### UNITED STATES ENVIRONMENTA L PROT E C T I ON AGENCY WASHING T ON

, D.C. 20 4 60

OFFICE OF CHEMICAL SAFETY AND POLLU TIO N PREVENTION



### MEMORANDUM



### Date: 02-DEC-20 14



### SUBJECT: Sodium Bentazon

- Preliminary Human Health Risk Assessment for Registration Review.

PC Code : 275200

, 103901 Decision No : 486719 Petition No : N / A DP Barcode : 0417312 Registration Nos.: NA Regu l atory Act i on: Registration Review Risk Assessment Case No.: 0182 Risk Assessment Tvpe: Single Chemica V

Aggregate
TXRNo.: CAS No.: 50723-80-3

, 25057-89

- 0 40 CFR: §180.355 MRIDNo

. : NA



### From: 

## Kelly M. Lowe, Environmental Scientist

# ~ _ George F. Kramer, Ph.D., Senior Chem i st • Anwar Y. Dunbar, Ph.D., Pharmacologist · ' 

# Jl

. --- Ri s k

### Assessme~t Branch 1 (RAB 1 ) 

# j/
Heal th Effects Di v ision (HED; 7509P)



### Through: Charles W. Smith III, Branch Chief
RABl / HED (7509 P) 

# ___ ,

To: Carolyn Schroeder Pesticide Reevaluation Divi s ion (7506P)

As part of Regi strat i on Review, the Pesticid e Re-evaluation Division (PRD) of OPP has requested that HED evalua te the hazard and exposure data and conduct occu pational and residential exposure assessme nts
, as needed

, to estimate the risk to human health that will result from the currently registered uses of pesticides

. This memorandum serves as HED's Preliminar y Registration Review risk assessm ent of the dietary, occupational and re sidentia l handler

, postapplication exposure, and aggregate risk from the registered uses of sodium bentazon.

A summary of the findings and an assessment of human risk resulting fro m the registe r ed uses

are provided 

### in thi s document. The risk assessment and the occupational /resi dential exposure and risk assessment were provided by Kelly L owe (RAB 1 ), the dietar y risk assessment and

re s idue chemistry review were provided by George Kramer (RAB 1 )

, the hazard characterization

was provided by Anwar Dunbar (RAB 1 ), and the drinking water assessment was provided by Stephen Wente of the Environment al Fate and Effects Division (E FED).

Pa ge I of40Bentazon Preliminary Human Health Risk Assessment D471312



### Table of Contents

1.0 Executive Summary

.. . .. .. .. .. .. ..... .. . . .... . ... . .. .. ................................................... ... . .. ................ 4
2.0 Recommendations

............................................................................................................... 6 2.1 Data Deficiencies/Data Needs

........................................................................................ 6 2.2 Tolerance Considerations

............................................................................................... 6 2.2.1 Enforcement Analytical Method

........................................................................... 6 2.2.2 Recommended Tolerances

.................................................................................... 7 2.2.3 Revisions to Established Tolerances

........................................ . ............................ 9 2.2.4 International Harmonization

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

...... . ... . ................................................................... . ... .. .. . ..... . .... 9 3.0 Ingredient Profile

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

............................................................................... . ............................ 9
3.2 Physical/Chemical Properties

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

......................................................................................... . .......................... 10
3.4 Anticipated Exposure Pathways

................................................................................... 12 3.5 Consideration ofEnvironmental Justice

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

............................................. 13
4.1 Toxicology Studies Available for Analysis

.................................................................. 13 4.2 Absorption, Distribution, Metabolism, & 

### Excretion (ADME)

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

.............................................................................................. 14 4.3 Toxicological Effects

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

...................................... 15
4.4.1 Completeness ofthe Toxicology Database

......................................................... 15
4.4.2 Evidence ofNeurotoxicity

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

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

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

................................................. 16
4.5.1 Dose-Response Assessment

................................................................................ 16 4.5.2 Recommendation for Combining Routes of Exposures for Risk Assessment..

.. 17
4.5.3 Cancer Classification and Risk Assessment Recommendation

.......................... 17 4.5.4 Summary of Points of Departure and Toxicity Endpoints Used in H uman Health
Risk Assessment

................................................................................... . ........ . .................. 1 7 4.6 Endocrine Disruptor Screening Program

........................................................... .. ......... 18
5. 0 Dietary Exposure and Risk Assessment

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

.......................................................................... 19 5 .1.1 Summary of Plant and Animal Metabolism Studies

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

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

................................................................... 20 5 .1.4 Residues of Concern Summary

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

.................................................................................................... 20
5.3 Drinking Water Residue Profile

................................................................................... 21 5.4 Dietary (Food + Drinking Water) Risk Assessment..

................................................... 21
6.0 Residential (Non-Occupational) Exposure/Risk Characterization

................................... 22 6.1 Residential Handler Exposure/Risk Estimates

............................................... . ............. 22
6.2 Residential Post-application Exposure/Risk Estimates

....................................... . ........ 23
6.3 Residential Risk Estimates for Use in Aggregate Assessment..

........ . .......................... 23 6.4 Spray Drift

........................................................................................ . ... . .. . .................... 24
6.5 Residential Bystander Post-Application Inhalation Exposure

...................... .. ........ .. ... . 24

Page 2 of40Bentazon Preliminary Human Health Risk Assessment D 471312

____________________________________________________________________________________________

Page 3 of 40 

### 7.0 Aggregate Exposure/Risk Characterization

................................ ................................ ...... 25

8.0 Cumulative Exposure/Risk Characterization

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

................................ ................................ . 27

10.0 References

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

................................ ....................... 32 Appendix B. Physical/Chemical Properties

................................ ................................ ................. 37 Appendix C. International Residue Limits

................................ ................................ .................. 38 7.1 Acute Aggregate Risk

................................ ................................ ................................ ... 25 7.2 Short

- and Intermediate

- Term Aggregate Risk

................................ ............................ 25 7.3 Chronic Aggregate Risk

................................ ................................ ................................ 26 7. 4 Cancer Aggregate Risk

................................ ................................ ................................ . 26

9.1 Handler Risk Assessment

................................ ................................ ............................. 27 9.2 Post

- Application Risk Assessment

................................ ................................ ............... 29 9.2.1 Inhalation Post

- Application Risk Assessment

................................ .................... 29 9.2.2 Dermal Post

- Application Risk Assessment

................................ ........................ 30Bentazon Preliminary Human Health Risk Assessment D 471312

____________________________________________________________________________________________

Page 4 of 40 

### 1.0 Executive Summary

Sodium bentazon (herein referred to as bentazon) is a selective, contact, early postemergent herbicide used to control a variety of broadleaf weeds and sedges. This preliminary risk assessment provides information to support the Registration Review of ben tazon, and addresses the exposures and risk estimates associated with all currently registered uses. Since the last risk assessment, new data have been submitted and policies have changed. This document incorporates changes made to the selected endpoints , toxicological points of departure (PODs), exposure and risk estimates, recommended tolerances, and the potential for spray

- drift exposure. All data requirements previously identified during the scoping process have been satisfied (G. Kramer, D375437, 17

- MAR

- 2010).

Hazard Assessment: In subchronic studies in rats and dogs and in chronic studies in all species, the most toxicologically significant effects were changes in hematological/coagulation parameters following bentazon administration through the oral route. In rats and rabbits, fetal effects occurred at doses that caused maternal toxicity. In the rat developmental toxicity study, maternal effects consisted of increased post

- implantation loss and fetal resorptions, and developmental effects cons isted of skeletal variations and reduced fetal weights. In the rabbit developmental toxicity study, at the highest dose tested, maternal effects consisted of partial abortions with resorptions, and developmental effects consisted of an increased incidence of no living fetuses. In the two

- generation reproductive toxicity study in rats, there was an increased quantitative offspring susceptibility. Offspring toxicity manifested as reduced absolute pup weights during lactation at a dose lower than where pare ntal systemic toxicity was observed. The sole parental effect was an increased incidence of kidney mineralization and liver microgranuloma. There were no effects on reproductive parameters.

In the acute neurotoxicity study, effects observed at the mid

- and high

- dose groups consisted of decreased motor activity in males on day 0. There were no effects in the subchronic neurotoxicity study, and bentazon was negative for immunotoxicity. In a 21

- day dermal toxicity study, no effects were observed up to 1000 mg/kg/day. Bentazon was not found to be mutagenic, and is classified as a Group “E” chemical (evidence of non

- carcinogenicity for humans) based upon lack of evidence of carcinogenicity in rats and mice.

Food Quality Protection Act (FQPA) Safe ty Factor (SF) Decision: The RAB1 risk assessment team determined that the FQPA SF can be reduced to 1X based on the following considerations: 1) the toxicology database for bentazon is adequate for risk assessment; 2) bentazon is not considered neurotox ic; 3) all fetal and offspring effects are well characterized and protected for; and 4) the exposure databases are sufficient and unlikely to underestimate exposure.

Dose Response Assessment: The acute neurotoxicity screening battery in the rat was selec ted for the acute dietary endpoint for all population s [no

- observed adverse

- effect level (NOAEL) = 50 mg/kg/day ] . The two

- generation reproductive study was selected for the chronic dietary endpoint for the general population, the incidental oral endpoint, and the inhalation endpoint (NOAEL = 15 mg/kg/day). Based upon a lack of effects in the 21

- day dermal toxicity study, and the low dermal absorption values for bentazon (1

- 2%) in the guideline dermal penetration study,

a quantitative dermal assessment is not required. Bentazon has been classified as a Group “E” chemical (evidence of non

- carcinogenicity for humans) based upon lack of evidence of carcinogenicity in rats and mice (TXR 010787, J. Rowe, 1/14/92). Therefore, a cancer exposure and risk assessme nt is not required.Bentazon Preliminary Human Health Risk Assessment D 471312

____________________________________________________________________________________________

Page 5 of 40 

### Dietary Risk Estimates (Food + Drinking Water ): Acute and chronic aggregate dietary (food and drinking water) exposure and risk assessments were conducted using the Dietary Exposure Evaluation Model

- Food Consumption Intake Database (DEEM

- FCID, ver. 3.16) which incorporates consumption data from Unit ed States Department of Agriculture (USDA) National Health and Nutrition Examination Survey, “ What We Eat in America ” (NHANES/WWEIA; 2003

- 2008). The acute and chronic analyses assumed tolerance

- level residues, 100% crop treated (CT), DEEM (ver. 7.81) defa ult processing factors, and modeled drinking water estimates. The resulting acute and chronic dietary risk estimates are not of concern to HED, and the subgroups with the greatest risk estimates utilized ≤73% of the acute population

- adjusted dose [aPAD; a ll infants (<1 year old)] and ≤78% of the chronic population

- adjusted dose [cPAD; all infants (<1 year old)], respectively.

Residential (Non

- Occupational) Exposure and Risk Assessment: There is the potential for residential exposure from the registered uses on ornamentals and turf. These uses have been assessed using the most up

- to

- date exposure policies and data available in the 2012 Residential Standard Operating Procedures (SOPs) . Since a dermal hazard was not identified, a quantitative dermal asse ssment was not conducted for the residential uses of bentazon. The inhalation exposure risk estimates for residential handlers are not of concern [ i.e., margins of exposure ( MOEs ) ≥ the level of concern (LOC) of 100; 10X uncertainty factor (UF) for inters pecies extrapolation, a 10X UF for intraspecies variability, and a 1X FQPA SF ] at baseline for all scenarios. All residential post

- application risk estimates are also not of concern (i.e., MOEs ≥ the LOC of 100). A quantitative spray drift assessment for bentazon is not required since the turf post

- application MOEs are protective for any potential exposures related to spray drift for bentazon.

Aggregate

- Risk Estimates: In accordance with FQPA, HED must consider and aggregate pesticide exposures and risk s from three major sources: food, drinking water, and residential exposures. Acute, chronic, short

- , and intermediate

- term aggregate assessments were included in this risk assessment. An aggregate cancer risk assessment was not performed because bentazo n is not considered to be a carcinogen. Acute and chronic aggregate risks are made up only of dietary sources; therefore, the exposure estimates provided in the dietary exposure analyses represent acute and chronic aggregate exposure, respectively. Short

- and intermediate

- term aggregate risks are made up of dietary and non

- dietary sources of exposure. Since bentazon is used on turf, residential handler and post

- application exposures are expected. Short

- term exposures exist for adults and children from t he registered turf application use ; intermediate

- term exposure is not anticipated, but since the short

- and intermediate

- term PODs are the same for bentazon, the short

term aggregate is protective of longer

- term exposures . All aggregate bentazon risk esti mates are not of concern to HED.

