i

EPA REGISTRATION DIVISION COMPANY NOTICE OF FILING FOR 

PESTICIDE PETITIONS PUBLISHED IN THE FEDERAL REGISTER 

EPA Registration Division contact: [insert name and telephone number with area 

code]

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

[Insert petition number]

EPA has received a pesticide petition ([insert petition number]) from BASF 

Corporation, P.O. Box 13528, Research Triangle Park, North Carolina, 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

Dimethomorph [(E,Z)4-[3-(4-chlorophenyl)-3-(3,4-dimethoxyphenyl)-1-oxo-2-

propenyl]-morpholine] in or on the raw agricultural commodity Leafy Vegetables at 16

parts per million (ppm). 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. Based upon the results of metabolism studies conducted on 

potato, grape, and lettuce, the nature of the residues in Grapes is considered to be 

understood. The results of the potato metabolism study show only negligible residues in 

tubers, 0.01-0.02 parts per million (ppm) total radioactive residues (TRR). This is in 

contrast to the aerial portions of the plant, which were found to have up to 23.5 ppm 

TRR, thus demonstrating that translocation of dimethomorph downward within the plant 

was not significant. Almost all of the radioactive residue (97.8%) was extractable from 

the plant at harvest. In the aerial portion of the plant, approximately 70% of the TRR was 
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identified as dimethomorph. No metabolites were identified that require regulation.

The results of the grape metabolism study showed that the TRR in/on grapes 

harvested 35 days following the last of four applications [0.8 lb active ingredient per acre 

(ai/A) per application for four consecutive weeks] for a total rate of 3.2 lb ai/A was 14.6 

ppm. Unmetabolized dimethomorph accounted for 87.3% of the TRR (12.7 ppm). No 

metabolites were identified that require regulation.

The results of the lettuce metabolism study showed that the TRR in/on lettuce leaves 

harvested 4 days following the last of 4 applications [approximately 1.0 lb ai/A per 

application with a 9 to 11 day spray interval], for a total rate of 4.1 lb ai/A, was 102 ppm. 

Of this total residue, 98.5% was extractable and unmetabolized dimethomorph accounted 

for greater than 93% of the extractable TRR. No metabolites were identified that require 

regulation.

2. Analytical method. A reliable method for the determination of dimethomorph 

residues in Grapes exists; this method is the FDA Multi-Residue Method, Protocol D, as 

published in the Pesticide Analytical Manual I.

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

magnitude of the residue in/on grapes. 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 preharvest interval (PHI) for all the crops. Detected residues of Dimethomorph in all crops 

support the proposed tolerances.

B. Toxicological Profile

1. Acute toxicity. i. Oral LD50 studies were conducted on dimethomorph 

technical:

a. An acute oral toxicity study in the Sprague-Dawley rat for dimethomorph technical 

with a LD50 of 4,300 milligrams/kilogram body weight (mg/kg b.w.) for males and 3,500 

mg/kg b.w. for females. Based upon EPA toxicity criteria, the acute oral toxicity

category for dimethomorph technical is Category III or slightly toxic.

b. An acute toxicity study in the CD-1 mouse for dimethomorph technical with a LD50 

of greater than 5000 mg/kg b.w. for males and 3699 mg/kg/b.w. for females. Based on 

the EPA toxicity category criteria, the acute oral toxicity category for dimethomorph 

technical is Category III or slightly toxic.

ii. Oral LD50 studies were conducted on the two isomers (E and Z) alone:

a. An acute oral toxicity study in the Wistar rat for the E-isomer with a LD50 greater 

than 5,000 mg/kg b.w. for males and approximately 5,000 mg/kg b.w. for females. 

 b. An acute oral toxicity study in the Wistar rat for the Z-isomer with a LD50 greater 

than 5,000 mg/kg b.w. for both males and females.

iii. An acute dermal toxicity study in the Wistar rat for dimethomorph technical with a 

dermal LD50 greater than 5,000 mg/kg b.w. for both males and females. Based on 

the EPA toxicity category criteria, the acute dermal toxicity category for 

dimethomorph is Category IV or relatively non-toxic.

