COMPANY NOTICE OF FILING OF PESTICIDE PETITION TO ESTABLISH 

PERMANENT DICLORMID TOLERANCES ON CORN COMMODITIES 

EPA Registration Division contact: Susan Stanton (7505P), 703-305-5218

EPA has received a pesticide petition (PP 9E7517 ) from Dow AgroSciences 

LLC, 9330 Zionsville Road – Indianapolis, IN 46268 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 permanent tolerance for residues of acetamide,

2,2-dichloro-N,N-di-2-propenyl- (dichlormid) CAS Reg. No. 37764–25–3 in or on the 

raw agricultural commodities Corn, field, forage; Corn, field, grain; Corn, field, stover; 

Corn, pop, grain; Corn, pop, stover; Corn, sweet, forage; Corn, sweet, kernel plus cob 

with husks removed and Corn, sweet, stover at 0.05 parts per million (ppm). Dichlormid 

(R-25788) is an herbicide safener that is used in the Dow AgroSciences LLC (DAS) 

acetochlor product line that is used for the control of grasses and broadleaf weeds in field 

corn, pop corn and sweet corn. Currently, time-limited tolerances on corn commodities 

are established. Initially on March 27, 2000 (65 FR 16143) (FRL-6498-7), EPA 

established time-limited tolerances under 40 CFR 180.469 for residues of dichlormid in 

or on field corn (forage, grain, stover), pop corn (grain, stover) at 0.05 ppm with an 

expiration date of March 27, 2002. Time-limited tolerances on corn commodities have 

been reestablished in 2002 (67 FR 51102) (FRL-7192-5); in 2005 (70 FRL-76697-76699) 

and on July 29, 2009, (74 FR 37621 (FRL-8422-2) EPA extended the time-limited 

tolerances for residues on field corn (forage, grain, stover); pop corn (grain, stover); and 

sweet corn (forage, kernel plus cob with husks removed, stover) with an 

expiration/revocation date of December 31, 2010. In 2010 EPA ARIA responded to DAS 

Petition 9E7517 (Memorandum, Dichlormid. Petition for the Use on Corn. Response to 

Registrant’s Comments, D372259, March 31, 2010) and recommended the establishment 

of permanent tolerances for dichlormid on field corn, sweet corn and popcorn 

commodities.

Prior to the conversion of the time-limited tolerances to permanent tolerances, 

several data gaps were identified in the 2005 EPA Human Health assessment (Hanson, 

D321928) and these were addressed in a summary report by Kaminski (MRID 47448101,

June 12, 2008). EPA’s requirements for additional residue chemistry data (D318075, D. 

Rate, Sept 14, 2005) were addressed in DAS response (Kaminski, MRID 47628301, 

November 24, 2008) and upon review EPA stated no additional MOR studies were 

required to support the existing tolerances (W. T. Drew, DP366892, August 11, 2009). In 

addition, new information for physical properties (MRIDs 47916901 and 47916902, 

2009), and an immunotoxicity study (MRID 48102801, 2010) have recently been 

submitted. In 2010, several additional toxicity studies were reported acceptable, 

(D369088, April 2010). And per D372259, March 31, 2010, EPA ARIA recommended 

the establishment of permanent tolerances for dichlormid in corn. 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 
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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 nature of the residue in plants is adequately understood 

based on a study depicting the metabolism of dichlormid in corn plants. The request for 

additional metabolite information in the 2005 EPA Human Health review (D321928) has

been addressed by Kaminski (MRID 47448101, June 12, 2008). The metabolism of 

dichlormid in corn is extensive and occurs via two metabolite pathways. In one pathway, 

dichlormid is a de-chlorinated and oxidized to generate N,N-diallyl glycolamide. An 

alternative pathway is the loss of an allyl group followed by oxidation to form 

dichloroacetic acid. There is also extensive incorporation into natural constituents. Per 

the EPA 2010 memo (D372259, March 2010), EPA ARIA and HED concluded the 

previously submitted plant metabolism study is adequate that dichlormid is the residue of 

concern for tolerance setting purposes.

2. Analytical method. An adequate enforcement method for residues of 

dichlormid in corn has been developed (MRID 44960101) and validated by the 

Analytical Chemical Laboratory (ACL) of EPA (Memo, D199230, G. Kramer, 08/29/94). 