Occupational Exposure and Risk Assessment: There is the potential for occupational exposure from the registered uses of bentazon. These uses have been assessed using the most up

- to

- date exposure policies and data avail able. Since no dermal hazard was identified for bentazon, a quantitative dermal assessment was not conducted for the occupational uses of bentazon. The occupational handler exposure and risk estimates indicate that the short

- and intermediate

- term inhala tion MOEs are not of concern to HED (i.e., MOE > the LOC of 100). Occupational post

application dermal exposure and risk estimates were not quantitatively assessed since a dermal hazard was not identified. In this case, the restricted

- entry interval (REI) is based on the acute toxicity of bentazon technical material, which would require a 24

- hour REI under 40 CFR 156.208 (c) (2).Bentazon Preliminary Human Health Risk Assessment D 471312

____________________________________________________________________________________________

Page 6 of 40 

### Based on the Agency's current practices, a quantitative non

- cancer occupational post

- application inhalatio n exposure assessment was not performed for bentazon at this time. If new policies or procedures are put into place, then the Agency may revisit the need for a quantitative occupational post

- application inhalation exposure assessment for bentazon

.

Enviro nmental Justice Considerations: Potential areas of environmental justice concerns, to the extent possible, were considered in this human health risk assessment, in accordance with U.S. Executive Order 12898, “Federal Actions to Address Environmental Justi ce in Minority Populations and Low

- Income Populations.”

Review of Human Research : This risk assessment relies in part on data from studies in which adult human subjects were intentionally exposed to a pesticide or other chemical. These data, which include studies from the Pesticide Handlers Exposure Database (PHED) 1.1 and the Agric ultural Handler Exposure Task Force (AHETF) database, are (1) subject to ethics review pursuant to 40 CFR 26, (2) have received that review, and (3) are compliant with applicable ethics requirements. For certain studies, the ethics review may have include d review by the Human Studies Review Board. Descriptions of data sources, as well as guidance on their use, can be found at the following Agency websites: http://www.epa.gov /pesticides/science/handler

- exposure

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

- app

- exposure

- data.html

.



### 2.0 Recommendations

HED has examined the toxicology and residue chemistry databases for bentazon. There are no residue chemistry, residential, occupational, or toxicology data deficiencies that would preclude the continuation of permanent tolerances for residues of bentazon as outlined in Table 2.2.2.1.

2.1 Data Deficiencies/Data Needs

None.

2.2 Tolerance Considerations

2.2.1 Enforcement Analytical Method

Plants: Adequate enforcement methods are available for the determination of residues of bentazon and its 6

- and 8

- hydroxy metabolites in/on plant commodities. The Pesticide Analytical Method Volume II (PAM II) lists Method II, a gas liquid chromatography (GLC) method with flame photometric detection for the determination of bentazon and its hydroxy metabolites in/on corn, rice, and soybeans; the limit of detection (LOD) for each compound is 0.05 ppm. Method III, modified from Method II, is available for the det ermination of bentazon and its hydroxy metabolites in/on peanuts and seed and pod vegetables with a LOD of 0.05 ppm for each compound. A validated analytical method for enforcement of the residue definition is also available, with a combined limit of quan titation (LOQ) of 0.03 ppm in high water content, high oil content, acidic, and dry commodities (http://www.efsa.europa.eu/en/efsajournal/doc/2822.pdf).

Livestock: Adequate enforcement methods are available in PAM II for the determination of residues of bentazon and its metabolite 2

- amino

- N

- isopropyl benzamide ( AIBA) in livestock commodities. The methods involve quantification by gas chromatography with flameBentazon Preliminary Human Health Risk Assessment D 471312

____________________________________________________________________________________________

Page 7 of 40 

### photometric or nitrogen

- specific Coulson conductivity detectors. LOQs range from 0.02 ppm in milk to 0.05 ppm for most other commodities. A validated analytical method for enforcement of the residue definition is available with an LOQ of 0.02 ppm for meat, milk, liver, and eggs (http://www.efsa.europa.eu/en/efsajournal/doc/2822.pdf).

The data re quirements for multiresidue methods (MRMs) are fulfilled (MRID# 44227401). The FDA MRMs are not suitable as enforcement methods since bentazon residues of concern were not successfully recovered by the FDA MRMs.

2.2.2 Recommended Tolerances

Permanent to lerances have been established in 40 CFR §180.355 for the combined residues of bentazon, including its metabolites and degradates in/on various raw agricultural commodities (RACs) ranging from 0.05 ppm to 10 .0 ppm.

The tolerance expression for bentazon re sidues in plant commodities [40 CFR §180.355(a)(1) and 40 CFR §180.355(c)] should be updated to reflect current Agency policy as follows :

“Tolerances are established for residues of bentazon, including its metabolites and degradates, in or on the commod ities in the table below. Compliance with the tolerance levels specified below is to be determined by measuring only the sum of bentazon (3

- (1

- methylethyl)

- 1 H

- 2,1,3

- benzothiadiazin

4(3 H )

- one 2,2

- dioxide) and its metabolites 6

- hydroxy bentazon (6

- hydroxy

- 3

- (1

- methylethyl)

- 1 H

2,1,3

- benzothiadiazin

- 4(3 H )

- one 2,2

- dioxide) and 8

- hydroxy bentazon (8

- hydroxy

- 3

- (1

- methylethyl)

- 1 H

- 2,1,3

- benzothiadiazin

- 4(3 H )

- one 2,2

- dioxide), calculated as the stoichiometric equivalent of bentazon, in or on the following commoditie s:”

The tolerance expression for bentazon residues in livestock [40 CFR §180.355(a)(2)] commodities should be updated to reflect current Agency policy as follows :

“Tolerances are established for residues of bentazon, including its metabolites and degra dates, in or on the commodities in the table below. Compliance with the tolerance levels specified below is to be determined by measuring only the sum of bentazon (3

- (1

- methylethyl)

- 1 H

- 2,1,3

- benzothiadiazin

4(3 H )

- one 2,2

- dioxide) and its metabolite 2

- amin o

- N

- isopropyl benzamide, calculated as the stoichiometric equivalent of bentazon, in or on the following commodities:”

Table 2.2.2.1 is a summary of the established and HED

- recommended tolerances for residues of bentazon.

Table 2.2.2.1. Tolerance Summary for Bentazon (40 CFR §180.355).

Commodity Established Tolerance (ppm) HED

Recommended Tolerance (ppm) Comments

(a) General. (1) Tolerances are established for the combined residues of the herbicide bentazon (3

- isopropyl

- 1 H

- 2,1,3

- benzothiadiazin

- 4(3 H

)

- one

- 2,2

- dioxide) and its 6

- and 8

- hydroxy metabolites in or on the following food commodities: Bean, dry, seed 0.05 0.05 Bean, succulent 0.5 0.50 Corn, field, forage 3.0 3.0 Corn, field, grain 0.05 0.05 Corn, field, stover 3.0 3.0 Corn, pop, grain 0.05 0.05Bentazon Preliminary Human Health Risk Assessment D 471312

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Page 8 of 40 Table 2.2.2.1. Tolerance Summary for Bentazon (40 CFR §180.355).

Commodity Established Tolerance (ppm) HED

Recommended Tolerance (ppm) Comments

Corn, sweet, kernel plus cob with husks removed 0.05 0.05

Cowpea, forage 10.0 10 Cowpea, hay 3.0 3.0 Flax, seed 1.0 1.0 Pea, dry, seed 1.0 1.0 Pea, field, hay 8.0 8.0 Pea, field, vines 3.0 3.0 Pea, succulent 3.0 3.0

Peanut 0.05 0.05 Peanut, hay 3.0 3.0 Pepper, nonbell 0.05 0.05 Peppermint, tops 1.0 1.0 Rice, grain 0.05 0.05 Rice, hulls 0.25 0.25 Rice, straw 3.0 3.0 Sorghum, grain, forage 0.20 0.20 Sorghum, grain, grain 0.05 0.05 Sorghum, grain, stover 0.05 0.05 Soybean, forage 8.0 8.0 Soybean, hay 8.0 8.0 Soybean, seed 0.05 0.05 Spearmint, tops 1.0 1.0 (2) Tolerances are established for the combined residues of the herbicide bentazon (3

- isopropyl

- 1 H

- 2,1,3

- benzothiadiazin

4(3 H )

- one

- 2,2

- dioxide) and its metabolite 2

- amino

- N

- isopropyl benzamide (AIBA) in or on the following food commodities:
Cattle, fat 0.05 0.05 Cattle, meat byproducts 0.05 0.05 Cattle, meat 0.05 0.05 Egg 0.05 0.05 Goat, fat 0.05 0.05 Goat, meat byproducts 0.05 0.05 Goat, meat 0.05 0.05 Hog, fat 0.05 0.05 Hog, meat byproducts 0.05 0.05 Hog, meat 0.05 0.05

Milk 0.02 0.02 Poultry, fat 0.05 0.05 Poultry, meat byproducts 0.05 0.05 Poultry, meat 0.05 0.05 Sheep, fat 0.05 0.05 Sheep, meat byproducts 0.05 0.05 Sheep, meat 0.05 0.05 (c) Tolerances with regional registrations. Tolerances with regional registration as defined in §180.1(m), are established for combined residues of the herbicide, bentazon (3

- isopropyl

- 1 H

- 2, 1,3

- benzothiadiazin

- 4(3 H )

- one

- 2,2

- dioxide) and its 6

- and 8

- hydroxy metabolites in or on the following food commodities: Clover, forage 1.0 1.0Bentazon Preliminary Human Health Risk Assessment D 471312

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Page 9 of 40 Table 2.2.2.1. Tolerance Summary for Bentazon (40 CFR §180.355).

Commodity Established Tolerance (ppm) HED

Recommended Tolerance (ppm) Comments

Clover, hay 2.0 2.0



### 2.2.3 Revisions to Established Tolerances

The tolerance expressions for bentazon need to be updated to reflect current Agency policy (see Section 2.2.2 ). HED is not recommending for any changes in the tolerance levels at this time

, although the values fo r cowpea, forage and bean, succulent should be updated to contain the appropriate number of significant figures

.

2.2.4 International Harmonization

U.S. permanent tolerances (listed in 40 CFR 180.355) and Maximum Residue Limits (MRLs) are summarized in Ap pendix C. The U.S., Mexico, Canada, and Codex residue definitions for crops are harmonized. For some raw agricultural commodities, the tolerances and MRLs for the U.S., Canada, Mexico, and Codex are harmonized; however, there are several commodities for which the tolerance and MRLs are not harmonized. There are discrepancies between the U.S. residue definition and the Codex residue definition for livestock commodities. Harmonization of the tolerance/MRL levels is not possible as the U.S. use patterns re quire a higher tolerance or the MRL level is below the LOQ of the enforcement method. These discrepancies have been bolded in Appendix C.

2.3 Label Recommendations

None.

3.0 Ingredient Profile

3.1 Chemical Identity

The chemical structure and nomenclature of bentazon are presented in Table 3.1.1.

Table 3.1.1. Nomenclature for Bentazon.
Common Name Bentazon Chemical Name (CAS) 3

- (1

- methylethyl)

- 1 H

- 2,1,3

- benzothiadiazin

- 4(3 H )

- one 2,2

- dioxide PC Codes 103901 bentazon sodium salt 275200 bentazon Chemical Abstracts Nos. 50723

- 80

- 3, 25057

- 89

- 0 Registration Review Case
No. 0182

Chemical Class Benzothiadiazinone herbicideBentazon Preliminary Human Health Risk Assessment D 471312

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Page 10 of 40 Table 3.1.1. Nomenclature for Bentazon. Chemical Structure



### 3.2 Physical/Chemical Properties

Bentazon is soluble (570 mg/L) in water

. The vapor pressure (<1 x 10

- 7 

### mm Hg) and Henry's Law Constant (5.55 x 10

- 11 

### atm m 3 

### /mol) indicate that the compound is relatively non

- volatile under field conditions

. The n

- octanol water partition coefficient (Log K ow 

### =

- 0.46) for bentazon indicat es a low potential for bioaccumulation

. A table of the physical/chemical properties for bentazon is provided in Appendix B.

3.3 Use Pattern

There are 11 end

- use product labels, and 4 special local need labels (SLNs), registered with bentazon as the active ingredient. All products are liquid formulations. The labeled use sites include various agricultural crops, non

- bearing food crops, non

- cr opland sites, roadsides, rights

of

- way, nursery stock, ornamentals, and turf (including athletic fields, commercial/residential settings, golf courses (not greens), recreational areas, and sod farms). Most of the uses are foliar, and are applied via aeria l , groundboom

, or handheld equipment. The maximum application rate supported by the registrants is 1.5 lb ai/A for any use site ; however, most use sites have a maximum single application rate of 1 lb ai/A (0.023 lb ai/gal). A summary of the current use

p attern is included in Table 3.3.1 below.

Table 3.3.1. Summary of Proposed Directions for Use of Bentazon.

Crop/Use Site Application

Timing and Type of Application Registered

Formulations Maximum

Application
Rate Limitation and Restrictions Personal
Pr otective Equipment (PPE) Max # apps/yr Min RTI

(days) REI

(hrs) PHI

(days)

Alfalfa (grown for seed production) Prior to flower

bud formation

Aerial, Groundboom

Soluble and

Emulsifiable Concentrates 1.5 lb ai/A

2 5

48 NA Long

sleeved shirt, long pants, gloves, shoes and socks;

some labels require protective

eyewear Beans (dry and succulent) Early

postemergence

Aerial, Groundboom 1.5 lb ai/A NA 30

Clover (grown for seed) Early

postemergence

Aerial, Groundboom 1.0 lb ai/A 5 36Bentazon Preliminary Human Health Risk Assessment D 471312

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Page 11 of 40 Table 3.3.1. Summary of Proposed Directions for Use of Bentazon.

