UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

MEMORANDUM 

DATE: 30-MAY-2013 

OFFICE OF CHEMICAL SAFETY AND 

POLLUTION PREVENTION 

SUBJECT: Topramezone: Human-Health Risk Assessment for (1) New Uses in Non-Crop 

Aquatic Sites and (2) Increased Maximum Application Rate for Currently 

Registered Terrestrial Uses in the Maintenance of Bare Grounds (Roadsides, 

Utility and Railroad Rights-of-Ways, Industrial Sites, and Tank Farms). 

PC Code: 123009 DP Barcode: D40031 0, D4040 14 

Registration No.: 7969-GET, 7969-XXX 

Regulatory Action: Section 3 

Decision No.: 462026, 465325 

Petition No.: 2F7997 

Risk Assessment Type: Single Chemical/Aggregate 

TXRNo.: NA 

Case No.: 7268 

CAS No.: 210631-68-8 

MRIDNo.: NA 40 CFR: §180.612 

FROM: Chester E. Rodriguez, Ph.Q., To~xic 1 g· 

Sarah J. Levy, Che~m·st Thomas Bloem, Chemis 

Risk Assessment Branch (RAB 1) 

Health Effects Division (HED; 7509P) 

THROUGH: DanaM. Vogel,DeputyDirector '.~~~--- George F. Kramer, Ph.D., Branch Senior Chemis~~.:::~".!SC:~-<~=---­ RAB 1/HED (7509P) 

TO: Kathryn Montague, RM 23 

Registration Division (RD; 7505P) 

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

estimating the risk to human health from exposure to pesticides. The Registration Division (RD) 

of OPP has requested that HED evaluate 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 all registered and proposed uses of topramezone ([3-(4,5-

dihydro-isoxazol-3-yl)-4-methylsulfonyl-2-methylphenyl](5-hydroxy-1-methyl-1H-pyrazol-4-

yl)methanone). A summary of the findings and an assessment of human risk resulting from the 

registered and proposed uses for topramezone are provided in this document. The risk 

assessment and hazard characterization were provided by Chester Rodriguez, the residue 

chemistry review and occupational/residential exposure assessment by Thomas Bloem (RABl), 

the dietary risk assessment by Sarah Levy (RABl), and the drinking water assessment by James 

Wolf of the Environmental Fate and Effects Division (EFED). 

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Topramezone Human-Health Risk Assessment DP#s 400310,404014 

Table of Contents 

2.0 HED Recommendations ...................................................................................................... ? 

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

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

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

2.2.2 Recommended Tolerances ......................................................................................... 8 

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

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

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

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

2.3.2 Recommendations from Occupational Assessment.. ............................................... lO 

3.0 Introduction ........ ....................... ........................................................................................ 10 

3.1 Chemical Identity ............................................................................................................ 10 

3.2 Physical/Chemical Characteristics .................................................................................. ! 0 

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

3.4 Anticipated Exposure Pathways ...................................................................................... l4 

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

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

4.2 Absorption, Distribution, Metabolism, and Excretion (ADME) .................................... 14 

4.3 Dermal Absorption .......................................................................................................... l4 

4.4 Toxicological Effects ...................................................................................................... 15 

4.5 Safety Factor for Infants and Children [FQPA SF) ........................................................ l6 

4.5.1 Completeness of the Toxicology Database .............................................................. l6 

4.5.2 Evidence of Neurotoxicity ....................................................................................... 16 

4.5.3 Evidence of Sensitivity/Susceptibility in the Developing or Young Animal .......... l7 

4.5.4 Residual Uncertainty in the Exposure Database ...................................................... l7 

4.6 Toxicity Endpoints and Points of Departure Selections ................................................. 17 

4.6.1 Dose-Response Assessment.. ................................................................................... !? 

4.6.2 Recommendation for Combining Routes of Exposure for Risk Assessment.. ........ 19 

4.6.3 Cancer Classification and Risk Assessment Recommendation ................................ 20 

4.6.4 Summary of Toxicity Endpoint and POD Selection ................................................ 20 

5.0 Dietary Exposure and Risk Assessment.. ........................................................................ 21 

5.1 Residues of Concern Summary and Rationale ................................................................ 21 

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

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

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

5.5 Dietary Risk Assessment ................................................................................. ............... 23 

5.5. 1 Description of Residue Data Used in Dietary Assessment.. .................................... 23 

5.5.2 Percent Crop Treated Used in Dietary Assessment.. ............................................... 24 

5.5.3 Acute Dietary Risk Assessment.. ............................................................................. 24 

5.5.4 Chronic Dietary Risk Assessment ........................................................................... 24 

5.5.5 Cancer Dietary Risk Assessment ............................................................................. 24 

6.0 Residential (Non-Occupational) Exposure/Risk Characterization ............................... 25 

6.1 Residential Handler Exposure ......................................................................................... 25 

6.2 Post-Application Exposure···························.······································ ............................ 25 

6.3 Residential Risk Estimates for Use in Aggregate Assessment ....................................... 27 

6.4 Residential Bystander Post-application Inhalation Exposure ......................................... 27 

6.5 Spray Drift. ....................... ................................................................. .. ............................ 28 

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7.0 Aggregate Exposure/Risk Characterization .................................................................. 28

7.1 Acute Aggregate Risk .................................................................................................... 28

7.2 Short-Term Aggregate Risk ........................................................................................... 29

7.3 Intermediate-Term Aggregate Risk................................................................................ 29

7.4 Long-Term Aggregate Risk ........................................................................................... 29

7.5 Cancer Risk .................................................................................................................... 30

8.0 Cumulative Exposure/Risk Characterization................................................................ 30

9.0 Occupational Exposure/Risk Characterization............................................................. 31

9.1 Short-/Intermediate-Term Handler Risk ........................................................................ 31

9.2 Post-Application Risk .................................................................................................... 33

10.0 References ......................................................................................................................... 34

Appendix A. Toxicology Profile and Executive Summaries .................................................. 36

A.1 Toxicology Data Requirements...................................................................................... 36

A.2 Toxicity Profiles............................................................................................................. 37

Appendix B. Physical/Chemical Properties of Topramezone ................................................ 41
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1.0 Executive Summary

BASF has submitted to the Agency a tolerance petition for topramezone in/on fish and shellfish 

in support of a new non-crop aquatic use (DP# 400310). Also petitioned by BASF and 

addressed in this document is an increase in the maximum application rate from 4 to 8 fl oz/A for 

currently registered non-crop terrestrial uses in areas where bare grounds must be maintained 

such as roadsides, utility and railroad right-of-ways, industrial sites, and tank farms (DP 

#404014). Topramezone ([3-(4,5-dihydro-3-isoxazolyl)-2-methyl-4-(methylsulfonyl)phenyl](5-

hydroxy-1-methyl-1H-pyrazol-4-yl)methanone) is a broad-spectrum, post-emergent herbicide 

used to control grassy and broadleaf weeds and is currently registered for use on residential 

turfgrass, golf courses, sod farms, non-crop ornamentals, rights-of-way, tree plantations, and 

other non-crop areas, as well as for application to corn (field, pop, seed, and sweet) with 

tolerances ranging from 0.01 to 0.15 ppm (40 CFR §180.612). The end-use product for the two 

proposed uses has the same composition: a soluble concentrate liquid formulation containing 

2.8-pound (lb) active ingredient (ai)/gallon. The proposed label for the aquatic use allows 

ground, aerial, and direct water application. The maximum single application rate proposed for 

the non-crop aquatic use is 0.35 lbs ai/acre for foliar application or sequential in-water 

applications to maintain a water concentration of 50 ppb for a recommended duration of 60 days.

Based on the proposed (aquatic and terrestrial) and registered uses, the U.S. population may be 

exposed to topramezone via food (corn, fish, and shellfish) and drinking water. In addition, there 

may be incidental oral, dermal, and inhalation exposure from the registered turf use (homeowner 

use allowed) and the proposed aquatic use. Post-application residential exposures resulting from 

recreational swimming in treated water can be expected for adults and children in the absence of 

label restrictions. In the occupational setting, applicators may be exposed via the dermal and 

inhalation routes while handling the pesticide for and during application. Dermal exposure is 

also anticipated for workers re-entering treated areas. 

Topramezone is a member of the class of herbicides known as 4-hydroxyphenylpyruvate 

dioxygenase (HPPD) inhibitors. Inhibition of the enzyme HPPD results in decreased carotenoid 

synthesis and ultimately bleaching of target plants. In mammals, HPPD is involved in the 

catabolism of the amino acid tyrosine, and its inhibition causes blood levels of tyrosine to rise; a 

condition known as tyrosinemia. Some of the toxicities resulting from tyrosinemia in laboratory 

animals include ocular, developmental, liver, and kidney effects. Topramezone exhibits a 

mammalian toxicity profile that is consistent with HPPD inhibition.

The primary target organs affected following oral administration of topramezone in animal 

toxicity studies were the eyes, thyroid, pancreas, and liver. The most sensitive species was the 

rat, and in rats and dogs, males were more sensitive than females. The effects on the eyes in 

chronic toxicity studies consisted of pannus (vascularization) and keratitis (cloudiness) of the 

cornea in both sexes. Hypertrophy and hyperplasia of the thyroid, hypertrophy, and focal 

necrosis of the liver, and degeneration of the pancreas were among the histopathology findings 

reported across different subchronic and chronic studies in rats and dogs. Results of chronic 

toxicity studies in dogs, mice, and rats also suggest decrements in body weights, body-weight 

gains, and food utilization (dogs only).

There was evidence for increased susceptibility following in utero exposures to rats and rabbits. 

In rabbits, fetal abnormalities including supernumerary thoracic vertebrae and supernumerary 
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13th rib were observed in the presence of maternal toxicity in six of eight developmental toxicity 

studies conducted in two different strains. In rats, developmental effects consisting of skeletal 

variations occurred in the presence of maternal toxicity. Increased maternal serum levels of 

tyrosine were reported in several developmental toxicity studies (several in rabbits and one in 

mice), consistent with the proposed mode of action for topramezone involving HPPD inhibition. 

In the rat two-generation reproductive toxicity study, there was no evidence of increased pre- or 

post-natal susceptibility; offspring effects occurred in the presence of maternal effects. The 

offspring effects consisted of (1) decreased pup body weight/body-weight gain in F2 (both sexes) 

and (2) increased time to preputial separation (F1 males). Maternal effects were consistent with 

HPPD inhibition (decreased body weights and body-weight gains, increased thyroid and kidney 

weights, and microscopic findings in the eyes, kidneys, and thyroid). No reproductive effects 

were reported.

Topramezone did not show any evidence of neurotoxicity in the acute (ACN) or subchronic 

(SCN) neurotoxicity studies, but in a rat developmental neurotoxicity (DNT) study, where dosing 

with topramezone took place during the prenatal as well as postnatal time periods, there was 

evidence for increased qualitative susceptibility. In the maternal animals, toxicity was limited to 

corneal opacity, whereas effects in the offspring included neurobehavioral and neuropathological 

changes. Offspring neurobehavioral effects consisted of a decreased auditory startle reflex at 

postnatal day 24 in both sexes (20-30%) and at postnatal day 60 for males (55%). There were 

also mild decreases in offspring absolute brain weights and neuropathological effects involving 

decreased brain morphometric measurements (e.g., hippocampus, and parietal cortex). 

Topramezone is classified as “not likely to be carcinogenic to humans at doses that do not alter 

rat thyroid hormone homeostasis.” The Cancer Assessment Review Committee (CARC) has 

determined that the thyroid tumors arise through a non-linear mode of action, and the chronic 

reference dose (cRfD) is expected to be protective of alterations in hormone homeostasis or that 

may result in thyroid tumor formation. Mutagenicity studies conducted on technical 

topramezone and its major metabolites did not demonstrate any mutagenic potential.

Dose-Response Assessment: The acute population-adjusted dose (aPAD) for the general U.S. 

population including infants and children was estimated at 0.008 mg/kg/day based on the lowestobserved adverse-effect level (LOAEL) of 8 mg/kg/day for offspring effects in a rat DNT study. 

A different aPAD for females (13-49 years old) was estimated at 0.005 mg/kg/day based on the 

no-observed adverse-effect level (NOAEL) of 0.5 mg/kg/day for developmental effects in a 

rabbit prenatal developmental toxicity study. The chronic population-adjusted dose (cPAD) 

estimated at 0.004 mg/kg/day was based on the NOAEL of 0.4 mg/kg/day from a rat chronic 

toxicity study. The point of departure (POD) for short- and intermediate-term dermal, inhalation 

and incidental oral risk assessments was 0.4 mg/kg/day based on the NOAEL in a rat twogeneration reproductive toxicity study. Since an oral study was used, a dermal-absorption factor 

(DAF) of 2.6% estimated from a rat dermal-penetration study was used for the dermal risk 

assessment and 100% absorption was assumed for inhalation exposures. The level of concern 

(LOC) for occupational/ residential dermal and inhalation exposures and residential incidental 

oral exposures are for margins of exposure (MOEs) <100. 

Food Quality Protection Act (FQPA) Decision: Based on the evaluation of the topramezone 

toxicity and exposure databases, it is recommended that the 10X FQPA Safety Factor (SF) be 

retained in the form of a database uncertainty factor for the acute dietary scenario for the general
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U.S. population including infants and children (for lack of a NOAEL), and be reduced to 1X for 

all other scenarios. This recommendation is based on the toxicity database with a DNT study 

being adequate for assessing the potential for increased pre- and postnatal susceptibility. 

Although there was qualitative evidence for susceptibility, clear NOAELs and LOAELs were 

established for developmental effects and the endpoints of concern (developmental and target 

organ toxicity) were used for assessing risks for appropriate populations of concern. 

Additionally, the dietary and residential exposure analyses are conservative in nature designed to 

provide conservative, health-protective estimates. 

Dietary Risk Estimates (Food + Drinking Water): Acute and chronic aggregate dietary (food + 

drinking water) exposure and risk assessments were conducted using the Dietary Exposure 

Evaluation Model software with the Food Commodity Intake Database (DEEM-FCID) Version 

3.16, which uses food consumption data from the U.S. Department of Agriculture’s National 

Health and Nutrition Examination Survey, What We Eat in America, (NHANES/WWEIA). The 

acute and chronic dietary assessments assumed tolerance-level residues, 100% crop treated, 

default processing factors (DEEM ver. 7.81), and modeled drinking water estimates. The 

majority of the acute and chronic dietary exposure estimates were based on drinking water 

residues from the proposed non-crop aquatic use. The resulting acute and chronic dietary 

exposure and risk estimates (food + drinking water) did not exceed the respective PAD for the 

general U.S. population or any subgroups and thus are below HED’s LOC. 

Residential (Non-Occupational) Exposure and Risk Assessment: Residential applicator 

(handler) scenarios were not assessed for the proposed uses due to the specific label directions 

for the proposed aquatic use (ponds, lakes, and reservoirs) and the specific use sites for the

terrestrial use (roadsides, utility and railroads rights-of-ways, industrial sites, and tank farms). 

Post-application residential exposures from recreational swimming activities were assessed for 

short-term only because such recreational activity is expected to be episodic. Moreover, shortterm risk assessment would be protective of intermediate-term exposures since both durations are 

based on the identical toxicity endpoint. The resulting MOE estimates are >100 and thus below 

HED’s LOC.

