EPA REGISTRATION DIVISION COMPANY NOTICE OF FILING FOR PESTICIDE 

PETITIONS PUBLISHED IN THE FEDERAL REGISTER 

EPA Registration Division contact: Andrew Ertman, (703) 308-9367

IR-4 

PP #1E7851 

EPA has received a pesticide petition (PP #1E7851) from Interregional Project 4 / IR-4, 

500 College Road East, Suite 201 W, Princeton, NJ 08540 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 by establishing a tolerance for residues of azoxystrobin: (methyl (E)-2-{2-[6-(2-

cyanophenoxy)pyrimidin-4-yloxy]phenyl}-3-methoxyacrylate) and the Z isomer of 

azoxystrobin, (methyl (Z)-2-{2-[6-(2- cyanophenoxy)pyrimidin-4-yloxy]pheny1}-3-

methoxyacrylate) in or on the following: 

Onion, bulb subgroup 3-07A at 1.0 parts per million 

Onion, green subgroup 3-07B, at 7.5 parts per million 

Caneberry subgroup 13-07A, at 5.0 parts per million 

Bushberry subgroup 13-07B, at 3.0 parts per million 

Small fruit vine climbing subgroup, except fuzzy kiwifruit, 13-07F, at 1.0 parts per 

million 

Low growing berry subgroup 13-07G, except cranberry, at 10.0 parts per million 

Vegetable, fruiting, subgroup 8-10A, at 0.2 parts per million 

Vegetable, fruiting, subgroups 8-10B, at 2.0 parts per million 

Fruit, citrus, group 10-10, at 10.0 parts per million 

Rapeseed subgroup 20A, at 1.0 parts per million 

Sunflower subgroup 20B, at 0.5 parts per million 

Cottonseed subgroup 20C, at 0.6 parts per million 

Wasabi, at 50.0 parts per million 

Dragon Fruit, at 2.0 parts per million 

And by amending the tolerance for residues of

Vegetable, tuberous and corm, subgroup 1C, at 6.0 parts per million

Upon approval of the aforementioned tolerances, it is proposed that 40 CFR 180.507 be amended 

to remove the established tolerances for the residues of azoxystrobin in or on the raw agricultural 

commodities: 

Onion, bulb, at 1.0 parts per million 

Onion, green, at 7.5 parts per million 

Bushberry subgroup 13B, at 3.0 parts per million 

Juneberry, at 3.0 parts per million 

Lingonberry, at 3.0 parts per million 

Salal, at 3.0 parts per million 

Grape, at 1.0 parts per million 
Strawberry, at 10.0 parts per million 

Tomato, at 0.2 parts per million 

Vegetable, fruiting, group 8, except tomato at 2.0 parts per million 

Fruit, citrus, group 10 at 10.0 parts per million 

Canola, seed, at 1.0 parts per million 

Cotton, undelinted seed, at 0.6 part per million 

Crambe, seed, at 0.5 parts per million 

Flax, seed at 0.5 parts per million 

Mustard, field, seed at 0.5 parts per million 

Mustard, Indian, seed at 0.5 parts per million 

Mustard, seed at 0.5 parts per million 

Rapeseed, Indian, at 0.5 parts per million 

Rapeseed, seed, at 0.5 parts per million 

Safflower, seed, at 0.5 parts per million 

Sunflower, seed, at 0.5 parts per million 

Potato, at 0.03 parts per million 

 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. The metabolism of azoxystrobin as well as the nature of the 

residues is adequately understood for purposes of the tolerances. Plant metabolism has 

been evaluated in four diverse crops, cotton, grapes, wheat and peanuts which should 

serve to define the similar metabolism of azoxystrobin a wide range of crops. Parent 

azoxystrobin is the major component found in crops. Azoxystrobin does not accumulate 

in crop seeds or fruits. Metabolism of azoxystrobin in plants is complex with more than 

15 metabolites identified. These metabolites are present at low levels, typically much 

less than 5% of the TRR. 

2. Analytical method. An adequate analytical method, gas chromatography with nitrogenphosphorus detection (GC-NPD) or in mobile phase by high performance liquid 

chromatography with ultra-violet detection (HPLC-UV), is available for enforcement 

purposes with a limit of detection that allows monitoring of food with residues at or above 

the levels set in these tolerances. The Analytical Chemistry section of the EPA concluded 

that the method(s) are adequate for enforcement. Analytical methods are also available for 

analyzing meat, milk, poultry and eggs which also underwent successful independent 

laboratory validations. 

