UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

MEMORANDUM 

Date: 04-JUN-2014 

OFFICE OF 

CHEMICAL SAFETY AND 

POLLUTION PREVENTION 

SUBJECT: Mesotrione. Human-Health Assessment Scoping Document in Support of 

Registration Review. 

PC Code: 122990 DP Barcode: D417231 

Decision No.: 486616 Registration No.: N/ A 

Petition No.: N/A Regulatory Action: Registration Review Scoping Document 

Risk Assessment Type: N/ A Case No.: 7256 

TXR No.: N/A CAS No.: 104206-82-8 

MRIDNo.: N/A 40CFR: §180 571~· 

FROM: Sarah J. Levy, Chemist ;~ q 

Kelly M. Lowe, Environmental Scie~tis 

Monique Perron, S.D., Toxicologist 171,; .. ", ..;J ~ Risk Assessment Branch 1 (RABI) 1 ....,,0 

Health Effects Division (HED, 7509P) 

TO: Jolene Trujillo 

Pesticide Re-Evaluation Division (PRD) (7508P) 

Attached is HED's human-health risk assessment scoping document for mesotrione to support 

Registration Review. 

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______ so rion~ Registration Review Huf!!an-Health Assessment Scoping Document 

Table of Contents 

Executive Summary ........................................................................................................................ 3 

1.0 Introduction .............................................................................................................................. 4 

2. 0 Hazard Characterization/ Assessment. ...................................................................................... 5 

3.0 Residue Chemistry ................................................................................................................... 6 

4.0 Dietary Exposure ..................................................................................................................... 7 

5.0 Residential Exposure ........................................................................................... .................... 8 

6.0 Aggregate-Risk Assessment .................................................................................................... 9 

7.0 Occupational Exposure ............................................................................................................ 9 

8.0 Public Health and Pesticide Epidemiology Data ................................................................... 10 

9.0 Tolerance Assessment and International Harmonization ...................................................... 11 

10.0 Environmental Justice .......................................................................................................... 11 

11.0 Cumulative ........................................................................................................................... 12 

12.0 Human Studies ..................................................................................................................... 12 

13.0 Risk-Assessment Updates> Data Deficiencies, and Label Revisions ................................... 13 

14.0 References............................................................................................................................ 13 

Attachment 1: Chemical Identity Tables ..................................................................................... 15 

Attachment 2: Mesotrione Acute, Subchronic> and Chronic Toxicity Profile ............................. 16 

Attachment 4: Summary of Registered Uses ............................................................................... 22 

Attachment 5: Mesotrione IRLS Sheet. ....................................................................................... 24 

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Executive Summary

HED has prepared a scoping document to support Registration Review of mesotrione (2-[4-

(methylsulfonyl)-2-nitrobenzoyl]-1,3-cyclohexanedione). Mesotrione is a triketone herbicide 

that inhibits the enzyme p-hydroxyphenyl-pyruvate dioxygenase (HPPD), disrupting carotenoid 

biosynthesis. This process leads to the destruction of chlorophyll, resulting in a bleaching effect 

in susceptible plants. Mesotrione is intended for preemergence and postemergence use for

selective control of annual broadleaf weeds. The most recent quantitative human-health risk 

assessment was performed in 2009, and was for the use of mesotrione on soybeans (Memo, S. 

Levy et al., 12-AUG-2009; D357890). HED notes that a qualitative assessment was conducted 

for a new use on corn in 2010 (Memo, S. Levy et al., 20-JAN-2010; D372995). There is 

currently one pending PRIA action for mesotrione for a new use on mesotrione-tolerant 

soybeans.

Mesotrione is formulated as liquid, granular, and dry-flowable formulations, and is currently 

registered for use on a variety of crops, with tolerances ranging from 0.01 ppm to 1.5 ppm (40 

CFR §180.571 (a)). Mesotrione is also registered for use on turf, including athletic fields, 

recreational areas, residential lawns (spot treatments only for liquids), and golf courses. The 

current registrations include some Special Local Need (SLN) registrations, which include 

applications to additional use sites (e.g., wildflowers and cuphea).

HED has evaluated the status of the human-health risk assessments for mesotrione to determine 

whether sufficient data are available and whether any updates are needed to support Registration 

Review. HED has considered all available data and human-health risk assessments for 

mesotrione with respect to its toxicity, exposure, and usage databases, and the most updated 

Agency science policy and risk assessment methodologies to determine the scope of work 

necessary to support Registration Review.

The toxicity database for mesotrione is complete as required by the 2007 revised 40 CFR 

Toxicology Data Requirements. No additional toxicological studies are currently required. In 

subchronic and chronic oral studies in the rat, mouse, and dog, mesotrione produced ocular, 

kidney, and liver effects, which are consistent with the mammalian toxicity profile for HPPD 

inhibitors caused by high tyrosine levels in the blood. Body weight decrements were also noted 

in mice and rats in multiple studies. Increased susceptibility was seen in developmental and 

reproduction toxicity studies with offspring effects observed at doses below maternal/parental 

toxicity. As part of Registration Review, the endpoints, doses, and safety factors used in the 

most recent human-health risk assessment will be re-evaluated according to current HED policy.

The residue chemistry database is adequate to support current Registration Review requirements. 

Adequate metabolism (crops, livestock, and rotational crops), storage stability, magnitude of the 

residue, and processing data are available to support the registered uses. Adequate methods are 

available for enforcement of the currently established tolerances. 

The dietary-exposure database is adequate to support current registration requirements. The last 

risk assessment provided unrefined chronic dietary (food + drinking water) exposure estimates 

that are below HED’s level of concern (LOC) for the general U.S. population and all population 

subgroups (Memo, S. Levy, 05-AUG-2009; D358158); all infants <1 year old were the most 

highly exposed population (5.8% cPAD). Based on toxicological considerations, assessment of 

acute dietary exposure is unnecessary. As part of Registration Review, a revised dietary 

exposure analysis may be required to reflect the most recent dietary exposure models, potential 
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revised estimated drinking water concentrations (EDWCs), and/or changes to the toxicological 

points of departure (PODs).

There is sufficient information available to assess occupational and residential exposure and risk 

from the registered uses. Residential handler and post-application exposure assessments were 

recently completed based upon HED’s 2012 Residential Standard Operating Procedures (SOPs)

and did not identify risk estimates of concern. However, a higher application rate for handheld 

equipment was identified during the label review process for the scoping document. This higher 

rate will need to be assessed for residential handlers during Registration Review. The residential 

post-application assessment will not be affected and will not need to be updated, unless policies 

or toxicological PODs change. The most recent occupational handler and post-application 

exposure assessments are reflective of current exposure policies and data, and did not identify 

risk estimates of concern. These assessments are protective of most registered uses, except for 

uses on sod farms and a SLN use on cuphea (an ornamental). During Registration Review, 

updated occupational assessments will be conducted to reflect all currently registered uses. In 

addition, assessments for all uses may be updated if toxicological PODs are revised. 

