UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

MEMORANDUM 

Date: June 3, 20 15 

OFFICE OF CHEMICAL SAFETY 

AND POLLUTION PREVENTION 

SUBJECT: Hexazinone: Draft Human Health Risk Assessment for Registration Review. 

PC Code: 10720 I 

Decision No.: 498287 

Petition No.: NA 

Risk Assessment Type: Single 

Chemical/ Aggregate 

TXRNo.: NA 

MRID No.: NJ\ 

DP Barcode: D424526 

Registration No.: NA 

Regulatory Action: Registration Review 

Case No.: 0266 

CAS No.: 51235-04-2 

40 CFR: § 180.396 

FROM: Sheila Piper, Risk Assessor M-(t~ Shal

Yang 

.u 

Yun

Shelat

g, 

, 

Ph.D.

Industr

, Toxicolo

ial ygenist/Oi; gist 7 ~ Asses 6 . so~ 

~ · 

Risk Assessment Branch VI 

THROUGH: Donna Davis, Acting Branch Chief /LJ~-z__,, Risk Assessment Branch VI li..).) 

Health Effects Division 

TO: Dana Friedman. Chemical Review Manager 

Jose Gayoso, Chemical Review Manager 

Tom Myers. Team Leader 

Kevin Costello, Branch Chief 

Risk Management and Implementation Branch I 

Pesticide Re-evaluation Division (7508P) 

The Health Effects Division (H ED) of the Office of Pesticide Programs (OPP) is charged with 

estimating the risk to human health from exposure to pesticides. As part of Registration Review, 

the Pesticide Re-evaluation Division (PRD) of OPP has requested that HED evaluate the hazard 

and exposure data and conduct dietary. occupational, residential, and aggregate exposure 

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

uses of hexazinone. 

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Hexazinone Human Health Risk Assessment DPNo. 424526

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HED has evaluated the toxicity and exposure databases for the active ingredient, hexazinone, and 

has conducted a human health risk assessment in support of Registration Review.

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

registered uses of hexazinone are provided in this document. The HED team members 

contributing to this risk assessment include Sheila Piper (risk assessment, chemistry, and dietary 

assessment), Shalu Shelat (occupational and residential assessment), and Yang Yung (hazard 

assessment). José Meléndez of the Environmental Fate and Effects Division (EFED) performed 

the drinking water assessment. 
Hexazinone Human Health Risk Assessment DPNo. 424526

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

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

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

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

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

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

2.2.3 Revisions to Petitioned-For Tolerances.................................................................... 7

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

3.0 Introduction........................................................................................................................ 8

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

3.2 Physical/Chemical Characteristics ............................................................................... 9

3.3 Pesticide Use Pattern...................................................................................................... 9

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

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

4.0 Hazard Characterization and Dose-Response Assessment.......................................... 14

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

4.2 Absorption, Distribution, Metabolism and Elimination .......................................... 15

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

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

4.4 Safety Factor for Infants and Children (FQPA Safety Factor) ............................... 16

4.4.1 Completeness of the Toxicology Database ................................................................. 16

4.4.2 Evidence of Neurotoxicity............................................................................................ 16

4.4.3 Evidence of Sensitivity/Susceptibility in the Developing or Young Animal ........... 17

4.4.4 Residual Uncertainty in the Exposure Database ...................................................... 17

4.5 Toxicity Endpoint and Point of Departure Selections............................................... 17

4.5.1 Dose-Response Assessment.......................................................................................... 17

4.5.2 Recommendation for Combining Routes of Exposure for Risk Assessment.......... 18

4.5.3 Cancer Classification and Risk Assessment Recommendations ............................. 19

4.5.4 Summary of Points of Departure and Toxicity Endpoints....................................... 20

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

5.0 Dietary Exposure and Risk Assessment......................................................................... 22

5.1 Residue of Concern Summary .................................................................................... 22

5.2 Food Residue Profile .................................................................................................... 22

5.3 Summary of Environmental Degradation.................................................................. 23

5.4 Water Residue Profile.................................................................................................. 23

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

5.5.1 Description of Residue Data Used in Dietary Assessment....................................... 25

 5.5.2 Percent Crop Treated Used in Dietary Assessment .............................................. 25

5.5.3 Acute Dietary Risk Assessment............................................................................... 25

5.4.4 Chronic Dietary Risk Assessment........................................................................... 26

5.5.5 Cancer Dietary Risk Assessment............................................................................. 26

5.5.6 Dietary Summary Table........................................................................................... 26

6.0 Residential Exposure/Risk Estimates............................................................................. 29

6.1 Spray Drift.................................................................................................................... 29

6.2 Risk Estimates from Lawn Deposition Adjacent to Agricultural Application.......... 30

 6.3 Residential Bystander Post-Application Inhalation Exposure............................32
Hexazinone Human Health Risk Assessment DPNo. 424526

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7.0 Aggregate Exposure/Risk Characterization.................................................................. 33

8.0 Cumulative Exposure/Risk Characterization ............................................................... 33

9.0 Occupational Exposure and Risk Estimates.................................................................. 33

9.1 Occupational Handler Exposure/Risk Estimates...................................................... 33

9.2 Occupational Post-Application Exposure/Risk Estimate ......................................... 45

9.2.1 Occupational Post-Application Inhalation Exposure/Risk Estimates................. 45

9.2.2 Occupational Post-Application Dermal Exposure/Risk Estimates...................... 45

10.0 Human Study Review ...................................................................................................... 46

11.0 Review of Incident Report............................................................................................... 46

12.0 References......................................................................................................................... 46

Appendix A. Toxicology Assessment........................................................................................ 47

A.1 Toxicology Data Requirements................................................................................... 48

A.2 Toxicity Profiles............................................................................................................ 49

Appendix B. Chemical Structures of Hexazinone and its Regulated Metabolites............. 52

Appendix C. International Residue Limits............................................................................ 55

Appendix D Food/Feed Use Patterns Subject to Registration for Hexazinone...............58

Appendix E. Risk Estimates Related to Spray Drift Exposure to Hexazinone from the 

Registered Agricultural Uses.............................................................................61
Hexazinone Human Health Risk Assessment DPNo. 424526

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1.0 Executive Summary

Hexazinone is a triazine-dione herbicide registered for use on alfalfa, blueberries, pasture and 

range grasses, pineapple, and sugarcane. It is also registered for use on ornamental plants, forest 

trees, and non-crop areas. There are no residential uses of the chemical. Hexazinone is used to 

control a variety of weed species and works through inhibition of photosynthesis. Hexazinone 

may be applied for pre- or post-emergence weed control by layby, directed spray, broadcast 

spray, or basal soil treatments and can be applied using either ground or aerial equipment. 

The toxicology database for hexazinone is complete, no additional data are required. Body 

weight decrement and liver toxicity were the most frequent effects shown in studies with 

hexazinone. Liver toxicity was seen in the chronic dog and mouse studies. Body weight 

decrement was seen in the chronic and reproductive toxicity studies in rats. In a reproduction 

study in rats, pup weight decrement occurred at the same dose as parental body weight 

decrement. No reproductive effects were seen in the study other than pup weight decrement. In 

the rat developmental toxicity study, developmental effects (kidneys with no papillae and 

misaligned sternebrae) were seen at a higher dose than the dose causing maternal toxicity. In the 

rabbit study, fetal weight decrements were seen at the same dose that caused maternal weight 

decreases.

The 21-day dermal study in the rabbit showed mild dermal irritation but no systemic toxicity was 

observed at the limit dose. A 28-day inhalation study in rats showed effects in the portal-of-entry 

as squamous and mucous cell metaplasia at the ventral base of the epiglottis and in the nose, 

nasal septum and nasopharynx. In an acute neurotoxicity study, reduced motor activity was 

observed in rats of both sexes, and decreased body temperature and increased incidences in 

posture and palpebral closure parameters were observed in females at the highest dose tested 

(500 mg/kg). In a subchronic neurotoxicity study, no neurotoxicity was observed up to the 

highest dose tested. There was no evidence of immunotoxicity in a rat immunotoxicity study.

Hexazinone is classified as "Group D chemical, not classifiable as to human carcinogenicity"

based on weight-of-evidence (WOE) considerations in carcinogenicity studies in rats and mice 

and no evidence of mutagenicity.

Hexazinone has low acute toxicity by the oral (Toxicity Category III), dermal (Toxicity Category 

IV), and inhalation (Toxicity Category III) routes. Primary eye irritation is severe, causing 

corneal opacity and moderate irritation in unwashed eyes (Toxicity Category I). Hexazinone 

causes mild skin irritation (Toxicity Category IV) but it is not a skin sensitizer.

There is no evidence of increased quantitative or qualitative susceptibility of the young following 

in utero and pre-and post-natal exposure to hexazinone based on the results from developmental 

studies conducted with rats and rabbits, as well as a two-generation reproduction study 

conducted with rats. Therefore, the risk assessment team concluded that the 10-fold Food Quality 

Protection Act (FQPA) Safety Factor may be reduced to 1x. Also, a target margin of exposure 

(MOE) of 100 is considered adequate for all exposure scenarios (10x) for interspecies 

extrapolation and 10x for intraspecies variability. The uncertainty factor of 30x was applied for 
Hexazinone Human Health Risk Assessment DPNo. 424526

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inhalation risk assessment (3x for interspecies extrapolation, 10x for intraspecies variation, and a 

1x FQPA SF) resulting in a level of concern (LOC) of 30.

The residue chemistry database for hexazinone is complete. Acceptable data were submitted 

depicting residues in target crops. These data are supported by storage stability data and were 

generated using adequately validated analytical methods. There is an analytical method to 

enforce the proposed tolerance. The nature of the residue in plants and livestock is adequately 

understood. The field trial data for hexazinone and its metabolites in/on warm-season pasture 

grass forage and hay was used to recalculate the maximum reasonably balanced dietary burden 

(MRBDB). The feeding study data indicate that the established tolerances for residues of 

hexazinone in/on ruminant meat, meat byproducts, and fat for cattle, goats, horses and sheep 

livestock commodities should be retained. Based on the dietary burden calculation and the 

residue profile in the feeding study, the Agency concludes that there are not likely to be 

quantifiable residues of hexazinone and its metabolites in eggs, poultry, and hog commodities, 

and a Category 3 of 40 CFR§180.6 (a)(3) should remain. 

EFED has determined that a new drinking water assessment should be conducted which 

considers the potential for hexazinone formation during water treatment. EFED shared with HED 

preliminary estimated drinking water concentrations (EDWCs) for various application scenarios 

and additional refinements were conducted. 

The acute aggregate (food and drinking water) dietary exposure estimates for various scenarios 

are below HED’s level of concern (<100 % of the acute population adjusted dose (aPAD)) for 

the U.S. population and all population subgroups. The worst case scenario was the North 

Carolina coastal rights-of-ways PRZM-GW that resulted in the combined acute dietary exposure 

and risk estimates from food and drinking water which utilized 23% of the aPAD for the U.S. 

population and 73% of the aPAD for children 1-2 years old at the 95th percentile, the most highly 

exposed population subgroup. For chronic, the dietary exposure is estimated to be 29% of the 

cPAD for the U.S. population, and 71% of the cPAD for children 1-2 years old, the population 

with the highest estimated chronic dietary exposure to hexazinone from the pasture/rangeland (2 

lbs ai application rate for WI sand) PRZM-GW scenario.

There are no registered residential uses of hexazinone; therefore, a residential handler and postapplication assessment was not conducted.

In the absence of systemic dermal toxicity, dermal handler and post-application exposure 

assessments were not conducted, and there is no risk associated with dermal exposure to 

workers. An occupational handler inhalation exposure and risk assessment was conducted. 

There are some occupational handler inhalation risk estimates of concern for the registered uses 

of hexazinone at baseline (i.e., no respirator). Occupational inhalation MOEs ranged from 0.8 to 

9,600 (LOC = 30) at baseline attire with labeled personal protective equipment (PPE; i.e., gloves 

and no respirator). The inhalation scenarios have been assessed for additional PPE which 

include PF5 respirators, PF10 respirators, and engineering controls. Some scenarios have risks 

of concern even with the consideration of engineering controls. The re-entry interval (REI) is 

based on the acute toxicity of hexazinone and a 48 hour REI is adequate for the registered uses. 
Hexazinone Human Health Risk Assessment DPNo. 424526

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

inhalation exposure assessment was not performed for hexazinone at this time. If new policies or 

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

post-application inhalation exposure assessment for hexazinone.

A quantitative non-occupational spray drift assessment was conducted for hexazinone. 

Children’s (1 to < 2 years old) incidental oral risk estimates from indirect exposure to 

hexazinone related to spray drift did not exceed HED’s level of concern at the edge of the treated 

field (MOEs ≥ 100). 

2.0 HED Recommendations

2.1 Data Deficiencies

There are no data deficiencies relating to toxicology, residue chemistry, or occupational exposure 

associated with this registration review for hexazinone. 

2.2 Tolerance Considerations

2.2.1 Enforcement Analytical Method

Adequate methods are available for purposes of enforcement of tolerances and data collection for 

residues of hexazinone and metabolites A, B, C, D, and E in/on plant commodities. For 

tolerance enforcement, the Pesticide Analytical Manual (PAM) Volume II lists Method I as 

available for the determination of hexazinone residues of concern in/on plant commodities. The 

combined limit of quantitation (LOQ) for hexazinone residues (parent and metabolites) by 

Method I in PAM Volume II, is 0.55 ppm. A liquid chromotography/mass spectroscopy (LC/MS) 

method (AMR 3783-96) is available as an enforcement method for livestock commodities. The 

reported LOQs were 0.02 ppm for hexazinone and metabolite B and 0.05 ppm for metabolites C, 

C-2, and F. 

2.2.2 Recommended Tolerances

Permanent tolerances are currently established for residues of the herbicide hexazinone, 

including its metabolite and degradates, in or on the commodities in the 40 CFR§180.396. The 

tolerance expression listed in the 40 CFR§180.396 complies with the HED interim tolerance 

expression policy (S. Knizner, 5/27/99). Previously, HED recommends that a tolerance for 

inadvertent hexazinone residues in/on corn stover, sorghum stover, and wheat straw at 0.50 ppm

be established.

Table 2.2.2. Tolerance Summary for Hexazinone, §180.396(3)(d)

 Commodity Proposed Tolerance 

(ppm)

HED-Recommended 

Tolerance (ppm)

Comments 

(correct commodity definition)

Corn stover -- 0.50

Sorghum stover -- 0.50

Wheat straw -- 0.50
Hexazinone Human Health Risk Assessment DPNo. 424526

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 *NA – Not applicable.

Note to PRD: Previously, HED recommended that residues in/on hog commodities are not 

expected. Therefore, the established tolerances for hog commodities that are listed in the 40 

CFR§180.396 for hexazinone should be removed.

2.2.3 Revisions to Petitioned Tolerances

None

2.2.4 International Harmonization

There are no established Codex maximum residue limits (MRLs) on hexazinone. Canadian 

MRLs are established on livestock commodities only. The Canadian tolerance expression for 

ruminant tissues include hexazinone and metabolite B and the tolerance is 0.04 ppm for livestock 

commodities. The Canadian tolerance expression for milk include hexazinone and metabolites B 

and C and the tolerance is 0.09 ppm for milk. The tolerance/MRL definition in the US and 

Canada are different; therefore, tolerance and MRLs cannot be harmonized at this time.

3.0 Introduction

Hexazinone [3-cyclohexyl-6-(dimethylamino)-1-methyl-1,3,5-triazine-2,4-(1H,3H)-dione] is 

used to control a variety of weed species including geratum, alder, and alexander grass and 

works through inhibition of photosynthesis. Hexazinone is a proprietary chemical of E.I. du 

Pont de Nemours Inc. which is the sole producer and primary registrant of this broad spectrum 

herbicide. It was first registered on November 1975 for general weed control in non-cropland 

areas. The most recent human health risk assessment for hexazinone was conducted 2002 

(D275621, C. Christensen, 8/22/02). 

3.1 Chemical Identity

Table 3.1. Hexazinone Nomenclature

Chemical Structure

Empirical Formula C12H20N4O2

Common Name Hexazinone

IUPAC name 3-cyclohexyl-6-dimethylamino-1-methyl-1,3,5-triazine-2,4(1H,3H)-

dione

CAS Name 3-cyclohexyl-6-(dimethylamino)-1-methyl-1,3,5-triazine-2,4(1H,3H)-

dione

N

N

N N

O

O
Hexazinone Human Health Risk Assessment DPNo. 424526

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Table 3.1. Hexazinone Nomenclature

CAS Registry 

Number 51235-04-2

Chemical Class Triazinone herbicide

3.2 Physical/Chemical Characteristics

Hexazinone is highly soluble in water (29,800 ppm), it has a relatively low vapor pressure (1.9 x 

10-7 mmHg), and a very low Henry’s Law Constant (2 x 10-12 atm-m3/mol). Based on these 

properties, it appears hexazinone is mobile in the environment, partitions into water more than to 

soil and has a very low potential to bioaccumulate.

