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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C. 20460

 OFFICE OF

CHEMICAL SAFETY AND

POLLUTION PREVENTION

Date: November 7, 2011

MEMORANDUM

SUBJECT: Amended: Tepraloxydim: Human Health Risk Assessment for New Tolerances 

on Imported Dry Bean and Dry Pea Subgroup 6C and Sunflower Subgroup 20B.

PC Code: 121005 DP Barcode: D395874

Decision No.: 440435 Registration Nos.: NA

Petition Nos.: 0E7788 Regulatory Action: Tolerance Assessment

Risk Assessment Type: Single chemical/ 

aggregate

Case No.: NA

TXR No.: NA CAS No.: 149979-41-9

MRID No.: NA 40 CFR: §180.573

FROM: Barry O’Keefe, Senior Biologist

Amelia Acierto, Chemist

Sheila Healy, Toxicologist

Risk Assessment Branch III

Health Effects Division (7509P)

THROUGH: Paula Deschamp, Branch Chief

Risk Assessment Branch III

Health Effects Division (7509P)

TO: Susan Stanton, RM 25

Herbicide Branch

Registration Division (7505P)

Introduction

This amendment of the recent HED risk assessment (DP384834, B. O’Keefe, 7/28/11) of 

tepraloxydim was completed to provide a more thorough characterization of the toxicological 

database for tepraloxydim. 

BASF Corporation, on behalf of Nippon Soda Company, has submitted a petition (Petition No. 

0E7788) proposing the establishment of tolerances for residues of the herbicide tepraloxydim 
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and its metabolites convertible to GP [3-(tetrahydropyran-4-yl)pentane-1,5-dioic acid], 

calculated as tepraloxydim, in/on the following imported raw agricultural commodities grown in 

Canada:

Pea and bean, dried shelled, except soybean, subgroup 6C..........0.10 ppm

Sunflower subgroup 20B ..............................................................0.25 ppm

Tepraloxydim is registered for use in Canada under the trade name EQUINOXTM EC Herbicide, 

an emulsifiable concentrate formulation containing 200 g/L (1.67 lb ai/gal) which is identical to 

EQUINOX EC Herbicide, registered in the US (EPA Reg. No. 8033-12) on canola, cotton, 

fallow land, non-cropland, and soybeans. The label was amended and approved by PMRA in 

April 2010 to include new uses on additional crops of Subgroup 6C and on sunflower. The 

product was previously labeled in Canada under the trade name ARAMOTM EC Herbicide 

(Canadian Reg. No. 27603). BASF has no plans to apply to register EQUINOX in the U.S for 

the new uses on dried beans and sunflower. 

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

toxicology and residue chemistry data and conduct dietary and aggregate exposure and risk 

assessments, as needed, to estimate the risk to human health that will result from these new 

tolerances on imported commodities.

A summary of the findings and an assessment of human risk resulting from the registered and 

proposed new uses of tepraloxydim are provided in this document. The risk assessment was 

provided by Barry O’Keefe, the hazard characterization by Sheila Healy, and the residue 

chemistry data review and the dietary assessment by Amelia Acierto. The drinking water 

assessment was provided by James Breithaupt of the Environmental Fate and Effects Division 

(EFED).
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Table of Contents

1.0 Executive Summary.......................................................................................................... 5

2.0 Regulatory Conclusions and Recommendations............................................................ 6

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

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

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

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

2.2.3 Recommended Tolerances.......................................................................... 9

2.2.4 Revisions to Petitioned-For Tolerances.................................................... 10

3.0 Ingredient Profile............................................................................................................ 10

3.1 Summary of Proposed Uses.................................................................................. 10

3.2 Structure and Nomenclature ................................................................................. 11

3.3 Physical and Chemical Properties......................................................................... 13

3.4 Anticipated Exposure Pathways ........................................................................... 13

3.5 Consideration of Environmental Justice ............................................................... 13

4.0 Hazard Characterization/Assessment........................................................................... 14

4.1 Toxicology Studies Available for Analysis.......................................................... 14

4.2 Absorption, Distribution, Metabolism, Excretion (ADME)................................. 15

4.2.1 Dermal Absorption.................................................................................... 15

4.3 Toxicological Effects............................................................................................ 15

4.4 Safety Factor for Infants and Children (FQPA Safety Factor) ............................. 17

4.4.1 Completeness of the Toxicity Database.................................................... 17

4.4.2 Evidence of Neurotoxicity ........................................................................ 18

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

18

4.4.4 Residual Uncertainty in the Exposure Database....................................... 19

4.5 Toxicity Endpoint and Point of Departure Selections.......................................... 19

4.5.1 Recommendation for Combing Routes of Exposures for Risk Assessment

19

4.5.2 Cancer Classification and Risk Assessment Recommendation................ 19

4.5.3 Summary of Points of Departure and Toxicity Endpoints Used in Human 

Risk Assessment ................................................................................................... 20

4.6 Endocrine Disruption............................................................................................ 21

5.0 Dietary Exposure/Risk Characterization ..................................................................... 22

5.1 Pesticide Metabolism............................................................................................ 22

5.1.1 Metabolism in Primary Crops................................................................... 22

5.1.2 Metabolism in Livestock........................................................................... 22

5.1.3 Drinking Water Residue Profile................................................................ 23

5.1.4 Food Residue Profile................................................................................. 24

5.2 Dietary Exposure and Risk ................................................................................... 27

5.2.1 Acute Dietary Exposure/Risk ................................................................... 28

5.2.2 Chronic Dietary Exposure/Risk ................................................................ 29

5.3 Anticipated Residue and Percent Crop Treated (%CT) Information.................... 29

6.0 Residential (Non-Occupational) Exposure/Risk Characterization ............................ 29

7.0 Aggregate Risk Assessments and Risk Characterization............................................ 30

8.0 Cumulative Risk Characterization/Assessment........................................................... 30
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9.0 Occupational Exposure/Risk Pathway.......................................................................... 31

Appendix A: Toxicology Assessment ....................................................................................... 31

A.1 Toxicology Data Requirements ................................................................................ 31

A.2 Toxicity Profiles........................................................................................................ 32

Appendix B: Physical and Chemical Properties..................................................................... 36

Appendix C: International Residue Limit Status................................................................... 37
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1.0 Executive Summary

Tepraloxydim is a herbicidal active ingredient (ai) intended for postemergence control of certain 

annual grasses and quackgrass, and is currently registered and formulated as EquinoxTM (1.67 lb 

ai/gal EC) for use on canola, cotton and soybean crops in the US. BASF Corporation, on behalf 

of Nippon Soda Company, submitted a petition (Petition No. 0E7788), proposing the 

establishment of tolerances for residues of the herbicide tepraloxydim and its metabolites 

convertible to GP [3-(tetrahydropyran-4-yl)pentane-1,5-dioic acid], calculated as tepraloxydim, 

in/on the following imported raw agricultural commodities grown in Canada: pea and bean, 

dried shelled, except soybean, subgroup 6C, and sunflower subgroup 20B.

Use Profile

BASF submitted a label for the 200 g/L (1.67 lb ai/gal) EQUINOX EC Herbicide which was 

previously labeled in Canada under the trade name ARAMOTM EC Herbicide (Canadian Reg.

No. 27603). The emulsifiable concentrate formulation is identical to EQUINOX EC Herbicide, 

registered in the U.S. (EPA Reg. No. 8033-12) on canola, cotton, fallow land, non-cropland, and 

soybeans. The label has been amended and approved by PMRA in April 2010 to include its use 

on the additional crops in Subgroup 6C and sunflower subgroup 20B. BASF noted that they

have no plans to apply for U.S. registration of EQUINOX use on the additional Subgroup 6C 

crops or on sunflower subgroup 20B crops at this time. Under the registered use pattern in 

Canada, tepraloxydim is applied as a broadcast foliar spray to crop subgroup 6C crops at up to 

0.045 lb ai/A (50 g ai/ha), and to sunflower subgroup 20B crops at up to 0.036 lb ai/A (40 g 

ai/ha), with preharvest intervals (PHIs) of 60 days for crops.

Toxicity/Hazard

The toxicological database for tepraloxydim is sufficient for the purpose of this risk assessment. The 

main target organs for tepraloxydim toxicity are the liver, the spleen/hematopoietic system and 

reproductive system. The reproductive system was affected at relatively high doses (in excess of 

LOAELs). Tepraloxydim also affected the hematopoietic system. Prenatal developmental toxicity

studies indicate that, relative to maternal animals, the developing rat fetus had increased quantitative 

and qualitative susceptibility to tepraloxydim while no increased susceptibility was evident in the 

developing rabbit fetus or rat pups. In both the acute and subchronic rat neurotoxicity studies, there 

were mild changes in motor activity and grip strength indices. None of the studies, including both 

neurotoxicity studies, reported treatment-related effects on brain weight or gross/microscopic lesions 

in the tissues of the nervous system.

Data are inadequate for an assessment of human carcinogenic potential because some evidence is 

suggestive of carcinogenic effects, but other equally pertinent evidence does not confirm,

therefore, quantification of human cancer risk is not required. The Agency, however, has 

determined that additional carcinogenicity studies are not required since the doses tested in both 

species, mice and rats, were adequate to assess the carcinogenic potential of tepraloxydim and 

that the chronic PAD (0.05 mg/kg/day) will adequately protect for all chronic effects, including 

carcinogenicity, likely to result from exposure to tepraloxydim.

Tepraloxydim has a low acute toxicity based on its classification in Toxicity Category III via the 

oral route, Toxicity Category III by the dermal route, and Toxicity Category IV by the inhalation 
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route of exposure. Tepraloxydim produces minimal eye irritation (Toxicity Category III), is a 

slight dermal irritant and is not a dermal sensitizer.

The 10X FQPA Safety Factor was retained for assessing the acute dietary risk (aRfD) for the 

general population in the form UFL since a LOAEL was used as the point of departure (i.e., a 

NOAEL was not identified in the critical study). Since NOAELs are used for assessing acute 

dietary risk of Females 13-49 and for chronic dietary exposure scenarios, the FQPA Safety 

Factor was reduced to 1X for these scenarios.

Drinking Water

No new estimated drinking water concentrations (EDWCs) were computed for the new 

tolerances on imported commodities from this petition. The estimated environmental 

concentrations (EECs) previously computed for surface water concentrations were used. Based 

on FIRST-IR modeling, the acute and chronic EECs are 1.4 and 0.7 μg/L, respectively.

Dietary Exposure (food and drinking water)

Unrefined dietary (food and drinking water) exposure analyses which were performed using the 

Dietary Exposure Evaluation Model (DEEM-FCIDTM, Version 2.03) indicate that acute and 

chronic dietary exposures to tepraloxydim from food and drinking water are well below HED’s 

level of concern (LOC) for tepraloxydim. Acute dietary exposure from food and drinking water 

at the 95th percentile of exposure represents <1% (0.74%) of the acute Population Adjusted Dose 

(aPAD) for the general U.S. population, and for children 1-2 years old, the most highly exposed 

subgroup, the exposure represents 2.2% of the aPAD. Chronic dietary exposure represents 2.4% 

of the chronic Population Adjusted Dose (cPAD) for the general U.S. population and 9.6% of the 

cPAD for children 1-2 years old, the population subgroup with the highest estimated chronic 

dietary exposure to tepraloxydim.

Residential Exposure

This document only presents the assessment of the proposed new tolerance for imported commodities. 

