UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C. 20460

OFFICE OF

CHEMICAL SAFETY AND

POLLUTION PREVENTION

MEMORANDUM

Date: March 5, 2014

SUBJECT: Clomazone: Human Health Risk Assessment for New Uses in/on Brassica, Head 

and Stem, Subgroup 5A; Rhubarb; and Pea, Southern (IR-4 Petition 2E8136)

PC Code: 125401 DP Barcode: D410435

Decision No.: 473594 Registration No.: 279-3052

Petition No.: 2E8136 Regulatory Action: Section 3 Registration

Risk Assessment Type: Single Chemical 

Aggregate

Case No.: 7203

TXR No.: NA CAS No.: 81777-89-1

MRID No.: NA 40 CFR: 180.425

FROM: Jessica Kidwell, Risk Assessor

Kelly O’Rourke, Occupational/Residential Exposure Assessor

Susan V. Hummel, Chemist

Bonnie Cropp-Kohlligian, Dietary Assessor

Angela Howard, PhD, DABT, Toxicologist

Risk Assessment Branch 4

Health Effects Division (7509P)

THROUGH: Elissa Reaves, Branch Chief

Risk Assessment Branch 4

Health Effects Division (7509P)

TO: Sidney Jackson, PM

Barbara Madden, Team Leader

Risk Integration, Minor Use and Emergency Response Branch 

Registration Division (7505P)

The Registration Division (RD) requested that the Health Effects Division (HED) conduct a 

human health risk assessment for the proposed new use of clomazone on Brassica, head and 

stem, subgroup 5A, rhubarb and pea, southern. This document provides the Health Effect 

Division’s (HED’s) human health risk assessment for clomazone.
CLOMAZONE/125401 Human Health Risk Assessment D410435

Page 2 of 49

1.0 Executive Summary........................................................................................................... 4

2.0 HED Recommendations.................................................................................................... 7

2.1 Data Deficiencies/Conditions of Registration........................................................... 7

2.2 Tolerance Considerations.......................................................................................... 8

2.2.1 Enforcement Analytical Method ............................................................................... 8

2.2.2 International Harmonization..................................................................................... 8

2.2.3 Recommended Tolerances......................................................................................... 8

2.2.4 Revisions to Petitioned-For Tolerances.................................................................... 9

2.3 Label Recommendations............................................................................................ 9

2.3.1 Recommendations from Residue Reviews................................................................ 9

2.3.2 Recommendations from Occupational Assessment................................................. 9

2.3.3 Recommendations from Residential Assessment..................................................... 9

3.0 Introduction........................................................................................................................ 9

3.1 Chemical Identity ....................................................................................................... 9

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

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

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

4.2 Absorption, Distribution, Metabolism, & Elimination (ADME) ......................... 12

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........................................................................................ 14

4.4.3 Evidence of Sensitivity/Susceptibility in the Developing or Young Animal........ 14

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..... 16

4.5.3 Cancer Classification and Risk Assessment Recommendation............................ 16

4.5.4 Summary of Points of Departure and Toxicity Endpoints Used in Human Risk 

Assessment............................................................................................................................... 16

5.0 Dietary Exposure and Risk Assessment......................................................................... 19

5.1 Metabolite/Degradate Residue Profile.................................................................... 19

5.1.1 Summary of Plant and Animal Metabolism Studies............................................. 19

5.1.2 Summary of Environmental Degradation.............................................................. 19

5.1.3 Comparison of Metabolic Pathways....................................................................... 20

5.1.4 Residues of Concern Summary and Rationale ...................................................... 20

5.2 Food Residue Profile ................................................................................................ 21

5.3 Water Residue Profile .............................................................................................. 22

5.4 Dietary Risk Assessment.......................................................................................... 23

5.4.1 Description of Residue Data Used in Dietary......................................................... 23

Assessment............................................................................................................................... 23

5.4.2 Percent Crop Treated Used in Dietary Assessment .............................................. 23

5.4.3 Acute Dietary Risk Assessment............................................................................... 24
CLOMAZONE/125401 Human Health Risk Assessment D410435

Page 3 of 49

5.4.4 Chronic Dietary Risk Assessment........................................................................... 24

5.4.5 Cancer Dietary Risk Assessment............................................................................. 24

5.4.6 Summary Table......................................................................................................... 24

6.0 Residential (Non-Occupational) Exposure/Risk Characterization ............................. 24

6.1 Spray Drift................................................................................................................. 24

6.2 Residential Bystander Postapplication Inhalation Exposure ............................... 25

7.0 Aggregate Exposure/Risk Characterization.................................................................. 25

7.1 Acute Aggregate Risk............................................................................................... 25

7.2 Short-Term Aggregate Risk .................................................................................... 26

7.3 Intermediate-Term Aggregate Risk........................................................................ 26

7.4 Chronic Aggregate Risk........................................................................................... 26

7.5 Cancer Aggregate Risk ............................................................................................ 26

8.0 Cumulative Exposure/Risk Characterization ............................................................... 26

9.0 Occupational Exposure/Risk Characterization ............................................................ 26

9.1 Short -Term Handler Risk....................................................................................... 26

9.2 Post-Application Risk............................................................................................... 27

9.2.1 Dermal Postapplication Risk ................................................................................... 28

9.2.2 Inhalation Postapplication Risk .............................................................................. 28

10.0 References......................................................................................................................... 29

Appendix A. Toxicology Profile and Executive Summaries .................................................. 30

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

Appendix C. Review of Human Research................................................................................ 49
CLOMAZONE/125401 Human Health Risk Assessment D410435

Page 4 of 49

1.0 Executive Summary

Clomazone is an herbicide used for pre-emergence control of weeds (annual grasses and broad 

leaves). It is registered for use on snap beans, succulent peas, cabbage, cotton, cucurbits, pepper, 

mint, rice, soybeans, sugarcane, and tuberous & corm vegetables (except potato). Tolerances for 

clomazone on these commodities are published in 40 CFR 180.425, including cabbage at 0.1 

ppm. Clomazone products are formulated as emulsifiable concentrates and microencapsulated 

formulations.

FMC Corporation has proposed a new use of the active ingredient (a.i.) clomazone on Brassica,

head and stem, subgroup 5A; rhubarb; and southern peas. The proposed uses will be added to the 

Command®3ME formulated end use product label containing 31.1% clomazone (EPA Reg. 

#279-3158). Command®3ME is a micro-encapsulated formulation designed to use water as its 

mode of dispersion, while remaining in an encapsulated state. Command®3ME is proposed to be 

applied pre-plant, pre-emergent, or early post-emergent to Brassica, head and stem, subgroup 

5A, rhubarb and southern peas using groundboom spray equipment at rates of 0.25 - 0.5, 1.5 and 

0.50 pounds ai per acre (lb ai/A), respectively. A maximum of 1 application is allowed per 

season.

The current application requests adding Brassica, head and stem, subgroup 5A; Rhubarb; and 

Pea, Southern; to the label for Command 3ME, and proposes the following tolerances.

Brassica, stem and head subgroup 5A 0.1 ppm

Rhubarb 0.3 ppm

Pea, Southern, succulent seed 0.05 ppm

Pea, Southern, dry seed 0.05 ppm

Pea, Southern, hay 0.05 ppm

At the same time, there is a request to revoke the tolerance for cabbage at 0.1 ppm, since cabbage 

will be covered by the new tolerance for Brassica, head and stem, subgroup 5A.

There is a potential for acute and chronic dietary exposures, as well as for short-term

occupational exposure to clomazone during mixing, loading, application, and post-application 

activities. The clomazone label requires occupational handlers to wear long sleeved shirts, long 

pants, chemical resistant gloves, shoes, and socks. There are no residential uses of clomazone.

Toxicology

The existing toxicological database is comprised of studies conducted with clomazone in the rat, 

mouse, rabbit and the dog. The primary target of clomazone is the liver, with hepatocellular 

cytomegaly noted in the chronic rat and mouse studies, hepatocellular necrosis in the chronic 

mouse study and increased liver weight observed in subchronic and chronic studies. There was 

one 28-day dermal toxicity study in rats that showed no effects up to the limit dose. There were 

no effects up to the limit dose in the chronic dog study. No inhalation toxicity studies were 

submitted, and the 28-day subchronic inhalation study was waived. 
CLOMAZONE/125401 Human Health Risk Assessment D410435

Page 5 of 49

Clomazone has low acute toxicity (Category III and IV) via the oral, dermal and inhalation 

routes. It is non-irritating to the eyes and mildly irritating to the skin. It is not a dermal sensitizer. 

No neurotoxicity studies with clomazone are available. Based on a WOE approach, the 

HASPOC concluded that a neurotoxicity battery is not required for clomazone at this time (see 

discussion in Section 4.3). There is no quantitative or qualitative evidence of susceptibility in the

developmental toxicity study in rabbits or in the 2-generation reproduction toxicity study in rats. 

Although qualitative susceptibility was observed in the developmental toxicity study in rats, the 

concern is low since there are clear NOAELs and LOAELs in the study and this study was used 

for risk assessment, and, therefore, is protective of the developmental effects.

Clomazone is absorbed, extensively metabolized by the liver and rapidly excreted in urine and 

feces, in rats, following oral administration. The absorption and elimination is almost complete 

with 97% of the radioactivity excreted within 168 hours.

There is no concern for mutagenicity. In the rat carcinogenicity study, there was no evidence of 

carcinogenicity. The mouse carcinogenicity study was inadequate to determine carcinogenic 

activity due to the lack of adverse effects at the highest dose tested. Despite the inadequacy of 

the mouse carcinogenicity study, EPA has determined that an additional mouse carcinogenicity 

study is not needed and that the rat chronic/carcinogenicity study will be adequate for assessing 

chronic risk, including cancer. This finding is based upon the following conclusions: (1) the rat is 

more sensitive than the mouse for the chronic assessment; (2) the consistent effect in rats 

(decreased body weight and increased liver weight) has been used as the point of departure

(POD) for the chronic assessment; (3) a new mouse study would only use doses well above the 

current POD for the chronic assessment; and (4) even if new mouse study identified positive 

carcinogenicity effects, that finding would not result in the adoption of a quantitative linear 

assessment of cancer risk due to the negative carcinogenicity finding in the rat study and the lack 

of a positive finding for genotoxicity. 

Dose Response Assessment

Toxicological endpoints were selected for dietary and occupational exposure scenarios. An 

acute reference dose (aRfD) of 1.0 mg/kg/day was established for females 13-49 years old based 

on a point of departure (POD) of 100 mg/kg/day from a developmental toxicity study in the rat.

An uncertainty factor (UF) of 100 (10-fold for interspecies extrapolation and 10-fold for 

intraspecies variability) was applied to the NOAEL to derive the RfD. The lowest observed 

adverse effect level (LOAEL) from this developmental study was 300 mg/kg/day based on 

indications of delayed ossification. The Food Quality Protection Act (FQPA) Safety Factor (SF) 

was reduced to 1X. An acute endpoint was not identified for the U.S. general population. The 

chronic reference dose (cRfD) of 0.84 mg/kg/day was established based on a POD of 84.4 

mg/kg/day from several co-critical studies (a 2-year chronic/carcinogenicity study in rats, a 90-

day oral toxicity study in rats and a 2-generation reproduction toxicity study in rats). An UF of 

100 (10-fold for interspecies extrapolation and 10-fold for intraspecies variability) was applied to 

the POD to derive the cRfD. The FQPA SF was reduced to 1X. Thus, the chronic population 

adjusted dose (cPAD) was also 0.84 mg/kg/day. A POD for dermal exposure was not selected 

because no dermal or systemic toxicity was observed in rats following repeated dermal 

application at the limit dose for 28 days. A short-term inhalation exposure POD (100 mg/kg/day) 
CLOMAZONE/125401 Human Health Risk Assessment D410435

Page 6 of 49

was selected from a developmental toxicity study in rats. Based on the use pattern, only a short 

term inhalation exposure scenario is applicable. 

Dietary Exposure and Risk

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. Both the acute and chronic 

assessments are highly conservative and incorporated tolerance level residues, assumed 100% 

crop treated and used default processing factors. Screening-level Tier I modeling was used to 

estimate drinking water concentrations. 

The acute dietary risk estimate at the 95th percentile of exposure utilized 3.0% of the acute 

population adjusted dose (aPAD) for females 13-49 years old. This is the only population 

subgroup for which an acute endpoint was selected. The acute dietary risk estimate for females 

13-49 years old is not of concern.

The chronic dietary risk estimates are ≤3.6% of the chronic population adjusted dose (cPAD) for 

all population subgroups. All Infants < 1 year of age is the most highly exposed subgroup, 

utilizing 3.6% of the cPAD, while the general US population utilizes 1.4% of the cPAD. The 

chronic dietary risk estimates are not of concern.

EPA has concluded that the chronic PAD for clomazone will be protective of any cancer risk 

posed by clomazone. Additionally, EPA is relying on the chronic dietary exposure assessment to 

evaluate cancer risk. 

Residential Non-Cancer Risks 

Currently, there are no registered or proposed residential uses for clomazone.

Aggregate Risk

In accordance with the FQPA, HED must consider and aggregate (add) pesticide exposures and 

risks from three major sources: food, drinking water, and residential exposures. Currently, there 

are no registered or proposed residential uses for clomazone, therefore, short- and intermediate 

term aggregate risk assessments are not required. In examining acute and chronic aggregate risk, 

HED has assumed that the only pathway of exposure relevant to the acute and chronic time 

frames is dietary exposure. Therefore, the acute and chronic aggregate risk is comprised of 

exposures to clomazone residues in food and drinking water and is equivalent to the acute and 

chronic dietary risk estimates. Both the acute and chronic dietary risk estimates are well below 

HED’s level of concern for the general population and all population subgroups. EPA has 

concluded that the chronic PAD for clomazone will be protective of any cancer risk posed by 

clomazone.
CLOMAZONE/125401 Human Health Risk Assessment D410435

Page 7 of 49

Occupational Risks 

The occupational handler exposure and risk estimates indicate that the short-term inhalation 

MOEs are not of concern to HED (i.e., MOEs > 100) without a respirator. A respirator is not 

required on the label.

Post-application dermal exposure and risk estimates were not evaluated as toxicity was not 

observed up to the limit dose in a dermal toxicity study, and no developmental or reproductive 

toxicity was seen in the database. The restricted entry interval (REI) is based on the acute 

toxicity of clomazone technical material. Clomazone is classified as a Toxicity Category IV for 

acute dermal toxicity, primary eye and skin irritation. Therefore, a 12-hour REI under 40 CFR 

156.208 (c) (2) (i) is required. The 12-hour REI, which currently appears on the Command®3M 

label, is adequate for the proposed uses.

