Dichlormid 

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

 

MEMORANDUM

Date: 01/13/2011

SUBJECT: Dichlormid; Human Health Risk Assessment for 

Limited Tolerances on Field Corn Commodities Permanent

PC Code: 900497

Decision No.: 419811

Petition No.: NA

Risk Assessment Type: Single chemical 

aggregate

TXR No.: NA

MRID No.: NA

FROM: Debra Rate, Ph.D., Biologist

Alternative Risk Integration and Assessment (ARIA) Team

Risk Integration, Minor Use, and Emergency Response Branch (RIMUERB)

Registration Division (RD; 7505P)

THROUGH: Pv Shah, Branch Chief

Inert Ingredients Assessment Branch (IIAB)/

TO: Susan Stanton

Herbicide Branch (HB)/

ARIA/RD of the Office of Pesticide Programs (OPP) is charged with re

human health that will result from converting the

for the registered uses of the chemical, dichlormid

used as an herbicide safener (inert ingredient) in pesticide formulations with the active 

ingredient, acetochlor on corn commodities

corn (field, pop, and sweet) commodities 

The risk assessment recommendations were prepared by Debra Rate (ARIA/RD). The risk 

assessment incorporates new toxicology assessments prepared by Anwar Dunbar (RAB1/HED)

recent residue chemistry reviews prepared by William Cutchin (ARIA/RD)

 Human Health Risk Assessment 

Page 1 of 8

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C. 20460 

OFFICE OF CHEMICAL SAFETY AND

 POLLUTION PREVENTION

; Human Health Risk Assessment for the Purpose of Making Time

Limited Tolerances on Field Corn Commodities Permanent. 

DP Barcode: D385691

Registration No.: 62719-367, 62719

62719-369, 62719-370, 62719

372, 62719-373

Regulatory Action: Section 3 Registration 

Single chemical Case No.: NA

CAS No.: 37764-25-3

40 CFR: 180.469

Debra Rate, Ph.D., Biologist

Alternative Risk Integration and Assessment (ARIA) Team

Risk Integration, Minor Use, and Emergency Response Branch (RIMUERB)

Registration Division (RD; 7505P)

Branch Chief

Inert Ingredients Assessment Branch (IIAB)/RD (7505P)

Herbicide Branch (HB)/RD (7505P)

ARIA/RD of the Office of Pesticide Programs (OPP) is charged with re-evaluating the risk to 

ealth that will result from converting the time-limited tolerances to permanent tolerances 

registered uses of the chemical, dichlormid (N,N-diallyl-2,2-dichloroacetamide) when 

used as an herbicide safener (inert ingredient) in pesticide formulations with the active 

n corn commodities. The time-limited tolerances for dichlormid in/on 

corn (field, pop, and sweet) commodities were due to expire 12/30/2010. 

The risk assessment recommendations were prepared by Debra Rate (ARIA/RD). The risk 

w toxicology assessments prepared by Anwar Dunbar (RAB1/HED)

residue chemistry reviews prepared by William Cutchin (ARIA/RD), and a

 DP#385691

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

OFFICE OF CHEMICAL SAFETY AND

POLLUTION PREVENTION

the Purpose of Making Time367, 62719-368, 

-371, 62719-

Section 3 Registration 

Risk Integration, Minor Use, and Emergency Response Branch (RIMUERB)

evaluating the risk to 

limited tolerances to permanent tolerances 

dichloroacetamide) when 

used as an herbicide safener (inert ingredient) in pesticide formulations with the active 

limited tolerances for dichlormid in/on 

The risk assessment recommendations were prepared by Debra Rate (ARIA/RD). The risk 

w toxicology assessments prepared by Anwar Dunbar (RAB1/HED),

, and a drinking 
Dichlormid Human Health Risk Assessment DP#385691

Page 2 of 8

water assessment was prepared by Alex Clem (Environmental Fate and Effects Division 

(EFED)). The current document reassesses the exposure and risk to human health from 

dichlormid resulting from the registered uses. The most recent human health risk assessment 

for dichlormid was prepared by B. Hanson (DP#321928, 11/15/2005). 

