UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

MEMORANDUM 

Date: September 3, 2014 

OFFICE OF 

CHEMICAL SAFETY AND 

POLLUTION PREVENTION 

SUBJECT: Dimethenamid!Dimethenamid-P. Human Health Risk Assessment for Proposed 

New Use on Cottonseed Subgroup 20C. 

PC Code: 120051, 129051 

Decision No.: 482296 

Petition No.: 3F8 197 

Risk Assessment Type: Single Chemical Aggregate 

TXRNo.: NA 

MRIDNo.: NA 

DP Barcode: D418 118 

Registration No.: 7969-156 

Regulatory Action: Section 3 

Case No.: 7223 

CAS No.: 87674-68-8, 1635 15-14-8 

40 CFR: §180.464 

FROM: I van eves, ORE, Risk Assessor -PO. . · f' . ·. 

Bonrue Cropp-Kohlhgtan, Envu~~~/,--. ~ Marquea King, Ph.D., Toxicolo~/~~ Risk Assessment Branch 4 {/ 

Health Effects Division (7509P) ~ 

THROUGH: Elissa Reaves, Ph.D., Branch Chief ~j,~~ -­ Susan V. Hummel, Branch Senior Scienti . 

Risk Assessment Branch 4, HED (7509P) 

TO: Kable Davis/Erik Kraft (RM25) 

Herbicide Branch 

Registration Division (7505P) 

Page I of 51 
Table of Contents 

1 Execut·ive Summary ................................................................................................................ 4 

2 HED Recommendations .......................................................................................................... 6 

2.1 Data Deficiencies ............................................................................................................ 7 

2.2 Tolerance Considerations ................................................................................................ 7 

2.2.1 Enforcement Analytical Method ................................................................................. 7 

2.2.2 Recommended Tolerances .............................................. ............................................ 7 

2.2.3 Revisions to Petitioned-For Tolerances ...................................................................... 8 

2.2.4 International Harmonization ....................................................................................... 8 

2.3 Label Recommendations ................................................................................................. 8 

2.3.1 Recommendations from Residue Reviews ................................................................. 8 

2.3.2 Recommendations from Occupational and Residential Assessments .. ...................... 8 

3 Introduction ............................................................................................................................. 8 

3.1 Chemical Identity ............................................................................................................ 8 

3.2 Physical/Chemical Characteristics ................................................................................ 10 

3.3 Pesticide Use Pattern ..................................................................................................... 10 

3.4 Anticipated Exposure Pathways ................................................................................... 11 

3.5 Consideration of Environmental Justice ....................................................................... 12 

4 Hazard Characterization and Dose-Response Assessment ............................................... 12 

4.1 Toxicology Studies Available for Analysis .................................................................. 12 

4.2 Absorption, Distribution, Metabolism, Excretion (ADME) ......................................... 13 

4.2.1 Dermal Absorption .................................................................................................... 13 

4.3 Toxicological Effects .................................................................................................... 13 

4.4 Safety Factor for Infants and Children (FQPA Safety Factor) ..................................... 14 

4.4.1 Completeness of the Toxicology Database ............................................................... 14 

4.4.2 Evidence of Neurotoxicity ........................................................................................ 15 

4.4.3 Evidence of Sensitivity/Susceptibility in the Developing or Young Animal ........... 15 

4.4.4 Residual Uncertainty in the Exposure Database ....................................................... 15 

4.5 Toxicity Endpoint and Point of Departure Selections .................................................. 15 

4. 5 .1 Dose-Response Assessment ...................................................................................... 15 

4.5.2 Recommendation for Combining Routes of Exposures for Risk Assessment.. ........ 17 

4.5 .3 Classification of Carcinogenic Potential. .................................................................. 17 

4.5.4 Summary of Toxicological Doses and Endpoints for Dimethenamid-P for Use in 

Human Health Risk Assessments ......................................................................................... 18 

5 Dietary Exposure and Risk Assessment .............................................................................. 19 

5. 1 Residues of Concern Summary and Rationale .............................................................. 19 

5.2 Food Residue Profile ..................................................................................................... 20 

5.3 Water Residue Profile ................................................................................................... 23 

5.4 Dietary Risk Assessment .............................................................................................. 24 

5 .4.1 Description of Residue Data Used in Dietary Assessment.. ..................................... 24 

5.4.2 Percent Crop Treated Used in Dietary Assessment .................................................. 24 

5.4.3 Acute Dietary Risk Assessment.. .............................................................................. 24 

5.4.4 Chronic Dietary Risk Assessment ............................................................................ 25 

5.4.5 Cancer Dietary Risk Assessment.. ............................................................................ 25 

Page 2 of 51 
Page 3 of 51

5.4.6 Summary Table......................................................................................................... 25

6 Residential (Non-Occupational) Exposure/Risk Characterization .................................. 26

6.1 Residential Handler Exposure....................................................................................... 26

6.2 Post-Application Exposure ........................................................................................... 28

6.3 Residential Risk Estimates for Use in Aggregate Assessment ..................................... 30

6.4 Residential Bystander Post-application Inhalation Exposure....................................... 31

6.5 Spray Drift .................................................................................................................... 32

7 Aggregate Exposure/Risk Characterization....................................................................... 32

7.1 Acute Aggregate Risk ................................................................................................... 32

7.2 Short-and Intermediate-Term Aggregate Risk.............................................................. 32

7.3 Chronic Aggregate Risk................................................................................................ 33

7.4 Cancer Aggregate Risk ................................................................................................. 33

8 Cumulative Exposure/Risk Characterization .................................................................... 33

9 Occupational Exposure/Risk Characterization ................................................................. 33

9.1 Short-/Intermediate-Term Handler Risk....................................................................... 33

9.2 Short-/Intermediate-Post-Application Risk .................................................................. 37

9.2.1 Dermal Post-application Risk ................................................................................... 37

9.2.2 Inhalation Post-application Risk............................................................................... 39

10 References.............................................................................................................................. 40

Appendix A. Toxicology Profile and Executive Summaries .................................................. 41

Appendix B. Physical/Chemical Properties............................................................................. 48

Appendix C. Review of Human Research ............................................................................... 51
Page 4 of 51

1 Executive Summary

This assessment provides information to support a proposed Section 3 use of dimethenamid-P on 

cottonseed subgroup 20C. This document addresses the exposures and risks associated with 

exposures resulting from the new proposed use and currently registered residential uses of 

dimethenamid and dimethemamid-P on turf and gardens. Tolerances of 0.01 ppm on cottonseed

subgroup 20C, 1.5 ppm on cotton gin byproducts, and 0.02 ppm in cotton, seed, refined oil are 

proposed in connection with this action. Tolerances will be established in 40 CFR §180. 464. 

Dimethenamid and dimethenamid-P are selective chloroacetamide-type herbicides registered for 

the control of annual broadleaf and grass weeds in a variety of field and vegetable crops. 

Dimethenamid is an equal part mixture of the S- and R-isomers (50:50, S:R); whereas, 

dimethenamid-P is enriched in the biologically active S-isomer (90:10, S:R). While there are 

minor inconsistencies between the two sets of toxicity data, [RS]-dimethenamid and [S]-

dimethenamid-P show similar toxicity (see Appendix A). For this risk assessment the toxicology 

data from the 5050 S: R dimethenamid isomer is considered appropriate to use in characterizing 

the hazard for the dimethenamid-P (90:10, S:R isomer). BASF is requesting an amendment to the 

Section 3 registration for Outlook® Herbicide (EPA Registration Number 7969-156), a 6.0 lb/gal 

emulsifiable concentrate (EC) formulation of dimethenamid-P, to add preplant, preemergence 

and early postemergence broadcast applications to members of cottonseed subgroup 20C. 

Preplant surface or preemergence applications may be made at up to 0.47 lb ai/A and an early 

postemergence application may be made at up to 0.98 lb ai/A. Sequential applications of a 

preplant or preemergence application followed by an early postemergence application at least 14-

days after the initial application may be made at up to 1.45 lb ai/A/season. No pre-harvest 

interval (PHI) is specified but the last application may be made two weeks after the R1 initial 

bloom stage. The restricted entry interval for the proposed use is 12 hours. The proposed label 

requires baseline clothing plus chemical-resistant gloves, and protective eyewear as personal 

protective equipment (PPE). Applications for the proposed are expected to be made with an 

aircraft, groundboom truck, chemigation, and/or handheld equipment.

Based on the application rate and label information, occupational exposure is expected to occur 

for short- and intermediate-term durations. Chronic exposure is not expected for the proposed 

use pattern. Potential routes of exposure include both dermal and inhalation. Non-occupational 

(residential) exposures are not anticipated from the proposed new use, although residential 

exposure is expected for currently registered products. The existing residential uses have been 

reassessed to reflect updates to HED’s 2012 Residential SOPs1along with policy changes for 

body weight assumptions. 

Hazard Characterization 

The primary target organ for dimethenamid (enriched (P) and racemic (RS) mixtures) is the liver 

and is displayed throughout the database and in all species tested. The toxicity in 90-day feeding 

studies in rats with [S]-dimethenamid-P and [RS]-dimethenamid were very similar with 

decreased body decreased body weights, increased cholesterol and changes in liver weights 

along with histopathology showing microscopic effects (centrilobular hypertrophy, periportal 

 

1 Available: http://www.epa.gov/pesticides/science/residential-exposure-sop.html
Page 5 of 51

eosinophilic inclusions and necrosis) in the liver. Chronic studies performed with [RS]-

dimethenamid in the rat, mouse and dog showed decreases in body weight and food efficiency as 

accompanying effects over time. At higher dose levels, liver pathology (hepatic lesions, bile 

duct hyperplasia, and tumors), stomach hyperplasia, and some indications of kidney effects were 

noted. Two 21-day dermal toxicity studies in rabbits were conducted on [RS]-dimethenamid and 

in one of those studies minor skin irritation was observed at all doses tested and a decrease in 

body weight gain was also seen at the lowest effect level. 

Points of Departure for Risk Assessment

The acute and chronic dietary points of departure (PODs) were based on a series of effects 

(depressed respiration, unsteady gait, poor general condition) which included the use of both the 

acute neurotoxicity study (general population) and a rabbit developmental study (females 13-49 

years) which displayed abortions, increased resorptions and post-implantation loss The shortand intermediate-term POD for dermal exposure (No observed adverse affect level (NOAEL = 

300 mg/kg/day) was based on decreased body weight in a 21 day dermal study in rabbits. The 

inhalation and incidental oral toxicity endpoint (NOAEL = 10 mg/kg/day) was selected from a 

subchronic and chronic oral toxicity study in dogs based on decreased body weight in females, 

increased relative to body liver weight in both sexes, increased periportal cytoplasmic 

vacuolation in liver in both sexes, and dilation of liver sinusoids in females. A subchronic 

inhalation toxicity study is not available, however, the Hazard and Science Policy Council 

(HASPOC), using a weight of the evidence (WOE) approach, concluded that a subchronic 

inhalation study is not required for dimethenamid-P at this time (TXR# 0056993). For acute and 

chronic dietary risk assessments, a 100X uncertainty factor was applied (interspecies factor of 

10X and intraspecies factor of 10X, FQPA factor of 1X). 

Summary of Acute and Chronic Dietary Exposure and Risk Estimates

Both the acute and chronic assessments are conservative and incorporated tolerance level 

residues, assume 100% crop treated and use default processing factors. Estimated drinking water 

concentrations (EDWCs) used in the assessments were generated using Tier I modeling. 

For the acute assessment, aggregate dietary (food and drinking water) exposures are below 

HED’s level of concern (<100% aPAD) at the 95

th percentile of exposure for all population 

subgroups. The acute dietary exposure at the 95

th percentile of exposure is estimated at 0.008399

mg/kg/day for the overall U.S. population, equivalent to <1% of the aPAD. The population 

subgroup with the highest estimated acute dietary exposure is All Infants <1 year of age, with an 

estimated exposure at the 95

th percentile of 0.026253 mg/kg/day, equivalent to 1.3% of the 

aPAD. 

For the chronic assessment, aggregate dietary (food and drinking water) exposures are below 

HED’s level of concern (<100% cPAD) for all population subgroups. The chronic dietary 

exposure is estimated at 0.003241 mg/kg/day for the general U.S. population, equivalent to 6.5% 

of the cPAD. The population subgroup with the highest estimated chronic dietary exposure is 

All Infants <1 year of age, with an estimated exposure of 0.008326 mg/kg/day, equivalent to 

17% of the cPAD. 
Page 6 of 51

Summary of Residential Exposure and Risk Estimates

All existing residential exposures have been reassessed to reflect updates to HED’s 2012 

Residential SOPs along with policy changes for body weight assumptions. No registered 

products resulted in residential handler or post-application risk estimates of concern. All risk 

estimates are greater than HED’s Level of Concern (LOC) of 100 and therefore not of concern. 

Dermal Margins of Exposure (MOEs) ranged from 250 to 5,300,000; Inhalation MOEs range 

from 7,700 to 1,500,000; and post-application MOEs range from 310 to 200,000.

Aggregating Exposures/Risk Estimates

The aggregate assessments of acute and chronic dietary exposure were based on food and water 

only. Short-/intermediate-term dietary exposure was aggregated with residential inhalation 

exposure because the PODs were based on the same study which showed toxicity effects in the 

liver. Dermal exposure was not included because the effect (body weight gain) was considered 

to be non-specific. Aggregate risk estimates (food, water and residential) were not of concern 

for HED (LOC=100); MOEs were 2,200 for adults and 1,100 for children (1<2 years of age).

Summary of Occupational Exposure and Risk Estimates

Occupational handler dermal and inhalation exposure and risk assessment are not of concern (i.e.

all MOEs ≥ 100) at baseline mitigation (no PPE), with one exception. The dermal exposure 

scenario of mixing and loading a liquid formulation of dimethenamid-P for aerial applications 

resulted in an MOE of 92. However, with the use of additional PPE (i.e., gloves) the risk 

estimate was mitigated to an MOE of 540. Dermal MOEs ranged from 92 to 9,100. Inhalation 

MOEs ranged from 3,100 to 140,000. Note that only engineering control (enclosed cockpit) data 

are available to assess risks to handlers operating aircrafts. Short- and intermediate-term postapplication risk estimates were not a concern on day 0 (12 hours following application) for all 

post-application activities (MOEs ranged from 5,100 to 15,000). 

Restricted Entry Interval (REI)

Under 40 CFR 156.208 (c) (2) (iii), active ingredients classified as Toxicity Category III or IV 

for acute dermal, eye irritation and primary skin irritation are assigned a 12-hour REI. 

Therefore, the label required REI of 12 hours is adequate to protect agricultural workers from 

post-application exposures to dimethenamid-P. 

Based on the Agency's current practices, a quantitative non-cancer occupational post-application 

inhalation exposure assessment was not performed for dimethenamid-P at this time. If new 

policies or procedures are put into place, the Agency may revisit the need for a quantitative 

occupational post-application inhalation exposure assessment for dimethenamid-P.

2 HED Recommendations

Deficiencies are outlined in Section 2.1 below. The specific tolerance recommendations are 

discussed in Section 2.2, and label modifications are discussed in Section 2.3.
Page 7 of 51

2.1 Data Deficiencies

HED has examined the residue chemistry database for dimethenamid, and pending submission of 

a revised Section F of the petition (see requirements under Proposed Tolerances), there are no 

residue chemistry issues that would preclude granting an amended registration for Outlook® 

Herbicide (EPA Registration Number 7969-156) to permit the proposed use on members of 

cottonseed subgroup 20C.

A subchronic inhalation study is required but being waived at this time due to a weight of the 

evidence approach which considered all of the available hazard and exposure information for 

dimethenamid.

2.2 Tolerance Considerations

2.2.1 Enforcement Analytical Method

An adequate enforcement method is available for determining residues of both dimethenamid 

and dimethenamid-P residues in plant commodities. The GC/NPD method (AM-0884-0193-1) 

has been validated by the Agency and submitted for publication in FDA’s Pesticide Analytical 

Manual (PAM), Volume II. The method does not separate the S- and R-isomers of 

dimethenamid. The limit of quantitation (LOQ; determined as the lowest level of method 

validation, LLMV) is 0.01 ppm. As tolerances are not required for livestock commodities, no 

analytical methods for livestock commodities are required.

2.2.2 Recommended Tolerances

Tolerances for plant commodities are established under §180.464, and are expressed in terms of 

dimethenamid per se. The tolerance definition proposed by BASF is in terms of dimethenamid 

per se. The tolerances proposed by BASF are listed in Table 2.2.2 along with the tolerance 

levels recommended by HED and corrected commodity definitions.