Aggregate-Risk Estimates: Acute and chronic aggregate risks are based only on dietary 

exposure from food and drinking water sources. Therefore, acute and chronic aggregate risks to 

topramezone are not of concern to HED (see dietary assessment above). A cancer aggregate-risk 

assessment was not performed because topramezone is classified as “not likely to be 

carcinogenic to humans at doses that do not alter rat thyroid hormone homeostasis” and doses at 

or below the cRfD are not expected to alter thyroid hormone homeostasis.

Short-term aggregate risk assessment was performed that includes exposure via food, water, and 

the residential use (proposed or currently registered) that resulted in the highest estimated 

exposure. For adults and children, activities associated with the currently registered residential 

turf use resulted in the highest residential exposure estimate. When all exposures were 

aggregated and compared to an appropriate estimate of hazard, all resulting MOE estimates were 

>100 and thus below HED’s LOC.

Occupational Exposure and Risk Assessment: Occupational handlers may be potentially 

exposed to topramezone during mixing/loading and applying activities associated with the 

proposed aquatic and terrestrial use. Estimated occupational handler dermal and inhalation risk 
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estimates are below HED’s LOC provided handlers use (1) baseline personal-protective 

equipment (PPE) including long-sleeved shirts and chemical-resistant gloves; and (2) 

engineering controls (closed system) are used for mixing/loading in support of aerial application 

for the aquatic use.

Occupational post-application exposure associated with the aquatic use is likely limited to 

persons who come in contact with treated water. A quantitative risk assessment was deemed 

unnecessary given the large MOE estimates for residential post-application recreational 

swimming activities. In the case of the terrestrial use, the post-application MOEs are not of 

concern; therefore, the restricted-entry interval (REI) for topramezone is based on the acute 

toxicity categories. Topramezone has been classified as having low acute toxicity (Toxicity 

Category III or IV) via the oral, dermal, and inhalation routes of exposure. It is a slight eye and 

dermal irritant (Toxicity Category III and IV), but is not a dermal sensitizer. Therefore, the 

Worker Protection Standard (WPS) interim REI of 12 hours is adequate to protect workers from 

post-application exposures to topramezone.

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.”

1

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

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

the Pesticide Handlers Exposure Database Version 1.1 (PHED 1.1); the Agricultural Handler 

Exposure Task Force (AHETF) database; the Outdoor Residential Exposure Task Force 

(ORETF) database; the Agricultural Re-entry Task Force (ARTF) database; and MRID 

48379401, are subject to ethics review pursuant to 40 CFR 26, have received that review, and are 

compliant with applicable ethics requirements. For certain studies, that 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: http://www.epa.gov/pesticides/science/handler-exposuredata.html and http://www.epa.gov/pesticides/science/post-app-exposure-data.html.

2.0 HED Recommendations

Provided the petitioner submits revised Sections B and F (see below), HED concludes that the 

toxicity, residue chemistry, and occupational/residential exposure databases support registration of 

the proposed non-crop aquatic use, the maximum application rate increase for the non-crop 

terrestrial use, and the establishment of the tolerances listed in Section 2.2. 

2.1 Data Deficiencies

Prior to Registration: Revised Section F - see Section 2.2.2; Revised Section B - see Section 

2.3. 

 

1

 (http://www.hss.energy.gov/nuclearsafety/env/guidance/justice/eo12898.pdf).
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Data that may be Necessary to Support Future Uses 

Residue Chemistry:

If, in the future, the petitioner alters the aquatic application scenario such that concentrations in 

water are >50 ppb, then fish/shellfish metabolism and/or magnitude of the residue studies may be 

required. In addition, HED notes that a poultry feeding study has not been submitted, and these 

data may be required to support future uses (residues of parent and the metabolite M670H02 

should be monitored). 

Occupational Residential Exposure: 

A dislodgeable foliar residues (DFR) study has not been submitted and is unnecessary for the 

proposed uses; however, future proposed uses may require the submission of these data. 

Toxicology:

For this action, the Hazard and Science Policy Council (HASPOC) waived the requirement for a 

28-day rat inhalation toxicity study. However, this study may be required for future actions that 

significantly increase occupational or residential inhalation exposures. 

2.2 Tolerance Considerations

2.2.1 Enforcement Analytical Method

HED concludes that the BASF method D0104 is appropriate for enforcement of the HEDrecommended topramezone livestock meat byproduct and fish/shellfish tolerances. In brief, 

homogenized samples are extracted in water, acidified with HCl, and partitioned with 

dichloromethane. The organic phase is collected and partitioned with ammonium formate (pH 10) 

with the aqueous phase collected and analyzed by liquid chromatography with tandem mass 

spectroscopy (LC/MS/MS). 

2.2.2 Recommended Tolerances

Table 2.2.2 is a summary of the proposed and HED-recommended tolerances for residues of 

topramezone per se (revised Section F is requested). In accordance with the most recent 

guidance concerning tolerance expressions, HED recommends that the tolerance expression for 

180.612(a)(1) be changed as indicated below. A revised Section F should be submitted which 

specifies the new tolerance expression and the HED recommended commodity definitions and 

tolerance levels. With the establishment of the tolerances indicated in Table 2.2.2, the currently 

established kidney (cattle, goat, horse, and sheep) and liver (cattle, goat, horse, and sheep) 

tolerances should be deleted. 

180.612(a) (1) Tolerances are established for residues of the herbicide topramezone, including its 

metabolites and degradates, in or on the commodities listed below. Compliance with the following

tolerance levels is to be determined by measuring only topramezone ([3-(4,5-dihydro-3-isoxazolyl)-2-

methyl-4-(methylsulfonyl)phenyl](5-hydroxy-1-methyl-1H-pyrazol-4-yl)methanone) in or on the 

following commodities:
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Table 2.2.2. Tolerance Summary.

Commodity Proposed 

Tolerance (ppm)

HED-Recommended 

Tolerance (ppm) Comments

fish 0.05 --

Revised commodity definition is 

requested.

fish-freshwater finfish -- 0.05

fish-saltwater finfish -- 0.05

shellfish 0.05 --

fish-shellfish, crustacean -- 0.05

fish-shellfish, mollusk -- 0.05

cattle, meat byproducts -- 0.80

These tolerances are recommended as a 

result of the increased livestock dietary 

burdens associated with the proposed use. 

goat, meat byproducts -- 0.80

horse, meat byproducts -- 0.80

sheep, meat byproducts -- 0.80

hog, meat byproducts -- 0.40

poultry, meat byproducts -- 0.02

2.2.3 Revisions to Petitioned-For Tolerances

Based on the livestock dietary burdens resulting from all proposed/registered uses, HED 

determined that the meat byproduct tolerances listed in Table 2.2.2 are appropriate. With the 

establishment of these tolerances, the currently established kidney (cattle, goat, horse, and sheep) 

and liver (cattle, goat, horse, and sheep) tolerances should be deleted as it is now general policy 

to establish meat byproduct tolerances rather than separate liver and kidney tolerances 

(Chemistry Science Advisory Council (ChemSAC); min_494.12-Jan-2011). 

2.2.4 International Harmonization

There are no Codex or Mexican maximum residue limits (MRLs) in/on fish/shellfish. Canada 

has established MRLs for residues of topramezone per se in/on the following: liver (cattle, goat, 

horses, and sheep) - 0.15 ppm; meat byproducts (except liver; cattle, goat, horses, and sheep) -

0.05 ppm; and hog meat byproducts - 0.05 ppm. Considering the proposed/registered 

topramezone uses, HED concludes that the Canadian MRLs are too low to permit harmonization

at this time.

 

2.3 Label Recommendations

HED concludes that the proposed labels are adequate provided the revisions indicated in 

Sections 2.3.1 and 2.3.2 are incorporated (revised Section B is requested). HED notes that all 

revisions are for the aquatic label Oasis®(EPA Reg. No. 7969-xxx).

2.3.1 Recommendations from Residue Reviews

HED requests the proposed Oasis®7969-xxx label (aquatic label) be revised as follows (revised 

Section B is requested): (1) text in the label relating to restrictions concerning the use of treated 

water for irrigation purposes should be changed from “food crop” to “food/feed crops” and from 

“non-food-crop” to “non-food/feed-crop”; (2) the text specifying that an irrigation intake may be 

turned back on if the concentration “at the intake” has dropped to ≤1 ppb should be changed to 

indicate that the irrigation intake may be turned back on provided the concentration “in the 
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treated area” has dropped to ≤1 ppb; (3) the section concerning application to flowing water 

“including moving water canals” should be changed to indicate “including non-irrigation moving 

water canals”; (4) the section concerning application to dewatered irrigation canals should 

indicate that residues must drop to ≤1 ppb at the most downstream end of the treated area prior to 

the use of the water for irrigation purposes; and (5) addition of a statement noting that potable 

use of treated water is not permitted until the concentration has dropped to ≤45 ppb.

2.3.2 Recommendations from Occupational Assessment

HED requests the proposed Oasis®7969-xxx label (aquatic label) be revised as follows (revised 

Section B is requested): (1) for in-water applications, the label should be changed to indicate 

that applicators must wear long-sleeved shirt; long pants; chemical-resistant gloves (Category A) 

and shoes plus socks; and (2) for in-water applications, mixer loaders in support of aerial 

application must use engineering controls (i.e., closed system).

3.0 Introduction

Topramezone is a broad-spectrum post-emergence herbicide (triketone class; group 27 

herbicide). Topramezone inhibits carotenoid biosynthesis in susceptible plants (HPPD inhibitor). 

In the absence of carotene, chlorophyll is rapidly degraded in sunlight. The chemical structure

and nomenclature of technical grade topramezone are presented in Tables 3.1.

3.1 Chemical Identity

Table 3.1. Topramezone Nomenclature.

Structure

Common name topramezone

Company experimental name BAS 670 H

IUPAC name [3-(4,5-dihydro-1,2-oxazol-3-yl)-4-mesyl-o-tolyl](5-hydroxy-1-methyl-1H-pyrazol-4-

yl)methanone

CAS name [3-(4,5-dihydro-3-isoxazolyl)-2-methyl-4-(methylsulfonyl)phenyl](5-hydroxy-1-methyl-1Hpyrazol-4-yl)methanone

CAS # 210631-68-8

End-use product/EP emulsifiable concentrate

3.2 Physical/Chemical Characteristics

The physical/chemical properties of topramezone are summarized in Appendix B. Based on its 

low vapor pressure of 7.5 x 10-13 mmHg, topramezone is not expected to be particularly volatile, 

and based on its low octanol:water partition coefficient (Log Kow) of -1.52 at pH 7.0, it is not 

expected to significantly partition into fatty tissue while being relatively water soluble.

3.3 Pesticide Use Pattern

Registered Uses: Topramezone is currently registered for application to golf courses, sod farms, O

N

N

N

CH3

OH S

O CH3

O O

CH3
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residential turfgrass, field corn, popcorn, sweet corn, and corn grown for seed. Topramezone is 

also registered for application to numerous non-crop terrestrial sites. 

Proposed Uses: The petitioner is proposing an increased application rate for the currently

registered non-crop terrestrial-application scenario (this use does not concern application to turf) 

and is proposing non-crop aquatic-application. Table 3.3.1 is a summary of the proposed uses. 

The proposed labels include the following general information, restrictions, and information 

concerning PPE/REI: 

General Information Concerning the Non-crop Aquatic-Application (Oasis®label): The 

proposed label specifies the following general information: (1) consult the appropriate state or 

local pesticide and/or water authorities before applying this product in or around public waters. 

Permits and postings of treatment notification may be required by state or local public agencies; 

(2) for aerial application, apply in a minimum spray volume of 2 gallons per acre (GPA). For 

application by boat or with ground equipment to submerged, floating, or shoreline vegetation, 

use boom-type, backpack, or hydraulic handgun equipment; apply in a sufficient spray volume 

(up to 100 GPA) to provide uniform distribution of the spray particles over the treated vegetation 

while minimizing runoff; (3) do not apply through irrigation equipment; (4) a surfactant or 

methylated seed oil should be added to the spray solution for post-emergent foliar application 

and application to exposed sediment where some weed growth is present; (5) Oasis® may be 

applied to exposed sediments of dewatered areas of aquatic sites. Upon inundation, all label 

restrictions apply to the use of water from these treated areas; and (6) there are no restrictions on 

use of the treated water for potable use (human or livestock) or for recreational purposes 

including swimming and fishing.

Restrictions Concerning the use of Water Treated with Topramezone for Purposes of Irrigation 

(Oasis®label): The label includes the following restrictions concerning the use of treated water 

for purposes of irrigation: (1) do not apply to waters used for food-crop irrigation (except corn), 

unless the irrigation intakes can be shut off until concentrations are ≤1 ppb at the intake 

(concentrations may be determined using FasTEST or other analytical techniques); (2) corn - do 

not irrigate corn if concentrations in treated water exceeds 25 ppb; (3) non-food-crop irrigation -

consult BASF Corporation before irrigation if concentrations in treated water exceed 1 ppb; (4) 

do not use treated water for hydroponic farming until the concentrations are ≤1 ppb; (5) do not 

use treated water to irrigate greenhouse or nursery plants until concentrations are ≤1 ppb; and (6) 

rotational crops - areas previously irrigated with treated water may be planted with corn. For 

other food crops and in areas irrigated with treated water containing concentrations exceeding 1 

ppb, consult BASF Corporation for site-specific risk evaluations before planting rotational crops 

or other plants. 

PPE and REI for Non-crop Aquatic-Application (Oasis®label) and Non-crop TerrestrialApplication (Frequency®

label): Excluding in-water application, the proposed topramezone 

product labels direct handlers to wear long-sleeved shirt; long pants; chemical-resistant gloves 

(Category A); shoes plus socks; and goggles, face shield, or safety glasses. For in-water 

application, the proposed labels direct handlers to wear short-sleeved shirt, long pants; shoes plus 

socks; and chemical-resistant gloves [Category A]. 

The non-crop terrestrial label indicates a 12-hour REI for agricultural uses and, for 

nonagricultural uses, indicates that reentry is permitted once the spray solution has dried. The 
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Page 12 of 41

non-crop aquatic label does not specify a REI.

Conclusions: HED concludes that the proposed use directions are adequate provide the labels 

are revised as indicated in Section 2.3 (a revised Section B is requested). 
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Page 13 of 41

Table 3.3.1. Summary of Proposed Oasis®(7969-xxx) Use Directions.1

End-use Product App. 

Timing App. Rate Max. No. App. per Season

Max. Seasonal 

App. Rate Use Directions and Limitations

Non-crop Terrestrial-Application 

Frequency®; SC; 

2.8 lb ai/gal; 

EPA Reg. No. 7969-281

pre-/postemergent0.09-0.35 lb 

ai/acre not specified 0.35 lb ai/acre

-Application using ground (≥10 GPA) and aerial (≥2 GPA) equipment is permitted. 

-Spot application is also permitted using a spray solution containing 0.25-0.5% of the formulated product. 

-Only soil-directed applications are described for Christmas tree, conifer, and hardwood plantations and 

field-grown ornamentals. 

-Application to greenhouses and shadehouses is prohibited; do not apply to areas that may be grazed or cut 

for hay. 