Table 3.2. Hexazinone Physical and Chemical Properties

Parameter Value

Molecular Weight 252.3 g

Water solubility (20°C) 2.98 g/100 @25oC

Vapor pressure (20°C) 1.9 x 10-7 mmHg@25oC

Henry’s Law Constant (25°C) 2 x 10-12 atm-m3/mol; @25oC

Octanol/water partition coefficient 

(25°C) log Kow = 1.95 

3.3 Pesticide Use Pattern

Hexazinone is currently formulated as pellets/tablets, dry flowable, and water dispersible 

granules, liquids, and granules. Products are applied using aerial or ground equipment, by hand, 

or using a hand-held, backpack, or pressurized sprayer. Hexazinone is registered for preemergent, post-emergence, layby, directed spray, and basal soil applications. The maximum 

single application rates for each crop or use site range from 1.125 to 8 lbs ai/A. For the pellet 

application, the maximum single application rate is 7000 pellets/A (7.5 lbs ai/A) and for tree 

injection or basal soil single stem injection, the maximum rate is 4 mL per each inch stem 

diameter. There are no registered residential uses. The uses and application rates are 

summarized in Table 3.3.

Table 3.3. Summary of Directions for Use of Hexazinone. 

Applic. Timing, 

Type, and Equip.

Formulation1

[EPA Reg. No.]

Maximum 

Applic. 

Rate

(lb ai/A)

Max. No. 

Applic. per 

Season

Max. Seasonal 

Applic. Rate 

(lb ai/A)

PHI (days) Use Directions and 

Limitations

Alfalfa

Ground

Aerial

Chemigation

Dry Bulk Fertilizer1

EC [352-392; 

5905-579; 

84229-35]

WDG/DF [352-

581; 352-634; 

1.5 1 1.5 30

Do not apply within 30 

days of harvest (cutting 

for hay), or feeding of 

forage or grazing. Do 

not exceed 1.5 pounds 

active ingredient 
Hexazinone Human Health Risk Assessment DPNo. 424526

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Table 3.3. Summary of Directions for Use of Hexazinone. 

Applic. Timing, 

Type, and Equip.

Formulation1

[EPA Reg. No.]

Maximum 

Applic. 

Rate

(lb ai/A)

Max. No. 

Applic. per 

Season

Max. Seasonal 

Applic. Rate 

(lb ai/A)

PHI (days) Use Directions and 

Limitations

352-665; 352-

666; 84229-32]

hexazinone per acre per 

year.

Do not apply within 30 

days of harvest (cutting 

for hay), or feeding of 

forage or grazing.

High Bush Blueberry

Spring before leave 

emergence

Ground

Dry Bulk Fertilizer1

EC [352-392; 

5905-579; 

84229-35]

WDG/DF [352-

581; 84229-32]

2 N/S N/S 90

Do not apply through 

any type of irrigation 

system. Do not apply to 

flooded field with 

standing water. 

Application to 

blueberry foliage will 

result in crop injury.

Low Bush Blueberry

Spring before leave 

emergence

Ground 

Dry Bulk Fertilizer1

EC [352-392; 

5905-579; 

84229-35]

WDG/DF [352-

581; 84229-32]

3 N/S N/S 450

Do not apply through 

any type of irrigation 

system.

Sugarcane

Pre- and postemergent, and layby

Ground

Aerial

EC [352-392; 

84229-35]

WDG/DF [352-

618; 352-633; 

352-581; 84229-

32]

3.6 (HI)

0.9 (LA)

0.5 (PR)

1.75 (TX) 

N/S

3.6 (HI)

1.5 (LA)

1 (PR)

1.75 (TX)

180 (HI)

234 (LA)

288 (PR)

234 (TX)

Do not feed sugarcane 

forage to livestock. Do 

not apply 

postemergence over the 

top to sugarcane 

beyond a height of 18 

inches.

Pineapple

Ground

Aerial

Handheld 

EC [352-392; 

5905-579; 

84229-35]

WDG/DF 

[84229-32; 352-

581]

3.6 (field

edges and 

roadside)

0.036 lbs 

ai/gallon N/S 3.6 181

Do not exceed 3.6 lbs 

ai per acre per crop. 

Intercrop period, postmulch pre-plant, postplant, post-emergence (3-

10 months after planting)

1.75

0.0175 lbs 

ai/gallon

Bermudagrass/Bahiagrass (Industrial Turf Grass)

Ground

EC [84229-35; 

5905-579]

WDG/DF [352-

581; 84229-32]

1.125 N/S N/S 60

Do not use on lawns, 

driveways, tennis 

courts, or other 

residential or 

recreational areas or 

golf courses

Pastures; Rangeland
Hexazinone Human Health Risk Assessment DPNo. 424526

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Table 3.3. Summary of Directions for Use of Hexazinone. 

Applic. Timing, 

Type, and Equip.

Formulation1

[EPA Reg. No.]

Maximum 

Applic. 

Rate

(lb ai/A)

Max. No. 

Applic. per 

Season

Max. Seasonal 

Applic. Rate 

(lb ai/A)

PHI (days) Use Directions and 

Limitations

Ground

EC [352-392; 

5905-579; 

84229-35] 

WDG/DF [352-

581; 84229-32]

2 1 2 60

Do not cut treated 

vegetation for feed, or 

graze livestock on 

treated areas for 60 

days following 

application at broadcast 

rates exceeding 4.5 

pints per acre.

Late winter to early 

summer

Hand dispersal

Handheld 

equipment

Pellets2[33560-

41]

4 

pellets/plant

600

pellets/acre

N/S N/S

Apply by hand to the

soil around specific 

plants or in a grid 

pattern for area control

Non-Crop Sites: Agricultural Rights of Way/Fence Rows/Hedge Rows; Airport/Landing Fields; Industrial Areas 

(outdoors); Sewage Disposal Areas; Non-Crop Sites; Intermittently Flooded Areas/Water; Drainage Systems

Ground

Aerial 

Airblast

EC [352-392; 

84229-35; 5905-

579]

8

(0.32 lb 

ai/gallon)

N/S N/S

Do not use on lawns, 

driveways, tennis 

courts, or other 

residential or 

recreational areas;

Ground 

Aerial (helicopter 

only) or (military

installations only)

WDG/DF [352-

626; 84229-32; 

352-581]

2.7- 8 N/S N/S 60

Not labeled for use on 

recreation areas or for 

direct application to 

paved areas (surfaces). 

Do not apply this 

product through any 

type of irrigation 

system. Do not use in 

nurseries, seed beds or 

ornamental plantings

Residential areas: Do 

not apply on areas such 

as lawns, walks, 

driveways, or tennis 

courts.

Ground

Handheld 

Aerial (military 

installations only)

G

[352-450; 

81927-31]

4- 8

(0.000134 

lbs ai/sq ft)

N/S N/S 60

For rates above 8 1b 

per acre, do not cut for 

forage or hay nor graze 

domestic animals for 1 

year.

Residential areas: Do 

not apply on areas such 

as lawns, walks, 

driveways, or tennis 

courts.

Hand dispersal

Handheld 

equipment

Pellets2[33560-

41]

7000 

pellets/A N/S N/S N/A None
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Table 3.3. Summary of Directions for Use of Hexazinone. 

Applic. Timing, 

Type, and Equip.

Formulation1

[EPA Reg. No.]

Maximum 

Applic. 

Rate

(lb ai/A)

Max. No. 

Applic. per 

Season

Max. Seasonal 

Applic. Rate 

(lb ai/A)

PHI (days) Use Directions and 

Limitations

2 pellets per 

inch of stem 

diameter

Christmas Tree Plantations

Pre- and early postemergence

Ground

Aerial

(helicopter only)

Chemigation

Handheld

EC [352-392; 

5905-579; 

84229-35]

WDG/DF [352-

626; 84229-32; 

352-581]

2

(0.2 lb 

ai/gallon)

1 1 N/A

Do not apply with airblast spray equipment. 

Do not use in 

Christmas tree seed 

beds or transplant 

nurseries. Apply only 

when trees are dormant 

for broadcast 

applications. 

Do not use in nurseries, 

seed beds, or 

ornamental plantings.

Forestry (various) and Forestry and Herbaceous Weed Release 

Pre and early postemergence

Ground

Aerial

(helicopter only)

Handheld

Single Stem 

Treatment

Tree Injection

Dry Bulk Fertilizer1

EC [352-392; 

5905-579; 

84229-35]

WDG/DF [352-

626; 352-581; 

84229-32]

4-5

2 lbs 

ai/gallon

N/S 5 N/A

Single Stem Treatment: 

Apply at the rate of 2-4 

rnl for each inch of 

stem diameter at breast 

height. Direct the 

treatment to the soil 

within 3 feet of the root 

collar of woody plants 

to be controlled.

Tree Injection: Inject 1 

ml of undiluted product 

through the bark of 

undesirable trees. Make 

injections at 4 inch 

intervals around the 

circumference of the 

tree. When using 

tubular injection 

equipment, inject near 

the ground level.

Spring or early Fall

Ground

Aerial

Handheld 

equipment 

G [352-603;

81927-31; 350-

450]

4.7 (Eastern)

4 (Western) N/S N/S N/A

Do not apply this 

product through any 

type of irrigation 

system. Do not use in 

nurseries, seed beds or 

ornamental plantings. 

Do not apply to trees 

grown for Christmas 

trees or ornamentals

Late winter to early 

summer

Hand dispersal

Pellets2[33560-

41]

Forestry: 

5800 

pellets/A

Release: 

N/S N/S N/A

Apply at a rate of 1,700 

to 5,800 pellets per acre 

for
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Table 3.3. Summary of Directions for Use of Hexazinone. 

Applic. Timing, 

Type, and Equip.

Formulation1

[EPA Reg. No.]

Maximum 

Applic. 

Rate

(lb ai/A)

Max. No. 

Applic. per 

Season

Max. Seasonal 

Applic. Rate 

(lb ai/A)

PHI (days) Use Directions and 

Limitations

Handheld 

equipment

3,800 

pellets/A

preharvest, site 

preparation, and 

wildlife openings, and

900 to 3,800 pellets per 

acre for release.

1. Bulk fertilizer application rate calculated for the maximum rate on the various labels: 40 pts of liquid product (12 lbs ai 

hexazinone) per ton of fertilizer OR 16 lbs of dry flowable product (12 lbs ai) per ton of fertilizer.

2. 700 pellets per pound of Pronone Power Pellet Herbicide with 75% Hexazinone = 0.001071 lbs ai/pellet

Conclusion

The proposed labels for hexazinone are adequate to allow evaluation of the residue data relative 

to the proposed uses. 

3.4 Anticipated Exposure Pathways

Humans may be exposed to hexazinone in food because hexazinone may be applied directly to 

growing crops. In addition, runoff, soil erosion and/or off-target spray drift can result in 

hexazinone reaching surface water and ground water, both of which can serve as sources of 

drinking water. Residential handler and post-application exposure is not expected since 

hexazinone is currently not registered for non-occupational use. In an occupational setting, 

handlers may be exposed while handling the pesticide prior to application, as well as during 

application. There is also a potential for post-application exposure for workers re-entering 

treated sites. 

3.5 Consideration of Environmental Justice

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

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

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

(http://epa.gov/compliance/ej/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 around the home that involve pesticide use in a residential 

setting. Extensive data on food consumption patterns are compiled by the U.S. Department of 

Agriculture (USDA) under the National Health and Nutrition Examination Survey, What We Eat 

in America, (NHANES/WWEIA). These food consumption patterns are used in pesticide risk 

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

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

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

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

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

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

estimates were not of concern. Further considerations are currently in development, as OPP has 
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committed resources and expertise to the development of specialized software and models that 

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

patterns among specific subgroups.

4.0 Hazard Characterization and Dose-Response Assessment

Hexazinone hazard was previously reviewed by HED’s Hazard Identification Assessment 

Review Committee in 2002 (TXR# 0051033). New data have been submitted since that review 

including acute and subchronic neurotoxicity, 28-day inhalation, and immunotoxicity studies. 

The risk assessment team has incorporated these data into this risk assessment and reevaluated 

the points of departure and toxicity endpoints for the acute and chronic dietary and the 

occupational and residential scenarios using current policies on selecting endpoints and 

uncertainty factors.

4.1 Toxicology Studies Available for Analysis

The toxicology database for hexazinone is complete; no additional data is required. The scientific 

quality of the database for hexazinone is relatively high and the toxicity profile can be 

characterized for a wide range of effects, including developmental, reproductive, neurotoxic, 

carcinogenic, mutagenic, and immunotoxic effects. The toxicity data requirements and toxicity 

profile are listed in Appendix A. The data from the following studies were used to evaluate the 

hazard potential of hexazinone: 

 Acute lethality studies (oral, dermal, inhalation, primary eye and dermal irritation, 

and dermal sensitization)

 Acute and subchronic neurotoxicity studies (rats)

 Subchronic oral toxicity studies (rats and dogs) 

 28-day inhalation study (rats)

 21-day dermal toxicity study (rabbits)

 Developmental (rats and rabbits) and reproductive toxicity (rats) studies

 Chronic oral toxicity studies (rats and dogs)

 Carcinogenicity studies (rats and mice)

 Metabolism studies (rats)

 Mutagenicity battery 

 Immunotoxicity study (rats)
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4.2 Absorption, Distribution, Metabolism, & Elimination (ADME)

A metabolism study (MRID 00109237, 0014016) was conducted to evaluate the absorption,

distribution, metabolism, and excretion of hexazinone in CD rats by gavage to groups of one 

male and one female rat at concentrations of 14 mg/kg or 1000 mg/kg. A third group of two

male and two female rats received unlabeled hexazinone (5 mg/kg/day) in the diet for three

weeks before being given a single 14 mg/kg radiolabeled gavage dose.

Mass balance was excellent and ranged from 95-102% recovery for all treatment groups. 

Based on the amount of radiolabel recovered in the urine and cage wash, absorption of the test

material was at least 83% with no dose- or sex-dependent differences noted. By 72 hours

after treatment, essentially none of the radiolabeled test material was present in the tissues. 

Urine was the primary route of elimination accounting for ~83% of the administered dose. 

Urinary elimination was rapid and ~96% complete within 48 hours of treatment. No

apparent sex or dose-related differences were found. Fecal excretion was a minor route of

elimination, accounting for ~16% of the dose and was rapid with ~95% occurring within 72

hours of treatment. Once again, no apparent sex or dose-related differences were found.

Essentially none of the parent compound was found in the urine or feces of male and female

rats following multiple low-dose or a single high-dose treatment with hexazinone. 

Three metabolites were identified in the urine of males and females (metabolite A and C,

~57% and ~28% of identified metabolites, respectively). Two of the metabolites were

identical to those found in the feces. The third metabolite (3-(cyclohexyl)-6-(methylamino)-

1-methyl-1, 3,5-triazine-2,4(1H,3H)-dione) (metabolite B, ~9% of urinary metabolites)

resulted from demethylation of the 6-dimethyl amine group to form a secondary amine

without hydroxylation of the 4-position on the cyclohexyl ring. Approximately 3% of the

urine metabolites were unidentified as polar compounds and 5% were isolated from the

hydrolyzed urine, suggesting they had undergone glucuronide or sulfate conjugation. No

differences between the sexes or dose groups in the metabolic conversion of hexazinone were

found.

4.2.1 Dermal Absorption

No dermal absorption study is available; however, since no dermal hazard has been identified for 

hexazinone, dermal endpoints were not selected for use in this risk assessment. 

4.3 Toxicological Effects

Body weight decrement and liver toxicity were the most frequent effects shown in studies with 

hexazinone. Liver toxicity was seen in the chronic dog and mouse studies. Body weight 

decrement was seen in the chronic and reproductive toxicity studies in rats.
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In a reproduction study in rats, pup weight decrement occurred at the same dose as parental body 

weight decrement. No reproductive effects were seen in the study other than pup weight 

decrement. In the rat developmental toxicity study, developmental effects (kidneys with no 

papillae and misaligned sternebrae) were seen at a higher dose than the dose causing maternal 

toxicity. In the rabbit study, fetal weight decrements were seen at the same dose that caused 

maternal weight decreases. Thus, no offspring susceptibility is seen in rat or rabbit prenatal 

studies or the rat reproduction study.

The 21-day dermal study in the rabbit showed mild dermal irritation but no systemic toxicity was 

observed at the limit dose. A 28-day inhalation study in rats showed effects in the portal-of-entry 

as squamous and mucous cell metaplasia at the ventral base of the epiglottis and in the nose, 

nasal septum and nasopharynx. In an acute neurotoxicity study, reduced motor activity was 

observed in rats of both sexes, and decreased body temperature and increased incidences in 

posture and palpebral closure parameters were observed in females only at the highest dose 

tested (500 mg/kg). In a subchronic neurotoxicity study, no neurotoxicity was observed up to the 

highest dose tested. There was no evidence of immunotoxicity in a rat immunotoxicity study.

Hexazinone is classified as "Group D chemical, not classifiable as to human carcinogenicity"

based on WOE considerations in carcinogenicity studies in rats and mice and no evidence of 

mutagenicity.

Hexazinone has low acute toxicity by the oral (Toxicity Category III), dermal (Toxicity Category 

IV) and inhalation (Toxicity Category III) routes. Primary eye irritation is severe, causing 

corneal opacity and moderate irritation in unwashed eyes (Toxicity Category I). Hexazinone 

causes mild skin irritation (Toxicity Category IV) but it is not a skin sensitizer.

