EPA REGISTRATION DIVISION COMPANY NOTICE OF FILING FOR PESTICIDE 

PETITIONS PUBLISHED IN THE FEDERAL REGISTER

EPA Registration Division contact: Shaunta Hill, (703) 347-8961

0F7751

EPA has received a pesticide petition (0F7751) 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 Grape at 3.5 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 the FFDCA; 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 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 pre-harvest 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 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-to-moderately 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.

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 NoObserved-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 SpragueDawley 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 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 

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 0.0143730 13.5

All infants (< 1 year) 0.0083360 9.1

Children 1-2 0.0261150 24.4

Children 3-5 0.0217070 20.4

Children 6-12 0.0144150 13.5

Youth 13-19 0.0114830 10.8

Adults 20-49 0.0139690 13.1

Adults 50+ yrs 0.0137380 12.9

Females 13 - 49 yrs 0.0133010 12.5

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 0.014373 0.000506 0.014879 13.5

All Infants (< 1 yr old) 0.11 0.008336 0.001658 0.009994 9.1

Children 1-2 years 0.11 0.026115 0.000751 0.026866 24.4

Children 3-5 years 0.11 0.021707 0.000703 0.02241 20.4

Children 6 – 12 years 0.11 0.014415 0.000485 0.0149 13.5

Youth 13-19 years 0.11 0.011483 0.000366 0.011849 10.8

Females 13-49 years 0.11 0.013969 0.000472 0.014441 13.1

Adults 20-49 years 0.11 0.013738 0.000497 0.014235 12.9

Adults + 50 0.11 0.013301 0.00047 0.013771 12.5

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.