Crop/Use Site Application

Timing and Type of Application Registered

Formulations Maximum

Application
Rate Limitation and Restrictions Personal
Pr otective Equipment (PPE) Max # apps/yr Min RTI

(days) REI

(hrs) PHI

(days)

Corn Early

postemergence

Aerial, Groundboom 1.5 lb ai/A NA 12

Flax Early

postemergence

Groundboom 1.0 lb ai/A NS 45

Non

- bearing food crops (almonds, apples, apricots, avocados, blackberries, blueberries, cherries, crabapples, dates, figs, grapes, grapefruit, lemons, limes, macadamias, nectarines, olives, oranges, peaches,

p ears, pecans, pistachios, plums, pomegranates, prunes, raspberries, tangelos, tangerines, walnuts) Postemergence

directed

Groundboom 1.0 lb ai/A NA NA

Non

- cropland sites, Roadsides, Rights

of

- way Postemergence

Groundboom, Handheld 1 lb ai/A; 0.023 lb ai/gal 7 NA

Nursery stock Postemergence

Groundboom, Handheld 1 lb ai/A; 0.023 lb ai/gal 7 NA

Ornamentals Postemergence

Groundboom, Handheld 1 lb ai/A; 0.023 lb ai/gal 7 NA

Peanuts Range from

cracking through pegging

Aerial, Groundboom 1.5 lb ai/A NA 50

Peas (dry and succulent) After 3 pairs of

leaves are present, do not apply when peas are in bloom

Aerial, Groundboom 1.5 lb ai/A NA dry peas = 30, succulen t peas = 10

Peppermint/ Spearmint Postemergence

Aerial, Groundboom 1.5 lb ai/A NA 20Bentazon Preliminary Human Health Risk Assessment D 471312

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Page 12 of 40 Table 3.3.1. Summary of Proposed Directions for Use of Bentazon.

Crop/Use Site Application

Timing and Type of Application Registered

Formulations Maximum

Application
Rate Limitation and Restrictions Personal
Pr otective Equipment (PPE) Max # apps/yr Min RTI

(days) REI

(hrs) PHI

(days)

Rice Postemergence

Aerial, Groundboom 1.0 lb ai/A NA NA

Sorghum Postemergence

( but not during crop heading or blooming )

Aerial, Groundboom 1.0 lb ai/A NA 12

Soybeans Postemergence

Aerial, Groundboom 1.5 lb ai/A NA 30

Turf (athletic fields, commercial/residenti al settings, golf courses (not greens), recreational areas, sod farms) Postemergence

Groundboom, Handheld 1 lb ai/A; 0.023 lb ai/gal 21

(per ennia l ryegrass) NA



### 3.4 Anticipated Exposure Pathways

Based on the registered bentazon application scenarios, dietary exposure is an anticipated exposure pathway as residues of bentazon may be found in/on crops, livestock commodities, and drinking water. There are residential uses of bentazon and potential for spray drift, so there is exposure in residential and non

- occupational settings. In an occupational setting, applicators may be exposed while handling the pesticide prior to application, as well as during application. There is also potential for post

- application exposure for workers re

- entering treated sites. This risk assessment considers all of the aforementioned exposure pathways based on t he existing uses of bentazon.

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, “Fed eral Actions to Address Environmental Justice in Minority Populations and Low

- Income Populations,” ( http://epa.gov/environmentaljustice/resources/policy/exec_order_12898.pdf ). As a part of every pesticide risk assessment, OPP considers a large variety of consumer subgroups according to well

- established procedures. In line with OPP policy, HED estimates risks to population subgroups from pesticide exposures that are based on patterns of that subgroup’s food and water consumption, and activities in and arou nd the home that involve pesticide use in a residential setting. Extensive data on food consumption patterns are compiled by the USDA NHANES/WWEIA ( 2003

- 2008)

, and are used in pesticide risk assessments for all registered food uses of a pesticide. These data are analyzed and categorized by subgroups based on age, season of the year, ethnic group, and region of the country. Additionally, OPP is able to assess dietary exposure to smaller, specialized subgroups and exposure assessments are performed when conditions or circumstances warrant. Whenever appropriate, no n

- dietary exposures based on home use of pesticide products and associated risks for adult applicators and for toddlers,Bentazon Preliminary Human Health Risk Assessment D 471312

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Page 13 of 40 

### youths, and adults entering or playing on treated areas post

- application are evaluated. Further considerations are currently in develo pment as OPP has committed resources and expertise to the development of specialized software and models that consider exposure to bystanders and farm workers as well as lifestyle and traditional dietary patterns among specific subgroups.

4.0 Hazard Chara cterization and Dose

- Response Assessment

Bentazon is a benzothiadiazinone contact herbicide that is manufactured by the BASF Corporation. Its herbicidal mode of action in plants is through inhibition of photosynthesis via inhibition of photosystem II (PS II). In mammals, bentazon’s effects are predominantly on the hematopoietic system.

4.1 Toxicology Studies Available for Analysis

The toxicological database for bentazon is complete for risk assessment purposes. Since the last risk assessment, the regu latory decisions for the developmental rat and chronic dog studies were updated for consistency with the agency’s current policies resulting in revised NOAEL and lowest

- observed adverse

- effect level (LOAEL) values (Dunbar et al. , 01

- OCT

- 14, D433967). The neurotoxicity screening batteries and a 28

- day rat immunotoxicity study have been submitted to the Agency and reviewed. In addition, HED’s Hazard Science and Policy Council (HASPOC) met on September 11, 2014 (TXR# 0057054) to evaluate the need for a repea ted exposure inhalation toxicity study for bentazon. The HASPOC concluded that based on a weight

- of

- evidence (WOE) approach considering all hazard and exposure data for bentazon, that a subchronic rat inhalation study was not required at this time. The r esults of the three newly submitted studies and revised regulatory decisions are included in this hazard assessment.

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

The ADME for bentazon is well characterized using a series of available studies. In an initial study comparing sodium bentazon and the free acid at a single oral dose of 4 mg/kg, the absorption and excretion of both forms appeared to be rapid and essentially equivalent based on (1) similar peak plasma concentration values (C m ax 

### ; 5.08 and 4.87 ug equivalents, respectively), (2) similar time to maximum concentrations (T max 

### ; 0.77 and 1.18 hours, respectively) and (3) similar half

- life values (T 1/2 

### ; 3.36 and 3

- 10 hours, respectively). Area under the curve (AUC) values (0.0626 a nd 0.0680 ug x hr/ml/mg/kg) were similar as well. No sex differences in patterns of excretion (>90% in urine) or urinary metabolite profiles were observed (>80% as free acid). At sacrifice, total radioactive residue in the carcass was less than 0.69% of the dose in all

groups.

In a second study, sodium bentazon and the free acid were administered using single and repeated oral dosing, intravenous (i.v.) dosing, and bile cannulation protocols at low

- and high

doses (~4 and 200 mg/kg). For the most par t, there was no difference in the above measured parameters for route of administration (oral vs. i.v.) and for magnitude of dose. AUC values were increased ~2

- 3

- fold when comparing the low

- and high

- dose groups. Biliary excretion of radioactivity amo unted to only 0.24

- 1.31% and 0.80

- 1.84% of the administered doses for the low

- and high

- dose groups respectively. The majority of radioactivity was eliminated within the first 24 hours (~91%). Parent bentazon was the major residue found in urine, amo unting to 77.37

- 91.02% of the dose among the orally dosed animals of the main experiment. A small amount of benzene ring hydroxylation was observed; 6

- OH

- bentazon was present in amounts upBentazon Preliminary Human Health Risk Assessment D 471312

____________________________________________________________________________________________

Page 1 4 of 40 

### to 6.34% of the dose, and the isomeric 8

- OH

- bentazon was present in trace amounts, 0

- 0.23% of the dose.

4.2.1 Dermal Absorption

In a dermal

- penetration study in rats, a single topical application of radioactive sodium bentazon in an aqueous solution was applied to the backs of male Sprague Dawley rats (24/dose le vel) at doses of 0.12, 1.2, 12.0, or 120.0 mg/kg (0.002, 0.02, 0.2, or 2.0 mg free acid/cm 2 

### ). Sodium bentazon did not appear to significantly penetrate the skin after 10 hours of exposure since a maximum of only 1

- 2% of the radioactivity was recovered ( primarily in the urine) at 72 hours post

- exposure. The dermal penetration factor was estimated to be 2% (sum of tissues, carcass, and excreta) for risk assessment purposes.

4.3 Toxicological Effects

In subchronic studies in rats and dogs and in chronic studies in all species, the most toxicologically significant effects were changes in hematological/coagulation parameters following bentazon administration through the oral route. In rats, subchronic oral exposure caused increased thromboplastin and proth rombin times (PT). In dogs, hemoglobin, hematocrit, and erythrocyte counts were significantly reduced in animals at both 6 weeks and at term. PT and reticulocytes were also elevated.

The effects in the chronic studies in rats, mice and dogs were simila r to those in subchronic studies. In a chronic/oncogenicity study in mice, PT were elevated. In addition, the incidence of hemorrhage in liver and heart was increased. In a chronic/oncogenicity study in rats, partial thromboplastin times (PTT) were elev ated. In a one

- year feeding study in dogs, at the highest dose tested, there were clinical signs (emaciation, dehydration, bloody stool, pale mucous membranes, moderated activity) and a slight to severe anemia (decreased hemoglobin, hematocrit, and erythr ocyte count, decreased reticulocytes, platelets, leukocytes, PTT), and abnormal red cell morphology) during the first 13 weeks.

In rats and rabbits, fetal effects occurred at doses that caused maternal toxicity. In the rat developmental toxicity study, m aternal effects consisted of increased post

- implantation loss and fetal resorptions, and developmental effects consisted of skeletal variations and reduced fetal weights. In the rabbit developmental toxicity study, at the highest dose tested, maternal eff ects consisted of partial abortions with resorptions, and developmental effects consisted of an increased incidence of no living fetuses.

In the two

- generation reproductive toxicity study in rats, there was increased quantitative offspring susceptibilit y. Offspring toxicity manifested as reduced absolute pup weights (≥5%) during lactation at a dose lower than where parental systemic toxicity was observed. The sole parental effect was an increased incidence of kidney mineralization and liver microgranul oma. There were no effects on reproductive parameters.

In the acute neurotoxicity study, effects observed at the mid

- and high

- dose groups consisted of decreased motor activity in males on day 0. There were no effects in the subchronic neurotoxicity study, and bentazon was negative for immunotoxicity. In a 21

- day dermal toxicity study, no effects were observed up to 1000 mg/kg/day.Bentazon Preliminary Human Health Risk Assessment D 471312

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Page 15 of 40 

### Bentazon was not found to be mutagenic, and is classified as a Group “E” chemical (evidence of

non

- carcinogenicity for humans) based upon lack of evidence of carcinogenicity in rats and mice.

Based on acute toxicity data, bentazon is categorized as havin g low lethality by the oral, inhalation, and dermal routes of exposure (Toxicity Categories III and IV). It is moderately irritating to the eye (Toxicity Category II) and slightly irritating to the skin (Toxicity Category III). Bentazon is also a dermal sensitizer.

4.4 Safety F actor for Infants and Children (FQPA SF)

The RAB1 risk assessment team determined that the FQPA SF can be reduced to 1X based on the following considerations described in greater detail in the sections below: 1) the toxicology da tabase for bentazon is adequate for risk assessment; 2) bentazon is not considered neurotoxic; 3) all fetal and offspring effects are well characterized and protected for; and 4) the exposure databases are sufficient and unlikely to underestimate exposure.

4.4.1 Completeness of the Toxicology Database

The existing toxicology database for bentazon is adequate for FQPA evaluation. Developmental toxicity studies in rats and rabbits, a two

- generation reproduction study in rats, and neurotoxicity studies in r ats are available for FQPA consideration.

4.4.2 Evidence of Neurotoxicity

The nervous system is not the target organ for bentazon, and the effects observed are well characterized. In the acute neurotoxicity study, a clear NOAEL was established for the e ffect observed (decreased motor activity), and this study is being used in endpoint selection. There was no evidence of neurotoxicity observed in the rest of the toxicology database, including the subchronic neurotoxicity study.

4.4.3 Evidence of Sensiti vity/Susceptibility in the Developing or Young Animal

There are no concerns or residual uncertainties for pre

- and post

- natal toxicity. There is evidence of increased quantitative offspring susceptibility in the two

- generation reproduction toxicity study (see Section 4.2); however, the concern is low since: 1) a clear NOAEL is established in the offspring; 2) the dose

- response for these effects are well defined and characterized; and 3) endpoints selected for risk assessment are protective of the observe d offspring and developmental effects.