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

inhalation exposure assessment was not performed for clomazone 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 clomazone. 

Human Studies Review

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 data, which include studies from 

PHED 1.1 and the AHETF database, are (1) subject to ethics review pursuant to 40 CFR 26, (2) 

have received that review, and (3) are compliant with applicable ethics requirements. For certain 

studies, the ethics review may have included review by the Human Studies Review Board. 

Descriptions of data sources, as well as guidance on their use, can be found at the Agency

website1. 

2.0 HED Recommendations

HED recommends for the proposed tolerance, with corrections specified below, and for the 

associated amended use. The current tolerance expression is in accord with our current guidance 

on tolerance expressions. The field trials for clomazone on broccoli, rhubarb, and southern peas 

are adequate. The enforcement analytical method is adequate. The residue data are supported by 

available storage stability data. 

HED concludes that there are no risk issues. Specific tolerance recommendations are discussed 

in section 2.2. Label recommendations are discussed in section 2.3. 

2.1 Data Deficiencies/Conditions of Registration

Toxicology: None.

 

1

http://www.epa.gov/pesticides/science/handler-exposure-data.html and 

http://www.epa.gov/pesticides/science/post-app-exposure-data.html
CLOMAZONE/125401 Human Health Risk Assessment D410435

Page 8 of 49

Residue Chemistry: None.

Occupational Assessment: None. 

2.2 Tolerance Considerations

2.2.1 Enforcement Analytical Method

Adequate enforcement methods are available for the determination of the residues of clomazone 

in plants. Briefly, samples are acid hydrolyzed, hexane extracted, Na2CO3 washed, and cleanedup with a Florisil column. The resulting samples are analyzed by gas chromatography (GC) 

using a nitrogen phosphorus detector (NPD) or mass spectrometer (MS). The limit of 

quantitation (LOQ) for this method is 0.05 ppm. A confirmatory procedure (GC/MS-SIM) is 

available (Method I, PAM II). Clomazone was determined in broccoli using the analytical 

method adapted from method FMC No. ACG 124. The LOQ (determined as the LLMV) was 

0.03 ppm for broccoli and rhubarb; and 0.05 ppm in southern pea commodities. The calculated 

LOQ and LOD, respectively, were 0.01850 and 0.006168 ppm in broccoli; 0.0394 and 0.0131 

ppm in rhubarb. The residue data were gathered with an adequate data collection method.

2.2.2 International Harmonization

There are no CODEX MRLs for residues of clomazone on any commodity. Canada has not 

established MRLs for the commodities in this petition.

2.2.3 Recommended Tolerances

HED recommends for the proposed tolerances, with corrections specified below in Table 2.2.3, 

and for the associated amended use. The current tolerance expression is in accord with our 

current guidance on tolerance expressions. When the tolerance for residues of clomazone on 

Brassica, head and stem, subgroup 5A is established, the tolerance on cabbage should be 

revoked.

Table 2.2.3. Tolerance Summary for Clomazone (§ 180.425)

Commodity Established/Proposed 

Tolerance (ppm)

Recommended 

Tolerance (ppm)

Comments

Correct Commodity Definition

Brassica, stem and head

subgroup 5A

0.1 0.10 Brassica, head and stem, subgroup 

5A. Tolerance changed to add a 

significant figure.

Rhubarb 0.3 0.30 Tolerance changed to add a 

significant figure.

Pea, Southern, succulent 

seed

0.05 0.05

Pea, Southern, dry seed 0.05 0.05

Pea, Southern, hay 0.05 0.05 Cowpea, hay and Cowpea, forage. 

Southern pea hay is a very minor 

feed, but cowpea is a type of 

southern pea.
CLOMAZONE/125401 Human Health Risk Assessment D410435

Page 9 of 49

2.2.4 Revisions to Petitioned-For Tolerances

Revisions are recommended to petitioned-for tolerances for consistent naming of commodities, 

and to add a significant figure. The recommended changes are documented in Table 2.2.3 above. 

Tolerances are being established for cowpea, forage, and cowpea, hay, rather than southern pea 

hay, because cowpea is a type of southern pea.

2.3 Label Recommendations

2.3.1 Recommendations from Residue Reviews

No label revisions are required; however, it should be noted that while the proposed maximum 

use rate on rhubarb is 1 application at 1.5 lb ai/A at dormancy, the submitted field trial data for 

rhubarb would support a second application at 1.0 lb ai/A a minimum of 50 days after the first 

application. If a second application on rhubarb is desired, the petitioner should submit an 

amended petition to reflect this proposed use.

2.3.2 Recommendations from Occupational Assessment

None.

2.3.3 Recommendations from Residential Assessment

There are no residential uses proposed with this petition.

3.0 Introduction

3.1 Chemical Identity

The chemical structure and nomenclature of the active ingredient, clomazone, are presented 

below in Table 3.1. 
CLOMAZONE/125401 Human Health Risk Assessment D410435

Page 10 of 49

Table 3.1 Test Compound Nomenclature

Chemical Structure

Empirical Formula C12H14ClNO2

Common Name Clomazone

Company experimental name FMC 57020

IUPAC name 2-(2-chlorobenzyl)-4,4-dimethylisoxazolidin-3-one

CAS Name 2-[(2-chlorophenyl)methyl]-4,4-dimethyl-3-isoxazolidinone

CAS Registry Number 81777-89-1

End-use product/EP Command ME, EPA Reg.. No. 279-3158

Chemical Class Isoxazolone

Known Impurities of Concern none

3.2 Physical/Chemical Characteristics

The physicochemical properties are presented in Appendix C. Clomazone is very soluble in 

water and a number of organic solvents used with pesticides. Its vapor pressure is relatively high 

(1.44 x 10 -4 mm Hg), indicating a potential concern for inhalation. The octanol/water partition 

coefficient indicates affinity for organic solvents over water, indicating a potential for 

bioaccumulation.

3.3 Pesticide Use Pattern

As summarized in Table 3.3, applications of Command® 3ME (EPA Reg. #279-3158) to preplant, pre-emergent, or early post-emergent Brassica, rhubarb and southern peas are proposed 

using groundboom spray equipment at rates of 0.25, 1.5 and 0.50 pounds ai per acre (lb ai/A), 

respectively. A maximum of 1 application is allowed per season. Clomazone products are 

formulated as emulsifiable concentrates and microencapsulated formulations. Applications are 

usually made as a single or split (2) pre-plant, or early post-emergence broadcast applications. 

Aerial and chemigation application are prohibited on the Command® label. See Section 2.3 for 

recommended modifications to the proposed label.
CLOMAZONE/125401 Human Health Risk Assessment D410435

Page 11 of 49

Table 3.3. Summary of Directions for Use of Clomazone

Applic. 

Timing, Type, 

and Equip.

Formulation

[EPA Reg. No.]

Applic.

Rate

(lb ai/A)

Max. No. 

Applic. 

per 

Season

Max.

Seasonal

Applic. Rate

(lb ai/A)

PHI

(days)

Use Directions and 

Limitations

Brassica, Head & Stem, Subgroup 5A; Direct Seeded Cabbage; Transplant Broccoli

Broadcast

application at 

pre-emergence

using 

groundboom

Microencapslated

(3 lb/gal)

[279-3158]

0.25 1 0.251 Not 

Specified

Use as a soil applied 

treatment prior to weed 

emergence.

Transplant Cabbage

Broadcast

application at 

pre-emergence

using 

groundboom

Microencapslated

(3 lb/gal)

[279-3158]

0.25-0.5 1 0.501 Not 

Specified

Use lower rate on 

coarse soils and higher 

rate on fine soils. Use

as a soil applied 

treatment prior to weed 

emergence.

Rhubarb

Broadcast 

application 

prior to leaf 

emergence 

using 

groundboom

Microencapslated

(3 lb/gal)

[279-3158]

1.5 1 1.51 Not 

Specified

Apply to dormant 

rhubarb.

Peas, Southern

Broadcast

application at 

pre-emergence

using 

groundboom

Microencapslated

(3 lb/gal)

[279-3158]

0.50 1 0.501 Not 

Specified

Use as a soil applied 

treatment prior to weed 

emergence.

1

 Not specifically detailed in Section B of the petition but clearly intended given the specified maximum single application rate 

and number of applications for the subject vegetable crops.

3.4 Anticipated Exposure Pathways

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

proposed new use of clomazone. Humans may be exposed to clomazone in food and drinking 

water, since application may result in clomazone reaching surface and ground water sources of 

drinking water. There are no residential uses of clomazone, so there is not likely to be exposure 

in residential or non-occupational settings. 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. 
CLOMAZONE/125401 Human Health Risk Assessment D410435

Page 12 of 49

Risk assessments have been previously prepared for the existing uses of clomazone. This risk 

assessment considers all of the aforementioned exposure pathways based on the proposed new 

uses of clomazone, but also considers the existing uses as well, particularly for the dietary

exposure assessment.

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 Continuing 

Survey of Food Intake by Individuals (CSFII) 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, season of the year, ethnic group, and region of the country. 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 postapplication 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.

4.0 Hazard Characterization and Dose-Response Assessment

4.1 Toxicology Studies Available for Analysis

The toxicology database for clomazone is adequate to support the currently registered uses. 

Exposure to clomazone is expected via the oral, dermal and inhalation routes. A route-specific 

dermal study was submitted, but no subchronic inhalation study has been submitted.

The Hazard and Science Policy Council (HASPOC) recently reviewed clomazone (TXR No. 

0056801). Based on a WOE approach considering all available hazard and exposure 

information, the HASPOC concluded that a neurotoxicity battery (acute and subchronic), a 28-

day inhalation toxicity study, a chronic/carcinogenicity study in the mouse, and an 

immunotoxicity study are not required at this time. 

4.2 Absorption, Distribution, Metabolism, & Elimination (ADME)

Clomazone is absorbed, extensively metabolized by the liver and rapidly excreted in urine and 

feces in rats following oral administration. Analysis of the metabolic products showed the 

presence of parent compound and sixteen identifiable metabolites. The majority of these 
CLOMAZONE/125401 Human Health Risk Assessment D410435

Page 13 of 49

products were eliminated in the urine and the feces within 24 hours with the predominant route 

of excretion being the urine. The quantities of metabolites varied with the dose regimen, sex and 

route of administration, but were the same qualitatively both in the urine and the feces in all 

groups. A total of 75-85% of the administered dose was recovered for all routes and doses after 

the first 24 hours, except in females in the single high dose group, where the total recovery was 

only 48% compared to males (75%). The total recovery after 48 hours was generally comparable 

between all groups and sexes and ranged from 91-100%. 

4.2.1 Dermal Absorption

There was no evidence of systemic toxicity at the limit dose in a 28 day dermal toxicity

clomazone study in rats, however dermal irritation was observed in dosed females at increased 

incidence and/or severity over controls. A dermal absorption study is not needed. 

4.3 Toxicological Effects

The primary target of clomazone is the liver, with hepatocellular cytomegaly noted in the chronic 

rat and mouse studies (chronic mouse study deemed unacceptable due to maximum tolerated 

dose (MTD) not achieved), hepatocellular necrosis in the chronic mouse study and increased 

liver weight observed in subchronic and chronic studies. Clomazone has low acute toxicity

(Category III and IV) via the oral, dermal and inhalation routes. It is non-irritating to the eyes 

and mildly irritating to the skin. It is not a dermal sensitizer. No neurotoxicity studies with 

clomazone are available. The HASPOC, based on a WOE approach, concluded that a 

neurotoxicity battery is not required for clomazone at this time. This approach considered all of 

the available hazard and exposure information including: 1) the lack of evidence for clinical 

signs of neurotoxicity or neuropathology in adult animals in subchronic and chronic studies; 2) 

liver is the target organ for clomazone, not the neurological system; 3) clomazone is absorbed 

and rapidly excreted in rats with 97% of the radioactivity excreted within 168 hours; and 4) the 

POD and endpoint for chronic dietary risk assessment is based on liver effects in rats which 

appear to be the most sensitive endpoint (TXR No. 0056801). There is no quantitative or 

qualitative evidence of susceptibility in the developmental toxicity study in rabbits or in the 2-

generation reproduction toxicity study in rats. In the developmental toxicity study in rats, 

delayed ossification occurred at doses that produced maternal effects (chromorhinorrhea and 

abdominogenital staining). Although qualitative susceptibility was observed in the 

developmental toxicity study in rats, the concern is low since there are clear NOAELs and 

LOAELs and this study was used for risk assessment, and, therefore, is protective of the 

developmental effects. 

There is no concern for mutagenicity. In the rat carcinogenicity study, there was no evidence of 

carcinogenicity. The mouse carcinogenicity study was inadequate to determine carcinogenic 

activity due to the lack of adverse effects at the highest dose tested. Despite the inadequacy of 

the mouse carcinogenicity study, EPA has determined that an additional mouse carcinogenicity 

study is not needed and that the rat chronic/carcinogenicity study will be adequate for assessing 

chronic risk, including cancer. This finding is based upon the following conclusions: (1) the rat is

more sensitive than the mouse for the chronic assessment; (2) the consistent effect in rats 

(decreased body weight and increased liver weight) has been used as the POD for the chronic 
CLOMAZONE/125401 Human Health Risk Assessment D410435

Page 14 of 49

assessment; (3) a new mouse study would only use doses well above the current POD for the 

chronic assessment; and (4) even if new mouse study identified positive carcinogenicity effects, 

that finding would not result in the adoption of a quantitative linear assessment of cancer risk due 

to the negative carcinogenicity finding in the rat study and the lack of a positive finding for 

genotoxicity. 

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

The chemical risk assessment team has recommended that the FQPA Safety Factor (SF) be 

reduced to 1X. The toxicity database for clomazone is adequate for a hazard evaluation and is 

considered adequate to evaluate risks to infants and children. Acceptable developmental toxicity

studies in the rat and rabbit and an acceptable reproduction study in the rat are available. Based 

on the results of the available toxicity studies, there is no evidence for neurotoxicity or 

immunotoxicity.

4.4.1 Completeness of the Toxicology Database

The toxicology database for clomazone is complete. Exposure to clomazone is expected via the 

oral, dermal, and inhalation routes. A route-specific dermal study was submitted, but no 

subchronic inhalation study has been submitted. 

