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(7/1/2006)

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[BASF Corporation]

[7F7260]

EPA has received a pesticide petition ([7F7260]) from [BASF Corporation], 

[P.O. Box 13528, Research Triangle Park, NC 27709] proposing, pursuant to section 

408(d) of the Federal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 346a(d), to 

amend 40 CFR part 180.

1. by establishing a tolerance for residues of

[metaflumizone] in or on the raw agricultural commodity [grape] at [0.04]

parts per million (ppm); [crop group 10: citrus fruits group] at [0.04] ppm; [crop 

group 14: tree nuts group] at [0.04] ppm; and [almond hulls] at [0.04] ppm. EPA 

has determined that the petition contains data or information regarding the 

elements set forth in section 408 (d)(2) of the FDDCA; however, EPA has not fully 

evaluated the sufficiency of the submitted data at this time or whether the data 

supports granting of the petition. Additional data may be needed before EPA rules 

on the petition.

A. Residue Chemistry

1. Plant metabolism. [In three plant metabolism studies (cabbage, tomato and 

cotton), the major component of the residue was metaflumizone. The major 

degradate was the ketone, M320I04 and an oxidized and cyclized metabolite, 

M320I23, was present in lesser amounts. These four compounds were defined as the 
residues of concern and were incorporated into an analytical method. In the 

confined rotational crop studies plant uptake was very limited and the residues were 

a mixture of minor and polar components.]

2. Analytical method. [BASF Analytical Method No. 531/0 was developed to 

determine residues of metaflumizone and its metabolites M320I04 and M320I23, the 

residues of concern in plants, and in crop matrices. In this method, residues of 

metaflumizone are extracted from plant matrices with methanol/water (70:30; v/v) 

and then partitioned into dichloromethane. For oily matrices, the residues are 

extracted with a mixture of isohexane/acetonitrile (1:1; v/v). The final 

determination of metaflumizone and its metabolites is performed by LC/MS/MS.]

3. Magnitude of residues. [Field trials were carried out in order to determine 

the magnitude of residue in grapes, citrus, and tree nuts. Twelve field trials were 

conducted for grape in the US and Canada. Twenty-three citrus trials were 

conducted in the US, including grapefruit, orange and lemon. Ten field trials were 

conducted in the US on pecans and almonds. Field trials were conducted in the 

required regions for each crop. Field trials were carried out using 4x the maximum 

label rate, the maximum number of applications and the minimum preharvest 

interval. In addition, processing studies were conducted on grapes and citrus to 

determine the concentration factors during normal processing of the raw 

agricultural commodities.]

B. Toxicological Profile

1. Acute toxicity. [Based on the available acute toxicity data, metaflumizone 

and its formulated product do not pose acute toxicity risks. For metaflumizone:

Oral LD50 Rat LD50 > 5000 mg/kg b.w. category IV

Oral LD50 Mouse LD50 > 5000 mg/kg b.w. category IV

Dermal LD50 Rat LD50 > 5000 mg/kg b.w. category IV

Inhalation LC50 Rat > 5.2 mg/L category IV

Eye Irritation Rabbit Not irritating category IV

Skin Irritation Rabbit Not irritating category IV

Skin Sensitization Guinea pig Not sensitizing (Maximization Test)]

2. Genotoxicty. [In a battery of three in vitro and two in vivo mutagenicity 

assays consisting of all required end-points (point mutation, chromosomal damage, 

and DNA damage and repair), the weight-of-the-evidence for metaflumizone 

indicates a lack of potential genotoxicity. 

Specifically, for the battery of three in vitro mutagenicity assays with 

metaflumizone, no positive responses were observed for increased revertant 
frequencies with and without metabolic activation [bacterial reverse mutation 

assay] or for increased mutant frequencies with and without metabolic activation 

[HGPRT locus assay]. Although there was a positive result for a statistically 

increased number of structurally aberrant metaphases in the chromosomes, which 

indicates clastogenic potential under in vitro conditions, this result was only 

observed without metabolic activation [cytogenicity study with V79 cells. 