Adequate residue data are available to support the proposed tolerances. The submitted data are 

adequate to support tolerances of 0.01 ppm and 1.5 ppm for residues of dimethenamid-P in/on 

cottonseed subgroup 20C and cotton gin byproducts, respectively. The recommended cottonseed 

subgroup 20C tolerance was set at the LOQ of the enforcement method and the recommended 

cotton gin byproduct tolerance was calculated using the Organization for Economic Cooperation 

and Development (OECD) tolerance calculation procedures. The submitted cotton processing 

study conducted at an exaggerated rate (3x) is adequate to support the proposed use and 

demonstrates that separate tolerances for residues of dimethenamid-P are not need for processed 

commodities of cotton. 
Page 8 of 51

Table 2.2.2. Tolerance Summary for Dimethenamid-P

Commodity Proposed Tolerance 

(ppm)

Recommended 

Tolerance (ppm)

Correct Commodity Definition

Comments

40 CFR §180.464(a)

Cottonseed subgroup 20C 0.01 0.01 Cottonseed subgroup 20C

Cotton, gin byproducts 1.5 1.5 Cotton, gin byproducts

Cotton, seed, refined oil 0.02 --

While data suggest a very slight 

potential for concentration of 

dimethenamid in refined oil, a 

separate tolerance in refined oil will 

not be needed since the exaggerated 

rate processing study demonstrates 

that the petitioned-for/recommended 

tolerance in/on cotton seed (0.01 

ppm) will be adequate to cover 

potential residues of dimethenamid 

in refined oil. 

2.2.3 Revisions to Petitioned-For Tolerances

A separate tolerance in refined oil will not be needed since the exaggerated rate processing study 

demonstrates that the petitioned-for/recommended tolerance in/on cotton seed (0.01 ppm) will be 

adequate to cover potential residues of dimethenamid-P in refined oil. 

2.2.4 International Harmonization

There are no established Codex, Canadian or Mexican maximum residue limits (MRLs) for 

dimethenamid/dimethenamid-P in/on cotton commodities (email from M. Negussie to B. CroppKohlligian dated 2/28/14). Therefore, there is no question about harmonization of the proposed 

tolerances.

2.3 Label Recommendations

2.3.1 Recommendations from Residue Reviews

No changes are required to the proposed label.

2.3.2 Recommendations from Occupational and Residential Assessments

None.

3 Introduction

3.1 Chemical Identity

Structure and nomenclature are reported in Table 3.1.
Page 9 of 51

Table 3.1. Dimethenamid-P Nomenclature.

Compound

Common name Dimethenamid-P (or S-Dimethenamid); 90:10, S:R isomer ratio

Company experimental name BAS 656H; SAN 1289

IUPAC name (S)-2-chloro-N-(2,4-dimethyl-3-thienyl)-N-(2-methoxy-1-methylethyl) acetamide

CAS name 2-chloro-N-(2,4-dimethyl-3-thienyl)-N-[(1S)-2-methoxy-1-methylethyl] 

acetamide

CAS registry number 163515-14-8

End-use product (EP) Not applicable

Compound

Common name M23

Chemical name N-(2,4-dimethyl-thiophen-3-yl)-N-(2-methoxy-1-methy-ethyl)-oxalamic acid

Compound

Common name M26

Chemical name 3-{[(2,4-dimethyl-thiophen-3-yl)-(2-methoxy-1-

methyethyl)carbamoyl]methylsulfanyl}-2-hydroxy-propionic acid

Compound

Common name M27

Chemical name [(2,4-dimethyl-thiophen-3-yl)-(2-methoxy-1-methylethyl)carbamoyl]-

methanesulfonate [standard depicted]

S

H3C

CH3

N

O

CH2Cl

H3C

H

O

CH3
Page 10 of 51

Table 3.1. Dimethenamid-P Nomenclature.

Compound

Common name M30

Chemical name 3-[(2-{(2,4-dimethyl-3-thienyl)[(1S)-2-methoxy-1-methylethyl]amino}-2-

oxoethyl)sulfinyl]-2-hydroxypropanoic acid

3.2 Physical/Chemical Characteristics

The physicochemical properties of dimethenamid-P are reported in Appendix B.

3.3 Pesticide Use Pattern

BASF has submitted a Section B of the petition proposing an amendment to the Section 3 

registration for Outlook® Herbicide (EPA Registration Number 7969-156), a 6.0 lb/gal 

emulsifiable concentrate (EC) formulation of dimethenamid-P, to add preplant, preemergence 

and early postemergence applications to members of cottonseed subgroup 20C. Preplant surface 

or preemergence applications may be made at up to 0.47 lb ai/A and an early postemergence 

application may be made at up to 0.98 lb ai/A. Sequential applications of a preplant or 

preemergence application followed by an early postemergence application at least 14-days after 

the initial application may be made at up to 1.45 lb ai/A/season. No preharvest interval (PHI) is 

specified but the last application may be made two weeks after the R1 initial bloom stage. 

Section B of the petition is draft supplemental labeling to the current Outlook® Herbicide label 

(EPA Registration Number 7969-156). The use directions of the draft supplemental labeling to 

the subject end-use product under consideration provided in Section B are summarized Table 

3.3.
Page 11 of 51

Table 3.3. Summary of Directions for Proposed Use of Dimethenamid-P.

Appl. Timing, 

Type, and Equip.

Formulation

[EPA Reg. 

No.]

Max. Appl. 

Rate 

(lb ai/A)

Max. 

No. 

Appl. 

per 

Season

Max. 

Seasonal 

Appl. 

Rate

(lb ai/A)

PHI

(days) Use Directions and Limitations

Cottonseed subgroup 20C: Cotton

Preplant surface, 

preemergence 

and/or 

postemergence 

foliar broadcast.

Ground, aerial or 

chemigation

6.0 lb/gal 

EC

[7969-156]

0.47

preplant surface 

or 

preemergence 

1 1.45 Not 

Specified

May be applied as single application 

or in sequential applications (preplant 

or preemergence followed by 

postemergence). Sequential 

applications must be separated by at 

least 14 days. No PHI is specified; 

however, postemergence applications 

may be made from first true leaf stage 

to the mid-bloom stage (i.e., two 

weeks after R1 initial bloom stage).

0.98 

postemergence

1

PHI = preharvest interval.

The current label for Outlook® Herbicide (EPA Registration Number 7969-156; Accepted 

3/20/14) specifies the following spray volume and rotational crop restrictions not provided in 

Section B of the petition:

 Ground Application: Apply in a minimum of 5 gallons of water per acre.

 Aerial Application: Apply in a minimum of 2 gallons of water per acre.

 Rotational Crop Restrictions: If any labeled crop treated with Outlook® Herbicide is lost 

to adverse weather or for other reasons, the area treated may be replanted to any of the 

labeled crops immediately, unless specified otherwise in the crop specific information 

section of this label. Fall seeded cereal crops may be planted 4 months or more following 

treatment. There are no rotational crop restrictions for the spring following the previous 

year’s application of Outlook® Herbicide.

The restricted entry interval for the proposed use is 12 hours. The proposed label requires 

baseline clothing plus chemical-resistant gloves, and protective eyewear as personal protective 

equipment (PPE).

3.4 Anticipated Exposure Pathways

The Registration Division has requested an assessment of human health risk to support the 

proposed new use of dimethenamid-P on cottonseed subgroup 20C: cotton. Humans may be 

exposed to dimethenamid-P in food and drinking water, since this chemical may be applied 

directly to growing crops and application may result in dimethenamid-P reaching surface and 

ground water sources of drinking water. In an occupational setting, applicators may be exposed 

while handling the pesticide prior to application, as well as during application. There is a 

potential for post-application exposure for workers re-entering treated fields. There are no 

proposed residential uses at this time; however, there are existing residential uses that have been 

reassessed to reflect updates to HED’s 2012 Residential SOPs2along with policy changes for 

body weight assumptions. The revision of residential exposures will impact the human health 

 

2 Available: http://www.epa.gov/pesticides/science/residential-exposure-sop.html
Page 12 of 51

aggregate risk assessment for dimethenamid-P.

3.5 Consideration of Environmental Justice

Potential areas of environmental justice concerns, to the extent possible, were considered in this 

human health risk assessment, in accordance with U.S. Executive Order 12898, "Federal Actions 

to Address Environmental Justice in Minority Populations and Low-Income Populations," 

(http://www.eh.doe.gov/oepa/guidance/justice/eo12898.pdf. As a part of every pesticide risk 

assessment, OPP considers a large variety of consumer subgroups according to well-established 

procedures. In line with OPP policy, HED estimates risks to population subgroups from pesticide 

exposures that are based on patterns of that subgroup’s food and water consumption, and 

activities in and around the home that involve pesticide use in a residential setting. Extensive 

data on food consumption patterns are compiled by the USDA under the National Health and 

Nutrition Survey/What We Eat in America (NHANES/WWEIA) and are used in pesticide risk 

assessments for all registered food uses of a pesticide. These data are analyzed and categorized 

by subgroups based on age and ethnic group. Additionally, OPP is able to assess dietary 

exposure to smaller, specialized subgroups and exposure assessments are performed when 

conditions or circumstances warrant. Whenever appropriate, non-dietary exposures based on 

home use of pesticide products and associated risks for adult applicators and for toddlers, youths, 

and adults entering or playing on treated areas post-application are evaluated. Further 

considerations are currently in development as OPP has committed resources and expertise to the 

development of specialized software and models that consider exposure to bystanders and farm 

workers as well as lifestyle and traditional dietary patterns among specific subgroups.

4 Hazard Characterization and Dose-Response Assessment

4.1 Toxicology Studies Available for Analysis

The toxicology database for dimethenamid-P is considered complete. Dimethenamid ([RS]-

dimethenamid) and dimethenamid-P ([S]-dimethenamid-P) are selective herbicides. 

Dimethenamid is a racemic 50:50 S:R isomer. Dimethenamid-P is enriched in the biologically 

active S-isomer (90:10, S:R). BASF stopped producing, marketing and selling the 50:50 S:R 

isomer for use in the US in 2002-2003 and has replaced it with dimethenamid-P (90:10, S:R). 

While there are minor inconsistencies between the two sets of toxicity data, [RS]-dimethenamid 

and [S]-dimethenamid-P show similar toxicity (see Appendix A). A subchronic inhalation 

toxicity study is not available. However, the Hazard and Science Policy Council (HASPOC), 

using a weight of the evidence (WOE) approach, concluded that a subchronic inhalation study is 

not required for dimethenamid-P at this time (TXR# 0056993). The toxicological studies for 

[S]-dimethenamid-P database are limited but include: 1) subchronic oral toxicity study in rats, 2) 

neurotoxicity battery in rats, 3) immunotoxicity in mice, 4) a mutagenicity battery, and 5) acute 

6-pack of studies. The toxicological studies currently in the [RS]-dimethenamid database which 

are used for bridging include: 1) subchronic oral toxicity study in rats, 2) chronic/carcinogenicity 

studies in rats and mice, 3) subchronic and chronic oral toxicity study in dogs, 4) developmental 

studies in rats and rabbits, 5) reproduction study in rats, 6) metabolism studies in rats, 7) a 

mutagenicity battery, and 8) acute 6-pack of studies. Therefore, the toxicity database for the 
Page 13 of 51

[RS] mixture is complete and the bridging studies to the [S]-dimethenamid-P toxicity data are 

complete (TXR# 0051920). New toxicity data have been received since the last risk assessment 

(B.Daiss, D348401, 8/27/08). These new data include reviews of acute and subchronic 

neurotoxicity and immunotoxicity studies. 

4.2 Absorption, Distribution, Metabolism, Excretion (ADME)

Oral rat metabolism studies with [RS]-dimethenamid showed extensive metabolism (>30 

metabolites). In the rat dimethenamid-P parent was extensively metabolized, being essentially 

complete within 3 days. Over 90% was excreted in the urine, feces, and bile within 7 days. 

Plasma data for the dimethenamid-P indicate that the Cmax was about 72 hours post 

administration both for a dose of 10 mg/kg bw and a dose of 1000 mg/kg/bw. The blood levels 

did not decrease significantly between 72 and 168 hours post dosing. Metabolism studies with 

[RS]-dimethenamid showed extensive metabolism (>30 metabolites). In the rat dimethenamid-P 

parent was extensively metabolized, being essentially complete within 3 days over 90% excreted 

in the urine, feces, and bile within 7 days. 

4.2.1 Dermal Absorption

Dermal absorption and dermal penetration studies are not available for either isomer. 

4.3 Toxicological Effects

The primary target organ for dimethenamid (enriched (P) and racemic (RS) mixtures) is the liver 

and is displayed throughout the database and in all species tested. The toxicity in 90-day feeding 

studies in rats with [S]-dimethenamid-P and [RS]-dimethenamid were very similar with 

decreased body decreased body weights, increased cholesterol and changes in liver weights 

along with histopathology showing microscopic effects (centrilobular hypertrophy, periportal 

eosinophilic inclusions and necrosis) in the liver. Chronic studies performed with [RS]-

dimethenamid in the rat, mouse and dog showed decreases in body weight and food efficiency as 

accompanying effects over time. At higher dose levels, liver pathology (hepatic lesions, bile 

duct hyperplasia, and tumors), stomach hyperplasia, and some indications of kidney effects were 

noted. Two 21-day dermal toxicity studies in rabbits were conducted on [RS]-dimethenamid and 

in one of those studies minor skin irritation was observed at all doses tested and a decrease in 

body weight gain was also seen at the lowest effect level. 

The concern for neurotoxicity is low based on the results of the newly submitted acute and 

subchronic neurotoxicity studies. The acute neurotoxicity study resulted in effects such as 

partially closed eyelids, lacrimation and slight salivation at the highest dose tested of (600 

mg/kg/bw). There were no treatment-related or toxicologically significant findings during the 

gross examination of rats or in the microscopic examination of neurological tissues. In the 

subchronic neurotoxicity study, there were no clinical signs seen and no adverse effects seen up 

to 323/390 mg/kg/bw day. Systemic effects seen were renal pelvic dilation in males (considered 

incidental) and a trend of higher liver weights in females was found at the lowest dose tested and 

were not considered adverse nor were they corroborated with any other guideline studies 
Page 14 of 51

submitted within the database. There were no liver histopathology or clinical chemistry 

measurements in the subchronic neurotoxicity study, however, the adversity of this finding is 

supported by the observation of multiple liver effects (increased cholesterol, increased total 

serum protein, increased liver weights, and enlarged centrilobular hepatocytes) in the 90-day rat 

study at doses of 98/119 (M/F) mg/kg/day and above. There was no neurotoxicity observed at 

higher doses nor in other guideline studies in the dimethenamid-P database. 

There is no concern for increased qualitative and/or quantitative susceptibility after exposure to 

either dimethenamid isomer in developmental toxicity studies in rats and rabbits, or a rat 

reproduction study. Developmental toxicity studies show increased post-implantation loss and 

minor skeletal variations in the rat, and late resorptions and minor skeletal variations in the rabbit 

at the highest dose tested (LOAEL, 425 mg/kg/day - [RS]-dimethenamid). In the rabbit, the 

developmental effects occurred at the same dose as maternal toxicity (LOAEL, 150 mg/kg/day), 

whereas in the rat, the developmental toxicity occurred at much higher doses than in the dams 

(LOAEL, 215 mg/kg/day). The chosen NOAEL of 75 mg/kg/day ([S]-dimethenamid) is 

considered protective for effects seen in both studies. The reproduction study resulted in 

decreases in body weight in both pups and parental animals at the same dose levels. The only 

other effects noted at the LOAEL of 150 mg/kg/day were increases in liver weights in both male 

and female parental animals. 

A review of the recently submitted immunotoxicity resulted in no immunotoxicity effects at the 

limit dose of 1167 mg/kg (MRID 49184307). There were, however, at this dose increased 

absolute and relative liver weights. 

A battery of mutagenicity studies with [S]-dimethenamid-P is negative for genetic mutations, 

including unscheduled DNA synthesis. However, mutagenicity studies with [RS]-dimethenamid 

showed positive results for unscheduled DNA synthesis and there were equivocal results in two 

dominant lethal studies. [RS]-dimethenamid has been classified as group “C” possible human 

carcinogen, based on an increasing trend for liver tumors (males) seen in the chronic 

toxicity/carcinogenicity rat study. There were no dose-related tumors seen in the mouse 

carcinogenicity study. For the purpose of risk characterization, the RfD approach should be 

used. The chronic RfD will be protective of both non-cancer and cancer effects. 