The Hazard and Science Policy Council (HASPOC) recently reviewed clomazone (TXR No. 

0056801). HASPOC, based on a WOE approach considering all available hazard and exposure 

information concluded that the acute and subchronic neurotoxicity studies, the subchronic 

inhalation study, the carcinogenicity study in mice and the immunotoxicity study are not required 

at this time. 

4.4.2 Evidence of Neurotoxicity

There are no acute or subchronic neurotoxicity studies available for clomazone. There was no 

evidence of neurotoxic effects in any animals in available subchronic, chronic, reproductive or 

developmental toxicity studies. Based on a WOE approach, the HASPOC concluded that the 

acute and subchronic neurotoxicity studies are not required at this time (TXR No. 0056801).

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

There was no evidence of increased quantitative or qualitative susceptibility in the prenatal 

developmental toxicity study in rabbits or in the reproductive toxicity study in rats with 

clomazone. In the developmental toxicity study in rats, delayed ossification occurred at doses 

that produced maternal effects (chromorhinorrhea and abdominogenital staining). Although 

qualitative susceptibility was observed in the developmental toxicity study in rats, the concern is 

low since there are clear NOAELs and LOAELs and this study was used for risk assessment and, 

therefore, is protective of the developmental effects.
CLOMAZONE/125401 Human Health Risk Assessment D410435

Page 15 of 49

4.4.4 Residual Uncertainty in the Exposure Database

Since the dietary and non-dietary exposure estimates were based on several conservative 

assumptions, HED does not believe that the exposure estimates are underestimated. The acute 

and chronic dietary assessments conducted with DEEM-FCID were screening level analyses.

The assessments utilized tolerance values and 100% crop treated was assumed for all 

commodities. The DEEM analysis also assumed that all drinking water will contain clomazone 

at the highest EDWC levels modeled by EFED for ground water or surface water. For these 

reasons it can be concluded that the DEEM-FCID analysis does not underestimate risk from 

acute or chronic exposure to acetochlor. 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

The detailed description of the toxicity studies used for selecting toxicity endpoints and points of 

departure for various exposure scenarios are presented in the appendix. The specific toxicity

endpoints and PODs are presented in Tables 4.5.4.1 and 4.5.4.2. Toxicological endpoints were 

selected for dietary/drinking water and occupational exposure scenarios. An acute reference dose 

(RfD; 1.0 mg/kg/day) for assessment of food and drinking water exposure to females age 13-49 , 

was selected from a developmental toxicity study in rats (NOAEL = 100 mg/kg/day). The 

endpoint of delayed ossification identified in the developmental toxicity study in rats was chosen 

for the acute dietary (females 13-49 years of age) endpoint because it was considered to be an 

adverse effect in the developing animal and results from a single exposure. An endpoint was not 

selected for the general population because no adverse effect in adult animals was identified that 

resulted from a single exposure. A chronic RfD (0.84 mg/kg/day) was selected from the cocritical studies of the chronic/carcinogenicity study in rats, the subchronic toxicity study in rats 

and the 2-generation reproduction toxicity study in rats. The endpoint of decreased body weight, 

body weight gain, food consumption and in increased absolute and relative liver weight in 

females and increased absolute liver weight in males was chosen for the chronic dietary (all 

populations) endpoint because the duration of the exposure in this study is appropriate for a 

chronic dietary endpoint and these effects represent the most sensitive endpoint. 

There are no residential uses of clomazone, therefore, an endpoint for the incidental oral 

exposure scenario was not selected. A point of departure (POD) for dermal exposure was not 

selected because no systemic toxicity was observed in rats following repeated dermal application 

at the highest dose tested for 28 days. Additionally, there are no quantitative sensitivities or 

uncertainties with clomazone to warrant an oral study for use in the dermal assessment. 

Therefore, a dermal assessment is not required. No inhalation toxicity studies were available for 

the short-term and intermediate-term inhalation scenarios. The HASPOC met on September 19, 

2013, to discuss the need for a subchronic inhalation study for clomazone (TXR No. 0056801).

The decision was made that the data requirement for this study can be waived. A short-term 

inhalation exposure POD (100 mg/kg/day) was selected from the developmental toxicity study in 

rats. The endpoint of chromorhinorrhea and abdominogenital staining was selected from the 
CLOMAZONE/125401 Human Health Risk Assessment D410435

Page 16 of 49

developmental toxicity study. This study was selected because the duration of the exposure in 

this study is appropriate for the short-term endpoint. Based on the use pattern, an intermediateterm inhalation exposure scenario is not required.

4.5.2 Recommendation for Combining Routes of Exposures for Risk Assessment

When there are potential residential exposures to the pesticide, aggregate risk assessment must 

consider exposures from three major sources: oral, dermal and inhalation exposures. Since there 

are no residential uses of clomazone, only aggregate exposure from food and water is required. A 

dermal endpoint was not selected. Because only inhalation exposure/risk was estimated in this 

assessment, combining risk from other routes of exposure (e.g. dermal) is not relevant.

4.5.3 Cancer Classification and Risk Assessment Recommendation

In the rat carcinogenicity study, there was no evidence of carcinogenicity. The mouse 

carcinogenicity study was inadequate to determine carcinogenic activity due to the lack of 

adverse effects at the highest dose tested. Despite the inadequacy of the mouse carcinogenicity 

study, EPA has determined that an additional mouse carcinogenicity study is not needed and that 

the rat chronic/carcinogenicity study will be adequate for assessing chronic risk, including 

cancer. This finding is based upon the following conclusions: (1) the rat is more sensitive than 

the mouse for the chronic assessment; (2) the consistent effect in rats (decreased body weight 

and increased liver weight) has been used as the POD for the chronic assessment; (3) a new

mouse study would only use doses well above the current POD for the chronic assessment; and 

(4) even if new mouse study identified positive carcinogenicity effects, that finding would not 

result in the adoption of a quantitative linear assessment of cancer risk due to the negative 

carcinogenicity finding in the rat study and the lack of a positive finding for genotoxicity. 

4.5.4 Summary of Points of Departure and Toxicity Endpoints Used in Human Risk 

Assessment

The points of departure, uncertainty factors, and toxicity endpoints are presented in the following 

tables. No endpoint is selected for dermal exposure scenarios. No hazard was identified at the 

maximum dermal dose tested.
CLOMAZONE/125401 Human Health Risk Assessment D410435

Page 17 of 49

Table 4.5.4.1 Summary of Toxicological Doses and Endpoints for Clomazone for Use in Dietary Human 

Health Risk Assessments

Exposure/ 

Scenario

Point of 

Departure

Uncertainty/FQPA 

Safety Factors

RfD, PAD, 

Level of 

Concern for 

Risk 

Assessment

Study and Toxicological Effects

Acute Dietary

(General 

Population 

including 

infants and 

children)

An endpoint was not selected for the general population because no adverse effect in adult animals 

was identified that resulted from a single exposure. A risk assessment is not required for this 

population subgroup.

Acute Dietary

(Females 13 –

49 years old)

NOAEL = 

100 

mg/kg/day

UFA= 10x

UFH=10x

FQPA SF= 1x

Acute RfD = 

1.0 mg/kg/day

aPAD = 1.0 

mg/kg/day

Developmental Toxicity Study - Rat

(MRID 00150291)

Developmental LOAEL = 300 mg/kg/day 

based on indications of delayed 

ossification in the form of either partial 

ossification or the absence of the 

manubrium, sternebrae 3-4, xiphoid, 

caudal vertebrae, and meta-carpals.

Chronic 

Dietary

(All 

Populations)

NOAEL = 

84.4

mg/kg/day

UFA= 10x

UFH=10x

FQPA SF= 1x

Chronic RfD 

= 0.84

mg/kg/day

cPAD = 0.84 

mg/kg/day

Two Year Chronic Toxicity Study –

Rats 

(MRID 00132586)

NOAEL = 84.4/112.9 mg/kg/day, 

males/females (highest dose tested)

LOAEL was not attained

Co-critical 90-day Oral Rat Study

(MRID 00132586)

NOAEL = 135.2/160.9 mg/kg/day, 

males/females

LOAEL = 273/319.3 mg/kg/day, 

males/females, based on decreased body 

weight, body weight gains, food 

consumption and increased absolute and 

relative liver weights in females and 

increased absolute liver weights in males. 

Co-critical 2-Generation Reproduction 

Toxicity Study

(MRID 00151108)

Parental NOAEL = 50 mg/kg/day

Parental LOAEL = 100 mg/kg/day based 

on statistically significantly decreased 

body weight & body weight gain during 

pre-mating, and decreased body weight 

during gestation & lactation M & F. In 

addition, decreased food consumption in 

females and hydronephritic kidneys in 

males.

Cancer (oral, 

dermal, 

inhalation)

The chronic endpoint is protective against any effects resulting from long-term exposure to 

clomazone.

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 
CLOMAZONE/125401 Human Health Risk Assessment D410435

Page 18 of 49

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.

Table 4.5.4.2 Summary of Toxicological Doses and Endpoints for Clomazone for Use in Occupational Human 

Health Risk Assessments

Exposure/ 

Scenario

Point of 

Departure

Uncertainty 

Factors

Level of Concern 

for Risk 

Assessment

Study and Toxicological Effects

Dermal Shortand 

IntermediateTerm

No hazard identified

Inhalation 

Short-Term (1-

30 days)

NOAEL= 

100

mg/kg/day

UFA= 10x

UFH=10x

Occupational 

LOC for MOE = 

100

Developmental Toxicity Study - Rat 

(MRID 00150291)

Maternal LOAEL = 300 mg/kg/day based 

on chromorhinorrhea and abdominogenital 

staining in maternal animals.

Cancer (oral, 

dermal, 

inhalation)

The chronic endpoint is protective against any effects resulting from long-term exposure to 

clomazone.

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). MOE = margin of exposure. LOC = level of concern. N/A = not applicable.
CLOMAZONE/125401 Human Health Risk Assessment D410435

Page 19 of 49

5.0 Dietary Exposure and Risk Assessment 

5.1 Metabolite/Degradate Residue Profile

5.1.1 Summary of Plant and Animal Metabolism Studies

Based on metabolism studies on soybeans, corn, cotton, sweet potatoes, tomatoes and bell 

peppers, and alfalfa, HED concludes that the nature of the residue in plants is adequately 

understood. The major metabolite was 2-chlorobenzyl alcohol. The postulated major route of 

metabolism of clomazone in plants is hydroxylation of the methylene bridge carbon of 

clomazone to form the carbinolamide; decomposition of the unstable intermediate, the 

carbinolamide, to form the isoxazolidinone moiety and 2-chlorobenzaldehyde. 2-

chlorobenzaldehyde reduces to the alcohol or is oxidized to the carboxylic acid. The alcohol, the 

carboxylic acid, and the isoxazolidinone metabolites form glycosides and/or amino acid 

conjugates. Minor pathways include hydroxylation of clomazone to form monohydroxylated and 

possibly dihydroxylated metabolites. Based on low levels of these metabolites found in crops, 

the residue of concern for regulatory and risk assessment purposes in plants is clomazone per se 

(PP#8E3628, M. J. Nelson, 4/22/92).

As there are no livestock feed stuffs currently associated with Brassica, rhubarb, or southern 

peas, issues pertaining to the nature of the residue in livestock are not germane to this petition.

The nature of the residue in plants and livestock is adequately understood. The residue of 

concern is clomazone per se as specified in 40 CFR 180.425.

5.1.2 Summary of Environmental Degradation

Vapor phase transport and microbial degradation appear to be the major routes of dissipation in 

the environment. Clomazone is stable to hydrolysis in acidic, neutral, and alkaline solutions and 

does not photodegrade in either water or on soil. In soil, clomazone is metabolized under aerobic 

conditions with half-lives ranging from 28-173 days, depending on soil type. Carbon dioxide is 

the major degradate. Under anaerobic conditions, clomazone readily degrades (t

1/2

: 13 days) to 

(N-[(2-chlorophenol)methyl]-3-hydroxy-2,2-dimethyl propanamide), which persists under 

anaerobic conditions. 

Clomazone has a moderately high vapor pressure of 1.44 x 10

-4 

mmHg and a high water 

solubility of 1100 mg/L. Considering its Henry’s Law Constant of 4.14 x 10

-8 

atm-m

3

/mol, 

clomazone is expected to remain in the water column as opposed to volatilizing. However, in the 

terrestrial environment, clomazone may volatilize from soil. Clomazone is moderately mobile 

with K

d

’s ranging from 1.5 to 7.4 (lower in sandy soils) and Koc’s from 139 to 608. 

In the field, Command 3 ME applied to bare soil at a rate of 1.25 lbs. a.i./A dissipated with a 

half-life of 139 days in an Iowa silty clay loam and 17 days in a Louisiana silt loam. In both 

studies, parent clomazone was not detected below 6 inches. Degradates were analyzed for but 

were not detected (detection limit: 0.01 ppm). It is not clear what factor most contributed to the 
CLOMAZONE/125401 Human Health Risk Assessment D410435

Page 20 of 49

difference in dissipation rates at these sites, but one possibility might be that the conditions at the 

Louisiana site favored volatilization. Also a possibility is different soil metabolism rates in the 

two soils, as exemplified in the aerobic soil metabolism study. Based on laboratory and field 

data, clomazone is not likely to contaminate ground water, however surface water contamination 

through runoff, spray drift, and vapor phase transport is possible. In surface water, clomazone 

will exist in the dissolved phase and bound to suspended particulates and sediment, and may 

persist with half-lives ranging from 1.5-2.5 months. The degradate N-[(2-chlorophenol) methyl]-

3-hydroxy-2,2-dimethyl propanamide may be found in surface water and will persist, especially 

under anaerobic conditions (Clomazone Summary Document: Registration Review: Initial 

Docket. January 2007. EPA-HQ-OPP-2006-0013).

5.1.3 Comparison of Metabolic Pathways

Plant metabolism studies are available for soybeans, corn, cotton, sweet potatoes, tomatoes and 

bell peppers, and alfalfa. The major metabolite was 2-chlorobenzyl alcohol. The postulated 

major route of metabolism of clomazone in plants is hydroxylation of the methylene bridge 

carbon of clomazone to form the carbinolamide; decomposition of the unstable intermediate, the 

carbinolamide, to form the isoxazolidinone moiety and 2-chlorobenzaldehyde. 2-

chlorobenzaldehyde reduces to the alcohol or is oxidized to the carboxylic acid. The alcohol, the 

carboxylic acid, and the isoxazolidinone metabolites form glycosides and/or amino acid 

conjugates. Minor pathways include hydroxylation of clomazone to form monohydroxylated and 

possibly dihydroxylated metabolites. 