No residential uses are being requested at this time; therefore, no residential risk assessment has been 

conducted.

Aggregate Risk

There is no residential exposure expected for tepraloxydim; therefore, the sources considered in the 

aggregate assessment are food and drinking water. Because the dietary assessment incorporates 

exposure from both food and drinking water, the dietary assessment addresses concern from aggregate 

exposure. 

2.0 Regulatory Conclusions and Recommendations

Provided a revised Section F (OPPTS 860.1550) is submitted, HED can recommend for 

permanent tepraloxydim tolerances for the imported commodities in pea and bean, dried shelled, 

except soybean, subgroup 6C and sunflower subgroup 20B. Additional data are needed as outlined 

in Section 2.1 below. The specific tolerance recommendations are discussed in Section 2.2.
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2.1 Data Deficiencies

The following must be provided prior to a tolerance being established or registration 

allowed:

860.1550 Proposed Tolerance

A revised Section F must be submitted to propose a tolerance of 0.20 ppm for sunflower

subgroup 20B to harmonize with the established MRL for residues of tepraloxydim in/on

sunflower in Canada. 

Note to RD: The petitioner should be notified that the following data are required for 

domestic registrations: 

TOXICOLOGY

870.3465 28-Day Inhalation Toxicity Study

A guideline 28 day inhalation toxicity study is required to fulfill current 40 CFR Part 158 

data requirements.

870.7800 Immunotoxicity Study

A guideline immunotoxicity study is required to fulfill current 40 CFR Part 158 data 

requirements. A guideline immunotoxicity submission is expected by the end of 2011.

RESIDUE CHEMISTRY

860.1650 Submittal of Analytical Reference Standards

The following reference standards for tepraloxydim metabolites in the National Pesticide 

Standards Repository have expired and the registrant is urged to submit new standards 

with new lot numbers or to recertify the lot numbers of the standard in the repository. 

The new standard or updated certificate of analysis must be sent to the Pesticide 

Repository. 

a) BH 620-DML (expired on 10/1/2010)

b) BH 620-OH-DMP (expired on 10/1/2010)

2.2 Tolerance Considerations

2.2.1 Enforcement Analytical Method

An adequate gas chromatography/mass spectrometry (GC/MS) enforcement method, BASF 

Analytical Method D9701/1, is available for the enforcement of tolerances for plant 

commodities. The method has been reported and reviewed in detail in conjunction with earlier 
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petitions (PP#8F04945, D243962, L Cheng, 10/3/2000 and PP#6E7046, D328044, N. Dodd, 

6/19/2007). The method is designed to determine the total residues of tepraloxydim and its 

metabolites. Parent tepraloxydim and related metabolites containing the 3-

tetrahydropyranylpentane-1,5-dione moiety are converted by oxidation to GP, and GP residues 

are subsequently methylated and determined as DMP (dimethyl 3-(tetrahydropyran-4-yl)pentane1,5-dioate). Residues of 5-OH-DP and related 5-hydroxy-metabolites containing the 3-hydroxy3-tetrahydropyranylpentane-1,5-dione moiety are oxidized to OH-GP and are subsequently 

methylated and quantified as OH-DMP (dimethyl 3-hydroxy-3-(tetrahydroxypyran-4-yl)pentane1,5-dioate). Ions 168, 182, and 213 are monitored for DMP, with ion 182 the typical quantitation 

ion. Ions 143 and 175 are monitored for OH-DMP, with ion 143 the typical quantitation ion. 

Residues are reported in terms of parent equivalents. The validated limit of quantitation (LOQ) 

for each of the residues of tepraloxydim and 5-OH-DP is 0.05 ppm. BASF Method D9701/1 has 

been successfully radiovalidated and has undergone an independent laboratory validation (ILV). 

HED has determined that a tolerance method validation by the Agency’s analytical laboratory is 

not necessary. 

Adequate GC/MS enforcement methods, BASF Analytical Method Nos. 389/0 and 975/1, are 

available for determining residues in livestock. The methods have been reported and also 

reviewed in detail in conjunction with the earlier petitions for tolerances for residues of 

tepraloxydim in or on imported commodities (PP#8F04945, D243962, L Cheng, 10/3/2000 and 

PP#6E7046, D328044, N. Dodd, 6/19/2007). The LOQ for residues of tepraloxydim, 5-OH-DP, 

and DL are 0.01 ppm each in milk, 0.05 ppm each in eggs, and 0.05 ppm each in livestock 

tissues. HED has determined that based on the successful radiovalidation and ILV studies on 

BASF Analytical Method Nos. 389/0 and 975/1, a tolerance method validation in the Agency’s 

analytical laboratory is not necessary.

A liquid chromatography/tandem mass spectrometry (LC/MS/MS) method (BASF Analytical 

Method D9704) is available for data collection in plant commodities. The method is a 

confirmatory method for the enforcement method in plants. It is a common moiety method and 

determines the residues of tepraloxydim and its metabolites containing the 3-

tetrahydropyranylpentane-1,5-dione moiety which are converted by oxidation to GP and 

determined as GP; and residues of metabolite 5-OH-DP and related hydroxy metabolites 

containing the 3-hydroxy-3-tetrahydropyranylpentane-1,5-dione moiety which is oxidized to 

OH-GP and determined as OH-GP. Residues of GP and OH-GP are expressed as the parent 

using molecular weight conversion factors. A slightly modified method (BASF Analytical 

Method D9704/1) was used to analyze the residues of tepraloxydim and its metabolites from the 

submitted crop field trials in support of the current petition. The validated LOQ for the 

combined residues of tepraloxydim and its metabolites in both dry bean seeds and sunflower 

seeds is 0.10 ppm (0.05 ppm for tepraloxydim derived from GP, and 0.05 ppm for 5-OH-DP 

derived from OH-GP).

2.2.2 International Harmonization

There are no Codex MRLs for residues of tepraloxydim. A Canadian MRL has been established 

for residues of tepraloxydim and its metabolites convertible to 3-perhydropyran-4-ylglutaric acid 

(GP) and 3-hydroxy-3-perhydropyran-4-ylglutaric acid (OH-GP), expressed as parent equivalent, 
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in sunflower crop subgroup 20B and dried shelled pea and bean, except soybean, crop subgroup 

6C. The US tolerance expression for plants is harmonized with the Canadian expression. An 

International Residue Limit (IRL) status sheet is appended to this document as Appendix C.

2.2.3 Recommended Tolerances

HED has examined the residue chemistry database for tepraloxydim. Pending submission of a

revised Section F, there are no residue chemistry issues that would preclude establishment of 

tolerances for residues of tepraloxydim as follows:

Pea and bean, dried shelled, except soybean, subgroup 6C ........... 0.10 ppm

Sunflower subgroup 20B ................................................................0.20 ppm

The tolerances for lentil, seed and pea, dry, seed should be revoked, as these are covered by the 

new subgroup 6C tolerance.

The tolerance expression for tepraloxydim in 40 CFR §180.573(a)(1), (a)(2), and (c) should be 

stated according to HED’s Interim Guidance on Tolerance Expression (5/27/09, S. Knizner) as 

follows:

40 CFR §180.573(a)(1)

“Tolerances are established for residues of tepraloxydim, including its metabolites and 

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

specified below is to be determined by measuring only the combined residues of tepraloxydim 

(2-[1-[[[(2E)-3-chloro-2-propen-1-yl]oxy]imino]propyl]-3-hydroxy-5-(tetrahydro-2H-pyran-4-

yl)-2-cyclohexen-1-one) and its metabolites convertible to GP (3-(tetrahydropyran-4-yl)pentane1,5-dioic acid) and OH-GP (3-hydroxy-3-(tetrahydropyran-4-yl)pentane-1,5-dioic acid), 

calculated as tepraloxydim.”

40 CFR §180.573(a)(2)

“Tolerances are established for residues of tepraloxydim, including its metabolites and 

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

specified below is to be determined by measuring only the combined residues of tepraloxydim 

(2-[1-[[[(2E)-3-chloro-2-propen-1-yl]oxy]imino]propyl]-3-hydroxy-5-(tetrahydro-2H-pyran-4-

yl)-2-cyclohexen-1-one) and its metabolites convertible to GP (3-(tetrahydropyran-4-yl)pentane1,5-dioic acid), OH-GP (3-hydroxy-3-(tetrahydropyran-4-yl)pentane-1,5-dioic acid), and GL (3-

(2-oxotetrahydropyran-4-yl)-1,5-dioic acid), calculated as tepraloxydim,”

40 CFR §180.573(c)

“A tolerance with regional registration, as defined in §180.1(m), is established for residues of 

tepraloxydim, including its metabolites and degradates, in or on the commodities in the table 

below. Compliance with the tolerance levels specified below is to be determined by measuring 

only the combined residues of tepraloxydim (2-[1-[[[(2E)-3-chloro-2-propen-1-

yl]oxy]imino]propyl]-3-hydroxy-5-(tetrahydro-2H-pyran-4-yl)-2-cyclohexen-1-one) and its 

metabolites convertible to GP (3-(tetrahydropyran-4-yl)pentane-1,5-dioic acid) and OH-GP (3-

hydroxy-3-(tetrahydropyran-4-yl)pentane-1,5-dioic acid), calculated as tepraloxydim.”
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2.2.4 Revisions to Petitioned-For Tolerances

The proposed tolerance of 0.25 ppm for imported sunflower subgroup 20B should be modified to 

0.20 ppm to harmonize with the established Canadian MRL.

Table 1. Tolerance Summary for Tepraloxydim.

Commodity Proposed Tolerance

(ppm)

Recommended Tolerance

(ppm)

Comments

(correct commodity definition)

40 CFR §180.573

Pea and bean, dried shelled, 

except soybean, subgroup 

6C

0.10 0.10

Sunflower subgroup 20B 0.25 0.20

3.0 Ingredient Profile

3.1 Summary of Proposed Uses

Tepraloxydim is a selective broad-spectrum cyclohexene oxime herbicide intended for 

postemergence control of certain annual grasses and quackgrass. Tepraloxydim is a systemic 

herbicide that enters the target weed through the foliage and translocates throughout the plant, 

inhibiting acetyl-coenzyme A carboxylase (ACCase) in the plant. Tolerances were previously

established in support of U.S. uses of tepraloxydim on canola, cotton, and soybean, and for 

imported commodities of flax, dry pea, and lentil from Canadian uses. Under the registered use 

pattern in Canada, tepraloxydim is applied to sunflower subgroup 20B crops and Crop Group 6, 

subgroup 6C, Dried shelled pea and bean (except soybean) crops.

BASF submitted a label for the 200 g/L (1.67 lb ai/gal) EQUINOX EC Herbicide which was 

previously labeled in Canada under the trade name ARAMOTM EC Herbicide (Canadian Reg.

No. 27603). The emulsifiable concentrate formulation is identical to EQUINOX EC Herbicide, 

registered in the U.S. (EPA Reg. No. 8033-12) on canola, cotton, fallow land, non-cropland, and 

soybeans. The label has been amended and approved by PMRA in April 2010 to include its use 

on the additional crops in Subgroup 6C and sunflower subgroup 20B. BASF noted that they

have no plans to apply for U.S. registration of EQUINOX use on the additional Subgroup 6C 

crops or on sunflower subgroup 20B crops at this time. Under the registered use pattern in 

Canada, tepraloxydim is applied as a broadcast foliar spray to crop group 6, subgroup 6C crops 

at up to 0.045 lb ai/A (50 g ai/ha), and to sunflower subgroup 20B crops at up to 0.036 lb ai/A 

(40 g ai/ha), with preharvest intervals (PHIs) of 60 days for crops.