Non-crop Aquatic-Application - in-water application (including submersed or floating weeds); flowing water application (including canals (slow moving))1

Oasis®SC;

2.8 lb ai/gal;

EPA Reg. No. 7969-xxx

pre-/postemergent

in-water 

concentration at 

application of 

20-50 ppb

not specified

in-water 

concentration at 

application of 20-

50 ppb

-Can be applied undiluted or diluted with water.

-The max. conc. that can be applied initially, and maintained through sequential application, is 50 ppb 

(application rate in lb ai/acre is based on calculation using the treated area and average depth). To maintain 

the desired conc., samples are collected/analyzed and additional product is added to raise the conc. to the 

desired level.

-Retreat the water to maintain the desired conc. for a min. of 60 days or until satisfactory weed control is 

achieved. 

-Boat and aerial application is permitted; application via a metering system is also describe for application to 

flowing water. 

Non-crop Aquatic-Application - shoreline and riparian areas within or adjacent to aquatic sites

Oasis®SC;

2.8 lb ai/gal;

EPA Reg. No. 7969-xxx

pre-/postemergent0.09-0.35 lb 

ai/acre not specified 0.35 lb ai/acre/year

-Dilute with water to achieve proper coverage of treated plants (include an adjuvant). 

-Sequential applications can be made throughout the growing seasons. 

-Boat, ground, and aerial application is permitted

Non-crop Aquatic-Application - foliar spot treatment

Oasis®SC;

2.8 lb ai/gal;

EPA Reg. No. 7969-xxx

pre-/postemergent

spray solution -

0.25-0.50% 

Oasis®

not specified 0.35 lb 

ai/acre/year

-To prepare the spray solution, thoroughly mix in water 0.25-0.50% Oasis®(adjuvant should be included). 

Spray coverage should be sufficient to moisten the leaves of the target vegetation but not to runoff. Ground 

and boat application is permitted

Non-crop Aquatic-Application - exposed sediment (including exposed sediment of dewatered irrigation canals)

Oasis®SC;

2.8 lb ai/gal;

EPA Reg. No. 7969-xxx

pre-/postemergent0.09-0.35 lb 

ai/acre not specified 0.35 lb ai/acre/year

-Dilute with water to achieve proper coverage of treated plants (include an adjuvant). 

-Sequential applications can be made throughout the growing seasons. 

-Ground application is permitted

-The proposed label indicates the following restrictions concerning the app. to dewatered irrigation canals: 

(1) only for use by Irrigation Districts in the western U.S. in canals that are seasonally filled and where the 

Irrigation District is aware of potential down-stream use of water and can ensure water is not used for 

irrigation purposes during the recharge or refill process; (2) app. by only Irrigation Districts, Irrigation Water 

Suppliers, or those applicators who are licensed or certified as aquatic pest control applicators and are 

authorized by the Irrigation District; (3) app. must be conducted a minimum of 14 days prior to reflooding. 

The initial flush of water during recharge or refill must not be used for irrigation purposes unless the conc. 

has been determined to be ≤1 ppb; and (4) after canals have been refilled with a continuous flow for a min. 

of 24 hours, canal water may then be used for irrigation purposes. 

1

 The application rate to flowing water is identical to that for other bodies of water.
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3.4 Anticipated Exposure Pathways

Based on the proposed and registered uses, the U.S. population may be exposed to topramezone 

in food (corn, fish, and shellfish) and water; in addition, the U.S. population may experience 

incidental oral, dermal, and/or inhalation exposure resulting from registered turf (homeowner 

application is permitted), golf course uses, and/or the proposed aquatic use (proposed label has 

no restrictions concerning the recreational use of treated water). In the occupational setting, 

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

application (dermal and inhalation). There is also potential for post-application exposure for 

workers re-entering treated areas (dermal; inhalation is anticipated to be negligible). 

4.0 Hazard Characterization/Assessment

Topramezone belongs to a class of herbicides that includes pyrasulfotole, mesotrione, and 

isoxaflutole. The herbicidal mode of action of these agents involves inhibition of HPPD, which 

eventually results in impairment of chlorophyll biosynthesis. In mammals, the HPPD-equivalent 

enzyme, tyrosine aminotransferase, is involved in the catabolism of the amino acid tyrosine, and 

its inhibition causes blood levels of tyrosine to rise; a condition known as tyrosinemia. Some of 

the toxicities resulting from tyrosinemia in laboratory animals include ocular, developmental, 

liver, and kidney effects.

4.1 Toxicology Studies Available for Analysis 

The toxicological database for topramezone is adequate for hazard characterization, toxicity 

endpoint selection, and FQPA safety factor evaluation. In the last risk assessment (Memo, K. 

Lowe et al., D388367; 02/12/2012), the only database deficiency noted was an immunotoxicity 

study (OPPTS 870.7800) as specified in 40 CFR Part 158 requirements. This study has yet to be 

submitted to the Agency and represents a pending data requirement for topramezone.

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

Following oral administration, radiolabeled topramezone was rapidly absorbed into the systemic 

circulation, with the highest plasma concentrations observed after 1 hour (the first time point 

measured). The estimated absorbed fraction, however, was only about 47% at the low dose 

tested of 10 mg/kg bw. Plasma elimination of radioactivity was biphasic, with the initial 

(primary) half-life estimate being about 5 hours and the terminal elimination half-life estimate 

being about 30 hours. The area under the plasma concentration curve (AUC) scaled more 

linearly with dose than it did with peak plasma levels. The majority of the dose was recovered 

within 48 hours in feces (73-91%) and urine (8-29%). Bile collected up to 48 hours post-dose 

accounted for 19-32% of the administered dose. Concentrations of radioactivity were 

consistently highest in liver followed by kidneys and, to some extent, in the thyroid. The parent 

chemical was the predominant compound identified in both urine (4.0-21.3% dose) and feces 

(66.3-91.7% dose). There were no apparent sex-dependent differences in ADME behavior 

noted.

4.3 Dermal Absorption

A DAF of 2.6% was used in the last risk assessment (memo, K. Lowe et al., 02/02/2012; 

D388367) based on the highest degree of skin penetration observed in a rat dermal penetration 

study. A DAF of 2.6% will be used to assess the potential risk associated with dermal exposures 
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to topramezone associated with the proposed uses.

4.4 Toxicological Effects

The effects observed following repeated oral exposures to topramezone are consistent with those 

expected from HPPD inhibition in mammals. In prenatal developmental toxicity studies (mouse 

and rabbit), where selected measured clinical parameters included serum measurements of 

tyrosine, orally administered topramezone resulted in dose-dependent increases in serum 

tyrosine, consistent with the induction of tyrosinemia. The elevated levels of tyrosine that may 

result in detrimental (adverse) effects have not been delineated. Therefore, this hazard 

characterization does not attempt to associate elevated levels of tyrosine to detrimental effects 

following topramezone administration.

The primary target organs affected following topramezone administration were the eyes, thyroid, 

and pancreas. The most sensitive species was the rat and, at least in rats and dogs, males were 

more sensitive than females. The effects on the eyes in chronic toxicity studies consisted of 

pannus (vascularization) and keratitis (cloudiness) of the cornea of both sexes. Hypertrophy and 

hyperplasia of the thyroid, hypertrophy and focal necrosis of the liver, and degeneration of the 

pancreas were among the histopathology findings reported across different subchronic and 

chronic studies in rats and dogs. Results of chronic toxicity studies in dogs, mice, and rats also 

suggest decrements in body weights, body-weight gains, and food utilization (dogs only). 

Inflammation of the urinary bladder was also noted in a dog subchronic-toxicity study.

There was evidence for increased prenatal susceptibility following in utero exposures to rats and 

rabbits. In six of eight developmental toxicity studies conducted in two different strains of 

rabbits, fetal abnormalities including supernumerary thoracic vertebrae and supernumerary 13th 

rib were observed in the presence of only increased maternal tyrosine blood level or body weight 

decrements toxicity. In the other two rabbit developmental studies, similar developmental 

effects were reported in the absence of any maternal toxicity. In rats, developmental effects 

consisting of skeletal variations occurred in the presence of maternal toxicity. Increased 

maternal serum levels of tyrosine were reported in several developmental toxicity studies 

(several in rabbits and one in mice), consistent with the proposed mode of action for 

topramezone involving HPPD inhibition. It should be noted that the fetal skeletal variations 

observed following exposure to topramezone have also been reported with other HPPD-inhibitor 

herbicides (e.g., mesotrione and isoxaflutole). 

In the rat two-generation reproductive toxicity study, there was no evidence of increased 

qualitative or quantitative pre- or postnatal susceptibility; offspring effects occurred in the 

presence of maternal effects. The offspring effects consisted of (1) decreased pup body 

weight/body-weight gain in F2 (both sexes) and (2) increased time to preputial separation (F1

males). Maternal effects were consistent with HPPD inhibition: decreased body weights and 

body-weight gains, increased thyroid and kidney weights, and microscopic findings in the eyes, 

kidneys, and thyroid. No reproductive effects were reported.

In a rat DNT study, where dietary dosing was performed during gestation and lactation, there 

was evidence of increased qualitative pre-/postnatal susceptibility. In the maternal animals, 

toxicity was limited to corneal opacity, whereas effects in the offspring included neurobehavioral 

and neuropathological changes. Offspring neurobehavioral effects consisted of a decreased 

auditory startle reflex at postnatal day 24 in both sexes (20-30%) and at postnatal day 60 for 

males (55%). There were also mild decreases in offspring absolute brain weights and 
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neuropathological effects involving decreased brain morphometric measurements (e.g., 

hippocampus, and parietal cortex). 

Topramezone did not show any evidence of neurotoxicity in the ACN or SCN studies. In the 

case of the ACN study, there was no toxicity reported up to the limit dose, while the effects in 

the SCN study were not neurotoxic in nature, but more consistent with those involving HPPD 

inhibition (e.g., corneal clouding, diffuse degeneration of the pancreas, and histopathological 

findings in the thyroid). 

In a rat dermal toxicity study with topramezone, toxicity was manifested as thyroid follicular cell 

hypertrophy with male rats being more sensitive than females.

Topramezone is classified as “not likely to be carcinogenic to humans at doses that do not alter 

rat thyroid hormone homeostasis.” The CARC determined that the thyroid tumors arise through 

a non-linear mode of action and the NOAEL (0.4 mg/kg/day) established for deriving the cRfD 

is not expected to alter thyroid hormone homeostasis nor result in thyroid tumor formation. 

Mutagenicity studies conducted with technical topramezone and its major metabolites did not 

demonstrate any mutagenic/genotoxic potential.

4.5 Safety Factor for Infants and Children [FQPA SF]

The 10X FQPA SF is retained for the acute dietary risk assessment for the U.S. general 

population including infants and children while being reduced to 1X for (1) the acute dietary risk 

assessment for females of child-bearing age (i.e., 13-49 years old), (2) the chronic dietary risk 

assessment for the U.S. general population, and (3) all non-dietary exposure scenarios. The 

rationale for these decisions is described below. 

4.5.1 Completeness of the Toxicology Database

The existing toxicology database for topramezone is adequate for FQPA SF evaluation. The 

following acceptable studies are available for FQPA consideration: developmental toxicity 

studies in mice, rats, and rabbits; a two-generation reproduction study in rats; ACN and SCN 

studies in rats; and a rat DNT study. A 10X FQPA safety factor (in the form of a database 

uncertainty factor) is not required for the lack of an immunotoxicity study since the PODs used 

for overall risk assessments are based on effects seen in target organs (e.g., eyes, thyroid, and 

liver) consistent with the actions of this chemical as an HPPD inhibitor. An immunotoxicity 

study is not likely to yield a lower POD and the preliminary results of the retrospective analyses 

provide strong support for not retaining the 10X FQPA SF as no immunotoxicity study available 

thus far has provided sensitive endpoints for use in deriving points of departure.

4.5.2 Evidence of Neurotoxicity 

There was no evidence of neurotoxicity or neuropathology to the adult nervous system either 

following a single oral administration to rats at the limit dose in the ACN study or following 

repeated dietary administration to rats in the SCN study.

In the DNT study, maternal effects were limited to corneal opacity and there was no evidence of 

neurotoxicity or neuropathology in the maternal animals. The effects in the offspring were 

neurobehavioral as well as neuropathological, consisting of a decreased auditory startle reflex at 

postnatal day 24 in both sexes (20-30%) and at postnatal day 60 for males (55%), mild decreases 
Topramezone Human-Health Risk Assessment DP#s 400310, 404014

Page 17 of 41

in absolute brain weights, and decreased brain morphometric measurements (e.g., hippocampus, 

and parietal cortex). 

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

In the prenatal developmental toxicity study with rats, there was evidence for increased 

qualitative, but not quantitative, susceptibility in the fetuses. Qualitative susceptibility was 

demonstrated by the occurrence of decreased fetal body weight and increased incidences of 

skeletal variations in the presence of decreased body weight gain in the maternal animals.

In six of eight rabbit studies, there was evidence for increased qualitative susceptibility. In the 

does, maternal toxicity was characterized as decreases in body weight, body weight gain, and 

food consumption, all in the presence of increased serum levels of tyrosine. In the fetuses, 

developmental toxicity was manifested as increased incidences of visceral findings (i.e., absent 

kidney and ureter) and/or multiple skeletal variations (i.e., delayed ossification, supernumerary 

13th rib and/or 27th presacral vertebrae). In two studies, skeletal variations were observed at high 

doses in the absence of any maternal toxicity.

In the two-generation reproduction study with rats, there was no evidence of increased 

susceptibility. Offspring toxicity was characterized as decreased pup weight and weight gain in 

F2 male and female pups and increased time to preputial separation in the F1 males. These 

effects were observed in the presence of parental/systemic toxicity that included (1) decreased 

body weight, (2) decreased body-weight gain in males, (3) increased thyroid and kidney weights 

of both sexes, and (4) microscopic findings in the eyes, kidney, and thyroid of both sexes.

In the DNT study, there was evidence for qualitative susceptibility. In the maternal animals, 

toxicity was limited to corneal opacity whereas effects in the offspring manifested as (1) 

neurobehavioral changes (decreased auditory startle reflex), (2) decreases in absolute brain 

weight, and (3) decreases in brain morphometric measurements (e.g., hippocampus, and parietal 

cortex). 

4.5.4 Residual Uncertainty in the Exposure Database

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

exposure analyses are conservative in nature. The dietary exposure assessment uses tolerancelevel residues and assumes 100% crop treated. The residential exposure assessment uses 

chemical-specific turf transferable residue data and the 2012 Residential Standard Operating 

Procedures (SOPs) and is considered health-protective.

4.6 Toxicity Endpoints and Points of Departure Selections

4.6.1 Dose-Response Assessment

Acute dietary for the general population including infants and children

HED has selected the offspring LOAEL of 8 mg/kg/day from the DNT study as the endpoint of 

concern for this exposure scenario and population. The LOAEL is based on decreased auditory 

startle reflex, decreases in brain weight, and brain morphometric parameters at the lowest dose 

tested. In this study, the offspring were exposed to the chemical in utero and during the lactation 

period (i.e., postnatally). Consequently, it is presumed that the effects of concern could manifest 
Topramezone Human-Health Risk Assessment DP#s 400310, 404014

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after a single exposure anytime during the dosing regimen (i.e., either pre- or postnatal 

exposure). A 1000-fold factor was used for deriving the aRfD for this exposure scenario. In 

addition to the conventional 100X UF (10X inter-and 10X intra species factors), the 10X FQPA 

SF was retained in the form of a UFL (i.e., LOAEL-to-NOAEL extrapolation) because a LOAEL 

was selected for risk assessment. Thus, the aRfD and aPAD are equivalent at 0.008 mg/kg body 

weight.