4.4.4 Residual Uncertainty in the Exposure Database

There are no residual uncertainties in the exposure database. The dietary and residential exposure analyses are conservative in nature

. The dietary exposure assessment used tolerance

level residues and assumed 100% CT. The residential exposure assessment uses the 2012 Residential SOPs and is considered health

- protective.Bentazon Preliminary Human Health Risk Assessment D 471312

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Page 16 of 40 

### 4.5 Toxicity Endpoints and Point of Departure Selections

4.5.1 D ose - Response Assessment

Since the last risk assessment for bentazon, the regulatory decisions for the developmental rat and chronic dog studies have been updated to be consistent with the agency’s current policies. The changes in these decisions and the submission of new data to the hazard database have led to revision of the previous endpoints. The PODs, UFs, and toxicity endpoints for dietary exposure assessment and occupational/residential exposure assessments are presented in Tables 4.4.1 and 4.4.2, respectively.

Acute Dietary Endpoint ( All Population s ): The acute neurotoxicity screening battery in the rat was selected for the acute dietary endpoint for all population s . An UF of 100X , which includes a 10X for interspecies extrapolation, a 10X for intraspecies variability, and a 1X FQPA SF was applied to the NOAEL of 50 mg/kg to generate an aPAD of 0.5 mg/kg for the general population. The LOAEL is 150 mg/kg based on decreased motor activity in males on day 0. This study is protective of the general population and is appropriate for the expected duration of exposure.

Chronic Dietary Endpoint (All populations): The two

- generation reproductive study was selected for the chronic dietary endpoint

. An UF of 100X , which includes a 10X for intersp ecies extrapolation, a 10X for intraspecies variability, and a 1X FQPA SF was applied to the NOAEL of 15 mg/kg/day to generate the cPAD of 0.15 mg/kg/day

. The LOAEL is 62 mg/kg/day based upon decreased absolute offspring body weights during lactation

. NO AEL and LOAEL values for all chronic oral exposure studies were similar across studies

. The NOAEL from the two

- generation reproductive study is considered protective of all effects seen in the longer term studies and it was selected based upon dose spacing considerations

. This study is protective of all populations.

Dermal Endpoints for all Durations: Based upon a lack of effects in the 21

- day dermal toxicity study, and the low dermal absorption values for bentazon (1

- 2%) in the guideline dermal penetration study, a dermal risk assessment is not required. Dermal equivalent doses calculated using potentially relevant ora l doses from the bentazon database result in values that are well above the limit dose.

Short

- and Intermediate

- Term Incidental Oral Endpoints: Similar to the chronic dietary endpoint for the general population, the offspring effects for the two

- generat ion reproductive study were chosen for the short

- and intermediate

- term incidental oral exposure scenarios. The LOC is 100 based upon a 10X UF for interspecies extrapolation, a 10X UF for intraspecies variability, and a 1X FQPA SF. This study is appropri ate for the population of concern (young children) and for the expected durations of exposure.

Short

- and Intermediate

- Term Inhalation Endpoints: Similar to the chronic dietary endpoint for the general population, the offspring effects for the two

- gener ation reproductive study were chosen for the short

- and intermediate

- term inhalation exposure scenarios. The LOC for the inhalation exposure scenarios is 100 based upon a 10X UF for interspecies extrapolation, a 10X UF for intraspecies variability, and a 1X FQPA SF (when applicable). The NOAEL from this study is protective of offspring effects that may result from exposure to pregnant and nursing females as well as adult effects seen throughout the database in subchronic and chronic studies. Inhalation e xposure is assumed to be equivalent to oral exposure.Bentazon Preliminary Human Health Risk Assessment D 471312

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Page 17 of 40 

### 4.5.2 Recommendation for Combining Routes of Exposures for Risk Assessment

Since the same study and effects (reproduction and fertility effects in the rat; decreased absolute pup body weights during lactation ) were used to select the PODs for the inhalation and incidental oral exposure routes, these routes should be combined. A dermal hazard was not identified; therefore, this route of exposure is not combined with the inhalation or incidental oral r outes.

4.5.3 Cancer Classification and Risk Assessment Recommendation

Bentazon has been classified as a Group “E” chemical (evidence of non

- carcinogenicity for humans) based upon lack of evidence of carcinogenicity in rats and mice (TXR 010787, J. Ro we, 1/14/92 ). Therefore, a cancer exposure and risk assessment is not required.

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

Table 4.5.4.1

. Summary of Toxicological Doses and Endpoints for Bentazon fo r Use in Dietary and Non

Occupational Human Health Risk Assessments

. Exposure/ Scenario POD Uncertainty/ FQPA SFs RfD, PAD, LO C

for Risk Assessment Study and Toxicological Effects

Acute Dietary (General Population, including Infants and Children) NOAEL =

50 mg/kg/day UF A = 10X

UF H = 10X FQPA SF = 1X Acute RfD = 0.5

mg/kg/day aPAD = 0.05 mg/kg/day Acute Neurotoxicity

- Rat

LOAEL = 150 mg/kg/day based on decreased motor activity in males on study day 0

.

Chronic Dietary (All Populations) NOAEL= 15

mg/kg/day UF A = 10X

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

0.15 mg/kg/day cPAD = 0.15 mg/kg/day Reproduction and fertility effects

-

Rat Offspring LOAEL = 62 mg/kg/day based on decreased absolute pup body weights during lactation.
Incidental Oral Short

- (1

- 30 days) and Intermediate

– Term (1

- 6 months) NOAEL= 15

mg/kg/day UF A = 10X

UF H = 10X FQPA S F= 1X Residential LOC

for MOE = 100 Reproduction and fertility effects

-

Rat Offspring LOAEL = 62 mg/kg/day based on decreased absolute pup body weights during lactation.

Dermal Short

- (1

- 30 days) and Intermediate

Term (1

- 6 months) Based upon a lack of dermal toxicity in the 21

- day dermal study, and the low absorption values

for bentazon (1

- 2%), a dermal risk assessment is not required.

Inhalation Short

- (1

- 30 days) and Intermediate

Term (1

- 6 months) NOAEL= 15

mg/kg/day UF A = 10X

UF H = 10X FQPA SF = 1X Residential LOC

for MOE = 100 Reproduction and fertility effects

-

Rat Offspring LOAEL = 62 mg/kg/day based on decreased absolute pup body weights during lactation.

Cancer (oral, dermal, inhalation) Classification: Bentazon has been classified as a Group “E” chemical (evidence of non

carcinogenicity for humans) based upon lack of evidence of carcinogenicity in rats and mice (TXR 010787, J. Rowe, 1/14/92 ). Therefore, a can cer exposure and risk assessment is not required.Bentazon Preliminary Human Health Risk Assessment D 471312

____________________________________________________________________________________________

Page 18 of 40 Point of departure (POD) = A data point or an estimated point that is derived from observed dose

- response data and used to mark the beginning of extrapolation to determine risk associated with lower environmentally relevant human

exposures. NOAEL = no

- observed adverse

- effec t level. LOAEL = lowest

- observed adverse

- effect level. UF = uncertainty factor. UF A = extrapolation from animal to human (interspecies). UF = uncertainty factor. UF A = extrapolation from animal to human (interspecies). UF H = potential variation in se nsitivity among members of the human population (intraspecies). FQPA SF = FQPA Safety Factor. PAD = population

- adjusted dose (a = acute, c = chronic). RfD = reference dose.

Table 4.5.4.2

. Summary of Toxicological Doses and Endpoints for Bentazon fo r Use in Occupational Human Health Risk Assessments

. Exposure/ Scenario P O D UFs LOC for Risk Assessment Study and Toxicological Effects

Dermal Short

- (1

- 30 days) and Intermediate

Term (1

- 6 months) Based upon a lack of dermal toxicity in the 21

- day dermal study, and the low absorption values

for bentazon (1

- 2%), a dermal risk assessment is not required.

Inhalation Short

- (1

- 30 days) and Intermediate

Term (1

- 6 months) NOAEL=

15 mg/kg/day UF A = 10X

UF H = 10X Occupational

LOC for MOE = 100 Reproduction and fertility effects

- Rat

Offspring LOAEL = 62 mg/kg/day based on decreased absolute pup body weights during lactation.

Cancer (oral, dermal, inhalation) Classification: Bentazon has been classified as a Group “E” chemical (evidence of non

carcinogenicity for humans) based upon lack of evidence of carcinogenicity in rats and mice (TXR 010787, J. Rowe, 1/14/92 ). Therefore, a cancer exposure and risk assessment is not required.
Point of departure (POD) = A data point or an estimated point that is derived from observed dose

- response data and used to mark the beginning of extrapolation to determine risk associated with lower environmentally relevant human

exposures. NOAEL = no

- observed adverse

- effe ct level. LOAEL = lowest

- observed adverse

- effect level. UF = uncertainty factor. UF A = extrapolation from animal to human (interspecies). UF H = potential variation in sensitivity among members of the human population (intraspecies). MOE = margin of ex posure. LOC = level of

concern

.



### 4.6 Endocrine Disruptor Screening Program

As required by Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) and Federal Food, Drug, and Cosmetic Act (FFDCA), EPA reviews numerous studies to assess potential adv erse outcomes from exposure to chemicals. Collectively, these studies include acute, subchronic, and chronic toxicity, including assessments of carcinogenicity, neurotoxicity, developmental, reproductive, and general or systemic toxicity. These studies i nclude endpoints which may be susceptible to endocrine influence, including effects on endocrine target organ histopathology, organ weights, estrus cyclicity, sexual maturation, fertility, pregnancy rates, reproductive loss, and sex ratios in offspring. F or ecological hazard assessments, EPA evaluates acute tests and chronic studies that assess growth, developmental and reproductive effects in different taxonomic groups. As part of its Registration Review decision for bentazon, EPA reviewed these data and selected the most sensitive endpoints for relevant risk assessment scenarios from the existing hazard database. However, as required by FFDCA section 408(p), bentazon is subject to the endocrine screening part of the Endocrine Disruptor Screening Program (EDSP).

EPA has developed the EDSP to determine whether certain substances (including pesticide active and other ingredients) may have an effect in humans or wildlife similar to an effect produced by a “naturally occurring estrogen, or other such endocri ne effects as the AdministratorBentazon Preliminary Human Health Risk Assessment D 471312

____________________________________________________________________________________________

Page 19 of 40 

### may designate.” The EDSP employs a two

- tiered approach to making the statutorily required determinations. Tier 1 consists of a battery of 11 screening assays to identify the potential of a chemical substance to interact wi th the estrogen, androgen, or thyroid (E, A, or T) hormonal systems. Chemicals that go through Tier 1 screening and are found to have the potential to interact with E, A, or T hormonal systems will proceed to the next stage of the EDSP where EPA will dete rmine which, if any, of the Tier 2 tests are necessary based on the available data. Tier 2 testing is designed to identify any adverse endocrine

- related effects caused by the substance, and establish a dose

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

Under FFDCA section 408(p), the Agency must screen all pesticide chemicals. Between October 2009 and February 2010, EPA issued test orders/data call

- ins for the first group of 67 chemicals, which contains 58 pesticide active ingredien ts and 9 inert ingredients. A second list of chemicals identified for EDSP screening was published on June 14, 2013 1 

### and includes some pesticides scheduled for registration review and chemicals found in water

. Neither of these lists should be construed as a list of known or likely endocrine disruptors.

For further information on the status of the EDSP, the policies and procedures, the lists of chemicals, future lists, the test guidelines and the Tier 1 screening battery, please visit our website. 2



### 5.0 Dietary Exposure and Risk Assessment D418592, G. Kramer, 02

- DEC

- 2014 (dietary

- exposure analysis for the current action) D422778, S. Wente, 11

- SEP

- 2014 (determination of degradates of concern drinking water)



### 5.1 Metabolite/Degradate Residue Profile

5. 1.1 Summary of Plant and Animal Metabolism Studies

The qualitative nature of the residue in plants is considered to be adequately understood (see 2/7/94 RED Chapter). Radiolabeled studies conducted at rates of up to 2.5 lb a i /A on beans, corn, soybeans, rice, and wheat indicate that bentazon is readily absorbed from foliage, roots and seeds, and translocates in some plant types. Bentazon is rapidly metabolized, conjugated, and incorporated into natural plant constituents. Metabolism involves the hydrox y lation of bentazon at the 6

- and 8

- position. The terminal residues of regulatory concern are bentazon, 6

- hydroxy bentazon, and 8

- hydroxy bentazon.

The qualitative nature of the residue in livestock is also considered to be adequately understood (see 2/ 7/94 RED Chapter). When dairy cattle were orally dosed with radiolabeled bentazon at levels of up to 20 ppm for 28 days, analysis showed that it was absorbed and rapidly eliminated in the urine. Bentazon and its metabolite, AIBA, are the regulated termin al residues in tissues and milk. Studies involving laying hens dosed with radiolabeled bentazon at 100 ppm in the diet for 5 days demonstrated that limited accumulation and metabolism occurs. Greater than 80% of the total radioactive residue (TRR) in tis sue and eggs was identified as unchanged bentazon. The highest radioactive residue levels were found in the liver, and 16% of the TRR in liver consisted of the N

glucuronide conjugate of bentazon. Bentazon and AIBA are the regulated terminal residues

1 See http://www.regulations.gov/#!documentDetail;D=EPA

- HQ

- OPPT

- 2009

- 0477

- 0074 for the final second list of
chemicals.