The summary of the proposed use directions for the intended crops is summarized in Table 2. 
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Table 2. Summary of Directions for Use of Tepraloxydim in Canada

Applic. 

Timing, Type, 

and Equip.

Formulation

Applic. Rate 

g ai/ha

(lb ai/A)

Max. No. 

Applic. per 

Season

Max. Seasonal 

Applic. Rate

g ai/ha

(lb ai/A)

PHI

(days)

Use Directions and 

Limitations

Crop Group 6, subgroup 6C, Dried shelled pea and bean (except soybean). Includes Lupinus, spp: (grain lupin,

sweet, white and white sweet lupin); Phaseolus, spp. (field bean, kidney bean, lima bean (dry), navy bean, pinto 

bean, tepary bean); Vigna spp (adzuki bean, blackeyed pea, catjang, cowpea, Chowder pea, moth bean, mung 

bean, rice bean, southern pea, urd bean); Broad bean (dry), chickpea, quard, lablab bean; lentil pea); Pisum spp. 

(field pea and pigeon pea). 1

Postemergence,

Broadcast, 

Foliar

Ground 

equipment

EQUINOX 

EC 

Herbicide 2

(1.67 lb 

ai/gal)

50

(0.045) NS4

50

(0.045) 60

Add Merge® (0.5% v/v) 

or DASH HC (0.41% v/v) 

adjuvant to tank mix. 

Application may be made 

from emergence to the 7-

trifoliate leaf stage for dry 

beans and from 

emergence to 9 leaf for 

dry pea. Do not apply 

EQUINOX EC herbicide 

by air.

Sunflower Subgroup 20B (sunflower seed, Calendula; castor oil plant; chinese tallow tree; euphorbia; evening 

primrose; jojoba; niger seed; rose hip; safflower; stokes aster; tallowood; tea oil plant; vernonia; cultivars, 

varieties, and/or hybrids of these) 3

Postemergence,

Broadcast, 

Foliar

Ground 

Equipment

EQUINOX 

EC 

Herbicide

1.67 lb/gal 

EC

33-40

(0.029-0.036) NS4

40

(0.036) 60

Application is made from 

emergence to 10 leaf 

stage. Add Merge® 

(0.5% v/v) or DASH HC 

(0.41% v/v) adjuvant to 

tank mix. Application is 

made at emergence to 10-

leaf stage. Do not apply 

EQUINOX EC herbicide 

by air.

1 Dry bean variety (of the genera Phaseolus, Lupinus and Vigna) may vary in their tolerance to herbicides, including 

to EQUINOX EC herbicide. Since not all dry bean varieties have been tested for tolerance to EQUINOX EC 

herbicide, first use of EQUINOX EC herbicide should be limited to a small area of each variety to confirm tolerance 

prior to adoption as a general field practice. Additionally, consult your seed supplier for information on the 

tolerance of specific varieties of dry beans to EQUINOX EC herbicide. 

2

For sale and use in the Prairie provinces and Peace River region of British Columbia only.

3All types including imazethapyr and imazamox tolerant sunflower with the CLEARFIELD trait.

4NS= not specified on label.

3.2 Structure and Nomenclature

Structure and nomenclature of tepraloxydim are reported in Table 3.
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Table 3. Tepraloxydim Structure and Nomenclature.

Chemical structure

O

OH

O

N

O Cl

CH3

Molecular Formula C17H24ClO4

Common name Tepraloxydim 1

Company experimental name BAS 620 H; DP

IUPAC name (5RS)-2-{(EZ)-1-[(2E)-3-chloroallyloxyimino]propyl}-3-hydroxy-5-

perhydropyran-4-ylcyclohex-2-en-1-one

CAS name 2-[1-[[[(2E)-3-chloro-2-propen-1-yl]oxy]imino]propyl]-3-hydroxy-5-(tetrahydro2H-pyran-4-yl)-2-cyclohexen-1-one

CAS registry number 149979-41-9

End-use product/EP AramoTM EC herbicide, Reg. No. 27603; a 1.67 lb ai/gal EC (200 g ai/L EC)

(same as EquinoxTM herbicide, EPA Reg. No. 8033-12; 1.67 lb ai/gal EC)

Chemical Class Cyclohexene oxime herbicide

Known Impurities of Concern None

Chemical structure:

Metabolite 

O

OH

O

N

O Cl

CH3

OH

Common name Metabolite: 5-OH-DP; BH 620-5-OH-DP

Chemical name 2-[1-[[[(2E)-3-chloro-2-propen-1-yl]oxy]imino]propyl]-3,5-hydroxy-5-

(tetrahydro-2H-pyran-4-yl)-2-cyclohexen-1-one

Chemical structure:

Oxidation product determined 

by analytical method 

O

COOH

COOH

Common name GP; BH 620-GP

Chemical name 3-(tetrahydropyran-4-yl)pentane-1,5-dioic acid
Page 13 of 37

Table 3. Tepraloxydim Structure and Nomenclature.

Chemical structure:

Oxidation product determined 

by analytical method

O

COOH

COOH

OH

Common name OH-GP; BH 620-OH-GP

Chemical name 3-hydroxy-3-(tetrahydropyran-4-yl)pentane-1,5-dioic acid

3.3 Physical and Chemical Properties

The physicochemical properties of tepraloxydim are reported in Appendix B. 

3.4 Anticipated Exposure Pathways

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

proposed new uses of tepraloxydim on imported dry bean and dry pea subgroup 6C and 

sunflower subgroup 20B commodities. For domestic uses, humans may be exposed to 

tepraloxydim in food and drinking water, since tepraloxydim may be applied directly to growing 

crops and application may result in tepraloxydim reaching surface and ground water sources of 

drinking water. In an occupational setting, applicators may be exposed while handling the 

pesticide prior to application, as well as during application. There is a potential for postapplication exposure for workers re-entering treated fields. There are no residential uses of 

tepraloxydim; thus, there is no exposure in residential or non-occupational settings. 

Several risk assessments have been previously prepared for the existing uses of tepraloxydim. 

This risk assessment considers all of the aforementioned exposure pathways based on the 

proposed new uses of tepraloxydim, 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 
Page 14 of 37

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, nondietary exposures based on home use of pesticide products and associated risks 

for adult applicators and for toddlers, youths, and adults entering or playing on treated areas 

post-application are evaluated. Further considerations are currently in development as OPP has 

committed resources and expertise to the development of specialized software and models that 

consider exposure to bystanders and farm workers as well as lifestyle and traditional dietary

patterns among specific subgroups.

4.0 Hazard Characterization/Assessment

References:

TEPRALOXYDIM – Human Health Risk Assessment for Tolerances on Imported Dry Pea, Flax and 

Lentil, S. Winfield, DP Number: 328441, 7/20/07

TEPRALOXYDIM – Report of the Hazard Identification Assessment Review Committee, G. Dannan, 

HED Doc. No.: 014515, DP Number: 243962, 2/26/01.

TEPRALOXYDIM – Report of the FQPA Safety Factor Committee, B. Tarplee, HED Doc. No. 014403, 

12/13/00.

The most recent risk assessment was supported by the HED HIARC report (HED Doc. No. 

014515, 2/26/01). HED has reevaluated the existing toxicity database in accordance with the 

2002 FQPA policy and has retained the 10X FQPA Safety Factor for lack of a NOAEL in the 

acute neurotoxicity study (aRfD, general population including infants and children). HED is no 

longer requiring a developmental neurotoxicity (DNT) study. Additionally, with the recent 

submission of a positive control dataset, the 870.6200 Neurotoxicity Battery has been upgraded 

to Acceptable/Guideline.

4.1 Toxicology Studies Available for Analysis

The existing toxicity database is adequate to characterize hazard and support the existing and 

requested food tolerances for tepraloxydim.

The following studies are available for consideration:

• Subchronic: Dietary 90-day toxicity (rat); dietary 90-day toxicity (dog)

• Developmental: rat and rabbit developmental toxicity studies 

• Reproduction: 2-generation reproduction (rat) 

• Chronic: chronic oral toxicity and carcinogenicity studies (rat); oral carcinogenicity (mouse); 

one-year oral toxicity (dog)

•Neurotoxicity: Acute and 90-day oral

• Mutagenicity battery

• Metabolism in rats

•Mode of action studies

• Several toxicity studies with 5-OH-tepraloxydim (5-OH-DP)
Page 15 of 37

4.2 Absorption, Distribution, Metabolism, Excretion (ADME)

Based on pharmacokinetics/metabolism studies in the rat, tepraloxydim is readily and almost 

completely absorbed after oral administration, but is rapidly excreted mainly via the urine. 

Biliary excretion was approximately 3 times greater than fecal elimination which suggests 

enterohepatic recirculation. The rat plasma half-life of radiolabeled tepraloxydim is 

approximately 4.4 and 10 hours at the low and high dose, respectively. No accumulation of 

radioactivity was observed in any tissue at 120 hours post-dosing. Numerous metabolites were 

detected in the urine, feces, and bile; the main metabolic pathway being oxidation of the pyran 

ring to lactone via a hydroxy metabolite, and cleavage of the oxime ether group with the imine 

and oxazol as products. At near plasma tmax (one hour post dosing), the plasma, liver, and kidney

contained the parent compound almost exclusively. The results indicate that the distribution, 

metabolism, and excretion of tepraloxydim are independent of dose level, sex, route of 

administration (oral vs. i.v.), and site of label (pyran vs. cyclohexanone).

4.2.1 Dermal Absorption

The dermal absorption rate was estimated from the results of the 28-day dermal toxicity study in 

rats (MRID 44467140) and the developmental rat toxicity studies (MRID 44467203/44467204). 

In the oral developmental toxicity study, the maternal NOAEL/LOAELs were 120/360 

mg/kg/day based on reduced maternal body weight gain and food intake. In the 28-day rat 

dermal toxicity study, there were no treatment-related clinical signs, or effects on body weight, 

food consumption, hematology, clinical chemistry, or organ weights. The systemic and dermal 

NOAEL was the limit dose of 1000 mg/kg/day and the LOAEL was unidentified. Assuming the 

dermal LOAEL is the limit dose of 1000 mg/kg/day, an approximate dermal absorption rate of 

36% was derived by relating the ratio of the LOAELs from the oral and dermal studies 

(360/1000 x 100). This conservative approach results in a dermal absorption rate of 36%. 

4.3 Toxicological Effects

The main target organs for tepraloxydim toxicity are the liver, the spleen/hematopoietic system 

and reproductive system. All subchronic and chronic toxicity/carcinogenicity feeding studies 

had one or more of these liver findings: increased incidences of hepatocellular foci, abnormal 

liver function parameters, increased relative liver weight, hepatocyte hypertrophy, in addition to 

increased hepatocellular neoplasms in the mouse and rat carcinogenicity studies. Bile 

accumulation including crystalline material was also reported within the liver cells and canaliculi 

at the relatively high dose of 325 mg/kg/day in the 13-week dog study. In a non-guideline rat 

oral feeding study, tepraloxydim weakly induced pentoxyresorufin-O-deethylase activity

(cytochrome P-450 activity), typically induced by polynuclear aromatic hydrocarbons such as 3-

methylcholanthrene; however, it failed to induce peroxisomal β-oxidation or alter the glutathione 

cellular levels.