4.4 Safety Factor for Infants and Children (FQPA Safety Factor)

Regarding FQPA, the toxicity database is complete and is considered adequate to evaluate risks 

to infants and children. All studies required as part of the 40 CFR Part 158 data requirements 

have been satisfied. There is no concern for increased qualitative and/or quantitative 

susceptibility following in utero and pre- or post-natal exposure. All guideline studies submitted 

have clearly defined NOAELs and LOAELs. Therefore, HED recommends that the 10x FQPA 

SF be reduced to 1x. 

4.4.1 Completeness of the Toxicology Database 

The toxicology database for dimethenamid-P is complete. Based on a WOE approach 

considering all the available hazard and exposure information for dimethenamid-P, the HED 
Page 15 of 51

HASPOC concluded that a subchronic inhalation toxicity study is not required at this time 

(TXR# 0056993). Acceptable studies are available and are adequate to evaluate the potential 

risks for infants and children. Those studies include: developmental, reproduction, chronic, 

subchronic, acute and subchronic neurotoxicity, and immunotoxicity. 

4.4.2 Evidence of Neurotoxicity

Acute and subchronic neurotoxicity studies are available for dimethenamid-P. However, the 

concern for neurotoxicity is low since clinical signs were not observed until a high dose after a 

single dose and were likely agonal and not necessarily attributed to neurotoxicity. The 

subchronic neurotoxicity study did not result in neurotoxic effect but resulted in systemic effects 

at higher doses. 

4.4.3 Evidence of Sensitivity/Susceptibility in the Developing or Young Animal 

There is no concern for increased qualitative and/or quantitative susceptibility following in utero

(rats and rabbits) and pre-and post-natal exposure (rats) to the [RS] or the [S] dimethenamid. 

NOAEL and LOAEL values for the fetal/pup effects observed in the developmental study and 

effects seen in the reproduction studies occurred at the same doses or higher than those which 

caused maternal toxicity. The rabbit developmental study was used as an acute dietary endpoint 

for females 13-49 years of age. The points of departure selected for risk assessment are 

protective of effects seen in these guideline studies. Therefore the acute and chronic dietary risk 

assessments are protective of potential fetal/offspring effects.

4.4.4 Residual Uncertainty in the Exposure Database

There are no residual uncertainties in the exposure database. The dietary risk assessment is 

conservative and will not underestimate dietary and/or non-dietary occupational exposure to 

dimethenamid-P. The acute and chronic dietary assessments conducted with DEEM-FCID were 

refined analyses. The assessments utilized anticipated residues, default processing factors, and 

available percent crop treated data. The DEEM analysis also used Tier 1 drinking water 

estimates. For these reasons it can be concluded that the DEEM-FCID analysis does not 

underestimate risk from acute or chronic exposure to thiabendazole. Similarly, HED does not 

believe that the non-dietary occupational exposures are underestimated because they are also 

based on conservative assumptions, including maximum application rates, and standard values 

for unit exposures and acreage treated/amount handled.

4.5 Toxicity Endpoint and Point of Departure Selections

4.5.1 Dose-Response Assessment

Acute Dietary (general population)

The acute rat neurotoxicity study (49184304) NOAEL is 200 mg/kg with a LOAEL of 600 

mg/kg, based on a number of clinical effects (slightly depressed respiration, semi-closed eyelids, 

piloerection, slightly unsteady gait, smeared fur in anogenital region, slight twitching, and poor 
Page 16 of 51

general condition) in females and some males. This endpoint is appropriate for the population of 

concern and is a result of a single dose. 

Acute Dietary (females 13-49 years of age)

The rabbit developmental toxicity study (41706809) NOAEL is 75 mg/kg/day with a maternal 

LOAEL of 150 mg/kg/day, based on abortions. The developmental NOAEL is 75 mg/kg/day. 

The developmental LOAEL is 150 mg/kg/day based on increased resorptions and postimplantation loss. The resorptions and post implantation loss are presumed to be the result from 

a single dose. The developmental endpoint is female specific and therefore appropriate for 

females 13-49 years of age. The acute endpoint is supported by a range-finding developmental 

study in rats with [S]-dimethenamid-P, which showed increased resorptions at 400 mg/kg/day.

Chronic Dietary

The chronic toxicity/carcinogenicity rat study (MRIDs 41706808/42030102) was selected based 

on liver effects (decreases in body weight, weight gain, and increased microscopic hepatic 

lesions in both sexes) observed at the LOAEL of 36 mg/kg/day (NOAEL of 5 mg/kg/day). The 

duration of this study and the route of exposure are appropriate for assessing chronic dietary 

exposure. This endpoint and POD are protective of adverse effects observed at higher doses in 

other studies. 

Incidental oral and Inhalation (short and intermediate) 

Co-critical studies based on the dog subchronic oral toxicity study (MRID 41615902) and the 

dog chronic oral study (MRID 41615903) were selected. The NOAEL of 10.1 mg/kg/day is 

based on the chronic dog study. The LOAEL of 33.6 mg/kg/day from the subchronic dog study 

is based on decreased body weight in females, increased relative to body liver weight in both 

sexes, increased periportal cytoplasmic vacuolation in liver in both sexes, and dilation of liver 

sinusoids in females. The Level of Concern of 100 is required for the short- and intermediateterm scenarios for inhalation exposure is based on the conventional uncertainty factor of 100. 

This includes 10x for interspecies extrapolation and 10x for intraspecies variation).

Dermal (short and intermediate)

There are two 21-day dermal toxicity studies in New Zealand White Rabbits used for points of 

departure for the dermal endpoint. In the first study (MRID 41662414), signs of toxicity were 

limited to decreased body weight gain in male rabbits at the 500 mg/kg/day dose level which was 

determined to be the LOAEL. No NOAEL was identified.

In a second study (MRID 41951301), [RS] dimethenamid (78.8%) at 1000 mg/kg/day for 21 

days exceeded the maximum tolerated dose producing severe local irritation and death (5/5 

males and 4/5 females). Dermal irritation was noted at 30 mg/kg/day but no systemic effects 

were observed. The systemic LOAEL was therefore established at 1000 mg/kg/day. The 

systemic NOAEL is 300 mg/kg/day. Therefore, when the studies are used in combination, the 

NOAEL of 300 mg/kg from the second dermal rabbit study may be used with the systemic 

effects noted in the first dermal rabbit study with a LOAEL of 500 mg/kg/day, based on 

decreased body weight gain.
Page 17 of 51

The route specific studies are appropriate for both the population and duration of exposure. The 

two 21-day dermal toxicity studies together provide data that can be used determine the LOAELs 

and NOAELs for dermal toxicity. An MOE 100 is required for the short- and intermediate-term 

scenarios for dermal exposure is based on the conventional uncertainty factor of 100. This 

includes 10x for interspecies extrapolation and 10x for intraspecies variation.

4.5.2 Recommendation for Combining Routes of Exposures for Risk Assessment

When there are potential occupational and residential exposures to a pesticide, the risk 

assessment must address exposures from three major sources: incidental oral, dermal and 

inhalation. It must be determined whether or not the individual exposures have the same 

toxicological effects. If they do, then they can be combined. For dimethenamid-P, the endpoints 

for inhalation and incidental oral were based on the same study, and therefore can be combined. 

However, the dermal assessment is based on non-specific effects (body weight gain only) and 

should not be combined. 

4.5.3 Classification of Carcinogenic Potential

Dimethenamid-P is classified as group “C” possible human carcinogen, based on weak evidence 

for carcinogenicity. The weak evidence is based only on an increasing trend for liver tumors in 

male rats at the highest dose. The liver tumors were not statistically significant for a pairwise 

test with controls. There is no evidence of cancer in male or female mice. The evidence for 

mutagenicity is equivocal. For [RS]-dimethenamid, only one study showed positive DNA 

synthesis in vitro while there was no evidence of mutagenicity in vivo. With the [S]-

dimethenamid, there is no evidence for gene mutation in the unscheduled DNS synthesis assay. 

There is lack of biological concern for the dominant lethal studies since the effects are not 

characteristic of a typical dominant lethal response but rather was a result of resorptions noted in 

the assay. Therefore, based on the weight of the evidence the agency is confident the chronic 

endpoint and point of departure is protective of the liver tumors observed in the male rats.
Page 18 of 51

4.5.4 Summary of Toxicological Doses and Endpoints for Dimethenamid-P for Use in 

Human Health Risk Assessments 

Table 4.5.4. Summary of Toxicological Doses and Endpoints for Dimethenamid-P for Use in Human Health Risk 

Assessments

Exposure/

Scenario

Point of 

Departure

(mg/kg/day)

Safety Factors

POD for Risk 

Assessment 

(mg/kg/day)

Study and Toxicological Effects

Acute Dietary 

(General Population, 

including Infants and 

Children)

NOAEL = 

200

UFA= 10x

UFH=10x

FQPA SF= 1x

aRfD = 2.0

aPAD = 2.0

Acute Neurotoxicity (MRID 49184305)

LOAEL= 600 mg/kg based on lacrimation, 

salivation, irregular and accelerated respiration, 

slight tremors, reduced exploration, unsteady 

gait, significantly reduced rearing \

Acute Dietary

(Females 13-49 years 

of age)

NOAEL = 75

UFA= 10x

UFH=10x

FQPA SF= 1x

aRfD = 0.75

aPAD = 0.75

Developmental Rabbit Study (MRID 

41706809)

Maternal; LOAEL = 150 mg/kg/day based on 

abortions (not considered acute effect).

Developmental; LOAEL = 150 mg/kg/day 

based on post-implantation loss

Chronic Dietary (All 

Populations) NOAEL= 5 

UFA= 10x

UFH=10x

FQPA SF= 1x

cRfD = 0.05

cPAD = 0.05

Chronic/carcinogenicity rat study (MRIDs 

41706808/42030102)

LOAEL = M/F; 36/49 mg/kg/day based on 

decreased body weight and body weight gain 

in both sexes, increased food conversion ratios 

in females, and increased microscopic hepatic 

lesions in both sexes.

Incidental Oral ShortTerm (1-30 days) and 

Intermediate-Term (1-

6 months)

NOAEL= 10 

UFA= 10 x

UFH = 10 x

Occupational 

LOC for MOE 

= 100

Subchronic/chronic oral dog studies (MRIDs 

41615902 & 41615903) 

Chronic dog NOAEL = 10 mg/kg/day

Chronic dog LOAEL = 48.7 mg/kg/day

Subchronic NOAEL = 4.72 mg/kg day

Subchronic LOAEL = 33.6 mg/kg/day based 

on decreased body weight in females, 

increased relative to body liver weight in both 

sexes, increased periportal cytoplasmic 

vacuolation in liver in both sexes, and dilation 

of liver sinusoids in females.

Dermal Short- Term 

(1-30 days) and

Intermediate-Term (1-

6 months)

NOAEL= 

300 

UFA= 10x

UFH=10x

Occupational 

LOC for MOE 

= 100

21 Day dermal rabbit study (MRIDs 

41662414/419513010)

LOAEL = 500 mg/kg/day based on decreased 

body weight gain only (non-specific)

Inhalation Short- Term 

(1-30 days) 

NOAEL= 10

UFA= 10 x

UFH = 10 x

Occupational 

LOC for MOE 

= 100

Subchronic/chronic oral dog studies (MRIDs 

41615902 & 41615903) 

Chronic dog NOAEL = 10 mg/kg/day

Chronic dog LOAEL = 48.7 mg/kg/day

Subchronic NOAEL = 4.72 mg/kg day

Subchronic LOAEL = 33.6 mg/kg/day based 

on decreased body weight in females, 

increased relative to body liver weight in both 

sexes, increased periportal cytoplasmic 

vacuolation in liver in both sexes, and dilation 

of liver sinusoids in females

Cancer (oral, dermal, 

inhalation)

“C” Possible human carcinogen. The cRfD is considered protective of the cancer effects.
Page 19 of 51

Point of Departure (POD) = A data point or an estimated point that is derived from observed dose-response data and used to mark the beginning of 

extrapolation to determine risk associated with lower environmentally relevant human exposures. NOAEL = no observed adverse effect level. LOAEL = 

lowest observed adverse effect level. UF = uncertainty factor. UFA = extrapolation from animal to human (interspecies). UFH = potential variation in 

sensitivity among members of the human population (intraspecies). UFL = use of a LOAEL to extrapolate a NOAEL. UFS = use of a short-term study for 

long-term risk assessment. UFDB = to account for the absence of key data (i.e., lack of a critical study). FQPA SF = FQPA Safety Factor. PAD = population 

adjusted dose (a = acute, c = chronic). RfD = reference dose. MOE = margin of exposure. LOC = level of concern. N/A = not applicable.

5 Dietary Exposure and Risk Assessment 

5.1 Residues of Concern Summary and Rationale

The dimethenamid risk assessment team has determined the residues of concern for dietary risk 

assessment and the tolerance expression and these are summarized in Table 5.1. 

Table 5.1. Summary of Metabolites and Degradates to be included in the Risk Assessment and Tolerance 

Expression

Matrix Residues included in Risk Assessment Residues included in 

Tolerance Expression

Plants

Primary 

Crop Parent Parent

Rotational 

Crop Parent Parent

Livestock

Ruminant N/A N/A

Poultry N/A N/A

Drinking Water Parent plus its degradates, dimethenamid

ethanesulfonic acid and dimethenamid oxanilic acid. Not Applicable

Plants

For existing and currently proposed uses, the nature of dimethenamid residues in plants is 

adequately understood based on available soybean, corn and sugar beet metabolism studies. The 

residue of concern for purposes of the tolerance expression and risk assessment is parent only. 

However, for future uses, new evidence including the new cotton gin byproducts field trial data 

suggest that additional residues of concern could rise to the level of significance from mid- to 

late-season foliar uses of dimethenamid on food crops. Hence, additional metabolism data may 

be required and residues of concern may need to be re-examined if mid- to late-season foliar uses 

of dimethenamid are proposed in the future. Also, sufficient magnitude of the residue data for 

known metabolites of dimethenamid may be needed for future uses.

Livestock

The nature of dimethenamid residues in livestock is adequately understood based on available 

goat and poultry metabolism studies. For existing and currently proposed uses, there is no 

reasonable expectation of finite residues of concern in livestock commodities (40 CFR 

§180.6(a)(3)). This decision is based on the available livestock metabolism data alone since 

feeding study data are not currently available. Hence, future new uses and/or significant 

increases in existing uses may precipitate the need for feeding study data.
Page 20 of 51

Drinking Water

In previous assessments, the residue of concern in drinking water was considered parent only; 

however, the current risk assessment team has determined that the residues of concern in 

drinking water are parent plus its degradates, dimethenamid ethanesulfonic acid and 

dimethenamid oxanilic acid. Although the degradates appear to be less toxic than parent (email 

from R. Kent to B. Cropp-Kohlligian dated 5/22/14), they are included as residues of concern 

since they were identified as potentially significant degradates in the available fate data and 

found in greater abundance than the parent in some of the available water monitoring data.

5.2 Food Residue Profile

Crop Field Trials

BASF has submitted field trial data for dimethenamid-P on cotton. Eleven field trials were 

conducted in the United States during the 2012 growing season in the North American Free 

Trade Agreement (NAFTA) Growing Zones 2 (GA; 1 trial), 4 (AR and MO; 3 trials), 6 (TX; 1 

trial), 8 (KS, OK, and TX; 4 trials), and 10 (CA; 2 trials). The petitioner reported that a twelfth 

site in CA was terminated due to crop failure and has been reinitiated for the 2013 growing 

season.

The submitted cotton field trial data was found adequate to support the proposed use. Data were 

collected with an adequate data-collection method and are supported by adequate storage 

stability data. Although 1 trial is missing from region 10, the number of trials (11) and 

geographical representation is deemed adequate since residues of dimethenamid-P were below 

the LOQ (<0.01 ppm) in/on all samples of undelinted cottonseed. Residues of dimethenamid-P

were <0.01-0.814 ppm (per trial averages) in/on samples of cotton gin byproducts. The 

submitted data are adequate to support tolerances of 0.01 ppm and 1.5 ppm for residues of 

dimethenamid-P in/on cottonseed subgroup 20C and cotton gin byproducts, respectively. The 

recommended cottonseed subgroup 20C tolerance was set at the LOQ of the enforcement method 

and the recommended cotton gin byproduct tolerance was calculated using the Organization for 

Economic Cooperation and Development (OECD) tolerance calculation procedures.