A rat metabolism study is available for clomazone. Sixteen metabolites including the parent 

compound were identified. The predominant metabolites were the isoxazolidinone metabolites 

(FMC 87010 (4’,5’-dihydrodiol-5-hydroxy-2-(2-chlorophenyl)methyl-4,4-dimethyl-3-

isoxazolidinone), FMC 83918 (4’,5’-di hydroxy-2-(2-chlorophenyl)methyl-4,4-dimethyl-3-

isoxazolidinone) and FMC 60217 (5’-hydroxy-2-(2-chlorophenyl)methyl-4,4-dimethyl-3-

isoxazolidinone). The predominant route of excretion was in the urine.

5.1.4 Residues of Concern Summary and Rationale

Based on metabolism studies on soybeans, corn, cotton, sweet potatoes, tomatoes and bell 

peppers, and alfalfa, HED concludes that the nature of the residue in plants is adequately 

understood. The residue of concern in plants is clomazone per se as specified in 40 CFR 

180.425. The residue of concern in ruminants and poultry is clomazone per se, although the 

current petition does not include any livestock feeds. Very low residues were reported in 

rotational crops. The residue of concern in rotational crops is clomazone per se. The residue of 

concern in drinking water was discussed at a Metabolism SARC meeting on 9/12/2000, and was 

determined to include clomazone per se, and the major environmental degradate FMC 65317 (N-

[(2-chlorophenyl)methyl]-3-hydroxy-2,2-dimethyl propanamide) (Kramer, G & Kidwell, J. 

10/2/00; D268905).
CLOMAZONE/125401 Human Health Risk Assessment D410435

Page 21 of 49

Table 5.1.4 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 Clomazone Clomazone

Rotational Crop Clomazone Clomazone

Livestock

Ruminant Clomazone Clomazone

Poultry Clomazone Clomazone

Drinking Water Clomazone + FMC 65317* Not Applicable

* FMC 65317 = N-[(2-chlorophenyl)methyl]-3-hydroxy-2,2-dimethyl propanamide

5.2 Food Residue Profile

Residue data are adequate to support the proposed new uses. Adequate metabolism and rotational 

crop data were submitted in support of earlier petitions. Adequate field trial data were 

submitted. The field trials reflected the proposed use pattern, and adequate geographic 

representation. The field trial data were collected using an adequate analytical method; and the 

data were properly supported by storage stability data. Samples were analyzed for clomazone, 

per se, which is the residue of concern. Residues were within the proposed tolerances of 0.10, 

0.3 ppm, and 0.05 ppm for clomazone in or on Brassica, head and stem, subgroup 5A, rhubarb, 

and southern pea commodities, respectively. No adjuvants were added in any of the field trials. 

No processing data were needed for the proposed new uses.

Broccoli: Following one preplant application of the 3 lb ai/gal ME formulation of clomazone at 

0.24-0.25 lb ai/A, residues of clomazone in/on broccoli flower head and stem harvested at a 52-

to 120-day PHI were all <LOQ (<0.03 ppm).

Brassica, head and stem, subgroup 5A: There are 2 representative commodities for Brassica, 

head and stem, subgroup 5A, broccoli or cauliflower, and cabbage. The broccoli residue data are 

discussed above. A tolerance has been established for residues of clomazone on cabbage at 0.1 

ppm (PP#4E4311, N. Dodd, D199086, 04/17/95, MRID 43077301). Command 4EC was 

applied at 0.5 lb ai/A as a single broadcast application in at least 10 gallons of water per acre, 

using ground equipment before seeding or transplanting cabbage. Clomazone is incorporated to 

a depth of 1 inch or less. Residues were reported to be non-quantifiable at less than 0.1 ppm 

except in one sample in which interferences were noted, and the limit of quantitation was 0.17 

ppm.

Rhubarb: Following two foliar broadcast applications of the 3 lb ai/gal ME formulation of 

clomazone at 2.49-2.76 (~1.7 – 1.8x) and 1.71-1.99 lb ai/A (~1.1 – 1.3x), respectively, residues 

of clomazone (and per trial averages) in/on rhubarb petioles harvested at a 41- to 44-day PHI 

were <0.03-0.180 (<0.033-0.114) and <0.03-0.076 (<0.03-0.062) ppm.
CLOMAZONE/125401 Human Health Risk Assessment D410435

Page 22 of 49

Southern Peas: Following one pre-emergent broadcast application of the 3 lb ai/gal ME 

formulation of clomazone at 0.484-0.501 lb ai/A, residues of clomazone in/on shelled succulent 

pea and fresh plants with pods and shelled dry pea and dry plants with pods and harvested at a 

62- to 77-day and 77- to 91-day PHIs, respectively, were all <LOQ (<0.05 ppm).

TABLE 5.2. Summary of Residue Data from Field Trials with Clomazone.

Commodity Analyte Total Rate

(lb ai/A)

PHI 

(days)

Residue Levels (ppm)1

n Sample 

Min.

Sample 

Max.

LAFT2 HAFT2 Median Mean Std. 

Dev.

Broccoli Clomazone 0.24-0.25 52-120 8 <0.03 <0.03 <0.03 <0.03 0.03 0.03 N/A

Rhubarb 

Petioles

Clomazone 2.49-2.76 41-44 4 <0.03 0.180 <0.033 0.114 0.046 0.060 0.038

1.71-1.99 4 <0.03 0.076 <0.03 0.062 0.044 0.045 0.017

Shelled 

Succulent 

Pea

Clomazone 0.484-0.501 62-77 4 <0.05 <0.05 <0.05 <0.05 0.05 0.05 N/A

Plants With 

Pods, Fresh

4 <0.05 <0.05 <0.05 <0.05 0.05 0.05 N/A

Shelled Dry 

Pea

77-91 4 <0.05 <0.05 <0.05 <0.05 0.05 0.05 N/A

Plants with 

Pods, Dry

4 <0.05 <0.05 <0.05 <0.05 0.05 0.05 N/A

1

 Except for sample min/max, values reflect per trial averages; n = no. of field trials. N/A = Not applicable.

2

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

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 the following memoranda: “Clomazone: 

Drinking Water Exposure Assessment for Proposed New Uses for Brassica (Head and Stem 

Subgroup 5A), Southern Peas, and Rhubarb” (Both memoranda under D408878 by J. Lin and 

dated 7/23/13 or 9/24/13). 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 FQPA Index Reservoir Screening Tool 

(FIRST) and the Tier 1 Rice model. Ground water EDWCs were generated using Pesticide Root 

Zone Model for Ground Water (PRZM-GW) and Screening Concentration In GROund Water 

(SCI-GROW). EDWCs were derived based on the maximum registered/proposed use rate (1.5 

lb ai/A existing for tuberous and corm vegetables and proposed for rhubarb) and the maximum 

registered use rate on rice (dry-seeded 0.8 lb ai/A). The Tier 1 Rice model (dry-seeded scenario) 

produced the highest EDWCs for both acute and chronic at 550 ppb and this estimate was used 

in both the acute and chronic dietary risk assessments. 
CLOMAZONE/125401 Human Health Risk Assessment D410435

Page 23 of 49

Table 5.3. EDWCs for the Clomazone Human Health Risk Assessment 

Source (Tier: Model) Maximum Annual Rate Acute

EDWC

(μg/L)

Chronic

EDWC

(μg/L)

Surface Water (Tier 1: FIRST) 1.5 lb ai/A 89.2 12.8

Surface Water (Tier 1: Rice Model)10.8 lb ai/A

(dry-seeded scenario)2 550

Ground Water (Tier 1: PRZM-GW) 1.5 lb ai/A 85.7 77.4

Ground Water (Tier 1: SCI-GROW) 1.5 lb ai/A 0.0338

1

 Calculates the water-column exposure expected on the day of application to a flooded rice paddy, accounting only 

for sorption to sediment as a dissipation process. No other degradation processes, such as hydrolysis, photolysis, or 

metabolism are considered. Hence, this exposure modeling is inclusive of all of the residues of concern (parent plus 

FMC 65317). 

2

 Clomazone used in dry-seeded rice culture is subject to dissipation (volatilization and aerobic metabolism) after 

application but prior to flooding; however, significant levels of the metabolite FMC 65317 are not expected to form 

during this interval under these aerobic conditions. The potential dissipation of the parent after application but prior 

to flooding was accounted for in the calculated concentration/use rate for clomazone (0.707 lb ai/A) used in the Tier 

1 Rice Model. [Reviewer Note: The maximum registered use rate for clomazone on wet-seeded rice (0.6 lb ai/A) is 

less than that used in the Tier 1 Rice Model.] 

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

Clomazone acute and chronic dietary exposure assessments were conducted using the DEEMFCID, Version 3.16, which incorporates 2003-2008 consumption data from USDA’s 

NHANES/WWEIA. 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 for the proposed 

Section 3 uses of clomazone on Brassica, head and stem (Subgroup 5A), rhubarb, and southern 

pea. This memorandum was reviewed by two peer reviewers of the DESAC, per DESAC SOP 

2012.1. Both the acute and chronic assessments are highly conservative and incorporated 

tolerance level residues, assumed 100% crop treated and used default processing factors. 

Screening-level Tier I modeling was used to estimate drinking water concentrations. 

5.4.1 Description of Residue Data Used in Dietary Assessment

Both the acute and chronic assessments incorporated tolerance level residues and used default 

processing factors.

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.
CLOMAZONE/125401 Human Health Risk Assessment D410435

Page 24 of 49

5.4.3 Acute Dietary Risk Assessment

The acute dietary risk estimate at the 95th percentile of exposure utilized 3.0% of the acute 

population adjusted dose (aPAD) for females 13-49 years old. This is the only population 

subgroup for which an acute endpoint was selected. The acute dietary risk estimate for females 

13-49 years old is not of concern.

5.4.4 Chronic Dietary Risk Assessment

The chronic dietary risk estimates are ≤3.6% of the chronic population adjusted dose (cPAD) for 

all population subgroups. All Infants < 1 year of age is the most highly exposed subgroup, 

utilizing 3.6% of the cPAD, while the general US population utilizes 1.4% of the cPAD. The 

chronic dietary risk estimates are not of concern.

5.4.5 Cancer Dietary Risk Assessment

EPA has concluded that the chronic PAD for clomazone will be protective of any cancer risk 

posed by clomazone. Additionally, EPA is relying on the chronic dietary exposure assessment to 

evaluate cancer risk. 

5.4.6 Summary Table

Table 5.4.6. Summary of Dietary (Food and Drinking Water) Exposure and Risk for Clomazone.

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

N/A N/A

0.011624 1.4

All Infants (<1 year old) 0.029942 3.6

N/A N/A

Children 1-2 years old 0.016899 2.0

Children 3-5 years old 0.014233 1.7

Children 6-12 years old 0.010243 1.2

Youth 13-19 years old 0.008475 1.0

Adults 20-49 years old 0.011576 1.4

Adults 50-99 years old 0.011451 1.4

Females 13-49 years old 0.030050 3.0 0.011536 1.4

6.0 Residential (Non-Occupational) Exposure/Risk Characterization

Currently, there are no registered or proposed residential uses for clomazone.

6.1 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 
CLOMAZONE/125401 Human Health Risk Assessment D410435

Page 25 of 49

airblast) employed for clomazone. 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). 2 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.

6.2 Residential Bystander Postapplication Inhalation Exposure

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

assessment was not performed for clomazone at this time primarily because of the low acute 

inhalation toxicity (Toxicity Category IV). 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, 20103. 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 clomazone.

7.0 Aggregate Exposure/Risk Characterization

In accordance with the FQPA, HED must consider and aggregate (add) pesticide exposures and 

risks from three major sources: food, drinking water, and residential exposures. In an aggregate 

assessment, exposures from relevant sources are added together and compared to quantitative 

estimates of hazard (e.g., a NOAEL or PAD), or the risks themselves can be aggregated. When 

aggregating exposures and risks from various sources, HED considers both the route and 

duration of exposure.

7.1 Acute Aggregate Risk

In examining acute aggregate risk, HED has assumed that the only pathway of exposure relevant 

to the acute time frame is dietary exposure. Therefore, the acute aggregate risk is comprised of 

exposures to clomazone residues in food and drinking water and is equivalent to the acute dietary

risk estimates summarized in Table 5.4.6 in Section 5.4.3. The acute dietary risk estimates are 

well below HED’s level of concern for the general population and all population subgroups.

 

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

3 Available: http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html
CLOMAZONE/125401 Human Health Risk Assessment D410435

Page 26 of 49

7.2 Short-Term Aggregate Risk

Currently, there are no registered or proposed residential uses for clomazone, therefore, a shortterm aggregate risk assessment is not required.

7.3 Intermediate-Term Aggregate Risk

Currently, there are no registered or proposed residential uses for clomazone, therefore, an 

intermediate-term aggregate risk assessment is not required.

7.4 Chronic Aggregate Risk

In examining chronic aggregate risk, HED has assumed that the only pathway of exposure 

relevant to the chronic time frame is dietary exposure. Therefore, the chronic aggregate risk is 

comprised of exposures to clomazone residues in food and drinking water and is equivalent to 

the chronic dietary risk estimates summarized in Table 5.4.6 in Section 5.4.4. The chronic risk 

estimates are below HED’s level of concern for all population subgroups. 

7.5 Cancer Aggregate Risk

EPA has concluded that the cPAD is protective of any cancer risk clomazone poses to humans. 

As noted above, chronic dietary exposure is 3.6 % of the cPAD for the highest exposed 

population subgroup. 

8.0 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 clomazone and any other substances and clomazone 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 clomazone 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/.

9.0 Occupational Exposure/Risk Characterization

9.1 Short -Term Handler Risk

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

application process. 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 on Brassica, rhubarb and southern peas. The quantitative 
CLOMAZONE/125401 Human Health Risk Assessment D410435

Page 27 of 49

exposure/risk assessment developed for occupational handlers is based on the following 

scenarios: 

1) Mixing/loading liquids for groundboom applications; and

2) Applying sprays via groundboom equipment.

Summary of Occupational Handler Non-Cancer Exposure and Risk Estimates

As summarized in Table 9.1, the occupational handler exposure and risk estimates indicate that 

the short-term inhalation MOEs are not of concern to HED (i.e., MOE > 100) without the use of 

a respirator. Only exposure from use on rhubarb was quantitatively assessed because its higher 

application rate is considered to be protective of the proposed uses on Brassica and Southern 

pea.