The reproductive system is a major target but was affected at relatively high doses (in excess of 

LOAELs established in repeat-dose mouse, rat and dog studies). In the mouse carcinogenicity 

feeding study, tepraloxydim caused morphological microscopic changes indicative of reduced 

secretory activity in the seminal vesicles and preputial glands in male mice. Increased uterine 
Page 16 of 37

sclerosis, decreased corpora lutea, and decreased follicles were observed in female mice. The 

frequencies of the changes were dose-dependent in the mid- and high-dose males (332 and 1035 

mg/kg/day) and females (490 and 1456 mg/kg/day). Additionally, increased incidences of focal 

calcification of the testes were observed in the high dose group (155 mg/kg/day) of the rat 

carcinogenicity feeding study. The male dog sex organs were also affected at high doses (325 

mg/kg/day) as evidenced in the 13-week toxicity study, by reduced epididymal and testicular 

weights associated with atrophy and azoospermia, and, in the supplementary one-year study, by 

diminished epididymal and prostatic secretory activities which were accompanied by a marked 

loss of acinar lumina and a moderate interacinar sclerosis at 248 mg/kg/day.

Tepraloxydim also affected the hematopoietic system. In dogs, hemolytic anemia was 

demonstrated by depressed hematocrit, hemoglobin, and RBCs as early as day 40/41 among the 

high dose (325 mg/kg/day) animals. Similar effects were also reported in dogs dosed at 248 

mg/kg/day beginning on Day 88 and throughout the one-year study period. These changes were 

accompanied by compensatory responses, including splenic hematopoiesis, femoral and sternal 

bone marrow hyperplasia, increased erythroid precursors and hemosiderin-laden macrophages, 

and splenic hemosiderosis. 

Prenatal developmental toxicity studies indicate that, relative to maternal animals, the developing 

rat fetus had increased quantitative and qualitative susceptibility to tepraloxydim while no 

increased susceptibility was evident in the developing rabbit fetus or rat pups. In the rat 

developmental toxicity study, the developmental toxicity LOAEL of 120 mg/kg/day, based on 

reduced fetal body weights, delayed ossification and the occurrence of hydroureter, is 3-fold less 

than the maternal toxicity LOAEL of 360 mg/kg/day, which is based on reduced body weight 

and body weight gain. There were additional developmental anomalies or malformations in the 

observed at 360 mg/kg/day, such as dilatation of both heart ventricles and filiform tails that were 

observed externally and corresponded to absent caudal and sacral vertebrae. In contrast, no 

developmental effects were seen in the rabbit prenatal toxicity study up to the highest tested dose 

of 180 mg/kg/day which was considered to be the maternal LOAEL due to reduced maternal 

body weight and food consumption (maternal NOAEL = 60 mg/kg/day). Also, in the rat 

multigeneration reproduction study, there was no increase in susceptibility since the NOAEL and 

LOAEL (50.6 and 260.0 mg/kg/day, respectively) were equal for both the offspring 

developmental systemic toxicity and the parental systemic toxicity. Further, there were no 

effects on any of the measured reproductive parameters up to and including the highest tested 

dose (reproductive NOAEL ≥260 mg/kg/day).

In both the acute and subchronic rat neurotoxicity studies, there were mild changes in motor 

activity and grip strength indices. On day 0 of the acute oral neurotoxicity study in rats, motor 

activity was decreased (by up to 40%) in all treated female groups (500, 1000 and 2000 mg/kg) 

while forelimb grip strength was slightly increased (by up to 28%) in all treated females. In the 

rat subchronic neurotoxicity study, motor activity was increased in the high dose females (428 

mg/kg/day in males and 513 mg/kg/day in females) at day 50 (37%) and in both sexes on day 85 

(28-44%). None of the studies, including both neurotoxicity studies, reported treatment-related 

effects on brain weight or gross/microscopic lesions in the tissues of the nervous system.
Page 17 of 37

Tepraloxydim has a low acute toxicity based on its classification in Toxicity Category III via the 

oral route, Toxicity Category III by the dermal route, and Toxicity Category IV by the inhalation 

route of exposure (Appendix Table A.2.1). Tepraloxydim produces minimal eye irritation 

(Toxicity Category III), is a slight dermal irritant, and is not a dermal sensitizer.

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

A 10X FQPA Safety Factor is retained for assessing the acute dietary risk (aRfD) for the general 

population in the form UFL since a LOAEL was used as the point of departure (i.e., a NOAEL 

was not identified in the critical study). However the critical effect observed at the LOAEL of 

500 mg/kg/day was neither severe nor irreversible; a dose-responsive decrease in motor activity

was observed in females on Day 0 in the absence of any other treatment related clinical signs 

(including FOB) or neurohistopathological effects. The dose-response relationship of 

tepraloxydim indicates that an uncertainty factor of 10X is sufficiently protective against the 

critical effect and any other adverse effects at the aRfD.

Since NOAELs are used for assessing acute dietary risk of Females 13-49 and for chronic dietary

exposure scenarios, the FQPA Safety Factor is reduced to 1X for these scenarios.

4.4.1 Completeness of the Toxicology Database

The toxicity database is complete except for immunotoxicity testing (OPPTS Guideline 

870.7800). Recent changes to 40 CFR §158 make these studies required for pesticide 

registration. Although immunotoxicity studies have not yet been submitted, there is no evidence 

of immunotoxicity in any study in the toxicity database for tepraloxydim. In the absence of 

specific immunotoxicity studies, EPA has evaluated the available tepraloxydim toxicity database 

to determine whether an additional database uncertainty factor is needed to account for potential 

immunotoxicity. No evidence of immunotoxicity was found. Treatment-related effects seen in 

the spleen (splenic hematopoiesis) and bone marrow (hyperplasia) are compensatory responses 

to tepraloxydim-induced hemolytic anemia. 

Due to the lack of evidence of immunotoxicity for tepraloxydim, EPA does not believe that 

conducting immunotoxicity study will result in a NOAEL less than that to derive the current 

cRfD of 5 mg/kg bw/day. Consequently, the EPA believes the existing data are sufficient for 

endpoint selection for exposure/risk assessment scenarios and for evaluation of the requirements 

under the FQPA, and an additional database uncertainty factor does not need to be applied.

A 28-day rat inhalation toxicity study was required in previous risk assessments based on 

expected exposure patterns. This study remains pending.
Page 18 of 37

4.4.2 Evidence of Neurotoxicity

In the acute oral neurotoxicity study in rats, decreased motor activity was observed on Day 0 

(29-41% below control, p < 0.05 for females, NS for males) and sustained until Day 7 in middose females only (~30%, 1000 mg/kg/day; p < 0.01). In the subchronic neurotoxicity study, 

increased motor activity was observed in females on Day 50 (28-44% above control) in both 

sexes on Day 85 at the highest dose tested (428 mg/kg/day, males; 513 mg/kg/day, females). 

HED priorly recommended a developmental neurotoxicity study (DNT). However, upon 

reevaluation of the data in accordance with the 2002 FQPA 10X Guidance Document, HED has

since concluded that there is no need for a DNT study. This decision is based on the following 

weight-of-evidence considerations: 1) neurotoxic effects (changes in motor activity and grip 

strength) were seen at high doses of 500 mg/kg (1⁄4 of the limit dose), 1000 mg/kg, and 2000 

mg/kg following bolus (gavage) dosing and at 428 mg/kg/day in males and 513 mg/kg/day in 

females following dietary administration in the subchronic neurotoxicity study; 2) in the twogeneration reproduction study, no clinical signs indicative of neurotoxicity were seen in the 

parental animals or offspring, nor was there evidence for increased susceptibility (the offspring 

LOAEL was 260 mg/kg/day based on decreased body weight/body weight gain during lactation; 

and 3) because the DNT will have to utilize testing of high doses (in order to elicit 

neurotoxicity), it will not yield a dose lower than that currently used for acute (40 mg/kg [aPAD 

=0.4 mg/kg/day] and 50 mg/kg [aPAD = 0.5 mg/kg/day]) and chronic (5 mg/kg/day [cPAD = 

0.05 mg/kg/day]) dietary risk assessments (there are no residential uses).

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

There are qualitative and quantitative prenatal susceptibility in the rat developmental toxicity

study. The developmental findings with a NOAEL of 40 mg/kg/day were well characterized and 

included increased developmental sensitivity in the form of reduced fetal body weights, delayed 

ossification (indicative of delayed maturation) and the presence of hydroureter at 120 mg/kg/day

(developmental LOAEL). Rare malformations (dilatation of both heart ventricles and filiform 

tail) were also detected at the high dose of 360 mg/kg/day. The maternal toxicity

NOAEL/LOAEL of 120/360 mg/kg/day was based on reduced body weight gain and food 

consumption. There are no qualitative or quantitative pre- or postnatal susceptibility issues in 

the available developmental toxicity study in rabbits and two-generation reproduction toxicity

study in rats.

There was no evidence of increased susceptibility following prenatal exposure to rabbits, nor was 

there evidence of increased susceptibility following pre- and/or postnatal exposure to rats (in the 

rat reproduction and fertility effects study). The degree of concern is low for the increased 

susceptibility seen in the developmental study in rats (prenatal exposure) since a clear 

NOAEL/LOAEL was established for developmental toxicity, and since the endpoints of concern 

are used for the most sensitive population of concern (i.e., Females 13-49). There is no residual 

uncertainty for pre- and/or postnatal toxicity.
Page 19 of 37

4.4.4 Residual Uncertainty in the Exposure Database

The database is adequate and there are no residual uncertainties for pre- and/or postnatal toxicity. 

Furthermore, there are no additional residual uncertainties with respect to exposure data. The 

dietary food exposure assessment utilizes proposed tolerance level residues and 100% CT 

information for all commodities. The drinking water assessment (screening level, Tier 1 

estimates) utilizes values generated by models and associated modeling parameters which are 

designed to provide conservative, health protective, high-end estimates of water concentrations. 

By using these screening-level assessments, acute and chronic dietary exposures/risks will not be 

underestimated. Additionally, there is no potential for residential exposure based on proposed 

and registered use patterns.

4.5 Toxicity Endpoint and Point of Departure Selections

4.5.1 Recommendation for Combining Routes of Exposures for Risk Assessment

As per FQPA, 1996, when there are potential residential exposures to a pesticide, aggregate risk 

assessment must consider exposures from three major sources: oral, dermal and inhalation 

exposures. An aggregate exposure risk assessment was not conducted because there are no 

residential uses for tepraloxydim at this time. However, aggregate food and drinking water 

exposures are considered in this assessment.

4.5.2 Cancer Classification and Risk Assessment Recommendation

In accordance with the 1999 EPA’s Draft Guidelines for Carcinogen Risk Assessment (March, 

2005), tepraloxydim was classified as "Data are inadequate for an Assessment of human 

carcinogenic potential because some evidence is suggestive of carcinogenic effects, but other 

equally pertinent evidence does not confirm a concern. The Agency, however, has determined 

that additional carcinogenicity studies are not required since the doses tested in both species, 

mice and rats, were adequate to assess the carcinogenic potential of tepraloxydim. The 

carcinogenicity study in mice was tested at the Limit Dose and in the rats, the highest dose tested 

resulted in liver tumors. The classification was based on the following weak and/or conflicting 

evidence for carcinogenicity (TXR No. 0014487):

 In rats, there was some evidence of carcinogenicity in the females based on an increased 

incidence of liver tumors only at the high dose in the carcinogenicity phase of the study, 

but was not supported by the results of the chronic phase in the same strain and sex of 

rats. 

