Page 1 of 37 **UNITED STA TES ENVIRONMENTA**  **L PROTECTION A GENCY** 

WA SHINGTON, D.C. 20460 OFFICE OF CHEMICAL SAFETY AND POLLUTION PREVENTION **Date:** November 7 , 20 1 1 **MEMORANDUM SUBJECT**  : **Am ended:**  **Tepraloxydim :**  Human Health Risk Assessment for New Toleranc es

on Imported Dry

Bean and Dry

Pea Subgroup 6C and Sunflower Subgroup 20B. **PC Code:** 121005 **DP Barcode:** D 3 95874 **Decision No.:** 440435 **Registration Nos. :**  NA **Petition Nos.:** 0E7788 **Regulatory Action:** Tolerance Assessment **Risk Assessment Type:** Singl e chemical/ aggregate **Case No.:** NA **T XR No.:**  NA **CAS No.:** 149979 - 41 - 9 **MRID No.:** NA **40 CFR:** §180. 573 **FROM** : Barry

O’Keefe , Senior Biologist Amelia Acierto, Chemist Sheila Heal y , 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 2 5

Herbicide Branch Registration Division (7505P) **Introduction** This amendment of the recent HED risk assessment (DP3 84834, B. O’Keefe, 7/28/11) of tepralox ydim was completed to provide a more thorough characterization of the toxicological database for tepralox ydim. BASF Corporation, on behalf of Nippon Soda Company , has submitted a petition (Petition No. 0E7788) propo sing the establishment of tolerances for residues of the herbicide tepralox ydimPage 2 of 37

and its metabolites convertible to GP [3 - (tetrahydropy ran - 4 - yl )pentane - 1,5 - dioic acid], calculated as tepralox ydi m, in/on the following imported raw agricultural commodities grown in Canada: Pea and bean, dried shelled, except soy bean, subgroup 6C .......... 0.1 0 ppm Sunflower subgroup 20B ................................ .............................. 0. 25 ppm Tepralox ydim is registered for use in Canada under the trade name EQUINOXTM EC Herbicide, an emulsifiable concentrate formulation containing 2 00 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 soy beans. 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 ARAMO TM 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 provid ed b y Barry O’Keefe, the hazard characterization by Sheila Heal y , 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 Divi sion (EFED).Page 3 of 37 **Table of Contents 1.0**  **Executive Summary** ................................ ................................ ................................ .......... 5 **2.0 Regulatory Conclusions and Recommendations**  ................................ ............................ 6 2.1 Data Deficiencies ................................ ................................ ................................ .... 7 2.2 Tolerance Considerati ons ................................ ................................ ........................ 7 2.2.1 Enforcement Anal yt ical Method ................................ ................................ . 7 2.2.2 International Harmonization ................................ ................................ ....... 8 2.2.3 Recommended Tolerances ................................ ................................ .......... 9 2.2.4 Revisions to Petiti oned - For Tolerances ................................ .................... 10 **3.0 Ingredient Profile**  ................................ ................................ ................................ ............ 10 3.1 Summary

of Proposed Uses ................................ ................................ .................. 10 3.2 Structure and Nomenclature ................................ ................................ ................. 11 3.3 Phy sical and Chem ical Properties ................................ ................................ ......... 13 3.4 Anticipated Exposure Pathway s ................................ ................................ ........... 13 3.5 Consideration of Environmental Justice ................................ ............................... 13 **4.0 Hazard Characterization/Assessment**  ................................ ................................ ........... 14 4.1 Toxicology

Studies Available for Analy sis ................................ .......................... 14 4.2 Absorption, Distribution, Metabolism, Excretion (ADME) ................................ . 15 4.2.1 Dermal Absorption ................................ ................................ .................... 15 4.3 Toxicological Ef

fects ................................ ................................ ............................ 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 L ivestock ................................ ................................ ........... 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 Characterizat**  **ion** ................................ ............ 30 **8.0 Cumulative Risk Characterization/Assessment**  ................................ ........................... 30Page 4 of 37

**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** ................................ ................................ ... 37Page 5 of 37

**1.0 Executive Summary**  Tepralox ydim is a herbicidal active ingredient (ai) intended for postemergence control of certain annual grasses and quackgrass , and is currentl y registered and formulate d as Equinox TM (1 .67 lb ai/ gal EC ) for use on canola, cotton and soy bean 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 herbici de tepralox ydim and its metabolites convertible to GP [3 - (tetrahydropy ran - 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 so ybean, sub group 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 ARAMO TM EC Herbicide (Canadian Reg . No. 27603). The emulsifiable co ncentrate 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 soy beans. The label has been amended and approved by PMRA in April 2010 to include its use on the a dditional crops in Subgroup 6C and s unflower subgroup 20B. BASF noted that they have no plans to appl y for U.S. registration of EQUINOX use on the additional Subgroup 6C crops or on s unflower subgroup 20 B crops at this time. Under the registered use patt ern in Canada, tepralox ydim 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 day s for crop s. Toxicity/Hazard The toxicological database for tepraloxydim is sufficient for the purpose of this risk assessment. The main target organs for tepralox yd im toxicity are the liver, the spleen/hematopoietic sy stem and reproductive s ys tem. The reproducti ve s ys tem was affected at relativel y high doses (in excess of LOAELs) . Tepraloxydim also affected the hematopoietic sy stem. Prenatal developmental toxicity studies indicate that, relative to maternal animals, the developing rat fetu s 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 mo tor 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 sy stem. 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 , the refo r e, quantification of human cancer risk is not required. The Agency, however, has determined that a dditional carcinogenicity studies are not required since the doses tested in both species, mice and rats, were adequate to assess the carcinogenic potential of tepralox ydim and that the chronic PAD (0.05 mg/kg/day) will adequately protect for all chronic e ffects, including carcinogenicity , likel y to result from exposure to tepralox ydim. Tepralox ydim has a low acute toxicity based on its classification in Toxicity Category III via the oral route, Toxicity