A new aggregate human-health risk assessment may be required during Registration Review to 

incorporate revised dietary exposure analyses and/or revised residential exposure assessments. 

No data deficiencies were identified for mesotrione. EPA anticipates conducting the following 

risk-assessment updates during Registration Review:

 Toxicology: 

o Reevaluate toxicity endpoint/dose selection, along with the Food Quality 

Protection Act Safety Factor (FQPA SF) based on current HED policy.

 Residue Chemistry: 

o None.

 Dietary Exposure: 

o A revised dietary-exposure analysis may be required to reflect the most recent 

dietary-exposure models, potential revised EDWCs, and/or changes to the 

toxicological PODs.

 Aggregate Exposure:

o New aggregate risk assessment may be required during Registration Review 

to incorporate revised dietary exposure analyses, revised residential exposure 

assessments, and/or changes to the toxicological PODs.

 Occupational/Residential Exposure: 

o Revised occupational and residential handler assessments will be necessary to 

reflect maximum application rates. 

o Revised occupational post-application assessments will be necessary to reflect 

all currently registered uses (including SLN registrations).

o Assessments for all residential and occupational uses may be updated if 

toxicological PODs are revised. 

1.0 Introduction

Mesotrione is a triketone herbicide that inhibits the enzyme HPPD, disrupting carotenoid 

biosynthesis. It is formulated as liquid, granular, and dry-flowable formulations, and is currently 

registered for use on a variety of crops as well as for use on turf, including athletic fields, 

recreational areas, residential lawns, and golf courses. The current registrations include some 
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SLN registrations, which include applications to additional use sites (e.g., wildflowers and 

cuphea). The most recent human-health risk assessment was performed in 2009 and was for the 

use of mesotrione on soybeans (Memo, S. Levy et al., 12-AUG-2009; D357890). There is 

currently one pending PRIA action for mesotrione for a new use on mesotrione-tolerant 

soybeans.

2.0 Hazard Characterization/Assessment

Mesotrione acts by inhibiting the HPPD enzyme, which results in decreased carotenoid synthesis 

and bleaching of target plants. In mammals, the amino acid tyrosine is catabolized by the 

tyrosine aminotransferase (TAT) enzyme to form the substrate 4-hydroxyphenylpyruvic acid 

(HPPA), which is then further catabolized by the HPPD enzyme for excretion. Inhibition of 

HPPD leads to the build-up of HPPA and, since the formation of HPPA by TAT is reversible, 

this build-up results in elevated levels of tyrosine in the blood (tyrosinemia). Tyrosinemia in 

laboratory animals results in ocular, developmental, liver, and kidney effects. TAT activity can 

vary depending on the species, therefore the degree of tyrosine accumulation differs among 

species. 

In a series of rat metabolism studies, radiolabeled mesotrione was readily absorbed and 

distributed throughout the body after single and repeated doses. Concentrations of radioactivity 

were highest in the liver and kidney with radioactivity also detected in the carcass, GI tract, 

spleen, bone, and blood. The majority of labeled mesotrione was excreted (predominantly as 

unchanged parent) via the urine and feces. Biliary excretion was more prominent for males than 

females. Increasing the dose or repeated doses had little effect on the pattern of excretion.

In subchronic and chronic oral studies in the rat, mouse, and dog, mesotrione produced ocular, 

kidney, and liver effects, which are consistent with the mammalian toxicity profile for HPPD 

inhibitors caused by high tyrosine levels in the blood. Body-weight decrements were also noted 

in mice and rats in multiple studies. Even though the rat was found to be the most sensitive 

species for these effects, HED’s Mechanism of Toxicity Science Advisory Review Committee 

(MTSARC) concluded that the mouse is a more appropriate model for assessing human risk for 

tyrosine-mediated toxicological effects (D. Nixon, 27-MAR-2001, TXR# 0051908). 

There was evidence of increased susceptibility of rats, mice, and rabbits in the developmental 

studies and mice in the reproduction toxicity study. Offspring effects in the developmental 

toxicity studies (delayed ossification and ancillary ribs and vertebrae) were seen at doses below 

those for maternal toxicity (decreased body-weight gain and food consumption in rats and 

abortions and clinical signs of toxicity in rabbits; no effects seen in mice). In the mouse 

reproduction toxicity study, tyrosinemia and ocular discharge were observed in offspring at 

doses below those for parental toxicity, which was evidenced by increased kidney weights and 

tyrosinemia. In the rat reproduction study, offspring susceptibility was not observed. 

Tyrosinemia was observed in parents and offspring at the same dose level.

Mesotrione was classified as having low acute toxicity via the oral, dermal, and inhalation routes

(Toxicity Categories III or IV). It is classified as a mild eye irritant, but it is not a dermal 

sensitizer or dermal irritant. 

There was no evidence of neurotoxicity or neuropathology seen in the acute and subchronic 

neurotoxicity studies.
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There was no evidence of carcinogenic potential in either the rat or mouse carcinogenicity 

studies and no concern for mutagenicity. Mesotrione is classified as “not likely to be 

carcinogenic to humans.”

An immunotoxicity study submitted since the last risk assessment (MRID #48748301) showed 

no evidence of immunotoxicity. 

HED previously requested a subchronic inhalation study to characterize the effects of mesotrione 

via the inhalation route. Since that request, the HED Hazard and Science Policy Council 

(HASPOC) concluded, using a weight-of-evidence approach, that the subchronic inhalation 

study was not required at this time (A. Dunbar, 27-JUN-2013; TXR #0056648). The endpoints 

and PODs from the last quantitative human-health risk assessment for mesotrione (S. Levy, 12-

AUG-2009; D357890) can be found in Attachment 3.

Conclusions: The toxicity database for mesotrione is complete as required by the 2007 revised 

40 CFR Toxicology Data Requirements. No additional toxicological studies are currently 

required. As part of registration review, the endpoints, doses, and safety factors used in the most 

recent risk assessment will be re-evaluated according to current HED policy.

3.0 Residue Chemistry

Permanent tolerances are established for residues of mesotrione, including its metabolites and 

degradates in/on a variety of crops, with tolerances ranging from 0.01 ppm to 1.5 ppm (40 CFR 

§180.571 (a)). There are currently no tolerances established for mesotrione in/on livestock 

commodities or for indirect/inadvertent residues in rotational crops.