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

There is no evidence of increased quantitative or qualitative susceptibility of the young following 

in utero and pre-and post-natal exposure to hexazinone based on the results from developmental 

studies conducted with rats and rabbits, as well as a two-generation reproduction study 

conducted with rats. The risk assessment team concluded that the 10-fold FQPA Safety Factor

may be reduced to 1x.

4.4.1 Completeness of the Toxicology Database

The toxicology database for hexazinone is complete and adequate to support risk assessments.

4.4.2 Evidence of Neurotoxicity

Hexazinone is not considered a neurotoxic chemical. In an acute neurotoxicity study, reduced 

motor activity in both sexes and some FOB findings (decreased body temperature and increased 

incidences in posture and palpebral closure parameters) in females were observed at 500 mg/kg 

on Day 0 only. These findings were considered treatment-related with an impairment of the 

overall condition of the animals following a gavage treatment, rather than direct neurotoxic 
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effects of the hexazinone exposure based on the absence of any neurohistopathological changes 

in the treated animals and the transient nature of the observed FOB and neurobehavioral 

assessments. In a subchronic neurotoxicity study, no neurotoxicity was observed in rats fed 

dietary concentrations of hexazinone up to the highest dose tested at 273/350 mg/kg/day 

(males/females, respectively) for 90 days. In addition, the toxicology database does not reveal 

any evidence of neurotoxic clinical signs, changes in brain weight, or histopathology of the 

nervous system in any study with hexazinone. 

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

The toxicology data on hexazinone provides no indication of enhanced sensitivity of infants and 

children based on the results from developmental studies conducted with rats and rabbits as well 

as a two-generation reproduction study conducted with rats. No quantitative or qualitative 

evidence of increased susceptibility was seen following in utero or pre-/post-natal exposure to 

rats or rabbits. In the rat developmental toxicity study, developmental effects (kidneys with no 

papillae and misaligned sternebrae) were seen at a higher dose than the dose causing maternal 

toxicity. In the rabbit study, fetal weight decrements were seen at the same dose that caused 

maternal weight decreases. In the two-generation reproduction study, offspring toxicity 

(decreased pup weights) was seen at the same dose that caused parental toxicity.

4.4.4 Residual Uncertainty in the Exposure Database

The exposure database is complete and there are no residual uncertainties in the exposure 

database that would result in an underestimation of risk. 

4.5 Toxicity Endpoint and Point of Departure Selections

4.5.1 Dose-Response Assessment

Acute Dietary Endpoint for the General Population (Including Females 13-49 Years of Age): An 

acute neurotoxicity study in rats (MRID 48931901) was selected with a NOAEL of 125 mg/kg 

and a LOAEL of 500 mg/kg based on reduced motor activity in both sexes and reduced body 

temperature and FOB findings in females. The route and the single exposure of this study are 

appropriate for acute dietary risk assessment. Previously, a developmental toxicity study in rats 

(MRID 40397501) was selected for female 13-49 years of ages with a NOAEL of 400 mg/kg/day 

and a LOAEL of 900 mg/kg/day based on increased incidence of kidneys with no papillae and 

misaligned sternebrae. The newly established point of departure (PoD) of 125 mg/kg from the 

acute neurotoxicity study is considered protective of this developmental effect which was seen at 

900 mg/kg/day (almost 10 folds higher than the PoD). The UF is 100x (10x for interspecies 

extrapolation, 10x for intraspecies variation and 1x for FQPA Factor). The aPAD for the general 

population is 1.25 mg/kg.
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Chronic Dietary Endpoint for the General Population: An one-year oral toxicity study in dogs 

(MRID 42162301) was selected with a NOAEL of 5.0 mg/kg/day and a LOAEL of 41.2/37.6 

(M/F) mg/kg/day based on body weight decrements, elevated clinical chemistry values (serum 

alkaline phosphatase, serum aspartate aminotransferase), and histopathologic lesions of the liver. 

An UF of 100x (10x for interspecies extrapolation and 10x for intraspecies variation and 1x for 

FQPA Factor) is applied to the NOAEL of 5.0 mg/kg/day to obtain a cRfD of 0.05 mg/kg/day. 

The population adjusted dose (cPAD) is 0.05 mg/kg/day.

Incidental Oral Exposure (Short-Term): A two-generation reproduction study in rats (MRID 

42066501) was selected with a NOAEL of 12 mg/kg/day and a LOAEL of 117/143 (M/F) 

mg/kg/day based on offspring toxicity seen as decreased pup weights at birth and during 

lactation. This study is appropriate for this exposure scenario since the sub-populations of 

interest (infants, toddlers, and young children) are considered for this endpoint selection. The UF 

is 100x (10x for interspecies extrapolation, 10x for intraspecies variation and 1x for FQPA 

Factor).

Dermal Exposure (Short-, Intermediate-Term): A 21-day dermal toxicity study in rabbits (MRID 

41309005) is available with a NOAEL of 1000 mg/kg/day (the limit dose) and no systemic 

toxicity was seen. Since no dermal toxicity was observed at the limit dose and there are no 

developmental toxicity concerns, risk assessment for short- and intermediate-term occupational 

dermal exposure is not necessary. 

Dermal Exposure (Long-Term): The current use pattern does not indicate a concern for longterm exposure/risk, and no long-term uses are proposed. Therefore, risk assessment for long-term 

dermal exposure is not needed. 

Inhalation Exposure (short and Intermediated-Term): A 28-day inhalation study in rats (MRID 

49221101) was selected with a NOAEL of 0.031 mg/L and a LOAEL of 0.11 mg/L based on 

effects seen in the portal-of-entry as squamous and mucous cell metaplasia at the ventral base of 

the epiglottis and in the nose, nasal septum and nasopharynx. The NOAEL (0.031 mg/L) is then 

converted to a Human Equivalent Concentration (HEC) and Human Equivalent Dose (HED)

based on the portal of entry effects, according to the Agency’s Reference Concentration (RfC) 

1994 Methodology for occupational and residential assessments and the latest HED inhalation 

guidance policy (2014). The uncertainty factor of 30x was applied (3x for interspecies 

extrapolation, 10x for intraspecies variation and a 1x FQPA SF). The interspecies uncertainty 

factor was reduced to 3x because of adjustment for species differences that affect 

pharmacokinetics.

Inhalation Exposure (Long-Term): The current use pattern does not indicate a concern for longterm exposure/risk, and no long-term uses are proposed. Therefore, risk assessment for long-term 

inhalation exposure is not needed.

4.5.2 Recommendation for Combining Routes of Exposures for Risk Assessment
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Hexazinone does not pose a dermal risk; therefore, quantification of dermal risk is not required. 

Dietary (food + water) exposure is the only component of an aggregate exposure analysis and 

risk assessment. The inhalation exposure was based on port of entry (not systemic effects) and 

should not be combined for risk assessment. 

4.5.3 Cancer Classification and Risk Assessment Recommendation

HED’s Carcinogenicity Peer Review Committee (CPRC) classified hexazinone as "Group D 

chemical, not classifiable as to human carcinogenicity” based on the following weight of 

evidence considerations. In rats, females showed no evidence for carcinogenicity; males showed 

a significant trend only for thyroid adenomas. In mice, the evidence of carcinogenicity was 

equivocal: a positive trend test for liver tumors was observed in female mice, but no significant 

difference was seen by pair-wise comparison. There is no evidence of mutagenicity for 

hexazinone (CPRC Report, July 27, 1994). No quantitative cancer risk assessment is required.
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4.5.4 Summary of Points of Departure and Toxicity Endpoints Used in Human Risk 

Assessment

 Table TABLE 4.5.4.1 Summary of Toxicological Doses and Endpoints for Use in Hexazinone Human 

Health Risk Assessments.

Exposure

Scenario

Point of Departure, 

Uncertainty/FQPA 

Safety Factors

RfD, PAD, LOC for 

Risk Assessment

Study and Toxicological Effects

Acute Dietary

(All Populations 

including Females 13-

49 Years of Age)

NOAEL = 125 mg/kg/day

UFA = 10x

UFH = 10x

FQPA SF = 1x

aRfD= 1.25 mg/kg

aPAD= 1.25 mg/kg

Acute neurotoxicity study in rats

(MRID 48931901)

LOAEL= 500 mg/kg based on 

reduced motor activity in both 

sexes, decreased body temperature 

and other FOB findings in females 

Chronic Dietary

(All Populations)

NOAEL = 5.0 mg/kg/day

UFA = 10x

UFH = 10x

FQPA SF = 1x

cRfD= 0.05 mg/kg/d

cPAD= 0.05 mg/kg/d

One-year oral toxicity study in dogs

(MRID 42162301)

LOAEL = 38 mg/kg/day, based on 

decreased body weight and 

hepatotoxicity as evidence by 

changes in clinical chemistry 

parameters and microscopic lesions.

Incidental Oral-

(Short-Term)

NOAEL= 12 mg/kg/day

UFA = 10x

UFH = 10x

FQPA SF = 1x

LOC for

MOE= 100

Two-gen reproduction study in rats

(MRID 42066501)

Offspring LOAEL= 117 mg/kg/day 

based on reduced pup weights at 

birth and during lactation.

Dermal 

(Short- and 

Intermediated-Term)

Quantification of dermal risk is not required due to lack of dermal, systemic, or 

developmental toxicity concerns. In a 21-day dermal toxicity study in rabbits, no systemic 

toxicity was observed, NOAEL=1000 mg/kg/day. 

Dermal 

(Long-Term)

No long-term dermal exposure anticipated from currently use pattern.

Inhalation 

(Short- and 

Intermediate-Term)

NOAEL= 0.031 mg/L

HEC=(see below)

HED=(see below)

UFA = 3x

UFH = 10x

FQPA SF = 1x

LOC for 

MOE = 30

28-day inhalation study in rats

(MRID 49221101) 

LOAEL= 0.11 mg/L/day, based on 

squamous and mucous cell 

metaplasia at the ventral base of the 

epiglottis and in the nose, nasal 

septum and nasopharynx (portal-ofentry). 

Occupational handler HEC=0.00391 mg/L

Occupational scenarios assigned a breathing rate of 8.3 L/min: HED=0.222 mg/kg/day

Occupational scenarios assigned a breathing rate of 16.7 L/min: HED=0.447 mg/kg/day

Occupational scenarios assigned a breathing rate of 29 L/min: HED=0.777 mg/kg/day

Inhalation

(Long-Term)

No long-term inhalation exposure anticipated from currently use pattern.

Cancer (Oral, Dermal, 

Inhalation)

Classification: Group D chemical, not classifiable as to human carcinogenicity.

No quantitative cancer risk assessment is required.

Point of Departure (POD) = data point or estimated point, derived from observed dose-response data, and used to mark the 

beginning of extrapolation to determine risk associated with lower environmentally relevant human exposures. NOAEL = no 

observed adverse effect level. LOAEL = lowest observed adverse effect level. UF = uncertainty factor. UFA = extrapolation 

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

(intraspecies). FQPA SF = FQPA Safety Factor. RfD= reference dose. PAD = population adjusted dose (a = acute, c = chronic). 

MOE = margin of exposure. LOC = level of concern. HEC = Human equivalent concentration. HED = Human equivalent dose. 
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4.6 Endocrine Disruption

As required by the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) and the Federal 

Food, Drug, and Cosmetic Act (FFDCA), EPA reviews numerous studies to assess potential 

adverse 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 include 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. For 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 most recent registration decision for hexazinone, 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), 

hexazinone 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 endocrine effects as the Administrator 

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

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

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

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

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

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

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

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

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 ingredients and 9 inert ingredients. A second list of 

chemicals identified for EDSP screening was published on June 14, 20131and 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

 

1 See http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPPT-2009-0477-0074 for the final second list of 

chemicals.

2 http://www.epa.gov/endo/
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5.0 Dietary Exposure and Risk Assessment

5.1 Residue of Concern Summary

The qualitative nature of the residues of hexazinone in plants and animals has been adequately 

identified/characterized and is understood. The HED Metabolism Assessment Review 

Committee (MARC) has reviewed the hexazinone toxicology and metabolism data (meeting 

dates 01/29/02 and 03/12/02) and recommends that the tolerance expression and risk assessment 

for plants should include hexazinone (parent) and metabolites A, B, C, D, and E. The tolerance 

expression for milk should include hexazinone (parent) and metabolites B, C, C-2, and F, and the 

tolerance expression for ruminant tissue should include hexazinone (parent) and metabolites B 

and F. The MARC also recommended that for the purposes of risk assessment estimates of 

dietary exposure and risk should be based on residue estimates of hexazinone and metabolites B, 

C, C-1, C-2, and F for ruminant commodities. The Agency has determined that tolerances for 

hexazinone residues in eggs, poultry and hog tissues are not required based on the results of the 

respective poultry metabolism and feeding studies (CFR §180.6(a)(3)). See Appendix B for 

names and structures of the metabolites.

Table 5.1. Summary of Metabolites and Degradates of Hexazinone.

Matrix Residues included in Risk 

Assessment

Residues included in Tolerance 

Expression 

Plants Primary 

Crop Hexazinone, metabolites A, B, 

C, D, and E

Hexazinone, metabolites A, B, C, 

Rotational D, and E

Crop

Poultry Not Required Not Required

Ruminant Hexazinone, metabolites B, C, 

C-1, C-2 and F

Milk- Hexazinone, B, C, C-2 and 

F

Tissues- Hexazinone, B and F

Drinking Water Hexazinone and metabolites 

G3170, A, A-1, B, C, D, I 

(JS472) and 2 (JT677)

Not Applicable

5.2 Food Residue Profile

The plant metabolism studies indicate that root uptake is the principal mechanism for the 

absorption of hexazinone by plants from soils. Hexazinone is translocated through the xylem to 

the foliage when it blocks the photosynthetic process. The submitted field trial studies 

demonstrated that, among registered crops, quantifiable residues are only expected in forage, 

stover, hay, and/or straw. Also, hexazinone residue of concern may transfer to milk and edible 

tissues of livestock as a result of ingestion of feed items such as alfalfa forage, hay, and meal;

grass forage and hay; and sugarcane molasses. The data from the limited field trials indicate that 

quantifiable residues occur in field corn stover and wheat straw. 
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HED reviewed previously submitted field trial data for hexazinone and its metabolites in/on 

warm-season pasture grass forage and hay and the study was deemed adequate. Residue values 

in the study have a potential impact on the livestock dietary burden; therefore, the potential 

dietary exposure to livestock from consuming hexazinone-treated feedstuffs was re-calculated 

using Agency guidance on calculating dietary exposure from the maximum theoretical dietary 

burden (S. Piper, D427006, June 2, 2015). The dairy cattle feeding study data indicate that the 

established tolerances for residues of hexazinone in/on ruminant meat, meat byproducts, and fat 

for cattle, goats, horses and sheep livestock commodities should be retained. Based on the 

dietary burden calculation and the residue profile in the feeding study, the Agency concludes that 

there are not likely to be quantifiable residues of hexazinone and its metabolites in/on eggs, 

poultry, and hog commodities, and a Category 3 of 40 CFR§180.6 (a)(3) should remain.

Previously the Agency indicated that extended field rotational crop trials and tolerances for 

inadvertent hexazinone residues in corn stover, sorghum stover, and wheat straw were required 

to support a 12-month rotational interval because the limited field trials indicated that 

quantifiable residues occur in field corn stover and wheat straw (S. Piper, D380507, August 16, 

2010). The Agency has determined that the available limited rotational field trial data can be 

used to established inadvertent tolerances for residues of hexazinone in corn stover, sorghum 

stover, and wheat straw at 0.50 ppm (Table 2.2.2); therefore, extended field rotational crop trials 

for corn stover, sorghum stover, and wheat straw are no longer required. 

5.3 Summary of Environmental Degradation

Based on the available information, hexazinone residues (parent and degradates) appear to be 

persistent and mobile in soil and aquatic environments. Leaching and runoffs are expected to be 

primary dissipation routes. Hexazinone is stable to hydrolysis and photolysis and degrades at 

moderately slow rates under aerobic soil metabolism conditions. Aerobic and anaerobic aquatic 

metabolism and anaerobic soil metabolism studies show slow degradation for hexazinone. 

Consistent with this persistence, field dissipation half-lives were 123 to 154 days for the parent 

compound in bare ground silt loam, silty clay loam, and sandy loam soils. Laboratory adsorption 

data show low water/soil partitioning for hexazinone (KOC = 38-77 mL/g). These data indicate 

that hexazinone is mobile, thus, combined with its persistence, having strong potential to leach to 

ground water systems, especially in soil systems such as loamy and sandy soils that are poor in 

organic matter.

5.4 Water Residue Profile

EDWCs for hexazinone were generated using the Surface Water Concentration Calculator 

(SWCC) computer model, the Pesticide Root Zone Model for Groundwater (PRZM-GW), and 

the Screening Concentration in Ground Water (SCI-GROW) model. Both point estimates and 

distributions of water residues were provided. EFED shared with HED preliminary EDWCs for 

the acute and chronic dietary exposures and provided additional refinements. EFED provided 

daily time series outputs that simulate 29 years of residues of hexazinone in drinking water for 
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various application scenarios (See Tables 5.5.6a-c). These scenarios encompass both surface 

water and groundwater for agricultural and non-agricultural uses of hexazinone. 