Although not required, data were also generated for metabolites M26 and M30. Like 

dimethenamid-P, residues of metabolites M26 and M30 were each below the LOQ in/on 

undelinted cottonseed. Residues (as per trial averages) of metabolites M26 and M30 were <0.01-

0.045 ppm and <0.01-0.483 ppm, respectively, in/on cotton gin byproducts. These data 

demonstrate the potential for significant levels of metabolites of dimethenamid-P resulting in/on 

plant commodities from mid- to late-season applications of dimethenamid-P. However, since 

cotton gin byproducts is only a minor dairy cattle feed item, this is not a concern for the current 

petition. It is of note that the combined residues of dimethenamid-P and its metabolites M26 and 

M30 in/on cotton gin byproduct (combined HAFT = 1.34 ppm) are less than the recommended 

tolerance (1.5 ppm).
Page 21 of 51

TABLE 5.2.1. Summary of Residue Data from Crop Field Trials with Dimethenamid-P

Commodity

Total 

Applic. 

Rate

lb ai/A

(g ai/ha)

PHI 

(days)

Residue Levels (ppm)1

n Min. Max. LAFT2 HAFT2 Median Mean Std. 

Dev.

Dimethenamid-P

Cotton, 

undelinted seed

1.437-

1.490

(1611.2-

1670.2)

54-103 11

<0.01 <0.01 <0.01 <0.01 0.01 0.01 N/A

Cotton gin 

byproducts <0.01 0.816 <0.01 0.814 0.031 0.114 0.236

M26

Cotton, 

undelinted seed

1.437-

1.490

(1611.2-

1670.2)

54-103 11

<0.01 <0.01 <0.01 <0.01 0.01 0.01 N/A

Cotton gin 

byproducts <0.01 0.052 <0.01 0.045 0.010 0.017 0.014

M30

Cotton, 

undelinted seed

1.437-

1.490

(1611.2-

1670.2)

54-103 11

<0.01 <0.01 <0.01 <0.01 0.01 0.01 N/A

Cotton gin 

byproducts <0.01 0.672 <0.01 0.483 0.050 0.097 0.141

1

 Except for sample min/max, values reflect per trial averages; n = no. of field trials. For calculation of median, mean, and 

standard deviation, the LOQ (0.01 ppm for each analyte) was used for any results reported as <LOQ in Table C.3. N/A = Not 

Applicable.

2

 LAFT = lowest average field trial; HAFT = highest average field trial.

Processed Food and Feed

BASF has submitted a processing study with dimethenamid-P on cotton. The submitted cotton 

processing study conducted at an exaggerated rate (3x) was considered adequate to support the 

proposed use. Data were collected with an adequate data-collection method and are supported 

by adequate storage stability data. The study demonstrates that separate tolerances for residues 

of dimethenamid-P are not needed for processed commodities of cotton. Residues of 

dimethenamid-P did not concentrate in cotton meal, hulls and crude oil. While data suggest a 

very slight potential for concentration of dimethenamid-P in refined oil, a separate tolerance in 

refined oil will not be needed since the exaggerated rate processing study demonstrates that the 

petitioned-for/recommended tolerance in/on cotton seed (0.01 ppm) will be adequate to cover 

potential residues of dimethenamid-P in refined oil. 

Although not required, data were also generated for metabolites M26 and M30. Like 

dimethenamid-P, residues of its metabolites M26 and M30 do not concentrate in cotton meal and 

hulls. Data indicate a very slight potential for concentration of residues of M30 in oil but not 

M26.

Submittal of Analytical Reference Standards

Analytical standards are currently available for dimethenamid (expiration 11/1/23; email from 

Theresa Cole, ACB, 2/28/14) and dimethenamid-P (expiration 7/1/16; email from Theresa Cole, 

ACB, 4/9/14).) in the EPA National Pesticide Standards Repository 
Page 22 of 51

Confined and Field Accumulation in Rotational Crops

Based on the current and proposed uses of dimethenamid/dimethenamid-P, requirements for 

confined/field accumulation in rotational crops are satisfied based on the acceptable confined 

rotational crop study. The submitted study includes data on winter wheat planted 141 DAT, 

lettuce planted 322 DAT, and carrots planted 332 DAT. The maximum concentration of any 

metabolite/degradate in harvested wheat was 0.01 ppm for the sulfoxide of thiolactic acid 

conjugate. Based on these data, HED determined that a 4-month rotational interval is adequate 

for fall-seeded cereal grains, and other crops may be planted the following spring. These 

recommendations are consistent with the rotational crop restrictions on the current label for 

Outlook® Herbicide (EPA Registration Number 7969-156; Accepted 3/20/14). See Directions 

for Use section above for details.

Proposed Tolerances

Tolerances for plant commodities are established under §180.464, and are expressed in terms of 

dimethenamid per se. The tolerance definition proposed by BASF is in terms of dimethenamid 

per se. The tolerances proposed by BASF are listed in Table 5.2.2 along with the tolerance 

levels recommended by HED and corrected commodity definitions.

Adequate residue data are available to support the proposed tolerances. The submitted data are 

adequate to support tolerances of 0.01 ppm and 1.5 ppm for residues of dimethenamid-P in/on 

cottonseed subgroup 20C and cotton gin byproducts, respectively. The recommended cottonseed 

subgroup 20C tolerance was set at the LOQ of the enforcement method and the recommended 

cotton gin byproduct tolerance was calculated using the Organization for Economic Cooperation 

and Development (OECD) tolerance calculation procedures. The submitted cotton processing 

study conducted at an exaggerated rate (3x) is adequate to support the proposed use and 

demonstrates that separate tolerances for residues of dimethenamid-P are not need for processed 

commodities of cotton. 

There are no established Codex, Canadian or Mexican maximum residue limits (MRLs) for 

dimethenamid-P in/on cotton commodities (email from M. Negussie to B. Cropp-Kohlligian 

dated 2/28/14). Therefore, there is no question about harmonization of the proposed tolerances.
Page 23 of 51

TABLE 5.2.2. Tolerance Summary for Dimethenamid-P

Commodity Proposed Tolerance 

(ppm)

Recommended 

Tolerance (ppm)

Correct Commodity Definition/

Comments

40 CFR §180.464(a)

Cottonseed subgroup 20C 0.01 0.01 Cottonseed subgroup 20C

Cotton, gin byproducts 1.5 1.5 Cotton, gin byproducts

Cotton, seed, refined oil 0.02 --

While data suggest a very slight 

potential for concentration of 

dimethenamid-P in refined oil, a 

separate tolerance in refined oil will 

not be needed since the exaggerated 

rate processing study demonstrates 

that the petitioned-for/recommended 

tolerance in/on cotton seed (0.01 

ppm) will be adequate to cover 

potential residues of dimethenamid-P

in refined oil. 

5.3 Water Residue Profile

The drinking water residues used in the dietary risk assessment were provided by the 

Environmental Fate and Effects Division (EFED) in a drinking water assessment (DWA; 

D422167, M. Biscoe, 8/14/14) entitled: “Dimethenamid-P: ADDENDUM Drinking Water 

Exposure Assessment for Existing Ornamental and Green Onion Uses and the Proposed Cotton 

Use.” Estimated Drinking Water Concentrations (EDWCs) for dimethenamid-P were calculated 

for the parent compound plus the dimethenamid ethanesulfonic acid and dimethenamid oxanilic 

acid degradates. These estimated drinking water concentrations (EDWCs) were incorporated 

directly into this dietary assessment in the DEEM-FCID into the food categories “water, direct, 

all sources” and “water, indirect, all sources.” 

EFED generated the surface water EDWCs using the Surface Water Concentration Calculator 

(SWCC) and groundwater EDWCs were generated using Pesticide Root Zone Model for Ground 

Water (PRZM-GW). EDWCs were derived based on the maximum registered use rate 

(ornamentals 3 lb ai/A/season), the maximum use rate on green onion (i.e., the scenario that 

resulted in the highest EDWCs in prior DWA) and the proposed use on cotton (1.45 lb ai/A). 

The maximum EDWCs calculated in this assessment are shown in Table 5.3. In surface water, 

the highest estimated peak (acute) concentration is 73 μg/L, the highest estimated 1-in-10 year 

annual average concentration is 27 μg/L, and the highest estimated 30-year annual average 

concentration is 16 μg/L. In groundwater, the estimated peak (acute) concentration is 153 μg/L, 

and the estimated post-breakthrough average (chronic) concentration is 140 μg/L. Because the 

maximum acute (groundwater 153 μg/L) and chronic (groundwater 140 μg/L) EDWCs were so 

close, 153 μg/L was used in both the acute and chronic dietary assessments to estimate residues 

in drinking water.
Page 24 of 51

Table 5.3. Maximum estimated drinking water concentrations (EDWCs) in parts per billion (μg/L) for 

dimethenamid plus its degradates, dimethenamid ethanesulfonic acid and dimethenamid oxanilic acid, for 

use in the dietary risk assessments.

Drinking Water Source 

(model) [Tier]

Model Scenario & 

Application Method

Acute Chronic Cancer

μg/L

Surface Water

(SWCC) [Tier 2]

New Jersey Nursery 

(Ornamentals)

Ground Application

Peak 

1-in-10 

Year

Chronic 

1-in-10 

Year

30-year Annual 

Average

73 27 16

Groundwater 

(PRZM-GW 30-year 

simulation) [Tier 1]

Wisconsin Corn

(Ornamentals)

Peak Post-Breakthrough Average

153 140

The drinking water models and their descriptions are available at the EPA internet site: 

http://www.epa.gov/oppefed1/models/water/. 

5.4 Dietary Risk Assessment

Acute and chronic aggregate dietary (food and drinking water) exposure and risk assessments 

were conducted using the Dietary Exposure Evaluation Model software with the Food 

Commodity Intake Database (DEEM-FCID) Version 3.16. This software uses 2003-2008 food 

consumption data from the U.S. Department of Agriculture’s (USDA’s) National Health and 

Nutrition Examination Survey, What We Eat in America, (NHANES/WWEIA). The analyses 

were conducted in support of a human health risk assessment for the proposed Section 3 use of 

dimethenamid-P on cottonseed subgroup 20C. 

5.4.1 Description of Residue Data Used in Dietary Assessment

Both the acute and chronic assessments are conservative and incorporated tolerance level 

residues, assume 100% crop treated and use default processing factors. Estimated drinking water 

concentrations (EDWCs) used in the assessments were generated using Tier I modeling.

5.4.2 Percent Crop Treated Used in Dietary Assessment

The acute and chronic assessments are based on the assumption that 100% of all commodities 

with tolerances will be treated.

5.4.3 Acute Dietary Risk Assessment

For the acute assessment, aggregate dietary (food and drinking water) exposures are below 

HED’s level of concern (<100% aPAD) at the 95

th percentile of exposure for all population 

subgroups. The acute dietary exposure at the 95

th percentile of exposure is estimated at 0.008399

mg/kg/day for the overall U.S. population, equivalent to <1% of the aPAD. The population 

subgroup with the highest estimated acute dietary exposure is All Infants <1 year of age, with an 
Page 25 of 51

estimated exposure at the 95

th percentile of 0.026253 mg/kg/day, equivalent to 1.3% of the 

aPAD. 

5.4.4 Chronic Dietary Risk Assessment

For the chronic assessment, aggregate dietary (food and drinking water) exposures are below 

HED’s level of concern (<100% cPAD) for all population subgroups. The chronic dietary 

exposure is estimated at 0.003241 mg/kg/day for the general U.S. population, equivalent to 6.5% 

of the cPAD. The population subgroup with the highest estimated chronic dietary exposure is 

All Infants <1 year of age, with an estimated exposure of 0.008326 mg/kg/day, equivalent to 

17% of the cPAD. 

5.4.5 Cancer Dietary Risk Assessment

Dimethenamid/dimethenami-P is classified as a Group C chemical (possible human carcinogen). 

Cancer dietary risk concerns due to long-term consumption of dimethenamid/dimethenamid-P

residues are adequately addressed by the chronic dietary exposure analysis using the reference 

dose; therefore, a separate cancer dietary exposure analysis was not performed.

5.4.6 Summary Table

A dietary assessment was conducted for the proposed and registered uses of 

dimethenamid/dimethenamid-P. The dietary risk estimates are below HED’s level of concern; see 

Table 5.4.6.1. 

Table 5.4.6.1. Summary of Dietary (Food and Drinking Water) Exposure and Risk for 

Dimethenamid/Dimethenamid-P.

Population Subgroup

Acute Dietary

(95th Percentile) Chronic Dietary Cancer

Dietary 

Exposure 

(mg/kg/day)

% aPAD*

Dietary 

Exposure

(mg/kg/day)

% cPAD*

Dietary 

Exposure

(mg/kg/day)

Risk

General U.S. Population 0.008399 <1 0.003241 6.5

N/A

All Infants (<1 year old) 0.026253 1.3 0.008326 17

Children 1-2 years old 0.013042 <1 0.004710 9.4

Children 3-5 years old 0.010635 <1 0.003980 8.0

Children 6-12 years old 0.008023 <1 0.002869 5.7

Youth 13-19 years old 0.006982 <1 0.002373 4.7

Adults 20-49 years old 0.008253 <1 0.003228 6.5

Adults 50-99 years old 0.007364 <1 0.003186 6.4

Females 13-49 years old 0.008361 1.1 0.003214 6.4
Page 26 of 51

6 Residential (Non-Occupational) Exposure/Risk Characterization

There are no proposed residential uses at this time; however, there are existing residential uses 

that have been reassessed in this document to reflect updates to HED’s 2012 Residential SOPs3

along with policy changes for body weight assumptions. The revision of residential exposures 

will impact the human health aggregate risk assessment for dimethenamid-P.

dimethenamid-P is registered for residential use on turfgrass, ornamentals, and tree plantations, 

and is formulated as an emulsifiable concentrate (EC) and granule (G). The currently registered 

end-use products (EPs) available for residential use include:

1. Tower Herbicide EC (EPA Reg. No. 7969-239; 63.9% dimethenamid-P), ,

2. Freehand 1.75G Herbicide (EPA Reg. No. 7969-273; 0.75% dimethenamid-P), and

3. Freehand CA 1.75G Herbicide (EPA Reg. No. 7969-358; 0.75% dimethenamid-P).

BASF Corporation is the registrant of all three products. 

6.1 Residential Handler Exposure

HED uses the term “handlers” to describe those individuals who are involved in the pesticide 

application process. HED believes that there are distinct tasks related to applications and that 

exposures can vary depending on the specifics of each task. Residential handlers are addressed 

somewhat differently by HED as homeowners are assumed to complete all elements of an 

application without use of any protective equipment.

The quantitative exposure/risk assessment developed for residential handlers is based on various 

exposure scenarios that involve mixing/loading/applying various formulations with manually 

pressurized handguns, hose-end sprayers, backpack sprayers, push-type rotary spreaders and 

belly grinders.

Residential Handler Non-Cancer Exposure and Risk Estimate Equations

The algorithms used to estimate exposure and dose for residential handlers can be found in the 

2012 Residential SOPs4.

Combining Exposures/Risk Estimates

Dermal and inhalation exposures to handlers were not aggregated because the toxicity endpoints 

for these exposure routes are not based on common toxicity effects in/of the liver. Dermal 

effects (body weight gain) were considered to be non-specific.

Summary of Residential Handler Non-Cancer Exposure and Risk Estimates

Summaries of the short-term dermal and inhalation risk estimates for residential handlers are 

included in Table 6.1. The maximum application rate for each exposure scenario is presented as 

the worst case scenario. All risk estimates are greater than the LOC of 100 and therefore not of 

concern (Dermal MOEs range from 250 to 5,300,000; Inhalation MOEs range from 7,700 to 

1,500,000). 

 

3 Available: http://www.epa.gov/pesticides/science/residential-exposure-sop.html

4 Available: http://www.epa.gov/pesticides/science/residential-exposure-sop.html
Page 27 of 51

Table 6.1. Residential Handler Non-cancer Exposure and Risk Estimates for Dimethenamid-P.