The HED Metabolism Assessment Review Committee (MARC) reviewed and discussed field 

corn, peanut, cranberry (cyclohexane-2-

14C label only), livestock, rotational crop, and drinking 

water studies for the herbicide mesotrione, as well as toxicological and environmental fate data, 

for determination of the residues of concern (Memo, S. Levy, et al., 26-APR-2001; 

D274111). Subsequent to this decision, registration for application of mesotrione to asparagus, 

cranberry (Section 18), berry crop group (group 13), lingonberry, flax, grass grown for seed, 

oats, okra, rhubarb, sorghum (grain and sweet), and sugarcane were approved by HED. HED 

concluded that for these crops, the residue of concern for risk assessment and tolerance 

enforcement is mesotrione (Memo, S. Levy, 05-DEC-2007; D335364).

The nature of the residue in ruminants and poultry has been adequately defined based on 

previously reviewed cattle and hen studies. HED previously concluded that the residue of 

concern in livestock commodities is mesotrione (HED MARC, 26-SEP-2001). In the last risk 

assessment for soybeans, HED noted that there was no reasonable expectation of quantifiable 

mesotrione residues of concern in eggs, milk, and the meat, fat, or meat byproducts of poultry 

and ruminants [40 CFR Category 180.6(a)(3)] as a result of any registered use. 

 

An acceptable high-performance liquid chromatography (HPLC) method with tandem massspectrometry detection (MS/MS), Method RAM 366/01, is available to analyze residues of 

mesotrione and metabolite (4-methanesulfonyl-2-nitro-benzoic acid (MNBA). This method was 

previously reviewed and has been forwarded to the U.S. Food and Drug Administration (FDA) 

for inclusion in the Pesticide Analytical Manual (PAM) Volume II as a confirmatory method. 

The method was adequately validated in conjunction with the analysis of several field trial and 

processing study samples. Based on the lowest level of method validation (LLMV), the limit of 
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quantitation (LOQ) was 0.01 ppm for each analyte in all soybean and corn commodities. It was 

previously determined that multiresidue methods (MRMs) are not adequate for tolerance 

enforcement.

Adequate field trial and processing data are available to support the use of mesotrione on the 

registered crops. An adequate number of trials were conducted in the appropriate geographical 

regions using the appropriate formulation applied at the maximum use rate. These studies are 

also supported by adequate storage stability data. 

Adequate confined and field rotational crop data are available. HED previously concluded that 

the residue of concern in rotated crops is mesotrione. Based on the currently registered uses and 

PBIs, residues in rotational crops are expected to be insignificant. 

Conclusions: The residue chemistry database is adequate to support current Registration Review 

data requirements. Adequate metabolism (crops, livestock, and rotational crops), storage 

stability, magnitude of the residue, and processing data are available to support the registered 

uses. Adequate methods are available for enforcement of the currently established tolerances. 

4.0 Dietary Exposure

The HED MARC concluded that the residue of concern in drinking water is mesotrione (Memo, 

S. Levy, APR-2001; D274111). All metabolites identified were present at low levels, and are 

not expected to be more toxic than the parent. 

No toxic effects attributable to a single exposure to mesotrione have been identified; therefore, 

an acute reference dose (aRfD) was not established for mesotrione, and an acute dietary exposure 

assessment was not required. HED has previously conducted a chronic dietary exposure 

analysis, which considered all currently registered uses (Memo, S. Levy, 05-AUG-2009; 

D358158). The analysis was conducted using the Dietary Exposure Evaluation Model – Food 

Consumption Intake Database (DEEM-FCID, ver. 2.03), which incorporates the food

consumption data from the United States Department of Agriculture (USDA) Continuing 

Surveys of Food Intakes by Individuals (CSFII; 1994-1996 and 1998) and assumed tolerancelevel residues and 100% crop treated. 

Dietary risk estimates were determined by considering exposures from both food and EDWCs. 

These EDWC values were provided in a 2008 memo from the Environmental Fate and Effects 

Division (EFED; Memo, K. Moore, 25-NOV-2008; D354510). EDWCs resulting from an 

experimental use permit (EUP) soybean application scenario was used as it resulted in greater 

EDWC values than from any other uses (i.e., more conservative). The EUP soybean application 

use rate is also the highest registered or proposed use rate for mesotrione. 

Mesotrione EDWCs in groundwater were estimated using the Tier 1 model SCI-GROW 

(Screening Concentration in Ground Water). EDWCs in surface water were estimated using the 

linked Tier 2 models Pesticide Root Zone Model (PRZM v3.12beta, 24-MAY-2001) and 

Exposure Analysis Modeling System (EXAMS v2.98.04, 18-AUG-2002), coupled with the input 

shell pe5.pl (16-NOV-2006). The surface water EDWC of 5.1 ppb (greater than the groundwater 

number) was incorporated in the DEEM-FCID into the food categories “water, indirect, all 

sources,” and “water, direct, all sources.” In the 2009 assessment, dietary exposure was 

estimated at 0.000140 mg/kg/day for the U.S. population (2.0% of the cPAD) and 0.000403 
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mg/kg/day (5.8% of the cPAD) for the most highly exposed population subgroup (all infants, <1 

year old) 

Conclusions: The dietary-exposure database is adequate to support current registration 

requirements. In the most recent risk assessment, chronic dietary exposures were not of concern 

to HED. However, as part of Registration Review, a revised dietary exposure analysis may be 

required to reflect the most recent dietary exposure models, potential revised EDWCs, and/or 

changes to the toxicological PODs.

5.0 Residential Exposure

Mesotrione is currently registered for use on turf, including athletic fields, recreational areas, 

residential lawns (spot treatments only for liquids), and golf courses. Both liquid and granular 

formulations are registered. Attachment 4 includes a summary of the use sites for mesotrione, 

including those related to residential areas. Residential exposures from the registered residential 

uses have been assessed in the most recent occupational and residential exposure (ORE) 

assessment for mesotrione (Memo, K. Lowe, 23-OCT-2013; D415329). 

For residential handlers, the following scenarios were assessed:

 Mixer/loader/applicator (M/L/A) of liquids with manually-pressurized handwand, 

 M/L/A of liquids with sprinkler can, 

 M/L/A of liquids with backpack sprayer, and 

 L/A of granulars with push-type spreader. 

For residential post-application exposure, the following scenarios were assessed: 

 Dermal exposure for adults and children from high-contact lawn activities, mowing, and 

golfing; and 

 Incidental oral post-application exposure for children (1 to <2 years old) from highcontact lawn activities.