Acute dietary for females of childbearing age (13-49 years old)

HED has selected the developmental NOAEL of 0.5 mg/kg/day from the developmental toxicity 

study in rabbits as the endpoint of concern for this exposure scenario and population. This 

NOAEL is based on increased skeletal variations observed in the fetuses following in utero

exposures to rabbits at 5 mg/kg/day (LOAEL). The in utero effects are the most sensitive 

endpoint for this sub-population (potentially pregnant females). The conventional 100-fold 

factor (10X inter- and 10X intra-species) was applied to the NOAEL. The FQPA SF of 10X was 

not retained for this exposure scenario for the following reasons: (1) the toxicology database is 

complete, (2) there were no residual uncertainties for pre-and or postnatal susceptibility, and (3) 

developmental effects are used as the endpoint of concern for this scenario. Thus, the aRfD and 

aPAD for females of childbearing age are equivalent at 0.005 mg/kg body weight.

Chronic dietary (all populations)

HED has selected the NOAEL of 0.4 mg/kg/day from the chronic toxicity/carcinogenicity study 

with rats for this exposure scenario. This NOAEL is based on increased incidences of corneal 

opacity, decreased body weight and body-weight gains in males, and histopathological 

evaluations in the thyroid, pancreas, and eyes of both sexes observed at 3.6 mg/kg/day (LOAEL). 

This endpoint/study is appropriate for this exposure scenario since the effects were observed in 

the most sensitive species following chronic exposure. The conventional 100-fold factor (10X 

inter- and 10X intra-species) was applied to the NOAEL (0.4 mg/kg/day). The FQPA SF was 

not retained for this exposure scenario since the toxicology database is complete and there were 

no residual uncertainties for pre-and or postnatal susceptibility. Thus, the cRfD and cPAD are 

equivalent at 0.004 mg/kg bw/day.

Short- and intermediate-term incidental oral

HED has selected the NOAEL of 0.4 mg/kg/day from the two-generation reproduction study for 

this exposure scenario. The NOAEL of 0.4 mg/kg/day is based on decreases in body weights 

and body-weight gains in the F2 generation offspring and increased time to preputial separation 

in the F1 male offspring seen at 4.2 mg/kg/day (LOAEL). These effects were observed in the 

offspring following approximately 13 weeks of treatment. Therefore, they are appropriate for 

the population subgroup (infants and children) and exposure duration (short- and intermediateterm) of concern. This POD addresses concern for (1) the fetal effects observed in the 

developmental toxicity study in rabbits (LOAEL = 5 mg/kg/day), (2) the offspring effects 

observed in the DNT study (LOAEL = 8 mg/kg/day), and (3) the effects observed in the SCN 

study (LOAEL = 4.2 mg/kg/day)

A MOE of 100, which includes the 10X inter- and 10X intra-species factors is adequate for this 

exposure scenario. The FQPA SF is reduced to 1X since (1) the toxicology database is complete, 

(2) there are no residual uncertainties for pre-and or postnatal susceptibility, and (3) the toxicity 

seen in the target organs is the endpoint of concern for this scenario.
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Short- and intermediate-term dermal

HED has selected the parental/systemic NOAEL of 0.4 mg/kg/day from the two-generation 

reproduction study. This NOAEL is based on decreases in body weights and body-weight gains 

in males; effects on the eyes (cornea opacity, cataracts, enlarged eye bulb, and chronic keratitis) 

and kidneys (increased kidney weights and pelvic dilatation) in both sexes; and effects on the 

thyroid (increased thyroid weights in males and flaky colloid in both sexes) at 4.2 mg/kg/day. 

This POD addresses concern for (1) the fetal effects observed in the developmental toxicity study 

in rabbits (LOAEL = 5 mg/kg/day), (2) the offspring effects observed in the DNT study (LOAEL 

= 8 mg/kg/day), and (3) the effects observed in the SCN study (LOAEL = 4.2 mg/kg/day). 

The available 28-day dermal toxicity study in rats was not selected since this study did not 

evaluate the developmental potential following dermal exposures to topramezone. 

Since an oral study was selected for the dermal endpoint, the DAF of 2.6% should be used to 

estimate a dermal-equivalent dose. Based on a DAF of 2.6%, the equivalent dermal NOAEL 

would be 15.4 mg/kg/day (0.4 mg/kg/day 0.026).

A MOE of 100, which includes the 10X inter- and 10X intra-species factors is adequate for this 

exposure scenario. The FQPA SF is reduced to 1X since (1) the toxicology database is complete, 

(2) there are no residual uncertainties for pre-and or postnatal susceptibility, and (3) the toxicity 

seen in the target organs is the endpoint of concern for this scenario.

Short- and intermediate-term inhalation

HED has selected the parental/systemic NOAEL of 0.4 mg/kg/day from the two-generation 

reproduction study. This NOAEL is based on decreases in body weights and body-weight gains 

in males; effects on the eyes (cornea opacity, cataracts, enlarged eye bulb, and chronic keratitis) 

and kidneys (increased kidney weights and pelvic dilatation) in both sexes; and effects of the 

thyroid (increased thyroid weights in males and flaky colloid in both sexes) at 4.2 mg/kg/day. 

This POD addresses concern for (1) the fetal effects observed in the developmental toxicity study 

in rabbits (LOAEL = 5 mg/kg/day), (2) the offspring effects observed in the DNT study (LOAEL 

= 8 mg/kg/day), and (3) the effects observed in the SCN study (LOAEL = 4.2 mg/kg/day). 

Since an oral dose was selected, 100% absorption was assumed via the inhalation route. 

Topramezone was placed in Toxicity Category IV for acute inhalation toxicity and has a low 

vapor pressure (7.5 x 10-13 mmHg). The HASPOC met on December 19th, 2012 (TXR 

#0056531) to decide on the need for a 28-day rat inhalation toxicity study. The committee’s 

decision does not require a 28-day inhalation toxicity study at this time.

A MOE of 100, which includes the 10X inter- and 10X intra-species factors is adequate for this 

exposure scenario. The FQPA SF is not retained since (1) the toxicology database is complete, 

(2) there are no residual uncertainties for pre-and or postnatal susceptibility, and (3) the toxicity 

seen in the target organs is the endpoint of concern for this scenario.

4.6.2 Recommendation for Combining Routes of Exposure for Risk Assessment

The Agency must consider risks from individual routes of exposure (oral, dermal, and inhalation) 

and perform an aggregate risk assessment if a common toxicity endpoint is established across 

different routes of exposure. Since short- and intermediate-term dermal, inhalation, and 
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incidental oral endpoints are based on the same toxicity endpoint, exposures via these routes may 

be aggregated.

4.6.3 Cancer Classification and Risk Assessment Recommendation

Topramezone is classified as “not likely to be carcinogenic to humans at doses that do not alter 

rat thyroid hormone homeostasis.” The CARC has determined that the thyroid tumors arise 

through a non-linear mode of action and the NOAEL (0.4 mg/kg/day) established for deriving 

the cRfD is not expected to alter thyroid hormone homeostasis nor result in thyroid tumor 

formation. 

4.6.4 Summary of Toxicity Endpoint and POD Selection 

The PODs, UFs, and toxicity endpoints are presented in Table 4.5.1 (dietary and nonoccupational assessments) and Table 4.5.2 (occupational assessments).

Table 4.5.1a. Summary of Toxicology Endpoints and PODs for Topramezone in Dietary and Residential Risk 

Assessment.

Exposure

Scenario POD

Uncertainty/ FQPA Safety 

Factors or LOC for Risk 

Assessment

Study and Toxicological Effects

Acute Dietary

(General population 

including infants 

and children)

LOAEL = 8 mg/kg bw UF = 100X

(for inter- and intra-species 

extrapolation)

FQPA SF = 10X

aRfD = 0.008 mg/kg bw

aPAD = 0.008 mg/kg bw

Developmental Neurotoxicity Study in Rats

Offspring LOAEL = 8 mg/kg bw based on 

decreased maximum auditory startle reflex 

response, decreased brain weights, and changes 

in brain morphology.

Acute Dietary 

(Females 13-49 

years old)

NOAEL = 0.5 mg/kg/day UF = 100X

(for inter- and intra-species 

extrapolation)

FQPA SF = 1X

aRfD = 0.005 mg/kg/day

aPAD = 0.005 mg/kg/day

Developmental Toxicity Study in Rabbits

Developmental LOAEL = 5 mg/kg/day based 

on alterations in skeletal ossification sites and 

increased number of pairs of ribs.

Chronic Dietary

(All populations)

NOAEL = 0.4 mg/kg/day UF = 100X

(for inter- and intra-species 

extrapolation)

FQPA SF = 1X

cRfD = 0.004 mg/kg/day

cPAD = 0.004 mg/kg/day

Chronic toxicity/Carcinogenicity Study in Rats

LOAEL = 3.6 mg/kg/day based on increased 

incidences of corneal opacity, decreased body 

weight and body-weight gains in males and 

histopathological evaluations in the eyes, 

thyroid and pancreas of both sexes.

Incidental Oral

(Short- and 

Intermediate-Term)

NOAEL = 0.4 mg/kg/day Residential LOC for MOE = 

100

Two-Generation Reproduction Study in Rats

Offspring LOAEL = 4.2 mg/kg/day based 

decreases in body weights and body-weight 

gains in the F2 generation offspring and 

increased time to preputial separation in the F1

male offspring.

Short- and 

Intermediate-Term, 

Dermal 

Oral NOAEL = 0.4 

mg/kg/day

(DAF = 2.6%)

Residential LOC for MOE = 

100

Two-Generation Reproduction Study in Rats

Parental LOAEL = 4.2 mg/kg/day based on 

decreased body weight, body-weight gain in 

males, increased thyroid and kidney weights of 

both sexes, and microscopic findings in eyes, 

kidney and thyroid of both sexes.
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Table 4.5.1a. Summary of Toxicology Endpoints and PODs for Topramezone in Dietary and Residential Risk 

Assessment.

Exposure

Scenario POD

Uncertainty/ FQPA Safety 

Factors or LOC for Risk 

Assessment

Study and Toxicological Effects

Short- and 

Intermediate-Term 

Inhalation

Oral NOAEL = 0.4 

mg/kg/day

(inhalation absorption = 

100%)

Residential LOC for MOE = 

100

Two Generation Reproduction Study in Rats

Parental LOAEL = 4.2 mg/kg/day based on 

decreased body weight, body-weight gain in 

males, increased thyroid and kidney weights of 

both sexes, and microscopic findings in eyes, 

kidney and thyroid of both sexes.

Cancer 

(Oral, dermal, 

inhalation)

In accordance with the 2005 EPA Guidelines for Carcinogen Risk assessment, topramezone was classified as 

“not likely to be carcinogenic to humans at doses that do not alter rat thyroid hormone homeostasis.” The CARC 

determined that the thyroid tumors arise through a non-linear mode of action and the NOAEL (0.4 mg/kg/day) 

established for deriving the cRfD is not expected to alter thyroid hormone homeostasis nor result in thyroid tumor 

formation.

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

of extrapolation to determine risk associated with lower environmentally relevant human exposures. NOAEL = no-observed adverse-effect level. 

LOAEL = lowest-observed adverse-effect level. UF = uncertainty factor. FQPA SF = FQPA Safety Factor. PAD = population-adjusted dose (a 

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

Table 4.5.2. Summary of Toxicology Endpoints and PODs for Topramezone in Occupational Risk Assessment.

Exposure

Scenario

Dose Used in Risk 

Assessment, UF

FQPA SF and LOC 

for Risk Assessment Study and Toxicological Effects

Short- and IntermediateTerm, Dermal Oral NOAEL = 0.4 

mg/kg/day

(DAF = 2.6%)

Occupational LOC 

for MOE = 100

Two-Generation Reproduction Study in Rats

Parental LOAEL = 4.2 mg/kg/day based on 

decreased body weight, body weight gain in 

males, increased thyroid and kidney weights of 

both sexes, and microscopic findings in eyes, 

kidney and thyroid of both sexes.

Short- and IntermediateTerm InhalationOral NOAEL = 0.4 

mg/kg/day

(inhalation absorption = 

100%)

Occupational LOC 

for MOE = 100

Two-Generation Reproduction Study in Rats

Parental LOAEL = 4.2 mg/kg/day based on 

decreased body weight, body weight gain in 

males, increased thyroid and kidney weights of 

both sexes, and microscopic findings in eyes, 

kidney and thyroid of both sexes.

Cancer 

(Oral, dermal, inhalation)

In accordance with the 2005 EPA Guidelines for Carcinogen Risk assessment, topramezone was 

classified as “not likely to be carcinogenic to humans at doses that do not alter rat thyroid hormone 

homeostasis.” The CARC determined that the thyroid tumors arise through a non-linear mode of 

action and the NOAEL (0.4 mg/kg/day) established for deriving the cRfD is not expected to alter 

thyroid hormone homeostasis nor result in thyroid tumor formation.

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

of extrapolation to determine risk associated with lower environmentally relevant human exposures. NOAEL = no-observed adverse-effect level. 

LOAEL = lowest-observed adverse-effect level. UF = uncertainty factor. FQPA SF = FQPA Safety Factor. MOE = margin of exposure. LOC = 

level of concern.

5.0 Dietary Exposure and Risk Assessment 

5.1 Residues of Concern Summary and Rationale

Topramezone metabolism studies in corn, ruminant, and poultry were previously submitted and 

reviewed (D310772, G. Kramer, 05/112005). These studies yielded similar results in that the 

parent compound was not extensively metabolized. However, significant differences were 

observed in the metabolic pathways. In corn, topramezone underwent hydrolytic cleavage to 

form the acid metabolites M670H05 and M670H08, while desmethylation formed M670H03. 

After cleavage, the pyrazole ring appeared to undergo complete catabolism and reincorporation 

within the carbon backbone of natural products such as starch, soluble polysaccharides, and fatty 

acids. The phenyl ring portion of the molecule also underwent degradation, resulting in the 
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incorporation of radioactivity into natural products. In ruminants, the proposed metabolic 

pathway involved hydroxylation of the parent compound at the 4-position of the isoxazole ring to 

form M670H02. The isoxazole ring was then cleaved to form the cyano metabolite (M670H01). 

The linkage between the phenyl and pyrazole rings remained intact in all of the metabolites 

identified. In poultry, the proposed metabolic pathway also involved hydroxylation of the parent 

compound at the 4-position of the isoxazole ring to form M670H02. Further N-demethylation of 

M670H02 occurred and formed the desmethyl hydroxy metabolite M670H04. M670H04 was 

only detected in the phenyl-labeled liver. The pyrazole ring of topramezone could also be 

cleaved to form the acid metabolite M670H05. Similar metabolic pathways were also observed 

in rotational crops, with M670H05 and M670H02 being the only metabolites identified. 