Table 9.1. Short-Term Occupational Handler Non-Cancer Exposure and Risk Estimates for Clomazone

Exposure Scenario Crop or 

Target

Inhalation 

Unit 

Exposure 

(μg/lb ai)1

Maximum 

Application 

Rate2

Area Treated or 

Amount 

Handled Daily3

Inhalation

(LOC = 100)

Baseline Dose 

(mg/kg/day)4 MOE5

Mixer/Loader

Mixing/loading 

liquid formulation 

for groundboom 

application

Rhubarb 0.219 1.5

lb ai/A 80 0.00033 300,000

Applicator

Groundboom 

application of liquid 

formulation

Rhubarb 0.34 1.5

lb ai/A 80 0.00051 200,000

1 Based on the “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table” ; Level of mitigation: no respirator.

2 Based on registered or proposed label (Reg. No. 279-3158).

3 Exposure Science Advisory Council Policy #9.1.

4 Inhalation Dose = Inhalation Unit Exposure (μg/lb ai) × Conversion Factor (0.001 mg/μg) × Application Rate (lb ai/acre) × Area 

Treated or Amount Handled (A/day) ÷ BW (80 kg).

5 Inhalation MOE = Inhalation NOAEL (100 mg/kg/day) ÷ Inhalation Dose (mg/kg/day).

9.2 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.
CLOMAZONE/125401 Human Health Risk Assessment D410435

Page 28 of 49

9.2.1 Dermal Postapplication Risk

Post-application dermal exposure and risk estimates were not evaluated as toxicity was not 

observed up to the limit dose in a dermal toxicity study, and no developmental or reproductive 

toxicity was seen in the database. 

Restricted Entry Interval

The restricted entry interval (REI) is based on the acute toxicity of clomazone technical material. 

Clomazone is classified in Toxicity Category IV for acute dermal toxicity, primary eye and skin 

irritation. Therefore, a 12-hour REI under 40 CFR 156.208 (c) (2) (i) is required. The 12-hour 

REI, which currently appears on the Command®3M label, is adequate for the proposed uses.

9.2.2 Inhalation Postapplication Risk

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

assessment was not performed for clomazone at this time primarily because of the low acute 

inhalation toxicity (Toxicity Category IV). 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, 20104. 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 post-application 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 clomazone.

Although a quantitative occupational post-application inhalation exposure assessment was not 

performed, an inhalation exposure assessment was performed for occupational/commercial 

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.

 

4 Available: http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html
CLOMAZONE/125401 Human Health Risk Assessment D410435

Page 29 of 49

10.0 References

Cropp-Kholligian, B. 12/6/2013. D410437. Clomazone. Acute and Chronic Aggregate Dietary

(Food and Drinking Water) Exposure and Risk Assessments for Proposed New Uses on 

Brassica, Head and Stem (Subgroup 5A), Rhubarb, and Southern Pea. 

Hummel, S., 9/5/2013, D410436. “Clomazone. PP#2E8136. Brassica, Head and Stem, 

Subgroup 5A; Rhubarb; and Pea, Southern. Summary of Analytical Methods and Residue Data.” 

EPA Memorandum.

Kramer, G. and Kidwell, J., 10/2/2000. D268905. “Ad Hoc RED Metabolism Assessment 

Review Committee (MARC) Meeting of 9/12/00. Clomazone. Residues of Concern in Drinking 

Water.” EPA Memorandum.

Lin, J. 7/23/2013. D408878. Clomazone: Drinking Water Exposure Assessment for Proposed 

New Uses for Brassica (Head and Stem, Subgroup 5A), Southern Peas, and Rhubarb.

Lin, J. 9/24/2013. D408878. Clomazone: Drinking Water Exposure Assessment for Proposed 

New Uses for Brassica (Head and Stem, Subgroup 5A), Southern Peas, and Rhubarb. Update.

O’Rourke, K. 12/17/2013. D410438.Clomazone. Occupational and Residential Exposure 

Assessment for a Proposed Use on Brassica, Rhubarb and Southern Peas. EPA Memorandum.

Rury, K. 1/8/2014. TXR No. 0056801. “Clomazone: Summary of Hazard and Science Policy

Council (HASPOC) Meeting of September 19, 2013: Recommendations on the need for multiple 

studies.” EPA Memorandum dated 
CLOMAZONE/125401 Human Health Risk Assessment D410435

Page 30 of 49

Appendix A. Toxicology Profile and Executive Summaries

A.1 Toxicology Data Requirements

The requirements (40 CFR 158.340) for food use for Clomazone are in Table 1. Use of the new guideline numbers 

does not imply that the new (1998) guideline protocols were used.

Study 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 21/28-Day Dermal

870.3250 90-Day Dermal

870.3465 90-Day Inhalation

yes

yes

yes

no

yes

yes

no

yes

-

no*

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

-

no*

yes

870.5100 Mutagenicity—Gene Mutation - bacterial

870.5300 Mutagenicity—Gene Mutation - mammalian

870.5xxx Mutagenicity—Structural Chromosomal Aberrations

870.5xxx Mutagenicity—Other Genotoxic Effects

yes

yes

yes

yes

yes

yes

yes

-

870.6100a Acute Delayed Neurotoxicity (hen)

870.6100b 90-Day Neurotoxicity (hen)

870.6200a Acute Neurotoxicity Screening Battery (rat)

870.6200b 90-Day Neurotoxicity Screening Battery (rat)

870.6300 Develop. Neurotoxicity

no

no

no

no

no

-

-

-*

-*

-

870.7485 General Metabolism

870.7600 Dermal Penetration

870.7800 Immunotoxicity

yes

no

yes

yes

no

no*

Special Studies for Ocular Effects

Acute Oral (rat)

Subchronic Oral (rat)

Six-month Oral (dog)

no

*Waived at HASPOC September 19, 2013 (TXR No. 0056801 )
CLOMAZONE/125401 Human Health Risk Assessment D410435

Page 31 of 49

A.2 Toxicity Profiles

Table 1. Acute Toxicity Profile – Clomazone

Guideline No. Study Type [species] MRID(s) Results a Toxicity 

Category

870.1100 Acute oral [rat] 00117121 LD50 2077.0 mg/kg –

1369.0 mg/kg III

870.1200 Acute dermal [rabbit] 00117122 LD50 >2000 mg/kg III

870.1300 Acute inhalation [rat] 00117123 LC50 =6.52 mg/L – 4.23 

mg/L IV

870.2400 Acute eye irritation [rabbit] 00117124

Almost non-irritating at 1 

hour in washed and 

unwashed eyes

III

870.2500 Acute dermal irritation [rabbit] 00117125 Minimally irritating at 24 

and 72 hours III

870.2600 Skin sensitization [guinea pig] 00117126 Non-sensitizer NA

Table A.2.2 Subchronic, Chronic and Other Toxicity Profile - Clomazone

Guideline 

No. 

Study Type MRID No. (year)/ 

Classification /Doses

Results

870.3100 90-Day oral toxicity 

rodents 00132586 (1982)

Males: 0, 1.4, 6.9, 34.5, 68.2, 

135.2, 273, 552.2 mg/kg/day

Females: 0, 1.6, 8.2, 41.9, 

83.4, 160.9, 319.3, 629.4 

mg/kg/day

NOAEL = 135.2/160.9 mg/kg/day, males/females

LOAEL = 273/319.3 mg/kg/day, males/females, 

based on decreased body weight, body weight gains, 

food consumption and increased absolute and 

relative liver weights in females and increased 

absolute liver weights in males

Acceptable/Guideline

870.3100 90-Day oral toxicity 

mouse

00132585 (1983)

0, 3, 15, 75, 150, 300, 600, 

1200 mg/kg/day

NOAEL 1200 mg/kg/day (limit dose)

LOAEL >1200 mg/kg/day

Acceptable/guideline

870.3200 28-Day dermal 

toxicity rats 46021101 (2003)

0 or 1000 mg/kg/day

systemic NOAEL = 1000 mg/kg/day.

systemic LOAEL = Not established

Acceptable/Guideline

870.3700a Prenatal 

developmental in 

rodents

00150291 (1984)

0, 100, 300, 600 mg/kg/day 

(gavage)

Maternal NOAEL = 100 mg/kg/day.

Maternal LOAEL = 300 mg/kg/day based on 

chromorhinorrhea and/or abdominogenital staining. 

Developmental toxicity NOAEL = 100 mg/kg/day 

Developmental toxicity LOAEL = 300 mg/kg/day 

based on indications of delayed ossification in the 

form of either partial ossification or the absence of 

the manubrium, sternebrae 3-4, xiphoid, caudal 

vertebrae, and meta-carpals. 

Acceptable/Guideline
CLOMAZONE/125401 Human Health Risk Assessment D410435

Page 32 of 49

Table A.2.2 Subchronic, Chronic and Other Toxicity Profile - Clomazone

Guideline 

No. 

Study Type MRID No. (year)/ 

Classification /Doses

Results

870.3700b Prenatal 

developmental in 

(New Zealand 

White) rabbits

00133220 (1982)

0, 30, 240, 1000/700 

mg/kg/day

Maternal NOAEL = 240 mg/kg/day 

LOAEL = 700 mg/kg/day based on effects seen at 

1000 mg/kg/day, which included mortality, 

abortions, decreased body wt. gain, and decreased 

defecation or no feces

Developmental NOAEL  700 mg/kg/day (HDT) 

LOAEL > 700 mg/kg/day

Acceptable/Guideline

870.3800 Two-Generation 

Reproduction and 

fertility effects

(CD) rats

00151108 (1984)

0, 5, 50, 100, 200 mg/kg/day Parental NOAEL = 50 mg/kg/day

Parental LOAEL = 100 mg/kg/day based on 

statistically significantly decreased body wt. & body 

wt. gain during pre-mating, and decreased body wt. 

during gestation & lactation M & F. In addition 

decreased food consumption in females and hydronephritic kidneys in males.

Developmental NOAEL = 50 mg/kg/day

Developmental LOAEL = 100 mg/kg/day based on 

decreased body weight in F2a and F2b litters

Acceptable/Guideline

870.4100b Chronic toxicity 

dogs

00150290 (1984)

Males: 0, 19, 94, 487, 1038 

mg/kg/day

Females: 0, 21, 106, 502, 

1012 mg/kg/day 

NOAEL 1038/1012 mg/kg/day, males/females 

(HDT)

LOAEL >1038/1012 mg/kg/day

Acceptable/Guideline

870.4200 Chronic 

toxicity/Carcinogeni

city

rats

00132586 (1984)

Males: 0, 0.9, 4.3, 21.5, 42.9, 

84.8 mg/kg/day

Females: 0, 1.1, 5.5, 27.8, 

56.5, 112.9 mg/kg/day

NOAEL = 84.4/112.9 mg/kg/day, males/females 

(highest dose tested)

LOAEL not attained

Not carcinogenic to rats

Acceptable/Guideline

870.4300 Carcinogenicity

mice 00132585, 00132587, 

00144244 (1983)

0, 3, 15, 75, 150, 300 

mg/kg/day

NOAEL = 300 mg/kg/day (highest dose tested)

LOAEL = >300 mg/kg/day

No evidence of carcinogenicity

Unacceptable/Guideline

870.5100 Gene Mutation

(Salmonella 

typhimurium and 

Escherichia coli

reverse gene 

mutation assay)

00142238 (1984)

FMC 65361 (>98%)

3-chloropivaloyl chloride 

(starting material in the 

clomazone manufacturing 

process)

Starting material FMC 65361 caused a positive 

mutagenic response in tester strain TA100 both in 

the absence and presence of microsomal activation.

Acceptable/Guideline

870.5100 Gene Mutation

(Salmonella 

typhimurium and 

Escherichia coli

reverse gene 

mutation assay)

00142243 (1984)

FMC 57090

hydroxamic acid, an 

intermediate in the 

manufacturing process for 

clomazone technical

In the absence of reported cytotoxicity, the test 

article [FMC 57090 (intermediate)] increased (more 

than doubling) the frequency of histidine prototrophy 

(his+) in both base substitution strains TA1535 and 

TA100 under both non-activation and activation 

(+S9) cultures in a dose-responsive manner at 5000 

and 10,000 μg/plate, i.e., a positive response.

Acceptable/Guideline

870.5100 Gene Mutation

(Salmonella 

00142242 (1983)

FMC 57090 (99%), 

In the absence of reported cytotoxicity, the test 

article [FMC 57090 (intermediate)] increased (2 to 
CLOMAZONE/125401 Human Health Risk Assessment D410435

Page 33 of 49

Table A.2.2 Subchronic, Chronic and Other Toxicity Profile - Clomazone

Guideline 

No. 

Study Type MRID No. (year)/ 

Classification /Doses

Results

typhimurium reverse 

gene mutation 

assay)

hydroxamine acid, an 

intermediate in the 

manufacturing process for 

clomazone.

3.5 fold) in the frequency of histidine prototrophy 

(his+) both base substitution strains TA1535 and 

TA100 under both in the presence or absence of S9 

activation. Metabolic activation system was not 

characterized. Therefore, under the conditions of 

this assay, the mutagenic potential cannot be 

ascertained.

Unacceptable

870.5100 Gene Mutation

(Salmonella 

typhimurium reverse 

gene mutation 

assay)

00142244 (1984)

FMC 22896 (>98%)

3-chloropivalic acid, an 

intermediate in the 

manufacturing process for 

clomazone

FMC 22896 (intermediate) was positive for 

mutagenicity in the base substitution strains TA100 

and TA1535 in the absence of overt cytotoxicity. 

Acceptable

870.5100 Gene Mutation

(Salmonella 

typhimurium and 

Escherichia coli 

reverse gene 

mutation assay)

00150292 (1984)

FMC 57020 

(clomazone, 93.4% a.i.)

The test article (technical) was assayed up to 

cytotoxic concentrations (5000 μg/plate), but in no 

instance were appreciably increased number of 

revertants to histidine prototrophy (his+) found in 

any of the tester strains, either in the presence or 

absence of metabolic activation.

Acceptable/Guideline

870.5375 Cytogenetics

In vitro mammalian 

cell cytogenetic 

assay in CHO cells

00144187 (1984)

FMC 57090 (98%)

hydroxamic acid, an 

intermediate in the 

manufacturing process for 

clomazone technical

The test article [FMC 57090 (intermediate)] did not 

induce a significant increase in presumed mutant 

colonies over control when assayed up to the limit of 

solubility (700 - 800 μg/mL).