I. CONCLUSIONS

ARIA recommends that the current time-limited tolerances supporting the use of the herbicide 

safener, dichlormid, in/on corn, field (forage, grain, and stover), corn, pop (grain and stover), and 

corn, sweet (grain and stover) at 0.05 ppm (40 CFR§180.469) be converted to permanent 

tolerances. 

The Hazard Identification Assessment Review Committee (HIARC) previously recommended 

that the FQPA SF be retained at 10X for enhanced sensitivity to infants and children since there 

was qualitative evidence of increased susceptibility in the rabbit developmental study and data 

gaps (HED DOC. NO. 013614, 08/05/1999) Based on the recent submission and evaluation of 

required toxicological studies and residue chemistry data, ARIA recommends that the Food 

Quality Protection Act (FQPA) Safety Factor (SF) be reduced from 10X (acute) and 30X 

(chronic) to 1X, eliminating the need for additional database uncertainty factors (UFDB). The 

reviews of the recently submitted toxicological studies did not result in a lower no-observable 

adverse-effect level (NOAEL) or lowest-observable adverse-effect level (LOAEL) for 

dichlormid. Therefore, the HIARC recommended toxicological endpoints and doses used for 

risk assessment remain unchanged. 

The current request does not require any change in tolerance value or use patterns. With the 

submission of data and studies that fulfill the previously cited data gaps, and the recommended 

reduction of the FQPA SF, a new comprehensive risk assessment for dichlormid is not required 

at this time. The most recent risk assessment (DP#321928, B. Hanson, 11/15/2005), is highly

conservative and supports the current use patterns and tolerances. The risk assessment indicates 

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

residues, including all anticipated dietary exposures from food and drinking water. The risk 

assessment also indicates aggregate and occupational risks are not of concern. 

In accordance with HED’s Interim Guidance on Tolerance Expressions (5/27/2009, S. Knizner),

and as requested in an Agency memo (DP#372259, W. Cutchin, 03/31/2010), the tolerance 

expression for dichlormid should be revised to state:

Tolerances are established for residues of dichlormid, including its metabolites and 

degradates, in or on the commodities in the table below. Compliance with tolerance 

levels specified below is to be determined by measuring only dichlormid (2,2-dichloroN,N-di-2-propenylacetamide) in or on the following commodities:

An adequate enforcement method for residues of dichlormid in corn has been developed and 

submitted to the Agency. Analysis is carried out using gas chromatography with nitrogen 

selective thermionic detection. The limit of quantitation is 0.01 ppm. Previously requested 

method modifications have been received and reviewed by the Agency, thus fulfilling this 

outstanding deficiency (MRID No. 44960101).
Dichlormid Human Health Risk Assessment DP#385691

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II. ACTION REQUESTED

Dow AgroSciences, Inc., has submitted a request to convert the current time-limited tolerances 

for corn commodities (40 CFR§180.469) to permanent tolerances. Data submitted by the 

petitioner to fulfill data gaps cited in previous risk assessments and chemistry reviews have been 

evaluated by the Agency. 

III. BACKGROUND

DP#321928, B. Hanson, 11/15/2005

DP#318075, D. Rate, 09/14/2005

Dichlormid is an herbicide safener used in pesticide formulations with the active ingredient, 

acetochlor, for use on corn commodities to control grass and broadleaf weeds. No new requested 

uses or tolerances are associated with this petition to make current time-limited tolerances 

permanent.

There are no existing or proposed residential uses for dichlormid, therefore the risk associated 

with residential exposure is below the Agency’s level of concern (LOC). Due to the data gaps 

cited in the previous risk assessment, the time-limited tolerances were extended, rather than 

made permanent in the most recent assessment (DP#321928, B. Hanson, 11/15/2005). 

The following data gaps were cited in the previous risk assessment and needed to be addressed 

prior to establishing permanent tolerances on the corn commodities, as requested: 

Chemistry

1. 860.1300: Nature of the Residue - Plants

The studies submitted (MRID No. 46015801) for the purpose of fulfilling the Guideline 

860.1300 is scientifically unacceptable and does not satisfy the requirements. It may be 

upgraded if additional metabolites are identified, including unknown A, to allow a more 

complete characterization of the nature of the residue of dichlormid in corn.