HED concluded that topramezone per se is the residue of concern, for purposes of tolerance 

enforcement and risk assessment, in corn, rotational crops, and ruminants (D310772, G. Kramer, 11-

May-2005). Conclusions concerning the residues of concern in poultry were not determined with the 

D310772 memorandum indicating that if future proposed uses significantly increase the poultry 

dietary burden, then a poultry feeding study, which monitors for residues of parent and metabolite 

M670H02, may be required. Table 5.1 is a summary of the residues of concern for purposes of 

tolerance enforcement and risk assessment. 

Table 5.1. Residues of Concern for Risk Assessment and Tolerance Expression Purposes. 

Matrix Residues included in Risk Assessment Residues included in Tolerance Expression

Plants Corn topramezone topramezone

Rotational Crop topramezone topramezone

Livestock Ruminant topramezone topramezone

Poultry --

1

--

1

Drinking Water topramezone Not Applicable

1

 Conclusions concerning the residues of concern in poultry were not determined with the D310772 memorandum indicating that 

if future proposed uses significantly increase the poultry dietary burden, then a poultry feeding study, which monitors for residues 

of parent and metabolite M670H02, may be required. 

5.2 Food Residue Profile

Topramezone is currently registered for application to field corn, popcorn, sweet corn, and corn 

grown for seed corn with tolerances established at the LOQ. The field corn processing studies 

also resulted in residues of <LOQ following treatments at rates up to 20X the registered rate. No 

additional residue chemistry data are required to support the corn use. Based on the corn 

application rate and the results of the confined/field rotational crop studies, residues in rotational 

crops were anticipated to be negligible at the labeled 28-day plant-back interval (PBI). The corn 

use is the only registered use which results in residues in/on food/feed commodities (D310772,

G. Kramer, 11-May-2005). 

Of the proposed uses, HED concludes that only the aquatic application scenario could potentially 

result in residues in/on food/feed commodities. The proposed aquatic label includes instruction 

for the direct application to water, near-shore foliar application, spot application (near-shore and 

aquatic), and application to exposed sediment. The proposed label does not include any 

restrictions concerning the use of the treated water for potable use or by livestock. 

Based on the proposed use and since the residue of concern in water is only topramezone, HED 

concludes that the aquatic application scenario will result in a maximum concentration in water 

of 50 ppb. Provided the petitioner submits a revised Section B, HED concludes the proposed 

aquatic use will not result in residues in/on irrigated food/feed crops or rotational crops. 
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Based on fish/shellfish metabolism studies, the bioconcentration factor (BCF) for both catfish 

and clam calculated from these studies (<1), and the low the octanol-water partition coefficient 

for topramezone (LogKOW = -1.52 at pH 7), HED is recommending for fish/shellfish tolerances 

for residues of only topramezone at the same concentration as the maximum water concentration 

(0.05 ppm). HED is also recommending for meat byproduct tolerances for ruminant (0.80 ppm), 

hog (0.40 ppm), and poultry (0.02 ppm) as a result of the consumption of treated water by 

livestock (bulk of livestock dietary burden is from consumption of treated water). For more 

information concerning these conclusions see D400949 (T. Bloem, 2/26/2013). 

5.3 Summary of Environmental Degradation 

Major routes of dissipation for topramezone are anaerobic microbial-mediated degradation, 

leaching, surface water runoff, and spray drift. Topramezone degrades to form M670H05 (15% 

of applied parent at 365 days), M670H01 (>15% of applied), and M670H 10 (>16% of applied). 

The degradation product M670H05 is mobile and persistent (half-life >350 days). Topramezone 

applications can lead to surface water contamination through spray drift and runoff. In addition, 

because it is persistent and mobile in soil, topramezone is expected to leach into ground water. 

In aerobic aquatic environments, topramezone degraded with total system half-lives ranging 

from 19 to 277 days. Topramezone degraded in aerobic aquatic environments to form M670H01 

(<10.3% of applied) degradation product. In anaerobic environments, topramezone degraded 

with total system half-lives ranging from 13 to 24 days. The major degradation products 

identified in anaerobic aquatic environments were M670H10 (41% to 48% of applied) minor 

degradation products and M670H01 (≤5.3% of applied). Based upon soil organic carbon 

coefficient, Koc, topramezone would fall into the mobile to moderately mobility class.

5.4 Water Residue Profile

The drinking water residues used in the dietary risk assessment were provided by EFED (J. 

Wolf, 01/29/2013; DP# 408687) and incorporated directly into the acute and chronic dietary 

assessments. Estimated drinking water concentrations (EDWCs) were incorporated directly into 

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

sources.” 

To date, no monitoring data are available for parent topramezone. The highest topramezone 

EDWC is expected to result from the direct aquatic applications. Although the highest proposed 

concentration in water is 50 ppb, the proposed use for water bodies with functional potable water 

intakes cannot exceed 45 ppb; therefore, this is the highest potential concentration recommended 

for drinking water. 

5.5 Dietary Risk Assessment

5.5.1 Description of Residue Data Used in Dietary Assessment

The acute and chronic analyses assumed tolerance-level residues, 100 percent crop treated 

(%CT), DEEM default processing factors, and modeled water values. Therefore, these analyses 

were considered highly conservative and could be further refined if needed through the use of 

anticipated residues (ARs) for all commodities, % market share data for the proposed 

commodities, %CT data for registered commodities, empirical processing factors, and/or 

monitoring data for drinking water. However, as there are no risk estimates of concern, 
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refinements are not necessary at this time.

5.5.2 Percent Crop Treated Used in Dietary Assessment

100% CT was assumed in the acute and chronic dietary assessments.

5.5.3 Acute Dietary Risk Assessment

Two separate acute analyses were conducted as there were two different PODs identified: one 

for the general U.S. population (including infants and children) and one for females 13-49 years 

of age. Both Tier 1 acute analyses assumed 100% CT, DEEM 7.81 default processing factors,

and tolerance-level residues. Drinking water was incorporated directly in the dietary 

assessments. The proposed use for water bodies with functional potable water intakes cannot 

exceed 45 ppb; therefore, this is the highest potential concentration recommended for drinking 

water. 

The acute dietary exposure and risk estimates (food + drinking water) were estimated at 

0.002544 mg/kg/day for the general U.S. population (32% of the aPAD) and 0.007840 

mg/kg/day (98% of the aPAD) for the most highly exposed population subgroup (all infants <1 

year old) and are thus below HED’s LOC. These results are shown for the 95th percentile of 

exposure, as all inputs were unrefined.

The resulting acute dietary exposure and risk estimate using the DEEM-FCID model at the 95th

percentile for females 13-49 years of age was 0.002508 mg/kg/day (50% of the aPAD) and is 

below HED’s LOC. 

Acute dietary exposure to topramezone is not of concern to HED for any population subgroup. 

5.5.4 Chronic Dietary Risk Assessment

The resulting chronic (food + drinking water) risk estimates were less than HED’s LOC for the 

U.S. general population (25% of the cPAD) and all population sub-groups; the most highly 

exposed population subgroup was all infants (<1 year old), which utilized 62% of the cPAD. 

Therefore, the chronic dietary exposure to topramezone is not of concern to HED.

 

5.5.5 Cancer Dietary Risk Assessment

A chronic cancer dietary assessment was not conducted since topramezone was classified as “not 

likely to be carcinogen at doses that do not alter rat thyroid homeostasis.” The cRfD is expected 

to be protective of thyroid alterations and tumor formation.
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5.4.6 Summary Table

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

Population Subgroup*

Acute Dietary1

(95th Percentile) Chronic Dietary2 Cancer

Dietary 

Exposure 

(mg/kg/day)

% aPAD

Dietary 

Exposure

(mg/kg/day)

% cPAD

Dietary 

Exposure

(mg/kg/day)

Risk

General U.S. Population 0.002541 32 0.000998 25

N/A N/A

All Infants (<1 year old) 0.007829 98 0.002487 62

Children 1-2 years old 0.004041 51 0.001487 37

Children 3-5 years old 0.003230 40 0.001263 32

Children 6-12 years old 0.002467 31 0.000913 23

Youth 13-19 years old 0.002098 26 0.000738 19

Adults 20-49 years old 0.002469 31 0.000989 25

Adults 50+ years old 0.002205 28 0.000971 24

Females 13-49 years old 0.002508 50 0.000978 25

* The highest dietary exposure estimate for each type of risk assessment is bolded.

1

 Acute dietary POD of 0.008 mg/kg/day applies to the general U.S. population, including infants and children. Acute dietary 

endpoint of 0.005 mg/kg/day applies to the females 13-49 years old population subgroup only. 

2

 Chronic dietary POD of 0.004 mg/kg/day applies to the general U.S. population and all population subgroups. 

6.0 Residential (Non-Occupational) Exposure/Risk Characterization

The following are summaries of the residential exposures associated with the proposed uses. 

Residential exposures resulting from the registered golf course and turfgrass uses have been 

previously assessed and yielded exposures which do not exceed HED’s LOC (D388367, K. Lowe, 

2-Feb-2012); it is noted that this previous assessment considered the 2012 residential SOPs. 

6.1 Residential Handler Exposure

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

application process. 

Non-crop Terrestrial-Application: The application sites specified in the proposed non-crop

terrestrial-application scenario are not associated with residential settings; therefore, a residential 

handler exposure assessment is unnecessary. 

Non-crop Aquatic-Application: Residential handler assessments were not conducted because 

the proposed use sites are not residential in nature and homeowner applications are unlikely. It is 

noted that the label includes the following statements which also imply commercial/professional 

applications: (1) state and/or local authorities are to be consulted prior to applying this product 

in or around public waters and (2) prior to retreatment, samples should be collected and analyzed 

for parent concentration to establish the amount of product to apply so as to not exceed the 

labeled maximum water concentration of 50 ppb.

6.2 Post-Application Exposure

Non-crop Terrestrial-Application: The application sites specified in the proposed non-crop

terrestrial-application scenario are not associated with residential/recreational settings; therefore,

a residential post-application exposure assessment is unnecessary. 
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Non-crop Aquatic-Application: Since there are no restrictions concerning the recreational use of 

treated water, post-application residential exposures resulting from swimming in treated water 

were calculated. HED notes that although only short-term exposures are anticipated, the shortterm assessments are protective of intermediate-term exposures as the short- and intermediate-term 

oral, inhalation, and dermal PODs are identical. 

The lifestages selected for each post-application scenario are based on an analysis provided as an 

Appendix in the 2012 Residential SOPs (http://www.epa.gov/pesticides/science/residentialexposure-sop.html). These lifestages are not the only lifestages that could be potentially exposed 

for these post-application scenarios; however, the assessment of these lifestages is protective for 

the exposures and risk estimates for any other potentially exposed lifestages. The following 

paragraphs are summaries of the anticipated inhalation, oral, and dermal exposures/risks. 

Inhalation: Based on the Henry’s law constant for topramezone (7.03 x 10-16 atm m3/mole), there is 

a low potential for volatilization from water and post-application inhalation exposures are 

anticipated to be negligible. 

Dermal and Oral: The following scenarios were assessed: ingestion of water while swimming and 

dermal exposure from water while swimming. Risks were calculated using the MOE approach, 

which is a ratio of the estimated exposure to the toxicological POD. The dermal and oral exposures 

were combined as the PODs for these routes are identical. Tables 6.2.1 and 6.2.2 are summaries of 

the oral and dermal exposures, respectively. Table 5.2.3 is a summary of the combined oral and 

dermal post-application exposures. The combined oral and dermal MOEs for adult and child 

swimmers are >100 (MOEs ≥1000). Therefore, residential post-application exposure does not 

exceed HED’s LOC. 

HED did not combine swimmer exposures from the proposed non-crop aquatic use with the 

exposures from the registered turf and/or golfer exposure due to the conservative nature of each 

of these individual assessments. 

Table 6.2.1. Short -Term Post-application Exposure - Ingestion of Water by Swimmers.

Exposure Scenario Cw1 (mg/L) IgR2 (L/hr) ET3 (hr/day) BW4(kg) Oral Dose5(mg/kg/day) MOE6

swimmer; adult 0.050 0.021 3.7 80 4.92 x 10-58,100

swimmer; child (3 - <6 years old) 0.049 3.0 19 3.83 x 10-41,000

1

 Cw = concentration in water = 50 ppb; based on the label instructions. 

2

 IgR = ingestion rate of water; based on 2011 EFH (Table 3-5). 

3

 ET =exposure time; based on 2011 EFH (Table 16-20). 

4

 BW = body weight; based on the Residential Pesticide Exposure Assessment SOP (February-2012). 

5

 Oral dose = (Cw x IgR x ET) ÷ BW (80 kg for adults and 19 kg for child (3 - <6 years old).

6

 MOE = NOAEL (0.4 mg/kg/day; adult and child) ÷ dose (mg/kg/day).

Table 6.2.2. Short -Term Post-application Exposure - Dermal Exposure from Water to Swimmers.

Exposure Scenario Cw1

(mg/L)

SA2

(cm2)

ET3

(hr/day) Kp4 CF5 (L/cm3)

BW6

(kg)

Dermal Dose in 

Oral Equvalents7

(mg/kg/day)

MOE8

swimmer; adult 0.050 19,500 3.7 9.6 x 10-7

0.001 80 4.40 x 10-8

9,100,000

swimmer; child (3 - <6 years old) 7,600 3.0 19 5.73 x 10-87,000,000

1

 Cw = concentration in water = 50 ppb; based on the label instructions. 

2

 SA = surface area; values based on the Residential Pesticide Exposure Assessment SOP (February-2012). 

3

 ET =exposure time; based on 2011 EFH (Table 16-20). 

4

 Kp = permeability coefficient = 10[-2.72 + (0.71 x log Kow) - (0.0061 x MW)] = 9.6 x 10-7; EPA 1992 default equation for organic 

compounds. 

5

 CF = conversion factor = 0.001 L/cm3.

6

 BW = body weight; based on the Residential Pesticide Exposure Assessment SOP (February-2012). 

7

 Dermal dose in oral equivalents = (Cw x SA x ET x Kp x CF) ÷ BW (80 kg for adults and 19 kg for child (3 - <6 years old).
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8

 MOE = NOAEL (0.4 mg/kg/day; adult and child) ÷ dose (mg/kg/day).

Table 6.2.3. Short -Term Post-application Combined Oral and Dermal Exposure for Adult and Child Swimmers.

Exposure Scenario

Oral Dose from 

Ingestion of Water1

(mg/kg/day)

Dermal Dose from 

Water2(oral 

equivalents; mg/kg/day)

Total Dose3

(mg/kg/day) MOE4

swimmer; adult 4.92 x 10-54.40 x 10-84.92 x 10-58,100

swimmer; child (3 - <6 years old) 3.83 x 10-45.73 x 10-83.83 x 10-41,000

1

 From Table 6.2.1.

2

 From Table 6.2.2.

3

 Total dose = oral dose + dermal dose in oral equivalents. 

4

 MOE = NOAEL (0.4 mg/kg/day; adult and child) ÷ total dose (mg/kg/day).