Importantly, the potential biological significance of this apparent chromosome 

damage observed in vitro only without metabolic activation, was evaluated in vivo 

using the mouse micronucleus assay. Testing in the in vivo micronucleus study with 

NMRI mice was conducted at a high dose level (2000 mg/kg b.w.) that demonstrated 

clinical symptoms of toxicity, including piloerection and poor general state, in 5 of 5 

animals. No significant or dose-related increases in chromosomal damage were 

observed in this in vivo test, indicating that metaflumizone does not cause 

chromosomal aberrations in intact animals. 

Moreover, it has also been recognized by U.S. EPA that more weight should be 

placed on in vivo systems than in vitro systems as expressed in the Agency’s weightof-evidence for genotoxic evaluation of a chemical included in the "Guidelines for 

Mutagenicity Risk Assessment" (Federal Register, September 24, 1986, Vol. 51: 

34006-34012). Thus, the negative in vivo results (non-clastogenicity for 

chromosomal aberrations) observed in the mouse micronucleus assay and the rat 

hepatocytes assay, should override the positive results obtained in the in vitro assay 

only without metabolic activation. Furthermore, it has been noted that in vitro 

systems may simulate abnormal physiological conditions from prolonged exposure 

to a chemical in the absence of S-9 metabolic activation [Brusick, D.J. (editor) 1987. 

Genotoxicity Produced in Cultured Mammalian Cell Assay by Treatment 

Conditions. Mutation Research, Vol. 189, No.1: 1-69] and [Sofuni, T. 1993. Japanese 

Guidelines for Mutagenicity Testing. Environmental and Molecular Mutagenesis, 

Vol. 21, No.1: 2-7]. Consequently, based on the weight-of-the-evidence presented 

above, metaflumizone does not pose a genotoxic concern.]

3. Reproductive and developmental toxicity. [Potential reproductive toxicity 

of metaflumizone was investigated in a two-generation reproduction toxicity study 

in Wistar rats by oral gavage administration. Originally, the highest dose tested by 

oral gavage was 75 mg/kg b.w../day, which induced both excessive maternal toxicity 

(very high incidences of poor general health in females during premating, gestation, 

and lactation; and statistically decreased food consumption, body weights, and body 

weight gain) as well as excessive developmental toxicity (statistically impaired pup 

body weights and body weight gain), which altogether resulted in high pup 

mortality. Consequently, a meaningful assessment of the potential reproductive 

toxicity of the test compound at this excessively toxic dose level was not possible. 

Thereafter, for the next two successive parental generations of rats, which were 

originally derived from the parents treated at 75 mg/kg b.w./day, the highest dose 

tested was 50 mg/kg b.w./day. 
Subsequently, the NOAEL for parental toxicity was 20 mg/kg b.w./day, based on the 

following effects for females at 50 mg/kg b.w./day (highest dose tested for two 

consecutive generations) -- increased incidences of poor general health in females 

during premating, gestation, and lactation; 3 of 25 dams with complete litter losses; 

and statistically significantly reduced body weights during premating, gestation, and 

lactation. 

The NOAEL for offspring/pup toxicity was 20 mg/kg b.w./day, based on a slight 

increased incidence of pup mortality at 50 mg/kg b.w./day. Whereas the NOAEL 

for fertility in this study was 50 mg/kg b.w./day (highest dose tested for two 

generations), the NOAEL for reproductive performance was considered to be 20 

mg/kg b.w./day, based on 3 of 25 dams with complete litter losses, of which 2 of these 

3 dams had indications of poor nursing for their first generation of pups. It is 

noteworthy that because most of the pup mortality was due to poor nursing in only 

2 of 25 dams, this finding may be considered to be incidental. Importantly, no 

comparable impairment of reproductive performance occurred for the succeeding 

parental generation treated by oral gavage administration at 50 mg/kg b.w./day. 

In a developmental (teratology) toxicity study in the Wistar rat, the results indicated 

that the NOAEL for maternal toxicity was 40 mg/kg b.w./day, based on statistically 

decreased food consumption and body weight gains at 120 mg/kg b.w./day (highest 

dose tested). The NOAEL for fetal (prenatal)/developmental toxicity was 120 mg/kg 

b.w./day (highest dose tested). In addition, there were no indications of any 

teratogenic effects in the rat fetuses at 120 mg/kg b.w./day (highest dose tested). 