For the hexazinone total toxic residues (TTRs; i.e., hexazinone plus its transformation products), 

the results of these drinking water assessments show that for surface water, the maximum acute 

EDWC is associated with the use on LA sugarcane. The maximum groundwater screening 

EDWC for acute exposure is associated with the use on NC coastal rights-of-way (Table 5.4a). 

Additionally, EFED calculated upperbound estimates of the EDWCs associated with hexazinone 

TTRs, including the unextracted residues (UERs) observed in the aerobic soil metabolism study

(Table 5.4b). It was noted that when the UERs were included, the peak EDWCs were the same 

as for the TTRs without the UERs.

EFED calculated refined groundwater EDWCs associated with hexazinone TTRs applied on 

pastures/rangeland rangeland (2 lbs ai application rate for WI sand). The results presented in 

Table 5.4c represent applications on sandy loam or sandy soils), for which the labeled 

application rate is smaller than for other types of soils. 

For the acute assessment, the entire 30-year distribution of estimated daily concentrations from 

various scenarios incorporated into the Pesticide Root Zone Model and Exposure Analysis 

Modeling System (PRZM/EXAMs) were used in the probabilistic analyses. For the chronic 

assessment, the average residue from each scenario shown in Tables 5.4a-c were used.

Table 5.4a. Maximum Estimated Drinking Water Concentrations for the Use of 

Hexazinone Total Toxic Residues (TTRs, excluding the unextracted residues)

DRINKING 

WATER SOURCE 

(MODEL USED) 

SCENARIO (USE) (rate modeled per year)

MAXIMUM ESTIMATED DRINKING WATER 

CONCENTRATION (EDWC) ( ppb)

Groundwater 

(PRZM-GW)

NC coastal1(rights-of-way) (8 lbs a.i.) Acute 3090

WI sand1(rights-of-way) (8 lbs a.i.) Chronic 2260

Surface water

(SWCC)

LA sugarcane with HI meteorological file

(sugarcane in HI) (3.6 lbs a.i.)

Acute 502

Chronic 206

Cancer 77.3

1 Scenario was used as a surrogate and run with the maximum application rate for rights-of-ways.

Table 5.4b. Maximum Estimated Drinking Water Concentrations for the Use of 

Hexazinone Total Toxic Residues (TTRs), including the Unextracted Residues (UERs) 

(these EDWCs provide an upperbound estimate of the TTRs)

DRINKING 

WATER SOURCE 

(MODEL USED) 

SCENARIO (USE) (rate modeled per year)

MAXIMUM ESTIMATED DRINKING WATER 

CONCENTRATION (EDWC) ( ppb)

Groundwater 

(PRZM-GW)

NC coastal1(rights-of-way) (8 lbs a.i.) Acute 3,710

Chronic 2,600

Surface water

(SWCC)

LA sugarcane with HI meteorological file

(sugarcane in HI) (3.6 lbs a.i.)

Acute 502

Chronic 207

Cancer 77.6

1 Scenario was used as a surrogate and run with the maximum application rate for rights-of-ways.

Table 5.4c. Refined Estimated Groundwater Drinking Water Concentrations for the Use 

of Hexazinone, for the TTRs
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DRINKING 

WATER SOURCE 

(MODEL USED)

SCENARIO (USE) (rate modeled per year) MAXIMUM ESTIMATED DRINKING WATER 

CONCENTRATION (EDWC) ( ppb)

Groundwater 

(PRZM-GW)

NC coastal1(pastures/rangeland) (2 lbs a.i.) Acute 773

WI sand1(pastures/rangeland) (2 lbs a.i.) Chronic 564

1 Scenario was used as a surrogate and run with the prescribed application rate for sandy loam and loamy sand soils 

on pasture/rangeland.

5.5 Dietary Risk Assessment

5.5.1. Description of Residue Data Used in Dietary Assessment

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

conducting using the Dietary Exposure Evaluation Model software with the Food Commodity 

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

data from the USDA’s NHANES/WWEIA. The drinking water estimates provided by EFED are 

modeled estimates, and were generated using the most conservative model available for the 

existing uses. The partially refined assessments assumed anticipated residues, DEEM default 

processing factors, and 100% crop treated (PCT) for the acute assessment and average PCT data 

for the chronic assessment. The acute and chronic approach to dietary risk exposure analysis will 

not underestimate risk to the general U.S. population or any population subgroup.

5.5.2 Percent Crop Treated Used in Dietary Assessment

The Biological and Economic Analysis Division (BEAD) has provided an updated Screening 

Level Usage Analysis (SLUA) for hexazinone (J. Alsadek, 01/22/2015) which includes both an 

average and maximum PCT for the established uses. 

For the acute dietary exposure assessment, maximum percent crop treated values were provided 

for the following commodities: alfalfa (5%); blueberries (15%); and sugarcane (10%); however, 

100% CT was assumed. For the chronic dietary exposure assessment, the average percent crop 

treated values were used for the following commodities: alfalfa (5%), blueberries (10%) and 

sugarcane (5%). Also, 5% CT (from alfalfa/sugarcane) was assumed for livestock commodities.

5.5.3 Acute Dietary Risk Assessment

The food only dietary exposure estimates contribute 83% of the aPAD at the 95th percentile for 

children 1-2 years, the most highly exposed population subgroup. The acute aggregate (food and 

drinking water) dietary exposure estimates for the various scenarios are below HED’s level of 

concern (<100 % aPAD) for the U.S. population and all population subgroups. The worst-case 

scenario (NC coastal rights-of-ways using the PRZM-GW distribution) resulted in combined 

dietary exposure and risk estimates from food and drinking water at the 95th percentile that 

utilized 23% of the aPAD for the U.S. population and 73% of the aPAD for children 1-2 years 

old, the most highly exposed population subgroup. The summary results for the general 

population and all population subgroups are shown below in Table 5.5.6.
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5.5.4 Chronic Dietary Risk Assessment

The food only dietary exposure estimates contribute 37% of the chronic population adjusted dose 

(cPAD) for children 1-2 years, the most highly exposed population subgroup. Combined chronic 

dietary exposure estimates for food and drinking water using the surface water LA sugarcane 

scenario are below HED’s level of concern. Using the DEEM-FCID software, dietary exposure 

is estimated to be 14% of the cPAD for the U.S. population, and 50% of the cPAD for children 

1-2 years old, the population with highest estimated chronic dietary exposure to hexazinone for 

the LA sugarcane water scenario.

For the chronic PRZM-GW rights-of-ways scenarios, some of the scenarios exceeded the levels 

of concern when using higher rates (8 lbs ai/A). Further examination of the labels indicated that 

for majority of uses the maximum labeled application rate is lower for coarse textured soils, like 

the soils in all PRZM-GW scenarios. When using the refined EDWCs at a 2 lbs ai/A application 

rate, which is the maximum labeled rate for pastures/rangeland for coarse textured soils, for WI 

sand PRZM-GW scenario, the dietary exposure is estimated to be 29% of the cPAD for the U.S. 

population, and 71% of the cPAD for children 1-2 years old, the population with the highest 

estimated chronic dietary exposure to hexazinone. The summary results for the general 

population and all population subgroups are shown below in Table 5.5.6c.

5.5.5 Cancer Dietary Risk Assessment

Hexazinone is classified as “Likely at high doses, but unlikely to be carcinogenic to humans at 

low doses.” Therefore, a cancer dietary exposure analysis is not required.

5.5.6 Dietary Summary Table

The acute and chronic dietary exposure and risks for hexazinone are summarized below. Only 

the population with the highest risk was shown (See dietary memo for detailed summary of all 

population subgroups).

Table 5.5.6a. Summary of Acute Dietary (Food and Drinking Water) Exposures and Risks 

for Hexazinone using Surface Water

Drinking Water 

Scenario

App. 

Method

App. 

Rate

(lb 

a.i./A)

Surface Waters EDWCs (ppb) Acute Food and Water 

Exposure and Risk Estimates at 

95th Percentile Acute

(1-in10-

year)

Chronic

(1-in-10-

year)

Cancer 

30-year 

Daily 

Average

National 

PCA1

(fraction) Population 

Subgroup2

Exposure 

(mkd)

% 

PAD

Tier II Estimated Drinking Water Concentrations (EDWCs) for Surface Water Based on Application of 

Hexazinone Products Modeled in the SWCC, for the TTRs (Excluding the UERs)

NC 

alfalfa/Alfalfa

Aerial 1.5 35.5 11.2 5.81 1.002 Children 

1-2

0.855439 68
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Drinking Water 

Scenario

App. 

Method

App. 

Rate

(lb 

a.i./A)

Surface Waters EDWCs (ppb) Acute Food and Water 

Exposure and Risk Estimates at 

95th Percentile Acute

(1-in10-

year)

Chronic

(1-in-10-

year)

Cancer 

30-year 

Daily 

Average

National 

PCA1

(fraction) Population 

Subgroup2

Exposure 

(mkd)

% 

PAD

LA sugarcane 

(HI met 

file)/Sugarcane in 

HI

Aerial 3.6 502 206 77.3 1.002 Children 

1-2

0.856927 69

CA wine grape/ 

Blueberries

Ground 2 20.9 12.7 8.58 1.002 Children 

1-2

0.856279 69

CA rights-ofway/CA 

impervious/Noncrop sites (weed 

and brush 

control)

Aerial

helicopt

er

6 204 88.0 45.2 1.003 Children 

1-2

0.856093 68

CA rights-ofway/CA 

impervious/Noncrop sites (weed 

and brush 

control)

Ground 8 260 112 52.5 1.003 Children 

1-2

0.856155 68

CA forestry (MI 

met file)/Conifer 

release in Eastern 

and Lakes states

Aerial 

helicopt

er

4 103 84.9 64.6 1.003 Children 

1-2

0.856599 69

OR Christmas 

trees/ Christmas 

trees

Aerial 2 28.9 21.8 18.8 1.003 Children 

1-2

0.857025 69

CA rangeland 

hay (NY met 

file)/Pastures/ 

Rangeland in 

Eastern US

Aerial 

helicopt

er

4 159 71.9 36.5 1.003 Children 

1-2

0.856597 69

PA 

turf/Bermudagra

ss/ Bahiagrass; 

Industrial 

turfgrass

Ground 1.125 10.4 8.24 6.05 1.002 Children 

1-2

0.856134 69

Tier II Estimated Drinking Water Concentrations (EDWCs) for Surface Water Based on Application of 

Hexazinone Products Modeled in the SWCC, for TTRs + UER

LA sugarcane 

(HI met 

file)/Sugarcane in 

HI

Aerial 3.6 10-01 502 207 77.6 Children 

1-2

0.856600 69

PA turf/ 

Bermudagrass/ 

Bahiagrass; 

Industrial 

turfgrass

Ground 1.125 01-03 10.4 8.25 6.06 Children 

1-2

0.856595 69
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Drinking Water 

Scenario

App. 

Method

App. 

Rate

(lb 

a.i./A)

Surface Waters EDWCs (ppb) Acute Food and Water 

Exposure and Risk Estimates at 

95th Percentile Acute

(1-in10-

year)

Chronic

(1-in-10-

year)

Cancer 

30-year 

Daily 

Average

National 

PCA1

(fraction) Population 

Subgroup2

Exposure 

(mkd)

% 

PAD

Bolded values represent the highest EDWCs in surface waters.

1 Guidance on Development and Use of Community Water System Drinking Water Intake Percent Cropped Area 

Adjustment Factors for use in Drinking Water Exposure Assessments: 2014 Update, dated 09/09/2014 and 

approved 09/12/2014. 

2 PCA for Turf-All Agriculture.

3 No PCAs have been issued for these non-agricultural uses.

Table 5.5.6b. Summary of Acute Dietary (Food and Drinking Water) Exposures and Risks 

for Hexazinone using Ground Water

Drinking Water Scenario

Highest 

Daily 

Value 

(ppb)

Post 

Breakthrough 

Average (ppb)

Cancer 30-

year Daily 

Average 

(ppb)

Acute Food and Water 

Exposure and Risk Estimates 

at 95th Percentile

Population 

Subgroup

Exposure 

(mkd)

% 

PAD

Hexazinone Ground Water Estimated Drinking Water Concentrations (EDWCs) Resulting 

from the Use of the Chemical on Rights-of-Ways, for the TTRs+UERs

Rights-of-way/Tier I 

Delmarva

2760 2110 1752 Children 1-2 0.856595 69

Rights-of-way/Tier I FL 

Citrus

2390 1990 1294 Children 1-2 0.862892 69

Rights-of-way/Tier I FL 

Potato

1530 1250 1800 Children 1-2 0.870681 70

Rights-of-way/Tier I GA 

Coast

1060 852 2166 Children 1-2 0.862892 69

Rights-of-way/Tier I NC 

Coastal

3710 2600 2485 Children 1-2 0.909053 73

Rights-of-way/Tier I WI 

Sand

2680 2390 3141 Children 1-2 0.899158 72

Bolded values represent the highest EDWCs in surface waters.

1 Guidance on Development and Use of Community Water System Drinking Water Intake Percent Cropped 

Area Adjustment Factors for use in Drinking Water Exposure Assessments: 2014 Update, dated 09/09/2014 

and approved 09/12/2014.

2 PCA for Turf-All Agriculture.

3 No PCAs have been issued for these non-agricultural uses.

Table 5.5.6c. Summary of Chronic Dietary (Food and Drinking Water) Exposures and 

Risks for Hexazinone

Drinking Water Scenario Post 

Breakthrough 

Average (ppb)

Chronic Food and Water 

Exposure and Risk Estimates

Population 

Subgroup

Exposure 

(mkd) % PAD

Maximum EDWCs for the use of Hexazinone Total Toxic Residues for the TTR

PRZM-GW NC Coastal (rights-of-way) (8 lbs ai) 2260 All Infants 0.126765 254
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Drinking Water Scenario Post 

Breakthrough 

Average (ppb)

Chronic Food and Water 

Exposure and Risk Estimates

Population 

Subgroup

Exposure 

(mkd) % PAD

SWCC LA Sugarcane with HI meterological file 

(3.6 lbs ai)

206 Children 1-2 0.024752 50

Groundwater EDWCs Resulting from the use of the Chemical on Rights-of-Ways for the TTR

Rights-of-way Tier1 FL Potatoes 951 All Infants 0.056090 112

Rights-of-way Tier1 GA Coast 765 All Infants 0.040637 92

Groundwater EDWCs Resulting from the use of the Chemical on Rights-of-Ways for the TTR + 

UERs

Rights-of-way Tier1 GA Coast 852 All Infants 0.051936 104

Rights-of-way Tier1 FL Potatoes 1250 All Infants 0.072234 145

PRZM-GW NC Coastal (rights-of-way) (8 lbs ai) 2600 All Infants 0.145122 290

Refined Estimated Groundwater Drinking Water Concentrations for the Use of Hexazinone for 

the TTRs

WI Sand (pastures/rangeland) (2 lbs ai) 564 Children 1-2 0.035565 71

6.0 Residential Exposure and Risk Estimates

There are no proposed or registered residential uses of hexazinone at this time, therefore no 

quantitative residential exposure assessment was performed. There are existing occupational 

uses that could result in drift onto residential areas and result in potential residential postapplication exposure. A residential spray drift assessment was performed for the highest 

application rate scenarios. 

6.1 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 offtarget 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 is based 

on a premise of compliant applications which, by definition, should not result in direct exposures 

to individuals because of existing label language and other regulatory requirements intended to 

prevent them.3 Direct exposures would include inhalation of the spray plume or being sprayed 

directly. Rather, the exposures addressed here are thought to occur indirectly through contact 

with impacted areas, such as residential lawns, when compliant applications are conducted. 

 

3 This approach is consistent with the requirements of the EPA’s Worker Protection Standard.
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Given this premise, 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 indirect 

exposure are the focus of this analysis analogous to how exposures to turf products are 

considered in risk assessment. 

In order to evaluate the drift potential and associated risks, an approach based on drift modeling 

coupled with techniques used to evaluate residential uses of pesticides was utilized. Essentially, 

a residential turf assessment based on exposure to deposited residues has been completed to 

address drift from the agricultural applications of hexazinone. In the spray drift scenario, the 

deposited residue value was determined based on the amount of spray drift that may occur at 

varying distances from the edge of the treated field using the AgDrift (v2.1.1) model and the 

Residential Exposure Assessment Standard Operating Procedures Addenda 1: Consideration of 

Spray Drift Policy. Once the deposited residue values were determined, the remainder of the 

spray drift assessment was based on the algorithms and input values specified in the recently 

revised (2012) Standard Operating Procedures for Residential Risk Assessment (SOPs). 

A screening approach was developed based on the use of the AgDrift model in situations where 

specific label guidance that defines application parameters is not available.4 AgDrift is 

appropriate for use only when applications are made by aircraft, airblast orchard sprayers, and 

groundboom sprayers. When AgDrift was developed, a series of screening values (i.e., the Tier 

1 option) were incorporated into the model and represent each equipment type and use under 

varied conditions. The screening options specifically recommended in this methodology were 

selected because they are plausible and represent a reasonable upper bound level of drift for 

common application methods in agriculture. These screening options are consistent with how 

spray drift is considered in a number of ecological risk assessments and in the process used to 

develop drinking water concentrations used for risk assessment. In all cases, each scenario is to 

be evaluated unless it is not plausible based on the anticipated use pattern (e.g., herbicides are 

not typically applied to tree canopies) or specific label prohibitions (e.g., aerial applications are 

not allowed). 