2. 860.1300: Nature of the Residue - Livestock

The studies submitted (MRID No. 46015802, 46015803) for the purpose of fulfilling the 

Guideline 860.1300 are scientifically unacceptable and do not satisfy the requirements. The 

studies do not adequately define the nature of the residues or the residue(s) of concern for 

dichlormid. They may be upgraded upon further identification of residues representing 10% 

and/or 0.05 ppm. 

3. 860.1340: Residue Analytical Methods

The requested revised method has not yet been received.

4. 860.1900: Field Accumulation in Rotational Crops

No studies in field accumulation in rotational crops have been submitted. The registrant should 

submit a field accumulation in rotational crop study in accordance with OPPTS Guideline, 

860.1900.
Dichlormid Human Health Risk Assessment DP#385691

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Toxicology:

1. Subchronic dermal and inhalation study

2. Neurotoxicity study

3. Metabolism studies

4. As per revisions to the 40CFR158:

Immunotoxicy studies

Due to the nature and number of data gaps and qualitative evidence of increased susceptiblilty in 

the rabbit developmental study, the FQPA SF was previously established at 10X for the acute 

assessment, and 30X for the chronic assessment. Both FQPA SFs contribute to the highly 

conservative nature of the results obtained in the previous risk assessment. 

The previous risk assessment (DP#321928, B. Hanson, 11/15/2005) was highly conservative 

using tolerance level residues in the dietary assessment, 100% crop treated, default processing 

factors, and maximum use rates for determining field trial and water exposure modeling residues. 

Previously, the dietary risk (food only) associated with the use of dichlormid was below the 

Agency’s LOC. The acute dietary risk estimates were 3.4% of the acute population-adjusted 

dose (aPAD) for the general U.S. population and 7.5% of the aPAD for the highest exposure 

group, all infants (< 1 year old). Chronic dietary risk estimates were 6.1% of the chronic 

population-adjusted dose (cPAD) for the general U.S. population and 15% of the cPAD for the 

highest exposure group, children 3-5 years old (DP#321927, B. Hanson, 11/07/2005). 

Previously, exposure and risk to drinking water was evaluated through the use of drinking water 

level of comparison (DWLOCs). A DWLOC is a theoretical upper limit on a pesticide’s 

concentration in drinking water in light of total aggregate exposure to a pesticide in food, 

drinking water, and through residential uses. A DWLOC will vary depending on the toxic 

endpoint, with drinking water consumption, and body weights. Different populations will have 

different DWLOCs. HED previously used DWLOCs internally in the risk assessment process as 

a surrogate measure of potential exposure associated with pesticide exposure through drinking 

water. In the absence of monitoring data for pesticides, it was used as a point of comparison 

against conservative model estimates of a pesticide’s concentration in water. As calculated in 

the most recent human health risk assessment for dichlormid (DP#321928, B. Hanson, 

11/15/2005), all DWLOCs exceeded the EFED modeled drinking water residue values provided 

for risk evaluation (DP#258095, A. Clem, 8/3/99). Therefore the Agency’s level of concern for 

drinking water exposure was not exceeded. 

Since the last risk assessment was completed, studies have been reviewed that address the data 

gaps listed above. The results below discuss the reviews and the impact of this data on the risk 

and exposure from use of dichlormid as a safener on corn (field, pop, and sweet). 

IV. RESULTS/DISCUSSION 

DP#372259, W. Cutchin, 03/31/2010

DP#369088 and 369089, A. Dunbar, 04/07/2010

DP#378513, A. Dunbar, 08/24/2010
Dichlormid Human Health Risk Assessment DP#385691

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The Agency has recently evaluated the residue chemistry deficiencies (DP#372259, W. Cutchin, 

03/31/2010) and the toxicology data gaps (DP#369088 and 369089, A. Dunbar, 04/07/2010 and 

DP#378513, A. Dunbar, 08/24/2010). 