Category I II b y the dermal route, and Toxicity Category IV by the inhalationPage 6 of 37

route of exposure. Tepraloxydim produces minimal eye irritation (Toxicity Category III), is a slight dermal irritant and is not a dermal sensitizer. T he 10X FQPA Safet y Factor was retained for assessing the acute dietary risk (aRfD) for the general population in the form UF L 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 FQP A Safet y Factor was reduced to 1X for these scenarios. Drinking W

ater N o new estimated drinking water concentrations (EDWCs) were computed for the new tolerances on imported commodities from this petition . T he estimated environmental concentrations (EECs) previous ly computed for surface water concentration s were used. Based on FIRST - IR modeling, the acute and chronic EEC s are 1.4 and 0.7 μg/L , respectivel y. Dietary Exposure (food and drinking water) Unrefined dietary (food and drinking water) exposure anal ys es which were performed using the Dietary Exposure Evaluation Model (DEEM - FCID TM , Version 2.03) indicate that acute and chronic dietary

exposure s to tepralox yd im from food and drinking water are well below HE D’s level of concern (L OC) for tepralox ydim . Acute dietary exposure from food and drinking water at the 95 th 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**  Provide d a revised Section F (OPPTS 860.1550) is submitted, HED can recommend for permanent tepraloxydim tolerances for the imported commodities in p ea 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.Page 7 of 37

**2.1 Data Deficiencies**  **The following must be provided prior to a tolerance being established or registration**  **allowed:** 860.15 50 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. 78 00 Immuno toxicity 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 Analy tical Reference Standards The following reference standards for tepralox ydi m 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 anal ys is 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 chromatograph y/mass spectrometry (GC/MS) enforcement method, BASF Analy tical Method D9701/1, is available for the enforcement of tolerances for plant commodit ies. The method has been reported and reviewed in detail in conjunction with earlierPage 8 of 37

petitions (PP#8F04945, D243962, LCheng, 10/3/2000 and PP#6E7046, D328044, N. Dodd, 6/19/2007). The method is designed to determine the total residues of tepraloxydim an d its metabolites. Parent tepralox yd im and related metabolites containing the 3 - tetrah ydrop yr an ylpentane - 1,5 - dione moiety are converted b y oxidation to GP, and GP residues are subsequently

methylated and determined as DMP (dimethyl 3 - (tetrahydropy ran - 4 - yl )pentane 1,5 - dioate). Residues of 5 - OH - DP and related 5 - hydroxy - metabolites containing the 3 - hydrox y 3 - tetrah ydrop yr an ylpentane - 1,5 - dione moiety are oxidized to OH - GP and are subsequentl y methylated and quantified as OH - DMP (dimethyl 3 - hydroxy - 3 - (tetrah ydroxy py ran - 4 - yl )pentane 1,5 - dioate). Ions 168, 182, and 213 are monitored for DMP, with ion 182 the ty pical quanti t ation ion. I ons 143 and 175 are monitored for OH - DMP, with ion 143 the ty pical quantitation ion. Residues are reported in terms of parent e quivalents. The validated limit of quantitation (L OQ) for each of the residues of tepralox ydim and 5 - OH - DP is 0.05 ppm. BASF Method D9701/1 has been successfull y radiovalidated and has undergone an independent laboratory validation (ILV). HED has determ ined that a tolerance method validation by the Agency ’s analy

tical laboratory

is not necessary . Adequate GC/MS enforcement methods, BASF Analy tical Method Nos. 389/0 and 975/1 , are available for determining residues in livestock. The methods have been r eported and also reviewed in detail in conjunction with the earlier petitions for tolerances for residues of tepralox ydim 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 Anal yt ical Method Nos. 389/0 and 975/1, a tolerance method validation in the Agency ’s anal yt ical laboratory

is not necessary . A liquid chromatograph y/tandem mass spectrometry (L C/MS/MS) method (BASF Anal yt ical 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 tepralox ydim and its metabolites containing the 3 - tetrah ydrop yr an ylpentane - 1,5 - dione moiety which are converted b y oxidation to GP and determined as GP; and residues of metabolite 5 - OH - DP and related h ydroxy metabolites containing the 3 - hydrox y - 3 - tetrah ydrop yran ylpentane - 1,5 - dione moiety which is oxidized to OH - GP and determined as OH - GP. Residues of GP and OH - GP ar e expressed as the parent using molecular weight conversion factors. A slightly modified method (BASF Anal yt ical Method D9704/1) was used to anal yz e the residues of tepralox ydim 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 tepralox ydim derived from GP, and 0.05 ppm for 5 - OH - DP derived from OH - GP). **2.2.2 Interna**  **tional Harmonization** There are no Codex MRLs for residues of tepralox yd im. A Canadian MRL has been established for residues of tepralox ydim and its metabolites convertible to 3 - perh ydropy ran - 4 - yl glutaric acid ( GP) and 3 - hydrox y - 3 - perhydropy ran - 4 - yl glutaric acid (OH - GP), expressed as parent equivalent,Page 9 of 37