Therefore, metaflumizone is considered to be neither a developmental toxicant nor a 

teratogenic agent in the rat. 

In a developmental (teratology) toxicity study in the Himalayan rabbit, the results 

indicated that the NOAEL for maternal toxicity was 100 mg/kg b.w./day, based on 

several clinical symptoms of toxicity (including ataxia and poor general state) 

occurring in 4 of 25 does at 300 mg/kg b.w./day, for which 2 of these 4 does had 

abortions prior to being sacrificed early, with a third doe at 300 mg/kg b.w./day 

being sacrificed moribund. Similarly, the NOAEL for fetal (prenatal) / 

developmental toxicity was 100 mg/kg b.w./day, based on slightly decreased mean 

fetal body weights as well as an increased rate for a certain skeletal variation, 

namely incomplete ossification of sternabrae. Because developmental toxicity was 

only observed at dose levels that were maternally toxic, metaflumizone is not 

selectively toxic to the fetal rabbit. 

Lastly, in this rabbit developmental toxicity study, there were no indications of any 

teratogenic effects in the rabbit fetuses at 300 mg/kg b.w./day (highest dose tested). 

Therefore, metaflumizone is not teratogenic in the rabbit.]

4. Subchronic toxicity. [In the Sprague-Dawley rat, treatment by oral gavage 

with metaflumizone for a subchronic duration (90-day timepoint in the chronic 

toxicity/carcinogenicity study) resulted in reduced food consumption and/or 
decreased mean body weight and/or body weight gains in males and females at 300 

mg/kg b.w./day and in increased incidences of hepatocellular centrilobular 

hypertrophy in the livers of males at 300 mg/kg b.w./day. Under the conditions of 

the study, the NOAEL for oral administration of metaflumizone for 90 days was 60 

mg/kg b.w./day.

In the beagle dog, treatment by oral gavage with metaflumizone for a subchronic 

duration (90-day timepoint in the chronic toxicity study) resulted in reduced body 

weight gain and/or decreased food consumption in several dogs at 30 mg/kg 

b.w./day and slightly decreased mean MCHC at 30 mg/kg b.w./day. Under the 

conditions of the study, the NOAEL for oral administration of metaflumizone for 90 

days was 12 mg/kg b.w./day.

For a subchronic (90-day) dermal toxicity study conducted with metaflumizone in 

Wistar rats, the results support a NOAEL of 100 mg/kg b.w./day, based on 

decreased food consumption (females) and decreased body weight gain in males and 

females at 300 mg/kg b.w./day, the next highest dose tested. Several microscopic 

changes were observed in female animals at 300 mg/kg b.w./day and above, but 

these morphologic changes were regarded to be indirect effects of the impaired body 

weight gain. 

For a subacute (28-day) inhalation toxicity study conducted with metaflumizone in 

Wistar rats, the results support a NOAEL of 0.03 mg/L, based on decreased food 

consumption (females) and decreased body weight / body weight gain (females) and 

several microscopic changes in the respiratory tract at 0.10 mg/L, the next highest 

dose tested. Several microscopic changes in non-respiratory tract tissues were 

observed in animals at these two dose levels, but these morphologic changes were 

regarded to be indirect effects of the impaired body weight / body weight gain. 

Testing for metaflumizone’s potential immunotoxicity, two studies were conducted, 

namely “28-Day Oral Immunotoxicity Study [by Thymic-Dependent Antibody 

Response (TDAR) Assay] in the Female Wistar Rat” and “28-Day Oral 

Immunotoxicity Study [by Natural Killer (NK) Cell Assay] in the Female Wistar 

Rat.” Results from both studies indicate a lack of immunotoxic potential for 

metaflumizone (BAS 320 I) up to the highest dose tested (HTD). Both Study 

Reports have been submitted to U.S. EPA (in 2011). 