 In mice, liver tumors were seen in females only at an excessively toxic dose. 

The CARC concluded that a cancer risk is not of a concern based on the following weight of 

evidence considerations:

 The liver tumors in female rats were seen only at the high dose (i.e., lack of dose 

response);

 The incidences of these tumors were within the ranges for the historical controls;
Page 20 of 37

 The liver tumors observed in one study were not seen in a parallel study conducted at the 

same dose and duration (i.e, tumorogenic potential not replicated); 

 In mice, liver tumors in were seen only at excessive doses (i.e., greater than the Limit 

Dose of 1000 mg/kg/day) which may have resulted in indirect effects that may not be 

present at lower doses;

 The liver tumors did not result in reduced latency in either species; 

 There is no concern for mutagenicity/genotoxicity; and 

 The NOAEL of 5 mg/kg/day used for deriving the chronic RfD is approximately 55-fold 

lower than the lowest dose (272 mg/kg/day) that induced liver tumors in rats.

Thus, for all these reasons, the Agency has determined that the chronic PAD (0.05 mg/kg/day) 

will adequately account for all chronic effects, including carcinogenicity, likely to result from 

exposure to tepraloxydim.

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

Assessment

Table 4. Summary of Toxicological Doses and Endpoints for Tepraloxydim for Use in Dietary and NonOccupational Human Health Risk Assessments

Exposure/ 

Scenario

Point of 

Departure

Uncertainty/FQP

A Safety Factors

RfD, PAD, 

Level of 

Concern for 

Risk 

Assessment

Study and Toxicological Effects

Acute Dietary 

(General 

Population, 

including 

Infants and 

Children)

LOAEL = 

500 mg/kg

UFA= 10 x

UFH= 10 x

FQPA SF retained 

as UFL = 10 x

Acute RfD = 

0.5 mg/kg

aPAD = 0.5 

mg/kg

Acute neurotoxicity screening battery 

LOAEL = 500 mg/kg based on decreased 

motor activity in females. (The NOAEL 

is not identified.)

Acute Dietary

(Females 13-

49 years of 

age)

NOAEL= 40 

mg/kg

UFA= 10 x

UFH= 10 x

FQPA SF = 1 x

Acute RfD = 

0.4 mg/kg

aPAD = 0.4 

mg/kg

Rat developmental toxicity 

LOAEL = 120 mg/kg based on findings of 

reduced ossification indicative of delayed 

maturation, and the occurrence of 

hydroureter.

Chronic 

Dietary (All 

Populations)

NOAEL=5 

mg/kg/day

UFA= 10 x

UFH= 10 x

FQPA SF= 1 x

Chronic RfD 

= 0.05 

mg/kg/day

cPAD = 0.05 

mg/kg/day

Rat carcinogenicity study 

LOAEL = 30 mg/kg/day based on male 

liver microscopic lesions (eosinophilic 

foci).

Incidental Oral 

Short- and

IntermediateTerm (1-30 

days; 1-6 

months)

These exposure scenarios do not apply to this risk assessment because there are no proposed or 

registered residential uses of tepraloxydim.
Page 21 of 37

Table 4. Summary of Toxicological Doses and Endpoints for Tepraloxydim for Use in Dietary and NonOccupational Human Health Risk Assessments

Exposure/ 

Scenario

Point of 

Departure

Uncertainty/FQP

A Safety Factors

RfD, PAD, 

Level of 

Concern for 

Risk 

Assessment

Study and Toxicological Effects

Dermal Shortand 

IntermediateTerm (1-30 

days; 1-6 

months)

These exposure scenarios do not apply to this risk assessment because there are no proposed or 

registered residential uses of tepraloxydim.

Inhalation 

Short- and 

IntermediateTerm (1-30 

days; 1-6 

months)

These exposure scenarios do not apply to this risk assessment because there are no proposed or 

registered residential uses of tepraloxydim.

Cancer (oral, 

dermal, 

inhalation)

The CARC placed tepraloxydim into category "Data are inadequate for an assessment of human 

carcinogenic potential" because some evidence is suggestive of carcinogenic effects, but other 

equally pertinent evidence does not confirm a concern" and determined that the quantification of 

human cancer risk is not required (CARC report dated 2/27/01, TXR 0014487).

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

mark the beginning of extrapolation to determine risk associated with lower environmentally relevant human exposures. NOAEL 

= no observed adverse effect level. LOAEL = lowest observed adverse effect level. UF = uncertainty factor. UFA = 

extrapolation from animal to human (interspecies). UFH = potential variation in sensitivity among members of the human 

population (intraspecies). UFL = use of a LOAEL to extrapolate a NOAEL. UFS = use of a short-term study for long-term risk 

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

= population adjusted dose (a = acute, c = chronic). RfD = reference dose. MOE = margin of exposure. LOC = level of concern. 

N/A = not applicable.

4.6 Endocrine Disruption

As required under FFDCA section 408(p), EPA has developed the Endocrine Disruptor 

Screening Program (EDSP) to determine whether certain substances (including pesticide active 

and other ingredients) may have an effect in humans or wildlife similar to an effect produced by 

a “naturally occurring estrogen, or other such endocrine effects as the Administrator may

designate.” The EDSP employs a two-tiered approach to making the statutorily required 

determinations. Tier 1 consists of a battery of 11 screening assays to identify the potential of a 

chemical substance to interact with the estrogen, androgen, or thyroid (E, A, or T) hormonal 

systems. Chemicals that go through Tier 1 screening and are found to have the potential to 

interact with E, A, or T hormonal systems will proceed to the next stage of the EDSP where EPA 

will determine which, if any, of the Tier 2 tests are necessary based on the available data. Tier 2 

testing is designed to identify any adverse endocrine related effects caused by the substance, and 

establish a dose-response relationship between the dose and the E, A, or T effect.

Between October 2009 and February 2010, EPA issued test orders/data call-ins for the first 

group of 67 chemicals, which contains 58 pesticide active ingredients and 9 inert ingredients. 

This list of chemicals was selected based on the potential for human exposure through pathways 

such as food and water, residential activity, and certain post-application agricultural scenarios. 

This list should not be construed as a list of known or likely endocrine disruptors.
Page 22 of 37

Tepraloxydim is not among the group of 58 pesticide active ingredients on the initial list to be 

screened under the EDSP. Under FFDCA Sec. 408(p), the Agency must screen all pesticide 

chemicals. Accordingly, EPA anticipates issuing future EDSP test orders/data call-ins for all 

pesticide active ingredients. 

5.0 Dietary Exposure/Risk Characterization

Reference: Tepraloxydim on Imported Crop Subgroup 6C (Dried Shelled Pea and Bean) and Sunflower Subgroup 

20B (PP#0E7788). Summary of Analytical Chemistry and Residue Data. DP382893, A. Acierto, 5/27/11.

5.1 Pesticide Metabolism

5.1.1 Metabolism in Primary Crops

No new plant metabolism data were submitted with this petition. However, the nature of the 

residue in the pea and bean, dried shelled, except soybean, subgroup 6C and the sunflower 

subgroup 20B is adequately understood based on the available data for leguminous and oilseed 

crops (soybean and canola). Tepraloxydim and the metabolites containing the 2-cyclohexen-1-

one moiety are the residues of concern for the pea and bean, dried shelled, except soybean, 

subgroup 6C and the sunflower subgroup 20B. HED has determined that the tolerance 

expression for the pea and bean, dried shelled, except soybean, subgroup 6C and the sunflower 

subgroup 20B should include the combined residues of tepraloxydim and its metabolites 

convertible to GP (3-(tetrahydropyran-4-yl)pentane-1,5-dioic acid) and OH-GP (3-hydroxy-3-

(tetrahydropyran-4-yl)pentane-1,5-dioic acid). No additional plant metabolism data are required 

for new uses on legume and oil seed plants.

5.1.2 Metabolism in Livestock

The nature of the residues of tepraloxydim in livestock is adequately understood based on the 

available metabolism data in goats and poultry. The residues of concern for livestock 

commodities are tepraloxydim and the metabolites containing the 2-cyclohexen-1-one moiety. 

HED has determined that the tolerance expression for livestock commodities should include the 

combined residues of tepraloxydim and its metabolites convertible to GP, OH-GP, and GL (3-(2-

oxotetrahydropyran-4-yl)pentane-1,5-dioic acid). No additional livestock metabolism data are 

required to support the current petition.
Page 23 of 37

5.1.3 Drinking Water Residue Profile

Reference: Tier I Drinking Water Assessment for Tepraloxydim. J. Breithaupt, DP338939, 5/1/07

No new estimated drinking water concentrations (EDWCs) were computed for the new 

tolerances on imported commodities from this petition. The estimated environmental 

concentrations (EECs) previous computed for surface water concentrations are the values 

provided by the Environmental Fate and Effects Division (EFED).

The uses on soybeans, cotton, and fallow ground were chosen for modeling since they contain 

the highest application rate of 0.0125 lb ai/A and two applications 14 days apart (maximum 

annual rate of 0.025 lb ai/A). The maximum application rate and minimal application interval 

were used for modeling, and result in relatively unrefined estimates.

The estimates of tepraloxydim concentrations in surface water were based on the FIRST model,

a Tier I model, and include two significant degradates, DP-1 and DP-2. DP-1 and DP-2 are 

included because these two residues were present in some of the environmental fate studies and 

are residues of concern based on the MARC memo (DP272004, L. Cheng, 2/2/01). DP-8 was 

not included in the modeling, because it was not observed in any of the fate studies. The FIRST 

modeling was performed with Index Reservoir (IR) scenarios and a percent cropped area (PCA) 

adjustment factor of 0.87 as a default value, according to the IR/PCA guidance from R.D. Jones 

et al (March 21, 2000). Based on FIRST-IR modeling, the acute EEC and chronic EEC are 1.4 

and 0.7 μg/L, respectively.

Ground water EECs were modeled using SCI-GROW, a screening level groundwater regression 

model, and also include DP-1 and DP-2. The SCI-GROW model provides high-end estimates of 

ground water concentrations of pesticides on soils that are known to be vulnerable to pesticide 

leaching (i.e., high sand content with shallow depth to groundwater). The ground water EEC is 

considered representative of both a peak and long-term average concentration because of the 

inherent nature of ground water (i.e., generally slow movement from source of contamination 

both vertically and horizontally). Based on SCI-GROW modeling, the EECs are not expected to 

exceed 0.002 μg/L.

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

http://www.epa.gov/oppefed1/models/water/. Table 5 summarizes the modeled EECs.

Table 5. Summary of Estimated Surface Water and Ground Water Concentrations for Tepraloxydim.

