) default processing factors were assumed for all commodities excluding grape 

raisin, grape juice, and citrus juice which were reduced to 1 based on empirical data. The 

acute dietary exposure estimate for females 13-49 years old was <1% the aPAD and, 

therefore, does not exceed EPA’s LOC. An endpoint 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 exposed population subgroup). 

2. Residential Risk: The proposed fire ant bait product (citrus fruit, grapes and tree nuts) is not 

expected to result in residential exposure since the proposed use 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 assessed. 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 LOCs 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 using the aggregate risk index approach. The 

combined residential handler and post-application 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, the 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 residential exposure. 

Intermediate-term exposures are possible for the pet care products; however, since the points 

of departure for the short- and intermediate-term durations are the same for metaflumizone, 

the short-term aggregate assessment is protective 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 dietary with residential post-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 conducting 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, inhalation and incidental oral routes are not the 

same (dermal LOC = 100, inhalation LOC = 1000, 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 indices of 3 for the general 

population, and 2 for children 1-2 years old. Because 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/proposed uses which result in chronic 

residential exposure, the chronic aggregate exposure assessment consists 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 assessment 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 result in occupational handler and post-application 

exposure. 

1. Short- and Intermediate-Term Handler Risk: Dermal and inhalation exposures/risks were 

estimated for handlers involved in mixing/loading activities for granular formulations for 

tractor-drawn spreader equipment, applying granulars 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 long-sleeved shirt and 

long pants and chemical-resistant gloves as dermal 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 single 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 period of weeks because they are commercial 

applicators who are completing multiple applications for multiple clients. Long-term 

exposures are not expected, therefore, a long-term assessment was not conducted. Dermal 

and inhalation risks were combined in this assessment, since the toxicological effects for 

these exposure routes were similar. A total aggregated risk index approach was used since 

the LOCs for dermal exposure (100) and inhalation exposure (1000) are different. The target 

aggregate risk index is 1; therefore, aggregate risk indices of less than 1 are risks of concern. 

The dermal and inhalation exposure risks 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 contact with treated surfaces is not expected, 

since all applications are directed towards the soil surface. In addition, workers are not 

expected to frequent areas infested with active fire ants. For these reasons, a quantitative 

dermal post-application assessment has not been conducted. 

3. Post-Application Inhalation Risk: Based on the Agency's current practices, a quantitative 

occupational post-application inhalation exposure assessment was not performed. However, 

there are multiple potential sources of post-application inhalation exposure to individuals 

performing post-application activities in previously treated fields. These potential sources 

include volatilization of pesticides and resuspension of dusts and/or particulates that contain 

pesticides. The Agency is in the process of evaluating current policies and procedures to 

identify the need for and, subsequently, the way 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 for a quantitative occupational post-application 

inhalation exposure assessment for metaflumizone. 

4. Restricted Entry Interval (REI): Metaflumizone is classified in Acute Toxicity Category IV 

for acute dermal toxicity, acute inhalation toxicity, primary eye irritation, primary dermal 

irritation and it is not a dermal sensitizer. Because 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 adequate to protect agricultural workers from 

post-application exposures. 

III. Environmental Risk

A summary of the environmental fate and ecological effects and risks of metaflumizone, as 

assessed in the Agency document entitled “Environmental Fate and Ecological Risk Assessment 
for the Proposed New Use Registration of Metaflumizone 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 potential for bioconcentration/bioaccumulation in 

aquatic and terrestrial systems. Due to the relatively 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 column, and eventually transported to the bottom 

sediment, where it would accumulate. 

Available data indicate that metaflumizone has the potential to bioaccumulate substantially in 

aquatic food webs, with a relatively high octanol/water partition coefficient and bioconcentration 

factor (BCF), and a relatively slow rate of depuration. 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 metaflumizone 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 described in the Proposed Regulatory Decision section. 

B. Ecological Risk 

Ecological risk characterization integrates the results of the exposure 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 quotient method. For this method, risk quotients 

(RQs) are calculated by dividing exposure estimates 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 indicate 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 sensitivity of earthworms and plants 

to metaflumizone, the low likelihood 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 organism 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 refined 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 foraging birds in treated areas. 
Some information suggests that wildlife may avoid areas of fire ant infestation while other 

information indicates that granulated pesticide products used for fire ant control may be 

available to animals. Based on refined analyses with the most sensitive toxicity endpoints 

available, acute exposure resulting 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 aggressive nature of fire ants, it may be unlikely 

that any wildlife would feed on or near fire ant 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 application, 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 application practices. For example, if metaflumizone 

fire ant bait application is applied only when fire ants are actively foraging, then there is the 

potential for a significant reduction in acute and chronic exposures to birds and mammals. 

The potential for exposure will remain for both transport to water and 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 exposure and risk of non-target wildlife to 

metaflumizone ant bait include: (1) lack of knowledge regarding aggregate exposure (e.g., 

direct consumption of granules, ingestion of granules that adhere to soil invertebrates, 

partitioning of dissolved metaflumizone to on-site sources of wildlife drinking water, and 

dermal exposure of granules released to surrounding soil and on-site 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 regarding the availability of metaflumizone fire ant bait granules 

to non-target wildlife, product labels will be required to contain single application and 

seasonal rate restrictions, directions for making applications only during 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, and therefore, risk to these taxonomic groups 

due solely to exposure from metaflumizone freely-dissolved in water is not expected. The 
toxicity data upon which these risks were quantified 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, concentrations in representative 

organisms of an aquatic food web were predicted using a bioaccumulation model. Results 

from this analysis indicate that acute and chronic risks to avian species are unlikely via 

consumption of contaminated aquatic prey. Similarly, results indicate that chronic risks to 

mammalian species are unlikely via this exposure pathway. Finally, an analysis of the 

potential metaflumizone bioconcentration in earthworms indicates that exposure and risks to 

insectivorous birds and mammals are substantially below the Agency’s levels of concern for 

endangered species. 

IV. Regulatory Decision 

The Agency is granting the first food uses of metaflumizone on citrus fruits, tree nuts, and grapes 

in bearing orchards and vineyards, formulated 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 proposed decision document for metaflumizone 

entitled “Proposed Conditional Registration of the Insecticide, Metaflumizone, on Citrus Fruits, 

Tree Nuts, and Grapes,” the associated risk assessments, and the proposed end-use product label 

in docket ID number EPA-HQ-OPP-2008-0168. No comments 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, and 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 demonstrate 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 concluded that the database is adequate for a risk 

assessment of the proposed uses. No additional studies are being requested. 

B. Labeling Requirements 
In 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 non-target plants and animals; and 3. Limit 

human exposure (dietary and occupational) 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 Altrevin 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 Pome 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 establishes the first food uses of metaflumizone, formulated as a bait for 

the control of fire ants. Fire ants can be found throughout the southeastern United States from 

Texas through Florida, extending as far north as Oklahoma and Virginia, and have been 

transported to New Mexico, California, 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 considers products that control public health pests 

to be in the public’s interest. 

Fire ants pose a serious public health risk to agricultural workers, particularly those who are 

involved in the production and harvest of labor-intensive 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 insecticide class, designated by the Insecticide 

Resistance Action Committee (IRAC) as Category 22B. Metaflumizone is a voltage-dependent 
sodium channel blocker that does not exhibit cross 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, consistent with the requirements of FIFRA section 3(c)(7)(B), 

EPA concludes that (i) it has satisfactory data pertaining to the proposed uses of metaflumizone 

in/on citrus fruit, tree nuts, and grapes; (ii) approving 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. Accordingly, the Agency is granting these conditional 

registrations.