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EPA REGISTRATION DIVISION COMPANY NOTICE OF FILING FOR 

PESTICIDE PETITIONS PUBLISHED IN THE FEDERAL REGISTER 

EPA Registration Division contact: [Shaunta Hill, 703/347-8961]

INSTRUCTIONS: Please utilize this outline in preparing the pesticide petition. In 

cases where the outline element does not apply, please insert “NA-Remove” and 

maintain the outline. Please do not change the margins, font, or format in your 

pesticide petition. Simply replace the instructions that appear in green, i.e., “[insert 

company name],” with the information specific to your action.

TEMPLATE:

[BASF Corporation]

[0F7695]

EPA has received a pesticide petition ([0F7695]) 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 by establishing a tolerance for residues of [ametoctradin, 5-

ethyl-6-octyl[1,2,4]triazolo[1,5-a]pyrimidin-7-amine] in or on the raw agricultural 

commodities [brassica, head and stem, subgroup, at 12 parts per million (ppm);

brassica, leafy greens, subgroup, at 50 ppm; grape at 5 ppm; hop, dried cones, at 9 

ppm; onion, bulb, subgroup, at 1.2 ppm; onion, green, subgroup, at 16 ppm; raisin 

at 8 ppm; vegetable, fruiting, group, at 2 ppm; vegetable, leafy, except brassica, 

group, at 70 ppm; vegetable, cucurbit, group, at 4.5 ppm; vegetable, tuberous and 

corm, subgroup, at 0.05 ppm ] and by establishing an exemption from the requirement 

of a tolerance [for the metabolites M650F03, (7-amino-5-ethyl[1,2,4]triazolo[1,5-

a]pyrimidine-6-y-l)acetic acid, and M650F04, 7-amino-5-ethyl[1,2,4]triazolo[1,5-

a]pyrimidine-6-carboxylic acid in all food crops.] EPA has determined that the 

petition contains data or information regarding the elements set forth in section 408 (d)(2) 

of 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. [Ametoctradin plant metabolism studies were performed 

in lettuce, tomato and potato. In all three plant metabolism studies, the metabolic 

pathways were comparable. Consequently, sufficient data are available to 

extrapolate the nature of the residue to other crops. In all three crops, unchanged 

parent compound ametoctradin was identified as the most prominent residue. In the 
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potato metabolism study with an exaggerated application rate of 1.5x, the two soil 

metabolites M650F03, (7-amino-5-ethyl[1,2,4]triazolo[1,5-a]pyrimidine-6-y-l)acetic 

acid, and M650F04, 7-amino-5-ethyl[1,2,4]triazolo[1,5-a]pyrimidine-6-carboxylic 

acid, in all food crops were found in small amounts in tubers.]

2. Analytical method. [The proposed enforcement method for ametoctradin

was fully validated. Ametoctradin is extracted with a mixture of methanol/water. 

An aliquot of the extract is centrifuged and partitioned against dichloromethane. 

The final determination of ametoctradin is performed by HPLC-MS/MS. This 

method has a limit of quantitation of 0.01 mg/kg and is suitable for enforcement 

purposes. ]

3. Magnitude of residues. [Supervised field trials were carried out to 

determine the magnitude of the residue in/on brassica, head and stem, subgroup;

brassica, leafy greens, subgroup; grape; hop; dried cones; onion, bulb, subgroup;

onion, green, subgroup; raisin; vegetable, fruiting, group; vegetable, leafy, except 

brassica; vegetable, cucurbit, group; and vegetable, tuberous and corm, subgroup. 

The number and locations of field trials are in accordance with OPPTS Guideline 

860.1500. Field trials were carried out using the maximum label rates, the maximum 

number of applications, and the minimum pre-harvest interval (PHI) for all the 

crops. Detected residues of BAS 650 F in all crops support the proposed tolerances.]

B. Toxicological Profile

1. Acute toxicity. 

[BAS 650 F and its formulated products have a favorable acute toxicity profile. 