2 See http://www.epa.gov/endo/

.Bentazon Preliminary Human Health Risk Assessment D 471312

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Page 20 of 40 

### in poultry commodities.

5.1.2 Summary of Environmental Degradation

Dissipation of bentazon is dependent on microbe

- induced degradation, leaching and surface water runoff. Bentazon is moderately resistant to degradation in aerobic mineral soils. Degradation in aquatic environments is dependent on photolysis. Degradation in soil is controlled by processes involving microbes in the presence of oxygen. Bentazon has a low binding affinity to soil and, therefore, may leach into ground water and runoff into surface waters. Leaching did not appear to be a major route of dissi pation in field studies, however. Bentazon dissipates rapidly under typical use conditions. The soil degradates of bentazon include AIBA, which is very mobile but not persistent, and N

- methylbentazon, which is not mobile.

5.1.3 Comparison of Metabolic Pathways

In plants, bentazon is rapidly metabolized, conjugated, and incorporated into natural plant constituents. Metabolism involves the hydroxylation of bentazon at the 6

- and 8

- position. In animals, metabolism of bentazon is much more limited. AIB A is a major metabolite in ruminants; and the N

- glucuronide conjugate of bentazon, in poultry. Trace amounts of 6

- OH

- bentazon and 8

- OH

- bentazon are formed in rats. AIBA is also the major environmental degradate.

5.1.4 Residues of Concern Summary

The re sidues of concern in primary crops, rotational crops, livestock, and drinking water, as identified by HED, are shown in Table 5.1.4 below.

Table 5.1.4. Summary of Metabolites and Degradates to be Included in the Risk Assessment.

Matrix Residues Included in Risk Assessment Residues Included in Tolerance Expression

Plants Primary Crops Bentazon, 6

- hydroxy Bentazon, and 8

- hydroxy Bentazon Bentazon, 6

- hydroxy Bentazon, and 8

- hydroxy
Bentazon Rotational Crops Bentazon, 6

- hydroxy Bentazon, and 8

- hydroxy Bentazon

Livestock Ruminants Bentazon and AIBA Bentazon and AIBA

Poultry

Drinking Water Bentazon, AIBA, O

- nitro

- N

isopropyl benzamide, O

- nitroso

N

- isopropylbenzamide, photoproduct 10, and 8

- Cl

bentazon Not Applicable



### 5.2 Food Residue Profile

A tolerance is currently established under 40 CFR §180.355(a)(1) for the combined residues of bentazon and its 6

- and 8

- hydroxy metabolites , in/on dry and succulent bean, corn, cowpea, flax, dry and succulent pea, peanut, pepper, peppermint, rice, sorghum, soybean, and spearmint from 0.05 to 10.0 ppm . In addition, permanent tolerances are established under 40 CFR §180.355 (a)(2) for the combined residues of bentazon and its metabolite AIBA in/on several livestock commodities at 0.05 ppm. Tolerances for th e combined residues of bentazon and its 6

- and 8

- hydroxy metabolites have been established under 40 CFR §180.355(c) in connection with regionalBentazon Preliminary Human Health Risk Assessment D 471312

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Page 21 of 40 

### registrations; these include tolerances for residues in/on clover, forage at 1.0 ppm, and clover, hay at 2.0 ppm.

The available crop and livestock magnitude of the residue data for bentazon are adequate to support the use on all registered crops. The f ield trial data reflect the proposed use patterns; an adequate number of trials were conducted in the appropriate geographic regions; and samples were analyzed for the residue of concern using validated data

- collection methods. The storage intervals

were also validated. Confined rotational crop data indicate that bentazon residues (bentazon, 6

- hydroxy bentazon, and 8

- hydroxy bentazon) may be taken up by rotational crops (39

- to 102

- day plantback intervals); however, field rotational crop studies demonstra te that plantback restrictions/tolerances for indirect or inadvertent residues for bentazon are not needed (MRIDs 4114666

- 01 to

- 08).

5.3 Drinking Water Residue Profile

Drinking water residues provided by EFED (Memo, S. Wente, 11

- SEP

- 2014; D422778) wer e incorporated directly into the acute and chronic dietary analyses as “water, direct, all sources” and “water, indirect, all sources.” The estimated drinking water concentrations (EDWCs) were Tier 1 estimates for ground water using the Tier 1 Rice Model. Based on two applicatio ns of 1.1 lbs ai/acre for a total application of 2.2 lbs ai/acre/year and a Kd of 0.898 (MRID 40470501), the Tier 1 Rice Model produces a surface water EDWC of 2112 μg/L for both acute and chronic risk

concern s. Therefore, EFED believes all of the other u ses of bentazon would produce EDWCs lower than this conservative value for both surface and groundwater.

5.4 Dietary (Food + Drinking Water) Risk Assessment

Acute and chronic aggregate dietary (food and drinking water) exposure and risk assessments were conducted using DEEM

- FCID, ver. 3.16 which incorporates consumption data from the USDA NHANES/WWEIA; 2003

- 2008. The acute and chronic analyses assumed toleran ce

- level residues, 100% CT, DEEM (ver. 7.81) default processing factors, and modeled drinking water estimates. The resulting acute food plus water risk estimates are below HED’s LOC (<100% aPAD) at the 95th percentile of the exposure distribution for the general U.S. population ( 23 % aPAD), and all population subgroups. The population subgroup with the greatest acute risk estimate was all infants (<1 year old), which utilized 73% of the aPAD. The resulting chronic risk estimates are also below HED’s LOC f or the U.S. general population (<100% cPAD), and all population subgroups. The most highly exposed population was all infants (<1 year old), with a chronic risk estimated that utilized 78% of the cPAD.Bentazon Preliminary Human Health Risk Assessment D 471312

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Page 22 of 40 Table 5.4.1. Summary of Dietary (Food and Drinki ng Water) Exposure Risk for Bentazon

.

Population Subgroup Acute Dietary (95 th Percentile) Chronic Dietary
Dietary Exposure (mg/kg/day) % aPAD Dietary Exposure (mg/kg/day) % cPAD

General U.S. Population 0.115806 23 0.044888 30 All Infants (<1 year old) 0.365354 73 0.116618 78 Children 1

- 2 years old 0.180165 36 0.066256 44 Children 3

- 5 years old 0.146590 29 0.055447 37 Children 6

- 12 years old 0.110968 22 0.039685 26 Youth 13

- 19 years old 0.096321 19 0.032767 22 Adults 20

- 49 years old 0.113997 23 0.044599 30 Adults 50

- 99 years old 0.101622 20 0.044111 29 Females 13

- 49 years old 0.115326 23 0.044424 30 *The values for the highest exposed population for each type of risk assessment are bolded.



### 6.0 Residential (Non

- Occupational) Exposure/Risk Characterization D418591, K. Lowe, 02

- DEC

- 2014



### There is the potential for residential handler and post

- application exposure from the registered uses on turf and ornamentals.

6.1 Residential Handler Exposure/Risk Estimates

The quantitative exposure/risk assessment developed for residential handlers is based on the following scenarios:

(1) mixing/loading/applying liquids to turf and gardens/trees with manually

- pressurized handwand, (2) mixing/loading/applying liquids to turf and gardens/trees with hose

- end sp rayer, and (3) mixing/loading/applying liquids turf and gardens/trees with backpack.

Table 6.1.1 provides a summary of the residential handler exposures and risk estimates for bentazon. Since there is no dermal hazard, a quantitative residential handler derm al assessment has not been conducted. The inhalation exposure risk estimates for residential handlers are not of concern (i.e., MOEs ≥ 100) at baseline for all scenarios; all MOEs are ≥ 75,000.

Table 6.1.1. Residential Handler Non

- cancer Exposure and Risk Estimates for Bentazon.

Scenario Application

Equipment/Method Application
Rate 1 Area

Treated or Amount Handled Daily Inhalation

Unit Exposure (mg/lb ai) 2 Inhalation

Dose (mg/kg/day) 3 Inhalation

MOE 4

Mixer/Loader/Applicator for Liquid Formulations

Gardens / Trees Manually

pressurized handwand 0.023 lb

ai/gallon 5 gallons 0.018 0.000026 580,000 Lawns / Turf

Gardens / Trees Hose

- end Sprayer 0.023 lb ai/gallon 11 gallons 0.0014 0.0000044 3,400,000

Lawns / Turf 1 lb ai/acre 0.5 acres 0.022 0.00014 110,000 Gardens / Trees Backpack 0.023 lb ai/gallon 5 gallons 0.14 0.0002 75,000 Lawns / Turf 1. Based on registered labels (see T able 3.3.1 ). 2. Based on HED’s 2012 Residential SOPs ( http://www.epa.gov/pesticides/science/residential

- exposure

- sop.html ).Bentazon Preliminary Human Health Risk Assessment D 471312

____________________________________________________________________________________________

Page 23 of 40 3. Inhalation Dose = Inhalation Unit Exposure (mg/lb ai) × Application Rate (lb ai/acre or gal) × Area T reated or Amount Handled (A/day or gallons/day) ÷ Body Weight (80 kg). 4. Inhalation MOE = Inhalation NOAEL (15 mg/kg/day) ÷ Inhalation Dose (mg/kg/day).



### 6.2 Residential Post

- application Exposure/Risk Estimates

The quantitative exposure/risk assessment for residential post

- application exposures is based on the following scenarios:

 Physical activities on turf: children 1 to < 2 years old (incidental oral).

The lifestages selected for each post

- application sce nario are based on an analysis provided as an Appendix in the 2012 Residential SOPs 3 

### . While not the only lifestage potentially exposed for these post

- application scenarios, the lifestage that is included in the quantitative assessment is health protective for the exposures and risk estimates for any other potentially exposed lifestage.

Table 6.2.1 provides a summary of the residential post

- application exposures and risk estimates for bentazon. All risk estimates for post

- application exposure are not of c oncern (i.e., MOEs ≥ 100); all MOEs are ≥ 1000 for children.

Table 6.2.1. Short

- Term Residential Post

- application Exposure and Risk Estimates for Bentazon.

Lifestage Post

- application Exposure Scenario Dose (mg/kg/day) 1 MOEs 2

Child 1 to< 2 year old Turf

Liquid formulation

1 lb ai/A Hand to Mouth 0.0152 1000
Object to Mouth 0.000456 32,000

Short

- and Intermediate

- term Incidental Soil

Ingestion 3.4E

- 05 440,000

1. Dose (mg/kg/day) equations provided in HED’s 2012 Residential SOPs ( http://www.epa.gov/pesticides/science/residential

- exposure

- sop.html )

. 2. MOE = POD ( i ncidental oral = 15 mg/kg/day) ÷ Dose (mg/kg/day). LOC = 100.



### 6.3 Residential Risk Esti mates for Use in Aggregate Assessment

Table 6.3.1 reflects the residential risk estimates that are recommended for use in the aggregate assessment for bentazon.

 The recommended residential exposure for use in the adult short

- term aggregate assessment refl ects inhalation exposure from handler applications using a backpack

sprayer.

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

term aggregate assessment reflects hand

- to

- mouth exposures from post

- application exposure to turf applications.

Table 6.3.1. Recommendations for the Residential Exposures for the Bentazon Aggregate Assessment.

Lifestage Exposure

Scenario Dose (mg/kg/day) 1 MOE 2

Dermal Inhalation Oral Total Dermal Inhalation Oral Total

Short

- term

Adult Handler

application via backpack

sprayer NA 0.0002 NA 0.0002 NA 75,000 NA 75,000

3 Available: http://www.epa.gov/pesticides/science/residential

- exposure

- sop.htmlBentazon Preliminary Human Health Risk Assessment D 471312

____________________________________________________________________________________________

Page 24 of 40 Table 6.3.1. Recommendations for the Residential Exposures for the Bentazon Aggregate Assessment.

Lifestage Exposure

Scenario Dose (mg/kg/day) 1 MOE 2

Dermal Inhalation Oral Total Dermal Inhalation Oral Total

Child 1 to < 2 year s old Hand

- to

mouth NA NA 0.0152 0.0152 NA NA 1000 1000

1. Dose = the highest dose for each applicable lifestage of all residential scenarios assessed. Total = dermal + inhalation + incidental oral (where

applicable). 2. MOE = the MOEs associated with the highest residential doses.



### 6.4 Spray Drift

Off

- target movement of pesticides can occur via many types of pathways and it is governed by a variety of factors. Sprays that are released and do not deposit in the application area end up off

target and can lead to exposures to those it may directly contact

. They can also deposit on surfaces where contact with residues can eventually lead to exposures (e. g., children playing on lawns where residues have deposited next to treated fields)

. The potential risk estimates from these residues can be calculated using drift modeling coupled with methods employed for residential risk assessments for turf products.

The approach to be used for quantitatively incorporating spray drift into risk assessment include assessing exposures for children (1 to < 2 years old) and adults who have contact with turf where residues are assumed to have deposited via spray drift thus resulting in an exposure scenario. Aside from the predicted residues available for transfer, the routes of exposure and assessment methodology is analogous to how exposures to turf products are considered in risk assessment.