Acceptable

870.5395 Cytogenetics

In vivo rat

00133222 (1982) Technical was negative. The incidence of 

aberrations and the aberrations/cell were not 

significantly increased.

Acceptable

870.5550 Other Effects 

In vitro UDS assay 

in primary rat 

hepatocytes

00133223 (1983)

FMC 57020 (clomazone, 

88.8%)

Clomazone was tested up to cytotoxicity (relative 

toxicity at 0.10 μL/mL was 88.6%), but in no 

cultures treated with test article was a significant 

increase in mean net nuclear counts indicative of 

UDS recorded.

Acceptable

870.7485 Metabolism and 

pharmacokinetics

00142234, 00142233 (1984) Clomazone is extensively metabolized by the liver 

and excreted in the urine and feces within 24 hours. 

Sixteen metabolites, including the parent, were 

identified; and the predominant route of excretion 

was in urine. 

Acceptable
CLOMAZONE/125401 Human Health Risk Assessment D410435

Page 34 of 49

A.3 Hazard Identification and Endpoint Selection 

A.3.1 Acute Reference Dose (aRfD) - Females age 13-49

Study Selected: Developmental Toxicity in Rats 

MRID No.: 00150291

Dose and Endpoint for Risk Assessment: NOAEL = 100 mg/kg/day based on delayed 

ossification observed at the LOAEL of 300 mg/kg/day. 

Comments about Study/Endpoint/Uncertainty Factors: The skeletal anomalies observed in 

this study are presumed to occur after a single dose (acute exposure) and are appropriate for 

females 13-49 years old because they occur in utero. The total UF is 100 (10X for interspecies 

uncertainty factor and 10X for intraspecies variability). The FQPA safety factor of 1X is 

applicable for acute dietary risk assessment. Therefore, the aPAD is equivalent to the aRfD of 

1.0 mg/kg/day.

Acute RfD (Females 13-49 years old) = (NOAEL) 100 mg/kg = 1.0 mg/kg/day

 (UF) 100

A.3.2 Acute Reference Dose (aRfD) - General Population including Infants and Children

A dose and endpoint were not selected for this population group because there were no effects 

observed in oral toxicology studies including maternal toxicity in the developmental toxicity

studies in rats and rabbits that are attributable to a single exposure (dose). A risk assessment is 

not required for this population subgroup.

A.3.3 Chronic Reference Dose (cRfD) 

Study Selected: 2-year chronic/carcinogenicity study in rats; 90-day oral toxicity study in rats; 

2-generation reproduction toxicity study in rats. 

MRID No.: 00132586; 00132586; 00151108

Dose and Endpoint for Risk Assessment: NOAEL = 84.4 mg/kg/day based on decreased body

weight, body weight gain, food consumption and in increased absolute and relative liver weight 

in females and increased absolute liver weight in males observed at the LOAEL of 273/319.3 

mg/kg/day in males and females, respectively.

Comments about Study/Endpoint/Uncertainty Factors: The NOAEL of 84.4 mg/kg/day

from the rat chronic carcinogenicity study was selected as the POD and supported by the cocritical studies of the 90-day oral toxicity study and the 2-generation reproduction toxicity study. 

The 90-day oral toxicity study had a NOAEL of 160.9 mg/kg/day in females and a LOAEL of 

319.3 mg/kg/day in females, based on decreased body weight, body weight gains, and food 

consumption and increased absolute and relative liver weights in females. In the 2-generation 

reproductive toxicity study, the parental NOAEL = 50 mg/kg/day with a LOAEL = 100 

mg/kg/day based on statistically significantly decreased body weight and body weight gain 

during pre-mating and decreased body weight during gestation and lactation in males and 

females, a statistically significant decrease in food consumption in females and hydro-nephritic 

kidneys in males. The NOAEL in the 2-generation reproduction toxicity study is lower (50 
CLOMAZONE/125401 Human Health Risk Assessment D410435

Page 35 of 49

mg/kg/day) than the NOAEL from the 2-year rat study (84.4 mg/kg/day), however, the NOAEL 

from the 2-year study was selected due to the longer duration of the study and the fact that the 

difference in the dose is due to the difference in the calculated food intake between the two 

studies. The 2-year rat study used actual consumption data (measured weekly) whereas the 2-

generation study used the standard food conversion values to estimate consumption. The total 

UF is 100 (10X for interspecies variability and 10X for intraspecies variability).

Chronic RfD (General Population) = (NOAEL) 84.4 mg/kg = 0.84 mg/kg

 (UF) 100

A.3.4 Incidental Oral Exposure (Short- and Intermediate-Term)

There are no residential uses of clomazone and therefore, no endpoints were selected for this 

exposure scenario.

A.3.5 Dermal Exposure (Short -Term)

No hazard was identified for quantification of risk following dermal exposure. In a 28-day

dermal toxicity study (MRID 46021101), no systemic toxicity was seen following repeated 

dermal application of clomazone technical (92.7% ai) to the hair-clipped, intact skin of ten 

Sprague-Dawley CD rats/sex/dose at dose levels of 0 or 1000 mg/kg bw/day (limit dose) for 6 

hours/day, 5 days/week during a 28-day period. Additionally, there are no quantitative 

sensitivities or uncertainties with clomazone to warrant an oral study for use in the dermal 

assessment. Therefore, a dermal assessment is not required. 

A.3.6 Inhalation Exposure (Short -Term) 

Study Selected: Developmental Toxicity Study in Rats

MRID No.: 00150291

Dose and Endpoint for Risk Assessment: 100 mg/kg/day based on a NOAEL of 100 

mg/kg/day, based on chromorhinorrhea and abdominogenital staining at the maternal LOAEL of 

300 mg/kg/day. 

Comments about Study/Endpoint/Uncertainty Factors: In the absence of a route-specific 

study, the oral developmental toxicity study in rats was selected and a 100% absorption factor 

was applied. The duration of this study is appropriate for this exposure scenario. The total UF is 

100 (10X for interspecies variability and 10X for intraspecies variability). 

A.3.7 Inhalation Exposure (Intermediate-Term) 

Study Selected: 2-year chronic/carcinogenicity study in rats; 90-day oral toxicity study in rats;

2-generation reproduction toxicity study in rats. 

MRID No.: 00132586; 00132586; 00151108

Dose and Endpoint for Risk Assessment: NOAEL = 84.4 mg/kg/day based on decreased body

weight, body weight gain, food consumption and in increased absolute and relative liver weight 

in females and increased absolute liver weight in males observed at the LOAEL of 273/319.3 

mg/kg/day in males and females, respectively.
CLOMAZONE/125401 Human Health Risk Assessment D410435

Page 36 of 49

Comments about Study/Endpoint/Uncertainty Factors: In the absence of a route-specific 

study, the co-critical oral studies were selected and a 100% absorption factor was applied. The 

duration of these studies is appropriate for this exposure scenario. The total UF is 100 (10X for 

interspecies variability and 10X for intraspecies variability). 

A.4 Executive Summaries

A.4.1 Subchronic Toxicity

870.3100 90-Day Oral Toxicity — Rat

In a subchronic toxicity study (MRID 00132586) FMC 57020 Technical (Purity 91.4 %, 

Reference E1756-146)was administered to 120 rats/sex/dose in the diet at concentrations of 0, 

20, 100, 500, 1000, 2000, 4000, or 8000 ppm. These concentrations resulted in mean 

concentrations of 0, 1.4, 6.9, 34.5, 68.2, 135.2, 273.0, or 552.2 mg/kg/day (males), and 0, 1.63, 

8.2, 41.9, 83.4, 160.9, 319.3, or 629.4 mg/kg/day (females) for up to 15 weeks. Interim 

sacrifices consisting of 10 rats/sex/group were conducted at 30 and 60 days and blood 

determinations and gross necropsy (tissues not saved) were performed on these rats. The final 

sacrifice consisted of 20 rats/sex/group, with hematological analysis, urinalysis, gross necropsy, 

and histopathological evaluation conducted. In addition, during the recovery phase of study for 

the 4000 and 8000 ppm groups, 5 rats/sex/group were sacrificed at 30, 60 and 90 days of 

recovery.

The toxic effects of this substance did not manifest themselves as overt clinical signs at any time 

during the study. The survival rate for this study was 100 % for all groups, control and treated.

Decreased mean body weights (87 - 95% of control) among males and females fed 8000 ppm 

achieved statistical significance (p < 0.01) throughout the study when compared with the respective control groups. Mean overall body weight gain for males and females was 84 and 75 %, 

(no statistical analysis performed) respectively of the control group means. Females fed 4000 

ppm had a mean overall body weight gain that was 86 % of the control mean and had 

significantly decreased (p < 0.01) mean absolute body weights (92 - 96 % of control) at several 

of the weekly weighings. The effects on body weight at the two highest doses were considered 

biologically significant adverse manifestations of test-substance exposure. 

Food consumption and food efficiency were also decreased among males and females at 8000 

ppm. Males had significantly (p < 0.05 or 0.01) decreased food consumption (92-96% of 

control) throughout much of the exposure period. Females also had significantly (p < 0.01) 

decreased food consumption values that ranged from 86 - 90% of control values throughout most 

of the study period. Overall food efficiency at this dietary level was decreased for males (84 %) 

and females (85 %) compared to the respective control groups.

Hematological analysis of animals treated with the test substance revealed no untoward effects. 

Plasma analysis for clinical chemistry changes related to test substance exposure revealed a 

statistically significant (p < 0.01) increase in plasma cholesterol levels among males and females 

fed 8000 ppm (55-77 %) and females fed 1000 (67 %) and 4000 ppm (44 %). A clear concentration-effect relationship was observed in both sexes. 
CLOMAZONE/125401 Human Health Risk Assessment D410435

Page 37 of 49

Among males and females fed 4000 and 8000 ppm, absolute mean liver weights, liver to body 

weight ratios, and liver to brain weight ratios were increased significantly (p < 0.01) compared to 

the respective control groups. Mean liver weights were also significantly increased among males 

and females fed 2000 ppm. However, only the 8000 ppm groups were observed to have significantly increased incidences (p < 0.05 or 0.01) of microscopic lesions in the liver compared to the 

control group. These lesions were characterized as minimal or mild megalocytosis of 

centrilobular hepatocytes. Since histopathology was not conducted at 4000 ppm but assumption 

could be made that at 4000 ppm some megalocytosis may have occurred. Because animals fed 

lower concentrations of the test diet had no histopathological correlates, it is unclear if these liver 

weight changes are of toxicological significance. 

Following 3 months of recovery the absolute and relative liver weights of 4000 and 8000 ppm 

groups were comparable to controls.

Under the conditions of this study, the LOAEL was 4000 ppm (273.0 and 319.3 mg/kg/day 

for males and females, respectively), based on changes in body weight, body weight gain, 

food consumption and increased absolute and relative liver weights in females and absolute 

liver weights in males. The NOAEL was 2000 ppm (135.2 and 160.9 mg/kg/day for males 

and females, respectively).

This subchronic oral toxicity study is classified as Acceptable/Guideline and satisfies the 

guideline requirement for a subchronic oral toxicity study [OPPTS 870.3100 (§82-1b)] in rats. 

870.3100 90-Day Oral Toxicity — Mouse

In a combined subchronic and oncogenicity study (MRID 00132585, 0013287 and 00144244) 

clomazone (88.8%, a.i.) was administered to 120 CD-1 mice/sex/dose in diet at dose levels of 0, 

20, 100, 500, 1000, 2000, 4000 or 8000 ppm (equivalent to 0, 3, 15, 75, 150, 300, 600 or 1200 

mg/kg/day for males and females) for 3 to 24 months. In the subchronic phase of the study

(MRID 00144244) 10 mice/sex/dose at 30 and 60 days and 20 mice/sex/dose at 90 days, were 

randomly selected for hematology and gross and histopathology. Animals sacrificed at 90 days 

from the 0, 20, 500, 2000 or 8000 ppm were evaluated histopathologically. Following evaluation 

of organ wt. data from the 90-day sacrifice, the remaining animals from the 4000 and 8000 ppm 

groups were removed from the study, sacrificed and examined. During the oncogenicity phase 

of the study 10 animals/sex/group were sacrificed at 6, 12, and 18 months for blood and 

histopathological evaluations. At terminal sacrifice (24 months) blood parameters were evaluated 

for 10 animals /sex/dose and a complete histopathological examination was performed on all 

animals. Tests for concentration, homogeneity and stability of the test material in the diet were 

all within acceptable limits.

There were no compound related effects between treated and control group for any time period 

for either clinical observations, mortality, body weight change, food consumption, hematology

and/or clinical chemistry values.
CLOMAZONE/125401 Human Health Risk Assessment D410435

Page 38 of 49

Absolute and relative liver weights were increased in males and females at several time points 

and dose levels. Statistically significant (p<0.01) increases were recorded for both sexes at 90 

days at 4000 and 8000 ppm for absolute liver weight (23 - 33%), liver to body weight (20 -

36%), and liver to brain weight ratios (20 - 36%). Hepatocellular cytomegaly was observed at 

8000 ppm in 11 of 20 males. Histopathology of 4000 ppm group was not performed. In the 

absence of other systemic toxicity findings, increased liver weights and cellular hypertrophy are 

considered adaptive changes and has no toxicological significance. Therefore, there were no 

adverse effects at the high dose of 2000 ppm in the carcinogenicity study.

 

NOAEL  8000 ppm ( 1200 mg/kg/d; Limit Dose) in the 3 month mouse feeding study.

LOAEL was not established.

NOAEL  2000 ppm (300 mg/kg/d) oncogenicity study (24 months).

LOAEL was not established.

Administration of FMC 57020 for up to 2-years did not result in a statistically significant 

increase in the incidence of neoplastic lesions. Dosing was not considered adequate based on the 

lack of a toxic effect on the animals.

CLASSIFICATION: The subchronic phase of the study was classified as Acceptable/Guideline 

and satisfies the guideline requirement for a subchronic oral toxicity study [OPPTS 870.3100]

in mice. The oncogenicity phase of the study in mice is classified as Unacceptable/Guideline 

and does not satisfy the guideline requirement for an oncogenicity study [OPPTS 870.4200b] in 

mice because dosing was not adequate.

870.3150 90-Day Oral Toxicity — Dog

This requirement is satisfied by a chronic dog study (MRID 00150290).