iv. A 4-hour inhalation study in Wistar rats for dimethomorph technical with a LC50 

greater than 4.2 mg/L for both males and females. Based on the EPA toxicity category
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criteria, the acute inhalation toxicity category for dimethomorph technical is Category IV 

or relatively non-toxic.

v. A skin irritation study was performed using New Zealand White rabbits. Based on 

the EPA toxicity criteria, the skin irritation toxicity category for dimethomorph technical 

in this study is Category IV or non-to-slightly irritating.

vi. An eye irritation study using New Zealand White rabbits demonstrated 

dimethomorph technical produced moderate conjunctival redness, slight to moderate 

chemosis and slight discharge three hours after treatment. Based on the EPA toxicity

criteria, the eye toxicity category for dimethomorph technical is Category III (slightly-tomoderately irritating).

2. Genotoxicty. i. Salmonella reverse gene mutation assays (2 studies) were 

negative up to a limit dose of 5,000 g/plate. Chinese hamster lung V79 cells were 

negative for mutations at the HGPRT locus at up to toxic doses in two studies.

ii. Two Chinese hamster lung (V79 cells) structural chromosomal studies were 

reportedly positive for chromosomal aberrations at the highest dose tested (HDT) 

(160 g/ml/-S9; 170 g/ml/+S9). However, dimethomorph induced only a weak 

response in increasing chromosome aberrations in this test system. In addition, 

these results were not confirmed in two micronucleus tests under in vivo conditions.

iii. Structural Chromosomal Aberration studies were weakly positive in human 

lymphocytic cultures, but only in S9 activated cultures treated at 422 g/ml, the 

highest dose tested (HDT), which was strongly cytotoxic. No increase in 

chromosomal aberrations was observed in the absence of S9 activation at all doses. 

Furthermore, the positive clastogenic response observed under the in vitro 

conditions was not confirmed in two in vivo micronucleus assays.

iv. Micronucleus assay (2 studies) indicated that dimethomorph was negative for 

inducing micronuclei in bone marrow cells of mice following i.p. administration of 

doses up to 200 mg/kg or oral doses up to the limit dose of 5,000 mg/kg. Thus, 

dimethomorph was found to be negative in these studies for causing cytogenic 

damage in vivo.

v. Dimethomorph was negative for inducing unscheduled DNA synthesis, in cultured 

rat liver cells, at doses up to 250 g/ml, a weakly cytotoxic level.

vi. Dimethomorph was negative for transformation in Syrian hamster embryo cells 

treated, in the presence and absence of activation, up to cytotoxic concentrations 

(265 g/ml/+S9; 50 g/ml/-S9).

3. Reproductive and developmental toxicity. i. A rat developmental toxicity study

with a Lowest-Observed-Effect Level (LOEL) for maternal toxicity of 160 mg/kg/day

and a No-Observed-Effect Level (NOEL) for maternal toxicity of 60 mg/kg/day. The 

NOEL for developmental toxicity is 60 mg/kg/day. Dimethomorph is not teratogenic in 

the Sprague-Dawley rat.

ii. A rabbit development toxicity study with a LOEL for maternal toxicity of 650 

mg/kg/day and a NOEL for maternal toxicity of 300 mg/kg/day. The NOEL for 

developmental toxicity is 650 mg/kg/day, the highest dose tested. Dimethomorph is not 

teratogenic in the New Zealand white rabbit.

iii. A two-generation rat reproduction study with a LOEL for parental systemic toxicity of 
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1000 ppm, or approximately 80 mg/kg/day, and a NOEL for parental systemic toxicity of 

300 ppm, or approximately 24 mg/kg/day. The NOEL for fertility and reproductive 

function was 1000 ppm, the highest concentration tested, or approximately 80 mg/kg 

b.w./day.

4. Subchronic toxicity. i. A 90-day dietary study in Sprague-Dawley rats with a 

NOEL of greater than or equal to 1000 ppm, the highest concentration tested, or 

approximately 73 mg/kg/day for males and 82 mg/kg/day for females.

ii. A 90-day dog dietary study with a NOEL of 450 ppm, or approximately 15 

mg/kg/day, and a LOEL of 1350 ppm, or approximately 43 mg/kg/day.