Several bentazon products have existing labels for use on turf, thus it was considered whether the risk assessment for turf may be considered protective of any type of exposure resulting from spray drift. If the maximum application rate on crops adjusted by the amount of drift exp ected is less than or equal to existing turf application rates, the existing turf assessment is considered protective of spray drift exposure. The maximum single application rate registered for bentazon is 1.5 lb ai/A

. The highest fraction of spray drift noted for any application method immediately adjacent to a treated field results in a deposition fraction of 0.26 4 

### of the application rate. A quantitative spray drift assessment for bentazon is not required because the maximum application rate for a crop/target site multiplied by the adjustment factor for drift of 0.26 is less than the maximum direct spray residentia l turf application rate (1 lb ai/A) 5 

### for any bentazon products. The turf post

- application MOEs are protective for any potential exposures related to spray drift for bentazon and have previously been discussed in Section 6.2.

6.5 Residential Bystander P ost

- Application Inhalation Exposure

Volatilization of pesticides may be a source of post

- application inhalation exposure to individuals nearby pesticide applications. The A gency sought expert advice and input on issues related to volatilization of pestic ides from its FIFRA Scientific Advisory Panel (SAP) in December 2009, and received the SAP’s final report on March 2, 2010 (http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html). The A gency has evaluated the SAP report and has developed a Volat ilization Screening Tool and a subsequent Volatilization Screening Analysis (http://www.regulations.gov/#!docketDetail;D=EPA

- HQ

-

4 Tier 1 output from the a erial application using fine to medium spray quality based on AgDrift ® output files.

5 1.5 lb ai/A x 0.26 = 0.39 ≤ 1 lb ai/A

.Bentazon Preliminary Human Health Risk Assessment D 471312

____________________________________________________________________________________________

Page 25 of 40 

### OPP

- 2014

- 0219).

During Registration Review, the A gency will utilize this analysis to determine if data (i.e., flux studies, r oute

- specific inhalation toxicological studies) or further analysis is required for bentazon.

7.0 Aggregate Exposure/Risk Characterization

In accordance with the FQPA, HED must consider and aggregate (add) pesticide exposures and risks from three major s ources: 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. Wh en aggregating exposures and risks from various sources, HED considers both the route and duration of exposure.

7.1 Acute Aggregate Risk

Acute aggregate risk results from exposure to residues in food and drinking water alone. The acute dietary exposur e analysis included both food and drinking water. Therefore, acute aggregate risk is equivalent to the acute dietary risk, as discussed in Section 5.4, above. All risk estimates are not of concern.

7.2 Short

- and Intermediate

- Term Aggregate Risk

Short

- and intermediate

- term aggregate exposure takes into account short

- and intermediate

- term residential exposure plus chronic exposure to food and water (considered to be a background exposure level). Bentazon is currently registered for uses that cou ld result in short

- term residential exposure, and it has been determined that it is appropriate to aggregate chronic exposure through food and water with short

- term residential exposures to bentazon. Intermediate

- term residential exposures are not anticip ated based on the registered uses.

For short

- term exposures, incidental oral and inhalation exposure risk assessments are appropriate to aggregate since the PODs for these routes are based on the same study/effects. The short

- term incidental oral and inh alation exposures are combined (where appropriate) with chronic dietary (food and water) exposure for determination of aggregate short

- term exposures. HED uses chronic dietary exposure when conducting short

- term aggregate assessments as they have determin ed that these will more accurately reflect exposure from food over the HED defined short

- term interval than will acute exposure.

Adults may potentially be exposed to bentazon through dermal, inhalation, and dietary (food and drinking water) routes. A de rmal hazard was not identified for bentazon; therefore, dermal risk estimates were not assessed and not included in the aggregate

. Adult handler inhalation exposures have been aggregated with dietary (food and water) exposures for the short

- term duration. The backpack scenario for mixing and loading liquids is the exposure scenario with the greatest exposure; therefore, the exposure estimates for this scenario are protective of other exposure scenarios.

For young children, due primarily to their hand

- t o

- mouth activities, short

- term oral (non

- dietary) exposures are expected along with dermal and dietary (food and drinking water) exposures.Bentazon Preliminary Human Health Risk Assessment D 471312

____________________________________________________________________________________________

Page 26 of 40 

### Only the incidental oral exposures have been aggregated with dietary exposures since a dermal hazard was not identi fied. Note that the non

- dietary residential exposures for children 1

- 2 years old are included in the aggregate assessment and are considered health protective for exposures and risk estimates for other potentially exposed lifestages. Typically, the dietary and non

- dietary exposures for the same child population are aggregated together, however, in the case of bentazon, infants <1 year old have the highest dietary exposure . Therefore, an aggregate assessment for infants <1 year old has also been included, in addition to the children 1

- 2 year olds, using the non

- dietary exposures for children 1

- 2 years old. The LOC is 100; therefore MOEs <100 are risk estimates of concern.

Tables 7.2.1 and 7.2.2 summarize the short

- term aggregate exp osures and risk estimates for infants (<1 year old), 1

- 2 year olds and adults. The aggregate short

- term MOEs are >100 for adults and children; therefore, aggregate exposures to bentazon are not of concern to HED.

Table 7.2.1. Short

- term Aggregate Risk C alculations for Children 1

- 2 Years Old.

Population LOC Dietary Exposure (mg/kg/day) 1 Incidental Oral Exposure (mg/kg/day) 2 Aggregate MOE (food, water, and residential) 3 All Infants (<1 year old) 100 0.116618 0.0152 110 Children 1

- 2 years old 0.066256 180

1 Dietary exposure = chronic dietary exposure from Table 5.4.1.

2 Incidental Oral Exposure = Hand

- to

- mouth exposure for children (1 to <2 years old) from Table 6.3.1

. 3 Aggregate MOE = NOAEL (15 mg/kg/day) ÷ ( dietary exposure + incidental oral exposure).

Table 7.2.2. Short

- Term Aggregate Risk Calculations for Adults.

Population LOC Dietary Exposure (mg/kg/day) 1 Inhalation Residential Exposure (mg/kg/day) 2 Aggregate MOE (food, water, and residential) 3

General U.S. Population 100 0.044888 0.0002 330

1 Dietary exposure = chronic dietary exposure from Table 5.4.1.

2 Inhalation exposure = high

- end inha lation residential exposure from Table 6.3.1.

3 Aggregate MOE = NOAEL (15 mg/kg/day) ÷ (dietary exposure + inhalation exposure).



### 7.3 Chronic Aggregate Risk

The chronic aggregate risk assessment results from long

- term exposure to residues in food and drinking water, as there are no residential scenarios that result in long

- term exposure. The chronic dietary exposure analysis included both food and drinking wa ter and, therefore, the chronic aggregate risk assessment is equivalent to the chronic dietary risk assessment discussed in Section 5.4, above. All risk estimates are not of concern.

7.4 Cancer Aggregate Risk

An aggregate cancer risk assessment was n ot performed because bentazon is not considered to be a carcinogen.

8.0 Cumulative Exposure/Risk Characterization

Unlike other pesticides for which EPA has followed a cumulative risk approach based on a common mechanism of toxicity, EPA has not made a common mechanism of toxicity finding as

to bentazon and any other substances and bentazon does not appear to produce a toxic metaboliteBentazon Preliminary Human Health Risk Assessment D 471312

____________________________________________________________________________________________

Page 27 of 40 

### produced by other substances. For the purposes of this tolerance action, therefore, EPA has not assumed that bentazon has a common mechanism of toxicity with other substances. For information regarding EPA’s efforts to determine which c hemicals have a common mechanism of toxicity and to evaluate the cumulative effects of such chemicals, see the policy statements released by EPA’s Office of Pesticide Programs concerning common mechanism determinations and procedures for cumulating effects from substances found to have a common mechanism on EPA’s website at http://www.epa.gov/pesticides/cumulative/

.

9.0 Occupational Exposure/Risk Characterization D418591, K. Lowe, 02

- DEC

- 2014



### 9.1 H andler Risk Assessment

The quantitative exposure/risk assessment developed for occupational handlers is based on the following scenarios which cover all the registered and proposed uses of bentazon:

 Mixing/loading liquids to support aerial applications,

 Mixing/loading liquids to support groundboom applications,

 Applying sprays with aircraft,

 Applying sprays with groundboom equipment,

 Flagging to support aerial spray applications,

 Mixing/loading/applying liquids via backpack,

 Mixing/loading/applying liq uids via mechanically

- pressurized handgun,

 Mixing/loading/applying liquids via manually

- pressurized handwand.

The occupational handler exposure and risk estimates indicate that the short

- and intermediate

term inhalation MOEs are not of concern to HED (i. e., MOE > 100) at baseline (no respirator). MOEs are all greater than or equal to 3,000

.
HED has no data to assess exposures to pilots using open cockpits. The only data available is for exposure to pilots in enclosed cockpits. Therefore, risks to pilo ts are assessed using the engineering control (enclosed cockpits) and baseline attire (long

- sleeve shirt, long pants, shoes, and socks); per the Agency’s Worker Protection Standard stipulations for engineering controls, pilots are not required to wear prot ective gloves for the duration of the application. With this level of protection, there are no risk estimates of concern for applicators.

The Agency matches quantitative occupational exposure assessment with appropriate characterization of exposure poten tial

. While HED presents quantitative risk estimates for human flaggers where appropriate, agricultural aviation has changed dramatically over the past two decades

. According the 2012 National Agricultural Aviation Association (NAAA) survey of their memb ership, the use of the Global Positioning System (GPS) for swath guidance in agricultural aviation has grown steadily from the mid 1990s. Over the same time period, the use of human flaggers for aerial pesticide applications has decreased steadily from ~15% in the late 1990s to only 1% in the most recent (2012) NAAA survey

. The Agency will continue to monitor all available information sourc es to best assess and characterize the exposure potential for human flaggers in agricultural aerial applications.Bentazon Preliminary Human Health Risk Assessment D 471312

____________________________________________________________________________________________

Page 28 of 40 Table 9.1.1. Occupational Handler Non

- Cancer Exposure and Risk Estimates for Bentazon.

Exposure Scenarios Crop / Target Category Application
Rate 1 Amount

Handled / Area Treated 2 Inhalation

Unit Exposures (ug/lb ai) 3 Inhalation

Dose (mg/kg/day) 4 Inhalation

MOE 5

Baseline (unless otherwise noted) Baseline

(unless otherwise noted) Baseline

(unless otherwise noted)

Mixer/Loader

Aerial application of liquid formulation Peas

, Peppermint, Spearmint 1.5 lb ai/acre

350 acres

0.219 0.00144 10,000

Clover, Non

- bearing food crops (almonds, apples, apricots, avocados, blackberries, blueberries, cherries, crabapples, dates, figs, grapes, grapefruit, lemons, limes, macadamias, nectarines, olives, oranges, peaches, pears, pecans, pistachios , plums,

pomegr anates, prunes, raspberries, tangelos,

tangerines, walnuts) 1 lb ai/acre 0.000959 16,000

Corn, Peanuts , Beans, Soybeans 1.5 lb ai/acre 0.00493 3,000 Sorghum, Rice, Alfalfa 1 lb ai/acre 0.00329 4,600

Groundboom applications with liquid formulation Golf course (fairways, tees, greens) 1 lb ai/acre 40 acres 0.00011 140,000

Nursery (ornamentals, vegetables, trees,

container stock) 1 lb ai/acre 60 acres 0.000164 91,000

Sod 1 lb ai/acre

80 acres 0.000219 68,000

Peas

, Peppermint, Spearmint 1.5 lb ai/acre 0.000329 46,000

Clover, Non

- bearing food crops (almonds, apples, apricots, avocados, blackberries, blueberries, cherries, crabapples, dates, figs, grapes, grapefruit, lemons, limes, macadamias, nectarines, olives, oranges, peaches, pears, pecans, pistachios, plums, pomegranates, prunes, raspberries, tangelos,

tangerines, walnuts) 1 lb ai/acre 0.000219 68,000

Corn, Peanuts , Beans, Soybeans 1.5 lb ai/acre 0.000821 18,000 Sorghum, Rice, Alfalfa 1 lb ai/acre 0.000548 27,000 Applicator

Aerial application of liquid formulation Peas

, Peppermint, Spearmint 1.5 lb ai/acre

350 acres 0.0049 (EC) 0.0000321

(EC) 470,000

(EC)

Clover, Non

- bearing food crops (almonds, apples, apricots, avocados, blackberries, blueberries, cherries, crabapples, dates, figs, grapes, grapefruit, lemons, limes, macadamias, nectarines, olives, oranges, peaches, pears, pecans, pistachios , plums,

pomegr anates, prunes, raspberries, tangelos,

tangerines, walnuts) 1 lb ai/acre 0.0000215 (EC) 700,000

(EC)

Corn, Peanuts , Beans, Soybeans 1.5 lb ai/acre 0.00011 (EC) 140,000

(EC)
Sorghum, Rice, Alfalfa 1 lb ai/acre 0.0000735 (EC) 200,000

(EC)

Groundboom applications with liquid formulation Golf course (fairways, tees, greens) 1 lb ai/acre 40 acres

0.34 0.00017 88,000

Nursery (ornamentals, vegetables, trees,

container stock) 1 lb ai/acre 60 acres 0.000255 59,000

Sod 1 lb ai/acre

80 acres 0.00034 44,000

Peas

, Peppermint, Spearmint 1.5 lb ai/acre 0.00051 29,000

Clover, Non

- bearing food crops (almonds, apples, apricots, avocados, blackberries, blueberries, cherries, crabapples, dates, figs, 1 lb ai/acre 0.00034 44,000Bentazon Preliminary Human Health Risk Assessment D 471312

____________________________________________________________________________________________

Page 29 of 40 Table 9.1.1. Occupational Handler Non

- Cancer Exposure and Risk Estimates for Bentazon.