Parent, DP-1 and DP-2

Surface Water Conc., ppb [μg/L]

a Ground Water Conc., ppb [μg/L]b

Acute (peak value) 1.4 0.002

Chronic (non-cancer) 0.7

a

From the Tier I FIRST - Index Reservoir model. Input parameters are based on the max. appl. rate of 0.0125 lb 

ai/A, min appl interval of 14 days, 2 applications, PCA 0.87, lowest non-sand Koc of 8.4 ml/g.

b

From the SCI-GROW model assuming a max. appl. rate of 0.0125 lb ai/A, a median Koc of 20.2 mg/g, and a halflife of 10.5 days.
Page 24 of 37

5.1.4 Food Residue Profile

Residues of Concern

Previously, it was determined that tepraloxydim and those metabolites containing the 2-

cylcohexen-1-one moiety are residues of concern for canola, cotton and soybean raw agricultural 

commodities. For the imported commodities that are the subject of this assessment (sunflower 

subgroup 20B, and dry bean and dry pea subgroup 6C), the residues of concern are also 

tepraloxydim and those metabolites containing the 2-cyclohexen-1-one moiety, and are detected 

as the combined residues of tepraloxydim and its metabolites convertible to GP and OH-GP. For 

dietary risk assessment, the combined residues of tepraloxydim and its metabolites convertible to 

GP and OH-GP should be used for sunflower subgroup 20B commodities, and the combined 

residues of tepraloxydim and its metabolites convertible to GP and OH-GP plus DD should be 

used for dry bean and dry pea subgroup 6C commodities.

Likewise, the residues of concern for livestock commodities are tepraloxydim and those 

metabolites containing the 2-cyclohexen-1-one moiety, but they are measured as the combined 

residues of tepraloxydim and its metabolites convertible to GP, OH-GP, and GL. Although GL 

by itself is not of concern, it serves as a marker for the significant metabolite DL due to 

conversion of the latter to GL by the analytical method.

GP and OH-GP are included in the tolerance expressions not because of their toxicity but 

because they are the products resulting from the conditions employed in the enforcement 

analytical method.

In drinking water, levels of tepraloxydim, DP-1 and DP-2 are included in the EECs. Although 

GP and FP were present at >10% of the total residue in some cases, these metabolites are 

significantly less toxic than parent and those residues still containing the 2-cyclohexen-1-one 

moiety.

HED does not require data pertaining to rotational crops to establish tolerances on imported 

commodities (HED sop 98.6, “Data Requirements for Import Tolerances,” Table 3, 12/3/98).
Page 25 of 37

Table 6. Summary of Tepraloxydim Residues to be included in the Risk Assessment and 

Tolerance Expression for Imported Dry Bean and Dry Pea Subgroup 6C and Sunflower 

Subgroup 20B **

Matrix Residues included in Risk 

Assessment

Residues included in 

Tolerance Expression

Imported Dry Bean 

and Dry Pea 

Subgroup 6C and 

Sunflower 

Subgroup 20B

Primary Crop: Flax 

(also Canola and 

Cotton), Sunflower 

Subgroup 20B

Parent, GP, OH-GP Parent, GP, OH-GP

Primary Crops: 

Lentil and Dry Bean 

and Dry Pea 

Subgroup 6C (also 

Soybean)

Parent, GP, OH-GP, DD Parent, GP, OH-GP 

Rotational Crop Parent* Parent*

Livestock Ruminant Parent and its metabolites 

convertible to GP, OH-GP, 

and GL

Parent and its metabolites 

convertible to GP, OH-GP, 

and GL Poultry

Drinking Water Parent, DP-1 and DP-2*** Not applicable

*applies to domestic uses

** Nomenclature:

DD: 2-[1-((3-chloroprop-2-(E)-en-1-yl)oximino)propyl]-5-(1,5-dihydroxypentan-3-yl)-3-hydroxycyclohex-2-en-1-

one

DP-1: 3-hydroxy-2-(1-iminopropyl)-5-(tetrahydropyran-4-yl)cyclohex-2-en-1-one

DP-2: 2-ethyl-6-(tetrahydropyran-4-yl)-4,5,6,7-tetrahydrobenzoxazol-4-one

GP: 3-(tetrahydropyran-4-yl)pentane-1,5-dioic acid

OH-GP: 3-hydroxy-3-(tetrahydropyran-4-yl)pentane-1,5-dioic acid

GL: 3-(2-oxotetrahydropyran-4-yl)pentane-1,5-dioic acid

***Although DP-8 (3-hydroxy-2-propionylamino-5-(tetrahydropyran-4-yl)cyclohex-2-en-1-one) was included as a 

residue of concern for drinking water in the MARC memo, the most recent drinking water memo points out DP-8 is 

not observed in any of the fate studies, and is therefore not included in the modeled EDWCs.

Crop Field Trials

Sunflower

The registrant submitted field trial data conducted in the U.S. and Canada to support the

proposed tolerance on the sunflower subgroup 20B. These data are adequate to fulfill data 

requirements. The results show that following a single broadcast foliar application of 

tepraloxydim at approximately 50 g ai/ha, the combined residues of tepraloxydim ranged from 

<0.10 ppm (less than combined LOQ) to 0.18 ppm in/on sunflower seed samples harvested at a 

PHI of 58-61 days. Only two of the ten treated samples contained quantifiable residues of 

tepraloxydim (<0.10 and 0.18 ppm), and these samples were collected at the trials located in 

Wisconsin and Saskatchewan, respectively. Combined residues were also <0.10 ppm in/on two 

treated sunflower seed samples harvested 61 days after application of tepraloxydim at the 
Page 26 of 37

exaggerated rate of 147 g ai/ha. The crop field study is supported by adequate storage stability 

data.

In the residue decline experiment, combined residues of tepraloxydim were <0.10 ppm in/on 

duplicate treated seed samples collected at 41, 50, 61, 70 and 80 days after treatment; therefore, 

the results are inconclusive with respect to decline at longer sampling intervals.

Dry Bean

The registrant submitted field trial data conducted at five locations in the U.S. and Canada to 

support the proposed tolerance on subgroup 5C dry beans and dry pea. These data combined 

with previously submitted Canadian field trial data for dry peas are adequate to fulfill data 

requirements for an import tolerance for a subgroup 6C tolerance. The results show that 

following a single broadcast foliar application of 50 g a.i./ha and harvest at PHIs of 53-63 days 

combined residues were <LOQ (<0.10 ppm) in all dry bean seed samples (<0.05 ppm for 

tepraloxydim derived from GP and <0.05 ppm for 5-OH-DP, derived from OH-GP). The crop 

field study is supported by adequate storage stability data. Residues from the residue decline 

studies were non-quantifiable at PHIs of 70 and 90 days. Similar results were found in the dry

pea field trials (used previously to establish an import tolerance for dry peas).

Summary of the residue data from the crop field trials for sunflower and bean is presented in 

Table 7.

TABLE 7. Summary of Residue Data from Crop Field Trials with Tepraloxydim.

Commodity

Total Applic. 

Rate

(g a.i./ha)

PHI 

(days)

Residue Levels (ppm)

n Min. Max. HAFT* Median

(STMdR)

Mean

(STMR) Std. Dev.

Total Tepraloxydim (including metabolites convertible to GP and OH-GP)

Sunflower seed

49-52 58-60 10 <0.1 0.18 0.14 <0.1 <0.1 0.05

147 61 2 <0.1 <0.1 <0.1 <0.1 <0.1 0

Dry bean seed 50-52 53-63 10 <0.1 <0.1 <0.1 <0.1 <0.1 0

1HAFT = Highest average field trial result

Processed Food and Feed

Sunflower

A sunflower plot was treated at an exaggerated rate of 147 g a.i./ha (0.131 lb ai/A); this is 

equivalent to 3.7x the proposed seasonal application rate. Combined residues in the duplicate 

treated RAC samples were 0.11 and 0.22 ppm (tepraloxydim, <0.05 ppm; 5-OH-DP, 0.06 and 

0.17 ppm). In duplicate treated meal samples, the combined residues were <0.10 and 0.13 ppm 

(tepraloxydim, <0.05 ppm; 5-OH-DP, 0.05 and 0.08 ppm). Residues were non-quantifiable in 

the refined oil. The processing data indicate that residues of tepraloxydim did not concentrate in 

sunflower meal or refined oil. Results are shown in Table 8. 
Page 27 of 37

TABLE 8. Residue Data from Sunflower Processing Study with Tepraloxydim.

RAC Processed 

Commodity

Total Rate

(g a.i./ha)

PHI

(days)

Tepraloxydim 

Residues 

(ppm)

5-OH-DP 

Residues 

(ppm)

Total 

Residues 

(ppm)

Processing 

Factor

Sunflower

(Replicate A)

Whole seed

147 61

<0.05 0.17 0.22 --

Meal <0.05 0.08 0.13 0.6x

Refined oil <0.05 <0.05 <0.1 0.5x

Sunflower

(Replicate B)

Whole seed <0.05 0.06 0.11 --

Meal <0.05 <0.05 <0.1 0.9x

Refined oil <0.05 <0.05 <0.1 0.9x

Dry Beans

No processed commodities are associated with dry bean.

Meat, Milk, Poultry, and Eggs

The feedstuff associated with the sunflower subgroup 20B is sunflower meal based on Table 1 

Feedstuffs (June 2008). No livestock feedstuffs are associated with dry beans except for cowpea 

(seed, forage, and hay). These livestock feeds may be fed to livestock in Canada destined for 

import into the U.S. These items, because of the low residue levels, will have an insignificant 

effect on the livestock dietary burdens. The maximum theoretical dietary burdens of 

tepraloxydim to livestock were previously calculated in conjunction with PP#8F4945 

(DP243962, L. Cheng, 10/3/00). For this petition (PP#0E7788), a reasonably balanced diet 

based on Table 1 Feedstuffs (June 2008) was determined. The established tolerances for 

livestock commodities are adequate to support the proposed tolerances. 

Confined Accumulation in Rotational Crops

Confined accumulation in rotational crops to establish tolerances are not required for import 

commodities (HED SOP 98.6, Data Requirements for Import Tolerances, Table 3, 12/3/98).

Field Accumulation in Rotational Crops

Rotational crop data are not required to establish tolerances on imported commodities (HED 

SOP 98.6, Data Requirements for Import Tolerances, Table 3, 12/3/98).

5.2 Dietary Exposure and Risk

Reference: Tepraloxydim: Acute and Chronic Dietary (Food and Drinking Water) Exposure and Risk Assessment 

for Residues on Imported Dry Bean and Sunflower Subgroup 20B. D384841, A. Acierto, 6/7/11.

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

conducted using the DEEM-FCIDTM, Version 2.03, which uses food consumption data from the 

USDA’s Continuing Surveys of Food Intakes by Individuals (CSFII) from 1994-1996 and 1998.
Page 28 of 37

The latest acute and chronic dietary risk assessments was conducted on dry pea, flax and lentil 

(D338371, N. Dodd, 7/17/07). The only change made to the last assessment is the addition of 

dry bean and sunflower subgroup 20B. The conservative acute and chronic dietary exposure 

assessments incorporated the same input parameters used in the previous assessment including 

toxicological endpoints and estimated drinking water concentrations. As in the previous 

assessment, the current assessment used residue values at the recommended and established 

tolerance levels and assumed that 100 percent of the crops were treated. Residues of the 

proposed food commodities were based on field trial data on dry bean and sunflower. There are 

no processed commodities for dry beans. Processing factors for the sunflower processed 

commodities (meal and refined oil) were set to 1 based on the studies demonstrating that residues 

did not concentrate in the sunflower processed fractions. 

5.2.1 Acute Dietary Exposure/Risk

The acute dietary exposure was estimated for females 13-49 years old separately from the 

general U.S. population since this population subgroup has a different toxicological endpoint. 

