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**EPA REGISTRATION DIVISION COMPANY NOTICE OF FILING FOR PESTICIDE PETITIONS PUB**  **LISHED IN THE FEDERAL REGISTER EPA**  **Registration Division contact:**  **[ Shaja Joyner, PM**  **- 20, (703)**  **- 308**  **- 3194**  **] INSTRUCTIONS:**  **Please utilize this outline in pr**  **eparing 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 app ear 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] requesting, 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 [Dimethomorph (BAS 550 F) [( E,Z)4
- [3
- (4
- chlorophenyl )
- 3
- (3,4
- dimethoxy

phenyl )
- 1
- oxo - 2
-propenyl ]
- morpholine] its metabolites and degradates] in or on the raw agricultural commodity [strawberry] at [1.0] parts per million (ppm) and to amend 40 CFR part 180 b [replacing] a tolerance for residues of [Dimethomorph (BAS 550 F) [(E,Z)4
- [3
- (4
- chlorophenyl)
- 3
- (3, 4
- dimethoxy phenyl )
- 1
- oxo - 2
-propenyl]
- morpholine] its metabolites and degradates] in or on the raw agricultural commodity [lettuce, head] from [10] ppm and [lettuce, leaf] at [10] ppm [ to 30 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 supp orts 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 strawberry i s considered to be understood. The results of the potato metabolism study demonstrated that only negligible total radioactive residues (TRR) were found in tubers, 0.01
- 0.02 parts per million (ppm
. 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 extracta ble from the plant at harvest. Inthe aerial portion of the plant, approximately 70% of the TRR was identified as dimethomorph
. No metabolites were identified that require2

regulation. The results of the grape metabolism study showed that the TRR in/on grapes harvested 35 day s following the last o f four applications [0.8 lb active ingredient per acre (ai/A) per application for four consecutive weeks] for a total rat e of 3.2 lb ai/A was 14.6 ppm. Unmetabolized dimethomorph accounted fo r 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. Sinc e the metabolism between the three representative crops is not different, these metabolism studies are considered to be adequate to understand the nature of the residue in diverse crop groups and as such, an additional metabolism study in strawberries is not required. ] 2. Analytical metho d. [ A reliable method for the determination of dimethomorph residues in plant matrices exists
. The determination of the dimethomorph residues in strawberries was performed according to the anal ytical BASF Method No. L0013, Method for the determination of g eometric isomers of BAS 550 F . The final determination of BAS 550 F was performed b y LC
- MS/MS at a L OQ of 0.005 mg/kg
. The method has been validated in the context of this residue study
. ] 3. Magnitude of residues. [ Supervised field trials were carried out to determine the magnitude of the residue in/on strawberries
. The number and locations of field trials are in accordance with OCSPP Guideline 860.1500 and Directive 98
- 02, Section 9. Eight field trials were conducted encompassing Regions 1 (PA; 1 trial), 2 (AL; 1 trial ) , 3 (FL ; 1 trial), 5 (WI ; 1 trial), 10 ( CA; 3 trials) and 12 (OR; 1 trial) during the 2013 growing season. The treated plot at each site received 3 applications of dimethomorph at a rate of 0.2 lb ai/A for a total seasonal rate of 0.6 lb ai/A with a PHIof 0 days after the last application. Detected residues of Dimethomorph in strawberries support the proposed tolerance. ] B. Toxicological Profile 1. Acute toxicity. [ i. Oral LD50 studies were conducted on dimethomorph technical: a. An acute or al toxicity study in the Sprague
- Dawley

rat for dimethomorph technical with a LD 50 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 slightl y t oxic. 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 toxicity3 category for dimethomorph technical is Category III or slightly