3. Magnitude of residues. Complete residue data to support the requested tolerances have 

been submitted. The requested tolerances are adequately supported.
In support of the requested tolerance, IR-4 has conducted the necessary trials in 

accordance with the requirements of the EPA Residue Chemistry Guidelines 860.1500 to 

determine the magnitude of residue of azoxystrobin in or on requested commodities. 

B. Toxicological Profile 

1. Acute toxicity. 

Acute toxicity NOAEL = < 200 mg/kg/day 

UF = 300 

Acute RfD = 0.67 mg/kg/day 

FQPA SF = 1X 

aPAD = Acute RfD + FQPA 

SF = 0.67 mg/kg/day

Acute neurotoxicity study in rates 

LOAEL = 200 mg/kg/day based on 

diarrhea and 2- hours post dose at all 

dose levels up to and including 20 

mg/kg/day (the LOAEL) 

2. Genotoxicty. Azoxystrobin was positive for forward gene mutation in mouse 

lymphoma cells, but was not mutagenic in the salmonella/mammalian activation gene 

mutation assay, showed some evidence of concentration-related induction of chromosomal 

aberrations over background in the presence of moderate to severe toxicity in the in vitro 

mammalian cytogenetics assay in human lymphocytes, caused no increase in the induction 

of micronuclei in the mouse bone marrow micronucleus assay, and did not increase the 

incidence of unscheduled DNA synthesis in rat hepatocytes/mammalian cells. 

3. Reproductive and developmental toxicity

Reproductive and 

Developmental 

toxicity) 

NOAEL = 25 mg/kg/day 

UF = 100 

FQPA SF = 1.X 

Prenatal developmental oral toxicity 

study in rates

LOA.EL = 100 mg/kg/day based on 

increased maternal diarrhea, urinary 

incontinence,: and salivation. 

4. Subchronic toxicity

Subchronic Toxicity NOAEL = 20 mg/kg/day 

UF = 100 

FQPA SF = 1.X 

90-Day feeding study in rats

LOA.EL = 211/223 mg/kg/day in 

males/females based on decreased 

body weight gain in both sexes and 

clinical signs indicative of reduced 

nutrition. 

5. Chronic Toxicity

Chronic Toxicity NOAEL = 18 mg/kg/day 

UF = 100 

Chronic RfD = 0.18 

mg/kg/day 

FQPA SF = 1.X 

cPAD = chronic RfD + FQPA 

SF = 0.18 mg/kg/day 

Combined chronic toxicity 

carcinogenicity feeding study in rates 

LOAEL = 34/117 mg/kg/day in 

males/females based on reduced body 

weights in both sexes and bile duct 

lesions in males. 

Azoxystrobin is classified “as not likely 

to be carcinogenic in humans” 

6. Animal metabolism. The metabolism of azoxystrobin as well as the nature of 

the residues is adequately understood.

7. Metabolite toxicology. There are no metabolites of concern based on 

a differential metabolism between plants and animals. 
8. Endocrine disruption. There is no evidence that azoxystrobin is an endocrine 

disrupter. 

C. Aggregate Exposure 

1. Dietary exposure. Acute (Tier III) and chronic (Tier III) dietary exposure 

evaluations were made for azoxystrobin using the Dietary Exposure Evaluation Model 

software with the Food Commodity Intake Database (DEEM-FCIDTM, version 2.16) from 

Exponent. All consumption data for these assessments were taken from the USDA’s 

Continuing Survey of Food Intake by individuals (CSFII) with the 1994-96 consumption 

database and the Supplemental CSFII children’s survey (1998) consumption database. 

These exposure assessments included all currently registered uses of azoxystrobin plus a 

proposed a proposed post-harvest use on potatoes. Residue data was taken from field trials 

where azoxystrobin was applied at the maximum intended use rate and samples were 

harvested at the minimum pre-harvest interval (PHI) to obtain maximum residue values. 

Calculated and projected percent crop treated (%CT) values were incorporated in these 

assessments. Anticipated residues in meat and milk were calculated by constructing 

theoretical nutritionally balanced diets. Drinking water estimates were included directly 

into the dietary exposure assessment using the higher of the estimated drinking water 

concentrations (EDWCs) for surface and ground water. 