Exposure 

Scenario

Application 

Equipment/

Method

Dermal 

Unit 

Exposure 

(mg/lb ai)

Inhalation 

Unit 

Exposure 

(mg/lb ai)

Maximum 

Application 

Rate1

Area 

Treated or 

Amount 

Handled 

Daily2

Dermal Inhalation

Dose 

(mg/kg/day)3

MOE4

(LOC=100)

Dose 

(mg/kg/day)5

MOE6

(LOC=100)

Liquid Formulation

Lawns/Turf

Hose-end 

Sprayer 13.4 0.022 1.5 lb ai/acre 0.5 acres 0.13 2,400 0.00021 49,000

Manuallypressurized 

handwand

63 0.018

0.15 lb ai/gal 5 gallons

0.59 510 0.00017 60,000

Backpack 130 0.14 1.2 250 0.0013 7,700

Gardens/Trees

Sprinkler can

58 0.0014 0.15 lb ai/gal

5 gallons 0.54 550 0.000013 770,000

Hose-end 

Sprayer 11 gallons 0.13 2,400 0.00021 49,000

Granular Formulation

Lawns/Turf

Push-type 

rotary 

spreader

0.81 0.0026 1.5 lb ai/acre 0.5 acres 0.0076 40,000 0.000024 410,000

Belly grinder 360 0.039 3.4x10-5

lb ai/ 

ft2 1,200 ft2 0.19 1,600 0.000020 500,000

Gardens/Trees

Hand 

Dispersal 160 0.38

3.4x10-5lb ai/ 

ft2 1,200 ft2

0.083 3,600 0.00020 52,000

Shaker can 

/Cup 0.0045 0.00054 0.000057 5,300,000 0.0000067 1,500,000

Spoon 6.2 0.087 0.0032 94,000 0.000045 220,00

1 Based on registered residential uses for dimethenamid-P (Refer to section 6.0).

2 Based on HED’s 2012 Residential SOPs (http://www.epa.gov/pesticides/science/residential-exposure-sop.html): Lawns/Turf; and Gardens/Trees

3 Dermal Dose = Dermal Unit Exposure (mg/lb ai) × Application Rate (lb ai/acre or gal or ft2

) × Area Treated or Amount Handled (A/day or gallons/day or 

ft2/day) × Dermal Absorption Factor (100 %) ÷ Body Weight (80 kg).

4 Dermal MOE = Dermal NOAEL (300 mg/kg/day) ÷ Dermal Dose (mg/kg/day).

5

Inhalation Dose = Inhalation Unit Exposure (mg/lb ai) × Application Rate (lb ai/acre or gal or ft2) × Area Treated or Amount Handled (A/day or gallons/day 

or ft2/day) ÷ Body Weight (80 kg).

6

Inhalation MOE = Inhalation NOAEL (10 mg/kg/day) ÷ Inhalation Dose (mg/kg/day).
Page 28 of 51

6.2 Post-Application Exposure

There is the potential for post-application exposure for individuals exposed as a result of being in 

an environment that has been previously treated with dimethenamid-P. The quantitative 

exposure/risk assessment for residential post-application exposures is based on the following 

scenarios: 

The scenarios, routes of exposure and lifestages of potential exposure include:

1. Physical activities on turf: adults (dermal) and children 1 to < 2 years old (dermal and 

incidental oral);

2. Mowing: adults (dermal) and children 11 to < 16 years old (dermal);

3. Golfing: adults (dermal), children 11 to < 16 years old (dermal), and children 6 to < 11 

years old (dermal); and

4. Contact with Treated Gardens and Trees: adults (dermal) and children 6 to <11 years old 

(dermal).

The lifestages selected for each post-application scenario are based on an analysis provided as an 

Appendix in the 2012 Residential SOPs5. While not the only lifestage potentially exposed for 

these post-application scenarios, the lifestage that is included in the quantitative assessment is 

health protective for the exposures and risk estimates for any other potentially exposed lifestage.

Residential Post-application Exposure Data and Assumptions

A series of assumptions and exposure factors served as the basis for completing the residential 

post-application risk assessment. Each assumption and factor is detailed in the 2012 Residential 

SOPs5: Lawns/Turf, and Gardens and Trees. 

Furthermore, a chemical specific Transferable Turf Residue (TTR) Study was submitted by the 

registrant (MRID# 47901302), reviewed by HED (D376733, I. Nieves, 3/16/11) and found to be 

acceptable for use in exposure and risk assessments. This study was designed to determine the 

transferable turf residue (TTR) of dimethenamid-P dislodged from turf treated with an 

emulsifiable concentrate formulation containing 63.9% dimethenamid-P as the active ingredient 

(Tower® Herbicide) and a spreadable granule formulation containing 0.75% dimethenamid-P 

(FreeHand® 1.75 G Herbicide) at three locations in the United States (Florida, New Jersey, and 

California). Transferable residues were sampled using the Modified California Roller technique. 

The TTR values used to quantify potential exposure risk by performing residential postapplication activities on lawns/turf were taken from the aforementioned study. For liquid 

formulations, the highest predicted dimethenamid-P TTR level detected was 0.0312 μg/cm2

(California site). For granular formulations, since dimethenamid-P TTR values were not 

detected above the LOQ at any sampling interval after application a TTR value of 0.00090 

μg/cm2, equivalent to 1⁄2 the LOQ value (0.00179 μg/cm2) is being used for human health 

exposure assessments.

 

5 Available: http://www.epa.gov/pesticides/science/residential-exposure-sop.html
Page 29 of 51

For post-application dermal exposure resulting from contact with previously treated gardens and 

trees, the default Dislodgeable Foliar Residue (DFR) calculation was done in the absence of 

chemical-specific data.

Residential Post-application Non-Cancer Exposure and Risk Equations

The algorithms used to estimate residential post-application exposure and dose can be found in 

the 2012 Residential SOPs5.

Combining Exposure and Risk Estimates

HED combines risk estimates resulting from separate post-application exposure scenarios when 

it is likely they can occur simultaneously based on the use pattern and the behavior associated 

with the exposed population and when the toxicological effects are similar. However, the 

incidental oral scenarios (i.e., hand-to-mouth, object-to-mouth, soil ingestion, and granule 

ingestion) should be considered inter-related and it is likely that they occur interspersed amongst 

each other, across time. Combining all three of these scenarios would be overly-conservative 

because of the conservative nature of each individual assessment. Therefore, the hand-to-mouth 

post-application exposure scenario for children 1 to < 2 years old is considered a protective 

estimate of children’s exposure to pesticides used on turf. 

Summary of Residential Post-application Non-Cancer Exposure and Risk Estimates

Table 6.2 presents the post-application MOE values calculated for adults and children after turf 

applications of dimethenamid-P. HED considers this liquid formulation risk estimates for postapplication exposure to be protective of the granular product, because of its lower transferability 

properties compared to that observed for the liquid formulation, Tower Herbicide (0.64% 

transferability for the liquid compared to 0.005% for the granular). This phenomena can be 

observed in the TTR study (MRID# 47901302) submitted by the registrant, BASF, where TTR 

values were not detected above the LOQ at any sampling interval for the granular formulation 

product. Post-application non-cancer risks do not exceed HED’s level of concern for any of the 

scenarios assessed (MOEs range from 310 to 200,000; LOC = 100). 
Page 30 of 51

Table 6.2. dimethenamid-P Residential Risk Estimates for Post-application Exposure.

Site Activity Route of 

Exposure

TC 

(cm2/hr)

TTR (Study)

/DFR (Default)

(μg/cm2)

Exposure 

Time

(hrs/day)

Short-Term

Average Daily 

Dose 

(mg/kg/day)

MOE

(LOC=100)

Adults

Max single application rate: 1.5 lbs ai/A1

Treated 

Lawns

High Contact Activities

Dermal

180,000

TTR 

(Lawns/Turf): 

0.0312

1.5 0.11 2,900

Mowing 5,500 1 0.0021 140,000

Golf 

Course 

Turf

Golfing 5,300 4 0.0083 36,000

Gardens

High Contact Activities 

(liquid and granular formulations)

8,400

DFR 

(Gardens/Trees): 

4.2

2.2 0.96 310

Trees and 

Retail 

Plants

1,700 1 0.089 3,400

Indoor 

Plants 220 1 0.011 26,000

Children

Max single application rate: 1.5 lbs ai/A1

Treated 

Residential 

Areas

High Contact Activities (1<2 years)

Dermal

49,000

0.0312

1.5 0.21 1,400

Mowing (11<16 years) 4,500 1 0.0025 120,000

Golfing (6<11 years) 2,900 4 0.011 27,000

Hand to Mouth Transfer of 

Pesticide Residue (1<2 years)

Oral N/A

Hand Residue 

(mg/cm2) 1.5 0.0043 2,300

0.00042

Object to Mouth Transfer of 

Pesticide Residue (1<2 years)

Object Residue 

(mg/cm2) 1.5 0.00013 77,000

0.031

Incidental Ingestion of Soil with 

Pesticide Residue (1<2 years)

Soil Residue 

(mg/cm2) N/A 0.000051 200,000

11.17

Incidental Granule Ingestion 

(1<2 years)

Ingestion Rate 

(g/day; 0.8% ai) N/A 0.20 980

0.3

Gardens

High Contact Activities 

(6<11 years)

(liquid and granular formulations)

Dermal

4,600

DFR 

(Gardens/Trees): 

4.2

1.1 0.66 460

Trees and 

Retail 

Plants

930 0.5 0.061 5,000

Indoor 

Plants 120 0.5 0.0078 38,000

1 Based on registered labels (Refer to Section 6.0).

6.3 Residential Risk Estimates for Use in Aggregate Assessment

Table 6.3 reflects the residential exposure scenarios and associated risk estimates that are 

recommended for use in the aggregate assessment for dimethenamid-P. 

 The recommended residential exposure for use in the adult aggregate assessment reflects 

handler inhalation exposure from liquid applications to turf via backpack sprayer.
Page 31 of 51

 The recommended residential exposure for use in the children 1<2 years old aggregate 

assessment reflects incidental oral exposure from post-application hand-to-mouth 

pesticide transfer from liquid application to residential turf.

Since it was determined that the effects noted for the dermal POD have no common toxicity 

effects with the incidental oral and/or inhalation PODs (same POD) the values recommended to 

be used for the aggregate assessment are based on the worst-case residential exposure estimates 

via the inhalation (adult male) and oral (child 1<2 years old) routes. Only short-term residential 

exposures are expected based on the Residential SOPs (2012). All residential handler and postapplication exposure estimate resulted in MOEs greater than 100, and are not of concern.

Table 6.3. Recommendations for the Short- and Intermediate-Term Residential Exposures for the dimethenamid-P

Aggregate Assessment

Lifestage

Handler Exposure 

(mg/kg/day) 1 Residential 

Handler Total 

Exposure 

(mg/kg/day)

Residential 

Handler 

Total MOE 2

Post-application Exposure 

(mg/kg/day) 3

Residential 

Postapplication 

Total Exposure 

(mg/kg/day)

Residential 

Postapplication 

MOE Dermal Inhalation Dermal Inhalation Oral 4

Adult 

Male N/A 0.0013 0.0013 7,700 N/A N/A N/A N/A N/A

Child

(1<2 years 

old)

N/A N/A N/A N/A N/A N/A 0.0043 0.0043 2,300

1 Handler exposure represents high-end handler exposure, where the exposure duration is appropriate to assess (Table 6.1). 

2 Residential Total MOE =Represents high-end handler exposure MOE (Table 6.1). Inhalation NOAEL = 10 mg/kg/day.

3 Post-application exposure represents high-end incidental oral exposure for the relevant exposure duration (Table 6.2).

4 Post-application Total MOE =Represents high-end post-application exposure MOE (Table 6.2). Incidental oral NOAEL = 10 mg/kg/day. 

Note: Only inhalation and oral exposure had common effects and therefore aggregated. Values for dermal exposure were not presented as they were not 

relevant for the aggregate assessment (i.e., no common effects).

6.4 Residential Bystander Post-application Inhalation Exposure

Based on the Agency's current practices, a quantitative post-application inhalation exposure 

assessment was not performed for dimethenamid-P at this time primarily because of the low 

acute inhalation toxicity (Toxicity Category III). However, volatilization of pesticides may be a 

source of post-application inhalation exposure to individuals nearby pesticide applications. The 

Agency sought expert advice and input on issues related to volatilization of pesticides from its 

Federal Insecticide, Fungicide, and Rodenticide Act Scientific Advisory Panel (SAP) in 

December 2009, and received the SAP’s final report on March 2, 20106. The Agency is in the 

process of evaluating the SAP report and may, as appropriate, develop policies and procedures to 

identify the need for and, subsequently, the way to incorporate post-application inhalation 

exposure into the Agency's risk assessments. If new policies or procedures are developed, the 

Agency may revisit the need for a quantitative post-application inhalation exposure assessment 

for dimethenamid-P.

 

6 Available: http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html
Page 32 of 51

6.5 Spray Drift

Spray drift is a potential source of exposure to those nearby pesticide applications. This is 

particularly the case with aerial application, but, to a lesser extent, spray drift can also be a 

potential source of exposure from the ground application methods (e.g., groundboom and 

airblast) employed for dimethenamid-P. The Agency has been working with the Spray Drift 

Task Force (a task force composed of various registrants which was developed as a result of a 

Data Call-In issued by EPA), EPA Regional Offices and State Lead Agencies for pesticide 

regulation and other parties to develop the best spray drift management practices (see the 

Agency’s Spray Drift website for more information). 7 The Agency is also taking means to 

qualitatively and qualitatively address spray drift as a potential source of exposure in risk 

assessments for pesticides through existing programs such as Ag Drift and chemical specific 

properties of pesticides. The potential for spray drift will be quantitatively evaluated for each 

pesticide during the Registration Review process which ensures that all uses for that pesticide 

will be considered concurrently. 

7 Aggregate Exposure/Risk Characterization

In accordance with the FQPA, HED must consider and aggregate pesticide exposures and risks 

from dietary (food and water) and residential (dermal, inhalation, and/or incidental oral) sources. 

When aggregating exposures and risks from these sources, HED considers the route and duration 

of exposure as well as the toxicological effects for each route. Aggregate risk assessments 

evaluate the combined risk from dietary exposure (food and water) and any non-occupational 

(residential) uses. Non-occupational (residential) exposures are not anticipated from the 

proposed new use, although residential exposure is expected for currently registered products. 

The existing residential uses have been reassessed in this document to reflect updates to HED’s 

2012 Residential SOPs8along with policy changes for body weight assumptions. As a result, the 

dimethenamid-P aggregate risk assessment was updated accordingly. 

Dimethenamid-P is classified as group “C” possible human carcinogen, based on an increasing 

trend for liver tumors (males) seen in the chronic rat study. There were no dose-related tumors 

seen in the mouse carcinogenicity study. Therefore, a cancer aggregate risk assessment is not 

required.

7.1 Acute Aggregate Risk

For the acute assessment, aggregate dietary (food and drinking water) exposures are below 

HED’s level of concern (<100% aPAD) at the 95th percentile of exposure for all population 

subgroups. Refer to section 5.4.3 for a more detailed discussion of the acute dietary assessment. 

7.2 Short-and Intermediate-Term Aggregate Risk

For the short-/intermediate-term aggregate assessment, exposures do not fall below HED’s level 

of concern (i.e., all MOEs are greater than 100). As summarized in Table 7.2, for adults and 

 

7 Available: http://www.epa.gov/opp00001/factsheets/spraydrift.htm 

8 Available: http://www.epa.gov/pesticides/science/residential-exposure-sop.html
Page 33 of 51

children, only handler inhalation exposure and post-application incidental oral exposure, 

respectively, were appropriate to aggregate with dietary exposure. 

Table 7.2 Short-Term and Intermediate Term Aggregate Risk Calculations

Population

Short- or Intermediate-Term Scenario

NOAEL 

mg/kg/day LOC1

Max 

Allowable 

Exposure2

mg/kg/day

Average 

Food and 

Water 

Exposure 

mg/kg/day

Residential 

Exposure 

mg/kg/day3

Total 

Exposure 

mg/kg/day4

Aggregate 

MOE (food, 

water, and 

residential)5

Adults

10 100 0.1 0.003241 0.0013 0.0045 2200

Child 0.004710 0.0043 0.0090 1100

1 LOC = 100 (based on the standard 10-fold inter- and 10-fold intra-species uncertainty factors, totaling 100)

2 Maximum Allowable Exposure (mg/kg/day) = NOAEL/LOC

3 Residential Exposure = [Oral exposure + Dermal exposure + Inhalation Exposure]. Refer to Table 6.3; only 

inhalation exposure is relevant for adults and incidental oral exposure for children.

4 Total Exposure = Avg Food & Water Exposure + Residential Exposure

5 Aggregate MOE = [NOAEL: 10 mg/kg/day/(Avg Food & Water Exposure + Residential Exposure)]

7.3 Chronic Aggregate Risk

For the chronic assessment, aggregate dietary (food and drinking water) exposures are below 

HED’s level of concern (<100% cPAD) for all population subgroups. Refer to section 5.4.4 for a 

more detailed discussion of the chronic dietary assessment. 

7.4 Cancer Aggregate Risk

Dimethenamid is classified as a Group C chemical (possible human carcinogen). Cancer dietary 

risk concerns due to long-term consumption of dimethenamid residues are adequately addressed 

by the chronic dietary exposure analysis using the reference dose; therefore, a separate aggregate 

cancer dietary exposure analysis was not performed.