Exposure Scenarios Crop / Target Category Application
Rate 1 Amount

Handled / Area Treated 2 Inhalation

Unit Exposures (ug/lb ai) 3 Inhalation

Dose (mg/kg/day) 4 Inhalation

MOE 5

Baseline (unless otherwise noted) Baseline

(unless otherwise noted) Baseline

(unless otherwise noted) grapes, grapefruit, lemons, limes, macadamias, nectarines, olives, oranges, peaches, pears, pecans, pistachios , plums, pomegranates, prunes, raspberries, tangelos,

tangerines, walnuts) Corn, Peanuts , Beans, Soybeans 1.5 lb ai/acre 0.00128 12,000 Sorghum, Rice, Alfalfa 1 lb ai/acre 0.00085 18,000 Mechanically

- pressurized Handgun Rights

- of

- way (e.g., utilities, railroad, roadways) 0.023 lb ai/gallon 1000

gallons 3.9 0.00112 13,000

Flagger

Aerial application of liquid formulation Peas

, Peppermint, Spearmint 1.5 lb ai/acre

350 acres 0.35 0.0023 6,500

Clover, Non

- bearing food crops (almonds, apples, apricots, avocados, blackberries, blueberries, cherries, crabapples, dates, figs, grapes, grapefruit, lemons, limes, macadamias, nectarines, olives, oranges, peaches, pears, pecans, pistachios , plums,

pomegr anates, prunes, raspberries, tangelos,

tangerines, walnuts) 1 lb ai/acre 0.00154 9,700

Corn, Peanuts , Beans, Soybeans 1.5 lb ai/acre 0.0023 6,500 Sorghum, Rice, Alfalfa 1 lb ai/acre 0.00154 9,700 Mixer/Loader/Applicator

Backpack Rights

- of

- way (e.g., utilities, railroad, roadways)

0.023 lb ai/gallon 40 gallons 2.58 0.0000296 510,000 Landscaping, turf (lawns, athletic fields,

parks, etc.) Manually

pressurized Handwand Landscaping, turf (lawns, athletic fields, parks, etc.) 30 0.000345 43,000

Mechanically

- pressurized Handgun Golf course (fairways, tees, greens) 1 lb ai/acre 5 acres 1.9 0.000119 130,000

Landscaping, turf (lawns, athletic fields,

parks, etc.)
1 Based on registered and proposed labels. 2 Exposure Science Advisory Council Policy #9.1. 3 Based on the “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table” (March 2014); Level of mitigation: Base line, EC = Eng. Controls. 4 Inhalation Dose = Inhalation Unit Exposure (μg/lb ai) × Conversion Factor (0.001 mg/μg) × Application Rate (lb ai/acre) × Area Treated (A/day) ÷ BW (80 kg). 5 Inhalation MOE = Inhalation NOAEL (15 mg/kg/day) ÷ Inhalation Dose (mg/kg/day).



### 9.2 Post

- Application Risk Assessment

9.2.1 Inhalation Post

- Application Risk Assessment

There are multiple potential sources of post

- application inhalation exposure to individuals performing post

- application activities in previously treated fields

. These potential sources include volatilization of pesticides and resuspension of dusts and/or partic ulates that contain pesticides. The A gency sought expert advice and input on issues related to volatilization of pesticides from its FIFRA SAP in December 2009, and received the SAP’s final report on March 2, 2010 ( http://www.epa.gov/scipoly/SAP/meetings/ 2009/120109meeting.html ). The A gencyBentazon Preliminary Human Health Risk Assessment D 471312

____________________________________________________________________________________________

Page 30 of 40 

### has evaluated the SAP report and has developed a Volatilization Screening Tool and a subsequent Volatilization Screening Analysis ( h ttp://www.regulations.gov/#!docketDetail;D=EPA

- HQ

- OPP

- 2014

- 0219 ). During Registration Review, the A gency will utilize this analysis to determine if data (i.e., flux studies, route

- specific inhalation toxicological studies) or further analysis is required for bentazon.

In addition, the Agency is continuing to evaluate the available post

- application inhalation exposure data generated by the Agricultural Reentry Task Fo rce. Given these two efforts, the Agency will continue to identify the need for and, subs equently, the way to incorporate occupational post

- application inhalation exposure into the A gency's risk assessments.

Although a quantitative occupational post

- application inhalation exposure assessment was not performed, an inhalation exposure assessmen t was performed for occupational/commercial handlers. Handler exposure resulting from application of pesticides outdoors is likely to result in higher exposure than post

- application exposure. Therefore, it is expected that these handler inhalation exposu re estimates would be protective of most occupational post

- application inhalation exposure scenarios.

9.2.2 Dermal Post

- Application Risk Assessment

A quantitative dermal post

- application assessment was not conducted because a dermal hazard for bentazon has not been identified.

Restricted

- Entry Interval The REI specified on the proposed label is based on the acute toxicity of bentazon. Bentazon is classified as acute toxicity category III and IV for acute oral, acute dermal, and acute inhalation toxicity. It is classified as toxicity category II for eye irritation potential and category III for skin irritation potential. It is a dermal sensitizer. Under 40 CFR 156.208 (c) (2), ai’s classified as Acute II for acute dermal, eye irritation or primary skin irrigation are assigned a 24

- hour REI. Therefore, the [156 subpart K] Worker Protection Statement interim REI of 24 hours is adequate to protect a gricultural workers from post

- application exposures to bentazon.

10.0 References

Previous Risk Assessments RED Chapter, 2/7/94 D. Rate, et al ., 08

- MAR

- 2006; D322258

Scoping Document G. Kramer, et al. , 17

- MAR

- 2010; D375437

HASPOC Memo J. Leshin, 15

- OCT

- 2014; TXR0057054

ORE Memo K. Lowe, 02

- DEC

- 2014 ; D418591

Dietary Memo G. Kramer, 02

- DEC

- 2014; D418592Bentazon Preliminary Human Health Risk Assessment D 471312

____________________________________________________________________________________________

Page 31 of 40 

### Drinking Water Memo S. Wente, 11

- SEP

- 2014; D422778

cc: K. Lowe (RAB1) RDI: RAB1 (10/29/14)
K. Lowe:S10948:PY

- S:(703)347

- 8989:7509P:RAB1Bentazon Preliminary Human Health Risk Assessment D 471312

____________________________________________________________________________________________

Page 32 of 40 

### Appendix A. Toxicology Profile and Executive Summaries

A.1 Toxicology Data Requirements The requirements (40 CFR 158.340) for food and nonfood uses for bentazon are in Table 1

. Use of the new guideline numbers does not imp ly that the new (1998) guideline protocols were used.

Study Technical Required Satisfied 870.1100 Acute Oral Toxicity

................................ ....................... 870.1200 Acute Dermal Toxicity

................................ .................. 870.1300 Acute Inhalation Toxicity

................................ .............. 870.2400 Primary Eye Irritation

................................ .................... 870.2500 Primary Dermal Irritation

................................ .............. 870.2600 Dermal Sensitization

................................ ..................... Yes Yes Yes Yes Yes Yes Yes

Yes Yes Yes Yes Yes 870.3100 Oral Subchronic (rodent)

................................ ............... 870.3150 Oral Subchronic (nonrodent)

................................ ......... 870.3200 21

- Day Dermal

................................ .............................. 870.3250 90

- Day Dermal

................................ .............................. 870.3465 90

- Day Inhalation

................................ .......................... Yes Yes Yes No No 1 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

................................ ................... No Yes No Yes Yes No

Yes No Yes Yes 870.5100 Mutagenicity

— Gene Mutation

- bacterial

..................... 870.5300 Mutagenicity

— Gene Mutation

- mammalian

................ 870.5xxx Mutagenicity

— Structural Chromosomal Aberrations

... 870.5xxx Mutagenicity

— Other Genotoxic Effects

....................... Yes Yes Yes Yes Yes

Yes Yes 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 No 870.7485 General Metabolism

................................ ...................... 870.7600 Dermal Penetration

................................ ........................ 870.7800 Immunotoxicity

................................ ............................. Yes Yes Yes Yes

Yes Yes
1. Study is not required at this time based upon weight of evidence decisions by the HASPOC. Decisions are discussed in detail in TXR# 0057054.Bentazon Preliminary Human Health Risk Assessment D 471312

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Page 33 of 40 

### A.2 Toxicity Profiles

Table A.2.1

. Acute Toxicity Profile

- Test Substance

. Guideline No. Study Type MRID(s) Results Toxicity Category

870.1100 Acute oral (rat) 00135394 LD 50 = 1,100 mg/kg III 870.1200 Acute dermal (rat) 00135399 LD 50 > 2,500 mg/kg III 870.1300 Acute inhalation (rat) 47030108 LC 50 > 5.1 mg/L IV

870.2400 Acute eye irritation (rabbit) 00072791 “Moderately irritating”

- irritation clearing within 8

- 16 days II

870.2500 Acute dermal irritation (rabbit) 00072790 Slight irritation at 72 hours IV

870.2600 Skin sensitization 00164714 265409 1 Sensitizer NA

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) 40222201 (1987)

acceptable/guideline (0, 400, 1200, 3600 ppm) M: 0, 25.3, 77.8, 243.3
F: 0, 28.9, 86.1, 258.3 mg/kg/day NOAEL = 77.8/86.1 mg/kg/day

.
LOAEL = 243.3/258.3 mg/kg/day, M/F, based on a diversity of effects, many reversible, including depressed mean body weights in females, a slight increase in food consumption in males, increased t hromboplastin and prothrombin times (males only), and increased kidney and liver weights. In addition, females in the 3, 600

- ppm group showed suggestive evidence for the presence of lung thrombi and dilated uterine horns.
870.3150 90

- Day oral

toxicity (Dog) 0091058 (1972)

unacceptable 0, 100, 300, 1000, 3000

ppm 0, 2.5, 7.5, 25

, and 75 mg/kg/day NOAEL = 2.5 mg/kg/day

.
LOAEL = 7.5 mg/kg/day based on prostatitis.

Note: According to the HIARC briefing package (page 190) this study was classified as unacceptable due to too few animals (3 per sex per dose). The study did not state the test material was technical bentazon. Finally, blood chemistry and hematological parameters were only measured during the pretreatment period, 6 and 13 weeks.
870.3200 21

- Day dermal

toxicity (Rabbit) 42885302 (1993)

acceptable/guideline 0, 250, 500, 1000 mg/kg/day NOAEL = 1000 mg/kg/day (HDT)

.
LOAEL >1000 mg/kg/day

.Bentazon Preliminary Human Health Risk Assessment D 471312

____________________________________________________________________________________________

Page 34 of 40 Table A.2.2

. Subchronic, Chronic , and Other Toxicity Profile

. Guideline
No. Study Type MRID No. (year)/ Classification /Doses Results

870.3700a Prenatal

developmental in (Rat) 40114201 (1986)

acceptable/guideline 0, 40, 100, 250 mg/kg/day Maternal NOAEL = 100 mg/kg/day

.
Maternal LOAEL = 250 mg/kg/day based on increased postimplantation loss.

Developmental NOAEL = 100 mg/kg/day

.
Developmental LOAEL = 250 mg/kg/day based on skeletal variations (incomplete or absent ossificatio n in the phalangeal nuclei of the extremities, the sternebrae and cervical vertebrae), and reduced body weights of fetuses surviving to day 21. 870.3700b Prenatal

developmental in (Rabbit) 40114202 (1987)

acceptable/guideline 0, 75, 150, 375 mg/kg/day Maternal/developmental NOAEL = 150 mg/kg/day

.
Maternal/developmental LOAEL = 375 mg/kg/day (HDT) based on 1 doe with partial abortions, and embryonic resorptions.

Developmental NOAEL =150 mg/kg/day

.
Developmental LOAEL = 375 mg/kg/day based upon no living fetuses.
870.3800 Reproduction and

fertility effects (Rat) 41054902 (1989)

0, 200, 800, 3200 ppm acceptable/guideline 0, 15, 62, 249 mg/kg/day Parental NOAEL = 62 mg/kg/day

.
Parental LOAEL = 249 mg/kg/day based on increased incidences of kidney mineralization and liver microgranuloma.

Offspring NOAEL = 15 mg/kg/day

.
Offspring LOAEL = 62 mg/kg/day based on decreased absolute pup body weights during lactation.