. i. Food. Acute exposure. Dietary exposure from currently registered and proposed uses are 

acceptable. The azoxystrobin acute dietary (food only) risk assessment was performed for 

all population subgroups using an acute reference dose (aRfD) of 0.67 mg/kg/day based an 

acute neurotoxicity study in rats with a LOAEL of 200 mg/kg/day and an uncertainty 

factor of 300X (100X for intra- and inter-species variability and 3X for absence of a 

NOAEL). No additional FQPA safety factor was applied. For the purpose of the aggregate 

risk assessment, the exposure value was expressed in terms of margin of exposure (MOE), 

which was calculated by dividing the LOAEL by the exposure for each population 

subgroup. In addition, exposure was expressed as a percent of the acute reference dose 

(%aRfD). At the 99.9th percentile, acute dietary (food only) exposure to the U.S. 

population resulted in a MOE of 4,461 (6.7% of the aRfD of 0.67 mg/kg/day). The most 

sensitive sub-population was infants (<1 year old) with a MOE of 2,111 (14.1% of the aRfD 

of 0.67 mg/kg/day). Since the benchmark MOE for this assessment is 300 and since EPA 

generally has no concern for exposures below 100% of the aRfD, Syngenta believes that 

there is a reasonable certainty that no harm will result from dietary (food only) exposure to 

residues arising from all current and proposed uses for azoxystrobin. 

Chronic exposure. The azoxystrobin chronic dietary (food only) risk assessment was 

performed for all population subgroups using a chronic reference dose (cRfD) of 0.18 

mg/kg/day based on a combined chronic toxicity/carcinogenicity study in rats with a 

NOAEL of 18 mg/kg/day and an uncertainty factor of 100X (for combined intra- and interspecies variability). No additional FQPA safety factor was applied. For the purpose of the 

aggregate risk assessment, the exposure value was expressed in terms of MOE, which was 

calculated by dividing the NOAEL by the exposure for each population subgroup. In 

addition, exposure was expressed as a percent of the chronic reference dose (%cRfD). 

Chronic dietary (food only) exposure to the U.S. population resulted in a MOE of 9,610 

(1.0% of the cRfD of 0.18 mg/kg/day). The most sensitive sub-population was children (1-2 

years old) with a MOE of 3,685 (2.7% of the cRfD of 0.18 mg/kg/day). Since the 

benchmark MOE for this assessment was 100 and since EPA generally has no concern for 
exposures below 100% of the cRfD, Syngenta believes that there is a reasonable certainty 

that no harm will result from dietary (food) exposure to residues arising from all current 

and proposed uses for azoxystrobin. 

Cancer. Azoxystrobin has been classified as “not likely to be a human 

carcinogen” based on the revised Cancer Guidelines. Therefore, no cancer 

risk assessment was performed for azoxystrobin.

ii. Drinking water. The Estimated Drinking Water Concentrations (EDWCs) of 

azoxystrobin were determined using Tier l screening models, SCI-GROW which estimates 

pesticide concentration in ground water and FIRST which estimates pesticide 

concentration in surface water. EDWCs of azoxystrobin from the currently registered uses 

plus the proposed sugarcane use were determined. Based on the SCI-GROW modeling, the 

highest groundwater EDWC for azoxystrobin is 3.1 ppb (acute and chronic) based on the 

currently registered use on turf. Based on the FIRST modeling, the turf use provided the 

highest surface water EDWCs of 173 ppb for acute and 33 ppb for chronic. Since the 

surface water EDWCs exceed the ground water EDWC, the surface water values were used 

for risk assessment purposes and will be considered protective for any ground water 

concentration concerns.

Acute Exposure from Drinking Water: The acute surface water EDWC of 173 ppb was input 

directly into the DEEM-FCIDTM software as “water, direct and indirect, all sources” to 

model the acute drinking water exposures. Exposure contributions at the 99.9%-ile of 

exposures were determined by taking the difference between the aggregate (food + 

drinking water) exposures and the food (alone) exposures for each population subgroup. 

Acute drinking water exposure U.S. population resulted in a MOE of 1,936 (15.4% of the 

aRfD of 0.67 mg/kg-bw/day). The most exposed sub-population was all infants (<1 year 

old) with a MOE of 725 (41.2% of the aRfD of 0.67 mg/kg/day). Since the benchmark 

MOE for this assessment was 100 and since EPA generally has no concern for exposures 

below 100% of the aRfD, Syngenta believes that there is a reasonable certainty that no 

harm will result from acute drinking water exposure to residues arising from all current 

and proposed uses for azoxystrobin.

Chronic Exposure from Drinking Water: The chronic surface water EDWC of 33 ppb was 

input directly into the DEEM-FCIDTM software as “water, direct and indirect, all sources” 

to model the chronic drinking water exposures. Chronic drinking water exposure to the 

U.S. population resulted in a MOE of 25,878 (0.4% of the cRfD of 0.18 mg/kg-bw/day). 