870.3200 28-Day Dermal Toxicity – Rat

In a 28-day dermal toxicity study (MRID 46021101), Clomazone Technical (92.7% a.i.; 

Reference # PL01-0346) was applied directly to the hair-clipped intact skin of 10 SpragueDawley CD rats/sex/dose at dose levels of 0 or 1000 mg/kg bw/day (limit dose) for 6 hours/day, 

5 days/week during a 28-day period. No treatment-related effects were observed in mortality, 

clinical signs, dermal effects, body weight, body weight gain, food consumption, 

ophthalmoscopic examination, hematology, clinical chemistry, organ weights, or macroscopic 

pathology. Epidermal hyperplasia and focal erosion of the epidermis in the treated and untreated 

skin and hyperkeratosis in the untreated skin were observed in the dosed females at increased 

incidence and/or severity over controls. Additionally, hyperplasia in the epidermis was observed 

in all dosed and control males; however, severity was increased from minimal to mild in both the 

treated and untreated skin. Abdominal skin (distant from the application site) was not affected 
CLOMAZONE/125401 Human Health Risk Assessment D410435

Page 39 of 49

indicating a lack of systemic effect. The Sponsor stated that similar findings on treated skin and 

untreated skin near the application site was most likely due to diffusion of the compound beneath 

the bandage. The study pathologist stated that the changes observed to the skin were adaptive 

changes due to minimal irritation of the test material and that these changes were expected to be 

fully reversible. The reviewers concur that the test compound resulted in only minimal skin 

irritation and did not consider this an adverse effect. 

This study is classified as Acceptable/Guideline and does satisfy the guideline requirement 

[OPPTS 870.3200] for a 28-day dermal toxicity study in rats. The LOAEL was not observed; 

however, the compound was tested at the limit dose (1,000 mg/kg).

870.3465 90-Day Inhalation – Rat

The HASPOC waived the requirement for this study on September 19, 2013 (Rury, 2013).

870.3700a Prenatal Developmental Toxicity Study - Rat

In a prenatal developmental toxicity study in the rat (MRID 00150291) one-hundred assumed 

pregnant Sprague-Dawley rats were divided into four groups of 25 and orally gavaged with 

either 100, 300 or 600 mg/kg of test material from days 6-15 of gestation. One additional group 

served a vehicle control group and received only corn oil. Dams were sacrificed on day 20 of 

gestation and necropsied. Half the viable fetuses were examined for skeletal effects using a 

modification of the Wilson technique and half examined for visceral effects. Standard statistical 

analyses were conducted on 13 of 15 parameters covering both dams and fetuses.

There were no compound related deaths. Non-treatment related deaths were associated with 

esophageal or lung puncture during the administration of compound. Clinical signs were 

observed only in dams receiving 300 and 600 mg/kg/d. Signs seen at 300 mg/kg/d consisted of 

chromorhinorrhea and/or abdominogenital staining in 4/24 dams. Signs seen at 600 mg/kg in 

23/23 dams were abdominogenital staining, decreased locomotion and/or chromorhinorrhea. 

Body weight gain in dams was decreased, but not statistically significant, at 600 mg/kg/d on days 

6-15 [-5.7%], 15-20 [-9.0%] and 0-20 [-7.2%]. Food consumption in dams at 600 mg/kg/d was 

however, meaningfully decreased only on days 6-13. [-12 %; p< 0.05]. Fetal body weights were 

decreased only for females at 600 mg/kg/d [-6.6%; p< 0.05] with male body weights [-3.3%] and 

total live fetal body weights [-5.0%] being generally comparable to controls and not statistically

significant. Minor malformation of the thoracic vertebrae was statistically significant at 600 

mg/kg when reported on a fetal incidence basis. Indications of delayed ossification in the form of 

either partial ossification or the absence of the following bones were reported as statistically

significant either on a litter or a fetal basis at 300 or 600 mg/kg: manubrium, sternebrae 3-4, 

xiphoid, caudal vertebrae, and meta-carpals. The fetal/litter incidences for sternebrae 3-4, at 300 

and 600 mg/kg/day were 2.8%/17.4% and 4.7%/22.7%, respectively, compared to 0%/0% in the 

controls. Normal variations were reported for sternebrae 2 and 5 at 300 and 600 mg/kg.

All other reported values for both dams and fetuses were comparable to controls.
CLOMAZONE/125401 Human Health Risk Assessment D410435

Page 40 of 49

The maternal NOAEL is 100 mg/kg. The maternal LOAEL is 300 mg/kg based on 

chromorhinorrhea and/or abdominogenital staining. The developmental NOAEL is 100 

mg/kg. The developmental LOAEL is 300 mg/kg based on indications of delayed 

ossification in the form of either partial ossification or the absence of the manubrium, 

sternebrae 3-4, xiphoid, caudal vertebrae, and meta-carpals.

This developmental toxicity study in the rat is classified Acceptable/Guideline and satisfies the 

guideline requirement for a developmental toxicity study [OPPTS 870.3700a (§83-3)] in the rat.

870.3700b Prenatal Developmental Toxicity Study - Rabbit

In a prenatal developmental toxicity study in the rabbit (MRID 00133220) four groups of 

assumed pregnant New Zealand white rabbits comprised of 18 animals per group were 

administered FMC 57020 in doses of either 30, 240 or 1000 mg/kg (reduced to 700 mg/kg on 

day 13-18 of gestation) from days 6-18 of gestation. An additional group served as control and 

received only the vehicle carboxy-methyl-cellulose. All animals were sacrificed on day 29 of 

gestation. 

Compound related toxicity at the high dose tested (HDT; 1000/700 mg/kg) included 3 deaths, 

and 3 abortions all after day 18. [animals dying were not animals aborting]. Net body mean 

weight gain [i.e. maternal body weight at day 29 minus the weight of the gravid uterus] for 

controls and treated groups was +87; +160; -60 and -85 grams respectively with the HDT being 

statistically significant [-85 grams; p<0.05]. Mean weight of the gravid uteri were comparable 

between dose groups ranging from 340-361 grams. Mean maternal body weight gain for days 6-

18 of gestation from controls to the HDT was +155; +219; +96 and -300 grams respectively. 

Ataxia was also reported for 2 animals in the HDT as well as red vaginal discharge in 4 rabbits 3 

of which aborted. Decreased or no defecation was also observed at 1000/700 mg/kg more 

frequently than at the lower doses. No other significant toxicological effects were noted for dams 

at either 30.0 or 240 mg/kg.

Examination of fetal and litter data indicated no meaningful developmental toxicological effects 

for either mean fetal data at the time of laparotomy, or external, skeletal or visceral compound 

related effects at any dose level. 

The maternal NOAEL is 240 mg/kg. The maternal LOAEL is 700 mg/kg based on the effects 

seen at 1000 mg/kg. (The assumption here is that the effects of maternal death, abortions, 

decreased body weight gain and deceased or no defecation may also have occurred at 700 mg/kg 

if the animals had been given this dose of 700 mg/kg during days 6-18).

The developmental NOAEL is 700 mg/kg. The developmental LOAEL is > 700 mg/kg since no 

higher dose was given for the days 13-18.

This study is classified as Acceptable/Guideline and does satisfy the guideline requirement for a 

developmental toxicity study [OPPTS 870.3700b (§83-3)] in the rabbit.
CLOMAZONE/125401 Human Health Risk Assessment D410435

Page 41 of 49

870.3800 Reproduction and Fertility Effects - Rat

In a 2-generation reproduction study in rats (MRID 00151108) two hundred and fifty [250] male 

and female Charles River CD strain rats were randomly assigned into 5 groups of 25 males and 

25 females per dose group and administered either 0, 100, 1000, 2000 or 4000 ppm (equivalent 

to 0, 5, 50, 100, or 200 mg/kg/day) of FMC 57020. 

There was no compound related mortality. Parental body weight in males during pre-mating was 

comparable to controls whereas female body weight was statistically significantly lower [p<0.05-

p<0.01] at 2000 and 4000 ppm as early as 2 and 5 weeks through to copulation [8 and 11 weeks 

later]. Premating body weight gain was also lower [p<0.01] for females in both generations at 

2000 ppm and 4000 ppm (26%;26% and 11%;13% respectively) Maternal body weight during 

periods of gestation (days 0-20) and lactation (days 0-21) were lower [p<0.05-0.01] at 2000 and 

4000 ppm for all generation and litters. Food consumption for treated males was generally 

comparable to controls during premating; however, food consumption for FO and F1 females was 

generally lower at 2000 and 4000 ppm with several occasions of statistical significance (p<0.05-

p<0.01). The only clinically significant observation was noted in the 4000 ppm female groups of 

the FO and F1 generations and consisted of urine soaked and/or yellow-brown stained fur.

Reproductive performance was comparable for all generations when compared to controls with 

the exception of a statistically significant [p<0.05] but apparently aberrant decreased fertility 

value for the F1b litter at 4000 ppm. Pup survival and pup body weight values were comparable 

to control values for all litters during lactation with the exception of a statistically significant 

decrease in pup body weight values at 2000 ppm and 4000 ppm for the F2a and F2b litters.

Statistically significant increases were noted for liver to body weight ratios in both males and 

females of the FO generation at 4000 ppm and in liver to brain weight ratios for males at 4000 

ppm. Statistically significant increases for liver to body weight ratios were also reported for F1

males and females in the 4000 ppm groups and females in the 2000 ppm group. However, 

absolute weights were not increased and histopathology was not remarkable indicating that 

increases may be attributable to a combination of enzyme induction and/or decreased body 

weight. There was also an increased incidence of dilated and distended pelvis of the kidney in 

the F1 males after the F2b mating in the 2000 and 4000 ppm groups when compared to the 

control group [1/23; 2/24; 1/23; 6/24; 7/24 equal to 4%; 8%; 4%; 25% and 29% control to high 

dose respectively]. These effects were not seen after F2a mating. This suggests that the effects 

occurred as adults but not in utero effect. Histopathology was conducted on the FO and F1

parental animals from the control and the 4000 ppm group as well as 10 male and 10 female F1b 

and F2b progeny from the control and the 4000 ppm dose groups randomly chosen from those 

subjected to necropsy examination. Any progeny which exhibited grossly apparent 

developmental anomalies were subjected to gross pathologic study and tissues retained by the 

pathologist. Tissues and organs examined for histopathology included the ovaries (with corpus), 

prostate, seminal vesicles, testes (with epididymides), uteri, and vagina, and all other tissues and 

organs appearing abnormal. All kidneys from the F1 parental generation were also examined 

microscopically as a result of the incidence of hydro-nephritic kidneys noted grossly.

Malformations reported were either those commonly occurring, not statistically significant 

and/or not dose responsive. Observations such as short, kinked and hair like tail, macrophthalmia 

and anophthalmia were reported as common observations. Limb abnormalities (i.e. 1 pup in the 
CLOMAZONE/125401 Human Health Risk Assessment D410435

Page 42 of 49

1000 ppm group and 1 in the 4000 ppm group) and the absence of the anal opening (1 pup in the 

4000 ppm group) raised concerns of teratogenicity. [NOTE: the absence of these effects in the 

rat teratology resulted in the rat teratology study being audited and re-examined by outside 

experts].

Parental NOAEL is 1000 ppm equivalent to 50 mg/kg/d.

Parental LOAEL is 2000 ppm equivalent to 100 mg/kg/d based on statistically significant 

decreases in premating body weight and body weight gain, statistically significant decreases in 

body weight during gestation and lactation, a statistically significant decrease in food 

consumption in females and hydro-nephritic kidneys in males.

Developmental NOAEL is 1000 ppm (50 mg/kg/d).

Developmental LOAEL is equal to 2000 ppm (100 mg/kg/d) based on a decreased body weight 

in F2a and F2b litters.

Reproductive NOAEL and LOAEL is  200 mg/kg/day.

This study is classified as Acceptable/Guideline and does satisfy the guideline requirements for 

a two-generation reproduction study [OPPTS 870.3800 (§83-4)] in the rat. 

870.4100a (870.4300) Chronic Toxicity – Rat

In a chronic toxicity/oncogenicity study (MRID 00132586), FMC 57020 Technical (Reference 

E1756-146) was administered to 5 groups of 120 CD (Sprague-Dawley) outbred albino rats/sex 

for a period of up to 24 months in the diet at concentrations of 0, 20, 100, 500, 1000, or 2000 

ppm. These dietary levels resulted in mean doses of 0, 0.9, 4.3, 21.5, 42.9, or 84.8 mg/kg/day

(males), and 0, 1.1, 5.5, 27.8, 56.5, or 112.9 mg/kg/day (females). After 15 weeks of treatment, 

20 rats/sex/group were chosen for hematology, urinalysis, and gross pathology to satisfy the 

requirements for the subchronic portion of the study; these results are discussed in a separate 

DER. During the chronic phase of the study, 10 randomly selected rats/sex/group were 

sacrificed at 6, 12, and 18 months for blood and histopathological evaluations. At the final 24-

month sacrifice, 10 rats/sex/group were bled for hematological analysis and a complete 

histopathological evaluation was performed on all rats.

Survival was not affected by the test substance in any of the treated groups compared to either of 

the control groups. No treatment-related clinical signs or alterations of body weight, food 

consumption, hematology or urinalysis parameters were observed. 

During the first year of treatment, males and females fed 1000 or 2000 ppm had slightly elevated 

total cholesterol plasma levels. Since this effect did not continue into the second year of 

treatment, the toxicological relevance of these alterations remains unclear.

At the 3-month sacrifice slight liver enlargement (p < 0.05, liver weight and ratio to body

weight) was evident among male and female rats treated with 2000 ppm and in females treated 
CLOMAZONE/125401 Human Health Risk Assessment D410435

Page 43 of 49

with 2000 ppm at the final 24-month sacrifice. Clear liver effects were seen at 4000 and 8000 

ppm. At other interim sacrifice time points, no significant differences were observed.

Histopathological analysis of the livers of treated males and females revealed increased 

incidences of hepatocytomegaly. These increases achieved statistical significance at various 

time points of sacrifice, but generally were not dose-related and often were more profound in the 

mid-dose groups. Therefore, the toxicological significance of this finding in this dose range 

remains obscured. 

The no-observed-adverse-effect level (NOAEL) is > 2000 ppm for males (84.4 mg/kg/day) 

and females (112.9 mg/kg/day) in this study. A lowest-observed-adverse-effect level 

(LOAEL) was not identified.

The administration of FMC 57020 Technical for up to 104 weeks did not result in a statistically

significant increase in the incidence of neoplastic lesions. 