Analysis is carried out using gas chromatography with nitrogen selective thermionic 

detection. A revised method was resubmitted to the EPA on 10/29/99.

3. Magnitude of residues. Field trial information in field corn (MRID 46353807, 

47628301) and sweet corn (DAS report BJK042403pkm, May 2003) with dichlormid 

have been previously submitted and reviewed. In 2005, EPA confirmed that the field 

trial data residue levels of dichlormid are < 0.01 ppm, but the appropriate tolerance level 

is 0.05 ppm for all corn RACs based on the enforcement methods’ LOQ of 0.05 ppm

(EPA, D321928, 2005). Per the EPA 2010 memo (D372259, March 2010), the EPA has 

determined that the residue chemistry database is adequate to established tolerances of

0.05 parts per million (ppm) based on the enforcement method LOQ for all corn 

commodities.

B. Toxicological Profile The toxicity database is adequate for the establishment of 

permanent tolerances in corn. Per the EPA 2010 memo (D369088, April 2010), several

new studies have been reviewed and found acceptable, with the exception of the 

subchronic neurotoxicity study which was technically listed as unacceptable according to 

the guidelines. However a repeat of that study at higher doses to establish a LOAEL 

value would not change the regulatory risk assessment endpoints for dichlormid.

1. Acute toxicity. Dichlormid has low acute toxicity, causes mild ocular irritation, 

severe skin irritation, and is mild skin sensitizer (MRID 44606401, 44606402, 44606403, 

44606404, 42807902, 44606405). The NOAEL for acute neurotoxicity was 1,500 mg

dichlormid/kg (MRID 46353805). EPA has previously established an acute RfD of 0.10 

mg/kg/day based on the maternal NOAEL of 10 mg/kg bw/day in the rat developmental 
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toxicity study (EPA, D321928, 2005).

2. Genotoxicity. Dichlormid was not mutagenic via in vitro assays including the 

Salmonella/microsome (Ames) assay, and the human lymphocyte cytogenetic assay (both 

assays with and without metabolic activation (MRID 41561404, 41561407). In the 

L5178Y mouse lymphoma assay, small increases in mutant frequency were observed 

only at cytotoxic concentrations, and were not considered to be significant (MRID 

41561405). In vivo, dichlormid was negative in the mouse micronucleus test and in the 

rat unscheduled DNA synthesis assay, when tested at the maximum tolerated dose 

(MRID 41561403, 44606409, 41561408).

3. Reproductive and developmental toxicity. In a multi-generation reproduction 

study in rats, the NOAEL for reproductive toxicity was greater than 500 ppm (48.5 mg/kg 

bw/day), the highest dose tested (MRID 46353801). In rats, the NOAEL for 

developmental toxicity was 40 mg/kg bw/day and the LOAEL was 160 mg/kg bw/day

based on marginally increased skeletal anomalies (MRID 44606408). The developmental 

NOAEL for rabbits was 30 mg/kg/day and the LOAEL was 180 mg/kg bw/day based on 

a small increase in post-implantation loss, an increased number of early resorptions, a 

decreased number of fetuses per litter and evidence of fetotoxicity- all observed in the 

presence of maternal toxicity at the same dose-level (MRID 44606407).

In assessing the potential for additional sensitivity of infants and children to residues of 

dichlormid, data from developmental toxicity studies in the rat and rabbit have been 

considered. The developmental toxicity studies are designed to evaluate adverse effects 

on the developing organism resulting from maternal pesticide exposure during gestation. 

There was not evidence to suggest that dichlormid was a selective developmental toxicant 

in either the rat or rabbit. In rats, there was no risk below maternally toxic doses as the 

NOAEL for developmental effects was 40 mg/kg bw/day, compared to the maternal 

NOAEL of 10 mg/kg bw/day. In the rabbit developmental toxicity study, the NOAEL for 

both maternal and developmental effects was 30 mg/kg bw/day. EPA has previously

concluded that the 10X FQPA safety factor should be retained in part due to an 

incomplete database, and in part due to the qualitative evidence of increased 

susceptibility demonstrated following in utero exposure in the prenatal developmental 

toxicity in rabbits. It should be noted that in the rabbit developmental toxicity study, the 