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 Can adian 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. Pendin g submission of a revised Section F , there are no residue chemistry issues that would preclude establishment of tolerances for residues of tepralox ydim as follows : Pea and bean, dried shelled, except soy bean, subgroup 6C ........... 0.10 ppm Sunflower sub group 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 tepralox ydim in 4 0 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. Kniz n er) 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 b y measuring only the combined residues of tepralox ydim (2 - [1 - [[[(2E) - 3 - chloro - 2 - propen - 1 - yl ]oxy]imino]propyl] - 3 - hydrox y - 5 - (tetrahydro - 2H - py ran - 4 - yl ) - 2 - cyclohexen - 1 - one) and its metabolites convertible to GP (3 - (tetrah ydropy ran - 4 - yl )pentane 1,5 - dioic acid) and OH - GP (3 - hydroxy - 3 - (tetrahydropy ran - 4 - yl )pentane - 1,5 - dioic acid), calculated as tepralox ydi m.” 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 b y measuring only the combined resi dues of tepralox ydim (2 - [1 - [[[(2E) - 3 - chloro - 2 - propen - 1 - yl ]oxy]imino]propyl] - 3 - hydrox y - 5 - (tetrahydro - 2H - py ran - 4 - yl ) - 2 - cyclohexen - 1 - one) and its metabolites convertible to GP (3 - (tetrah ydropy ran - 4 - yl )pentane 1,5 - dioic acid), OH - GP (3 - hydroxy - 3 - (tetrah ydropy r an - 4 - yl )pentane - 1,5 - dioic acid), and GL (3 - (2 - oxotetrahydropy

ran - 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 tepralox ydim, includin g 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 tepralox ydim (2 - [1 - [[[(2E) - 3 - chloro - 2 - propen - 1 - yl ]oxy]imino] propyl] - 3 - hydroxy - 5 - (tetrahydro - 2H - py ran - 4 - yl ) - 2 - cyclohexen - 1 - one) and its metabolites convertible to GP (3 - (tetrah ydrop yran - 4 - yl )pentane - 1,5 - dioic acid) and OH - GP (3 - hydrox y - 3 - (tetrahydrop yran - 4 - yl )pentane - 1,5 - dioic acid), calculated as tepraloxydim.”Page 10 of 37

**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. 2 5 0. 2 0 **3 .0**  **Ingredient Profile 3.1**  **Summary of Proposed Uses** Tepralox ydim is a selective broad - spectrum cyclohexene oxime herbicide intended for postemergence control of certain annual grasses and quackgrass. Tepraloxydim is a sy stemic herbicide that enters the target weed through the foliage and translocates throughout the plant, inhibiting acetyl - coenzyme A carbox yl ase (ACCase) in the plant. Tolerances were previously established in support of U.S. uses of tepralox ydi m on canola, cotton, and soy bean, 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 soy bean) 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 ARAMO TM 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 soy beans. The label has been amended and approved by PMRA in April 2010 to include its use on the additional crops in Subgroup 6C and s unflower subgroup 20B. BASF noted that they have no plans to appl y for U.S. registration of EQUINOX use on the additional Subgroup 6C crops or on s unflower subgroup 20 B crops at this time. Under the registered use pattern in Canada, tepralox ydim 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 day s for crops. The summary

of the proposed use directions for the intended crops is summarized in Table 2 .Page 11 of 37

**Table 2**  **. Summary of Directions for Use of Tepraloxydim in Canada**  Applic. Timing, T ype, and Equip. Form

ulation 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, sp p : (grain lupin, swe et, white and white sweet lupin); Phaseolus, spp. (field bean, kidney bean, lima bean (dry), navy b ean, pinto bean, tepary bean); Vigna spp (adzuki bean, blackeyed pea, catjang, cow pea, 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 ) NS 4 50 (0.045) 60 Add Merge® (0.5% v/v)

or DASH H C (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 Equip me nt EQUINOX

EC Herbicide 1.67 lb/gal EC 33 - 4 0

(0.029 - 0.0 36 ) NS 4 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 stag e. 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 spe cific 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. 3 All types including imazethapyr and imazamox tolerant sunflower with the CLEARFIELD trait. 4NS= not specif

ied on label. **3 .2**  **Structure and Nomenclature** Structure and nomenclature of tepraloxydim are reported in Table 3 .Page 12 of 37

**Table 3. Tepraloxydim Structure and**  **Nom enclature**  **.** Chemical structure

O O H O N O Cl

C H 3

Molecular Formula C 17 H 24 ClO 4 Common name Tepraloxydim 1 Com pany experimental name BAS 620 H; DP IUPAC name (5 RS ) - 2 - {(EZ ) - 1 - [(2 E) - 3 - chloroallyloxyimino]propyl} - 3 - hydroxy - 5 - perhydropyran - 4 - ylcyclohex - 2 - en - 1 - one CAS name 2 - [1 - [[[(2 E) - 3 - chloro - 2 - propen - 1 - yl]oxy]imino]propyl] - 3 - hydroxy - 5 - (tetrahydro 2H - py ran - 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; 1.6 7 lb ai/gal EC) Che mical Class C yclohexene oxime herbicide Known Impurities of Concern None Chemical structure: Metabolite