 

5. Chronic toxicity. [In the Sprague-Dawley rat, treatment by oral gavage 

with metaflumizone for a 2-year chronic duration resulted in dose-related increased 

incidences of hepatocellular centrilobular hypertrophy in the livers of males and 

females at 60 mg/kg b.w./day and at 300/200 mg/kg b.w./day and hepatocellular 

basophilic alteration in males at 60 and 300 mg/kg b.w./day. [NOTE: Beginning the 

first day of Week 3, the dose level of the high-dose females was lowered from 300 to 

200 mg/kg b.w./day, due to an adverse effect of -71% decreased body weight gain as 

compared to controls.] 
Therefore, the no-observable-adverse-effect-level (NOAEL) for systemic toxicity 

following oral administration of metaflumizone for 24 months to Sprague-Dawley 

rats was 30 mg/kg b.w./day for males and females. Importantly, treatment with 

metaflumizone to rats for 2 years resulted in no test substance-related neoplastic 

findings, and therefore, the NOAEL for oncogenicity was 300/200 mg/kg b.w./day 

(highest dose tested). 

In the CD-1 mouse, treatment by oral gavage with metaflumizone for an 18-month

chronic duration resulted in a treatment-related increased incidence of increased 

brown pigment in the spleens of male and female animals administered 1000 mg/kg 

b.w./day (highest dose tested), as compared to controls. Under the conditions of the 

study, the NOAEL for systemic toxicity following oral administration of 

metaflumizone for 18 months to CD-1 mice was 250 mg/kg b.w./day (the next 

highest dose tested) for males and females. Importantly, treatment with 

metaflumizone to mice for 18 months resulted in no test substance-related neoplastic 

findings, and therefore, the NOAEL for oncogenicity was 1000 mg/kg b.w./day 

(highest dose tested).

In the beagle dog, treatment via gelatin capsules with metaflumizone for a 12-month 

chronic duration resulted in reduced body weight gain and/or decreased food 

consumption in several dogs at 30 mg/kg b.w./day and slightly decreased mean 

MCHC at 30 mg/kg b.w./day. Under the conditions of the study, the NOAEL for 

oral administration of metaflumizone for 12 months was 12 mg/kg b.w./day. 

Threshold Effect. For estimated chronic exposure, the calculation of the chronic 

reference dose (chronic RfD) is based on the results of the chronic toxicity studies in 

the rat, mouse, and dog, and the two-generation reproduction study in the rat. For 

metaflumizone, the lowest NOAEL for chronic toxic effects is 12 mg/kg b.w./day 

from the 12-month dog study. A safety factor of 100 is applied to the NOAEL of 12 

mg/kg b.w./day, which results in a chronic RfD of 0.12 mg/kg b.w./day.

Non-Threshold Effect. Since there were no test substance-related neoplastic 

findings following long-term treatment with metalfumizone to mice for 18 months 

or to rats for 24 months, the NOAEL for oncogenicity in both studies was 

established at the respective highest doses tested. Therefore, metaflumizone should 

be classified as "not likely to be a human carcinogen."]

6. Animal metabolism. [In the rat, goat and hen metabolism studies, the 

majority of the dose was rapidly excreted in the feces. The low levels that were 

absorbed were distributed throughout various tissues. Metaflumizone was the 

major component of the extractable residues in all tissues, milk, eggs and is the only 

residue of concern. Metabolism of metaflumizone occurs by hydroxylation and 

conjugation on either of the phenyl rings or at the ethylene bridge and are the major 

routes of detoxification. Cleavage of the semicarbazide bond to yield M320I04 also 

occurs, usually with accompanying conjugation. The only residue of concern is 
metaflumizone.]

7. Metabolite toxicology. [Toxicity of the metabolites of metaflumizone with 

potential exposure to humans was concurrently evaluated during toxicity testing of 

the parent except for the metabolite M320I23 that was not observed in the rat 

metabolism study. The Z-isomer (M320I02) of metaflumizone was evaluated in 

additional toxicity tests to confirm no differences between the minor Z-isomer 

component and metaflumizone with a 9 to 1 E-isomer to Z-isomer ratio, 

respectively. The results show no toxicological concerns:

Toxicity Studies with the metabolite M320I23 of metaflumizone

(a) Acute Toxicity Study with Metabolite M 320I023

The metabolite M 320I023 of metaflumizone demonstrates low acute toxicity via the 

oral route of exposure in the rat.