A chemical-specific turf transferable residue (TTR) study was submitted for mesotrione and used 

in the residential assessment. None of the residential handler or post-application scenarios 

assessed resulted in risk estimates of concern (i.e., all margins of exposure (MOEs) ≥ the LOC of 

300). Based on a review of the registered labels for mesotrione for this scoping document, a 

slightly higher rate for application of liquid formulations to turf was identified for handheld 

equipment. This higher rate will need to be assessed for residential handlers during Registration 

Review. The post-application assessment will not be affected and will not need to be updated, 

unless policies or toxicological PODs change.

Spray Drift/Bystander Exposure

Residential exposures resulting from off-site transport (e.g., spray drift or volatilization) may 

occur as a result of applications of mesotrione. In the most recent ORE assessment (Memo, K. 

Lowe, 23-OCT-2013; D415329), potential exposures from spray drift were evaluated, and it was 

determined that a quantitative spray drift assessment for mesotrione was not required because the 

maximum application rate for a crop/target site multiplied by the adjustment factor for drift was 

less than the maximum direct spray residential turf application rate. Therefore, the turf postapplication MOEs are protective for any potential exposures related to spray drift for the 

currently registered uses of mesotrione. The Agency is in the process of evaluating bystander 
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exposures resulting from volatilization, and the need for volatilization risk assessment for 

mesotrione will be examined during registration review.

Conclusions: The residential exposure database is adequate to support the Registration Review 

process for mesotrione. Residential handler and post-application exposure assessments were 

recently completed based upon HED’s Residential SOPs; however, a higher application rate for 

handheld equipment was identified during the label review process. This higher rate will need to 

be assessed. The post-application assessment and spray drift assessment will not be affected and 

will not need to be updated, unless policies or toxicological PODs change.

6.0 Aggregate-Risk Assessment

The most recent aggregate-risk assessment was performed in conjunction with the 2009 HED 

human-health risk assessment (Memo, S. Levy et al., 12-AUG-2009; D357890). Since an acute 

dietary endpoint was not identified, an acute aggregate assessment was not performed. Separate 

short-term and intermediate-term aggregate assessments were conducted for mesotrione. The 

short- and intermediate-term aggregate risks were made up of dietary and non-dietary (residential 

turf use) sources of exposure, and were not of concern to HED. Chronic (long-term) aggregate 

risk is made up only of dietary sources; therefore, the chronic dietary exposure estimates 

represents chronic aggregate exposure, and were not of concern to HED. Aggregate cancer risk 

was not calculated because mesotrione was classified as “not likely to be carcinogenic to 

humans.”

Conclusions: A new aggregate risk assessment may be required during Registration Review to 

incorporate revised dietary exposure analyses and/or revised residential exposure assessments. 

7.0 Occupational Exposure

Occupational handler and post-application exposures are expected based on the registered

agricultural uses of mesotrione. Attachment 4 provides a summary of the occupational use 

pattern. The current registrations include some SLN registrations, which include applications to 

additional use sites (e.g., wildflowers and cuphea) and/or different application methods than 

those currently on registered labels (e.g., aerial application to corn for dry flowable 

formulations). Current formulations include liquid, granular, and dry flowable products. The 

application rates range from 0.078 – 0.25 lb ai/A, and applications can be made pre-plant, preemergence, or early post-emergence. 

Occupational Handlers

There is the potential for dermal and inhalation exposure to occupational handlers from the 

currently registered use pattern of mesotrione. In the most recent exposure assessment for 

mesotrione (Memo, K. Lowe, 23-OCT-2013, D415329), assessments were conducted for 

mixers/loaders, applicators and flaggers for aerial, groundboom and chemigation applications of 

a liquid formulation. The assessment was based on the latest HED exposure policies and data, 

maximum application rates (~ 0.25 lb ai/A), and maximum area treated per day or gallons 

handled for the proposed uses. Handler' exposure and risks were calculated at baseline (long 

pants, a long-sleeved shirt, no chemical-resistant gloves, and no respirator) and with personalprotective equipment (PPE) when necessary (e.g., chemical-resistant gloves, respirators, and 

engineering controls). 
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Dermal and inhalation risk estimates were not of concern (i.e., MOEs ≥ 300) with the use of 

chemical-resistant gloves as specified on the proposed labels for the action. Based on a review 

of the registered labels for mesotrione for this scoping document, it appears that this recent 

assessment covers most of the occupational handler scenarios anticipated for the registered uses 

of mesotrione; however, there were a couple of use patterns identified that will need to be 

assessed during Registration Review:

 

1) For turf (including golf courses, residential lawns, athletic fields, and non-residential turf 

areas), there is a higher rate that was identified for handheld equipment that has not been 

assessed. 

2) There are SLN registrations for corn that allow for aerial applications of dry flowable 

formulations. This scenario has not been assessed previously.

3) There is a SLN registration for applications to cuphea (an ornamental) that has not been 

assessed previously.

4) There is a SLN registration for applications to wildflowers that has not been assessed 

previously.

Occupational Post-Application

There may be the potential for post-application dermal exposure to workers following 

applications of mesotrione to agricultural crops and commercial use sites. In the most recent 

exposure assessment for mesotrione (Memo, K. Lowe, 23-OCT-2013, D415329), occupational 

post-application assessments were conducted for the proposed crops for early-season activities 

since most applications are made early post-emergence. The assessment was based on the latest 

HED exposure policies and data and maximum application rates (~ 0.25 lb ai/A). A pilot 

dislodgeable foliar residue (DFR) study was submitted for mesotrione which was deemed 

acceptable for use in risk assessment. Using chemical-specific residue data, no risk estimates of 

concern were identified for mesotrione (i.e., all MOEs ≥ 300) on the day of application. 

Based on a review of the registered labels for mesotrione for this scoping document, it appears 

that this recent assessment covers the occupational post-application scenarios anticipated for 

most of the registered uses; however, there were a couple of use patterns identified that will need 

to be assessed during Registration Review: 

1) For sod farms, there are post-application activities (e.g., maintenance activities, 

harvesting of sod, and transplanting/planting sod) that have a higher exposure potential 

than what has been assessed previously.

2) For the SLN on cuphea (ornamentals), a post-application assessment for nursery crops 

will need to be conducted. 

Conclusions: The occupational exposure database is adequate to support the Registration 

Review process for mesotrione. The most recent occupational handler and post-application 

exposure assessment is reflective of current exposure policies and data, and did not identify risks 

of concern. This assessment is protective of most registered uses, except for uses on sod farms 

and a SLN use on cuphea (an ornamental). During Registration Review, updated occupational 

assessments will be conducted to reflect all currently registered uses. In addition, assessments 

for all uses may be updated if toxicological PODs are revised. 