Chemistry (DP#372259, W. Cutchin, 03/31/2010):

860.1300: Nature of the Residue – Plants: Upon evaluation of the registrant’s responses to the 

cited data deficiencies (above), and re-evaluation of the original studies submitted, the Agency

has determined that the previously submitted plant metabolism study is adequate. The residue of 

concern was determined to be the parent, dichlormid. It was also determined that should 

additional uses of dichlormid on crops other than corn be requested, the nature of the residue 

data on those commodities will be required.

860.1300: Nature of the Residue – Livestock: Upon consideration of the registrant’s comments 

and responses to the cited data deficiencies (above), and re-evaluation of the original submitted 

studies, the Agency has determined that the previously submitted livestock metabolism study is 

adequate for the current use on corn. 

860.1340: Residue Analytical Methods: The requested revised method has since been received 

by the Agency and a copy will be forwarded to the FDA.

860.1900: Field Accumulation in Rotational Crops: Following consideration of the registrants 

responses and re-evaluation of the original studies, the Agency determined that no field 

rotational crop data is required for the current uses of dichlormid. However, it was also 

determined that additional data will be required should the registrant request higher use rates or 

shorter plant back intervals (PBIs).

Toxicology (DP#369088 and 369089, A. Dunbar, 04/07/2010 and DP#378513, A. Dunbar, 

08/24/2010):

In response to the registrant’s comments the following studies were determined to be 

acceptable/guideline: Subchronic Inhalation in rats (MRID No. 00155678), Acute Neurotoxicity

in rats (MRID No. 46353805), and Metabolism (MRID No. 46353802 and 46353803). The third 

metabolism study (MRID No. 46366001) was determined to be acceptable/non-guideline. The 

final study reviewed in Agency memo (DP#369088 and 369089, A. Dunbar, 04/07/2010), 

Subchronic Neurotoxicity (MRID No. 46353806) was determined to be unacceptable/guideline. 

The Agency also reviewed an immunotoxicity study (rat feeding) and determined that the study

is acceptable/guideline (DP#378513, A. Dunbar, 08/24/2010).

All of the toxicology and residue chemistry data gaps for use on corn (field, pop, and sweet), 

have been fulfilled. Uncertainty factors associated with database deficiencies can be removed.

Impact on Aggreaget Risk:

There are no existing or proposed residential uses for dichlormid, therefore aggregate risk is 

based on dietary exposure from food and water. A dietary (food and water) exposure and risk 

assessment was performed incorporating the EDWCs (DP#258095, A. Clem, 08/03/1999) into 

water, direct (all sources) and water, indirect (all sources), and the HIARC determined 
Dichlormid Human Health Risk Assessment DP#385691

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toxicological endpoints in the Agency’s dietary exposure model (DEEM-FCIDTM, Version 2.03). 

Analysis using the current FQPA SFs (10X acute, 30X chronic) and appropriate toxicological

endpoints (See Attachment 1) resulted in acute risk (95th percentile) at 16% of the aPAD for the 

general US population and 56% of the aPAD for the highest exposed population (All infants 

<1year) and chronic risk at 13% of the cPAD for the general US population and 34% of the 

cPAD for the highest exposed population subgroup (All infants < 1year). Using the same 

residue values, appropriate toxicological endpoints and the recommended FQPA SF reduced 

values (1X) resulted in an acute risk (95th percentile) of 2% of the aPAD for the general US 

population and 6% of the aPAD for the highest exposed population (All infants <1 year), and 

<1% cPAD, for the general US population and 1% of the cPAD for the highest exposed 

subpopulation (All infants <1 year). All of the dietary analyses (food and water) were well 

below the Agency’s LOC for the general US population and all population subgroups, whether 

the new recommended FQPA SF was included or not.

Permanent tolerances for corn commodities are supported by the previous risk assessment, 

recently reviewed studies, and the new dietary analyses discussed above. A comprehensive risk 

assessment for dichlormid to make current time-limited tolerances on corn commodities 

permanent, is not required at this time.

Occupational Exposure and Risk Associated with the Use of Dichlormid on Corn

Occupational exposures may occur via dermal and/or inhalation routes. The HIARC has

identified toxicological endpoints of concern for occupational exposure. However, based on the 

use patterns for dichlormid on corn (pre-emergence soil or early post-emergence foliar 

applications) no potentially significant post-application or long-term exposure is expected. 