8 Cumulative Exposure/Risk Characterization

Unlike other pesticides for which EPA has followed a cumulative risk approach based on a 

common mechanism of toxicity, EPA has not made a common mechanism of toxicity finding as 

to dimethenamid-P and any other substances and dimethenamid-P does not appear to produce a 

toxic metabolite produced by other substances. For the purposes of this tolerance action, 

therefore, EPA has not assumed that dimethenamid-P has a common mechanism of toxicity with 

other substances. For information regarding EPA’s efforts to determine which chemicals have a 

common mechanism of toxicity and to evaluate the cumulative effects of such chemicals, see the 

policy statements released by EPA’s Office of Pesticide Programs concerning common 

mechanism determinations and procedures for cumulating effects from substances found to have 

a common mechanism on EPA’s website at http://www.epa.gov/pesticides/cumulative/.

9 Occupational Exposure/Risk Characterization

9.1 Short-/Intermediate-Term Handler Risk
Page 34 of 51

HED uses the term handlers to describe those individuals who are involved in the pesticide 

application process. HED believes that there are distinct job functions or tasks related to 

applications and exposures can vary depending on the specifics of each task. Job requirements 

(amount of chemical used in each application), the kinds of equipment used, the target being 

treated, and the level of protection used by a handler can cause exposure levels to differ in a 

manner specific to each application event. 

Based on the anticipated use patterns and current labeling, types of equipment and techniques 

that can potentially be used, occupational handler exposure is expected from the proposed uses. 

The quantitative exposure/risk assessment developed for occupational handlers is based on 

several scenarios which include mixing/loading/applying the liquid formulation of 

dimethenamid-P. The use profile is summarized in Section 3.3. Methods of application include 

aerial, chemigation, groundboom, and handheld equipment. Flagging for aerial use is also a 

potential source of worker exposure. Refer to Table 9.1 for a detailed list of each scenario.

Occupational Handler Exposure Data and Assumptions

A series of assumptions and exposure factors served as the basis for completing the occupational 

handler risk assessments. Each assumption and factor is detailed below on an individual basis.

Application Rate: Refer to table 9.1.

Unit Exposures: It is the policy of HED to use the best available data to assess handler exposure. 

Sources of generic handler data, used as surrogate data in the absence of chemical-specific data, 

include PHED 1.1, the AHETF database, or other registrant-submitted occupational exposure 

studies. Some of these data are proprietary (e.g., AHETF data), and subject to the data 

protection provisions of FIFRA. The standard values recommended for use in predicting handler 

exposure that are used in this assessment, known as “unit exposures”, are outlined in the 

“Occupational Pesticide Handler Unit Exposure Surrogate Reference Table9”, which, along with 

additional information on HED policy on use of surrogate data, including descriptions of the 

various sources, can be found at the Agency website10. 

Area Treated or Amount Handled: The area treated or amount handled is based on HED 

ExpoSAC Policy No. 9.1. Refer to Table 9.1 for these assumptions for each scenario.

Exposure Duration: HED classifies exposures from 1 to 30 days as short-term and exposures 30 

days to six months as intermediate-term. Exposure duration is determined by many things,

including the exposed population, the use site, the pest pressure triggering the use of the 

pesticide, and the cultural practices surrounding that use site. For most agricultural uses, it is 

reasonable to believe that occupational handlers will not apply the same chemical every day for 

more than a one-month time frame; however, there may be a large agribusiness and/or 

commercial applicators who may apply a product over a period of weeks (e.g., completing 

multiple applications for multiple clients within a region). For the proposed use on cotton 

subgroup 20C both short- and intermediate-term exposures are expected from occupational use. 

 

9 Available: http://www.epa.gov/opp00001/science/handler-exposure-table.pdf

10 Available: http://www.epa.gov/pesticides/science/handler-exposure-data.html
Page 35 of 51

Since the PODs for short- and intermediate-term exposure are the same, the short-term 

assumptions and risk calculations are protective of both durations.

Mitigation/Personal Protective Equipment: Results are presented for “baseline,” defined as a 

single layer of clothing consisting of a long sleeved shirt, long pants, shoes plus socks, no 

protective gloves, and no respirator, as well as baseline with various levels of PPE as necessary 

(e.g., gloves, respirator, etc). The dimethenamid-P product labels direct mixers, loaders, 

applicators and other handlers to wear long-sleeved shirts, long pants, shoes plus socks, 

protective eyewear and chemical-resistant gloves.

Combining Exposures/Risk Estimates:

Dermal and inhalation exposures to workers were not aggregated because the toxicity endpoints 

for these exposure routes are not based on common toxicity effects in/of the liver. Dermal 

effects (body weight gain) were considered to be non-specific.

Summary of Occupational Handler Non-Cancer Exposure and Risk Estimates

The results of the occupational handler exposure and risk assessment indicate that short- and 

intermediate-term dermal and inhalation risk estimates are not of concern (i.e. all MOEs ≥ 100) 

at baseline mitigation (no PPE), except for the dermal exposure scenario of mixing and loading a 

liquid formulation of dimethenamid-P for aerial applications which resulted in an MOE of 92. 

With the use of additional PPE (i.e., gloves) the risk estimate MOE is mitigated to 540. 

Inhalation MOEs ranged from 3,100 to 140,000 at baseline. Note that only engineering control 

(enclosed cockpit) data are available to assess risks to handlers operating aircrafts.

The Agency matches quantitative occupational exposure assessment with appropriate 

characterization of exposure potential. While HED presents quantitative risk estimates for human 

flaggers where appropriate, agricultural aviation has changed dramatically over the past two 

decades. According the 2012 National Agricultural Aviation Association (NAAA) survey of 

their membership, the use of GPS for swath guidance in agricultural aviation has grown steadily 

from the mid 1990’s. Over the same time period, the use of human flaggers for aerial pesticide 

applications has decreased steadily from ~15% in the late 1990’s to only 1% in the most recent 

(2012) NAAA survey. The Agency will continue to monitor all available information sources to 

best assess and characterize the exposure potential for human flaggers in agricultural aerial 

applications.

HED has no data to assess exposures to pilots using open cockpits. The only data available are 

for exposure to pilots in enclosed cockpits. Therefore, risks to pilots are assessed using the 

engineering control (enclosed cockpits) and baseline attire (long-sleeve shirt, long pants, shoes, 

and socks); per the Agency’s Worker Protection Standard stipulations for engineering controls, 

pilots are not required to wear protective gloves for the duration of the application. With this 

level of protection, there are no risk estimates of concern for applicators.
Page 36 of 51

Table 9.1. Occupational Handler Non-Cancer Exposure and Risk Estimates for dimethenamid-P. 

Exposure Scenario Crop or 

Target

Level of 

Concern

Dermal Unit 

Exposure 

(μg/lb ai)1

Inhalation Unit 

Exposure (μg/lb 

ai)1

Maximum 

Application 

Rate2

Area 

Treated or 

Amount 

Handled 

Daily3

Dermal Inhalation

Mitigation 

Level Mitigation Level Dose (mg/kg/day)4 MOE5 Dose (mg/kg/day)6 MOE7

Mixer/Loader

Mixing/Loading Liquids for 

Aerial Applications

Cotton 

Subgroup 

20C

100

220

(baseline)

37.6

(baseline + 

gloves)

0.219

(baseline: no 

respirator)

1.0 lb ai/A

1,200

3.25 (baseline)

0.555

(baseline + 

gloves)

92

(baseline)

540

(baseline 

+gloves)

0.0032

(baseline)

3,100

(baseline)

Mixing/Loading Liquids for 

Chemigation Applications 350

0.948

(baseline)

320

(baseline)

0.00094

(baseline)

11,000

(baseline)

Mixing/Loading Liquids for 

Groundboom Applications 200

0.541

(baseline)

550

(baseline)

0.00054

(baseline)

19,000

(baseline)

Applicator

Applying Liquids with Aerial 

Equipment Cotton 

Subgroup 

20C

100

2.08

(Eng. Controls)

0.0049

(Eng. Controls)

1.0 lb ai/A

1,200

0.0308

(Eng. Controls)

9,700

(Eng. 

Controls)

0.0000724

(Eng. Controls)

140,000

(Eng. 

Controls)

Applying Liquids with 

Groundboom Equipment

78.6

(baseline)

0.34

(baseline)

200

0.194

(baseline)

1,500

(baseline)

0.00084

(baseline)

12,000

(baseline)

Flagger

Flagging Liquids for Aerial 

Applicaitons 

Cotton 

Subgroup 

20C

100

11

(baseline)

0.35

(baseline) 1.0 lb ai/A 350

0.047

(baseline)

6,300

(baseline)

0.0015

(baseline)

6,700

(baseline)

1 Based on the “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table” (March 2013); Level of mitigation: Baseline, PPE (i.e., gloves), Eng. Controls.

2 Based on proposed label use (EPA Reg No. 7969-156).

3 Exposure Science Advisory Council Policy #9.1.

4 Dermal Dose = Dermal Unit Exposure (μg/lb ai) × Conversion Factor (0.001 mg/μg) × Application Rate (lb ai/acre or gal) × Area Treated or Amount Handled (A or gal/day) × DAF (100%) ÷ BW 

(80 kg).

5 Dermal MOE = Dermal NOAEL (300 mg/kg/day) ÷ Dermal Dose (mg/kg/day).

6 Inhalation Dose = Inhalation Unit Exposure (μg/lb ai) × Conversion Factor (0.001 mg/μg) × Application Rate (lb ai/acre or gal) × Area Treated or Amount Handled (A or gal/day) ÷ BW (80 kg).

7 Inhalation MOE = Inhalation NOAEL (10 mg/kg/day) ÷ Inhalation Dose (mg/kg/day).
Page 37 of 51

9.2 Short-/Intermediate-Post-Application Risk

HED uses the term post-application to describe exposures that occur when individuals are 

present in an environment that has been previously treated with a pesticide (also referred to as reentry exposure). Such exposures may occur when workers enter previously treated areas to 

perform job functions, including activities related to crop production, such as scouting for pests 

or harvesting. Post-application exposure levels vary over time and depend on such things as the 

type of activity, the nature of the crop or target that was treated, the type of pesticide application, 

and the chemical’s degradation properties. In addition, the timing of pesticide applications, 

relative to harvest activities, can greatly reduce the potential for post-application exposure.

9.2.1 Dermal Post-application Risk

Exposure Duration: HED classifies exposures from 1 to 30 days as short-term and exposures 30 

days to six months as intermediate-term. For dimethenamid-P, since toxicological endpoints are 

the same for both durations (short-, and intermediate), short-term risk estimate quantification is 

presented in this memo and considered protective of longer exposure durations. 

Transfer Coefficients: It is the policy of HED to use the best available data to assess postapplication exposure. Sources of generic post-application data, used as surrogate data in the 

absence of chemical-specific data, are derived from ARTF exposure monitoring studies, and, as 

proprietary data, are subject to the data protection provisions of FIFRA. The standard values 

recommended for use in predicting post-application exposure that are used in this assessment, 

known as “transfer coefficients”, are presented in the ExpoSAC Policy 311” which, along with 

additional information about the ARTF data, can be found at the Agency website12. Table 

6.2.2.1 provides a summary of the anticipated post-application activities and associated transfer 

coefficients for the proposed crops/use sites.

Table 6.2.2.1. Anticipated Post-Application Activities and Dermal Transfer Coefficients.

Proposed Crops

Policy Crop 

Group 

Category

Crop 

Height

Foliage 

Density

Transfer 

Coefficients 

(cm2/hr)

Activities

Cotton Subgroup 20C

Field / row 

crop, low / 

medium

Low

Full/Min 210 Scouting

Full/Min 70 Weeding, Hand

Application Rate: Maximum rate of 1.0 lb dimethenamid-P/A was used. Refer to the proposed 

use pattern table in section 3.3 for more details.

Exposure Time: The average occupational workday is assumed to be 8 hours. 

Dislodgeable Foliar Residues: Chemical-specific dislodgeable foliar residue data have not been 

submitted for dimethenamid-P. Therefore, this assessment uses HED’s default assumption that

 

11 Available: http://www.epa.gov/pesticides/science/exposac_policy3.pdf

12 Available: http://www.epa.gov/pesticides/science/post-app-exposure-data.html
Page 38 of 51

25% of the application is available for transfer on day 0 following the application and the 

residues dissipate at a rate of 10% each following day.

Dislodgeable Foliar Residue (DFR): In accordance with 40CFR158, DFR data are required for 

all occupational (e.g., crop, nursery, greenhouse use sites) or residential (e.g., ornamental and 

vegetable gardens, pick your own farms, retail tree farms) uses that could result in postapplication exposure to foliage. In the absence of chemical-specific DFR data, EPA uses default 

values. The 2012 Standard Operating Procedures for Residential Pesticide Exposure 

Assessment includes an analysis of a number of DFR studies, which resulted in the selection of a 

revised default values for the fraction of the application rate available for transfer after a foliar 

application (FAR). These values are based on an analysis of 19 DFR studies. Since that time, the 

Agricultural Re-entry Task Force has submitted information (MRID 49299201) that corrects an 

application rate error made in the original submission of “ARF039 – Determination of Dermal 

and Inhalation Exposure to Reentry Workers During Chrysanthemum Pinching in a Greenhouse” 

(EPA MRID 45344501). As a result, the range of FAR values was revised from 2% - 89% to 2% 

- 47%. In the data, a large range of transferability is observed and this variability can potentially 

be attributable to many factors such as active ingredient; formulation; field conditions in the 

studies; weather conditions (e.g., humidity); or many other difficult to quantify factors. 

Although witnessed across multiple chemicals, this range in FAR values is not expected when 

considering DFR data for a single chemical. At this time, the ARTF submission did not alter the 

selection of 25% as the reasonable, high-end default value. Because DFR data are not available 

for dimethenamid-P, EPA is using the default value of 25%. Although there may be a small 

degree of uncertainty in the use of the default DFR value for dimethenamid-P (i.e., there is a 

small chance that the FAR value may exceed the applicable default value), it is likely that the 

health-protective aspects of EPA’s occupational post-application assessment methodology will 

more than compensate for this potential uncertainty. For example, when assessing residential 

and occupational post-application exposure to gardens and ornamentals, EPA assumes the 

following: exposures occur to zero-day (i.e., day of application ) residues every day of the 

assessed exposure duration (i.e., EPA assumes that no dissipation or degradation occurs, it 

doesn’t rain, etc); individuals perform the same post-application activities performed in the 

transfer coefficient study day after day (e.g., weeding, harvesting, pruning, etc.); and individuals 

engage in these post-application activities for a high-end amount of time every day (represented 

by data reflecting time spent gardening based on survey data).

Given the conservatisms discussed above and the potential compounding nature of these 

conservatisms, EPA is able to rely upon the calculated exposure estimates with confidence that 

exposure is not being underestimated. 

Since the highest estimated occupational post-application exposure using default DFR values for 

dimethenamid-P is minimal in comparison to the level of concern (i.e., the calculated MOE is 

greater than 2 times higher than the level of concern, (MOE = 5,100 compared to the LOC of 

100); EPA is waiving the 40CFR DFR data requirement. In this instance, it is unlikely that 

chemical-specific DFR data would be needed to further refine exposure assessments or would 

add appreciably to our overall understanding of the availability of dislodgeable foliar pesticide 

residues for dimethenamid-P. 
Page 39 of 51

Occupational Post-application Non-Cancer Dermal Risk Estimates

Table 6.2.2.2. Occupational Post-application Non-Cancer Exposure and Risk Estimates for dimethenamidP.

Crop/Site Activities Transfer Coefficient 

(cm2/hr) DFR1

Dermal Dose

At Day 0 

(mg/kg/day)2

MOE3

At Day 0

LOC=100

Short- and Intermediate-term

Cotton Subgroup 20C

Scouting 210

2.8

0.059 5,100

Weeding, Hand 70 0.020 15,000

1 DFR = Application Rate × F × (1-D)t × 4.54E8 μg/lb × 2.47E-8 acre/cm2; where F = 0.25 and D = 0.10 per day 

2 Daily Dermal Dose = [DFR (μg/cm2) × Transfer Coefficient × 0.001 mg/μg × 8 hrs/day × dermal absorption (100%)]  BW (80 kg).

3 MOE = POD (300 mg/kg/day) / Daily Dermal Dose

Restricted Entry Interval

The REI specified on the proposed label is based on the acute toxicity of dimethenamid-P. 