Oral LD50 > 2000 mg/kg b.w. (category III).

(b) Subchronic Toxicity Study with Metabolite M 320I023

In the Sprague-Dawley rat, treatment by oral gavage with metabolite M 320I023 of 

metaflumizone for a subchronic (90-day) duration resulted in systemic toxicity 

effects of increased relative liver weights (females) and increased incidences of liver 

hepatocellular centrilobular hypertrophy in males and females at 1000 mg/kg 

b.w./day (highest dose tested), as compared to controls. Under the conditions of the 

study, the NOAEL for oral administration of the metabolite M 320I023 of 

metaflumizone for 90 days was 200 mg/kg b.w./day (next highest dose tested) in 

males and females. 

(c) Mutagenicity/Genotoxicity Studies with Metabolite M 320I023 

In a battery of three in vitro and one in vivo mutagenicity assays consisting of all 

required end-points (point mutation, chromosomal damage, and DNA damage and 

repair), the weight-of-the-evidence for the metabolite M 320I023 (parent ketone) of 

metaflumizone insecticide indicates a lack of potential genotoxicity. 

Specifically, for the battery of three in vitro mutagenicity assays with metabolite M 

320I023 of metaflumizone, no positive responses were observed for increased 

revertant frequencies with and without metabolic activation [bacterial reverse 

mutation assay] or for increased mutant frequencies with and without metabolic 

activation [HGPRT locus assay]. Although there was a positive result for a 

statistically increased number of structurally aberrant metaphases in the 

chromosomes, which indicates clastogenic potential under in vitro conditions, this 

result was only observed with metabolic activation [cytogenicity study with V79 

cells]. 

Importantly, the potential biological significance of this apparent chromosome 

damage observed in vitro only with metabolic activation, was evaluated in vivo 

using the mouse micronucleus assay. Testing in this in vivo micronucleus study with 

NMRI mice was conducted at a high dose level (2000 mg/kg b.w.), that 
demonstrated no clinical symptoms of toxicity but which represents the limit dose 

for this assay. No significant or dose-related increases in in vivo chromosomal 

damage were observed, indicating that the metabolite M 320I023 of metaflumizone 

does not cause chromosomal aberrations in intact animals. 

Moreover, it has also been recognized by U.S. EPA that more weight should be 

placed on in vivo systems than in vitro systems as expressed in the Agency’s weightof-evidence for genotoxic evaluation of a chemical included in the "Guidelines for 

Mutagenicity Risk Assessment" (Federal Register, September 24, 1986, Vol. 51: 

34006-34012). Thus, the negative in vivo results (non-clastogenicity for 

chromosomal aberrations) observed in the mouse micronucleus assay should 

override the positive results obtained in the in vitro assay only with metabolic 

activation. Furthermore, it has been noted that in vitro systems may simulate 

abnormal physiological conditions [Brusick, D.J. (editor) 1987. Genotoxicity 

Produced in Cultured Mammalian Cell Assay by Treatment Conditions. Mutation 

Research, Vol. 189, No.1: 1-69]. Additionally, it has been reported in the literature 

that S-9 metabolic activation does not often have adequate cofactors for activating 

detoxifying mechanisms found in the whole animal system [Ashby, J. 1983. The 

unique role of rodents in the detection of possible human carcinogens and mutagens. 

Mutation Research, Vol. 115: 117-213] [Galloway, S.M. 1994. Chromosome 

Aberrations Induced In Vitro: Mechanisms. Delayed Expression, and Intriguing 

Questions. Environmental and Molecular Mutagenesis, Vol. 23, Supplement 24: 44-

53]. Consequently, based on the weight-of-the-evidence presented above, the 

metabolite M 320I023 of metaflumizone does not pose a genotoxic concern. 