6.3 Residential Risk Estimates for Use in Aggregate Assessment

The residential exposure/risk resulting from the registered turf and golf course uses were 

previously calculated and are summarized in D388367 (K. Lowe, 2-Feb-2012); it is noted that 

this assessment considered the 2012 residential SOPs. Based on the residential exposure 

estimates from all proposed and registered uses and under the criteria that the uses which result 

in the highest exposures should be used in aggregate assessment, HED concludes that aggregate 

risk calculations should employ the following residential exposure estimates (see Table 6.3 for a 

summary): 

● For adults, short-term aggregate assessments should consider the post-application exposure 

resulting from the registered turf use (physical activities on turf). 

● For children, short-term aggregate assessments should consider combined dermal and 

incidental oral (hand-to-mouth) post-application exposures to children 1- <2 years old resulting 

from the registered turf use. The post-application incidental oral scenarios (hand-to-mouth), 

object-to-mouth, and soil ingestion were not combined due to the conservative nature of each 

individual assessment. The incidental oral scenario which yielded the highest exposure (hand-tomouth) was combined with post-application dermal. This combination is considered a protective 

estimate of children’s exposure to pesticides used on turf. 

● For children, intermediate-term aggregate assessments should consider incidental soil 

ingestion exposure for children 1- <2 years old resulting from the registered turf use. 

Table 6.3. Residential Exposures for use in Topramezone Aggregate Exposure Assessments.

Population

Residential Handler Post-application

Total Exposure 

(mg/kg/day) MOE Total Exposure (mg/kg/day) MOE

Short-term

adult1

Residential handler exposure should not be used for 

aggregate assessment as it is lower than the postapplication exposure.0.00083 480

child (1- <2 years old)1not applicable 0.0019 210

Intermediate-term (assessment was conducted to address potential soil ingestion)

child (1- <2 years old)1not applicable 3.0 x 10-6130,000

1

 Exposure resulting from the registered turf use (see D388367, K. Lowe, 2-Feb-2012).

6.4 Residential Bystander Post-application Inhalation Exposure

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

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

inhalation toxicity (Toxicity Category IV), low vapor pressure (7.5 x 10-13 mm Hg), low Henry’s 

law constant (7.03 x 10-16 atm m3/mole), and the low proposed use rate. However, volatilization 
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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 (FIFRA) 

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

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

Agency is in the process of evaluating the SAP report and may, as appropriate, develop policies 

and procedures to identify the need for and, subsequently, the way to incorporate postapplication inhalation exposure into the Agency's risk assessments. If new policies or 

procedures are developed, the Agency may revisit the need for a quantitative post-application 

inhalation exposure assessment for topramezone.

6.5 Spray Drift

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

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

potential source of exposure from the ground application method employed for topramezone. 

The Agency has been working with the Spray Drift Task Force, EPA Regional Offices, and State 

Lead Agencies for pesticide regulation and other parties to develop the best spray-driftmanagement practices (see the Agency’s Spray Drift website for more information at 

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

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

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

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

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

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

methods. After the policy is in place, the Agency may impose further refinements in spray-driftmanagement practices to reduce off-target drift with specific products with significant risk 

estimates associated with drift.

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

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

exposure assessment was performed for flaggers (MOE = 3300; no PPE). This exposure 

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

protective of residential exposure resulting from spray drift. 

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, or the risks themselves can be aggregated. When aggregating exposures and 

risks from various sources, HED considers both the route and duration of exposure.

7.1 Acute Aggregate Risk

Acute aggregate risk is made up only of dietary sources; therefore, the acute exposure estimates 

provided in the acute dietary exposure analysis represent acute aggregate exposures. The acute 

dietary assessment did not result in exposure estimates above HED’s LOC (see Table 5.4.6).
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7.2 Short-Term Aggregate Risk

Short-term aggregate exposures were made up of average dietary exposures from food, drinking 

water (the main driver in the dietary assessment due to the aquatic use), and residential exposures 

from either the proposed or registered uses. The sum of these exposures was compared to 

appropriate quantitative estimate of hazard, and the resulting risk estimate was expressed as a 

MOE. HED’s LOC is an MOE <100.

For adults and children, the highest estimated residential exposure was associated with postapplication physical activities from the currently registered turf use (D388367, K. Lowe, 02-Feb2012). For adults, this is the sum of high-end post-application dermal and inhalation estimated

exposures; whereas, for children, the highest residential exposure estimate is from incidental oral 

and dermal exposure. Although incidental oral exposures are more likely with children 1<2 

years old, the exposure estimates are high-end and protective of older children more likely to 

engage in recreational swimming activities. Children 1-2 years of age were also the subgroup 

predicted to have the highest dietary burden at 98 and 62% of the aPAD and cPAD, respectively. 

The resulting aggregate short-term MOE are >100 and therefore not of concern to HED (Table 

7.2.1).

Table 7.2.1. Short-Term Aggregate Risk Calculations.

Population NOAEL

(mg/kg/day) LOC

Average Food 

and Water 

Exposure 

(mg/kg/day)1

Residential 

Exposure 

(mg/kg/day)2

Total Exposure 

(mg/kg/day)3

Aggregate MOE 

(food, water, and 

residential)4

General U.S. 

Population 0.4 100 0.000998 0.00083 0.00183 220

Children 1-2 

years old 0.4 100 0.001487 0.0019 0.00339 120

1

 Average Food and Water Exposure = Dietary exposure (Table 5.6.1).

2

 Residential Exposure = [Incidental oral exposure (i.e., Hand-to-Mouth) + Dermal exposure + Inhalation Exposure] (Table 6.3.1).

3 Total Exposure = Average Food & Water Exposure + Residential Exposure.

4

7.3 Intermediate-Term Aggregate Risk

Intermediate-term residential exposures are not expected based on the proposed aquatic and 

terrestrial uses. However, intermediate incidental oral exposures (soil ingestion) for children 1<2 

years old have been previously assessed for the registered turf use. The resulting aggregate 

short-term MOE are >100 and therefore not of concern to HED.

Table 7.2.2. Intermediate-Term Aggregate Risk Calculations.

Population NOAEL

(mg/kg/day) LOC

Average Food 

and Water 

Exposure 

(mg/kg/day)1

Residential 

Exposure 

(mg/kg/day)2

Total Exposure 

(mg/kg/day)3

Aggregate MOE 

(food, water, and 

residential)4

Children 1-2 

years old 0.4 100 0.001487 3.0 x 10-6

0.00149 270

1

 Average Food and Water Exposure = Dietary exposure (Table 5.6.1).

2

 Residential Exposure = [Incidental oral exposure (i.e., Hand-to-Mouth) + Dermal exposure + Inhalation Exposure] (Table 6.3.1).

3 Total Exposure = Average Food & Water Exposure + Residential Exposure.

4

7.4 Long-Term Aggregate Risk

Long-term residential exposures are not expected from the registered or proposed uses. 

Therefore, chronic (long-term) aggregate risk is made up only of dietary sources and the chronic 
Topramezone Human-Health Risk Assessment DP#s 400310, 404014

Page 30 of 41

dietary exposure analysis represents chronic aggregate exposure. The chronic dietary assessment 

did not result in exposure estimates that are of concern to HED (see Table 5.4.6)

7.5 Cancer Risk

Aggregate cancer risk was not performed because topramezone is classified as “not likely to be 

carcinogenic to humans at doses that do not alter rat thyroid hormone homeostasis,” and doses at 

or below the cRfD are not expected to alter thyroid hormone homeostasis.

8.0 Cumulative Exposure/Risk Characterization

Pyrasulfotole, mesotrione, isoxaflutole, and topramezone belong to a class of herbicides that 

inhibit the liver enzyme HPPD, which is involved in the catabolism (metabolic breakdown) of 

tyrosine (an amino acid derived from proteins in the diet). Inhibition of HPPD can result in 

elevated tyrosine levels in the blood, a condition called tyrosinemia. HPPD-inhibiting herbicides 

have been found to cause a number of toxicities in laboratory animal studies including ocular, 

developmental, liver, and kidney effects. Of these toxicities, the ocular effect (corneal opacity) 

is highly correlated with the elevated blood tyrosine levels. In fact, rats dosed with tyrosine 

alone show ocular opacities similar to those seen with HPPD inhibitors. Although the other 

toxicities may be associated with chemically induced tyrosinemia, other mechanisms may also 

be involved. 

There are marked differences among species in the ocular toxicity associated with inhibition of 

HPPD. Ocular effects following treatment with HPPD inhibitor herbicides are seen in the rat but 

not in the mouse. Monkeys also seem to be recalcitrant to the ocular toxicity induced by HPPD 

inhibition. The explanation of this species-specific response in ocular opacity is related to the 

species differences in the clearance of tyrosine. A metabolic pathway exists to remove tyrosine 

from the blood that involves a liver enzyme called tyrosine aminotransferase (TAT). In contrast 

to rats where ocular toxicity is observed following exposure to HPPD-inhibiting herbicides, mice 

and humans are unlikely to achieve the levels of plasma tyrosine necessary to produce ocular 

opacities because the activity of TAT in these species is much greater compared to rats. Thus, 

humans and mice have a highly effective metabolic process for handling excess tyrosine. 

HPPD inhibitors (e.g., nitisinone) are used as an effective therapeutic agent to treat patients 

suffering from rare genetic diseases of tyrosine catabolism. Treatment starts in childhood but is 

often sustained throughout patient’s lifetime. The human experience indicates that a therapeutic 

dose (1 mg/kg/day dose) of nitisinone has an excellent safety record in infants, children, and 

adults and that serious adverse health outcomes have not been observed in a population followed 

for approximately a decade. Rarely, ocular effects are seen in patients with high plasma tyrosine 

levels; however, these effects are transient and can be readily reversed upon adherence to a 

restricted protein diet. This indicates that an HPPD inhibitor in it of itself cannot easily 

overwhelm the tyrosine-clearance mechanism in humans. 

Therefore, exposure to environmental residues of HPPD-inhibiting herbicides are unlikely to 

result in the high blood levels of tyrosine and ocular toxicity in humans due to an efficient 

metabolic process to handle excess tyrosine. In the future, assessments of HPPD-inhibiting 

herbicides will consider more appropriate models and cross species extrapolation methods. 

Therefore, EPA has not conducted cumulative risk assessment with other HPPD inhibitors 

(D341612; dated 7/02/2007).
Topramezone Human-Health Risk Assessment DP#s 400310, 404014

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9.0 Occupational Exposure/Risk Characterization

9.1 Short-/Intermediate-Term Handler Risk

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 proposed uses. The 

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

following scenarios: 

● Mixing/loading soluble-concentrate (SC) formulations for aerial application

● Mixing/loading SC formulations for groundboom application

● Applying sprays aerially (fixed-wing aircraft; closed cab) 

● Applying sprays by groundboom equipment

● Flagger in support of aerial application

● Mixing/loading/applying using backpack sprayer (spot treatment)

● Mixing/loading/applying using manually pressurized handwand sprayer (spot treatment)

● Mixing/loading/applying using mechanically pressurized handgun sprayer (spot treatment)

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 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 the current proposed topramezone uses, exposures are expected to be short-term and 

intermediate-term in duration. It is noted that the short-term assessments are protective of 

intermediate-term exposures as the short- and intermediate-term inhalation and dermal PODs are 

identical. Long-term exposures are not expected. 

Occupational handler exposure assessments are completed by HED using different levels of risk 

mitigation. Typically, HED uses a tiered approach. The lowest tier is designed as the baseline 

exposure scenario (i.e., long-sleeve shirt, long pants, shoes, socks, no respirator). If risk estimates 

are of concern at baseline attire, then increasing levels of PPE (i.e., gloves, respirators) are 

evaluated. If risk estimates remain a concern with maximum PPE, then engineering controls (i.e., 

enclosed cabs or cockpits, water-soluble packaging, and closed mixing/loading systems) are 

evaluated. This approach is used to ensure that the lowest level of risk mitigation that provides 

adequate protection is selected, since the addition of PPE and engineering controls involves an 

additional expense to the user and (in the case of PPE) also involves an additional burden to the 

user due to decreased comfort and dexterity and increased heat stress and respiratory stress. 

Conclusions: Table 9.1 summarizes the dermal, inhalation, and combined dermal/inhalation 

exposures and risk estimates (dermal and inhalation combined as identical POD) for topramezone. 
Topramezone Human-Health Risk Assessment DP#s 400310, 404014

Page 32 of 41

MOEs were calculated assuming baseline PPE (long-sleeved shirt, long pants, shoes plus socks, and 

no protective gloves clothing) as well as baseline PPE plus protective gloves. The mixer/loader 

scenario in support of aerial application for the non-crop aquatic scenario resulted in a risk estimate 

of concern assuming baseline PPE plus protective gloves; therefore this scenario was also assessed 

assuming DL (double layer/coveralls) and EC (engineering control). 

Provided handlers wear protective gloves as specified on the proposed labels and the labels are 

revised as indicated below, the combined dermal and inhalation MOEs are >100 (MOEs ≥170). 

Therefore, occupational handler exposures do not exceed HED’s LOC. 

A revised Section B specifying the following is requested: (1) for in-water applications, applicators 

must wear long-sleeved shirt, long pants, chemical-resistant gloves, and shoes plus socks and (2) 

for in-water applications, mixer loaders in support of aerial application must use engineering 

controls (i.e., closed system).

Table 9.1. Short-/Intermediate-Term Occupational Exposure and Risk Estimates for Topramezone. 

Unit Exposure1

(μg/lb ai handled) Application Rate2 Units TreatedPer Day3

Daily Dose4

(mg/kg/day)

Short-/Intermediate-Term MOE5

Dermal and

Inhalation Combined

Mixer/Loader - Liquid - Aerial - Typical Field Crop (aquatic)

Dermal:

NG: 220

WG: 37.6

DL: 29.1

EC: 8.6

Inhalation:

NR: 0.219 

EC: 0.083

1.36 lb ai/acre 350 acres

Dermal:

NG: 0.0341

WG: 0.00582

DL: 0.00452

EC: 0.00133

Inhal:

NR: 0.0013

EC: 0.000494

Dermal:

NG: 12

WG: 69

DL: 88

EC: 300

Inhalation:

NR: 310

EC: 810

NG/NR: 12

WG/NR: 56

DL/NR: 69

EC/EC: 220

Mixer/Loader - Liquid - Aerial - Typical Field Crop (terrestrial)

Dermal:

NG: 220

WG: 37.6

Inhalation:

NR: 0.219

0.35 lb ai/acre 350 acres

Dermal:

NG: 0.00878

WG: 0.0015

Inhal:

NR: 0.000335

Dermal:

NG: 46

WG: 270

Inhalation:

NR: 1200

NG/NR: 44

WG/NR: 220

Mixer/Loader - Liquid - Groundboom - Typical Field Crop (aquatic)

Dermal:

NG: 220

WG: 37.6

Inhalation:

NR: 0.219

1.36 lb ai/acre 80 acres

Dermal:

NG: 0.00777

WG: 0.00133

Inhal:

NR: 0.000298

Dermal:

NG: 51

WG: 300

Inhalation:

NR: 1300

NG/NR: 49

WG/NR: 240

Mixer/Loader - Liquid - Groundboom - Typical Field Crop (terrestrial)

Dermal:

NG: 220

WG: 37.6

Inhalation:

NR: 0.219

0.35 lb ai/acre 80 acres

Dermal:

NG: 0.002

WG: 0.000341

Inhal:

NR: 0.0000766

Dermal:

NG: 200

WG: 1200

Inhalation:

NR: 5200

NG/NR: 190

WG/NR: 980

Applicator - Liquid - Fixed-wing Aircraft (closed cab) - Typical Field Crop (aquatic)

Dermal:

EC: 5

Inhalation:

NR: 0.068

1.36 lb ai/acre 350 acres

Dermal:

EC: 0.000774

Inhal:

EC: 0.000405

Dermal:

EC: 520

Inhalation:

EC: 990

EC/EC: 340

Applicator - Liquid - Fixed-wing Aircraft (closed cab) - Typical Field Crop (terrestrial)

Dermal:

EC: 5

Inhalation:

NR: 0.068

0.35 lb ai/acre 350 acres

Dermal:

EC: 0.000199

Inhal:

EC: 0.000104

Dermal:

EC: 2000

Inhalation:

EC: 3800

EC/EC: 1300
Topramezone Human-Health Risk Assessment DP#s 400310, 404014

Page 33 of 41

Table 9.1. Short-/Intermediate-Term Occupational Exposure and Risk Estimates for Topramezone. 