Dimethenamid-P is classified as Toxicity Category III via the dermal route, Toxicity Category III 

for eye irritation potential and Toxicity Category IV for skin irritation potential. It is a mild skin 

sensitizer. Short- and intermediate-term post-application risk estimates were not a concern on 

day 0 (12 hours following application) for all post-application activities. Under 40 CFR 156.208 

(c) (2) (iii), ai’s classified as Acute III or IV for acute dermal, eye irritation and primary skin

irritation are assigned a 12-hour REI. Therefore, the [156 subpart K] Worker Protection 

Statement interim REI of 12 hours is adequate to protect agricultural workers from postapplication exposures to dimethenamid-P.

9.2.2 Inhalation Post-application Risk

Based on the Agency's current practices, a quantitative post-application inhalation exposure 

assessment was not performed for dimethenamid-P at this time primarily because of the low 

acute inhalation toxicity (Toxicity Category III), and the low proposed use rate (1.0 lb ai/A). 

However, there are multiple potential sources of post-application inhalation exposure to 

individuals performing post-application activities in previously treated fields. These potential 

sources include volatilization of pesticides and resuspension of dusts and/or particulates that 

contain pesticides. The Agency sought expert advice and input on issues related to volatilization 

of pesticides from its Federal Insecticide, Fungicide, and Rodenticide Act Scientific Advisory 

Panel (SAP) in December 2009, and received the SAP’s final report on March 2, 201013. The 

Agency is in the process of evaluating the SAP report as well as available post-application 

inhalation exposure data generated by the ARTF and may, as appropriate, develop policies and 

procedures, to identify the need for and, subsequently, the way to incorporate occupational postapplication inhalation exposure into the Agency's risk assessments. If new policies or 

procedures are put into place, the Agency may revisit the need for a quantitative occupational 

post-application inhalation exposure assessment for dimethenamid-P.

Although a quantitative occupational post-application inhalation exposure assessment was not 

performed, an inhalation exposure assessment was performed for occupational/commercial 

 

13 Available: http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html
Page 40 of 51

handlers. Handler exposure resulting from application of pesticides outdoors is likely to result in 

higher exposure than post-application exposure. Therefore, it is expected that these handler 

inhalation exposure estimates would be protective of most occupational post-application 

inhalation exposure scenarios.

10 References

- B. Daiss, 8/27/08, D348401, Dimethenamid-P Human Health Risk Assessment for Proposed 

Use of Dimethenamid-P on Turfgrass on Golf Courses.

- I. Nieves, 7/1/14, D418117, Dimethenamid-P (dimethenamid-P). Occupational and 

Residential Exposure Assessment for a Proposed Use on Cotton Subgroup 20C.

- B. Cropp-Kohlligian, 6/14/14, D418115, Dimethenamid-P. New Use and Tolerance in/on 

Cottonseed Subgroup 20C. Summary of Analytical Chemistry and Residue Data.

- B. Cropp-Kohlligian, 8/28/14, D418116, Dimethenamid/Dimethenamid-P. Acute and Chronic

Aggregate Dietary (Food and Drinking Water) Exposure and Risk Assessments for Proposed 

New Use on Cottonseed Subgroup 20C.

- M. Biscoe, 8/14/14, D422167, Dimethenamid-P: ADDENDUM Drinking Water Exposure 

Assessment for Existing Ornamental and Green Onion Uses and the Proposed Cotton Use. 

- M. King, B. Cropp-Kohlligian, I. Nieves, D414651 (TXR# 0056993), Dimethenamid-P

(DMTA-P): Summary of Hazard and Science Policy Council (HASPOC) Meeting of June 19, 

2014: Recommendations on the Need for a 28-day Inhalation Study.
Page 41 of 51

Appendix A. Toxicology Profile and Executive Summaries

A.1 Toxicology Data Requirements

The requirements (40 CFR 158.340) for dimethenamid//dimethenamid-P are in Table 1. Use of 

the new guideline numbers does not imply that the new (1998) guideline protocols were used.

Table 1. Guideline Data Requirements

Test Technical

Required Satisfied

870.1100 Acute Oral Toxicity.......................................................

870.1200 Acute Dermal Toxicity..................................................

870.1300 Acute Inhalation Toxicity..............................................

870.2400 Primary Eye Irritation....................................................

870.2500 Primary Dermal Irritation..............................................

870.2600 Dermal Sensitization .....................................................

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

870.3100 Oral Subchronic (rodent)...............................................

870.3150 Oral Subchronic (nonrodent).........................................

870.3200 21-Day Dermal..............................................................

870.3250 90-Day Dermal..............................................................

870.3465 90-Day Inhalation..........................................................

yes

yes

yes

no

yes

yes

yes

yes

-

waived

870.3700a Developmental Toxicity (rodent) ..................................

870.3700b Developmental Toxicity (nonrodent) ............................

870.3800 Reproduction .................................................................

yes

yes

yes

yes

yes

yes

870.4100a Chronic Toxicity (rodent)..............................................

870.4100b Chronic Toxicity (nonrodent)........................................

870.4200a Oncogenicity (rat)..........................................................

870.4200b Oncogenicity (mouse) ...................................................

870.4300 Chronic/Oncogenicity ...................................................

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

870.5100 Mutagenicity—Gene Mutation - bacterial.....................

870.5300 Mutagenicity—Gene Mutation - mammalian ...............

870.5375 Mutagenicity—Structural Chromosomal Aberrations...

870.5900 Mutagenicity—Other Genotoxic Effects.......................

yes

yes

yes

yes

yes

yes

yes

yes

870.6100a Acute Delayed Neurotox. (hen).....................................

870.6100b 90-Day Neurotoxicity (hen) ..........................................

870.6200a Acute Neurotox. Screening Battery (rat).......................

870.6200b 90-Day Neuro. Screening Battery (rat) .........................

870.6300 Develop. Neuro .............................................................

no

no

yes

yes

no

-

-

yes

yes

-

870.7485 General Metabolism......................................................

870.7600 Dermal Penetration........................................................

870.7800 Immunotoxicity .............................................................

yes

-

yes

yes

-

yes
Page 42 of 51

A.2 Toxicity Profiles

Table A.2.1. Acute Toxicity Profile -[RS]-dimethenamid [PC 129051]

Guideline No. Study Type MRID(s) Results Toxicity Category

870.1100 Acute oral/rats 

[Sprague Dawley]

TXR# 008285

41662409

(1989) 

44097602

(1992)

LD50 = 2140 

mg/kg (males)

LD50 = 1297 

mg/kg (females)

LD50 = 1570 

mg/kg mean both 

sexes 

LD50 = 500

III

II-III

870.1200 Acute dermal/rabbits

[NZW]

41662410 

(1988)

LD50 = >2000 

mg/kg

III

870.1300 Acute inhalation/rats

[Wistar] TXR# 008285

41662411

(1986)

LC50 = 4.99 mg/L III

870.2400 Acute eye irritation/rabbits 41662412

(1988) 

Minimally 

irritating 

III

870.2500 Acute dermal irritation/ rabbits 41662413

(1988)

Minimally 

irritating

IV

870.2600 Skin sensitization [Guinea Pigs] 41662407

(1987) 

Mild skin 

sensitizer 

Sensitizer

Table A.2.2. Acute Toxicity Profile -[S] dimethenamid-P [PC 120051] 

Guideline No. Study Type MRID(s) Results Toxicity 

Category*

870.1100 Acute oral/rats

[Sprague Dawley]

44097603

(1996)

LD50 = 429 mg/kg males 

LD50 = 531 mg/kg females

LD50 =480 mg/kg both sexes.

II

870.1200 Acute 

dermal/rabbits

[NZW]

44332234

(1996)

LD50 = >2000 mg/kg III

870.1300 Acute inhalation 

[Sprague Dawley]

44332235

(1996)

LC50 = 2.2 mg/L III

870.2400 Acute eye irritation 

[NZW]

44332238

(1996)

Minimally irritating III

870.2500 Acute dermal 

irritation [NZW]

44332239

(1996)

Minimally irritating IV

870.2600 Skin sensitization 

[Guinea Pigs]

44097604 Mild skin sensitizer Sensitizer
Page 43 of 51

Table A.2.3. Subchronic, Chronic and Other Toxicity Profile for [RS]-dimethenamid

Guideline No./ 

Study Type

MRID No. (year)/ 

Classification /Doses Results

870.3100

90-Day 

Feeding/Sprague 

Dawley rat 

41615901 (1986)

Doses: 0, 50, 150, 500, 

1500, 3000 ppm [M/F: 

0/0/, 3.5/3.9, 10.0/11.8, 

33.5/40.1, 98/119, 

204/238 mg/kg/day]

Acceptable in TXR# 

008285

NOAEL=33.5/40.1 mg/kg/day [500 ppm]

LOAEL=98/119 mg/kg/day [1500 ppm] based on decreased 

body weight and body weight gain, increased total protein in 

males; in females, increased cholesterol, increased adj liver 

weight and centrilobular hepatocytic enlargement.

870.3150

90-Day oral 

toxicity (dog)

41615902 (1986 [Doses: 

0, 100, 750, 2000 

ppm][M/F: 0/0, 4.72/4.98, 

33.6/39.7, 89.6/87.4 

mg/kg/day]

[From std tables(dry): 0, 

2.5, 18.75, 50 mg/kg/day]

[From std tables(wet): 0, 

7.5, 56.25, 150 

mg/kg/day]

Acceptable TXR# 008285

NOAEL = 4.72/4.98 mg/kg/day [100 ppm ]

LOAEL =33.6/39.7 mg/kg/day [750 ppm] based on 

decreased body weight and body weight gain in females, 

increased rel. liver wt in both sexes, increased periportal 

vacuolation in both sexes and dilation of liver sinusoids in 

females.

870.3200

21/28-Day dermal 

toxicity (NZW 

rabbit)

41662414 (1989)

Doses: 0, 50, 150, 500 

mg/kg/day

Acceptable in TXR# 

010012

LOAEL = 500 mg/kg/day based on decreased body weight 

gain. 

870.3200

21/28-Day dermal 

toxicity (NZW 

rabbit)

419513010 (1991)

Doses: 0, 30, 300, 1000 

mg/kg/day

LOAEL = 1000 mg/kg/day based on severe systemic toxicity 

and mortality. 

The NOAEL is 300 mg/kg/day.

870.3700a

Prenatal 

developmental in 

(Sprague Dawley 

rats)

41615904 (1987) [Doses: 

0, 50, 215, 425 

mg/kg/day]

Vehicle is 0.5% CMC, 10 

ml/kg

Acceptable in TXR# 

008285

Maternal NOAEL = 50 mg/kg/day

LOAEL =215 mg/kg/day based on body weight decrement 

on GD 12 (but not a single dose effect) and body weight and 

food consumption decrease, both GD 6-9 & 6-16

Developmental NOAEL = 215 mg/kg/day

LOAEL=425 mg/kg/day based on increased post 

implantation loss.

Prenatal 

Developmental 

(NZW/Rabbit) 

41706809 (1988) Doses: 

0, 37.5, 75, 150 

mg/kg/day

Acceptable TXR# 008469 

N/L change from previous

Maternal NOAEL=75 mg/kg/day

LOAEL=150 mg/kg/day based on slight body weight 

decrement (80g, GD 12-15), body weight loss (75g GD 15-

19) and 2 abortions and in a 20 litter/group range-finding 

study, death (13/20) and abortions (7/20) at 250 mg/kg/day

Developmental NOAEL=75 mg/kg/day

LOAEL=150 mg/kg/day based on SS fetal incidence of 

irregular parietals and hyoid angulated. Litter incidence was 

nominally elevated by 50% and 100%, respectively, and 

nominally increased post implantation loss (double control). 

870.3800

Reproduction and 

fertility effects

(Wistar rats)

41615905 (1990) Doses: 

0, 100, 500, 2000 ppm 

[M/F; 0/0, 7/8, 36/40, 

150/160 mg/kg/day] 

Parental/Systemic NOAEL = 36/40 mg/kg/day [500 ppm]

LOAEL =150/160 mg/kg/day [2000 ppm] based on decrease 

body weight, body weight gain, food consumption and abs & 

relative liver weight increase. 
Page 44 of 51

Table A.2.3. Subchronic, Chronic and Other Toxicity Profile for [RS]-dimethenamid

Guideline No./ 

Study Type

MRID No. (year)/ 

Classification /Doses Results

Acceptable TXR# 008285

Reproductive NOAEL = 150/160 mg/kg/day [2000 ppm] 

LOAEL = None

Offspring NOAEL = 40 mg/kg/day [500 ppm]

LOAEL = 160mg/kg/day [2000 ppm] based on f1 pup weight 

decrement at LD 21 and f2 pup weight decrease at LD day 

7and 21.

870.4100b

Chronic toxicity 

(dog)

41615903 (1990)

0, 25, 250, 1250 ppm 

[M/F 0/0, 1.95/2.1, 

10.1/9.1, 48.7/49.3 

mg/kg/day]

[From std tables(dry): 0, 

0.625, 6.25, 31.25 

mg/kg/day]

[From std tables(wet): 0, 

2.5, 18.75, 50 mg/kg/day]

Acceptable TXR# 008285

NOAEL = 10.1/9.1 mg/kg/day [250ppm]

LOAEL =48.7/49.3 mg/kg/day [1250ppm] based on 

decreased body wt & body wt gains [43% to 60%,0-26wk] 

both sexes 100% in males wk 26-52] alkaline phosphatase 

increased in females 109-2185 throughout study and 80% in 

males. Portal vacuolation in males; vacuoles not lipid or 

glycogen 

870.4200 b

Carcinogenicity

(mouse)

41662415 (1990)

0,30, 300, 1500, 3000 

ppm [M/F: 0/0, 3.8/4.1, 

40.8/40.1, 205/200, 

431/411 mg/kg/day

Acceptable TXR# 008315

NOAEL = 300 ppm (M/F: 40.8/40.1 mg/kg/day)

LOAEL = 1500 ppm (M/F: 205/200 mg/kg/day) based on 

decreased body weight gain in both sexes. 

No treatment related tumors were seen at adequate doses.

870.4300 Chronic/

carcinogenicity 

(Sprague Dawley 

rat)

41706808 & 42030102 

(1990) 0, 100, 700,1500 

ppm [M/F: 0/0, 5.1/6.8, 

36/49, 80/109 mg/kg/day]

Acceptable TXR# 008315 

& 008975

NOAEL = 100 ppm [M/F: 5.1/6.8 mg/kg/day]

LOAEL = 7000 ppm [M/F: 36/49 mg/kg/day] based on 

decreased body weight and body weight gain in both sexes 

and microscopic hepatic lesions in both sexes. 

A dose related increased incidence of liver tumors in males 

(benign and malignant combined) were seen at 1500 ppm, 

both exceeding historical controls. 

Cancer Peer Rev (TXR# 012143 & 012831) characterized 

[RS]-dimethenamid as a Group C - possible human 

carcinogen, and recommended that for the purpose of risk 

assessment the Reference dose approach should be used for 

human risk assessment)

Gene Mutation

870.5100 Bacterial 

Reverse mutation

41596542 (1989)

Reverse mutation in S. 

typhimurium strains TA 

98, TA100, TA1535, 

TA1537, TA1538

Acceptable TXR# 008285

Strains tested at 1000-10000 μg/plate, -S9 and 1000-6500 

μg/plate, +S9. Cytotoxicity and precipitation were noted at 

higher doses. 

Test was negative, +/-S9. 

Cytogenetics 

870.5395 Mouse 

erythrocyte 

micronucleus test

43648401 (1993)

In vivo Bone marrow 

erythrocyte micronucleus 

test

Acceptable inn TXR# 

011053 

CD-1 mice dosed at 710 mg/kg in two daily doses. LD50 = 

1417 mg/kg. Bone marrow erythrocytes harvested 24 and 48 

hours later.

Test negative. 
Page 45 of 51

Table A.2.3. Subchronic, Chronic and Other Toxicity Profile for [RS]-dimethenamid

Guideline No./ 

Study Type

MRID No. (year)/ 

Classification /Doses Results

Cytogenetics 

870.5395 Mouse 

erythrocyte 

micronucleus test

41822703 (1986)

In vivo Bone marrow 

erythrocyte micronucleus 

test. Unacceptable in 

TXR# 008469

Mice dosed 0-1000 mg/kg in single doses. Mice showed no 

toxicity; only one mouse died. 

Test negative. 

Chromosomal 

aberration test 

870.5375

41596543 (1985)

In vitro chromosomal 

aberration test in Chinese 

hamster ovaries (CHO)

Unacceptable in TXR# 

008285 & acceptable in 

TXR# 009070

Cells in 125-150 μg/mL, -S9 and 400 to 500 μg/mL, +S9; all 

doses were cytotoxic. Study needs repeating at no cytotoxic 

doses. 

Test considered equivocally positive. 