5. Chronic toxicity. i. A 2-year chronic toxicity study in Sprague-Dawley rats with 

a NOEL of 200 ppm or approximately 9 mg/kg/day for males and 12 mg/kg/day for 

females. The LOEL for systemic toxicity is 750 ppm, or approximately 36 mg/kg/day for 

males and 58 mg/kg/day for females.

ii. A 1-year chronic toxicity study in dogs with a NOEL of 450 ppm, or approximately

14.7 mg/kg/day and a LOEL of 1350, or approximately 44.6 mg/kg/day.

iii. A 2-year oncogenicity study in Sprague-Dawley rats with a NOEL for systemic 

toxicity of 200 ppm, or approximately 9 mg/kg/day for males and 11 mg/kg/day for 

females. The LOEL for systemic toxicity was 750 ppm, or approximately 34 mg/kg/day

for males and 46 mg/kg/day for females. There was no evidence of increased incidence 

of neoplastic lesions in treated animals. The NOEL for oncogenicity is 2000 ppm, the 

highest concentration tested, or approximately 95 mg/kg/day for males and 132 

mg/kg/day for females.

iv. A 2-year oncogenicity study in CD-1 mice with a NOEL for systemic toxicity of 100 

mg/kg/day and a LOEL of 1,000 mg/kg/day. There was no evidence of increased 

incidence of neoplastic lesions in treated animals. The NOEL for oncogenicity is 1,000 

mg/kg/day, the highest dose tested.

6. Animal metabolism. Results from the livestock and rat metabolism studies 

show that orally administered dimethomorph was rapidly excreted by the animals. The 

principal route of elimination is the feces.

7. Metabolite toxicology. There were no metabolites identified in plant or animal 

commodities which require regulation.

8. Endocrine disruption. Collective organ weights and histopathological findings 

from the two-generation reproduction study in rats, as well as from the subchronic and 

chronic toxicity studies in two or more animal species, demonstrate no apparent 

estrogenic effects or effects on the endocrine system. There is no information available 

that suggests that dimethomorph technical would be associated with endocrine effects.

C. Aggregate Exposure

1. Dietary exposure. An assessment was conducted to evaluate the potential risk 

due to chronic dietary exposure of the U.S. population and sub-populations to residues of 
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dimethomorph. This analysis included all currently proposed tolerances listed in U.S. 40 

CFR § 180.493 and the proposed tolerances for grapes.

i. Food. Acute Dietary Exposure Assessment

An acute assessment was not needed since the U.S. EPA Toxicological Endpoint 

Selection (TES) Committees had previously evaluated the dimethomorph toxicity data, 

including developmental and maternal toxicity in the developmental toxicity studies and 

determined there was no toxicologic endpoints for acute dietary exposure and a 

quantitative acute dietary exposure and risk assessment were not required. 

Chronic Dietary Exposure Assessment

A Tier 1 chronic dietary exposure assessment was conducted assuming tolerance level 

residues and 100% crop treated factors for all registered and proposed crops. The EPA 

Food Commodity Ingredient Database (FCID) was also used in Exponent's Dietary

Exposure Evaluation Module (DEEM-FCID) software. Inadvertent residues in animal 

commodities (i.e. meat, meat byproducts, milk, eggs) were not considered as a result of 

grain forage since studies have shown dimethomorph does not accumulate in animal 

tissues or milk and tolerance values for these commodities are not required by the EPA.

Dietary exposure estimates were compared against the established dimethomorph chronic 

Population Adjusted Dose (cPAD) of 0.11 mg/kg b.w./day for all populations. Results of 

the chronic dietary assessments are listed in the table below. The estimated chronic 

dietary exposure from crops (both established and proposed tolerances) was less than 

25% of the cPAD for all subpopulations (Table 1). Additional refinements such as the 

use of anticipated residues would further reduce the estimated chronic dietary exposure. 

The results in the Table below demonstrate that there are no safety concerns for any 

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

FQPA standard of reasonable certainty of no harm.

Table 1. Summary of Chronic Dietary Exposure Assessment considering crops with 

established and proposed tolerances for Dimethomorph.