toxic. ii. Oral LD 50 studies were conducted on the two isomers (E and Z) alone: c. An acute oral toxicity study in the Wistar rat for the E
- isomer with a LD 50 greater than 5,000 mg/kg b.w. for males and approximately 5,000 mg/kg b.w. for females. d. An acute oral toxicity study in the Wistar rat for the Z
- isomer with a LD 50 greater than 5,000 mg/kg b.w. for both males and females. iii. An acute dermal toxicity study in the Wis tar rat for dimethomorph technical with a dermal LD 50 greater than 5,000 mg/kg b.w. for bo th males and females. Based on the EPA toxicity

category criteria, the acute dermal toxicity category for dimethomorph is Category IVor relatively non - toxic. iv. A 4
- hour inhalation study in Wistar rats for dimethomorph technical with a L C 50 greater than 4.2 m g/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 - slightl y 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 e ye irritation category for dimethomorph technical is Category III (slightl y- to - moderatel y 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 cy to toxic doses in two studies. ii. Structural Chromosomal Aberration studies were presumptivel y weakly positive in human ly mphocy tic cultures, but only

in S9 activated cultures treated at 422  g/ml, the highest dose tested (HDT), which was strongl y c ytotoxic. 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 n ot confirmed in two in vivo micronucleus assays. iii. 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 cy togen etic damage in vivo. iv. Dimethomorph was negative for transformation in Sy rian hamster embryo cells treated, in the presence and absence of activ ation, up to cy totoxic 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 604 mg/kg/day
. Dimethomorph is not teratogenic in the Sprague
- Dawley rat. ii. A rabbit development toxicity study with a LOELfor maternal toxicity of 650 mg/kg/day

and a NOEL for mater

nal 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 LOE L for parental sy stemic toxicity of 1000 ppm, or approximately 80 mg/kg/day , and a NOEL for parental sy stemic toxicity

of 300 ppm, or approximately 24 mg/kg/day
. The NOEL for fertility and reproductive function was 1000 ppm, the highest concentration teste d, 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 1 50 ppm or approximately

9.4 mg/kg/day

for males and 11.9 mg/kg/day for females. The LOEL for s ys temic toxicity is 450 ppm, or approximately 36.2 mg/kg/day

for males and 57.7 mg/kg/day for females. ii. A 1
- ye ar chronic toxicity study in dogs with a NOEL of 450 ppm, or approximately

14.7 mg/kg/day

and a LOEL of 1350 ppm, or approximately 44.6 mg/kg/day
. iii. A 2
- ye ar oncogenicity study in Sprague
- Dawley

rats with a NOEL for systemic toxicity of 200 ppm, or approximately 8.8 mg/kg/day

for males and 11.3 mg/kg/day

for females. The LOEL for s ys temic toxicity was 750 ppm, or approximately

33.9 mg/kg/day

for males and 46.3 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

94.6 mg/kg/day

for males and 132.5 mg/kg/day for females. iv. A 2
- ye ar oncogenicity study in CD
- 1 mice with a NOEL for s ys temic toxicity of 100 mg/kg/day and a LOELof 1,000 mg/kg/day
. There was no ev idence of increased incidence of neoplastic lesions in treated animals. The NOEL for oncogenicity is 1,000 mg/kg/day, the highest dose tested. v. A subchronic neurotoxicity study in Wistar rats with a NOEL of 432.9 mg/kg/day in males or 510.1 mg/kg/day in females. There was no evidence of neurotoxicity
. vi. A subchronic immunotoxicity study in male Wistar rats with a NOEL of 2400 ppm, equivalent to 184 mg/kg/day 432.9 mg/kg/day . There was no evidence of an immunotoxic potential
. ] 6. Animal metabolism. [ Re sults from the livestock and rat metabolism studies show that orally

administered dimethomorph was ra pidly excreted by

the animals. The principal route of elimination is via the feces. ]5 7. Metabolite toxicology
. [ There were no metabolites identified in p lant 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 sy stem. There is no information available that suggests that dimethomorph technical would be associated with endocrine effects. ] C. Aggregate Exposure 1. Die tary 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 CF R § 180.493 and the proposed tolerance for strawberry at 1.0 ppm
. ] 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 dimethomor ph toxicity

data, and determined there was no toxicological endpoint attributable to a single dose and a quantitative acute dietary exposure and risk assessment are not required. Chronic Dietary