O O H O N O Cl

C H 3

O H Common name Metabolite: 5 - OH - DP; BH 620 - 5 - OH - DP Chemical name 2 - [1 - [[[(2 E) - 3 - chloro - 2 - propen - 1 - yl]oxy]imino]propyl] - 3,5 - hydroxy - 5 - (tetrahydro - 2H

- py ran - 4 - yl) - 2 - cyclohexen - 1 - one Chemical structure: Oxidation product determined by analytical method O C O O H C O O H

Common name GP; BH 620 - GP Chemical name 3 - (tetrahydropyran - 4 - yl)pentane - 1,5 - dioic acidPage 13 of 37

**Table 3. Tepraloxydim Structure and**  **Nom enclature**  **.** Chemical structure: Oxidation product determined by analytical method O C O O H C O O H O H 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 phy sicochemical properties of tepraloxydim ar e 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 tepralox yd im on imported dry bean and dry

pea subgroup 6C and sunflower subgroup 20B commodities . For domestic uses, humans may be exposed to tepralox ydim in food and drinking water, since tepralox yd im may be applied directly

to growing crops and application may result in tepraloxydim reachi ng surface and ground water sources of drinking water. In an occupational setting, applicators may be exposed while handling the pesticide prior to application, as well as during application. There is a potential for post application exposure for workers re - entering treated fields. There are no residential uses of tepralox ydim; thus, there is no exposure in residential or non - occupational settings. Several risk assessments have been previousl y prepared for the existing uses of tepralox ydim. This risk assessment considers all of the aforementioned exposure pathways based on the proposed new uses of tepralox yd im, but also considers the existing uses as well, particularl y 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 Addres s Environmental Justice in Minority Populations and L ow - Income Populations,” http://www.eh.doe.gov/oepa/guidance/justice/eo12898.pdf . As a part of every

pesticide risk assessment, OP P considers a large variet y 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 consumpt ion, 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 pesticid e risk assessments for all registered food uses of a pesticide. These data are anal yz ed and categorized by

subgroups based on age, season of the year, ethnic group, and region of thePage 14 of 37

country . Additionally , OPP is able to assess dietary exposure to smalle r, 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, youth s, and adults entering or playing on treated areas post - application are evaluated. Further considerations are currentl y in development as OPP has committed resources and expertise to the development of specialized software and models that consider exposur e to b ys tanders and farm workers as well as lifestyl e and traditional dietary patterns among specific subgroups. **4 .0**  **Hazard Characterization/Assessment** References:

TEPRALOXYDIM

– Human Health Risk Assessm ent 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

– R eport of the FQPA Safety Factor Committee, B. Tarplee, HED Doc. No. 014403, 12/13/00. The most recent risk assessment was supported b y the HED HIARC report (HED D oc. No. 014515, 2/26/01). HED has reevaluated the existing toxicity database in accordance w ith the 2002 FQPA policy

and has retained the 10X FQPA Safety Factor for lack of a NOAE L in the acute neurotoxicity

study (aRfD, general population including infants and children). HED is no longer requiring a developmental neurotoxicity ( DNT ) study . Add itionally , 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** T he e xisting toxicity

database is adequate to characterize hazard and support the existing and requested food tolerances for tepralox ydim . The following studies are available for consideration :

•  Subchronic: Dietary

90 - day toxicity (rat); dietary 90 - day

toxi city (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, tepralox yd im is readily and almost completely

absorbed after oral administration, but is rapidly excreted mainly

via the urine. Biliary excretion was approxim ately 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 o bserved 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 py ran ring to lactone via a h ydroxy 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 tepralox ydim are indepe ndent of dose level, sex, route of administration (oral vs. i.v.), and site of label (p yr an vs. cyclohexanone). **4.2.1 Dermal Absorption**  T he dermal absorption rate was estimated from the results of the 28 - day dermal toxic ity

study in rats (MRID 44467140) and the developmental rat toxicity studies (MRID 44467203/44467204). In the oral developmental toxicity study , the maternal NOAEL/LOAEL s 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 sy stemic and dermal NOAEL wa s the limit dose of 1000 mg/kg/day and the L OAEL wa s 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 LOAEL s from the oral and de rmal studies (360/1000 x 100). This conservative a pproach results in a dermal absorption rate of 36% . **4 .3**  **Toxicological Effects** The main target organs for tepralox ydim toxicity are the liver, the spleen/hematopoietic sy stem and reproductive s ys tem. 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, hepatocy te h yp ertrophy , in addition to increased hepatocellular neoplasms in the mouse and rat carcinogenicity studies. Bile accumulation including cry stalline material was also reported within the liver cells and canaliculi at the relativel y high dose of 325 mg/kg/day in the 13 - we ek dog study . In a non - guideline rat oral feeding study, tepralox yd im weakly induced pentoxy

resorufin - O - deethylase activity ( cy tochrome P - 450 activity) , t ypicall y induced b y poly nuclear aromatic hydrocarbons such as 3 - methylcholanthrene ; however, it faile d to induce peroxisomal β - oxidation or alter the glutathione cellular levels . The reproductive s ys tem i s a major target but was affected at relativel y high doses (in excess of LOAELs established in repeat - dose mouse, rat and dog studies ) . In the mouse carcinogenicit y feeding study, tepralox yd im caused morphological microscopic changes indicative of reduced secretory activity in the seminal vesicles and preputial gland s in male mice. Increased uterinePage 16 of 37

sclerosis, decreased corpora lutea, and decreased foll icles 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 w ere observed in the high dose group (155 mg/kg/day) of the rat carcinogenici ty