Chronic drinking water exposure to the most exposed sub-population (infants <1 year old) 

resulted in a MOE of 7,893 (1.3% of the cRfD of 0.18 mg/kg-bw/day). Since the 

Benchmark MOE for this assessment was 100 and since EPA generally has no concern for 

exposures below 100% of the cRfD, Syngenta believes that there is a reasonable certainty 

that no harm will result from chronic drinking water exposure to residues arising from all 

current and proposed uses for azoxystrobin. 

Non-dietary exposure. Risk assessments were conducted for non-dietary uses of 

azoxystrobin since it is currently registered for residential use outdoors on turf and 

ornamentals and for use in residentially applied paint. Azoxystrobin may be applied to 

turf at rates of up to 1.19 lb a.i./acre (not to exceed 5 lb a.i./acre per year) and to 
ornamentals at rates of up to 0.75 lb a.i./acre (not to exceed 5 lb a.i./acre per year). The 

maximum concentration of azoxystrobin in paint is 1% a.i. (w/w). A short-term handler 

risk assessment was required for adults because there is a residential handler inhalation 

exposure scenario. Both short- and intermediate-term risk assessments were required for 

toddlers based on the potential for hand-to-mouth, object-to mouth, and soil ingestion 

exposure from treated turf. For incidental non-dietary oral and inhalation exposures to 

azoxystrobin, a NOAEL of 25 mg/kg/day was used for short-term exposure and a NOAEL 

of 20 mg/kg/day was used for intermediate-term exposure. No dermal assessment is 

required. 

For inhalation exposure scenarios, the MOE for adults (U.S. population) making 

applications of treated paint is 1,406 for short-term exposure. For post-application 

exposure to treated turf, the non-dietary oral MOEs for children 1-6 years are 1,399 for 

short-term exposure and 1,927 for intermediate-term exposure. Since the EPA’s 

benchmark MOE for azoxystrobin is 100, the residential exposures for both adults and 

children do not exceed EPA’s level of concern. 

Cumulative Effects. Cumulative Exposure to Substances with a Common Mechanism of Toxicity. 

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”. Azoxystrobin is related to the naturally occurring strobilurins. 

Syngenta has concluded that further consideration of a common mechanism of toxicity is 

not appropriate at this time since there is no data to establish whether a common 

mechanism exists with any other substances.

D. Safety Determination 

US. population The acute dietary exposure analysis (food plus water) showed that exposure 

from all registered and proposed azoxystrobin crop uses would result in a MOE of 1,349 

(22.1% of the aRfD) for the general U.S. population, which exceeds the benchmark MOE of 

300. The chronic dietary exposure analysis (food plus water) showed that exposure from 

all registered and proposed azoxystrobin crop uses resulted in a MOE of 7,007 (1.4% of the 

cRfD) which exceeds the benchmark MOE of 100. Based on the completeness and 

reliability of the toxicity data supporting these petitions, Syngenta believes that there is a 

reasonable certainty that no harm will result from aggregate exposure to residues arising 

from all current and proposed azoxystrobin crop uses, including anticipated dietary 

exposure from food, water, and all other types of non-occupational exposures.

1. Infants and Children The acute dietary exposure analysis (food plus water) showed that 

exposure from all registered and proposed azoxystrobin crop uses would result in a MOE 

of 539 (55.3% of the aRfD) for the most sensitive population subgroup, infants <1 year old, 

which exceeds the benchmark MOE of 300. The chronic aggregate dietary (food and 

water) exposure analysis showed that exposure from all registered and proposed 

azoxystrobin crop uses would result in a MOE of 3,042 (3.1% of the cRfD) for the most 

sensitive population subgroup, children (1-2 years old), which exceeds the benchmark 

MOE of 100. For short-term exposures, the dietary (food and water) exposure was 

aggregated with the residential exposure (MOE 1,399) resulting in a short-term aggregate 
MOE of 815 for the most sensitive population subgroup, children 1-6 years old. For 

intermediate-term exposures, the food plus water exposure was aggregated with the 

residential exposure (MOE 1,927) resulting in an intermediate-term aggregate MOE of 863 

for children 1-6 years old. The EPA has determined that there is reliable data support 

using the standard MOE and uncertainty factor (100X for chronic and 300X for acute) for 

azoxystrobin and that an additional safety factor of 10 is not necessary to be protective of 

infants and children. Based on the completeness and reliability of the toxicity data 

supporting these petitions, Syngenta believes that there is a reasonable certainty that no 

harm will result to infants and children from aggregate exposure to residues arising from 

all registered and proposed azoxystrobin crop uses, including anticipated dietary exposure 

from food, water, and all other types of non-occupational exposures. 

F. International Tolerances There are no Codex, Canadian, or Mexican MRLs for 

azoxystrobin in or on the proposed commodities. Therefore harmonization of tolerances is 

not an issue.