No treatment-related effects were observed at the highest dose tested (2000 ppm; 84.4 

mg/kg/day). Inspite of the absence of systemic toxicity at this dose, the HIARC concluded that 

this dose was adequate to assess the chronic toxicity and carcinogenicity in rats. This conclusion 

was based on the results obtained in the 90-day oral toxicity (MRID 00132586) and the two 

generation reproduction study in rats. In the 90-day study, the LOAEL was 4000 ppm (319 

mg/kg/day) and the NOAEL was 2000 ppm (160 mg/kg/day) based on statistically significant 

decrease in body weight and body weight gain in female rats. In the two generation reproduction 

study (MRID 00151108), the LOAEL was 2000 ppm (100 mg/kg/day) and the NOAEL was 

1000 ppm (50 mg/kg/day).

This chronic study in rats is classified as Acceptable/Guideline and satisfies the guideline 

requirement for a chronic toxicity study [OPPTS 870.4100a (§83-1)] in rats.

The oncogenicity phase of study in rats is classified as Acceptable/Guideline and satisfies the 

guideline requirement for a combined chronic toxicity/oncogenicity study in rats [OPPTS 

870.4300 (§83-2)].

870.4100b Chronic Toxicity - Dog

In a chronic toxicity study (MRID 00150290) FMC 57020 (88.8% a.i.) was administered to 

6/sex/dose dogs in diet at dose levels of 0, 100, 500, 2500, or 5000 ppm for one year 

(approximately, M: 0, 19, 94, 487, and 1038 mg/kg/day; F: 0, 21, 106, 502, and 1012 

mg/kg/day). Measures were taken of body weight, food consumption, hematology, clinical 

chemistry, and organ weights. At the 3 month interim sacrifice, 2/sex/dose were sacrificed.

Treatment with clomazone up to 5000 ppm had no effect on mortality, food consumption body

weights and body weight gains, hematology and/or clinical chemistry and macro or 

micropathology of any organs. High dose (1012 mg/kg/day) females had reduced percentage 

(12%) of hematocrit level at 1 month, increased platelet count at 3 (44%) and 6 (58%) months 

and increased eosinophil percentage (250%) at 6 months. Statistically significant increases in 
CLOMAZONE/125401 Human Health Risk Assessment D410435

Page 44 of 49

cholesterol levels above control values were noted for males and females of the 5000 ppm (1038 

and 1012 mg/kg/day) group at 1 and 3 months (37 to 56%), and for those in the 2500 ppm group 

at 3 months (females, 502 mg/kg/day increased 26%) and 12 months (males, 487 mg/kg/day

increased 20%). At 12 months the levels of GGT were increased relative to controls for males of 

the 2500 and 5000 ppm (487 and 1038 mg/kg/day, 113% and 100%, respectively) groups and 

females of the 2500 ppm (502 mg/kg/day increased 106%) group. The above changes in 

hematology and/or clinical chemistry parameters are within the control ranges and are not 

considered toxicologically relevant.

A treatment related trend for higher (10 - 46%) absolute and relative liver weights at the interim 

and terminal sacrifices was present in males and females. Statistical significantly higher (46%) 

relative liver weights occurred in males of the 5000 ppm (1038 mg/kg/day) group compared to 

the control group at terminal sacrifice. Relative brain weight for males in the 5000 ppm (1038 

mg/kg/day) were increased (25%) when compared to controls. All macroscopic observations 

and microscopic lesions were considered incidental to the study and not treatment related. The 

changes in cholesterol values and liver weights were not reflected in morphological change upon 

microscopic examination of the liver.

Based on the above findings, the NOAEL of 500 ppm (12.5 mg/kg/day) established earlier (see 

HED Doc. No. 004173) has been changed to  5000 ppm (1038 mg/kg/day for males and 1012 

mg/kg/day for females) since no systemic toxicity was observed at the highest dose tested (5000 

ppm). The LOAEL was not established in this study. Highest dose tested (HDT) is > limit test 

of 1,000 mg/kg/day.

This chronic toxicity study in the dog is classified as Acceptable/Guideline and does satisfy the 

guideline requirement for a chronic oral study [OPPTS 870.4100 (§83-1(b)] in dog.

870.4200a Carcinogenicity Study - rat

See 870.4100a

870.4200b Carcinogenicity (feeding) - Mouse

In a combined subchronic and oncogenicity study (MRID 00132585, 00132587 and 00144244) 

clomazone (88.8%, a.i.) was administered to 120 CD-1 mice/sex/dose in diet at dose levels of 0, 

20, 100, 500, 1000, 2000, 4000 or 8000 ppm (equivalent to 0, 3, 15, 75, 150, 300, 600 or 1200 

mg/kg/day for males and females) for 3 to 24 months. In the subchronic phase of the study 

(MRID 00144244) 10 mice/sex/dose at 30 and 60 days and 20 mice/sex/dose at 90 days, were 

randomly selected for hematology and gross and histopathology. Animals sacrificed at 90 days 

from the 0, 20, 500, 2000 or 8000 ppm were evaluated histopathologically. Following evaluation 

of organ wt. data from the 90-day sacrifice, the remaining animals from the 4000 and 8000 ppm 

groups were removed from the study, sacrificed and examined. During the oncogenicity phase 

of the study 10 animals/sex/group were sacrificed at 6, 12, and 18 months for blood and 

histopathological evaluations. At terminal sacrifice (24 months) blood parameters were evaluated 

for 10 animals /sex/dose and a complete histopathological examination was performed on all 
CLOMAZONE/125401 Human Health Risk Assessment D410435

Page 45 of 49

animals. Tests for concentration, homogeneity and stability of the test material in the diet were 

all within acceptable limits.

There were no compound related effects between treated and control group for any time period 

for either clinical observations, mortality, body weight change, food consumption, hematology

and/or clinical chemistry values.

Absolute and relative liver weights were increased in males and females at several time points 

and dose levels. Statistically significant (p<0.01) increases were recorded for both sexes at 90 

days at 4000 and 8000 ppm for absolute liver weight (23 - 33%), liver to body weight (20 -

36%), and liver to brain weight ratios (20 - 36%). Hepatocellular cytomegaly was observed at 

8000 ppm in 11 of 20 males. Histopathology of 4000 ppm group was not performed. In the 

absence of other systemic toxicity findings, increased liver weights and cellular hypertrophy are 

considered adaptive changes and has no toxicological significance. Therefore, there were no 

adverse effects at the high dose of 2000 ppm in the carcinogenicity study.

NOAEL  8000 ppm ( 1200 mg/kg/d; Limit Dose) in the 3 month mouse feeding study.

LOAEL was not established.

NOAEL  2000 ppm (300 mg/kg/d) oncogenicity study (24 months).

LOAEL was not established.

Administration of FMC 57020 for up to 2-years did not result in a statistically significant 

increase in the incidence of neoplastic lesions. Dosing was not considered adequate based on the 

lack of a toxic effect on the animals.

CLASSIFICATION: The HIARC classified the mouse oncogenicity study as 

Unacceptable/Guideline and does not satisfy the guideline requirement for an oncogenicity 

study [OPPTS 870.4200b] in mice because dosing was not adequate. Systemic toxicity was not 

observed at the highest dose tested. HED has reevaluated the database and determined that a 

new mouse study is not required because a new study would need to test at doses above 300 

mg/kg/day and the current chronic reference dose would be protective of any effects observed in 

mice at these higher doses. 

870.7485 Metabolism-Rat

In a general metabolism study (MRID 00142234) ten male and ten female animals were divided 

into two groups of 5 males and 5 females per group and fasted for 18 hours prior to receiving 

either a single oral (low) dose of 5.0 mg/kg of radio-labeled test compound by gavage, or a 

single oral (high) dose of 900.0 mg/kg of radio-labeled test material by gavage in corn oil. Total 

radio-activity was approximately 20 micro curies per test animal.

A third group of 5 males and 5 females were also fasted for 18 hours and anaesthetized with 

ether prior to shaving the rear leg for access to the safenous vein. 14 C FMC 57020 dissolved in 
CLOMAZONE/125401 Human Health Risk Assessment D410435

Page 46 of 49

de-ionized water was then injected into the vein at a dose of about 3-4 mg/kg and 20 micro 

curies.

A last group of 5 animals per sex per dose were also fasted for 18 hours before administration of 

un-labeled FMC 57020 in corn oil by gavage. The animals were given food and water ad libitum

for 14 days and were dosed daily by gavage with un-labeled FMC 57020 at a dose of 5.0 mg/kg. 

Rats were again fasted for 18 hours prior to being given 14 C labeled FMC 57020 by gavage at a 

dose of 5.0 mg/kg equivalent to 20 micro curies.

After the administration of radio-active compound all animals in all groups remained of fast for 

an additional 6 hours prior to being returned to laboratory rat diet and were fed ad libitum.

Urine and feces samples were collected at periodic intervals over 7 days at which time the 

animals were sacrificed by exsanguination. Rats were then dissected and the following organs 

and tissues obtained for radioactive counting: brain, heart, kidney, spleen, skin, bone, leg muscle, 

adipose tissue, and gonads (uterus and ovaries for females; testes, prostate and seminal vesicles 

for males) and carcass.

Analysis of metabolic products by HPLC, TLC, GS/MS, NMR and scintillation counting showed 

the presence of parent chemical and 16 identifiable metabolites. The majority of these products 

were eliminated in the urine and the feces within 24 hours with the predominant route of 

excretion being the urine. The total amount of the administered dose recovered after the first day

(24 hours) ranged between 75-85% for all routes and doses with the exception of females in the 

single high dose group where the total recovery was only 48 %, compared to males which was 

75%. The total recovery after 48 hours was generally comparable between all groups and ranged 

between 91-100%. The quantities of metabolites varied with the dose regimen, sex, and route of 

administration but were the same qualitatively both in the urine and the feces in all groups.

The observed quantitative differences between the groups can be summarized as follows:

(1) excretion (48%) in the high dose was lowest in females in the 24 hour period. Examining the 

total weight of the excreta revealed that the amount of feces from the females was substantially

suppressed in the first day.

(2) the total amount of 5-hydroxy FMC 57020 was highest in the single oral low dose group but 

not in the multiple oral low dose group indicating the possibility of an enzyme induction effect.

(3) both single oral low and high dose groups gave a high percentage of 5-hydroxy FMC 57020 

in their feces samples especially in the first day feces indicating the possibility of entero-hepatic 

circulation. This possibility was further enhanced by the fact that less than 1% of the fecal and 

urinary metabolites was un-metabolized parent compound.

(4) it was reasonable to assume that 5-OH FMC 57020-conjugate formed in the liver was 

excreted to the gastrointestinal tract via the bile duct and this conjugate was readily cleaved to 

5-OH FMC 57020 and excreted in the feces.

(5) in the multiple oral low dosed group, the amounts of di-hydroxylated, tri-hydroxylated and 
CLOMAZONE/125401 Human Health Risk Assessment D410435

Page 47 of 49

di-hydrodiol metabolites were increased significantly, indicating that an induction effect on the 

mixed function oxidase (MFO) system (possibly the cytochrome p-450 system) had developed.

The predominant metabolites included: 5-hydroxy FMC 57020; 4', 5-dihydroxy FMC 57020; 

4', 5' -dihydrodiol-5-hydroxy FMC 57020; 4', 5'-dihydrodiol FMC 57020, N-[(2'-chlorophenyl) 

methyl]-N-hydroxy-2-methyl-2-carboxy propanamide (FMC 87008) and a dihydroxylated 

derivative of FMC 57020. Metabolites were excreted both free and as conjugates. 

Residual 14C in tissues was, in general, very low. Most of the tissues had residues of less than 

twice the background.

Single oral 5.0 mg/kg (low) dose: Values higher than twice the back ground were detected in the 

lungs, spleen, kidney, liver, blood, skin, hair, and carcass of both sexes. The highest residue was 

generally found in the hair, the organs involved in the metabolism and excretion of the 

compound, the liver, kidney and the blood.

Single oral 900.0 mg/kg (high) dose: Residue levels higher than twice the background were 

detected in the same organs as the low dose.

Intravenous dose: Residue levels higher than twice the background were detected in the same 

tissues as those found for oral administration.

Multiple dose (14 days): Residue values higher than twice the background were detected in the 

same tissues as for the single oral dose.

This metabolism study in the rat is classified Acceptable/Guideline and satisfies the 

requirements for a metabolism and pharmacokinetics study [OPPTS 870.7485 (§85-1) in rats. 

870.7800 Immunotoxicity

The HASPOC waived the requirement for this study on September 19, 2013 (TXR No. 0056801, 

Rury, 2013).
CLOMAZONE/125401 Human Health Risk Assessment D410435

Page 48 of 49

Appendix B. Physical/Chemical Properties

Table C1. Physico-Chemical Properties of Clomazone

Parameter Value Reference

Molecular Weight 239.7 Calculated

Melting point/range 25 C, broad range MRID 00144241

pH 6.89 + 14 (supernatant 

of slurry)

MRID 00144241

Density 1.187 g/mL MRID 00144241

Water solubility ( mg/L at unspecified C) 1100 mg/L MRID 00144241

Solvent solubility (mg/L at unspecified C) >200 mg/L in Tenneco 

500-100

 4.5-5.0 mg/L in Isopar 

M

 >90 mg/L in refined 

soybean oil

 Infinite in dimethyl 

formamide

 Infinite in 

cyclohexanone

MRID 00144241

Vapor pressure at 25 C 1.92 x 10 -2Pa (1.44 x 

10 -4 mm Hg)

MRID 00144241

Dissociation constant (pKa) N/A neither acidic nor 

basic

MRID 00144241

Octanol/water partition coefficient Log(KOW) 350 (log p = 2.54) MRID 00144241

UV/visible absorption spectrum Not available
CLOMAZONE/125401 Human Health Risk Assessment D410435

Page 49 of 49

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 data, which include studies from 

PHED 1.1; the AHETF database; and the ARTF database, are (1) subject to ethics review 

pursuant to 40 CFR 26, (2) have received that review, and (3) are compliant with applicable 

ethics requirements. For certain studies, the ethics review may have included review by the 

Human Studies Review Board. Descriptions of data sources, as well as guidance on their use, 

can be found at the Agency website5. 

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.

Agricultural Re-entry Task Force (ARTF) data base (SOP #3.1)

 

5

http://www.epa.gov/pesticides/science/handler-exposure-data.html and 

http://www.epa.gov/pesticides/science/post-app-exposure-data.html