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 weight s associated with atrophy and azoospermia , and, in the supplementary one - year study, b y diminished epididy

mal and prostatic secretory activities which were accompanied b y a marked loss of acinar lumina and a moderate interacinar sclerosis at 248 mg/kg/day . Tepralox ydim also affected the hematopoietic s ys tem. In dogs, hemoly tic anemia was demonstrated b y 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 dose d at 248 mg/kg/day beginning on D ay 88 and throughout the one - ye ar study period. These changes were accompanied b y compensatory responses, including splenic hematopoiesis, femoral and sternal bone marrow h yp erplasia, 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 t epraloxydim while no increased susceptibility

was evident in the developing rabbit fetus or rat pups . In the rat developmental toxicity

study , the developmental toxicity L OAEL of 12 0 mg/kg/day , based on reduced fetal body weights, delayed ossification and the occurrence of h ydroureter, is 3 - fold less than the maternal toxicity L OAEL of 36 0 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 externall y 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 te sted 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 NOAE L and LOAEL (50.6 and 260.0 mg/kg/day , respectivel y) were equal for both the offspring developmental s ys temic toxicity and the parental sy stemic toxicity . Further, there were no effects on an y 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 r ats, 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

w as 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 sy stem.Page 17 of 37

Tepralox ydim has a low acute toxicity based on its classification in Toxicity Category III via the oral route, Toxicity

Category I II b y 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 Safet y Factor i s retained for assessing the acute dietary risk (aRfD) for the general population in the form UF L since a LOAEL was used as the point of dep arture ( 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 a bsence of any

other treatment related clinical signs (including FOB) or neurohistopathological effects. The dose - response relationship of tepralox ydim indicates that an uncertainty factor of 10X is sufficientl y 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 FQP A Safet y Factor i s reduced to 1X for these scenarios. **4 .**  **4 .1**  **Completeness of the Toxicology Da tabase**  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 i mmunotoxicity studies have not yet been submitted, there is no evidence of immunotoxicity in an y study in the toxicity

database for tepraloxydim . In the absence of specific immunotoxicity

studies, EPA has evaluated the available tepraloxydim toxicity data base 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 (hy perpla sia) are compensatory responses to tepralox yd im - induced hemoly tic anemia. Due to the lack of evidence of immunotoxicity for tepralox ydim , 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 d oes 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 D ay 0 (29 - 41% below control, p < 0.05 for females, NS for males ) and sustained until Day 7 in mid dose females onl y (~30%, 1000 mg/kg/day ; p < 0.01) . In the subchronic ne urotoxicity study , increased motor activity

was observed in females on Day 50 (28 - 44% above control) in both sexes on D ay

85 at the highest dose tested (428 mg/kg/day , males ; 513 mg/kg/day , females) . HED priorl y recommended a developmental neurotoxicity s tudy (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) neurot oxic 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) do sing and at 428 mg/kg/day in males and 513 mg/kg/day in females following dietary a dministration in the subchronic neurotoxicity study ; 2) in the two generation reproduction study , no clinical signs i ndicative of neurotoxicity were seen in the parental animals or offspring , nor was there evidence for increased susceptibility ( th e offspri ng 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 currentl y 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 h ydroureter at 120 mg/kg/day (developmental LOAEL). Rare malf ormations (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 qualit ative 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 increas ed susceptibility following pre natal 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). T here is no residual uncertainty for pre - and/or postnatal toxicity .Page 19 of 37

**4.4.4 Residual Uncertainty in the Exposure Database**  T he database is adequate and there are no residual uncertainties for pre - and/or postnatal toxicity . Furthermo re, there are no additional residual uncertainties with respect to exposure data. The dietary food exposure assessment utilizes proposed tolerance level residues and 100% CT in formation for all commodities. The drinking water assessment ( screening level, Tier 1 estimates) utilizes values generated b y model s and associated modeling parameters which are designed to provide conservative, health protective, high - end estimates of water concentrations. By using thes e screening - level assessments, acute and chro nic 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 exposure s 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 tim e. However, aggregate food and drinking water exposures are considered in this assessment. **4.5. 2**  **Cancer Classification and Ri sk Assessment**  **Recommendation** In accordance with the 199 9 EPA’s Draft Guidelines for Carcinogen Risk Assessment (March, 2005), tepralox ydim was classified as **"** Data are inadequate for an Assessment of human carcinogenic potential because some evidence is suggestive of carcinogenic effects, but other equally pert inent 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 tepralox yd im. The carcinogenicity

study in mice was tested at the L imit 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 b y the results of the chronic phase in the same strain and sex of rats .  In mice, liver tumors were seen in females onl y 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 see n onl y at the high dose (i.e., lack of dose response);  The incidences of these tumors were within the ranges for the historical control s;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 onl y at excessive doses (i.e., greater than the L imit 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 /g enotoxicity ; 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 adequatel y account for all chronic effects, including carcinogenicity , likely to result from exposure to tepralox yd im . **4.5.3 Summary of Poi**  **nts of Departure and Tox i**  **city Endpoints Used in Human Risk Assessment**  **Table 4**  **. Summary of Toxicological Doses and Endpoints for Tepraloxydim for Use in Di**  **etary and Non**   ** Occupational Hum** **an 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** Ac ute Dietary (General Population, including Inf ants and Children) LOAEL =