LOAEL for both maternal and developmental toxicity was 180 mg/kg bw/day. The 

effects on resorptions at this dose were observed in the presence of substantial maternal 

toxicity as evidenced by clinical toxicity, reduced feed consumption (up to 48% lower 

than controls), and body weight loss (-3.8g during the treatment period compared with an 

average weight gain in controls of 272g). Also, a multi-generation study has been 

completed (MRID 46353801). In 2005, EPA noted that the data gap for FQPA 

considerations had been addressed, but that metabolism studies were still needed to 

reassess reduction of the FQPA factor (EPA, D321928, 2005). In 2010 (D372259, March 

2010), EPA reviewed and accepted the repeat Oral Dose rat metabolism study (MRID 

46366001) and the biotransformation,tissue distribution and extraction studies (MRID 

46353802, 46353803). Thus, Dow AgroSciences believes that the current 10X FQPA 

safety factor should be reduced to 1X in the future. For expediency of this petition;
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however, the previously established FQPA factor of 10X will be retained for the risk 

assessment.

4. Subchronic toxicity. In a 90-day dietary toxicity study in dogs, the NOAEL

was 5 mg/kg bw/day while in rats the 90-day dietary NOAEL was 20 ppm (1.4 and 1.6 

mg/kg bw/day in males and females respectively) (MRID 41419401, 44606461). In a 14-

week rat inhalation study, the NOAEL was 2.0 mg/m3 (MRID 00155678). In a 

subchronic rat neurotoxicity study, there was no evidence of neurotoxicity at 750 ppm 

(55.4 mg/kg bw/day for males, 61.2 mg/kg bw/day for females), the highest dose-level 

tested (MRID 46353806). Due to the lack of an established LOAEL this study has 

technically been listed as unacceptable according to the guidelines; however, a repeat of 

this study at higher doses to establish a LOAEL would not change the regulatory risk 

assessment endpoints for dichlormid. In a functional immunotoxicity study in female 

rats, there was no evidence of immunotoxicity at 1000 ppm (85.9 mg/kg bw/day), the 

highest dose tested (MRID 48102801). This immunotoxicity study has recently been 

reviewed and found acceptable by the EPA, per the August 24, 2010 DER D378513.

5. Chronic toxicity. The NOAEL in the two-year rat chronic study was 100 ppm 

(6.5 and 7.5 mg/kg bw/day for males and females, respectively) (MRID 44529402). In 

an 18-month oncogenicity study, the NOAEL was 50 ppm (7.0 and 9.2 mg/kg/day for 

males and females, respectively) (MRID 44529401). It was concluded, there was no 

evidence of oncogenicity associated with dichlormid treatment in rats or mice. Based on 

available chronic toxicity data, the cRfD for dichlormid was previously established as

0.017 mg/kg bw/day based on the 90-day feeding studies in dogs with a NOAEL of 5 

mg/kg bw/day along with a UF of 300 (EPA, D321928, 2005). The data gaps have now 

been filled (MRID 46353805, 46353806, 46366001, 46353802, 46353803, 46353801, 

48102801), and Dow AgroSciences LLC; therefore, proposes that the currently applied 

300X UF should be reduced in the future and a revised uncertainty factor of 100X UF be 

applied to the previous POD resulting in a revised cRfD of 0.05 mg/kg/day. For this 

petition, however, the previously established cRFD of 0.017 mg/kg/day will be used.

6. Animal metabolism. Dichlormid was well absorbed, extensively metabolized 

and eliminated mainly in the urine within 24 hours. A significant proportion of the dose, 

up to 11%, was exhaled as CO2 (MRID 46353803). Per the 2010 memo (D372259, 

March 2010), the EPA has determined that the previously submitted livestock 

metabolism study is adequate for the current use on corn and that no livestock tolerances 

are required for use in corn.

7. Metabolite toxicology. No unique plant or soil metabolites have been identified 

that warrant a separate toxicological assessment.

8. Endocrine disruption. There is no indication in the dichlormid toxicology

database of adverse effects associated with endocrine disrupter activity.