The acute toxicity studies place technical BAS 650 F in the toxicity category III for 

the acute oral and the acute dermal category and category IV for the acute 

inhalation. BAS 650 F is category IV for both eye and skin irritation and is not a 

dermal sensitizer. ]

2. Genotoxicty. [BAS 650 F was tested for its genotoxic potential in a battery 

of six in vitro or in vivo studies covering the required endpoints of point mutations, 

chromosomal damage and DNA damage and repair. BAS 650 F did not 

demonstrate any genotoxic effects. BAS 650 F was negative for inducing mutations 

in both an in vitro Ames test and an in vitro forward mutation assay in mammalian 

cells (HPRT test with and without metabolic activation). Both an in vitro and an in 

vivo chromosome aberration assay (with and without metabolic activation) showed 

no evidence of a clastogenic effect. An in vivo micronucleus test and an in vivo

unscheduled DNA synthesis (UDS) test were also negative. These studies 

demonstrate that BAS 650 F is not genotoxic.]

3. Reproductive and developmental toxicity. [The reproductive and 

developmental toxicity of ametoctradin was investigated in a 2-generation rat 

reproduction study as well as in rat and rabbit developmental toxicity studies. In the 

reproduction study, there were no effects on fertility. There were no parental 

toxicity or pup effects at any of the tested doses (up to and including the limit dose). 
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The resulting parental systemic and developmental toxicity NOAEL’s are 1000 

mg/kg bw.

In the rat developmental toxicity study, the administration of ametoctradin elicited 

no signs of maternal toxicity, had no influence on gestational parameters and 

induced no signs of developmental toxicity at the dose levels tested (up to and 

including the limit dose). Based on these results, the no observed adverse effect level 

(NOAEL) in rat for maternal and prenatal developmental toxicity is the limit dose 

level of 1000 mg/kg bw/d.

The administration of ametoctradin to rabbits elicited no signs of maternal toxicity, 

had no influence on gestational parameters and induced no signs of developmental 

toxicity at the dose levels tested (up to and including the limit dose). Based on these 

results, the no observed adverse effect level (NOAEL) in rabbit for maternal and 

prenatal developmental toxicity is the limit dose level of 1000 mg/kg bw/d.]

4. Subchronic toxicity. [The subchronic toxicity of ametoctradin was 

investigated in 90-day feeding studies with rats, mice and dogs as well as a dermal 

28-day repeat dose study with rats. Dosing at limit doses (about 1000 mg/kg bw) in 

these studies caused no substance-related adverse findings. Due to the lack of 

adverse findings, target organs were not identified. The lowest NOAEL in 

subchronic oral toxicity studies was 912 mg/kg bw/day in the dog 90-day study.

The neurotoxic potential of ametoctradin was studied following both acute and 

subchronic oral administration in the rat. In the acute neurotoxicity study there 

were no test-item related findings in the clinical examinations, functional 

observational battery or the measurement of motor activity at doses up to and 

including the limit dose (2000 mg/kg bw). Nor did neuropathology reveal any 

indications for neurotoxicity at the limit dose. Therefore, ametoctradin did not 

cause neurotoxicity up to the limit dose of 2000 mg/kg body weight in animals of 

both sexes.

Ametoctradin was also tested in rats in a subchronic neurotoxicity study at doses up 

to 15000 ppm in the diet (921.2 mg/kg bw, male and 1077.2 mg/kg bw, female) over a 

period of three months. There were no test-item related findings in the clinical 

examinations, functional observational battery or the measurement of motor 

activity. The neuropathological treatment-related findings (included brain weight 

determination, necropsy and neuropathological examinations by light microscopy) 

also showed no treatment-related findings. In summary, ametoctradin did not show 

any neurotoxic potential up to the limit dose of 15000 ppm (921.2 mg/kg bw, male 

and 1077.2 mg/kg bw, female).]

5. Chronic toxicity. [The results of long-term oral exposure studies indicate 

that ametoctradin is not carcinogenic in mice or rats. The chronic 

toxicity/oncogenicity studies with ametoctradin included a 12-month feeding study 

with Beagle dogs, an 18-month C57BL/6 J Rj mouse feeding study and a 24-month 
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Wistar rat chronic/oncogenicity study.

At the limit dose in Beagle dogs, Wistar rats and C57BL/6 J Rj mice there was no 

test substance-related adverse findings or evidence of carcinogenicity. The resulting 

NOAEL’s in the mouse oncogenicity study were 6000 ppm for both sexes (1099 

mg/kg bw for the male and 1543 mg/kg bw for the female). In the rat 

chronic/oncogenicity study the NOAEL’s were 15000 ppm for both sexes (870.7 

mg/kg bw for the male and 979.3 mg/kg bw for the female). In the chronic dog 

study, the NOAEL’s were 30000 ppm for both sexes (848 mg/kg bw for the male and 

936 mg/kg bw for the female).]