The surface water EEC used for the acute dietary assessment is 1.4 ppb and was incorporated in 

the DEEM-FCID model as the food categories “water, direct all sources” and “water, indirect, all 

sources”. Based on the assumptions described above, the acute dietary exposure of females 13-

49 years old as well as the general U.S. population and all population subgroups are well below 

HED’s level of concern at the 95th percentile of exposure. Combined dietary exposure from food 

and drinking water for females 13-49 years old at the 95th percentile of exposure is estimated to 

be 0.001844 mg/kg/day, equivalent to <1% (0.46%) of the acute Population Adjusted Dose 

(aPAD). For the general U.S. population, the exposure is estimated to be 0.003713 mg/kg/day, 

equivalent to <1% (0.74%) of the aPAD. For children 1-2 years old, the most highly exposed 

subgroup, the exposure is estimated to be 0.010897 mg/kg/day, equivalent to 2.2% of the aPAD.

Table 9. Summary of Dietary (Food and Drinking Water) Exposure and Risk for Tepraloxydim.

Population Subgroup

Acute Dietary

(95th Percentile) Chronic Dietary Cancer

aPAD Dietary 

Exposure 

(mg/kg/day)1

% aPAD

Dietary 

Exposure

(mg/kg/day)1

% cPAD

Dietary 

Exposure

(mg/kg/day)

Risk 

General U.S. Population 0.5 0.003713 <1 0.001213 2.4 N/A2 N/A2

All Infants (< 1 year old) 0.5 0.005947 1 0.001761 4

N/A N/A

Children 1-2 years old 0.5 0.010897 2.2 0.004825 9.6

Children 3-5 years old 0.5 0.006858 1 0.003404 7

Children 6-12 years old 0.5 0.004459 <1 0.002092 4

Youth 13-19 years old 0.5 0.002612 <1 0.001089 2

Adults 20-49 years old 0.5 0.001902 <1 0.000817 2

Adults 50+ years old 0.5 0.001560 <1 0.000721 1
Page 29 of 37

Table 9. Summary of Dietary (Food and Drinking Water) Exposure and Risk for Tepraloxydim.

Population Subgroup

Acute Dietary

(95th Percentile) Chronic Dietary Cancer

aPAD Dietary 

Exposure 

(mg/kg/day)1

% aPAD

Dietary 

Exposure

(mg/kg/day)1

% cPAD

Dietary 

Exposure

(mg/kg/day)

Risk 

Females 13-49 years old 0.4 0.001844 <1 0.000774 2

1The values for the highest exposed population are bolded.

2Data are inadequate for an assessment of human carcinogenic potential.

5.2.2 Chronic Dietary Exposure/Risk

The chronic dietary exposure and risk estimates are conservative since they assume that 100% of 

crops are treated and that the residues are present at tolerance levels. The chronic surface water 

EEC for tepraloxydim is 0.7 ppb. The water residues were incorporated directly into the DEEMFCID into the food categories “water, direct, all sources” and “water, indirect, all sources.” 

Combined chronic dietary exposure estimates for food and drinking water are well below HED’s 

level of concern. Using the DEEM-FCID software, dietary exposure is estimated to be 0.001213

mg/kg/day for the general U.S. population equivalent to 2.4% of the chronic Population Adjusted 

Dose (cPAD). Dietary exposure is estimated to be 0.004825 mg/kg/day, equivalent to 9.6% of 

the cPAD, for children 1-2 years old, the population subgroup with the highest estimated chronic 

dietary exposure to tepraloxydim.

5.3 Anticipated Residue and Percent Crop Treated (%CT) Information

The acute and chronic dietary assessments are screening-level assessments using residues at 

tolerance levels and assuming that 100% of requested crops are treated.

6.0 Residential (Non-Occupational) Exposure/Risk Characterization

This document addresses an application for tolerances of tepraloxydim on imported dry beans 

and sunflower subgroup 20B commodities, and therefore is not expected to result in residential 

exposure. Additionally, tepraloxydim is registered in the US to control grass weeds in canola, 

cotton and soybean crops, as well as fallow and non-cropland in agricultural settings (i.e., 

tepraloxydim is not intended for use in public or residential settings). Therefore, residential 

exposure is not expected and no residential risk assessment was conducted.

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

assessment was not performed for (chemical) at this time primarily because of the low acute 

inhalation toxicity (Toxicity Category III and IV), low vapor pressure (1.1 x 10-7hPa at 20 C), 

and the low proposed use rate (0.033 to 0.124 lb ai/A). 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, 2010 
Page 30 of 37

(http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html). 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 tepraloxydim.

Spray drift is always a potential source of exposure to residents nearby to spraying operations. 

This is particularly the case with aerial application, but, to a lesser extent, could also be a 

potential source of exposure from the ground application method employed for [chemical]. The 

Agency has been working with the Spray Drift Task Force, 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 at 

http://www.epa.gov/opp00001/factsheets/spraydrift.htm). On a chemical by chemical basis, the 

Agency is now requiring interim mitigation measures for aerial applications that must be placed 

on product labels/labeling. The Agency has completed its evaluation of the new database 

submitted by the Spray Drift Task Force, a membership of U.S. pesticide registrants, and is 

developing a policy on how to appropriately apply the data and the AgDRIFT computer model to 

its risk assessments for pesticides applied by air, orchard airblast and ground hydraulic methods. 

After the policy is in place, the Agency may impose further refinements in spray drift 

management practices to reduce off-target drift with specific products with significant risks 

associated with drift.

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

performed as a result of pesticide drift from neighboring treated agricultural fields, an inhalation 

exposure assessment was previously performed for flaggers for domestic aerial applications. 

This exposure scenario is representative of a worse case inhalation (drift) exposure and may be 

considered protective of most outdoor agricultural and commercial post-application inhalation 

exposure scenarios. 

7.0 Aggregate Risk Assessments and 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.

There is no residential exposure expected for tepraloxydim; therefore, the sources considered in 

the aggregate assessment are food and drinking water. Because the dietary assessment 

incorporates exposure from both food and drinking water, the dietary assessment addresses 

concern from aggregate exposure. Refer to Section 5.2, which discusses dietary exposure (food 

and water).

8.0 Cumulative Risk Characterization/Assessment
Page 31 of 37

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 mammalian mechanism of 

toxicity finding as to tepraloxydim and any other substances and tepraloxydim 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 tepraloxydim has a common mammalian 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 Pathway

This document addresses risk resulting from use of tepraloxydim on imported dry beans and 

sunflower subgroup 20B commodities. Therefore, occupational exposure and risk is not 

expected.

Appendix A: Toxicology Assessment

A.1 Toxicology Data Requirements

The requirements (40 CFR 158.500) for food uses for tepraloxydim are in Table A.1. Use of the 

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

Table A.1. Toxicology Data Requirements for Food Use - Tepraloxydim

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

yes

yesa

yes

yes

yes

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

yes

---
Page 32 of 37

Table A.1. Toxicology Data Requirements for Food Use - Tepraloxydim

Study

Technical

Required Satisfied

870.5100 Mutagenicity—Gene Mutation - bacterial

870.5300 Mutagenicity—Gene Mutation - mammalian

870.5375 Mutagenicity—Structural Chromosomal Aberrations

870.5395 Mutagenicity—Other Genotoxic Effects

870.5550 Mutagenicity—Unscheduled DNA synthesis

yes

yes

yes

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

yes

yes

no

---

---

yes

yes

---

870.7485 General Metabolism

870.7600 Dermal Penetration

870.7800 Immunotoxicity

yes

nob

yes

yes

nob

no

a A 28-day inhalation study is required.

b The available dermal absorption study (MRID 44467211) is classified Unacceptable/Non-guideline.

A.2 Toxicity Profiles

Table A.2.1 Acute Toxicity Profile - Tepraloxydim 

Guideline 

No.

Study Type MRID Results Toxicity 

Category

870.1100 Acute oral (rat) 44467131 LD50 = 5000 mg/kg III

870.1200 Acute dermal (rabbit) 44496403 LD50 > 2000 mg/kg III

870.1300 Acute inhalation (rat) 44467132 LC50 > 5.1 mg/L IV

870.2400 Acute eye irritation (rabbit) 44467133 minimal eye irritation III

870.2500 Acute dermal irritation (rabbit) 44467134 slight dermal irritation IV

870.2600 Skin sensitization (guinea pig) 44467135 not a dermal sensitizer N/A

Table A.2.2 Subchronic, Chronic and Other Toxicity Profile

Guideline 

No. 

Study Type MRID No. (year)/ 

Classification /Doses

Results

870.3100 90-Day oral 

toxicity (rat)

44467137 (1996)

Acceptable/guideline

0, 300, 3000, or 5000 ppm 

M: .0, 22, 223, and 383 

mg/kg/day 

F: 0, 26, 257, and 440 

mg/kg/day

NOAEL = 22 mg/kg/day

LOAEL = 223 mg/kg/day based on decreased 

body weight, body weight gain, and proximal 

kidney tubule changes in males in addition to 

clinical chemistry findings indicative of 

kidney and liver toxicity in both sexes.

870.3150 90-Day oral 

toxicity (dog)

44467139 (1997) 

Acceptable/guideline

0, 400, 2000, or 10,000 

ppm

Males: 0, 12.9, 63.3, and 

325.0 mg/kg/day 

Females: 0, 14.3, 68.0, and 

357.7 mg/kg/day

NOAEL = 12.9 mg/kg/day

LOAEL = 63.3 mg/kg/day based on increased 

liver and thyroid weights in addition to spleen 

histopathology findings and other changes 

indicative of hemolytic compensatory anemia 

in females.
Page 33 of 37

Table A.2.2 Subchronic, Chronic and Other Toxicity Profile

Guideline 

No. 

Study Type MRID No. (year)/ 

Classification /Doses

Results

870.3200 28-Day dermal 

toxicity (rat)

44467140 (1997)

Acceptable/guideline

0, 50, 200, or 1000 

mg/kg/day

NOAEL (Dermal or Systemic) = 1000 

mg/kg/day

LOAEL (Dermal or Systemic) > 1000 

mg/kg/day.

870.3700a Prenatal 

developmental in 

(rat)

44467203 (1995) 

Acceptable/guideline

0, 40, 120, and 360 

mg/kg/day

Maternal NOAEL = 120 mg/kg/day

LOAEL = 360 mg/kg/day based on findings of 

decreased body weight gain and a marginal 

decrease in food intake (at days 6-8 only).

Developmental NOAEL = 40 mg/kg/day

LOAEL = 120 mg/kg/day based on reduced 

fetal body weights, retarded ossification 

indicative of delayed maturation and the 

occurrence of hydroureter.

870.3700b Prenatal 

developmental in 

(rabbit)

44496404 (1995)

Acceptable/guideline

0, 20, 60, or 180 mg/kg/day 

Maternal NOAEL = 60 mg/kg/day

LOAEL = 180 mg/kg/day based on decreased 

body weight and food consumption.

Developmental NOAEL ≥ 180 mg/kg/day 

LOAEL >180 mg/kg/day.

870.3800 Reproduction and 

fertility effects

(rat)

44467205 (1997)

Acceptable/guideline

0, 100, 500, or 2500 ppm

Premating doses 

F0 Males: 0, 10.2, 50.9, 

and 253.1 mg/kg/day 

F0 females: 0, 11.2, 54.7, 

and 273.8 mg/kg/day 

F1 males: 0, 10.0, 50.3, and 

266.9 mg/kg/day 

F1 females: 0, 11.0, 55.3, 

and 278.0 mg/kg/day.