Therefore, as indicated from the results of the mammalian toxicity studies as well as 

the mutagenicity assays, metabolite M 320I023 of metaflumizone does not 

demonstrate more adverse toxicity when compared to metaflumizone. 

Toxicity Studies with the Z-Isomer of metaflumizone

(a) Acute Toxicity Study with Z-Isomer

The Z-isomer of metaflumizone demonstrates low acute toxicity via the oral route of 

exposure in the rat. 

Oral LD50 > 5000 mg/kg b.w. (category IV).

(b) Subchronic Toxicity Study with Z-Isomer

In the Sprague-Dawley rat, treatment by oral gavage with the Z-isomer of 

metaflumizone for a subchronic (90-day) duration resulted in impaired body weight 

gain only in females at the mid-dose (300 mg/kg b.w./day) and the high-dose (1000 

mg/kg b.w./day), as compared to controls. Several microscopic changes were 

observed in female animals at these two dose levels, but all morphologic changes 

were regarded to be indirect effects of the impaired body weight gain. Under the 

conditions of the study, the NOAEL for oral administration of the Z-isomer of 

metaflumizone for 90 days was 1000 mg/kg b.w./day (highest dose tested) in males 

and 100 mg/kg b.w./day (lowest dose tested) in females. 
(c) Mutagenicity/Genotoxicity Study with Z-Isomer

In an in vitro mutagenicity assay with the Z-isomer of metaflumizone, there were no 

positive responses observed for increased revertant frequencies with and without 

metabolic activation [bacterial reverse mutation assay].

Therefore, as indicated from the results of the mammalian toxicity studies as well as 

the mutagenicity assay, the minor isomer of metaflumizone, namely the Z isomer, 

does not demonstrate more adverse toxicity when compared to metaflumizone.]

8. Endocrine disruption. [Data from the reproduction / developmental 

toxicity and short-and long-term repeated dose toxicity studies with metaflumizone 

in the rat, rabbit, mouse, or dog, do not suggest any endocrine disruption activity. 

This information is based on the absence of any treatment-related effects from the 

histopathological examination of reproductive organs as well as a low level of 

concern for possible effects on fertility, reproductive performance, or any other 

aspect of reproductive function, or on growth and development of the offspring.]

C. Aggregate Exposure

1. Dietary exposure.

i. Food. [

Metaflumizone and its metabolites (M320I04, M320I23) are expressed as the parent 

compound (metaflumizone). A dietary exposure analysis was conducted for grape, 

crop group 10 – citrus fruits group, crop group 14 – tree nuts group at the tolerance 

of 0.04 ppm. 

Acute Dietary Food Exposure: The Health Effects Division (HED) of EPA has 

determined that there are no toxic effects attributable to a single dose of 

metaflumizone for the general populations including infants and children. 

Therefore, a quantitative acute dietary exposure and risk assessment for these subpopulations is not required. 

 

Acute dietary assessments were conducted to evaluate the potential risk due to acute 

dietary exposure to females 13 – 49 years old. The ARfD for metaflumizone is 1.0 

mg/kg bw/day. The FQPA safety factor for metaflumizone has been set to 1. 

Therefore, the aPAD is 1.0 mg/kg bw/day. The tier 1 acute dietary exposure 

estimates were based on the proposed tolerance values, 100 percent crop treated 

values, concentration/processing factors and consumption data from the USDA 

Continuing Survey of Food Intake by Individuals (CSFII 1994 - 1996, 1998) and the 

EPA Food Commodity Ingredient Database (FCID) using Exponent's Dietary 

Exposure Evaluation Module (DEEM-FCID) software. Drinking water exposure 

was included in the dietary exposure analysis. Tolerances for meat, milk, egg, and 

poultry are not required. 
Exposure estimates for the metaflumizone acute dietary assessments were well 

below U.S. EPA’s level of concern (See tables below). The estimated acute dietary 

exposure for females 13 – 49 years old was 0.03 %. Additional refinements such as 

the use of anticipated residues and predicted percent crop treated would further 

reduce the estimated acute dietary exposure.