8.0 Public Health and Pesticide Epidemiology Data

The OPP Incident Data System (IDS) and the Centers for Disease Control and 

Prevention/National Institute for Occupational Safety and Health (CDC/NIOSH) Sentinel Event 
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Notification System for Occupational Risk-Pesticides (SENSOR) databases were consulted for 

pesticide incident data on the active ingredient mesotrione (PC code: 122990). The purpose of 

the database search was to identify potential patterns in the frequency and severity of the health 

effects attributed or potentially attributed to mesotrione exposure. Mesotrione is not included in 

the Agricultural Health Study (AHS).

For the Main IDS (which contains incidents resulting in higher severity outcomes and provides 

more detail with regard to case specifics), there were two incidents reported for the single 

chemical active ingredient mesotrione in the database from January 1, 2009 to January 15, 

2014. These two incidents were reported as moderate severity. There were 13 additional 

incidents reported involving more than one chemical. One incident was classified as major 

severity and 12 incidents were classified as moderate severity. In Aggregate IDS (which 

contains incidents resulting in less severe human incidents (minor, unknown, or no effects 

outcomes)), there were 20 reported incidents involving mesotrione from January 1, 2009 to 

January 15, 2014. These incidents were all classified as minor severity. Overall, there are few 

incidents involving mesotrione reported to IDS. A query of SENSOR-Pesticides from 1998-

2010 identified 4 cases, stemming from 3 events, involving mesotrione. Multiple active 

ingredients were implicated in all 4 cases. Three of the cases were classified as low severity and 

one case was reported as moderate. The low frequency and low severity of acute poisoning 

cases (also referred to as human incident data) reported for mesotrione in both the IDS and 

SENSOR-Pesticides does not trigger an EPA concern at this time. The Agency will continue to 

monitor the incident information, and if the magnitude and frequency of reported acute poisoning 

events increases, additional analysis will be performed. 

Conclusions: The Agency has reviewed the available incident data for mesotrione. Based on the 

low frequency and generally low severity of incident cases reported for mesotrione to either the

IDS or SENSOR-Pesticides, there does not appear to be a concern at this time that would warrant 

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

concern is triggered additional analysis will be conducted during Registration Review.

9.0 Tolerance Assessment and International Harmonization

U.S. permanent tolerances (listed in 40 CFR 180.571) are summarized in Attachment 5. All U.S. 

tolerances/Canadian maximum residue limits (MRLs) are harmonized, with the exception of 

cranberries. The U.S. cannot harmonize with Canada as the method LOQ (0.02 ppm in the U.S.) 

is higher than the Canadian MRL (0.01 ppm). During Registration Review, HED may look into 

the possibility of harmonizing with Canada for the cranberry tolerance.

10.0 Environmental Justice

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

most recent mesotrione human-health risk assessment, in accordance with U.S. Executive Order 

12898, “Federal Actions to Address Environmental Justice in Minority Populations and LowIncome Populationsa

.” The OPP typically considers the highest potential exposures from the 

legal use of a pesticide when conducting human-health risk assessments, including, but not 

limited to, people who obtain drinking water from sources near agricultural areas, the variability 

of diets within the U.S., and people who may be exposed when harvesting crops. Should these 

 

a http://www.epa.gov/compliance/environmentaljustice/resources/policy/exec_order_12898.pdf
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highest exposures indicate potential risks of concern, OPP further refines the risk assessments to 

ensure that the risk estimates are based on the best available information.

11.0 Cumulative

The Hazard and Science Policy Council (HASPOC) met on June 28, 2007 to discuss the mode of 

action and human relevance of HPPD inhibiting herbicides. The following is a summary of their 

decision regarding the need for a cumulative risk assessment (HASPOC Memo, 17-DEC-2007).

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. One explanation for this species-specific response in ocular opacity may be related to 

species differences in the clearance of tyrosine. A metabolic pathway exists to remove tyrosine 

from the blood that involves the liver enzyme 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. 

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 observation indicates that an HPPD inhibitor in it and of itself 

cannot easily overwhelm the tyrosine-clearance mechanism in humans.

Therefore, exposures 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. The Agency continues to study the complex 

relationships between elevated tyrosine levels and biological effects in various species. In the 

future, assessments of HPPD-inhibiting herbicides may consider more appropriate models and 

cross species extrapolation methods. Therefore, EPA has not conducted cumulative risk 

assessment with other HPPD inhibitors. 

12.0 Human Studies

Past mesotrione risk assessments rely in part on data from studies in which adult human subjects 

were intentionally exposed to a pesticide to determine their dermal and inhalation exposure. 

Many such studies, involving exposure to many different pesticides, comprise generic pesticide 

exposure databases such as the Pesticide Handlers Exposure Database (PHED), the Outdoor 

Residential Exposure Task Force (ORETF) Database, and the Agricultural Reentry Task Force 

(ARTF) Database. EPA has reviewed all the studies supporting these multi-pesticide generic 

exposure databases, and has found no clear and convincing evidence that the conduct of any of 

them was either fundamentally unethical or significantly deficient relative to the ethical 

standards prevailing at the time the research was conducted. All applicable requirements of 

EPA’s Rule for the Protection of Human Subjects of Research (40 CFR Part 26) have been 

satisfied, and there is no regulatory barrier to continued reliance on these studies.
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13.0 Risk-Assessment Updates, Data Deficiencies, and Label Revisions

No data deficiencies were identified for mesotrione. EPA anticipates conducting the following 

risk-assessment updates during Registration Review:

 Toxicology: 

o Reevaluate toxicity endpoint/dose selection, along with the Food Quality 

Protection Act Safety Factor (FQPA SF) based on current HED policy.

 Residue Chemistry: 

o None.

 Dietary Exposure: 

o A revised dietary-exposure analysis may be required to reflect the most recent 

dietary-exposure models, potential revised EDWCs, and/or changes to the 

toxicological PODs.

 Aggregate Exposure:

o New aggregate risk assessment may be required during Registration Review 

to incorporate revised dietary exposure analyses, revised residential exposure 

assessments, and/or changes to the toxicological PODs.

 Occupational/Residential Exposure: 

o Revised occupational and residential handler assessments will be necessary to 

reflect maximum application rates. 

o Revised occupational post-application assessments will be necessary to reflect 

all currently registered uses (including SLN registrations).

o Assessments for all residential and occupational uses may be updated if 

toxicological PODs are revised. 