Unit Exposure1

(μg/lb ai handled) Application Rate2 Units TreatedPer Day3

Daily Dose4

(mg/kg/day)

Short-/Intermediate-Term MOE5

Dermal and

Inhalation Combined

Applicator - Liquid - Groundboom - Open Cab - Typical Field Crop (aquatic)

Dermal:

NG: 78.6

WG: 16.1

Inhalation:

NR: 0.34

1.36 lb ai/acre 80 acres

Dermal:

NG: 0.00278

WG: 0.000569

Inhal:

NR: 0.000463

Dermal:

NG: 140

WG: 700

Inhalation:

NR: 860

NG/NR: 120

WG/NR: 390

Applicator - Liquid - Groundboom - Open Cab - Typical Field Crop (terrestrial)

Dermal:

NG: 78.6

WG: 16.1

Inhalation:

NR: 0.34

0.35 lb ai/acre 80 acres

Dermal:

NG: 0.000715

WG: 0.000147

Inhal:

NR: 0.000119

Dermal:

NG: 560

WG: 2700

Inhalation:

NR: 3400

NG/NR: 480

WG/NR: 1500

Flagger (terrestrial)

Dermal:

NG: 11

WG: 12

Inhalation:

NR: 0.34

0.35 lb ai/acre 80 acres

Dermal:

NG: 0.000100

WG: 0.000109

Inhal:

NR: 0.000123

Dermal:

NG: 4000

WG: 3700

Inhalation:

NR: 3300

NG/NR: 1800

WG/NR: 1700

Mixer/Loader/Applicator - Liquid - Backpack - Broadcast - Rights-of-way, Forestry, Aquatic Areas; 

Mixer/Loader/Applicator - Liquid - Backpack - Soil-Directed - Christmas Tree Farm, Nursery

Dermal:

NG: 8260

WG: 8260

Inhalation:

NR: 2.58

0.014 lb ai/gal 40 gall

Dermal:

NG: 0.0015

WG: 0.0015

Inhal:

NR: 0.000018

Dermal:

NG: 270

WG: 270

Inhalation:

NR: 22,000

NG/NR: 270

WG/NR: 270

Mixer/Loader/Applicator - Liquid - Backpack - Broadcast - Industrial/Commercial

Dermal:

NG: 2510

WG: 2500

Inhalation:

NR: 30

0.014 lb ai/gal 40 gall

Dermal:

NG: 0.000458

WG: 0.000455

Inhal:

NR: 0.00021

Dermal:

NG: 870

WG: 880

Inhalation:

NR: 1900

NG/NR: 600

WG/NR: 600

Mixer/Loader/Applicator - Liquid - Manually Pressurized Handwand - Broadcast -

Industrial/Commercial, Aquatic Areas

Dermal:

NG: 100000

WG: 430

Inhalation:

NR: 30

0.014 lb ai/gal 40 gal

Dermal:

NG: 0.0182

WG: 0.0000783

Inhal:

NR: 0.00021

Dermal:

NG: 22

WG: 5100

Inhalation:

NR: 1900

NG/NR: 22

WG/NR: 1400

Mixer/Loader/Applicator - Liquid - Mechanically Pressurized Handgun - Broadcast -

Industrial/Commercial, Aquatic Areas

Dermal:

NG: 1300

WG: 390

Inhalation:

NR: 3.9

0.014 lb ai/gal 1000 gal

Dermal:

NG: 0.00592

WG: 0.00177

Inhal:

NR: 0.000683

Dermal:

NG: 68

WG: 230

Inhalation:

NR: 590

NG/NR: 61

WG/NR: 170

1

 Unit Exposures are from the Occupational Pesticide Handler Unit Exposure Surrogate Reference Table (Revised March-2012); 

NG = no gloves; WG = with gloves; DL = double layer/coveralls; EC = engineering control; NR = no respirator. 

2

 Application rates based on the proposed label; 1.36 lb ai/A is derived from the proposed non-crop aquatic-application label and 

assumes a water depth of 10 feet. 

3

 Values are taken from HED’s ExpoSAC Policy #9: “Standard Values for Daily Acres Treated in Agriculture,” which was 

revised on July 5, 2000.

4

 Average Daily Dose (ADD) = Unit Exposure x Application Rate x Units Treated x Absorption Rate (2.6% dermal absorption; 

inhalation absorption is assumed to be 100%) x (1 mg/1000 μg) ÷ Body Weight (80 kg).

5

 MOE = margin of exposure = NOAEL ÷ ADD (dermal + inhalation). Short- and intermediate-term NOAEL = 0.4 mg/kg/day.

9.2 Post-Application Risk

Occupational post-application dermal exposure following aquatic application of topramezone is 

likely limited to persons who contact treated water to perform tests, such as testing the 
Topramezone Human-Health Risk Assessment DP#s 400310, 404014

Page 34 of 41

concentration of topramezone in water to determine if retreatment is necessary. Since the postapplication combined dermal and oral (ingestion of water) exposure to adult recreational 

swimmers resulted in a MOE of 8100, HED concludes that post-application occupational 

exposure is less than HED’s LOC and a quantitative assessment is unnecessary. Although the 

proposed non-crop terrestrial label does include instructions for application to Christmas tree, 

conifer, and hardwood plantations and field-grown ornamental production, the proposed use is for 

weed control and does not involve foliar application to the desired plant (confirmed via email 

communication with the petitioner; Jeffry Britt BASF to Grant Rowland EPA RD). Therefore, 

post-application dermal occupational exposures are anticipated to be negligible. 

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

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

inhalation toxicity (Toxicity Category IV), low vapor pressure (7.5 x 10-13 mm Hg), low Henry’s 

law constant (7.03 x 10-16 atm m3/mole), and the low proposed use rate. However, there are 

multiple potential sources of post-application inhalation exposure to individuals performing postapplication 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 FIFRA

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

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

process of evaluating the SAP report as well as available post-application inhalation exposure 

data generated by the ARTF and may, as appropriate, develop policies and procedures, to identify 

the need for and, subsequently, the way to incorporate occupational post-application inhalation 

exposure into the Agency's risk assessments. If new policies or procedures are put into place, the 

Agency may revisit the need for a quantitative occupational post-application inhalation exposure 

assessment for topramezone.

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

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

handlers. Handler exposure resulting from application of pesticides outdoors is likely to result in 

higher exposure than post-application exposure. Therefore, it is expected that these handler 

inhalation exposure estimates would be protective of most occupational post-application 

inhalation exposure scenarios.

10.0 References

Memo, M. Clock-Rust et al., D319704, 7/14/2005. “Topramezone/BAS670H: Amendment to 

the Human Health Risk Assessment for New Active Ingredient Dated May 11 For Uses Proposed 

on Field, Pop, Seed and Sweet Corn (DP290075).”

Memo, M. Clock-Rust et al., D352696, 2/20/2009. “Topramezone: Human-Health Risk 

Assessment for Uses Proposed on Non-crop Ornamentals, Rights-of-Way, Tree Plantations, and 

Other Non-Crop Areas.”

Memo, J. Wolf, D408687, D401166, 01/29/3013, “Drinking Water Exposure Assessment for a 

Proposed Increase of the maximum use rate of Topramezone Frequency Herbicide (EPA Reg. 

No. 7969-281) for non-cropland2uses, and Proposed New Use for Direct Applications to 

 

2

For preemergence and post-emergence weed control in Christmas tree, conifer, and hardwood plantations; field grown 

ornamental production; and non-cropland areas such as railroad, utility, highway, and pipeline rights-of-way; highway 
Topramezone Human-Health Risk Assessment DP#s 400310, 404014

Page 35 of 41

Aquatic Environments (Oasis Aquatic Herbicide, EPA File Symbol No. 7969-GGO)” 

Memo, S. Levy, D400310, “Topramezone. Acute and Chronic Aggregate Dietary (Food + 

Drinking Water) Exposure and Risk Assessment for the Section 3 Registration Action Uses on 

Non-Crop Aquatic Sites and Increased Maximum Application Rates for Currently Registered 

Terrestrial Uses.”

Memo, K. Lowe, D388367, 2/2/2012. “Topramezone: Occupational and Residential 

Exposure/Risk Assessment for Proposed Uses on Golf Courses, Sod Farms, and Residential 

Turfgrass.”

Memo, K. Rury, D400310, D404014, 01/30/2013. “Topramezone: Summary of Hazard and 

Science Policy Council (HASPOC) Meetings of December 6, 2012 and December 19, 2012: 

Reconsideration on the Need for a 28-day Inhalation study. 

Memo, T. Bloem, D400949, 2/26/2013. Topramezone. Section 3 Registration Concerning 

Noncrop Aquatic-Application. Summary of Analytical Chemistry and Residue Data. 

Memo, T. Bloem, D400948, 2/26/2013. Topramezone. Section 3 Registration Concerning 

Application to Noncrop Aquatic and Noncrop Terrestrial Areas. Occupational and Residential 

Exposure and Risk Assessment.

 

guardrails, delineators, and sign posts; utility substations, petroleum tank farms, pumping installations, farmyards and around 

farm buildings; fence rows, storage areas, airports, and non-irrigation ditches.
Topramezone Human-Health Risk Assessment DP#s 400310, 404014

Page 36 of 41

Appendix A. Toxicology Profile and Executive Summaries

A.1 Toxicology Data Requirements

The requirements (40 CFR 158.340) for food uses for topramezone are in Table A.1. Use of the 

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

Table A.1. Study Requirements for Food Uses for Topramezone.

Study Technical

Required Satisfied

870.1100 Acute Oral Toxicity

870.1200 Acute Dermal Toxicity

870.1300 Acute Inhalation Toxicity

870.2400 Primary Eye Irritation

870.2500 Primary Dermal Irritation

870.2600 Dermal Sensitization

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

870.3100 Oral Subchronic (rodent)

870.3150 Oral Subchronic (nonrodent)

870.3200 21-Day Dermal

870.3250 90-Day Dermal

870.3465 90-Day Inhalation

yes

yes

yes

no

no

yes

yes

yes

-

-

870.3700a Developmental Toxicity (rodent)

870.3700b Developmental Toxicity (nonrodent)

870.3800 Reproduction

yes

yes

yes

yes

yes

yes

870.4100a Chronic Toxicity (rodent)

870.4100b Chronic Toxicity (nonrodent)

870.4200a Oncogenicity (rat)

870.4200b Oncogenicity (mouse)

870.4300 Chronic/Oncogenicity

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

870.5100 Mutagenicity—Gene Mutation - bacterial

870.5300 Mutagenicity—Gene Mutation - mammalian

870.5xxx Mutagenicity—Structural Chromosomal Aberrations

870.5xxx Mutagenicity—Other Genotoxic Effects

yes

yes

yes

yes

yes

yes

yes

yes

870.6100a Acute Delayed Neurotoxicity (hen)

870.6100b 90-Day Neurotoxicity (hen)

870.6200a Acute Neurotoxicity Screening Battery (rat)

870.6200b 90-Day Neurotoxicity Screening Battery (rat)

870.6300 Develop. Neurotoxicity

no

no

yes

yes

no

-

-

yes

yes

-

870.7485 General Metabolism

870.7600 Dermal Penetration

870.7800 Immunotoxicity

yes

yes

yes

yes

yes

no

Special Studies for Ocular Effects

 Acute Oral (rat)

 Subchronic Oral (rat)

 Six-month Oral (dog)

no

no

no

-

-

-
Topramezone Human-Health Risk Assessment DP#s 400310, 404014

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A.2 Toxicity Profiles

Table A.2.1. Acute Toxicity Profile on Topramezone.

OPPTS Guideline Study Type Results Toxicity Category

870.1100 Acute oral toxicity / rat LD50 2000 mg/kg (males and females) III

870.1200 Acute dermal toxicity / rat LD50 2000 mg/kg (males and females) III

870.1300 Acute inhalation toxicity / 

rat LC50 5.05 mg/L (males and females) IV

870.2400 Primary eye irritation / 

rabbit Slight irritant III

870.2500 Primary dermal irritation / 

rabbit Slight irritant IV

870.2600 Dermal sensitization / 

guinea pig Non-Sensitizer --

Table A.2.2. Subchronic, Chronic, and Other Toxicity Profile for Topramezone.

Guideline No/ Study 

Type/

MRID Nos.

Doses/Classification Results

870.3100

Subchronic Oral

- Rat

45902203, 45902204 (2001, 2003)

(0, 15, 30 ppm)

M:0, 1.1, 2.1 mg/kg/day

F:0, 1.3, 2.5 mg/kg/day

Acceptable/guideline

Males: NOAEL =1.1 mg/kg/day, LOAEL = 2.1 

mg/kg/day based on diffuse degeneration in the pancreas.

Females: NOAEL = 2.1 mg/kg/day, the LOAEL was not 

established.

870.3100

Subchronic Oral

- Mouse

45902202 (2000)

(0, 125, 1000, 8000 ppm)

M: 0, 3 7, 288, 2289 mg/kg/day 

F: 0, 51, 406, 3010 mg/kg/day 

Acceptable/guideline

NOAEL = 2289/3010 mg/kg/day (M/F).

LOAEL = not established.

870.3150

Subchronic Oral

- Dog

45902205 (2002)

(0, 3000, 9000, 25000 ppm)

0, 182, 535, 1511 mg/kg/day (M)

0, 205, 624, 1712 mg/kg/day(F)

Acceptable/guideline

Males: NOAEL = 535 mg/kg/day, and the LOAEL = 

1511 mg/kg/day based on decreased body-weight gain, 

impaired food efficiency, and inflammation of the urinary 

bladder. 

Females: NOAEL = 1712 mg/kg/day, the LOAEL for 

females is not established. 

870.3200

28-Day dermal toxicity

- Rat

45902206 (2002)

0, 100, 300, 1000 mg/kg/day

Acceptable/Guideline

Males: NOAEL = 100 mg/kg/day, the LOAEL = 300 

mg/kg/day based on thyroid follicular cell hypertrophy. 

Females: NOAEL = 300 mg/kg/day, the LOAEL = 1000 

mg/kg/day based on thyroid follicular cell hypertrophy.