6. Animal metabolism. [Rat, goat and hen metabolism studies were conducted

to determine the nature of ametoctradin residues in animals. All studies were 

conducted with radio labeled ametoctradin. In ruminants and poultry ametoctradin 

is rapidly absorbed and excreted. Ametoctradin is metabolized in goats and hens by 

oxidation of the aliphatic side chain to the respective terminal carboxylic acid and 

subsequent stepwise oxidative cleavage of the side chain (loss of C2-units) analogous to 

the -oxidation of fatty acids. The metabolic pathways in rats, goats and hens were 

qualitatively similar.]

7. Metabolite toxicology. [No metabolites of toxicological concern were 

identified. M650F03 and M650F04, soil metabolites of BAS 650 F, were evaluated for 

toxicological relevance. These metabolites are structurally similar to each other and to the 

parent ametoctradin. To further investigate the metabolites’ properties, genotoxicity 

studies and sub-chronic dietary studies in the rat were conducted. M650F03 was not 

genotoxic in an Ames test (with and without S-9 activation) or in an HPRT test in CHO cells 

(with and without S-9 activation). No sign of chromosomal aberrations was present in vitro

(V79 cells, with and without S-9 activation) or in vivo (NMRI mice, micronucleus test). The 

90-day dietary study demonstrated that as with the parent, administration of M650F03 at 

dose levels up to and including the limit dose resulted in no adverse substance-related 

findings. M650F04 was not genotoxic in an Ames test (with and without S-9 activation) or 

in an HPRT test in CHO cells (with and without S-9 activation). M650F04 caused no 

clastogenic effects in vitro (V79 cells, with and without S-9 activation). The 90-day dietary 

study demonstrated that as with the parent, administration of M650F04 at dose levels up to 

and including the limit dose resulted in no adverse substance-related findings. Studies with 

the M650F03 and M650F04 metabolites confirmed that they are not toxicologically 

relevant.] 

8. Endocrine disruption. [No specific tests have been conducted with 

ametoctradin to determine whether the chemical may have an effect in humans that 

is similar to an effect produced by a naturally occurring estrogen or other endocrine 

effects. However, there were no significant findings in other relevant toxicity studies 

(e.g., sub-chronic and chronic toxicity, developmental toxicity and multi-generation 

reproductive studies) which would suggest that ametoctradin produces any 

endocrine disruption.]
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C. Aggregate Exposure

1. Dietary exposure. [The dietary exposure assessment for ametoctradin was 

conducted using tolerance level residues, 100% crop treated factors, and default 

processing factors. The crops and residue values used in the assessment were: 

brassica, head and stem, subgroup, = 12 parts per million (ppm); brassica, leafy 

greens, subgroup = 50 ppm; grape = 5 ppm; hop, dried cones = 9 ppm; onion, bulb, 

subgroup = 1.2 ppm; onion, green, subgroup = 16 ppm; raisin = 8 ppm; vegetable, 

fruiting, group = 2 ppm; vegetable, leafy, except brassica, group = 70 ppm; 

vegetable, cucurbit, group = 4.5 ppm; vegetable, tuberous and corm, subgroup =

0.05 ppm. An acute dietary endpoint was not determined because there was no 

toxicological effect from a single exposure to ametoctradin. The chronic dietary 

endpoint is based on a NOAEL of 871 mg/kg bw – day with a safety factor of 100 

which resulted in a cPAD = 8.71 mg/kg bw –day. ]

i. Food. [

Acute Dietary Exposure Assessment

An acute assessment was not needed since there were no toxic effects attributable to 

a single dose. Therefore, a quantitative acute dietary exposure and risk assessment 

were not required. 

Acute Dietary Exposure Assessment

The chronic dietary exposure is shown in the table below. The exposure includes all 

food commodities and drinking water. The dietary (food + drinking water) utilized 

less than 1% of the cPAD for all populations. 

Table 1. Summary of Chronic Dietary Exposure Assessment 

Considering All Proposed Tolerances for ametoctradin. The assessment includes 

food + drinking water.