500 mg/kg UF A= 10 x

UF H = 10 x FQPA SF retained as UF L = 10 x Ac ute RfD =

0. 5 mg/kg aPAD = 0.5 mg/kg Ac ute neurotoxicity screening battery

LOAEL = 500 mg/kg based on decreased mo tor activity in females. (The NOAEL is not ident ified . ) Ac ute Dietary (Females 13 - 49 years of age) NOAEL= 40

mg/kg UF A= 10 x

UF H = 10 x FQPA SF = 1 x Ac ute RfD =

0.4 mg/kg aPAD = 0.4 mg/kg Rat developmental toxicity

LOAEL = 120 mg/kg based on findings of reduced ossification ind icative of delayed maturation, and the occurrence of hydroureter. Chronic Dietary (All Populations) NOAEL=5

mg/kg/day UF A= 10 x

UF H = 10 x FQPA SF= 1 x Chronic RfD

= 0.05 mg/kg/day cPAD = 0.05 mg/kg/day Rat c arcinogenicity study

LOAEL = 30 mg/kg/day based on male liver microscopic lesions (eosinophilic foci). Incidental Oral Short - and Intermediate Term (1 - 30 days; 1 - 6 mo nths) These exposure scenarios do not apply to this risk assessment because there are no pr oposed or

registered residential uses of tepraloxydim.Page 21 of 37

**Table 4**  **. Summary of Toxicological Doses and Endpoints for Tepraloxydim for Use in Di**  **etary and Non**   ** Occupational Hum** **an 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 Short and Intermediate Term (1 - 30 days; 1 - 6 mo nths) These exposure scenarios do not apply to this risk assessment because there are no proposed or

registered residential uses of tepraloxydim. Inhalation Short - and Intermediate Term (1 - 30 days; 1 - 6 mo nths) 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 quantif ication of human cancer risk is not required (CARC report dated 2/27/01, TXR 0 0 14487). 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 deter mine risk associated with lower environmentally relevant human exposures. NOAEL = no observed adverse effect level. LOAEL = lowest observed adverse effect level. UF = uncertainty factor. UF A = extrapolation from animal to human (interspecies). UF H = p otential variation in sensitivity among members of the human population (intraspecies). UF L = use of a LOAEL to extrapolate a NOAEL. UF S = use of a short - term study for long - term risk assessment. UF DB = 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 concer n. 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 s imilar to an effect produced b y a “naturally

occurring estrogen, or other such endocrine effects as the Administrator may designate.” The EDSP employ s a two - tiered approach to making the statutorily required determinations. Tier 1 consists of a battery of 11 screening assay s to identify the potential of a chemical substance to interact with the estrogen, androgen, or th yroid (E, A, or T) hormonal sy stems. Chemicals that go through Tier 1 screening and are found to have the potential to interact with E, A, or T hormonal sy stems 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 an y 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 issu ed test orders/data call - ins for the first group of 67 chemicals, which contains 58 pesticide active ingr edients and 9 inert ingredients. This list of chemicals was selected based on the potential for human exposure through pathway s such as food and water, residential activity , and certain post - application agricultural scenarios. This list should not be con strued as a list of known or likely endocrine disruptors.Page 22 of 37

Tepralox ydim 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. Accordingl y, 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 soy bean, subgroup 6C and the sunflower subgroup 20B is adequately und erstood based on the available data for leguminous and oilseed crops (so ybean and canola). Tepralox ydim and the metabolites containing the 2 - cyclohexen - 1 - one moiety

are the residues of concern for the pea and bean, dried shelled, except soy bean, subgroup 6C and the sunflower subgroup 20B . HED has determined that the tolerance expression for the pea and bean, dried shelled, except soy bean, subgroup 6C and the sunflower subgroup 20B should include the combined residues of tepralox ydim and its metabolites co nvertible to GP ( 3 - (tetrahydropy ran - 4 - yl )pentane - 1,5 - dioic acid) and OH - GP ( 3 - hydrox y - 3 - (tetrah ydrop yr an - 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 Livest**  **ock** The nature of the residues of tepralox ydim in livestock is adequatel y 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 - oxotetr ahydrop yr an - 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 Assessme nt for Tepraloxydim. J. Breithaupt, DP338939, 5/1/07 N o new estimated drinking water concentrations (EDWCs) were computed for the new tolerances on imported commodities from this petition . T he estimated environmental concentrations (EECs) previous comput ed for surface water concentration s are the values provided b y the Environmental Fate and Effects Division (EFED) . The uses on so ybeans, 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 day s 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 relativel y unrefined estimates. The estimates of tepraloxydim concentrations in surface water were based on the FIRST model, a Tier I model, and include two signif icant 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 ba sed on the MARC memo (DP272004, L . Cheng, 2/2/01) . DP - 8 was not included in the modeling, because it was not observed in an y 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 E E Cs 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 E E C is considered representative of both a peak and long - term average concentration because of the inhe rent nature of ground wate r ( i.e. , generall y 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**  **W ater Concentrations**  **for Tepraloxydim.** Parent, DP - 1 and DP - 2 Surface Water Conc., ppb [ μg/L ] a Ground W ater Conc., ppb [ μg/L ] b Ac ute (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 half