870.3700a

Prenatal developmental 

- Rat 

45902207 (2003)

0, 100, 300, 1000 mg/kg/day

Acceptable/Guideline

Maternal: NOAEL = not established, the LOAEL = 100 

mg/kg/day based on decreased body-weight gains.

Developmental: NOAEL = not established, the LOAEL = 

100 mg/kg/day based on decreased fetal body weight and 

increased incidences of skeletal variation.

870.3700b

Prenatal developmental 

- NZW Rabbit

45902210 (2003)

0, 0.5, 5, 50, 450 mg/kg/day

Acceptable/Guideline

Maternal: NOAEL = not established, the LOAEL= 0.5 

mg/kg/day based on increased serum tyrosine level.

Developmental: NOAEL = 0.5 mg/kg/day, the LOAEL = 

5 mg/kg/day based on alterations in skeletal ossification 

sites and increased number of pairs of ribs.

870.3700b

Prenatal developmental 

- NZW Rabbit

45902211 (2003)

0, 5, 50, 500 mg/kg/day

Unacceptable/Guideline

Maternal: NOAEL = not established. LOAEL = 5 

mg/kg/day based on increased tyrosine level.

Developmental: Unable to established because fetal 

skeletons were not evaluated.
Topramezone Human-Health Risk Assessment DP#s 400310, 404014

Page 38 of 41

Table A.2.2. Subchronic, Chronic, and Other Toxicity Profile for Topramezone.

Guideline No/ Study 

Type/

MRID Nos.

Doses/Classification Results

870.3700b

Prenatal developmental 

- NZW Rabbit

45902212 (2003)

0, 1.5, 5.0 mg/kg/day

Acceptable/Non-guideline

Maternal: NOAEL = not established. LOAEL = 1.5 

mg/kg/day based on increased serum tyrosine level.

Developmental: NOAEL = not established, the LOAEL = 

1.5 mg/kg/day based on an increased incidence of absent 

kidney and ureter and increased incidences of 

supernumerary thoracic vertebrae and supernumerary 13th 

rib.

870.3700b

Prenatal developmental 

- NZW Rabbit

45902213 (2003)

0, 1.5, 5.0 mg/kg/day

Acceptable/Non-guideline

Maternal: NOAEL = 5.0 mg/kg/day. LOAEL was not 

established. Developmental: NOAEL = not established, 

the LOAEL for N33 and N17/CFR 1-2 was 1.5 mg/kg/day 

based on increased presence of supernumerary thoracic 

vertebrae and supernumerary 13th rib. No effect was 

observed for N17/CFR 3 at 0.5 mg/kg/day (the only dose 

tested). 

870.3700b

Prenatal developmental 

- NZW Rabbit

46020301 (2003)

0, 5, 50, 450 mg/kg/day

Acceptable/Guideline

Maternal: NOAEL = 450 mg/kg/day. LOAEL not 

established.

Developmental: NOAEL = not established. LOAEL = 5 

mg/kg/day based on visceral findings (fluid-filled 

abdomen, pale liver, and dark content of the stomach and 

intestines) and alterations in skeletal development (i.e., 

incomplete ossification of the vertebrae and talus, and 

supernumerary thoracic vertebrae and 13th rib).

870.3700b

Prenatal developmental 

- Himalayan Rabbit

46020302 (2003)

0, 50, 150, 450 mg/kg/day

Acceptable/Guideline

Maternal: NOAEL = 150 mg/kg/day. LOAEL = 450 

mg/kg/day based on decreased body weight body-weight 

gains, food consumption and increased incidences of 

abortion and lack of defecation. No serum tyrosine level 

was measured.

Developmental: NOAEL = not established. LOAEL = 50 

mg/kg/day based on decreased fetal weight and increased 

an incidence of visceral malformations, and skeletal 

malformations, variations, and unclassified abnormalities.

870.3700b

Prenatal developmental 

- NZW Rabbit

46020303 (2003)

0, 0.5, 5, 50, 450 mg/kg/day

Acceptable/Guideline

Maternal: NOAEL = 450 mg/kg/day. LOAEL = not 

established.

Developmental: NOAEL = 0.5 mg/kg/day. LOAEL = 5 

mg/kg/day based on increased presence of 27 pre-sacral 

vertebrae and increased an incidence of full 

supernumerary 13th rib.

870.3700b

Prenatal developmental 

- Himalayan Rabbit

46020304 (2003)

0, 50, 150, 450 mg/kg/day

Acceptable/Guideline

Maternal: NOAEL=450 mg/kg/day. LOAEL= not 

established.

Developmental: NOAEL = not established. LOAEL = 50 

mg/kg/day based on an increased incidence of extra 

sternebral ossification sites and supernumerary 13th rib. 

870.3700a

Prenatal developmental 

- Mouse

45902208, 45902209 (2003)

0, 30, 200, 1000 mg/kg/day

Acceptable/guideline

Maternal: NOAEL = not established. LOAEL = 30 

mg/kg/day based on increased serum tyrosine level. 

Developmental: NOAEL = 1000 mg/kg/day. LOAEL = 

not established.

870.3800

Reproduction and 

fertility effects

- Rat

45902214 (2003)

(0, 4, 40, 400, 4000 ppm)

M: 0, 0.4, 4.2, 42.2, 426.8 

mg/kg/day

F: 0, 0.5, 4.6, 46.9, 471.9 mg/kg/day

Acceptable/guideline

Parental/system:

NOAEL = 0.4/0.5 mg/kg/day (M/F). LOAEL = 4.2/4.6 

mg/kg/day (M/F) based on decreased body weight, bodyweight gain in males, increased thyroid and kidney 

weights of both sexes, and microscopic findings in eyes, 

kidney and thyroid of both sexes.

Reproductive:

NOAEL = 426.8/471.9 mg/kg/day (M/F). LOAEL = not 

established

Offspring:

NOAEL = 0.4/0.5 mg/kg/day (M/F). LOAEL = 4.2/4.6 

mg/kg/day (M/F) based on decreased pup weight and 

weight gain in F2 male and female pups and increased 

time to preputial separation in the F1 males. 
Topramezone Human-Health Risk Assessment DP#s 400310, 404014

Page 39 of 41

Table A.2.2. Subchronic, Chronic, and Other Toxicity Profile for Topramezone.

Guideline No/ Study 

Type/

MRID Nos.

Doses/Classification Results

870.4300

Chronic toxicity 

-Rat

45902217 (2002)

(0, 6, 60, 600, 6000 ppm)

M: 0, 0.4, 3.9, 42.0, 422.6 

mg/kg/day

F: 0, 0.5, 5.3, 53.2, 535.0 mg/kg/day

Acceptable/guideline

NOAEL = 0.4/0.5 mg/kg/day (M/F). LOAEL = 3.9/5.3 

mg/kg/day (M/F) based on effects on the eyes consisting 

of opacity, pannus, and chronic keratitis of the cornea in 

both sexes. In addition, thyroid hypertrophy was noted in 

males.

870.4200a

Carcinogenicity

-Rat

45902222 (2003)

(0, 6, 60, 600, or 6000 ppm)

M: 0, 0.4, 3.6, 36.4, 381.5 

mg/kg/day

F: 0, 0.5, 4.7, 50.8, 524.1 mg/kg/day

Acceptable/Guideline

NOAEL = 0.4/0.5 mg/kg/day (M/F). LOAEL = 3.6/4.7 

mg/kg/day (M/F) based on increased incidences of corneal 

opacity, decreased body weight and body-weight gains 

(males only) and histopathological evaluations in the 

thyroids, pancreas, and eyes of both sexes. Neoplastic 

pathology showed increased incidences of follicular cell 

adenomas in the thyroid glands of both sexes.

870.4100b

Chronic toxicity

- Dog

45902215, 45902216 (2002)

(0, 100, 500, 3000/2600, 9000/7800, 

25000/22000 ppm). 

M: 0, 2.9, 15.3, 81, 248, 688 

mg/kg/day

F: 0, 3.1, 15.4, 92, 287, 780 

mg/kg/day

Acceptable/guideline

For males, NOAEL = 2.9 mg/kg. LOAEL = 15.3 

mg/kg/day based on increased incidence of thyroid C-cell 

hyperplasia.

For females, NOAEL = 15.4 mg/kg/day. LOAEL = 92 

mg/kg/day based on decreased body weight, body-weight 

gain and food efficiency. 

870.4200b

Carcinogenicity 

- Mouse

45902221 (2002)

(0, 80, 800, 8000 ppm)

M: 0, 19, 194, 1903 mg/kg/day

F: 0, 26, 256, 2467 mg/kg/day

Acceptable/guideline

NOAEL = not established. LOAEL = 19/26 mg/kg/day 

(M/F) based on decreased body weight and body-weight 

gains in males. No serum tyrosine level was measured. 

No treatment-related tumors were demonstrated.

870.5100

Gene mutation

Salmonella 

typhimurium

45902225 (1999)

Acceptable/guideline

No indication of a mutagenic response in any strain at any 

level up to cytotoxic concentrations either with or without 

S9 activation.

870.5100

Gene mutation

Salmonella 

typhimurium

45902226 (2002)

Acceptable/Guideline

No indication of a mutagenic response in any strain at any 

level up to cytotoxic concentrations either with or without 

S9 activation. 

870.5100

Gene mutation

Salmonella 

typhimurium

45902227 (2002)

Acceptable/Guideline

No indication of a mutagenic response in any strain at any 

level up to cytotoxic concentrations either with or without 

S9 activation.

870.5100

Gene mutation

Salmonella 

typhimurium

45902228 (2003)

Acceptable/Guideline

Based on these considerations, it was concluded that there 

was confirmed evidence of a mutagenic response in S. 

typhimurium TA98 in the non-activated portion of both 

the plate incorporation and pre-incubation assays. The 

effect was, however, observed at high concentrations 

( 3000 μg/plate– plate incorporation and 2500 μg/plate–

pre-incubation). It was further concluded that the 

mutagenic effect was likely due to impurities in the test 

article because: 1) the response was seen at high 

concentrations including and exceeding the limit dose, 2)

bacterial gene mutation assays conducted with other lots 

of the test material were negative up to the limit dose (see 

MRID Nos. 45902225 through 45902227, and 3) the ai

used in the current study has the lowest percentage of 

purity (95.8% versus 97.7 to 99.3% ai for the other lots). 

870.5100

Gene mutation

Salmonella 

typhimurium

45902229 (2001)

Acceptable/Guideline

No indication of a mutagenic response in any strain up to 

cytotoxic levels either with or without S9 activation.

870.5300

In vitro Mammalian 

Cell Gene Mutation

45902230

Acceptable/guideline

No indication that topramezone induced a mutagenic 

response, either in the presence of absence of S9 

activation. 
Topramezone Human-Health Risk Assessment DP#s 400310, 404014

Page 40 of 41

Table A.2.2. Subchronic, Chronic, and Other Toxicity Profile for Topramezone.

Guideline No/ Study 

Type/

MRID Nos.

Doses/Classification Results

870.5375

In vitro Mammalian 

Chromosome 

Aberration 

45902233 (2002)

Acceptable/guideline

Topramezone-induced a clastogenic response in the 

presence of S9 activation with significant effects recorded 

only at an insoluble limit concentration. 

870.5375

In vitro Mammalian 

Chromosome 

Aberration 

45902232 (1999)

Acceptable/guideline

Topramezone-induced a clastogenic response in the 

presence of S9 activation with significant effects recorded 

only at an insoluble limit concentration.

870.5395

In vivo Mouse Bone 

Morrow Micronucleus

45902234 (1999)

Acceptable/guideline

No evidence that topramezone was clastogenic or 

aneugenic. 

870.5550

UDS

45902302 (1999)

Acceptable/Guideline

No evidence that topramezone-induced UDS, as 

determined by radioactive tracer procedures [nuclear 

silver grain counts] at any concentration tested.

870.6200

Acute Neurotoxicity

- Rat

45902303 (2002)

0, 125, 500, 2000 mg/kg

Acceptable/guideline

NOAEL = 2000 mg/kg/day, no neurotoxicity observed.

870.6200

Subchronic 

neurotoxicity

- Rat 

45902201 (2002)

(0,60,600,6000 ppm)

M: 0, 4.2, 43.8, 432.9 mg/kg/day

F: 0, 5.0, 50.9, 510.1 mg/kg/day

Acceptable/guideline

No neurotoxicity observed.

Systemic NOAEL = not established. LOAEL = 4.2/5/0 

mg/kg/day (M/F) based on elevated levels of granular 

casts and transitional epithelial cells in the urinary 

sediment of the males, increased incidences of corneal 

clouding in females, minimal diffuse degeneration of the 

pancreas (both sexes), and slight to moderate flaky colloid 

in the thyroid of the males.

870.6300

Developmental 

Neurotoxicity

-Rat

45902304 (2003)

0, 8, 80, 800 mg/kg/day

Acceptable/Non-guideline

Maternal: NOAEL = not established. LOAEL = 8 

mg/kg/day based on corneal opacities.

Offspring: NOAEL = not established. LOAEL = 8 

mg/kg/day based on decreased auditory startle reflex 

response 

870.7485

Metabolism

45902305, 45902306 (2002)

1, 100, 200, 400, 500 mg/kg

Acceptable/Guideline

Absorption of [14C]-topramezone following a single oral 

dose was rapid but limited, with the highest plasma 

concentrations observed at 1 hour (first time point 

measured). Oral absorption is estimated to be 

approximately 20% of the administered dose. The 

majority of the dose was recovered within 48 hours in the 

feces (73-91% dose) and urine (8-29% dose). 

870.7600

Rodent In Vivo Dermal 

Penetration Study - Rat

45902307 (2002)

Doses 0, 0.004, 0.068, or 3.36 mg 

ai/cm2.

The majority of the applied dose for each group was not 

absorbed (91.0-98.3% dose), with the greatest amount of 

the non-absorbed material being recovered from the skin 

wash (90.8-96.0% dose). Absorbed radioactivity was low 

and accounted for 0.16-2.60% of the dose for all groups 

for all exposures. 
Topramezone Human-Health Risk Assessment DP#s 400310, 404014

Page 41 of 41

Appendix B. Physical/Chemical Properties of Topramezone

Table B1. Physicochemical Properties of Topramezone.

Parameter Value

Melting point/range 220.9 C - 222.2 C

pH 2.9 (1% deionized water)

Density (20 C) 1.425 g/cm3

Water solubility (20 C)

 pH g/L

 3 0.06

 5 0.98

 7 15

 9 23.4

Solvent solubility (g/100 mL at 20 C)

 Solvent Solubility

 Acetone <1.0

 Acetonitrile <1.0

 Dichloromethane 2.5 - 2.9 

 Ethyl acetate <1.0

 Methanol <1.0

 n-heptane <1.0

 N,N-dimethylformamide 11.4-13.3

 1-octanol <1.0

 2-propanol <1.0

 Toluene <1.0

Vapor pressure at 20 C and 25 C <1.0 x 10–12 hPa (7.5 x 10-13 mmHg)

Dissociation constant (pKa) 4.06

Octanol/water partition coefficient Log(KOW) at 20 C

 Buffer pH Log Kow

 4 – 0.81

 7 – 1.52

 9 – 2.34

UV/visible absorption spectrum

 λ, nm ξ, mol-1cm-1

 207 27 077

 272 8601

 300 5800

 410 410