Reproductive NOAEL = 249 mg/kg/day

.
Reproductive LOAEL was not observed

. 870.4100b Chronic toxicity

(Dog) 41054901, 42133201

(1989, 1991) acceptable/guideline 0, 100, 400, 1600 ppm 0, 3.2, 13.1, 52.3 mg/kg/day NOAEL = 13.1 mg/kg/day

.
LOAEL = 52.3 mg/kg/day upon clinical signs (emaciation, dehydration, bloody stool, pale mucous membranes, moderated activity) and slight to severe anemia (decreased hemoglobin, hematocrit, and erythrocyte count, decreased reticulocytes, platelets, leukocytes, PTT, and abnormal red c ell morphology) during the first 13 weeks.Bentazon Preliminary Human Health Risk Assessment D 471312

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Page 35 of 40 Table A.2.2

. Subchronic, Chronic , and Other Toxicity Profile

. Guideline
No. Study Type MRID No. (year)/ Classification /Doses Results

870.4200 Chronic/

Carcinogenicity (Rat) 00142832, 40871702

(1984, 1988) acceptable/guideline 0, 200, 800, 4000 ppm
M: 0, 9, 35, 180 mg/kg/day F: 0,11, 45, 244 mg/kg/day NOAEL = 9 mg/kg/day

.
LOAEL = 35/45 mg/kg/day, males/females, based on increased water consumption, changes in urinalysis and hematology/coagulation parameters, and decreased absolute and relative thyroid weight.

(no) evidence of carcinogenicity

. 870.4300 Carcinogenicity

(mouse) 00142831, 00142833,

40871701, 40934101 (1982, 1985, 1988) acceptable/guideline 0, 100, 400, 2000 ppm M: 0, 12, 47, 242 mg/kg/day
F: 0, 12, 48, 275 mg/kg/day NOAEL = 12 mg/kg/day

.

LOAEL = 47/48 mg/kg/day based on increased prothrombin time, increased liver and kidney weights, calcification of the tunica albuginea, and islet cell hyperplasia of the pancreas.

(no) evidence of carcinogenicity

.

870.5100 Gene Mutation

-

Salmonella typhimurium 00158382 (1983)

acceptable/guideline Strains TA 1535, 1537, 1538, 98, and 100 tested from 20

- 5000 μg/plate ± metabolic activation. Negative up to limit dose.

870.5100 Gene Mutation

-

Salmonella typhimurium and Escherichia coli 00158383 (1985)

acceptable/guideline Strains TA 1535, 1537, 1538, 98, 100, WP2 uvrA tested from 20

- 5000 μg/plate ± metabolic activation. Negative up to limit dose.

870.5300 In vitro

mammalian cell gene mutation assay with Chinese hamster ovary cells 42129610 (1991)

acceptable/guideline Cells tested ±metabolic activation from 100

- 5000 μg/mL. Negative up to limit of solubility.

870.5300 In vitro

mammalian cell gene mutation assay with Chinese hamster ovary cells (CHO

K1

- BH4) 00158385 (1985)

acceptable/guideline 1.25

- 15 mg/ml Cells tested ±metabolic activation from 1250

- 15,000 μg/mL

. Negative up to highest dose tested.

870.5395 In vivo mouse

bone marrow micronucleus

assay 00158388 (1985)

acceptable/guideline Mice were exposed to 200

- 800 mg/kg of bentazon

. Negative up to maximum tolerated dose.

870.5550 Unscheduled

DNA synthesis in primary mouse hepatocytes 00158386 (1985)

acceptable/guideline Hepatocytes were exposed to test substance at concentrations ranging from 2.51

- 1004 μg/mL. Negative up to cytotoxic dose.

870.6200a Acute

neurotoxicity screening battery 48970707 (2012)

acceptable/guideline 0, 50, 150, 400 mg/kg Systemic NOAEL = 400 mg/kg

. Systemic LOAEL was not established. Neurotoxicity NOAEL = 50 mg/kg

. Neurotoxicity LOAEL = 150 mg/kg based on decreased motor activity in males on study day 0

.Bentazon Preliminary Human Health Risk Assessment D 471312

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Page 36 of 40 Table A.2.2

. Subchronic, Chronic , and Other Toxicity Profile

. Guideline
No. Study Type MRID No. (year)/ Classification /Doses Results

870.6200b Subchronic

neurotoxicity screening battery 48970708 (2004)

acceptable/guideline 0, 300, 1000 or 3500 ppm (0, 21.9/27.0, 73.6/86.4 or 258.1/306.3 mg/kg bw/day [M/F]) Systemic NOAEL = 3500 ppm (258.1 and 306.3 mg/kg bw/day [M/F])

. Systemic LOAEL was not established. Neurotoxicity NOAEL = 3500 ppm (258.1 and 306.3 mg/kg bw/day [M/F])

. Neurotoxicity LOAEL was not established.
870.7485 Metabolism and

pharmacokinetics (rat) 40481801 (1987)

acceptable/guideline Recoveries of radioactivity in urine after oral dosing (88.1

- 95.9% of the dose) indicate extensive absorption of the compound from the GI tract

. No differences between the sexes or among dose groups were found. At sacrifice, total radioactive residue in the carcass was less than 0.69% of the dose in all groups. Experiments with bile duct

- cannulated rats indicated that biliary excretion of radioactivity amounted only to 0.24

- 1.31% of the dose at 3.6 mg/kg and to 0.80

- 1.84% of the dose at 195 mg/kg

. Parent bentazon was the major metabolite found in urine, amounting to 77.37

- 91.02% of the dose among the orally dosed animals of the main experiment. A small amount of benzene ring hydroxylation wa s observed: 6

- OH

- bentazon was present in amounts up to 6.34% of the dose. The isomeric 8

- OH

- bentazon was present in trace amounts, 0.0

- 0.23% of the dose.
870.7485 Metabolism and

pharmacokinetics (rat) 00158379 (1979)

acceptable/guideline The absorption and excretion of the free acid form of bentazon or its sodium salt in male rats after oral administration appear to be rapid and essentially equivalent

. No sex differences in the absorption, metabolism or excretion of sodium bentazon are apparent based on equivalent excretion half

- lives (4 hours), pattern of excretion (>90% in urine), or urinary metabolite identification (>80% as free acid). No radioactivity was recovered in the expired air or carcass.
870.7600 Dermal

penetration (rabbit) 00158380 (1985)

acceptable/guideline 0.12, 1.2, 12, 120 mg/kg Single topical application of radioactive sodium bentazon did not appear to significantly penetrate the skin since a maximum of only 1

- 2% of the radioactivity was recovered (primarily in the urine) at 72 hours. Negligible amounts of dermally applied radio activity were retained in the liver, kidneys, GI tract, and carcass. For risk assessment purposes, dermal penetration is estimated to be 1

- 2%.
870.7800 Immunotoxicity 48970709 (2012) acceptable/guideline 0, 300, 1000

, or 3000 ppm (0, 105, 331, 1094 mg/kg bw/day [F]) Systemic NOAEL = 1094 mg/kg bw/day

. Systemic LOAEL was not established. Immunotoxicity NOAEL = 1094 mg/kg bw/day

. Immunotoxicity LOAEL was not established.Bentazon Preliminary Human Health Risk Assessment D 471312

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Page 37 of 40 

### Appendix B. Physical/Chemical Properties

Physicochemical Properties of Bentazon
Molecular mass 240.3 Melting point/range 137

- 139°C Water solubility (22  C) 570 mg/L Vapor pressure (25  C) <1 x 10

- 7 mm Hg Density/ Sp. gravity g/cm

- 3 1.47 at 20  C Henry’s Law Constant 5.55 x 10

- 11 atm m 3 /mol Octanol/water partition coefficient (Log K ow )

- 0.46 at pH 7.0

Solvent solubility (g/100 g solvent, 20 o C) Acetone.: 150.7 Benzene : 3.3 Chloroform: 18.0 Ethanol: 86.1 Ethyl acetate: 61.6 Cyclohexane: 0.02Bentazon Preliminary Human Health Risk Assessment D 471312

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Page 38 of 40 

### Appendix C. International Residue Limits

International Residue Limits ( 275200, 103901 ; 09/22/14)

Summary of U.S. Tolerances and International MRLs 1



### . Residue Definition U.S. Canada Mexico 1 

### Codex 2



### 40CFR180.355 (a) General. (1) Tolerances are established for the combined residues of the herbicide bentazon (3

- isopropyl

1 H

- 2,1,3

- benzothiadiazin

- 4(3 H )

- one

2,2

- dioxide) and its 6

- and 8

- hydroxy metabolites 3

- (1

- methylethyl)

- 1 H

2,1,3

- benzothiadiazin

4(3 H )

- one 2,2

- dioxide, including the metabolites 6

- hydroxy

3

- (1

- methylethyl)

- 1 H

2,1,3

- benzothiadiazin

4(3 H )

- one 2,2

- dioxide and 8

- hydroxy

3

- (1

- methylethyl)

- 1 H

2,1,3

- benzothiadiazin

4(3 H )

- one 2,2

- dioxide Sum of bentazone, 6

- hydroxybentazone and 8

- hydroxybent azone expressed as bentazone.

The residue is not fat

soluble.

Commodity Tolerance (ppm)/Maximum Residue Limit (mg/kg) Commodity U.S. Canada Mexico 1 

### Codex 2



### Bean, dry, seed 0.05 0.5 beans (type not defined 0.04 (*) beans, dry

Bean, succulent 0.5 0.5 beans (type not defined) 0.01 (*) beans, except broad bean and soya bean (green pods and immature seeds)

0.01 (*) beans, shelled (succulent= immature seeds) Corn, field, forage 3.0 Corn, field, grain 0.05 0.05 0.01 (*) cereal grains
Corn, field, stover 3.0 0.4 (fodder dry) Corn, pop, grain 0.05 0.01 (*) cereal grains Corn, sweet, kernel plus cob with husks removed 0.05 0.01 (*)

Cowpea, forage 10.0 Cowpea, hay 3.0 Flax, seed 1.0 0.05

Pea, dry, seed 1.0 3 peas (type not defined) 1 (field pea dry)

Pea, field, hay 8.0 Pea, field, vines 3.0

Pea, succulent 3.0 3 peas (type not defined) 1.5 peas (pods and succulent=immature seeds)
Peanut 0.05 0.05 0.05 (*) Peanut, hay 3.0Bentazon Preliminary Human Health Risk Assessment D 471312

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Page 39 of 40 

### Summary of U.S. Tolerances and International MRLs 1



### . Pepper, nonbell 0.05 Peppermint, tops 1.0 Rice, grain 0.05 0.05 0.01 (*) cereal grains Rice, hulls 0.25 Rice, straw 3.0 Sorghum, grain, forage 0.20 Sorghum, grain, grain 0.05 0.15 0.01 (*) cereal grains Sorghum, grain, stover 0.05 Soybean, forage 8.0 Soybean, hay 8.0 Soybean, seed 0.05 0.05 0.01 (*) soya bean (dry) Spearmint, tops 1.0 MRLs with NO U.S. Equivalent
Alfalfa fodder 0.5 Barley straw and fodder, dry 0.3 Cereal grains 0.01 (*) Hay or fodder (dry) of

grasses 2

Herbs 0.1
Linseed 0.02 (*) Millet fodder, dry 0.3 Oat straw and fodder, dry 0.3
Potato 0.1 Onion, bulb 0.1 0.04 Rye straw and fodder, dry 0.3 Spring onion 0.08 Triticale straw and fodder, dry 0.3

Wheat straw and fodder, dry 0.3 Barley 0.1
Blueberries 0.05
Leeks 0.1
Pearl millet 0.15
Proso millet 0.15
Wheat 0.1
Residue Definition U.S. Canada Mexico 1 

### Codex 2 

### U.S.
40CFR180.355 2) Tolerances are established for the combined residues of the herbicide bentazon (3

- isopropyl

- 1 H

2,1,3

- benzothiadiazin

4(3 H )

- one

- 2,2

- dioxide) and its metabolite 2

- amino

- N

isopropyl benzamide (AIBA) Bentazon

Commodity Tolerance (ppm)/Maximum Residue Limit (mg/kg)Bentazon Preliminary Human Health Risk Assessment D 471312

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Page 40 of 40 

### Summary of U.S. Tolerances and International MRLs 1



### . Commodity U.S. Canada Mexico Codex Cattle, fat 0.05 Cattle, meat byproducts 0.05 Cattle, meat 0.05 Egg 0.05 0.01 (*) Goat, fat 0.05 Goat, meat byproducts 0.05 Goat, meat 0.05 Hog, fat 0.05 Hog, meat byproducts 0.05 Hog, meat 0.05
Milk 0.02 0.01 (*) Poultry, fat 0.05 Poultry, meat byproducts 0.05 0.07 Poultry, meat 0.05 0.03 (fat) Sheep, fat 0.05 Sheep, meat byproducts 0.05 Sheep, meat 0.05 Completed by: M. Negussie, 09/25/14

1 Bolded values indicate that the tolerance and MRLs are not harmonized.

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

3 (*) = absent at the limit of quantitation.

(c) Tolerances with regional registrations. Tolerances with regional registration as defined in §180.1(m), are established for combin ed residues of the herbicide, bentazon (3

- isopropyl

- 1 H

- 2,1,3

- benzothiadiazin

- 4(3 H )

- one

- 2,2

- dioxide) and its 6

- and 8

- hydroxy metabolites in or on the following food commodities:

Commodity Parts per million

Clover, forage 1.0

Clover, hay 2.0