Table 1. Summary of Acute Dietary Exposure and Risk for Metaflumizone 

Considering Grape, Crop Group 10 – Citrus Fruits Group, Crop Group 14 – Tree 

Nuts Group and Drinking Water. 

Population Exposure Estimate %aPAD

Subgroups (mg/kg b.w./day)

Females (13-49 years old) 0.000301 0.03

aPAD = acute population adjusted dose (aPAD = 1.0 mg/kg bw/day)

Chronic Dietary Food Exposure: 

A tier 1 dietary exposure assessment was conducted for all sub-populations 

including infants and children. The ADI for metaflumizone is 0.12 mg/kg bw/day. 

The FQPA safety factor for metaflumizone has been set to 1. Therefore, the cPAD 

is 0.12 mg/kg bw/day. The tier 1 chronic dietary exposure estimates were based on 

the proposed tolerance values, 100 percent crop treated values, 

concentration/processing factors and consumption data from the USDA Continuing 

Survey of Food Intake by Individuals (CSFII 1994 - 1996, 1998) and the EPA Food 

Commodity Ingredient Database (FCID) using Exponent's Dietary Exposure 

Evaluation Module (DEEM-FCID) software. Drinking water exposure was included 

in the dietary exposure analysis. Tolerances for meat, milk, egg, and poultry are not 

required. 

Exposure estimates for the metaflumizone chronic dietary assessments were well 

below U.S. EPA’s level of concern (See tables below. The most highly exposure subgroup was children 1-2 years old and the exposure accounted for 0.25% of the 

cPAD. Additional refinements such as the use of anticipated residues and predicted 

percent crop treated would further reduce the estimated chronic dietary exposure.

Table 2. Summary of Chronic Dietary Exposure and Risk for Metaflumizone 

Considering Grape, Crop Group 10 – Citrus Fruits Group, Crop Group 14 – Tree 

Nuts Group, and Drinking Water.

Population Exposure Estimate %cPAD

Subgroups (mg/kg b.w./day)

U.S. Population 0.015792 0.07

All Infants (< 1 year old) 0.008408 0.05

Children (1-2 years old) 0.019314 0.25

Children (3-5 years old) 0.019165 0.19

Children (6-12 years old) 0.01567 0.10
Youth (13-19 years old) 0.013229 0.16

Females (13-49 years old) 0.016063 0.05

Adults (20-49 years old) 0.015845 0.05

Adults (50+ years old) 0.016113 0.05

cPAD = chronic population adjusted dose (cPAD = 0.12 mg/kg bw/day)]

ii. Drinking Water. [The estimated drinking water concentrations (EDWCs)

used in this assessment were from the HED human health assessment of 

metaflumizone, January 26, 2010. The EDWC values were calculated using the 

highest application rate (4 x 0.002 lb ai/acre). The acute and chronic surface water 

EDWCs were 0.0399 and 0.0157 ppb, respectively. The acute and chronic ground 

water EDWC was 2.64 x 10-5ppb. The drinking water exposure was included in the 

dietary assessment. ]

2. Non-dietary exposure. [

Metaflumizone is registered for fire ant bait. This use can result in residential 

exposure. The EPA HED has evaluated these uses and determined the exposure. 

The exposure and MOE values in the below tables are from the HED document 

January 24, 2006. The MOE values were calculated using the a short-term dermal 

NOAEL = 100 mg ai/kg bw/day and short-term incidential oral NOAEL = 20 mg 

ai/kg bw/day. The calculated MOEs for all homeowner and toddler exposures are 

greater than 100 and therefore do not exceed EPA’s level of concern. 

Table 3. Summary of Residential and Recreational Post-Application Exposure and 

Risks from use of Fire Ant Bait. 

Fire Ant Bait mg/kg bw/day MOE

Toddler oral hand to mouth (turf 

grass) 0.000015 1333333

Toddler oral ingestion of granules 0.013 1538

Toddler oral object to mouth (turf) 0.00000093 21505376

Adult dermal pos-app (Res. Turf) 0.000232 431034

Toddler dermal post-app (Res. 