Population

Subgroups

Exposure Estimate

(mg/kg b.w./day) %cPAD

U.S. Population 0.037532 0.4

All Infants 0.022184 0.3

Children 1-2 years 0.054469 0.6

Children 3-5 years 0.050184 0.6

Children 6-12 years 0.037335 0.4

Youth 13-19 years 0.030329 0.3

Adults 20-49 years 0.036924 0.4

Adults 50+ years 0.037945 0.4

Females 13 - 49 0.037273 0.4

%cPAD = percent of chronic population adjusted dose 

Exposure estimates based on tolerance values, default 

processing factors, and 100% CT for all crops/commodities
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The results indicate that the exposure for ametoctradin is well below the EPA level 

of concern.

The risk assessment was repeated with contribution from the metabolite residues in 

rotational crops. The highest total residue value of 0.8 ppm was observed in the 

field rotational crop study, derived from the sum of the M650F03 and M650F04 

residues in parent equivalents from a 118-day wheat straw sample. For this 

assessment, this value of 0.8 ppm was applied to all crops in the DEEM database 

that could possibly be considered for crop rotation. 315 commodities were included. 

In addition, this value was also applied to potato commodities, since it is higher than 

the proposed tolerance in potatoes. The result of this assessment is shown in Table 

2.

Table 2. Chronic Dietary Risk Assessment considering 

parent residue on target crops and 0.8 ppm 

metabolite residue in rotational crops

(315 commodities included)

Consumer Group %ADI

US Population (total) 0.4

All infants (<1 yr) 0.4

Children 1-2 yrs 0.8

Children 3-5 yrs 0.7

Children 6-12 yrs 0.5

Youth 13-19 yrs 0.4

Adults 20-49 yrs 0.5

Adults 50+ 0.5

Females 13-49 yrs 0.5

This assessment is overly conservative, especially considering the fact that 

metabolite residues in rotational crops were relatively low in consumer food items, 

compared to feed items. When the results from the two risk assessments are 

compared, it can be seen that there is no significant difference in the consumer risk 

assessment when the two soil metabolites are included. All consumer groups are 

below 1% of the ADI for both assessments.] 

ii. Drinking water.

[The drinking water exposure was modeled for all proposed uses using the proposed 

label directions and the appropriate environmental fate data for ametoctradin. The 

highest drinking water values were obtained from the PA tomato scenario. Based 

on the PRZM/EXAMS model, the peak EDWCs for chronic exposure are estimated 

to be 0.206 ug/L in surface water.
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Acute Aggregate Exposure and Risk (Food and water)

Toxicology studies have shown that ametoctradin poses no acute dietary risk. 

Therefore an acute aggregate exposure assessment was not required.

Short- and Intermediate Term Aggregate Exposure and Risk (food, water, and 

residential)

Residential uses for ametoctradin are not being pursued, therefore a short and 

intermediate term aggregate exposure and risk assessment was not required.

Chronic Aggregate Exposure and Risk (food and water)

The aggregate chronic risk includes residues of ametoctradin from food and water 

(Table 1). The results demonstrate there are no safety concerns for any 

subpopulation based on the proposed new uses, and that the results clearly meet the 

FQPA standard of reasonable certainty of no harm.]

2. Non-dietary exposure. [Residential uses for ametoctradin are not being 

pursued, therefore, a non-dietary exposure and risk assessment was not required. ]

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." Unlike other 

pesticides for which EPA has followed a cumulative risk approach based on a 

common mechanism of toxicity, EPA has not made a common mechanism of toxicity 

finding as to ametoctradin. In addition, ametoctradin does not produce a toxic 

metabolite produced by other substances. Therefore, for the purposes of this 

tolerance action, BASF assumes that ametoctradin does not have a common 

mechanism of toxicity with other substances.]

E. Safety Determination

1. U.S. population. [Based on this risk assessment, BASF concludes that there 

is a reasonable certainty that no harm will result to the general population from the 

aggregate exposure to ametoctradin.]

2. Infants and children. [Based on this risk assessment, BASF concludes that 

there is a reasonable certainty that no harm will result to infants or children from 

the aggregate exposure to ametoctradin.]

F. International Tolerances

[A maximum residue level (MRL) has not been established for ametoctradin

in any crop by the Codex Alimentarius Commission.]