14.0 References

HED Memoranda Relevant to Registration Review.

Author Barcode Date Title

K. Lowe D415329 10/23/13 Mesotrione. REVISED Occupational and Residential Exposure 

Assessment for Proposed Label Amendments Affecting 

Registered Uses on Corn, Sugarcane, Grasses Grown for Seed, 

Cranberry, Grain Sorghum, and Soybeans, and a Reassessment 

of Residential Uses.

K. Lowe D342065 10/9/07 HED’s Review of “Determination of Transferable Turf Residue 

Dissipation from Turf Treated with Mesotrione.

H. Podall D263245 2/24/00

E. Evans and 

S. Recore

D417803 2/6/14 Mesotrione: Tier I Review of Human Incidents.

S. Levy D335364 12/5/07

S. Levy et al. D357890 8/12/09

S. Levy et al. D372995 1/20/10

S. Levy D358158 8/5/09

D. Nixon TXR# 0051908 3/27/01

A. Dunbar TXR#0056648 6/27/13

S. Levy D274111 4/26/01

S. Levy D335364 12/5/07

HASPOC NR 12/17/07 The Mode of Action and Human Relevance of HPPD-Inhibiting 

Herbicides – Revised Interim Policy.
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Attachments: 

Attachment 1: Chemical Identity Tables.

Attachment 2: Mesotrione Acute, Subchronic, and Chronic Toxicity Profile.

Attachment 3: Mesotrione Endpoint Selection Tables.

Attachment 4: Summary of Registered Uses.

Attachment 5: Mesotrione International Residue Limit Status (IRLS) Sheet.

cc: S. Lowe (RAB1), K. Lowe (RAB1), M. Perron (RAB1)

RDI: RAB1 (2/26/14), C. Smith (2/26/14), D. Vogel (3/5/14)

S. Levy:S10953:PY-S:(703)305-073:7509P:RAB1
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Attachment 1: Chemical Identity Tables.

Table 1.1. Test Compound Nomenclature.

Compound

Common name Mesotrione

Company experimental name ZA1296

IUPAC name 2-(4-mesyl-2- nitrobenzoyl)cyclohexane-1,3-dione

CAS name 2-[4-(methylsulfonyl)-2-nitrobenzoyl]-1,3-cyclohexanedione

CAS registry number 104206-82-8

End-use product (EP) 4 lb/gal SC (Callisto® Herbicide; EPA Reg. No. 100-1131)

Compound

Common name MNBA

Chemical name 4-(methylsulfonyl)-2-nitrobenzoic acid

Table 1.2. Physicochemical Properties of the Technical Grade Test Compound Mesotrione.

Parameter Value Reference

Melting range 148.7-152.5°C RD Memo, H. Podall, 

2/24/2000; D263245. pH 3.4 (1% dispersion in water; 25°C)

Density 1.46 g/mL, 20°C

Water solubility 20°C

160 ppm, unbuffered water

0.22 g/100 mL, pH 4.8

1.5 g/100 mL, pH 6.9

2.2 g/100 mL, pH 9

Solvent solubility 20°C

0.37 g/100 mL, methanol

1.7 g/100 mL, ethyl acetate

0.27 g/100 mL, toluene

10.4 g/100 mL, acetonitrile

<0.03 g/100 mL, heptane

8.1 g/100 mL, acetone

Vapor pressure 4.3 x 10-8torr, 20°C

Dissociation constant, pKa 3.12, 20°C

Octanol/water partition coefficient 20°C

log POW = 0.11 in unbuffered water

log POW = 0.90 in pH 5 buffer

log POW <-1 at pH 7 and 9 buffered water

UV/visible absorption spectrum Absorption maximum in methanol at 256 

mu, with a molar extinction coefficient of 

2.24 x 104 M cm.

O O

O

NO2

SO2CH3

NO2

SO2CH3

HOOC
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Attachment 2: Mesotrione Acute, Subchronic, and Chronic Toxicity Profile.

2.1 Toxicology Data Requirements.

Study requirements (40 CFR 158.340) for use of mesotrione are below. Use of the new 

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

Study

Technical

Required Satisfied

870.1100 Acute Oral Toxicity.......................................................

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

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

870.2400 Acute Eye Irritation.......................................................

870.2500 Acute Dermal Irritation .................................................

870.2600 Skin Sensitization..........................................................

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

870.3100 90-Day Oral Toxicity in Rodents..................................

870.3150 90-Day Oral Toxicity in Nonrodents.............................

870.3200 21/28-Day Dermal Toxicity ..........................................

870.3250 90-Day Dermal Toxicity ...............................................

870.3465 90-Day Inhalation Toxicity ...........................................

yes

yes

yes

no

no1

yes

yes

yes

--

--

870.3700a Prenatal Developmental Toxicity (rodent) ....................

870.3700b Prenatal Developmental Toxicity (nonrodent) ..............

870.3800 Reproduction and Fertility Effects ................................

yes

yes

yes

yes

no2

yes

870.4100a Chronic Toxicity (rodent)..............................................

870.4100b Chronic Toxicity (nonrodent)........................................

870.4200a Carcinogenicity (rat)......................................................

870.4200b Carcinogenicity (mouse) ...............................................

870.4300 Combined Chronic Toxicity/Carcinogenicity ...............

yes

yes

yes

yes

yes

yes

yes

yes3

yes

yes

870.5100 Mutagenicity—Bacterial Reverse Mutation Test..........

870.5300 Mutagenicity—Mammalian Cell Gene Mutation Test...

870.5xxx Mutagenicity— Structural Chromosomal Aberrations...

870.5xxx Mutagenicity—Other Genotoxic Effects.......................

yes

yes

yes

yes

yes

yes

yes

yes

870.6200a Acute Neurotoxicity Screening Battery (rat).................

870.6200b 90-Day Neurotoxicity Screening Battery (rat) ..............

870.6300 Developmental Neurotoxicity .......................................

yes

yes

no

yes

yes

--

870.7485 Metabolism and Pharmacokinetics................................

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

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

yes

no

yes

yes

--

yes

1 HED HASPOC concluded that the subchronic inhalation study was not required at this time (A. Dunbar, 27-JUN-2013, TXR#0056648). 

2 Study is classified as unacceptable/not upgradable, but the rabbit is not considered the relevant species for human-health risk assessment;

therefore, this deficiency is not considered a data gap at this time.

3 The combined chronic toxicity/carcinogenicity study satisfies the requirement of the study.

2.2 Toxicity Profiles.

Table 2.2.1. Acute Toxicity Data for Mesotrione.