Parental/Systemic NOAEL (M/F) = 50.6/55 

mg/kg/day

LOAEL (M/F) = 260/276 mg/kg/day based on 

decreased body weight/weight gain and food 

consumption.

Reproductive NOAEL ≥ 260 mg/kg/day

LOAEL > 260 mg/kg/day .

Offspring NOAEL (M/F) = 50.6/55 mg/kg/day

LOAEL M/F = 260/276 mg/kg/day based on 

reduced pup body weight gain and lower pup 

body weight during lactation.

870.4100a Chronic toxicity

(rat)

44467145 (1997) 

Acceptable/guideline

0, 100, 600, or 3000 (male) 

or 4000 ppm (females)

Males: 0, 5, 29, and 154 

mg/kg/day

Females: 0, 6, 38, and 273 

mg/kg/day

NOAEL (M/F) = 29/38 mg/kg/day

LOAEL (M/F) =154/273 mg/kg/day based on 

reduced body weight, weight gain, and food 

efficiency in addition to microscopic liver 

lesions (eosinophilic foci in both sexes and 

cellular polymorphism in females).

870.4100b Chronic toxicity 

(dog)

44467146 (1997) 

Acceptable/guideline

0, 100, 400, or 2000 ppm

Males: 0, 3.0, 11.5, and 

56.0 mg/kg/day 

Females: 0, 3.1, 12.5, and 

60.6 mg/kg/day

NOAEL =11.5mg/kg/day

LOAEL = 56.0 mg/kg/day based on reduced 

epididymal and prostate activities, transitional 

epithelial hyperplasia of the urinary bladder, 

abnormal liver function, and liver foci.

870.4100b Chronic toxicity -

Supplementary 

(dog)

44467147 (1997) 

Acceptable/Non-guideline

0, or 8000 ppm

Males: 0, or 248 mg/kg/day 

Females: 0, or 265 

mg/kg/day

NOAEL < 248 mg/kg/day

LOAEL = 248 mg/kg/day based on anemia 

and hepatobiliary toxicity in both sexes; focal 

hemorrhage of bladder’s transitional epithelia 

and testicular toxicity (males only).
Page 34 of 37

Table A.2.2 Subchronic, Chronic and Other Toxicity Profile

Guideline 

No. 

Study Type MRID No. (year)/ 

Classification /Doses

Results

870.4200 Carcinogenicity

(rat)

44467201 (1997)

Acceptable/guideline

0, 100, 600, or 3000 (male) 

or 4000 ppm (females)

Males: 0, 5, 30, and 155 

mg/kg/day

Females: 0, 6, 38, and 272 

mg/kg/day

NOAEL (M/F) = 5/38 mg/kg/day

LOAEL (M/F) = 30/272 mg/kg/day based on

eosinophilic foci in males and eosinophilic 

foci and cellular polymorphism in females in 

addition to other findings in females including 

decreased body weight, weight gain, food 

intake, and food efficiency.

Some evidence of carcinogenicity

870.4300 Carcinogenicity

(mouse)

44467202 (1997)

Acceptable/guideline

0, 200, 1800, or 5000 ppm

Males: 0, 37, 332, and 

1035 mg/kg/day

Females: 0, 52, 490, and 

1456 mg/kg/day

NOAEL (M/F) = 37/52 mg/kg/day

LOAEL (M/F) = 332/490 mg/kg/day based on 

decreased body weight/weight gain in both 

sexes, increased relative liver weight and 

altered foci (eosinophilic and basophilic) in 

males, and uterine sclerosis.

Female mice developed liver tumors at an 

excessively toxic dose.

Some evidence of carcinogenicity

870.5100 Gene Mutation

Bacterial reverse 

mutation assay

44467206 (1993)

Acceptable/guideline

Negative ± S9 up to 5000 μg/ml with 

cytotoxicity at this concentration or at 2500 

μg/ml.

870.5300 Gene Mutation

Mammalian 

(CHO/ HPRT) 

forward mutation 

assay

44467207 (1995)

Acceptable/guideline

Negative ± S9 up to cytotoxic and 

precipitating concentrations (3000 μg/ml).

870.5300 Cytogenetics

Chromosomal 

aberrations (CHO 

cells)

44467209 (1993)

Acceptable/guideline

Negative ± S9 up to its limit of solubility at 

1000 μg/ml.

870.5395 Micronucleus 

Assay (mouse)

44467208 (1995)

Acceptable/guideline

Negative for clastogenic/aneugenic activity in 

male/female mouse bone marrow up to 500 

mg/kg (animals died at 600 mg/kg).

870.5550 UDS in primary 

male rat 

hepatocytes

44467210 (1996)

Acceptable/guideline

Negative up to 500 μg/ml; cytotoxic at  100 

μg/ml.

870.6200a Acute 

neurotoxicity 

screening battery

44467136 (1997)

Acceptable/guideline

0, 500, 1000, or 2000 

mg/kg

NOAEL = < 500 mg/kg

LOAEL = 500 mg/kg based on decreased 

motor activity in females

870.6200b Subchronic 

neurotoxicity 

screening battery

44467141 (1997)

Acceptable/guideline

0, 400, 1,500, or 6,000 ppm

Males: 0, 28, 103, or 428 

mg/kg/day

Females: 0, 33, 124, or 513 

mg/kg/day

NOAEL (M/F) = 103/124 mg/kg/day

LOAEL (M/F) = 428/513 mg/kg/day based on 

increased motor activity as well as decreased 

body weights, food consumption, and food 

efficiency.
Page 35 of 37

Table A.2.2 Subchronic, Chronic and Other Toxicity Profile

Guideline 

No. 

Study Type MRID No. (year)/ 

Classification /Doses

Results

870.7485 Metabolism and 

pharmacokinetics

(species)

[44496405 (1993), 

5101301 (1996), 45101302 

(1996), 45101303 (1997)

Acceptable/guideline

In pharmacokinetics/metabolism studies in the 

rat, tepraloxydim was readily and almost 

completely absorbed after oral administration 

(single dose of 30 or 300 mg/kg), but was 

rapidly excreted mainly via the urine (65-

80%). Excretion was nearly 2-3 fold higher in 

the bile than the feces, which suggests 

enterohepatic recirculation. The rat plasma 

half-life of radiolabeled tepraloxydim is nearly 

4.4 and 10 hours at the low and high dose, 

respectively. No accumulation of radiolabel

was observed in any tissue at 120 hours postdosing. A large number of metabolites were 

detected in the urine, feces, and bile; the main 

metabolic pathway being oxidation at the 

pyran ring to the lactone via a hydroxy 

metabolite, and cleavage of the oxime ether 

group with the imine and oxazol as products. 

At near plasma tmax (one hour post dosing), the 

plasma, liver, and kidney almost exclusively 

contained the parent compound. The results 

indicate that the distribution, metabolism, and 

excretion of tepraloxydim is independent from 

dose levels, sex, route of administration (oral 

vs. i.v.), or site of label (pyran vs. 

cyclohexanone).

870.7600 Dermal 

penetration 

(species)

44467211 (1997)

Unacceptable/nonguideline

The available rat dermal absorption study is 

considered unacceptable. A dermal absorption 

rate of 36% was derived based on the results 

of a 28-day dermal toxicity study in rats and 

developmental toxicity study in rats.
Page 36 of 37

Appendix B: Physical and Chemical Properties

Table B. Physicochemical Properties of Tepraloxydim.

Parameter Value Reference

Molecular Weight 341.8 PMRA Proposed 

Regulatory Decision 

Document PRDD2004-01 

Melting point/range 72.5-74.4 C

pH 3.9

Density 1.284 g/mL at 20 C

Water solubility 0.43 g/L at 20 C (pH 6.5)

7.25 g/L at 20 C (pH 9)

Solvent solubility Solvent

Acetone

Methanol

2-Propanol

Ethyl acetate

Acetonitrile

Dichloromethane

Toluene

n-Heptane

1-Octanol

Olive oil

g/100 mL at 20 C

70

33

16

69

77

119

82

1.0

15

8.0

Vapor pressure 1.1 x 10-7

hPa at 20 C

2.7 x 10-7hPa at 25 C

Dissociation constant, pKa pKa = 4.58 at 20 oC

Octanol/water partition coefficient, 

Log(KOW)

pH

pure water

4

7

9

Log Kow

1.5

2.44

0.20

-1.15

UV/visible absorption spectrum Λ

204

225

258

290

300

ε (1 x Mol-1 x cm-1)

9.5 x 103

4.6 x 103

1.1 x 104

6.8 x 103

3.1 x 103
Page 37 of 37

Appendix C: International Residue Limit Status

TEPRALOXYDIM (PC Code 121005; 04/14/2011)

Table C. Summary of US and International Tolerances and Maximum Residue Limits

Residue Definition:

US Canada Mexico2 Codex3

40 CFR 180.573:

Plants: tepraloxydim (2-[1-

[[[(2E)-3-chloro-2-

propenyl]oxy]imino]propyl]-3-

hydroxy-5-(tetrahydro-2Hpyran-4-yl)-cyclohexene-1-one) 

and its metabolites convertible 

to GP (3-(tetrahydropyran-4-

yl)pentane-1,5-dioic acid) and 

OH-GP (3-hydroxy-3-

(tetrahydropyran-4-yl)pentane1,5-dioic acid), calculated as 

tepraloxydim 

Livestock: combined residues 

of tepraloxydim and its 

metabolites convertible to GP, 

OH-GP, and GL (3-(2-

oxotetrahydropyran-4-yl)-1,5-

dioic acid), calculated as 

tepraloxydim

Plants:(EZ)-(RS)-2-{1-[(2E)-3-

chloroallyloxyimino]propyl}-3-

hydroxy-5-perhydropyran-4-ylcyclohex-2-

en-1-one,

including metabolites convertible to 3-

perhydropyran4-ylglutaric acid and 3-hydroxy-3-

perhydropyran-4-

ylglutaric acid, as parent equivalent

Livestock:(EZ)-(RS)-2-{1-[(2E)-3-

chloroallyloxyimino]propyl}-3-

hydroxy-5-perhydropyran-4-ylcyclohex-2-

en-1-one,

including metabolites convertible to dimethyl 

3-

(perhydropyran-4-yl)glutarate, dimethyl 3-

hydroxy-3-

(perhydropyran-4-yl)glutarate and dimethyl 

3-(pentan5-olid-3-yl)glutarate, as parent equivalent

None

Commodity1 Tolerance (ppm) /Maximum Residue Limit (mg/kg)

US Canada Mexico2 Codex

Pea and bean, dried shelled, 

except soybean, subgroup 6C

0.10 0.1 Dried shelled pea and 

bean, except soybean 

(Crop subgroup 6C)

Sunflower subgroup 20B 0.20 0.2 Sunflowers (Crop 

Subgroup 20B)

Completed: M. Negussie; 05/17/2011

1

Includes only commodities of interest for this action. Tolerance values should be the HED recommendations and 

not those proposed by the applicant.

2 Mexico adopts US tolerances and/or Codex MRLs for its export purposes.

3 * = absent at the limit of quantitation; Po = postharvest treatment, such as treatment of stored grains. PoP = 

processed postharvest treated commodity, such as processing of treated stored wheat. (fat) = to be measured on the 

fat portion of the sample. MRLs indicated as proposed have not been finalized by the CCPR and the CAC.