Population sub-group

Chronic Exposure 

(mg/kg bw/day) %cPAD

US Population 0.008577 7.8

All infants (< 1 year) 0.005436 4.9

Children 1-2 0.0162585 14.8

Children 3-5 0.013308 12.1

Children 6-12 0.0084945 7.7

Youth 13-19 0.0064905 5.9

Adults 20-49 0.00818175 7.4

Adults 50+ yrs 0.00847875 7.7

Females 13 - 49 yrs 0.007917 7.2
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ii. Drinking water. The chronic drinking water values used in this analysis were 

the values proposed by EPA Federal Register Notice, September 29, 2003, Volume 68, 

No. 188. The chronic drinking water value used was 28.3 ug/L. 

Table 2. Summary of Chronic Drinking Water Exposure Assessment Considering 

the Maximum Estimated Chronic Drinking Water Concentration for 

Dimethomorph.

Population sub-group Chronic Exposure (mg/kg bw/day) %cPAD

US Population 0.000506 0.46

All infants (< 1 year) 0.001658 1.51

Children 1-2 0.000751 0.68

Children 3-5 0.000703 0.64

Children 6-12 0.000485 0.44

Youth 13-19 0.000366 0.33

Adults 20-49 0.000472 0.43

Adults 50+ yrs 0.000497 0.45

Females 13 - 49 yrs 0.00047 0.43

Acute Aggregate Exposure and Risk (Food and water)

Since the U.S. EPA Toxicological Endpoint Selection (TES) Committees has evaluated 

the dimethomorph toxicity data and determined there was no toxicologic endpoints for 

acute dietary exposure, the determination of an acute aggregate exposure and risk 

evaluation was not required. 

Chronic Aggregate Exposure and Risk (food and water)

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

(Table 3). Exposures from residential uses are not included in the chronic aggregate 

assessment. The results demonstrate there are no safety concerns for any subpopulation 

based on established and new uses, and that the results clearly meet the FQPA standard of 

reasonable certainty of no harm.

Table 3. Estimated Chronic Aggregate Exposure and Risk for Dimethomorph.

Population Subgroup

cPAD 

(mg/kg/day)

Food 

Exposure 

(mg/kg/day)

Water 

Exposure 

(mg/kg/day)

Total 

Exposure 

(mg/kg/day) % cPAD

U.S. Population 0.11 0.008577 0.000506 0.009083 8.3

All Infants (< 1 yr old) 0.11 0.005436 0.001658 0.007094 6.4

Children 1-2 years 0.11 0.0162585 0.000751 0.0170095 15.5

Children 3-5 years 0.11 0.013308 0.000703 0.014011 12.7

Children 6 – 12 years 0.11 0.0084945 0.000485 0.0089795 8.2

Youth 13-19 years 0.11 0.0064905 0.000366 0.0068565 6.2

Females 13-49 years 0.11 0.00818175 0.000472 0.00865375 7.9
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Adults 20-49 years 0.11 0.00847875 0.000497 0.00897575 8.2

Adults + 50 0.11 0.007917 0.00047 0.008387 7.6

2. Non-dietary exposure. Dimethomorph is not registered for use on any sites that 

would result in residential exposure. Therefore, a residential exposure and risk 

assessment was not conducted.

D. Cumulative Effects

There is no information to indicate that any toxic effects produced by 

dimethomorph would be cumulative with those of any other chemical. The fungicidal 

mode of action of dimethomorph is unique; dimethomorph inhibits cell wall formation 

only in Oomycete fungi. The result is lysis of the cell wall that kills growing cells and 

inhibits spore formation in mature hyphae. This unique mode of action and limited pest 

spectrum suggest that there is little or no potential for cumulative toxic effects in 

mammals. In addition, the toxicity studies submitted to support this petition do not 

indicate that dimethomorph is a particularly toxic compound. No toxic end-points of 

potential concern were identified.

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 dimethomorph residues.

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 dimethomorph residues.

F. International Tolerances

There are no Canadian, Mexican, or Codex MRLs established for dimethomorph 

for the commodities associated with this request; consequently, a discussion of 

international harmonization is not relevant.