Guideline No./Study Type MRID# Results Toxicity Category

870.1100/Acute oral 44373512 LD50 > 5000 mg/kg IV

870.1200/Acute dermal 44373514 LD50 > 2000 mg/kg III

870.1300/Acute inhalation 44373516 LC50 > 4.75 mg/L IV

870.2400/Acute eye irritation 44373518 Mild eye irritant IV

870.2500/Acute dermal irritation 44373520 Not a dermal irritant IV

870.2600/Skin sensitization 44373522 Not a dermal sensitizer ---
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Table 2.2.2. Subchronic, Chronic and Other Toxicity Profile for Mesotrione.

Guideline 

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

870.3100

90-Day Oral 

Toxicity in Rodents 

(rat)

44505020 (1997)

Acceptable/guideline

0, 2.5, 5, 7.5, or 150 ppm

M: 0, 0.21, 0.41, 0.63, or 

12.46 mg/kg/day 

F: 0, 0.23, 0.47, 0.71, or 

12.46 mg/kg/day

NOAEL = 0.41/0.47 mg/kg/day (M/F).

LOAEL = 0.63/0.71 mg/kg/day (M/F) based upon 

corneal lesion in males.

870.3100

90-Day Oral 

Toxicity in Rodents 

(rat)

44505019 (1995)

Acceptable/guideline

0, 1, 125, 1250, or 12500 

ppm

M: 0, 0.09, 11, 112, or 

1111 mg/kg/day 

F: 0, 0.10, 13, 126, or 

1213 mg/kg/day

NOAEL = 0.09/0.10 mg/kg/day (M/F).

LOAEL = 11/13 mg/kg/day (M/F) based upon 

corneal abnormalities in both sexes and decreased 

body-weight gain in males.

870.3100

90-Day Oral 

Toxicity in Rodents 

(mouse)

44505022 (1997)

Acceptable/guideline

0, 10, 50, 350, or 7000 

ppm

M: 0, 1.7, 8.4, 61.5, or 

1212 mg/kg/day 

F: 0, 2.4, 12.4, 80.1, or 

1537 mg/kg/day

NOAEL = 1212/1537 mg/kg/day (M/F).

LOAEL > 1212/1537 mg/kg/day (M/F).

No effects noted.

870.3150

90-Day Oral 

Toxicity in NonRodent (dog)

44505023 (1997)

Acceptable/guideline

M & F: 0, 100, 600, or 

1000 mg/kg/day

NOAEL = 1000 mg/kg/day (M/F).

LOAEL > 1000 mg/kg/day (M/F).

No effects noted.

870.3200 21-Day Dermal 

Toxicity (rabbit)

44505024 (1997)

Acceptable/guideline

M & F: 0, 10, 500 or 

1000 mg/kg/day

NOAEL = 1000 mg/kg/day (M/F).

LOAEL > 1000 mg/kg/day (M/F).

No systemic effects noted.

870.3700a

Prenatal 

Developmental in 

Rodent (rat)

44920801 (1999)

Acceptable/guideline

F: 0, 100, 300, or 1000 

mg/kg/day

Maternal NOAEL = 100 mg/kg/day.

LOAEL = 300 mg/kg/day based upon decreased 

maternal body-weight gains and decreased food 

consumption.

Developmental NOAEL not established.

LOAEL = 100 mg/kg/day based upon delays in 

skeletal ossification and changes in manus/pes

ossification assessments.

870.3700a

Prenatal 

Developmental in 

Rodent (mouse)

44920802 (1997), 

44901708 (1999)

Acceptable/guideline

F: 0, 10, 60, 150, or 600 

mg/kg/day

Maternal NOAEL = 600 mg/kg/day.

LOAEL > 600 mg/kg/day; No effects noted.

Developmental NOAEL = 150 mg/kg/day

LOAEL = 600 mg/kg/day based upon decreased 

ossification of the cervical vertebrae centra.
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Table 2.2.2. Subchronic, Chronic and Other Toxicity Profile for Mesotrione.

Guideline 

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

870.3700b

Prenatal 

Developmental in 

Non-Rodent (rabbit)

44901707 (1999), 

44505032 (1999) 

Unacceptable/not 

upgradable

F: 0, 100, 250, or 500 

mg/kg/day

Maternal NOAEL = 100 mg/kg/day.

LOAEL = 250 mg/kg/day based upon abortions and 

clinical signs of toxicity.

Developmental NOAEL not established.

LOAEL = 100 mg/kg/day based upon delayed 

ossification of the 7th cervical transverse process 

and odontoid and increases in extra full 13th rib and 

27 pre-sacral vertebra.

Study classified as unacceptable because a 

developmental NOAEL was not established and 

dosing was initiated in several groups prior to 

completion of implantation.

870.3800 Reproduction and 

Fertility Effects (rat)

44505033 (1997)

Acceptable/guideline

0, 2.5, 10, 100 or 2500 

ppm

M: 0, 0.3, 1.1, 11.7, or 

287.7 mg/kg/day 

F: 0, 0.3, 1.2, 12.4, or 

311.4 mg/kg/day

Parental/Systemic NOAEL not established.

LOAEL = 0.3 mg/kg/day (M/F) based upon 

significantly increased plasma tyrosine levels and 

increased liver weights in F2 males.

Offspring/Systemic NOAEL not established.

LOAEL = 0.3 mg/kg/day (M/F) based upon 

significantly increased plasma tyrosine levels in F2

male pups.

Reproductive NOAEL = 0.3 mg/kg/day.

LOAEL = 1.1/1.2 mg/kg/day (M/F) based upon 

decreased F2 mean litter size.

870.3800

Reproduction and 

Fertility Effects 

(mouse)

44505034 (1997)

Acceptable/guideline

0, 10, 50, 350, 1500 or 

7000 ppm

M: 0, 2.1, 10.1, 71.4, 

306.7 or 1455.5 

mg/kg/day 

F: 0, 2.4, 11.7, 82.5, 

362.7, or 1652.3 

mg/kg/day

Parental/Systemic NOAEL = 10.1/11.7 (M/F).

LOAEL = 71.4/82.5 mg/kg/day (M/F) based upon 

increased kidney weights and tyrosinemia in the F1

males.

Offspring/Systemic NOAEL not established; 

LOAEL = 2.1/2.4 mg/kg/day (M/F) based upon 

tyrosinemia and ocular discharge in the F1 and F2

offspring.

Reproductive NOAEL = 1455.5/1652.3 mg/kg/day 

(M/F); LOAEL > 1455.5/1652.3.