In many cases, risks are of concern when the screening level estimates for spray drift are used as 

the basis for the analysis. In order to account for this issue and to provide additional risk 

management options additional spray drift deposition fractions were also considered. These drift 

estimates represent plausible options for pesticide labels

6.2 Risk Estimates from Lawn Deposition Adjacent to Agricultural Applications

Hexazinone is used on numerous agricultural crops and can be applied via aerial and 

groundboom equipment. The pesticide is also registered on non-agricultural crop sites such as 

forestry areas and rights of ways. For the non-crop sites, hexazinone can be applied via aerial, 

groundboom, and airblast equipment. For the purposes of the spray drift assessment, the most 

protective agricultural use rates as well as the non-agricultural crop sites (e.g., forestry and noncrop sites) are assessed. The spray drift risk estimates are based on an estimated deposited 

 

4http://www.agdrift.com/ 
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residue concentration as a result of the screening level agricultural application scenarios. The 

recommended drift scenario screening level options are listed below: 

 Groundboom applications are based on the AgDrift option for high boom height and 

using very fine to fine spray type using the 90th percentile results. 

 Aerial applications are based on the use of AgDrift Tier 1 aerial option for a fine to 

medium spray type and a series of other parameters which will be described in more 

detail below (e.g., wind vector assumed to be 10 mph in a downwind direction for entire 

application/drift event).5

 Orchard airblast applications are based on the AgDrift option for Sparse 

(Young/Dormant) tree canopies. 

Only the incidental oral risk estimates for children 1<2 years old were calculated for hexazinone 

because no adverse systemic effect was identified in the dermal toxicity study. Children’s (1<2 

years old) incidental oral risk estimates from indirect exposure to hexazinone related to spray 

drift result in buffers of 0 feet for groundboom and aerial applications, and were not of concern. 

The highest exposure resulted from drift following hexazinone applications using aerial 

equipment for children 1 to <2 years old where the MOE is 380, with a LOC =100. See Table 

5.1.2 for detailed results.

 

5 AgDrift allows for consideration of even finer spray patterns characterized as very fine to fine. However, this 

spray pattern was not selected as the common screening basis since it is used less commonly for most agriculture. If 

assessors identify this use pattern it should be used as the screening criteria and deposition values associated with it 

are provided in Table 1 below. Justification for including this spray quality should be included in any assessment 

based on specific label directions for its use. 
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Table 5.1.2. Children Incidental Oral Risk Estimates (MOEs) Related to Spray Drift Exposure to 

Hexazinone from the Registered Agricultural Uses.1,2

Crop/Rate 

Group Spray Type/ Nozzle Configuration Application Rate (lbs ai/A)

Estimated or 

Adjusted TTRt

(ug/cm2)

At Edge 

HtM MOE 

Non-Crop Sites

Aerial Fine to Medium

8 0.8892

380

Groundboom High Boom Very fine to Fine 530

Airblast Sparse 690

Forestry3

Aerial Fine to Medium

5 0.55575

610

Groundboom High Boom Very fine to Fine 840

Sugarcane

Aerial Fine to Medium

3.6 0.40014

850

Groundboom High Boom Very fine to Fine 1,200

1. The highest application rate for an agricultural crop application is for aerial and ground applications to 

sugarcane use sites with an application rate of 3.6 lbs ai per acre. This use site and application equipment is 

representative of the other currently registered crop use sites. 

2. The full spray drift risk estimate table, including various levels of nozzle type and release height can be 

found in Appendix E.

3. There is some uncertainty associated with the drift predictions associated with forestry uses because in 

some situations pesticides like hexazinone are applied in rugged terrain using rotary aircraft and smaller 

droplets. A more appropriate modeling approach is currently under development for such situations. Even 

so, this would not alter the risk conclusions for the current human health risk assessment spray drift 

scenario because, in the case of hexazinone, if the 100% of application rate assumption is used rather than 

the screening level assumptions, there would be no risks of concern for the incidental oral risk estimates for 

children. 

6.3 Residential Bystander Post-Application Inhalation Exposure

Volatilization of pesticides may be a source of post-application inhalation exposure to 

individuals nearby pesticide applications. The Agency sought expert advice and input on issues 

related to volatilization of pesticides from its Federal Insecticide, Fungicide, and Rodenticide Act 

Scientific Advisory Panel (SAP) in December 2009, and received the SAP’s final report on 

March 2, 2010 (http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html). The 

Agency has evaluated the SAP report and has developed a Volatilization Screening Tool and a 

subsequent Volatilization Screening Analysis6. During Registration Review, the Agency will 

utilize this analysis to determine if data (i.e., flux studies, route-specific inhalation toxicological 

studies) or further analysis is required for hexazinone.

 

6 Available at: http://www.regulations.gov/#!docketDetail;D=EPA-HQ-OPP-2014-0219.
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7.0 Aggregate Exposure/Risk Characterization

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

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

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

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

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

duration of exposure. 

For hexazinone, there are currently no registered residential uses, nor are any proposed. 

Therefore, at this time, dietary (food + water) exposure is the only component of an aggregate 

exposure analysis and risk assessment. As shown in Sections 5.5.3 and 5.5.4, there are no 

aggregate dietary (food plus water) risks of concern for hexazinone when further refined. 

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 hexazinone and any other substances. For the purposes of this assessment, therefore, EPA has 

not assumed that hexazinone has a common mechanism of toxicity with other substances. For 

information regarding EPA’s efforts to determine which chemicals have a common mechanism 

of toxicity and to evaluate the cumulative effects of such chemicals, see the policy statements 

released by EPA’s Office of Pesticide Programs concerning common mechanism determinations 

and procedures for cumulating effects from substances found to have a common mechanism on 

EPA’s website at http://www.epa.gov/pesticides/cumulative/.

9.0 Occupational Exposure and Risk Estimates

9.1 Occupational Handler Exposure/Risk Estimates

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

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

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

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

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

manner specific to each application event. 

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

that can potentially be used, occupational handler exposure is expected from the registered uses. 
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The quantitative exposure and risk assessment developed for occupational handlers is based on 

the scenarios listed in Table 9.1.1. 

Occupational Handler Exposure Data and Assumptions

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

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

Application Rate: The maximum single application rates are listed in Appendix D. 

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

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

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

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

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

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

“Occupational Pesticide Handler Unit Exposure Surrogate Reference Table7”, which, along with 

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

various sources, can be found at the Agency website8. 

For the dry bulk fertilizer scenarios, HED assumed a closed mixing/loading scenario for 

commercial impregnation of dry bulk fertilizer, and an open mixing/loading scenario for growerowned equipment impregnation of dry bulk fertilizer. For all applications of dry bulk fertilizer, 

HED assumed the use of an open-cab spreader. 

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

ExpoSAC Policy 9.1. HED does not have data regarding the mixing/loading or the application 

of hexazinone-impregnated dry bulk fertilizer. The mixing/loading processing rate for 

commercial impregnation of dry bulk fertilizer has been estimated to be 960 tons of fertilizer 

processed per 8 hour day based on information supplied by a registrant concerning the chemical 

alachlor (as referenced in its reregistration eligibility document (RED) 

document). Mixing/loading for on-farm impregnation of dry bulk fertilizer was then assessed 

using an estimate of 160 acres/day. Application of dry bulk fertilizer was assessed assuming 

application to up to 320 acres/day for commercial equipment and 160 acres/day for growerowned equipment. 

The amount/area treated for each scenario is listed in the Occupational Handler Table (Table 

9.1.1). 

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

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

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

 

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

8 Available: http://www.epa.gov/pesticides/science/handler-exposure-data.html
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pesticide, and the cultural practices surrounding that use site. For most agricultural uses, it is 

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

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

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

multiple applications for multiple clients within a region). 

For hexazinone, based on the registered use pattern, short- and intermediate-term exposures are 

expected. However, since the short- and intermediate-term inhalation POD is the same for both 

durations, the assessment is protective of both durations. 

Mitigation/Personal Protective Equipment: Estimated inhalation exposure were calculated for 

various levels of PPE. According to the currently registered hexazinone labels, occupational 

handlers must wear baseline attire and chemical-resistant gloves. Results are presented for 

“baseline”, defined as a single layer of clothing consisting of a long sleeved shirt, long pants, 

shoes plus socks, no protective gloves, and no respirator, as well as baseline with various levels 

of inhalation PPE as necessary (e.g., PF5 respirator and PF10 respirator) as well as engineering 

controls. 

Summary of Occupational Handler Non-Cancer Exposure and Risk Estimates

There are some occupational handler risk estimates of concern for the registered uses of 

hexazinone at baseline, PPE, and engineering control mitigation. The LOC for occupational 

handler inhalation risk estimates is a MOE of 30. At baseline, occupational inhalation MOEs 

ranged from 0.8 to 9,600. A summary of risk estimates is provided in Table 9.1.1.

The tree injection use directions do not indicate that the formulation for tree injection is in a 

ready to use packaging therefore its anticipated that a handler may mix and load the formulation 

for the tree injection application. This mixing and loading exposure scenario has been assessed 

for ground application to forestry use sites and should be considered a surrogate for the tree 

injection application. 

In general, the mixing and loading handler activities with the dry flowable and water dispersible 

granular formulations result in MOEs of concern at baseline attire with no respirator. Below is a 

summary of the scenarios grouped by formulation and PPE: 

The following mixing/loading dry flowable scenarios are not of concern with the use of a PF5 

respirator:

 Aerial application for bermudagrass/ bahiagrass; 

 Airblast for non-crop areas; 

 Chemigation application for pineapple and alfalfa; and 

 All groundboom applications.

The following mixing/loading dry flowable scenarios are not of concern with the use of a PF10 

respirator:
Hexazinone Human Health Risk Assessment DPNo. 424526

Page 36 of 64

 Aerial application for pasture/rangeland, blueberry (low and high bush), pineapple, and 

christmas tree; 

 Chemigation application for sugarcane and christmas tree; and,

 Groundboom application for sugarcane.

The following mixing/loading dry flowable scenarios are not of concern with the use of 

Engineering Controls:

 Aerial application for non-crop areas, forestry, alfalfa, and sugarcane.

 Impregnation of dry bulk fertilizer for on-farm treatment.

The following mixing/loading dry flowable scenarios are of concern with the use of Engineering 

Controls:

 Impregnation of dry bulk fertilizer for commercial treatment.

The following mixing/loading granule scenarios are not of concern with the use of a PF5 

respirator:

 Aerial application for non-crop and forestry use sites.

The following mixing/loading liquid scenarios are not of concern with the use of a PF5 

respirator:

 Aerial application for forestry use sites.

The following mixing/loading liquid scenarios are of concern with the use of Engineering 

Controls:

 Impregnation of dry bulk fertilizer for commercial treatment.

In general, the applicator handler activities do not result in MOEs of concern at baseline attire 

with no respirator, with the exception of the following:

The following applicator liquid scenarios are not of concern with the use of a PF5 respirator:

 Airblast application for non-crop use sites.

The following applicator granule scenarios are of concern with the use of Engineering Controls:

 Aerial application for non-crop and forestry use sites.

The following applicator pellet formulation are not of concern with the use of a PF5 respirator:

 Hand dispersal application for non-crop and forestry use sites.

In general, the mixer/loader/applicator activities do not result in MOEs of concern at baseline 

attire with no respirator, with the exception of the following:

The following mixer/loader/applicator scenarios are not of concern with the use of a PF5 

respirator:

 Dry flowable and liquid formulation with mechanically- pressurized handgun for forestry 

use sites.
Hexazinone Human Health Risk Assessment DPNo. 424526

Page 37 of 64



Table 9.1.1. Occupational Handler Non-Cancer Exposure and Risk Estimates for Hexazinone.

Exposure 

Scenario Crop or Target

Inhalation Unit Exposure (μg/lb ai)1

Maximum

Application 

Rate2

Area 

Treated or 

Amount 

Handled 

Daily3

Inhalation Risk Estimates4(LOC = 30)

Baseline PF5 PF10 Engineering 

Controls

Baseline

MOE

PF5

MOE

PF10

MOE

Engineering 

Control

MOE

Mixer/Loader

Mixer/Loader Dry 

Flowable/Water 

Dispersible 

Granules for 

Aerial Application

Bermudagrass/ 

Bahiagrass

8.96 1.792 0.896 0.24

1.125

350

10 51 100 660

Pastures/ rangeland 2 5.7 29 57 370

Non-Crop 8 1.4 7.1 14 93

Low bush blueberry 2 5.7 29 57 370

High bush blueberry 3 3.8 19 38 250

Pineapple 1.75 6.5 32 65 420

Christmas Tree 2 5.7 29 57 370

Forestry 5

1200

0.66 3.3 6.6 43

Alfalfa 1.5 2.2 11 22 140

Sugarcane 3.6 0.92 4.6 9.2 60

Mixer/Loader Dry 

Flowable/Water 

Dispersible 

Granules for 

Airblast 

Application

Non-crop 8.96 1.792 0.896 0.24 8 40 12 62 120 810

Mixer/Loader Dry 

Flowable/Water 

Dispersible 

Granules for 

Chemigation 

Application

Pineapple

8.96 1.792 0.896 0.24

1.75

350

6.5 32 65 420

Christmas Tree 2 5.7 29 57 370

Alfalfa 1.5 7.6 38 76 490

Sugarcane 3.6 3.2 16 32 210

Mixer/Loader Dry 

Flowable/Water 

Dispersible 

Granules for 

Groundboom 

Application

Bermudagrass/ 

Bahiagrass

8.96 1.792 0.896 0.24

1.125

80

44 220 440 2900

Pastures/ rangeland 2 25 120 250 1600

Non-Crop 8 6.2 31 62 400

Low bush blueberry 3 17 83 170 1100
Hexazinone Human Health Risk Assessment DPNo. 424526

Page 38 of 64

Table 9.1.1. Occupational Handler Non-Cancer Exposure and Risk Estimates for Hexazinone.

Exposure 

Scenario Crop or Target

Inhalation Unit Exposure (μg/lb ai)1

Maximum

Application 

Rate2

Area 

Treated or 

Amount 

Handled 

Daily3

Inhalation Risk Estimates4(LOC = 30)

Baseline PF5 PF10 Engineering 

Controls

Baseline

MOE

PF5

MOE

PF10

MOE

Engineering 

Control

MOE

High bush blueberry 2 25 120 250 1600

Pineapple 1.75 29 140 290 1900

Christmas Tree 2 25 120 250 1600

Forestry 5 10 50 100 650

Alfalfa 1.5

200

13 66 130 860

Sugarcane 3.6 5.5 28 55 360

Mixer/Loader 

Granules for 

Aerial Application

Non-crop

1.7 0.34 0.17 0.083

8 350 13 65 130 270

Forestry 4.7 1200 6.5 32 65 130

Mixer/Loader 

Granules for 

Ground 

Application

Non-crop

1.7 0.34 0.17 0.083

8 80 57 280 570 1200

Forestry 4.7 80 97 490 970 2000

Mixer/Loader 

Liquids for Aerial 

Application

Bermudagrass/bahiag

rass

0.219 0.0438 0.0219 0.083

1.125

350

410 2100 4100 1900

Pastures/ rangeland 2 230 1200 2300 1100

Low bush blueberry 3 160 780 1600 710

High bush blueberry 2 230 1200 2300 1100

Pineapple 1.75 270 1300 2700 1200

Non-crop 8 58 290 580 270

Christmas Tree 2 230 1200 2300 1100

Forestry 5

1200

27 140 270 120

Alfalfa 1.5 91 450 910 420

Sugarcane 3.6 38 190 380 170

Mixer/Loader 

Liquids for 

Airblast 

Application

Non-crop

0.219 0.0438 0.0219 0.083 8 40 510 2600 5100 2300

Mixer/Loader Pineapple 0.219 0.0438 0.0219 0.083 1.75 350 270 1300 2700 1200
Hexazinone Human Health Risk Assessment DPNo. 424526

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Table 9.1.1. Occupational Handler Non-Cancer Exposure and Risk Estimates for Hexazinone.