Turf) 0.00039 256410

Adult golfer dermal post-app 

(turf) 0.000016 6250000

Child golfer dermal post-app 

(turf) 0.0000272 3676471

Toddler oral (hand to mouth + 

object to mouth) 0.000016 1250000

 

3. Aggregate exposure.

[Acute Aggregate Risk: 
No acute residential/recreational exposure are expected. The acute aggregate 

risk includes only exposure from food and water. The food and drinking water 

exposure accounts for less than 1 % aPAD which is below HED’s level of 

concern. 

Short-/Intermediate Term Aggregate Risk:

There is the potential for short-term, non-dietary exposure of children and 

adults to metaflumizone from the use as fire ant bait. Therefore, the shortterm aggregate exposure includes residential exposure, food and water 

exposure. The target MOE for metaflumizone aggregate risk is 100. 

Table 7. Summary of Short-/Intermediate Term Aggregate Risk from Fire Ant 

Bait Use.

Food + 

water

Non-dietary 

oral Dermal Aggregate

Population SubGroup MOE MOE MOE MOE

US population 250,000 NA 431,034 158,228

All infants (< 1 yr old) 322,581 1333333 256,410 129,032

Children 1-2 65,574 1333333 256,410 50,251

children 3-5 90,090 1333333 256,410 63,492

Children 6-12 166,667 NA 3,676,471 159,439

Youth 13-19 285,714 NA 3,676,471 265,111

Adults 20-49 363,636 NA 431,034 197,239

Adults 50 + years 338,983 NA 431,034 189,753

The aggregate MOE values are all greater than the HED level of concern which 

indicates that the aggregate use is below HED’s level of concern. 

Chronic Aggregate Risk:

No chronic residential/recreational exposure are expected. The chronic aggregate 

risk includes only exposure from food and water. The chronic food and drinking 

water exposure for all sub-populations are below HED’s level of concern. ]

D. Cumulative Effects [Section 408(b)(2)(D)(v) 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.

The EPA is currently developing methodology to perform cumulative risk 

assessments. At this time, there is no available data to determine whether 

metaflumizone has a common mechanism of toxicity with other substances or how 

to include this pesticide in a cumulative risk assessment.]
E. Safety Determination

1. U.S. population. [Using the conservative exposure assumptions described 

above and based on the completeness and the reliability of the toxicity data, BASF 

has estimated the aggregate exposure to metaflumizone are well below the EPA’s 

level of concern. ]

2. Infants and children. [All subpopulations based on age were considered. 

Infants and children aggregate risk is well below remained below EPA’s level of 

concern. BASF, considering a worst-case situation, concludes with reasonable 

certainty that no harm will result to infants or children from aggregate exposure to 

metaflumizone residues.]

F. International Tolerances

[Maximum residue levels (MRLs) have been established for metaflumizone 

by the Codex Alimentarius Commision (CODEX) in potato, tomato, pepper, 

eggplant, Brussels sprout, Chinese cabbage, lettuce, and animal products. 

Harmonized EU MRLs have been established for metaflumizone in potato, tomato, 

pepper, eggplant, leafy brassica, Brussels sprout, lettuce and similar, and animal 

products. 

Codex (based on parent only)

Potato 0.02

Tomato 0.6

Pepper, inc chili pepper 0.6

Eggplant 0.6

Brussels sprout 0.8

Chinese cabbage 6

Lettuce 7

Swine (all) 0.02

Bovine (meat, kidney, liver, fat, offal) 0.02

Sheep, goat (meat, kidney, liver, fat, offal) 0.02

Milk 0.01

Cream 0.02

EU harmonized (based on parent + M320I04)

Potato 0.05

Tomato 0.6

Pepper, inc chili pepper 1

Eggplant 0.6

Brussels sprout 1

Head cabbage 1

Leafy brassica 6

Lettuce and similar except scarole 10
Swine (all) 0.02

Bovine (meat, kidney, liver, fat, offal) 0.02

Sheep, goat (meat, kidney, liver, fat, offal) 0.02

Poultry (meat, liver, kidney, offal) 0.02

Poultry fat 0.1

Milk and cream 0.02

Eggs 0.02

]