life of 10.5 days.Page 24 of 37

**5 .1.**  **4 Food Residue Profile**  **Residues of Concern** Previously , it was determined that t epralox ydim and those metabolites containing the 2 - cylcoh exen - 1 - one moiet y are residues of concern for canola, cotton and so ybean raw agri cultural commodities . For the imported commodities that are the subject of this assessment (sunflower subgroup 20B , and dry b ean and dry p ea s ubgroup 6C ), the residues of concern are also tepralox ydim and those metabolites containing the 2 - cyclohexen - 1 - on e moiety , and are detected as the combined residues of tepralox ydim 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 sunf lower subgroup 20B commodities, and the combined residues of tepralox ydim and its metabolites convertible to GP and OH - GP plus DD should be used for dry b ean and dry p ea s ubgroup 6C commodities. Likewise, the residues of concern for livestock commodities are tepralox yd im and those metabolites containing the 2 - cyclohexen - 1 - one moiety , but they are measured as the combined residues of tepralox ydim and its metabolites convertible to GP, OH - GP, and GL . Although GL by itself is not of concern, it serves as a m arker for the significant metabolite DL due to conversion of the latter to GLby the anal yt ical 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 anal yt ical method. In drinking water, levels of tepralox yd im, 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 significantl y 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**  **Tol erance 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 (al so 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 tepralox ydim at approximately 50 g ai/ha, the combined residues of tepralox yd im ranged from <0.10 ppm (less than combined L OQ) to 0.18 ppm in/ on sunflower seed samples harvested at a PHIof 58 - 61 day s. Onl y two of the ten treated samples contained quantifiable residues of tepralox ydim (<0.10 and 0.18 ppm), and these samples were collected at the trials located in Wisconsin and Saskatchewan, res pectivel y. Combined residues were also <0.10 ppm in/on two treated sunflower seed samples harvested 61 day s after application of tepraloxydim at thePage 26 of 37

exaggerated rate of 147 g ai/ha. The crop field study is supported b y adequate storage stability data. In the residue decline experiment, combined residues of tepralox ydim were <0.10 ppm in/on duplicate treated seed samples collected at 41, 50, 61, 70 and 80 day s after treatment; therefore, the results are inconclusive with respect to decline at longer sampli ng 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 PHI s of 53 - 63 day s combined residues we re <LOQ (<0.10 ppm) in all dry bean seed samples (<0.05 ppm for tepralox ydim 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 w ere non - quantifiable at PHIs of 70 and 90 day s. 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 i s prese nted 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 (includin g 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 1 HAFT = Highest average field trial result **Processed Fo od 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 (tepralox ydim, <0.05 ppm; 5 - OH - DP, 0.05 and 0.08 ppm). Residues were non - quantifiable in the refined oil. The process ing data indicate that residues of tepralox yd im did not concentrate in s unflower 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 f eedstuff associated with the sunflower subgrou p 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. T hese items, because of the low residue levels, will have an insignificant effect on the livestock dietary burdens. The maximum theoretical dietary burdens of tepralox ydim to livestock were previousl y 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 Accumula**  **tion 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** Rotation al 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 c onducted using the DEEM - FCID TM , Version 2.03, which uses food consumption data from the USDA’s Continuing Survey s of Food Intakes by Individuals (C SFII) 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 recomm ended and established tolerance levels and assumed that 100 percent of the crops were tre ated. 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 b ased 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 separatel y 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 i s 1.4 ppb and was incorporated in the DEEM - FCID model as the food categories “w ater, 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 95 th percentile of exposure. Combined dietary exposure from food and drinking water for female s 13 - 49 years old at the 95 th percentile of exposure is estimated to be 0.001844 mg/kg/day , equivalent to <1% (0.46%) of the acute Population Adj usted Dose (aPAD) . F or 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 Ac ute Dietary (95th Percentile) Chronic Dietary Cancer aPAD Dietary

Exposure (mg/kg/day) 1 % aPAD Dietary E xposure (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 1Page 29 of 37

**Table 9**  **. Summary of Dietary (Food and Drinking Water)**  **Exposure and Risk for Tepraloxydim .**  Population Subgroup Ac ute Dietary (95th Percentile) Chronic Dietary Cancer aPAD Dietary