Exposure 

Scenario Crop or Target

Inhalation Unit Exposure (μg/lb ai)1

Maximum

Application 

Rate2

Area 

Treated or 

Amount 

Handled 

Daily3

Inhalation Risk Estimates4(LOC = 30)

Baseline PF5 PF10 Engineering 

Controls

Baseline

MOE

PF5

MOE

PF10

MOE

Engineering 

Control

MOE

Liquids for 

Chemigation 

Application

Christmas Tree 2 230 1200 2300 1100

Alfalfa 1.5 310 1600 3100 1400

Sugarcane 3.6 130 650 1300 590

Mixer/Loader 

Liquids for 

Groundboom 

Application

Bermudagrass/ 

bahiagrass

0.219 0.0438 0.0219 0.083

1.125

80

1800 9100 18000 8300

Pastures/ rangeland 2 1000 5100 10000 4700

Low bush blueberry 3 680 3400 6800 3100

High bush blueberry 2 1000 5100 10000 4700

Pineapple 1.75 1200 5800 12000 5400

Non-crop 8 260 1300 2600 1200

Christmas Tree 2 1000 5100 10000 4700

Forestry 5 410 2000 4100 1900

Alfalfa 1.5

200

540 2700 5400 2500

Sugarcane 3.6 230 1100 2300 1000

Mixer/Loader Dry 

Flowable/Water 

Dispersible 

Granules for 

Impregnation for 

Bulk Fertilizer 

Application

Alfalfa

No Data No Data No Data 0.24

12 lbs ai/ton

960 tons

(Commercial 

Treatment)

No Data No Data No Data 6.4

Low bush blueberry 24 lbs ai/ton No Data No Data No Data 3.2

High bush blueberry 16 lbs ai/ton No Data No Data No Data 4.8

Forestry 32 lbs ai/ton No Data No Data No Data 2.4

Alfalfa

8.96 1.792 0.896 0.24

12 lbs ai/ton

160 tons

(On Farm 

Treatment)

2.1 10 21 130

Low bush blueberry 24 lbs ai/ton 1 5.2 10 68

High bush blueberry 16 lbs ai/ton 1.6 7.8 16 100

Forestry 32 lbs ai/ton 0.78 3.9 7.8 50

Mixer/Loader 

Liquids for 

Impregnation for 

Bulk Fertilizer 

Application

Alfalfa

No Data No Data No Data 0.083

12 lbs ai/ton

960 tons

(Commercial 

Treatment)

No Data No Data No Data 19

Low bush blueberry 24 lbs ai/ton No Data No Data No Data 9.3

High bush blueberry 16 lbs ai/ton No Data No Data No Data 14

Forestry 32 lbs ai/ton No Data No Data No Data 7

Alfalfa 0.219 0.0438 0.0219 0.083 12 lbs ai/ton 160 tons 85 430 850 390
Hexazinone Human Health Risk Assessment DPNo. 424526

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Table 9.1.1. Occupational Handler Non-Cancer Exposure and Risk Estimates for Hexazinone.

Exposure 

Scenario Crop or Target

Inhalation Unit Exposure (μg/lb ai)1

Maximum

Application 

Rate2

Area 

Treated or 

Amount 

Handled 

Daily3

Inhalation Risk Estimates4(LOC = 30)

Baseline PF5 PF10 Engineering 

Controls

Baseline

MOE

PF5

MOE

PF10

MOE

Engineering 

Control

MOE

Low bush blueberry 24 lbs ai/ton (On Farm 

Treatment)

43 210 430 190

High bush blueberry 16 lbs ai/ton 64 320 640 290

Forestry 32 lbs ai/ton 32 160 320 150

Applicator

Applicator for 

Sprays via Aerial 

Application

Bermudagrass/ 

bahiagrass

No Data No Data No Data 0.0049

1.125

350

No Data No Data No Data 9200

Pastures/ rangeland 2 No Data No Data No Data 5200

Low bush blueberry 3 No Data No Data No Data 3400

High bush blueberry 2 No Data No Data No Data 5200

Pineapple 1.75 No Data No Data No Data 5900

Non-crop 8 No Data No Data No Data 1300

Christmas Tree 2 No Data No Data No Data 5200

Forestry 5

1200

No Data No Data No Data 600

Alfalfa 1.5 No Data No Data No Data 2000

Sugarcane 3.6 No Data No Data No Data 840

Applicator for 

Sprays via Airblast

Application

Non-crop 4.71 0.942 0.471 0.068 8 40 12 59 120 810

Applicator for 

Sprays via 

Groundboom 

Application

Bermudagrass/ 

bahiagrass

0.34 0.068 0.034 0.043

1.125

80

580 2900 5800 16000

Pastures/ rangeland 2 330 1600 3300 9000

Low bush blueberry 3 220 1100 2200 6000

High bush blueberry 2 330 1600 3300 9000

Pineapple 1.75 370 1900 3700 10000

Non-crop 8 81 410 810 2300

Christmas Tree 2 330 1600 3300 9000

Forestry 5 130 650 1300 3600

Alfalfa 1.5 200 170 870 1700 4800
Hexazinone Human Health Risk Assessment DPNo. 424526

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Table 9.1.1. Occupational Handler Non-Cancer Exposure and Risk Estimates for Hexazinone.

Exposure 

Scenario Crop or Target

Inhalation Unit Exposure (μg/lb ai)1

Maximum

Application 

Rate2

Area 

Treated or 

Amount 

Handled 

Daily3

Inhalation Risk Estimates4(LOC = 30)

Baseline PF5 PF10 Engineering 

Controls

Baseline

MOE

PF5

MOE

PF10

MOE

Engineering 

Control

MOE

Sugarcane 3.6 73 360 730 2000

Applicator for 

Granules via 

Aerial Application

Non-crop

No Data No Data No Data 1.3

8 350 No Data No Data No Data 17

Forestry 4.7 1200 No Data No Data No Data 8

Applicator for 

Granules via

Tractor-drawn 

Spreader 

Application

Non-crop

1.2 0.24 0.12 0.22

8 80 81 400 810 440

Forestry

4.7 140 690 1400 750

Applicator for 

Sprays via 

Mechanicallypressurized 

Handgun 

Application

Pineapple (edging 

rates) 3.9 0.78 0.39 No Data 0.036 1000 gallons 440 2200 4400 No Data

Applicator for 

Granules (pellets) 

via Hand Dispersal

Non-Crop

470 94 47 No Data

7.5 1 18 88 180 No Data

Pasture/ rangeland 0.64 1 210 1000 2100 No Data

Forestry 6.2 1 21 110 210 No Data

Forestry Release 4.1 1 33 160 330 No Data

Applicator for Dry 

Bulk Fertilizer via 

Tractor Drawn 

Spreader

Low bush blueberry

1.2 0.24 0.12 0.22

3

320

(Commercial 

Treatment)

54 270 540 290

High bush blueberry 2 81 400 810 440

Forestry 5 32 160 320 180

Alfalfa 1.5 110 540 1100 580

Low bush blueberry 3

160

(On Farm 

Treatment)

110 540 1100 580

High bush blueberry 2 160 810 1600 880

Forestry 5 65 320 650 350

Alfalfa 1.5 220 1100 2200 1200

Flagger

Liquid 

Applications

Bermudagrass/ 

bahiagrass 0.35 0.07 0.035 No Data 1.125 350 450 2300 4500 No Data
Hexazinone Human Health Risk Assessment DPNo. 424526

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Table 9.1.1. Occupational Handler Non-Cancer Exposure and Risk Estimates for Hexazinone.

Exposure 

Scenario Crop or Target

Inhalation Unit Exposure (μg/lb ai)1

Maximum

Application 

Rate2

Area 

Treated or 

Amount 

Handled 

Daily3

Inhalation Risk Estimates4(LOC = 30)

Baseline PF5 PF10 Engineering 

Controls

Baseline

MOE

PF5

MOE

PF10

MOE

Engineering 

Control

MOE

Pastures/ rangeland 2 250 1300 2500 No Data

Low bush blueberry 3 170 850 1700 No Data

High bush blueberry 2 250 1300 2500 No Data

Pineapple 1.75 290 1400 2900 No Data

Non-crop 8 63 320 630 No Data

Christmas Tree 2 250 1300 2500 No Data

Forestry 5 100 500 1000 No Data

Alfalfa 1.5 340 1700 3400 No Data

Sugarcane 3.6 140 710 1400 No Data

Granular 

Applications

Forestry Pellets

0.15 0.03 0.015 No Data

6.2142

350

190 950 1900 No Data

Forestry 4.7 250 1300 2500 No Data

Non-crop 8 150 740 1500 No Data

Mixer/Loader/Applicator

Dry 

Flowable/Water 

Dispersible 

Granules for 

Backpack 

Applications

Non-Crop

2.58 0.516 0.258 No Data

0.32

lbs ai/gallon

40

gallons

1100 5400 11000 No Data

Christmas Tree farm 0.2

lbs ai/gallon 1700 8700 17000 No Data

Forestry

2

lbs ai/gallon 170 870 1700 No Data

Pineapple (edging 

rate)

0.036

lbs ai/gallon

9600 48000 96000 No Data

Dry 

Flowable/Water 

Dispersible 

Granules for 

MechanicallyPressurized 

Handgun

Non-Crop

3.9 0.78 0.39 No Data

0.32

lbs ai/gallon

1000

gallons

50 250 500 No Data

Christmas Tree farm 0.2

lbs ai/gallon

80 400 800 No Data

Forestry 2

lbs ai/gallon 8 40 80 No Data
Hexazinone Human Health Risk Assessment DPNo. 424526

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Table 9.1.1. Occupational Handler Non-Cancer Exposure and Risk Estimates for Hexazinone.

Exposure 

Scenario Crop or Target

Inhalation Unit Exposure (μg/lb ai)1

Maximum

Application 

Rate2

Area 

Treated or 

Amount 

Handled 

Daily3

Inhalation Risk Estimates4(LOC = 30)

Baseline PF5 PF10 Engineering 

Controls

Baseline

MOE

PF5

MOE

PF10

MOE

Engineering 

Control

MOE

Pineapple edging 0.036

lbs ai/gallon 440 2200 4400 No Data

Liquid for 

Backpack 

Applications

Non-Crop

2.58 0.516 0.258 No Data

0.32

lbs ai/gallon

40

gallons

1100 5400 11000 No Data

Christmas Tree farm 0.2

lbs ai/gallon 1700 8700 17000 No Data

Forestry 2

lbs ai/gallon 170 870 1700 No Data

Pineapple edging 0.036

lbs ai/gallon

9600 48000 96000 No Data

Liquids for 

MechanicallyPressurized 

Handgun

Non-Crop

3.9 0.78 0.39 No Data

0.32

lbs ai/gallon

1000

gallons

50 250 500 No Data

Christmas Tree farm 0.2

lbs ai/gallon 80 400 800 No Data

Forestry 2

lbs ai/gallon 8 40 80 No Data

Pineapple edging 0.036

lbs ai/gallon 440 2200 4400 No Data

Granules (Pellets) 

for Backpack 

Applications

Non-Crop

23.8 4.76 2.38 No Data

7.5 1 200 1000 2000 No Data

Pasture/ rangeland 0.64 1 2300 12000 23000 No Data

Forestry (pellets) 6.2 1 240 1200 2400 No Data

Forestry Release 4.1 1 370 1800 3700 No Data

Granules for 

Backpack 

Applications

Non-Crop 8 1 190 940 1900 No Data

Forestry and Forestry 

Release 4.7 1 320 1600 3200 No Data

Granules (Pellets) 

for Belly Grinder 

Applications

Non-Crop

62 12.4 6.2 No Data

7.5 1 130 670 1300 No Data

Pasture/ rangeland 0.64 1 1600 7800 16000 No Data

Forestry (pellets) 6.2 1 160 810 1600 No Data
Hexazinone Human Health Risk Assessment DPNo. 424526

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Table 9.1.1. Occupational Handler Non-Cancer Exposure and Risk Estimates for Hexazinone.

Exposure 

Scenario Crop or Target

Inhalation Unit Exposure (μg/lb ai)1

Maximum

Application 

Rate2

Area 

Treated or 

Amount 

Handled 

Daily3

Inhalation Risk Estimates4(LOC = 30)

Baseline PF5 PF10 Engineering 

Controls

Baseline

MOE

PF5

MOE

PF10

MOE

Engineering 

Control

MOE

Forestry Release 4.1 1 250 1200 2500 No Data

Granules for Belly 

Grinder 

Applications

Non-Crop 8 1 130 630 1300 No Data

Forestry and Forestry 

Release 4.7 1 210 1100 2100 No Data

Granules (Pellets) 

for Rotary 

Spreader 

Applications

Non-Crop

10 2 1 No Data

7.5

5

95 480 950 No Data

Pasture/ rangeland 0.643 1100 5600 11000 No Data

Forestry (pellets) 6.21 110 580 1100 No Data

Forestry Release 4.07 180 880 1800 No Data

Granules for 

Rotary Spreader 

Applications

Non-Crop 8 89 450 890 No Data

Forestry and Forestry 

Release 4.7 150 760 1500 No Data

 1 Based on the “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table” (Feb 2015); Level of mitigation: Baseline, PPE, Eng. Controls.

 2 Based on registered labels (See Table 4.1).

 3 Exposure Science Advisory Council Policy #9.1 and assumptions in the Occupational Exposure Handler Spreadsheet (February 2015).

 4 Inhalation MOE = Inhalation HEC (mg/kg/day) ÷ Inhalation Dose (mg/kg/day).
Hexazinone Human Health Risk Assessment DPNo. 424526

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9.2 Occupational Post-application Exposure/Risk Estimates

HED uses the term post-application to describe exposures that occur when individuals are 

present in an environment that has been previously treated with a pesticide (also referred to as reentry exposure). Such exposures may occur when workers enter previously treated areas to 

perform job functions, including activities related to crop production, such as scouting for pests 

or harvesting. Post-application exposure levels vary over time and depend on such things as the 

type of activity, the nature of the crop or target that was treated, the type of pesticide application, 

and the chemical’s degradation properties. In addition, the timing of pesticide applications, 

relative to harvest activities, can greatly reduce the potential for post-application exposure.

9.2.1 Occupational Post-application Inhalation Exposure/Risk Estimates

There are multiple potential sources of post-application inhalation exposure to individuals 

performing post-application activities in previously treated fields. These potential sources 

include volatilization of pesticides and resuspension of dusts and/or particulates that contain 

pesticides. The Agency sought expert advice and input on issues related to volatilization of 

pesticides from its Federal Insecticide, Fungicide, and Rodenticide Act Scientific Advisory Panel 

(SAP) in December 2009, and received the SAP’s final report on March 2, 2010 

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

evaluated the SAP report and has developed a Volatilization Screening Tool and a subsequent 

Volatilization Screening Analysis (http://www.regulations.gov/#!docketDetail;D=EPA-HQOPP-2014-0219). During Registration Review, the Agency will utilize this analysis to determine 

if data (i.e., flux studies, route-specific inhalation toxicological studies) or further analysis is 

required for hexazinone.

In addition, the Agency is continuing to evaluate the available post-application inhalation 

exposure data generated by the Agricultural Reentry Task Force. Given these two efforts, the 

Agency will continue to identify the need for and, subsequently, the way to incorporate 

occupational post-application inhalation exposure into the Agency's risk assessments.

9.2.2 Occupational Post-application Dermal Exposure/Risk Estimates

Occupational Post-application Dermal Exposure Data and Assumptions

No dermal hazard was identified for hexazinone, therefore a dermal post-application risk 

assessment was not completed. 

Restricted Entry Interval

The REI specified on the registered labels is 48 hours. Hexazinone is classified as Toxicity 

Category IV via the dermal route, dermal irritation, and is not a skin sensitizer. Hexazinone is 

Toxicity Category III for oral and inhalation potential, however, it is a Category I for eye 

irritation. Based on the acute toxicity of hexazinone a 48 hour REI is adequate.
Hexazinone Human Health Risk Assessment DPNo. 424526

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10.0 Human Study Review

This risk assessment relies in part on data from studies in which adult human subjects were 

intentionally exposed to a pesticide or other chemical. These data, which include studies from 

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

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

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

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

website9. 

11.0 Review of Incident Report

The Incident Data System (IDS) analysis from January 1, 2010 through March 12, 2015, shows 

two incidents reported involving hexazinone in Main IDS and 21 incidents reported to Aggregate 

IDS. Further, a query of SENSOR-Pesticides 1998-2011 identifies a total of 13 cases involving 

hexazinone. Four of these cases involved the single active ingredient hexazinone. These 

incidents were classified as low severity. Based on the low frequency and low severity of 

incident cases reported for hexazinone in both IDS and National Institute of Occupational Safety 

and Health Sentinel Event Notification System for Occupational Risks (NIOSH SENSORPesticides), there does not appear to be a concern at this time that would warrant further 

investigation. The Agency will continue to monitor the incident information and if a concern is 

triggered, additional analysis will be conducted.

The Agricultural Health Study (AHS) is also a potential source of information associated with 

human health effects associated with certain pesticides. Hexazinone is not included in the AHS, 

and therefore this study does not provide information for this report.

12.0 References

Christensen, C. (2002). Revised. HED Chapter for the Hexazinone Tolerance Reassessment 

Eligibility Decision. DP Number: D275621, dated August 22, 2002.

Piper, S. (2015). Hexazinone: Updated Dietary Burden for Beef and Dairy Cattle. DP Number: 

D427006, dated June 2, 2015.

Piper, S. (2015). Hexazinone. Acute and Chronic Aggregate Dietary (Food and Drinking Water) 

Exposure and Risk Assessments to Support Registration Review. DP Number: D427004, dated 

June 2, 2015.

Melendez, J. (2015). Estimated Drinking Water Concentrations for the Registration Review of 

Hexazinone, DP Number: D424532, dated April 23, 2015.

 

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

http://www.epa.gov/pesticides/science/post-app-exposure-data.html
Hexazinone Human Health Risk Assessment DPNo. 424526

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Recore, S. (2015) Hexazinone: Tier I Update Review of Human Incidents/Epidemiology for 

Draft Risk Assessment. DP Number: D427025, dated April 29, 2015.