Exposure Assessment A Tier 1 chronic dietary

exposure asses sment was conducted assuming tolerance level residues and 100% crop treated factors for all registered crops and the propose d new use for strawberry
. The EPA Food Commodity Ingredient Database (FCID) was also used in Exponent's Dietary

Exposure Evaluation Module (DEEM
- FCID) software. Tolerances for animal commodities (i.e. meat, meat b yproducts, milk, eggs) are not required since metabolism studies have shown dimethomorph residues will not occur in animal commodities from the consumption of dime th omorp h res i dues in livestock feed. Furthermore, there are no livestock feedstuf fs associated with strawberry
. Therefore, dimethomorph tolerances for residues in animal commodities do not need to be established. Dietary e xposure estimates (food + drinking wat er) wer e compared against the established dimethomorph chronic Population Adjusted Dose (cPAD) of 0.11 mg/kg b.w./day f or all populations. Results of the chronic dietary a ssessments are listed in the table below. The estimated chronic dietary e xposure 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 and crop treatment factors would further reduce the estimated chronic dietary e xposure . The results in the Table below demonstrate that there are no risk concerns for any subpopulation based on established and new strawberry , and that the results clearl y 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 and drinking water**  **.**6
**Population sub -**  **group Chronic Exposure**  **(mg/kg bw/day) %cPAD**  **US Population 0.012933**  **11.8 All infants (< 1 year)**  **0.010746 9.8**  **Chil dren 1**  **- 2**  **0.026544 24.1**  **Children 3 -**  **5 0.022276**  **20.3 Children 6**  **- 12**  **0.012695 11.5**  **Youth 13 -**  **19 0.008745**  **8.0 Adults 20**  **- 49**  **0.012406 11.3**  **Adults 50+ yrs 0.012718**  **11.6 Females 13**  **- 49 yrs**  **0.01202 10.9**  ] ii. Drinking water. [ The chronic drinking water value s used in this analysis were the values proposed by

E PA, September 15, 2011, “Dimethomorph: Human Health Risk Assessment to Support Amen ded Use on Grapes, Bulb Vegetables, Leafy B rassica Veg etables and Leafy

Vegetables”. The chronic drinking water value us ed was 24.7 ug/L
. Acute Aggregate Exposure and Risk (Food and water) The U.S. EPA Toxicological Endpoint Selection (TES) Committees has evaluated the dimethomorph toxicity

data and determined there was no endpoint attributable to a single dose , therefore an acute aggregate exposure and risk evaluation is not required. Chronic Aggregate Exposure and Risk (food and water) The aggregate chronic risk includes residues of dimethomorph from food and water . The results in Table 1 demonstrate there are no risk concerns for any subpopulation based on established and new uses, and that the results clearl y meet the FQPA standard of reasonable certainty

of no harm. ] 2. Non
- dietary exposure
. [ Dimethomorph is not registered for use on any sites that would result in residenti al exposure. Therefore, a residential exposure and risk assessment was not conducted **.** Also, a short
- term aggregate risk assessment is not required **.** ] D. Cumulative Effects [ There is no information to indicate that any toxic effects produced b y dimethomorph would be cumulative with those of any other chemical. The fungicidal mode of action of dimethomorph is unique; dimethomorph inhibits cell wall for mation only in Oomycet e fungi. The result is ly sis of the cell wall that kills growing cells and inhibits spo re 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. Inaddition, the toxicity studies submitted to support this petition do n ot indicate that dimethomorph is a particularl y toxic compound. No toxic end
-points of7

potential concern were identified. ] E. Safety Determination 1. U.S. population. [ Based on this risk assessment, BASF concludes that there is a reasonable certainty

th at no risk concerns 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 risk concerns 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 strawberry ; consequently , a discussion of international harmonization is not relevant. ]