C. Aggregate Exposure
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1. Dietary exposure. The following established endpoints from the EPA 2005 

Human Health Assessment of dichlormid (D321928) are used to conduct a risk 

assessment for chronic and acute dietary and water exposure of the U.S. population 

subgroups to residues of dichlormid: aRfd = 0.10 mg/kg/day; aPAD =0.010 mg/kg/day; 

cRfD = 0.017 mg/kg/day and cPAD = 0.0017 mg/kg/day. The Dietary Exposure 

Evaluation ModelTM (DEEM-FCID, ver. 2.16, Exponent, Inc., Washington, DC-20036) 

software was employed. DEEM contains food consumption data as reported by

respondents in the USDA Continuing Surveys of Food Intake by Individuals (CSFII) 

conducted in 1994-1996 and 1998 and food translation to RACs, as indicated by

EPA/USDA FCID recipe set as of August, 2002.

i. Food. This Tier-I assessment considers residues at tolerance levels of 0.05 ppm 

for all consumed corn commodities at 100% crop treated (CT), it also includes the DEEM 

7.81 default processing factor of 1.5 for corn syrup. These results are conservative 

(health protective) risk estimates. Refinements such as use of percent crop-treated 

information and/or anticipated residue values would yield lower estimates of dietary

exposure.

ii. Drinking water. The previous EPA estimates of potential drinking water 

exposures have been directly incorporated in the DEEM-FCID into the food categories 

“water, direct, all sources” and “water, indirect, all sources.” Per the EPA 2005 Human 

Health Assessment of dichlormid (D321928), drinking water estimate concentrations 

were calculated for groundwater using Screening Concentration in Groundwater (SCIGROW, modeling, and surface water estimate concentrations were calculated using 

Generic Estimated environmental Concentration (GENEEC) modeling. These models 

provide a coarse screen for assessing whether a pesticide is likely to be present in 

drinking water at concentrations which would exceed human health levels of concern.

For acute exposure, the maximum estimated concentration of dichlormid in surface and 

ground water concentration was 27.3 and 0.046 ppb, respectively. For chronic exposure, 

the estimated concentration of dichlormid in surface and ground water concentration was 

8.98 and 0.046 ppb, respectively.

2. Non-dietary exposure. The general population is not expected to be exposed to 

dichlormid through non-dietary routes, because dichlormid is used only on agricultural 

crops, and is not used in or around the home.

D. Cumulative Effects

The potential for cumulative effects of dichlormid and other substances that have 

a common mechanism of toxicity have been considered. There is no reliable information 

to suggest that dichlormid has any toxic effects that arise from toxic mechanisms 

common to other substances. Therefore, a consideration of common mechanism and 

cumulative effects with other substances is not appropriate for dichlormid.
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E. Safety Determination

1. U.S. population

i. Chronic Risk. Using the conservative exposure assumptions described earlier, 

and based on the completeness and reliability of the toxicity data base for dichlormid, the 

food and water chronic exposure estimate for the general U.S. population is 0.000294

mg/kg/day or 1.7% of the cRfD. The most highly exposed subgroup are infants (<1 year)

with an estimated food and water exposure of 0.000758 mg/kg/day or 44.6% of the 

cPAD.

ii. Acute Risk. Modeled acute exposures from DEEM for food and water at the 

95th percentile were 0.001568 mg/kg/day, or 1.57% of the aRfD for the general 

population. The most highly exposed subgroup are infants (<1 year) with an estimated 

food and water acute exposure of 0.005998 mg/kg/day, or 60% of the aPAD.

All population subgroups have shown potential Tier-I (worst-case) exposure below 100% 

of the PAD. EPA generally has no concern for exposures below 100% of the PAD, thus 

there is a reasonable certainty that no harm will result from aggregate exposure to 

dichlormid residues.

2. Infants and children. Per the preceding discussion and based on the recent 

reviews of several additional toxicity studies, Dow AgroSciences LLC maintains that an 

additional FQPA 10X as well as the previous 3X chronic database uncertainty factors are 

no longer warranted for the safety of infants and children. Reliable data support the 

appropriate use of a 100-fold uncertainty factor (MOE) to account for interspecies 

extrapolation and intraspecies variability. However, for the expediency of this petition,

the previously established PAD values were used along with the conservative exposure 

assumptions in food and water. Estimates indicate the highest potentially exposed 

subpopulation of infants does not have an aggregate exposure to dichlormid above the 

PAD. Therefore, based on the completeness and reliability of the toxicity data base and 

the conservative exposure assessment, Dow AgroSciences LLC concludes that there is a 

reasonable certainty that no harm will result to infants and children from aggregate 

exposure to dichlormid residues.

F. International Tolerances

There is neither a Codex proposal nor Canadian or Mexican limits for residues of 

dichlormid in corn commodities.