Shelat. S. (2015) Hexazinone. Occupational and Residential Exposure Assessment for 

Registration Review, DP Number: D426399, dated June3, 2015.
Hexazinone Human Health Risk Assessment DPNo. 424526

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APPENDIX A: TOXICOLOGY ASSESSMENT

A.1 Toxicology Data Requirements

The requirements (40CFR §158.340) for food use of hexazinone are in Table A.1, below. Use of 

the new guideline numbers does not imply that the new (1998) guideline protocols were used. 
Hexazinone Human Health Risk Assessment DPNo. 424526

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TABLE A.1 Toxicology Data Requirements for Hexazinone.

Test Technical

Required Conducted

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 (non-rodent)

870.3200 21/28-Day Dermal

870.3250 90-Day Dermal

870.3465 90-Day Inhalation

yes

yes

yes

no

yes

yes

yes

yes

no

yes

870.3700a Developmental Toxicity (rodent)

870.3700b Developmental Toxicity (non-rodent)

870.3800 Reproduction

yes

yes

yes

yes

yes

yes

870.4100a Chronic Toxicity (rodent)

870.4100b Chronic Toxicity (non-rodent)

870.4200a Oncogenicity (rat)

870.4200b Oncogenicity (mouse)

870.4300 Chronic/Oncogenicity

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

870.5100 Mutagenicity—Gene Mutation (bacterial)

870.5300 Mutagenicity—Gene Mutation (mammalian)

870.5375 Mutagenicity—Structural Chromosomal Aberrations

870.5395 Mutagenicity—Other Genotoxic Effects 

870.5500 Mutagenicity—Other Genotoxic Effects

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

870.6100a Acute Delayed Neurotoxicity (hen)

870.6100b 90-Day Neurotoxicity (hen)

870.6200a Acute Neurotoxicity Screening Battery (rat)

870.6200b 90-Day Neurotoxicity Screening Battery (rat)

870.6300 Developmental Neurotoxicity

no

no

yes

yes

no

no

no

yes

yes

no

870.7485 General Metabolism

870.7600 Dermal Penetration 

870.7800 Immunotoxicity

yes

no

yes

yes

yes

yes

A.2 Toxicity Profiles

TABLE A.2.1 Acute Toxicity Profile for Hexazinone

Guideline 

Number

Study Type MRID(s) Results Toxicity 

Category

870.1100 Acute oral [Rat] 41235004 LD50 = 1200 mg/kg (M,F) III
Hexazinone Human Health Risk Assessment DPNo. 424526

Page 50 of 64

870.1200 Acute dermal [Rabbit] 00104974 LD50 ≥ 5278 mg/kg IV

870.1300 Acute inhalation [Rat] 41756701 LC50 ≥ 3.94 mg/L (4 hours) III

870.2400 Acute eye irritation [Rabbit] 00106003 Irreversible corneal opacity I

870.2500 Acute dermal irritation [Rabbit] 00106004 Mild skin irritation IV

870.2600 Skin sensitization [Guinea pig] 41235005 Not a sensitizer (Buehler test) NA

TABLE A.2.2 Subchronic, Chronic and Other Toxicity Profile for Hexazinone

Guideline Number/ 

Study Type

MRID(s) [year]/ 

Classification/Doses Results

870.3100

90-Day oral toxicity 

[rat]

0010977 [1973]

Acceptable/guideline

0, 200, 1000, 5000 ppm

M: 0, 16, 81, 440 mg/kg/day

F: 0, 16.4, 87.3, 451 mg/kg/day

NOAEL = 81/87.3 mg/kg/day (M/F)

LOAEL = 440/451 mg/kg/day (M/F) based on decreases 

in body weight and food efficiency.

870.3150

90-Day oral toxicity 

[dog]

00114484 [1973]

Acceptable/guideline

0, 200, 1000, 5000 ppm

M: 0, 5.1, 25.9, 122.5 mg/kg/day

F: 0, 7, 31.6, 137.3 mg/kg/day

NOAEL= 25.9/31.6 [M/F] mg/kg/day

LOAEL= 122.5/137.3 [M/F] mg/kg/day based on 

decreased body weight gains, increased liver weights, 

and increased alkaline phosphatase levels in both sexes. 

870.3200

21-day dermal 

toxicity

[rabbit]

41309005 [1989]

Acceptable/guideline

0,50,400,1000 mg/kg/day

6 hr/day, 21 consecutive days 

NOAEL=1000 mg/kg/day [M/F]

No effects seen at the limit dose

870.3465

28-day inhalation 

[rat]

49221101 [2013]

Acceptable/guideline

0, 0.031, 0.11, 0.31, 1.05 mg/L

6 hr/day, 5 day/wk

NOAEL= 0.031 mg/L

LOAEL= 0.11 mg/L based on squamous and mucous 

cell metaplasia at the ventral base of the epiglottis and 

in the nose, nasal septum and nasopharynx (portal of 

entry effects).

870.3700a

Prenatal 

developmental

[rat]

40397501 [1987]

Acceptable/guideline 

0, 40, 100, 400, 900 mg/kg/day

(GD 7-16, gavage)

Maternal NOAEL = 100 mg/kg/day

LOAEL = 400 mg/kg/day based on decreased food 

consumption and body weight gains on days 7 -17. 

Developmental NOAEL= 400 mg/kg/day.

LOAEL= 900 mg/kg/day based on decreased female 

fetal weight, increased incidence of kidneys with no 

papilla (malformation), and an increased incidence of 

misaligned sternebrae (variation).

870.3700a

Prenatal 

developmental

[rat]

00114486 [1974]

Unacceptable/upgradeable

0, 18.9, 94.5, 482 mg/kg/day

(GD 6-15, in diet)

Maternal NOAEL= 94.5 mg/kg/day

LOAEL= 482 mg/kg/day based on decreased body 

weight, body weight gain and food efficiency.

Developmental NOAEL= 482 mg/kg/day (HDT).

870.3700b

Prenatal 

developmental 

[rabbit]

45677801 [2002]

Acceptable/guideline

0, 20, 50, 125, 175 mg/kg/day

(GD 7-28, gavage)

Maternal NOAEL = 50 mg/kg/day

LOAEL = 125 mg/kg/day based on a decreased body 

weight gains and food consumption, increased 

abortions, death and clinical signs.

Developmental NOAEL = 50 mg/kg/day.

LOAEL= 125 mg/kg/day based on decreased fetal 

weights in both sexes.

870.3700

Prenatal 

developmental

[rabbit]

00028863 [1980]

Unacceptable/upgradeable 

0, 20, 50, 125 mg/kg/day

(GD 6-19, gavage)

Maternal NOAEL = 50 mg/kg/day

LOAEL = 125 mg/kg/day based on decreased body 

weight gain and food consumption.

Developmental NOAEL= 50 mg/kg/day 

LOAEL = 125 mg/kg/day based on possible skeletal 

abnormalities and total abnormalies. No historical 
Hexazinone Human Health Risk Assessment DPNo. 424526

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TABLE A.2.2 Subchronic, Chronic and Other Toxicity Profile for Hexazinone

Guideline Number/ 

Study Type

MRID(s) [year]/ 

Classification/Doses Results

control, and no individual litter data available. New 

study was being conducted. 

870.3800

Reproduction and 

fertility effects

[rat]

42066501 [1991]

Acceptable/guideline

0, 200, 2000, 5000 ppm

M: 0, 11.8, 117, 294 mg/kg/day

F: 0, 14.3, 143, 383 mg/kg/day

Parental/Systemic NOAEL = 11.8/14.3 [M/F] 

mg/kg/day

LOAEL = 117/143 [M/F] mg/kg/day based on 

decreased body weights and body weight gains in F1 

males and F0 and F1 females.

Offspring NOAEL = 11.8/14.3 [M/F] mg/kg/day

LOAEL = 117/143 [M/F] mg/kg/day based on 

decreased pup body weights at birth and during 

lactation.

Reproductive NOAEL= 294/383 [M/F] mg/kg/day.

No reproductive effects seen.

870.4100b

One-year toxicity 

[dog]

42162301 [1991]

Acceptable/guideline

0, 200, 1500, 6000 ppm

M: 0, 5.0, 41.2, 161 mg/kg/day

F: 0, 4.9, 37.6, 167 mg/kg/day

NOAEL = 5.0/4.9 [M/F] mg/kg/day

LOAEL = 41.2/37.6 [M/F] mg/kg/day based on 

decreased body weight and hepatotoxicity as evidence 

by changes in clinical chemistry parameters and 

microscopic lesions.

870.4300

Combined Chronic/ 

Carcinogenicity 

[rat]

00108638 [1977]

Acceptable/guideline

0, 200, 1000, 2500 ppm

M: 0, 10.2, 53.4, 138.3 

mg/kg/day

F: 0, 12.5, 67.5, 178.6 mg/kg/day

NOAEL = 10.2/12.5 [M/F] mg/kg/day

LOAEL = 53.3/67.5 [M/F] mg/kg/day based on 

decreased body weight and food efficiency.

No evidence of carcinogenicity.

870.4300

Carcinogenicity

[mouse]

00079203 [1981], 

41359301[1989], 42509301 

[1992], 43202901[1994]

Acceptable/ guideline

0, 200, 2500, 10000 ppm

M: 0, 28, 366, 1635 mg/kg/day

F: 0, 34, 450, 1915 mg/kg/day

NOAEL= 28 mg/kg/day [M]/ 450 mg/kg/day [F]

M: LOAEL= 366 mg/kg/day based on gross liver and 

centrilobular hepatocyte hypertrophy; 

F: LOAEL=1915 mg/kg/day based on decreased body 

weights, increased relative liver weight/gall bladder 

weights, hyperplastic nodules and centrilobular 

hepatocyte hypertrophy. 

Evidence of carcinogenic potential was equivocal.

870.5100

Gene Mutation

Reverse mutation in 

Salmonella

40826201 [1977]

Unacceptable/guideline

200, 400, 600, 800, 1000 μg/plate 

(-S9)

400, 800, 1200, 1600, 2000 

μg/mL (+S9)

No mutagenic potential was seen, but doses insufficient 

to cause cell toxicity

870.5300

Gene Mutation

Hamster CHO 

cells/HPRT assay

00076956 [1980]

Acceptable/guideline

Trial 1: 2.0, 11.1, 13.1, 13.9, 14.3 

mM (-S9); 2.0, 7.9, 8.9, 9.3, 9.9 

mM (+S9)

Trial 2: 2.0, 5.9, 11.1, 13.1, 13.9 

mM (-S9); 2.0, 7.9, 8.9, 9.3, 9.9 

mM (+S9)

No evidence of mutagenic effect either in the presence 

or the absence of S9 activation.
Hexazinone Human Health Risk Assessment DPNo. 424526

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TABLE A.2.2 Subchronic, Chronic and Other Toxicity Profile for Hexazinone

Guideline Number/ 

Study Type

MRID(s) [year]/ 

Classification/Doses Results

870.5375

In vitro mammalian 

chromosome 

aberration test

00130709 [1982]

Acceptable/guideline

Trial 1: 1.58, 3.94, 15.85, 19.82 

mM (-S9); 0.32, 3.17, 7.93, 15.85 

mM (+S9)

Trial 2: 1.58, 3.94, 7.93, 15.85 

mM (-S9); 0.32, 3.17, 7.93, 15.85 

mM (+S9)

Positive for chromosome aberrations with or without 

S9.

870.5385

In vivo cytogenetics 

assay in rat bone 

morrow cells

00131355 [1982]

Unacceptable/guideline

100, 300, 1000 mg/kg by gavage

No evidence of clastogenic potential but insufficient 

animals and cell were tested.

870.5395

Mammalian 

erythrocyte 

micronucleus test

45124401 [2000]

Acceptable/guideline

1000, 2000, 3000 mg/kg

No evidence of clastogenic or aneugenic effect in bone 

morrow at toxic doses.

870.5500

UDS in rat 

hepatocytes

00130708 [1983]

Acceptable/guideline

Trial 1: 1x10-5, 1x10-4, 1x10-3, 

1x10-2, 0.1, 1.0, 10.0, 30 mM

Trial 2: 1x10-5, 1x10-4, 1x10-3, 

1x10-2, 0.1, 1.0, 5.0, 10.0, 30 mM

No evidence of genotoxic potential at precipitating 

concentrations.

870.6200

Acute neurotoxicity

[rat]

48931901 [2012]

Acceptable/guideline

0, 32.25, 125, 500 mg/kg

gavage

NOAEL= 125 mg/kg

LOAEL= 500 mg/kg based on reduced motor activity in 

both sexes, decreased body temperature and increased 

incidences in posture and palpebral closure in females.

870.6200

Subchronic 

neurotoxicity 

[rat]

48379701 [2011]

Acceptable/guideline

0, 100, 300, 1250, 5000 ppm

M: 0, 6, 17, 68, 273 mg/kg/day

F: 0, 7, 20, 81, 350 mg/kg/day

Systemic NOAEL= 68/81 mg/kg/day [M/F]

LOAEL= 273/350 mg/kg/day based on reduced body 

weights and gains and reduced food consumption.

No neurotoxicity was seen.

870.7800

Immunotoxicity

[female rat]

48963501 [2012]

Acceptable/guideline

0, 100, 300, 1250, 5000 ppm 

0, 7, 23, 89, 376 mg/kg/day

NOAEL = 376 mg/kg/day (HDT)

No evidence of immunotoxicity.

870.7485

Metabolism and 

pharmacokinetics

[rat]

00140162, 00109237 [1980, 

1982]

Acceptable

Hexazinone was rapidly absorbed and excreted, no 

difference in males and females at high or low dose 

levels. No parent was recovered in urine or feces. Two 

major metabolites were recovered from feces and urine, 

in addition to lesser amount of a third metabolite and 

small amounts conjugated products from urine.

Appendix B. Chemical Structures of Hexazinone and its Regulated Metabolites 

(Metabolites A through F)
Hexazinone Human Health Risk Assessment DPNo. 424526

Page 53 of 64

Common Name/Code

Chemical name Structure

Hexazinone

3-cyclohexyl-6-(dimethylamino)-1-

methyl-1,3,5-triazine-2,4-(1H,3H)-

dione

N

N

N

O

O

CH3

N

CH3

CH3

Metabolite A

3-(4-hydroxycyclohexyl)-6-

(dimethylamino)-1-methyl-1,3,5-

triazine-2,4-(1H,3H)-dione

Metabolite A-1 is hydroxylated at the 

2- position of the cyclohexyl ring; 

Metabolite A-2 is hydroxylated at the 

3-position of the cyclohexyl ring. 

N

N

N

O

O

CH3

N

CH3

CH3

HO

Metabolite B

3-cyclohexyl-6-(methylamino)-1-

methyl-1,3,5-triazine-2,4-(1H,3H)-

dione

N

N

N

O

O

CH3

N

H

CH3

Metabolite C

3-(4-hydroxycyclohexyl)-6-

(methylamino)-

1-methyl-1,3,5-triazine-2,4-(1H,3H)-

dione

Metabolite C-1 is hydroxylated at the 

2- position of the cyclohexyl ring; 

Metabolite C-2 is hydroxylated at the 

3- position of the cyclohexyl ring. 