Therefore, the previous occupational assessment (DP#321928, B. Hanson, 11/15/2005) is 

protective for the proposed use pattern. For dichlormid, margins of exposure (MOEs) of 100 are 

required for handlers of agricultural crops in order for risks not to be of concern to HED. For all 

previously assessed handler scenarios, short- and intermediate-term MOEs were greater than the 

target MOE of 100 and, therefore, risks do not exceed HED’s level of concern. Therefore, there 

are no risk concerns associated with the use pattern.
Dichlormid Human Health Risk Assessment DP#385691

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Attachment 1: Toxicological Endpoints for Dichlormid.

Table 1. Summary of Toxicological Dose and Endpoints for Dichlormid Use in Human Risk Assessment 1.

Exposure

Scenario

Dose 

(mg/kg/day) 

and Factors

FQPA SF and 

Endpoint for Risk 

Assessment

Study and Toxicological Effects

Acute Dietary

all populations

including infants 

and children

NOAEL= 10 

mg/kg

UF = 100

Acute RfD = 

0.10 mg/kg/day

FQPA SF = 10

aPAD = acute RfD

FQPA SF

= 0.010 mg/kg/day

Developmental Toxicity Study - rat

Maternal LOAEL = 40 mg/kg/day based on 

decreased body weight gain and food 

consumption (most significant on days 7-10 

of dosing).

Chronic Dietary

all populations

NOAEL= 6.5 

mg/kg/day

UF = 100

Chronic RfD = 

0.065 mg/kg/day

FQPA SF = 30

cPAD = chr RfD

FQPA SF

= 0.0022 mg/kg/day

Extra 3x UF due to data 

gap for the chronic 

toxicity study in dogs.

2-year Study –Rat

LOAEL = 32.8 mg/kg/day (c?) based liver 

clinical pathology / histopathology and 

increased liver weight. 

Dermal Absorption 100% default; neither a dermal aborption study nor a dermal toxicity study (for 

extrapolation) is available in the database.

Short-Term

Dermal

Oral NOAEL = 

10.0 MOE = 100 Developmental toxicity Study – rats

Maternal LOAEL = 40 mg/kg/day based on 

decreased body weight gain and food 

consumption (most significant on days 7-10 

of dosing). This dose/endpoint/study was 

used for deriving the aRfD. Dermal 

toxicity study is not available. 100% 

dermal absorption factor should be used for 

this risk assessment.

Intermediate- and 

Long-Term

(Dermal)

Oral NOAEL = 

6.5

MOE = 100 2-year study - rat

LOAEL = 32.8 mg/kg/day () based on 

liver clinical pathology/histopathology and 

increased liver weight.

This dose/endpoint/study was used for 

deriving the cRfD. 100% dermal 

absorption factor should be used for this 

risk assessment.

Inhalation

(All Durations)

2 μg/L 14-week inhalation study

LOAEL = 19.9 μg/L based on clinical 

signs, increased liver and kidney weights, 

gross pathology and non-neoplastic 

histopathology. The route of exposure in 

this study is appropriate for this risk 

assessment.

NOAEL = 6.5 LOAEL = 32.8 Feeding/
Dichlormid Human Health Risk Assessment DP#385691

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Table 1. Summary of Toxicological Dose and Endpoints for Dichlormid Use in Human Risk Assessment 1.

Exposure

Scenario

Dose 

(mg/kg/day) 

and Factors

FQPA SF and 

Endpoint for Risk 

Assessment

Study and Toxicological Effects

Cancer mg/kg/day based on 

decreased BWG, 

decreased FE, 

increased liver weight, 

and liver histopath.

No evidence of 

carcinogenicity.

Carcinogenicity Study in rats

1 UF = uncertainty factor; FQPA SF = FQPA Safety Factor; NOAEL = no observed adverse effect level; LOAEL = 

lowest observed adverse effect level; PAD = population adjusted dose (a=acute, c=chronic); RfD = reference dose; 

LOC = level of concern; MOE = margin of exposure.