Exposure (mg/kg/day) 1 % aPAD Dietary E xposure (mg/kg/day) 1 % cPAD Dietary Exposure (mg/kg/day) Risk Females 13 - 49 years old 0.4 0.001844 <1 0.000774 2 1 The values for the highest exposed population are bolded. 2 Data are inadequate for an assessment of human carcinogenic potential . **5 .2.2**  **Chronic Di etary 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 level s . The chronic surface water EEC for tepralox ydim is 0.7 ppb. The water residues were incorporated directly into the DEEM FCID into the food categories “water, direct, all sources” and “water, indirect, all sources.” C ombined 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 0.00121 3 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 0.00482 5 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) Informatio n**  The acute and chronic dietary assessment s are screening - level assessment s using residues at tolerance levels and assuming that 100% of requested crops are treated. **6 .0**  **Resident ial (Non**  **- Occupational) Exposure/Risk Characterization**  This document addresses an application for tolerances of tepralox ydim on imported dry beans and sunflower subgroup 20B commodities, and therefore is not expected to result in residential exposure. Additionally , tepralox ydim is registered in the US to control grass weeds in canola, cotton and soy

bean crops, as well as fallow and non - cropland in agricultural settings ( i.e. , tepra loxydim 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 expo sure 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 - 7 hPa at 20  C ), and the low proposed use rate (0. 033 to 0.124 lb ai/A). Howe ver, 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 Insecticid e, Fungicide, and Rodenticide Act Scientific Advisory Panel (SAP) in December 2009, and received the SAP’s final report on March 2, 2010Page 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 Ag ency may revisit the need for a quantitative post - application inhalation exposure assessment for tepralox ydim . Spray drift is alway s a potential source of exposure to residents nearby to spraying operations. This is particularly

the case with aerial appl ication, 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 pestic ide 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 appropriatel y apply the data and the AgDRIFT computer model to its risk assessments for pesticides applied b y 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) e xposure 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 residentia l 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 conce rn 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 foll owed 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 b y 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 b y EPA’s Office of Pesticide Programs concerning common mechanism determinations and procedures for cumulating effects from substance s found to have a common mechanism on EPA’s website at http://www.epa.gov/pesticides/cumulative/. **9 .0**  **Occupational Exposure/Risk Pathway** This docume nt addresses risk resulting from use of tepralox ydim 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. 50 0) for food uses for tepralox ydim 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 Irritatio n 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

Derma l 870.3465 90 - Day

Inhalation yes yes yes yes yes a 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 Metab olism 870.7600 Dermal Penetration 870.7800 Immunotoxicity yes no b yes yes

no b 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 Ac ute oral (rat) 44467131 LD 50 = 5000 mg/kg III 870.1200 Ac ute dermal (rabbit) 44496403 LD 50 > 2000 mg/kg III 870.1300 Ac ute inhalation (rat) 44467132 LC 50 > 5.1 mg/L IV 870.2400 Ac ute eye irritation (rabbit) 44467133 minimal eye irritation III 870.2500 Ac ute dermal irritation (rabbit) 44467134 slight dermal irritation IV 870.2600 Skin sensitization (guinea pi g) 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)

Accep table/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 addit ion 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)

Acceptabl e/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)

A cceptable/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, transitio nal 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 efficien cy . **Som e 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. **Som e evidence of carcinogenicity**  870.5100 Gene Mutation

Bacterial reverse mutation assay 44467206 (1993)

Acceptable/guideline Negative ± S9 up to 5000 μg/ml with cy totoxicity 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 Cy

togenetics 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 Ac ute

neurotoxicity screening battery 44467136 (1997)

Accept able/guideline 0, 500, 1000, or 2000 mg/kg NOAEL = < 500 mg/kg LOAEL = 500 mg/kg based on decreased mo tor activity in females 870.6200b Subchronic

neurotoxicity screening battery 44467141 (1997)

Acceptable/guideline 0, 400, 1,500, o r 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) A cceptable/guideli ne 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 radiolab eled tepraloxydim is nearly 4.4 and 10 hours at the low and high dose, respectively. No accumulation of radio label wa s observed in any tissue at 120 hours post dosing. A large number of metabolites were detected in the urine, feces, and bile; the main me tabolic 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 exclus ively 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)

Una cceptable/non guideli ne 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 d evelopmental 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 Prop osed 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 - 7 hPa 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 10 3 4.6 x 10 3 1.1 x 10 4 6.8 x 10 3 3.1 x 10 3Page 37 of 37

**Appendix C**  **: International Residue Limit Sta**  **tus**



### TEPRALOXYDIM (PC Code 121005 ; 04/14/2011 ) **Table C. Summary of US and International Tolera**  **nces and Maximum Residue Limits** Residue Definition : US Canada Mexico 2 Codex 3 40 CFR 180.573: Plants: tepraloxydim (2 - [1 - [[[(2E) - 3 - chloro - 2 - propenyl]oxy]imino]propyl] - 3 - hydroxy - 5 - (tetrahydro - 2H pyran - 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)p entane 1,5 - 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 - [(2 E) - 3 - chloroallyloxyimino]propyl} - 3 - hydroxy - 5 - perhydropyran - 4 - ylcyclohex - 2 - en - 1 - one, including metabolites convertible to 3 - perhydropyran 4 - yl glutaric acid and 3 - hydroxy - 3 - perhydropyran - 4 - ylglutaric acid, as parent equivalent Livestock:(EZ

) - (RS ) - 2 - {1 - [(2 E) - 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 - (pentan 5 - olid - 3 - yl)glutar ate, as parent equivalent None

Commodity 1 Tolerance (ppm) /Maximum Residue Limit (mg/kg) US Canada Mexico 2 Codex Pea and b ean, dried shelled, except soybean, subgroup 6C 0.10 0.1 Dr ied shelled pea and bean, except soybean (Crop subgroup 6C) Sunflow er s ubgroup 20B 0.2 0 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.