UDS in rat 

hepatocytes

870.5550

41822702 (1986)

In vitro unscheduled 

DNA synthesis in rat 

hepatocytes

Unacceptable in TXR# 

008469

Cell in 1.0-100 nl/mL. No cytotoxicity was seen. 

Test was negative. 

UDS in rat 

hepatocytes

870.5550

43648402 (1993)

In vivo unscheduled DNA 

Synthesis in rat 

hepatocytes

Acceptable to EEC 

requirements TXR# 

011053

Fisher 344 rat administered SAN 582H doses of 158 or 500 

mg/kg. Sampled 2-4 and 12-14 hours after dosing. Only 0.2-

3.6% cells in repair, but negative control was less than zero. 

Test was negative for UDS at 158 and 500 mg/kg.

UDS in rat 

hepatocytes

870.5550

41596544 (1989)

In vitro unscheduled 

DNA synthesis in rat 

hepatocytes

Acceptable in TXR# 

008285 

SAN 582H administered at 0.01 to 50 μg/mL. Unscheduled 

DNA synthesis was seen well below cytotoxic doses. 

Unequivocally positive for UDS. 

Test positive. 

UDS in rat 

hepatocytes

870.5550

41662416 (1990)

In vitro unscheduled 

DNA synthesis in rat 

hepatocytes.

Acceptable in TXR# 

008469

SAN 582H administered at 0.0128 to 1000 μg/mL to rat 

primary cultures of hepatocytes. Doses at 1000 μg/mL were 

cytotoxic. No UDS was noted.

Test negative for UDS. 

Dominant Lethal

870.5450

43209201 (1994) 

(Hazleton)

Dominant lethal in CR 

rats

Acceptable in TXR# 

011053

Male Charles River rats (40-55) administered SAN 582H in 

single oral doses of 275, 550 or 1100 mg/kg were mated 

starting at 10 weeks to 40-55 female undosed CR rats. 

Increased dead implants at week 1 and week 2 may suggest a 

dominant lethal effect. These were mostly late implant 

deaths, which some consultants claim are not characteristic 

of a dominant lethal effect. .

Dominant Lethal

870.5450

43814401 (1995) 

(Microbiological Assoc.) 

Dominant lethal in 

Sprague Dawley rats

Male Sprague Dawley rats (40-60) administered SAN 582H 

in single oral doses of 275, 550 or 1100 mg/kg were mated 

starting the day after dosing in Trial 1 and 2 days after 

dosing in Trial 2 to 80-120 female undosed Sprague Dawley 

rats . Each male was mated to 2 females over a five day 
Page 46 of 51

Table A.2.3. Subchronic, Chronic and Other Toxicity Profile for [RS]-dimethenamid

Guideline No./ 

Study Type

MRID No. (year)/ 

Classification /Doses Results

sequence. Results equivocal, but not considered to negate 

results from MRID# 43209201.

Note: Both the high dose rabbit and rat developmental 

studies showed increased late and early resorptions. 

BALB/3T3 cell 

transformation 

NG

41822701 (1986)

per-1996 in vitro cell 

transformation 

Unacceptable in TXR# 

008469

BALB/3T3 cells administered SAN 582H at 15.0 to 100 

μg/mL. No transformed cells were noted, but several 

inadequacies were noted in the test report. Number of cells 

transformed. Cell transformation yields variable results and 

is not an acceptable methodology. 

Test negative 

870.7485

Metabolism and 

pharmacokinetics

(Wistar rats)

41596545 (1989) & 

42289501 (1992)

Single low and high doses 

of [14C] SAN 582H and 

after repeat doses of SAN 

582H were administered

Unacceptable in TXR# 

008285

Acceptable in TXR# 

009867. 

Extensively metabolized, being essentially complete within 3 

days and over 90% being excreted in the urine, feces and bile 

within 7 days. Total excretion products with the highest 

concentrations (in % of administered dose) in the male and 

female, respectively, were parent 1.4% and 1.2%, *M1- 3.3 

& 7.2%, *M2- 3.6% & 9.8%, M3- 0.6% & 0.4%, M14- 2.8% 

& 3.3%, *M16- 5.1% & 3.3%, M17- 0.6% & 3.3%, M19-

1.1% & 1.4%. Parent was initially conjugated with 

glutathione and most metabolism taking place with the 

glutathione conjugate. No significant differences in 

metabolism were seen between males and females. Up to 45 

putative metabolites were reported in the urine and up to 50 

were reported in the feces. Of these metabolites, 31 were 

identified. Of the unidentified metabolites none exceeded 

3.0% and most being less than 1% of the administered dose.

Chemical name of 

excretion products 

exceeding 5% in 

the multidose 10 

mg/kg study in 

males or females.

M1 is N-(2,4-dimethyl-3-thienyl)-N-(2-hydroxy-1-methylethyl)-2-(methyl-thio)-acetamide

M2 is N-(2,4-dimethyl-3-thienyl)-MN-(2-hydroxy-1-methylethyl)-2-(methyl-sulfinyl)-

acetamide

M16 is N-(2-hydroxymethyl-4-methyl-3-thienyl)-N-(2-methoxy-1-metylethyl)-2-

(methylsulfinyl)-acetamide

Table A.2.4. Subchronic, Chronic and Other Toxicity Profile for [S]-dimethenamid-P (PC 120051)

Guideline No./ 

Study Type

MRID No. (year)/ 

Classification /Doses Results

870.3100

90-Day 

Feeding/Sprague 

Dawley Rat 

44332242 (1996)

Doses: 0, 500, 1500, 3000 

ppm [M/F: 0/0/, 37/40, 

110/125, 222/256 

mg/kg/day]

Acceptable in TXR# 

0050183

NOAEL=37/40 mg/kg/day [500 ppm]

LOAEL=110/125 mg/kg/day [1500 ppm] based on 

decreased body weight and body weight gain in males and 

females, increased gamma-glutamyl transferase in both 

sexes, increased cholesterol in males, increased abs. and rel. 

liver weight and periportal hepatocytic hypertrophy and 

periportal eosinophilic inclusions in males, centrilobular 

hypertrophy in females and liver necrosis in females.
Page 47 of 51

Table A.2.4. Subchronic, Chronic and Other Toxicity Profile for [S]-dimethenamid-P (PC 120051)

Guideline No./ 

Study Type

MRID No. (year)/ 

Classification /Doses Results

870.3700a

Prenatal 

developmental in 

(Sprague Dawley 

rats)

44332243 (1996) [Doses: 

0, 25, 150, 300 

mg/kg/day] Vehicle is 

0.5% CMC, 10 ml/kg 

Acceptable in TXR# 

0050183

Maternal LOAEL = 150 mg/kg/day based on a decrease in 

body weight/gain and feed consumption (clinical signs at 

300 mg/kg/day). 

Maternal NOAEL is 25 mg/kg/day. 

Developmental LOAEL is 150 mg/kg/day based on an 

increased incidence of incomplete ossification of the second 

sternal central and/or pelvic pubis. The developmental 

NOEL is 25 mg/kg/day.

Gene Mutation

870.5100 Bacterial 

Reverse mutation

Reverse mutation 

44332244 (1997) 

S. typhimurium TA1535; 

E. coli WP2uvrA

Acceptable in TRX# 

0052635

S. typhimurium exposed to 500-4000 μg/plate +/- S9.

E. coli exposed to 20-5000 μg/plate +/-S9 using the Std plate 

incorp method or 4-2500 μg/plate +/-S9 using the 

preincubation modification to the std test. Highest doses 

were cytotoxic. 

All assays were negative.

Gene Mutation

870.5100 Bacterial 

Reverse mutation

Reverse mutation 

44332245 (1997) 

S. typhimurin TA1535, 

TA1537, TA 98, TA100; 

E. coli WP2uvrA

Acceptable in TRX# 

0052635 

Exposed to 20-5000 μg/plate in a plate incorporation assay. 

Marginal cytotoxicity at limit dose of 5000 μg/plate +/- S9. 

Assays were negative with both bacteria +/- S9. 

Gene Mutation

870.5100 Bacterial 

Reverse mutation

Reverse mutation 

44332246 (1997) 

S. typhimurin TA100.

Acceptable in TRX# 

0052635 

Repeat of MRID# 44123502. S. typhimurium TA100 was 

exposed to 100-5000 μg/plate -S9. 

Assay was negative.

Gene Mutation

870.5100 Bacterial 

Reverse mutation

Reverse mutation 

44123502 (1996) & 

resubmitted 44332250 

(1996) 

S. typhimurin TA1535, 

TA1537, TA 98, TA100; 

E. coli WP2uvrA

Acceptable in TRX# 

0052636 

Exposed to 100-5000 μg/plate, +/-S9, in a plate 

incorporation assay. Insolubility seen at 333 & 5000 

μg/plate, but no toxicity at any dose. +/- S9. 

Assays were negative with both bacteria + S9, however, -S9 

induced 1.5 fold increases at 333 μg/plate and 4.1 fold 

increases in reverents in TA100 strain at 5000 μg/plate. 

This mutagenic response was reproducible at 100 to 5000 

μg/plate. 

Mammalian cell 

mutation

870.5300

In vitro CHO/HGPRT 

mutation assay

44123501 (1996) & 

resubmission as 

44332248

Acceptable TXR# 12312

Chinese hamster ovary (CHO) cells were exposed to 100-

400 μg/mL, -S9, and 100-450 μg/mL, +S9. Slight 

cytotoxicity was seen at the highest dose and severe toxicity 

was seen at 500 μg/mL. 

Test was negative for mutagenic effects, +/- S9. 

Cytogenetics in 

Chinese Hamster 

Ovary (CHO) cells 

870.5375

Chromosomal aberrations 

in vitro

44332247 (1996)

CHO cells were exposed to 2-120 μg/mL -S9; cytotoxic at 

120 μg/mL. CHO cells were exposed to 15-120 μg/mL 

+S9; cytotoxic at 500 μg/mL. 

Assay was negative +/-S9.
Page 48 of 51

Table A.2.4. Subchronic, Chronic and Other Toxicity Profile for [S]-dimethenamid-P (PC 120051)

Guideline No./ 

Study Type

MRID No. (year)/ 

Classification /Doses Results

Acceptable TXR# 

0052635

Cytogenetics; 

mouse erythrocyte 

micronucleus test 

870.5395

ICR mice in vivo test

44332249 (1996)

Acceptable TRX# 

0052635

Mice (5/sex) were exposed to i.p. injections of 103, 205, 410 

mg/kg. 

Assay was negative, indicating no clastogenic or aneugenic 

response.

Other Effects 

870.5550

UDS in mammalian 

cell culture 

Rat hepatocyte cell in 

vitro test 

44332251 (1996)

Acceptable TRX# 

0052635

Cells tested at 7.8-125 μg/mL. Cytotoxicity and insolubility 

were seen at 250 μg/mL. 

Test was negative for UDS. 

Acute 

Neurotoxicity 

870.6200 

0, 60, 200, & 600 mg/kg 

Acceptable

49184304 (2013)

NOAEL = 200 mg/kg

LOAEL= 600 mg/kg based on lacrimation, salivation, 

irregular and accelerated respiration, slight tremors, reduced 

exploration, unsteady gait, significantly reduced rearing 

Subchronic 

Neurotoxicity 

870.6200

0, 19, 63 & 323mg/kg –M

0, 23, 71, & 390 mg/kg- F

Acceptable 

49184305 (2013)

NOAEL for systemic toxicity 63 mg/kg based a trend of 

higher liver weights in females (pelvic dilation seen was 

considered incidental).

LOAEL 323 mg/kg

Immunotoxicity 

870.7800

0, 120, 385 & 1167 

mg/kg

Acceptable 

49184307 (2013)

The systemic LOAEL of female C57BL/6J Rj mice treated 

with BAS 656-PH was 1500 ppm (385 mg/kg bw/day) based 

on increased absolute and relative liver weight. The 

NOAEL was 500 ppm (120 mg/kg bw/day).

The immunotoxicity NOAEL in female C57BL/6J Rj mice 

for BAS 656-PH was 4000 ppm (1167 mg/kg bw/day) which 

was equivalent to the limit dose for the study. A LOAEL 

was not established. 

Appendix B. Physical/Chemical Properties
Page 49 of 51

Table B.1. Physicochemical Properties of Technical Grade Dimethenamid-P.

Parameter Value Reference

Melting point/range <-50oC MRID 47005001

pH 3.3 (in 1% aqueous emulsion)

Density 1.195 g/ml

Water solubility 1449 ±17 mg/L (pH 6.16)

Solvent solubility 20.8g/100 ml in hexane; soluble in all 

proportions in tetrahydrofuran, isopropyl alcohol, 

acetone, CAN, DMSO, DCM, toluene and noctanol.

Vapor pressure 1.88 (±0.29) x 10-5 mm Hg

Dissociation constant, pKa No dissociation

Octanol/water partition coefficient 77.6 and 1.89 (POW and log POW)

UV/visible absorption spectrum ε = 7560; 33 nm

Table B.2. Tolerance Summary for Dimethenamid/Dimethenamid-P excluding Livestock Feed 

Crops/Commodities.

Commodity

Established

Tolerance

(ppm)

Recommended 

Tolerance(s) 

Under Current 

Petition

(ppm)

Comments

Bean, dry, seed 0.01 --

Beet, garden, roots 0.01 --

Beet, garden, tops 0.01 --

Beet, sugar, molasses 0.01 --

Beet, sugar, roots 0.01 --

Beet, sugar, tops 0.01 --

Corn, field, grain 0.01 --

Corn, pop, grain 0.01 --

Corn, sweet, kernel plus cob w/husks 

removed

0.01 --

Cottonseed subgroup 20C -- 0.01 Crops in this subgroup include: 

cottonseed; cultivars, varieties, 

and/or hybrids of these.

Garlic 0.01 -- Under §180.1(g) this tolerance also 

applies to great headed garlic and 

serpent garlic.

Hops, dried cones 0.05 --

Horseradish 0.01 --

Leek 0.01 --

Onion, bulb 0.01 -- Under §180.1(g) this tolerance also 

applies to garlic; great headed 

garlic; serpent garlic; Chinese 

onion; pearl onion; potato onion; 

and shallot, bulb.

Onion, green 0.01 -- Under §180.1(g) this tolerance also 

applies to lady's leek; leek; wild 

leek; Beltsville bunching onion; 
Page 50 of 51

Table B.2. Tolerance Summary for Dimethenamid/Dimethenamid-P excluding Livestock Feed 

Crops/Commodities.

Commodity

Established

Tolerance

(ppm)

Recommended 

Tolerance(s) 

Under Current 

Petition

(ppm)

Comments

fresh onion; tree onion, tops; Welsh 

onion; and shallot, fresh leaves.

Onion, Welsh 0.01 --

Peanut 0.01 --

Pumpkin 0.01 -- Tolerance with regional restriction 

established under 40 CFR 

180.464(c).

Radish, roots 0.01 --

Radish, tops 0.01 --

Rutabaga, roots 0.01 --

Rutabaga, tops 0.1 --

Shallot, bulb 0.01 --

Shallot, fresh leaves 0.01 --

Squash, winter 0.01 -- Tolerance with regional restriction 

established under 40 CFR 

180.464(c).

Sorghum, grain, grain 0.01 -- Under §180.1(g) this tolerance also 

applies to Sorghum spp. [sorghum, 

grain, sudangrass (seed crop), and 

hybrids of these grown for its seed].

Soybean, seed 0.01 --

Turnip, greens 0.1 -- Under §180.1(g) this tolerance also 

applies to broccoli raab (raab, raab 

salad), hanover salad, turnip tops 

(turnip greens).

Turnip, roots 0.01 --

Turnip, tops 0.1 --

Vegetable, tuberous and corm, subgroup 

1C

0.01 -- Crops in this subgroup include: 

arracacha; arrowroot; artichoke, 

Chinese; artichoke, Jerusalem; 

canna, edible; cassava, bitter and 

sweet; chayote (root); chufa; 

dasheen; ginger; leren; potato; 

sweet potato; tanier; turmeric; yam 

bean; yam, true.
Page 51 of 51

Appendix C. Review of Human Research

This risk assessment relies in part on data from studies in which adult human subjects were 

intentionally exposed to a pesticide or other chemical. These studies were determined to require 

a review of their ethical conduct, have received that review and have been determined to be 

ethical.

The PHED Task Force, 1995. The Pesticide Handlers Exposure Database, Version 1.1. Task Force 

members Health Canada, U.S. Environmental Protection Agency, and the National Agricultural Chemicals 

Association, released February, 1995.

The Agricultural Handler Exposure Task Force (AHETF), 2011. The Occupational Handler Unit Exposure 

Surrogate Reference Table. U.S. Environmental Protection Agency. Released June 21, 2011.