N

N

N

O

O

CH3

N

H

CH3

HO
Hexazinone Human Health Risk Assessment DPNo. 424526

Page 54 of 64

Common Name/Code

Chemical name Structure

Metabolite D

3-cyclohexyl-1-methyl-1,3,5-triazine2,4,6-(1H,3H,5H)-trione N

N

NH

O

O

CH3

O

Metabolite E

3-(4-hydroxycyclohexyl)-1-methyl1,3,5-triazine-2,4,6-(1H,3H,5H)-trione N

N

NH

O

O

CH3

O

HO

Metabolite F

3-cyclohexyl-6-amino-1-methyl1,3,5-triazine-2,4-(1H,3H)-dione N

N

N

O

O

CH3

NH2

Appendix C: International Residue Limits 
Hexazinone Human Health Risk Assessment DPNo. 424526

Page 55 of 64

Hexazinone (107201; Date of Request: 3/18/2015)

Summary of US and International Tolerances and Maximum Residue Limits 

Residue Definition:

US Canada Mexico1 Codex

40 CFR 180.396 (a) General (1)

Plant: Compliance with the tolerance levels 

specified in this paragraph is to be determined 

by measuring only the sum of hexazinone, 3-

cyclohexyl-6-(dimethylamino)-1-methyl-1,3,5-

triazine-2,4-(1H, 3H)-dione, and its plant 

metabolites: metabolite A, 3-(4-

hydroxycyclohexyl)-6-(dimethylamino)-1-

methyl-1,3,5-triazine-2,4-(1H, 3H)-dione, 

metabolite B, 3-cyclohexyl-6-(methylamino)-1-

methyl-1,3,5-triazine-2,4-(1H, 3H)-dione, 

metabolite C, 3-(4-hydroxycyclohexyl)-6-

(methylamino)-1-methyl-1,3,5-triazine-2,4-(1H, 

3H)-dione, metabolite D, 3-cyclohexyl-1-

methyl-1,3,5-triazine-2,4,6-(1H, 3H, 5H)-trione, 

and metabolite E, 3-(4-hydroxycyclohexyl)-1-

methyl-1,3,5-triazine-2,4,6-(1H, 3H, 5H)-trione, 

calculated as the stoichiometric equivalent of 

hexazinone

None None

Commodity

US Canada Mexico1 Codex

Alfalfa, forage 2.0

Alfalfa, hay 4.0

Alfalfa, seed 2.0

Blueberry 0.6

Grass, forage 250

Grass, hay 230

Pineapple 0.6

Sugarcane, cane 0.6

Sugarcane, molasses 4.0

40 CFR 180.396 (2) Canada Mexico1 Codex
Hexazinone Human Health Risk Assessment DPNo. 424526

Page 56 of 64

Summary of US and International Tolerances and Maximum Residue Limits 

Residue Definition:

US Canada Mexico1 Codex

Livestock: Compliance with the 

tolerance levels specified in this 

paragraph is to be determined by 

measuring only the sum of hexazinone, 

3-cyclohexyl-6-(dimethylamino)-1-

methyl-1,3,5-triazine-2,4-(1H, 3H)-

dione, and its animal tissue

metabolites: metabolite B, 3-

cyclohexyl-6-(methylamino)-1-methyl1,3,5-triazine-2,4-(1H, 3H)-dione, and 

metabolite F, 3-cyclohexyl-6-amino-1-

methyl-1,3,5-triazine-2,4-(1H, 3H)-

dione, calculated as the stoichiometric 

equivalent of hexazinone

All livestock commodity 

except poultry: 3-

cyclohexyl-6-

(dimethylamino)-1-

methyl-1,3,5-triazine2,4-(1H,3H)-dione, 

including the metabolite 

3-cyclohexyl-1-methyl6-(methylamino)-1,3,5-

triazine-2,4-(1H,3H)-

dione, expressed as 

hexazinone equivalents

None

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

US Canada Mexico1 Codex

Cattle, fat 0.1 0.04

Cattle, meat 0.5 0.04

Cattle, meat byproducts 4.0 0.04 meat byproducts of 

cattle

Goat, fat 0.1 0.04

Goat, meat 0.5 0.04

Goat, meat byproducts 4.0 0.04 meat byproducts of 

goats

Sheep, fat 0.1 0.04

Sheep, meat 0.5 0.04

Sheep, meat byproducts 4.0 0.04 meat byproducts of 

sheep

Horse, fat 0.1 0.04

Horse, meat 0.5 0.04

Horse, meat byproducts 4.0 0.04 meat byproducts of 

horses

Hog, fat Revoke 0.04

Hog, meat Revoke 0.04

Hog, meat byproducts Revoke 0.04 meat byproducts of 

hogs
Hexazinone Human Health Risk Assessment DPNo. 424526

Page 57 of 64

Summary of US and International Tolerances and Maximum Residue Limits 

Residue Definition:

US Canada Mexico1 Codex

40 CFR 180.396 (3) Compliance with 

the tolerance level specified in this 

paragraph is to be determined by 

measuring only the sum of hexazinone, 

3-cyclohexyl-6-(dimethylamino)-1-

methyl-1,3,5-triazine-2,4-(1H, 3H)-

dione, and its metabolites: metabolite 

B, 3-cyclohexyl-6-(methylamino)-1-

methyl-1,3,5-triazine-2,4-(1H, 3H)-

dione, metabolite C, 3-(4-

hydroxycyclohexyl)-6-(methylamino)-

1-methyl-1,3,5-triazine-2,4-(1H, 3H)-

dione, metabolite C-2, 3-(3-

hydroxycyclohexyl)-6-(methylamino)-

1-methyl-1,3,5-triazine-2,4-(1H, 3H)-

dione, and metabolite F, 3-cyclohexyl6-amino-1-methyl-1,3,5-triazine-2,4-

(1H, 3H)-dione, calculated as the 

stoichiometric equivalent of 

hexazinone.

3-cyclohexyl-6-

(dimethylamino)-1-

methyl-1,3,5-triazine2,4-(1H,3H)-dione, 

including the metabolites 

3-cyclohexyl-1-methyl6-(methylamino)-1,3,5-

triazine-2,4-(1H,3H)-

dione and 3-(3-

hydroxycyclohexyl)-1-

methyl-6-(methylamino)-

1,3,5-triazine-2,4-

(1H,3H)-dione, 

expressed as hexazinone 

equivalents

None

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

US Canada Mexico1 Codex

Milk 11 0.09

Completed: M. Negussie; 03/30/15 

1 Mexico adopts US tolerances and/or Codex MRLs for its export purposes.
Hexazinone Human Health Risk Assessment DPNo. 424526

Page 58 of 64

Appendix D: Food/Feed Use Patterns Subject To Reregistration for Hexazinone (PC Code 107201).

Site

Application Type

Application Timing

Application Equipment

Formulation

[EPA Reg. 

No.]

Max. Single 

Application 

Rate

(lb ai/A)

Max. # 

Apps./

Season

Maximum 

Seasonal 

Rate

(lb ai/A)

Preharvest

or

Pregrazing 

Interval 

(Days) Use Directions and Limitations 1

Alfalfa (grown for hay)

Broadcast application

Dormant, non-dormant, and 

semi-dormant

Ground or aerial

90% SC

[352-378]

1.35

0.675

(for alfalfa less 

than one year 

old)

1 1.35/year 30 Use prohibited in ND and SD.

Broadcast application

Dormant, non-dormant, and 

semi-dormant

Ground or aerial

2 lb/gal EC

[352-392]

75% DF

[352-581]

1.5

For the EC 

formulation 

only: 0.75

(for alfalfa <1 

year old)

1 1.5/year 30

(75% DF 

only)

Alfalfa (grown for seed)

Broadcast application

Dormant, non-dormant, and 

semi-dormant

Ground or aerial

90% SC

[352-378]

2 lb/gal EC

[352-392]

75% DF

[352-581]

0.5 1 0.5 Not 

specified 

(NS)

Use limited to CA. A maximum rate of 0.5 

lb ai/A is specified for fields with sandy 

loam or loamy sand soils having 1-2% OM 

and on seed alfalfa that has been established 

for only one growing season.

Alfalfa (grown for forage)

Broadcast application

Dormant

Ground

2 lb/gal EC

[MT940001]

[WY920001]

1.0 1 1.0 30

(75% DF)

Use limited to MT, ND, SD, and WY for 

established stands of forage alfalfa. 

Application to soils with <1.5% OM is 

prohibited for the EC formulation.
Hexazinone Human Health Risk Assessment DPNo. 424526

Page 59 of 64

Site

Application Type

Application Timing

Application Equipment

Formulation

[EPA Reg. 

No.]

Max. Single 

Application 

Rate

(lb ai/A)

Max. # 

Apps./

Season

Maximum 

Seasonal 

Rate

(lb ai/A)

Preharvest

or

Pregrazing 

Interval 

(Days) Use Directions and Limitations 1

75% DF

[ND970002]

[SD970001]

Blueberry 2

Broadcast application

Spring of fruiting year (prior 

to budbreak)

Ground

2 lb/gal EC

[ME980002]

75% DF

[ME980003]

2.0 NS 2.0 450 Use limited to ME for established lowbush 

blueberries. Do not exceed 2.0 or 1.8 lb 

ai/A if soil has been respectively treated 

with the EC or DF formulations of 

hexazinone within the past 8 years.

Broadcast application

Dormant (prior to budbreak)

Ground

2 lb/gal EC

[NC830012]

2.0 NS NS 50 Use limited to NC. Application may be 

made in sufficient water to provide thorough 

and uniform coverage, usually 20 gal/A.

Pineapple

Broadcast or directed spray 

application

Ground or aerial

90% SC

[352-378]

2 lb/gal EC

[352-392]

75% DF

[352-581]

1.8 NS 3.6/crop 

cycle

181 Broadcast applications may be made 

between successive pineapple crops, 

preplant after rows have been mulched, and 

postplant prior to active growth. Three to 

ten months after planting, directed spray 

applications may be made to the soil 

between crop rows. Broadcast applications 

may be made in 100-400 gallons of water/A 

using ground equipment, or in at least 10 

gal/A using aerial equipment. Directed 

sprays may be applied at 50-200 gal/A using 

ground equipment. Directed spot treatments 

are also permitted at 0.9-1.8 lb ai/100 gal 

prior to floral induction.

Pasture

Broadcast application

Ground

90% SC

[352-378]

2 lb/gal EC

1.125 1 1.125 

(implied)

60 Use limited to Bermuda grass/Bahia grass 

pastures. Applications may be made in a 
Hexazinone Human Health Risk Assessment DPNo. 424526

Page 60 of 64

Site

Application Type

Application Timing

Application Equipment

Formulation

[EPA Reg. 

No.]

Max. Single 

Application 

Rate

(lb ai/A)

Max. # 

Apps./

Season

Maximum 

Seasonal 

Rate

(lb ai/A)

Preharvest

or

Pregrazing 

Interval 

(Days) Use Directions and Limitations 1

[352-392]

75% DF

[352-581]

minimum of 25 gal/A using ground 

equipment. 

Basal soil application 

(undiluted)

Ground

2 lb/gal EC

[352-392]

2-4 mL of 

product for each 

inch of stem 

diameter

NS 0.67/year NS Use limited to brush control in pastures and 

rangelands. No restrictions on grazing by 

domestic animals nor on cutting surrounding 

vegetation for forage and hay when product 

is applied as a basal soil treatment. Basal soil application

Ground

75% DF

[352-581]

2 lb/1 gal

[2-4 mL of 

suspension for 

each inch of 

stem diameter]

NS 0.67/year NS

Rangeland

Basal soil application 

(undiluted)

Ground

2 lb/gal EC

[352-392]

2-4 mL of 

product for each 

inch of stem 

diameter

NS 0.67/year NS Use limited to brush control in pastures and 

rangelands. No restrictions on grazing by 

domestic animals nor on cutting surrounding 

vegetation for forage and hay when product 

is applied as a basal soil treatment. Basal soil application

Ground

75% DF

[352-581]

2 lb/1 gal

[2-4 mL of 

suspension for 

each inch of 

stem diameter]

NS 0.67/year NS

Sugarcane

Broadcast application

Preemergence and 

postemergence

Ground or aerial

90% SC

[352-378]

2 lb/gal EC

[352-392]

75% DF

[352-581]

3.6 1 3.6/crop 

cycle (18-24 

months)

180 Use limited to HI. Application may be 

made with a nonionic surfactant at 0.25% 

v/v.
Hexazinone Human Health Risk Assessment DPNo. 424526

Page 61 of 64

Site

Application Type

Application Timing

Application Equipment

Formulation

[EPA Reg. 

No.]

Max. Single 

Application 

Rate

(lb ai/A)

Max. # 

Apps./

Season

Maximum 

Seasonal 

Rate

(lb ai/A)

Preharvest

or

Pregrazing 

Interval 

(Days) Use Directions and Limitations 1

Sugarcane (continued)

Broadcast application

Preemergence (in fall) and 

postemergence (in spring 

before active cane tillering 

begins)

Ground or aerial

90% SC

[352-378]

2 lb/gal EC

[352-392]

75% DF

[352-581]

0.9 NS 0.45/year for 

the 90% SC

1.5/year for 

the 2 lb/gal 

EC and 75% 

DF

234 Use limited to LA.

Broadcast application

Preemergence and 

postemergence

Ground or aerial

90% SC

[352-378]

2 lb/gal EC

[352-392]

75% DF

[352-581]

0.45-0.5 NS 0.9/crop 

cycle

288 Use limited to PR.

Preemergence, early 

postemergence, and/or 

directed layby

Ground or aerial

90% SC

[352-378]

2 lb/gal EC

[352-392]

75% DF

[352-581]

0.9 NS 1.8/crop 

cycle

234 Use limited to TX. Two treatments are 

allowed (one early treatment plus one 

directed treatment at layby), provided 60 

days have elapsed and at least 3" of rainfall 

have occurred.

Sugarcane (continued)

Preemergence, early 

postemergence, or directed 

layby

Ground or aerial

90% SC

[TX940008]

0.45 1 0.45 NS Tank mix use with diuron (Karmex DF 

Herbicide) limited to TX. Application may 

be made in a minimum of 5 gal/A by air or 

in a minimum of 25 gal/A using ground 

equipment. The feeding of sugarcane forage 

to livestock is prohibited. Use on gravelly 
Hexazinone Human Health Risk Assessment DPNo. 424526

Page 62 of 64

Site

Application Type

Application Timing

Application Equipment

Formulation

[EPA Reg. 

No.]

Max. Single 

Application 

Rate

(lb ai/A)

Max. # 

Apps./

Season

Maximum 

Seasonal 

Rate

(lb ai/A)

Preharvest

or

Pregrazing 

Interval 

(Days) Use Directions and Limitations 1

or rocky soils, thinly-covered subsoils,

coarse-textured soils with <2% OM, or on 

any soil with <1% OM is prohibited. The 

planting of any crop other than sugarcane 

within 18 months of the last application is 

prohibited.

1 The restricted entry interval (REI) for the 90% SC (EPA Reg. No. 352-378), 2 lb/gal EC (EPA Reg. No. 352-378), and 75% DF (EPA Reg. No. 352-581) 

formulations is 24 hours.

2 A REFS search, conducted 7/26/01, listed blueberries as a use site for the Federal labels of the 2 lb/gal EC (EPA Reg. No. 352-392) and the 90% SC (EPA 

Reg. No. 352-378). However, upon label examination of these products, it was determined that there are no Section 3 registrations of hexazinone on 

blueberries; only Section 24(c) registrations exist.
Hexazinone Human Health Risk Assessment DPNo. 424526

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Appendix E. Risk Estimates Related to Spray Drift Exposure to Hexazinone from the 

Registered Agricultural Uses.

Table A.1. Children Incidental Oral Risk Estimates (MOEs) Related to Spray Drift Exposure to Hexazinone 

from the Registered Agricultural Uses.1

Crop/Rate 

Group Spray Type/ Nozzle Configuration Application Rate (lbs ai/A)

Estimated 

TTRt (ug/cm2)

At Edge 

HtM MOE 

Sugarcane

Aerial

Fine to Medium

3.6 0.40014

850

Medium to Coarse 1,000

Coarse to Very Coarse 1,200

Very Fine to Fine 590

AT401, M, 10 mph, 37% SD 940

WASP, M, 10 mph, 37% SD 1,000

AT401, C, 10 mph, 25% SD 1,100

WASP, C, 10 mph, 25% SD 1,300

AT401, VC, 10 mph, 20% SD 1,300

WASP, VC, 10 mph, 20% SD 1,600

Groundboom

High Boom Very fine to Fine 1,200

Low Boom Very fine to Fine 2,600

High Boom Fine to Medium/Coarse 4,500

Low Boom Fine to Medium/Coarse 6,600

Forestry2

Aerial

Fine to Medium

5 0.55575

 610 

Medium to Coarse 750 

Coarse to Very Coarse 860 

Very Fine to Fine 420 

AT401, M, 10 mph, 37% SD 670 

WASP, M, 10 mph, 37% SD 720 

AT401, C, 10 mph, 25% SD 800 

WASP, C, 10 mph, 25% SD 920 

AT401, VC, 10 mph, 20% SD 900 

WASP, VC, 10 mph, 20% SD 1,100 

Groundboom

High Boom Very fine to Fine 840 

Low Boom Very fine to Fine 1,900 

High Boom Fine to Medium/Coarse 3,200 

Low Boom Fine to Medium/Coarse 4,800 

Non-Crop Sites

Aerial

Fine to Medium

8 0.8892

 380 

Medium to Coarse 470 

Coarse to Very Coarse 540 

Very Fine to Fine 260 

AT401, M, 10 mph, 37% SD 420 

WASP, M, 10 mph, 37% SD 450 

AT401, C, 10 mph, 25% SD 500 

WASP, C, 10 mph, 25% SD 580 

AT401, VC, 10 mph, 20% SD 560 

WASP, VC, 10 mph, 20% SD 710 

Groundboom High Boom Very fine to Fine 530 

Low Boom Very fine to Fine 1,200 
Hexazinone Human Health Risk Assessment DPNo. 424526

Page 64 of 64

Table A.1. Children Incidental Oral Risk Estimates (MOEs) Related to Spray Drift Exposure to Hexazinone 

from the Registered Agricultural Uses.1

Crop/Rate 

Group Spray Type/ Nozzle Configuration Application Rate (lbs ai/A)

Estimated 

TTRt (ug/cm2)

At Edge 

HtM MOE 

High Boom Fine to Medium/Coarse 2,000 

Low Boom Fine to Medium/Coarse 3,000 

Airblast

Sparse 690 

Normal 33,000 

Dense 2,300 

Vineyard 12,000 

1. The highest application rate for an agricultural crop application is for aerial and ground applications to 

sugarcane use sites with an application rate of 3.6 lbs ai per acre. This use site and application equipment is 

representative of the other currently registered crop use sites. 

2. There is some uncertainty associated with the drift predictions associated with forestry uses because in 

some situations pesticides like hexazinone are applied in rugged terrain using rotary aircraft and smaller 

droplets. A more appropriate modeling approach is currently under development for such situations. Even 

so, this would not alter the risk conclusions for the current human health risk assessment spray drift 

scenario because, in the case of hexazinone, if the 100% of application rate assumption is used rather than 

the screening level assumptions, there would be no risks of concern for the incidental oral risk estimates for