870.4100a Chronic Toxicity

(mouse)

44505026 (1997) 

Acceptable/guideline

0, 10, 50, 350, or 7000 

ppm

M: 0, 1.5, 7.8, 56.2, or 

1114 mg/kg/day

F: 0, 2.1, 10.3, 72.4, or 

1494.5 mg/kg/day

NOAEL = 56.2/72.4 mg/kg/day (M/F).

LOAEL = 1114/1494.5 mg/kg/day (M/F) based 

upon decreases in body-weight gain and food 

utilization in males.

870.4100b Chronic Toxicity

(dog)

44505027 (1997)

Acceptable/guideline

M & F: 0, 10, 100, or 600 

mg/kg/day

NOAEL was not established.

LOAEL = 10 mg/kg/day based upon evidence of 

tyrosinemia in both sexes and increased incidence 

of erythrophagocytosis in the mesenteric lymph 

nodes of females.

870.4200a Carcinogenicity (rat) See 870.4300 See 870.4300
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Table 2.2.2. Subchronic, Chronic and Other Toxicity Profile for Mesotrione.

Guideline 

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

870.4200b Carcinogenicity 

(mouse)

44505028 (1997)

Acceptable/guideline

0, 10, 350 or 7000 ppm 

M: 0, 1.4, 49.7 or 898 

mg/kg/day

F: 0, 1.8, 63.5 or 1103 

mg/kg/day

NOAEL = 49.7/63.5 mg/kg/day (M/F).

LOAEL = 898/1103 mg/kg/day (M/F) based upon 

decreased body weight, body-weight gain, and food 

efficiency in males.

No evidence of carcinogenicity.

870.4300

Combined Chronic 

Toxicity/Carcinogen

icity (rat)

44505035 (1997), 

44505036 (1998)

Acceptable/guideline

0, [1.0, 2.5], 7.5, 100 or 

2500 ppm

M: 0, [0.06, 0.16], 0.48, 

6.48 or 159.9 mg/kg/day

F: 0, [0.08, 0.19], 0.57, 

7.68, or 189.5 mg/kg/day

NOAEL = 0.16/0.19 mg/kg/day (M/F) (The 

NOAEL only applies to ocular lesions; a NOAEL 

was not determined for kidney and liver weights or 

hepatocyte fat vacuolation in males).

LOAEL = 0.48/0.57 mg/kg/day (M/F) based upon 

ocular lesions, increases in kidney and liver 

weights, and hepatocyte fat vacuolation in males.

No evidence of carcinogenicity.

870.5100 Bacterial reverse 

mutation

44373526 (1993)

Acceptable/guideline

There was no evidence of induced mutant colonies 

over background.

870.5300 In vitro mammalian 

cell gene mutation

44373525 (1994)

Acceptable/guideline

There were no treatment-related increases in mutant 

frequency in the presence or absence of S9 

activation.

870.5375 In vitro mammalian 

cytogenetics assay 

44373524 (1994)

Acceptable/guideline

Not clastogenic with S9 activation and equivocal for 

clastogenic activity without S9 activation.

870.5395

Bone marrow 

micronucleus 

(mouse)

44373527 (1994)

Acceptable/guideline

There was no significant increase in the frequency 

of micronucleated polychromatic erythrocytes in 

bone marrow after any treatment time.

870.6200a

Acute Neurotoxicity 

Screening Battery 

(rat)

44505017 (1997), 

44505018 (1997)

Acceptable/guideline

M & F: 0, 20, 200 or 

2000 mg/kg/day

NOAEL = 2000 mg/kg/day (M/F).

LOAEL > 2000 mg/kg/day (M/F).

No effects noted.

870.6200b

Subchronic 

Neurotoxicity 

Screening Battery 

(rat)

44505025 (1997)

Acceptable/guideline

M: 0, 0.2, 8.25 or 403 

mg/kg/day

F: 0, 0.23, 9.29 or 467 

mg/kg/day

NOAEL = 0.20/0.23 mg/kg/day (M/F).

LOAEL = 8.25/9.29 mg/kg/day (M/F) based upon 

corneal opacities and/or vascularization of the 

cornea of the eye in males.

870.7485 Metabolism and 

Pharmacokinetics

44505101 (1995) 

44505102 (1996) 

44505103 (1996)

44505104 (1996) 

44505105 (1996) 

44505106 (1996)

Acceptable/guideline

1 or 100 mg/kg single oral 

dose

1 mg/kg single iv dose

1 mg/kg repeated dose

50 mg/kg single oral dose

Radiolabeled mesotrione was readily absorbed and 

distributed throughout the body after single and 

repeated doses. Concentrations of radioactivity 

were highest in the liver and kidney. Majority of 

labeled mesotrione was excreted via the urine and 

feces. The major component in urine and feces was 

unchanged parent. Biliary excretion was more 

prominent for males than females. Increasing the 

dose or repeated doses had little effect on the 

pattern of excretion. 

870.7800 Immunotoxicity

48748301 (2012)

Acceptable/guideline

0, 110, 332 or 1168 

mg/kg/day

NOAEL = 5000 ppm.

LOAEL not established.
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Attachment 3: Mesotrione Endpoint Selection Tables (from 2009 Risk Assessment).

Table 3.1. Summary of Toxicological Doses and Endpoints for Mesotrione for Use in Dietary and NonOccupational Human-Health Risk Assessments.

Exposure/ 

Scenario

Point of 

Departure

Uncertainty/FQPA 

Safety Factors

RfD, PAD, LOC 

for Risk 

Assessment

Study and Toxicological Effects

Acute Dietary

(All Populations) Not applicable Not applicable Not applicable

No adverse effects attributable to a 

single dose were observed. As a 

result, no hazard was identified and 

an endpoint was not selected to 

assess this exposure scenario.

Chronic Dietary 

(All Populations)

LOAEL = 

2.1 mg/kg/day

UFA = 10X

UFH = 10X

FQPA SF/UFL = 3X

cRfD = 0.007 

mg/kg/day

cPAD = 0.007 

mg/kg/day

Reproduction Study (mouse) 

Offspring LOAEL = 2.1/2.4 

mg/kg/day (M/F) based on 

tyrosinemia and ocular discharge.

NOAEL not established.

Incidental Oral 

Short-Term (1-30 

days) and 

Intermediate-Term 

(1-6 months)

LOAEL = 

2.1 mg/kg/day

UFA = 10X

UFH = 10X

FQPA SF/UFL = 3X

Residential LOC for 

MOE = 300

Reproduction Study (mouse) 

Offspring LOAEL = 2.1/2.4 

mg/kg/day (M/F) based on 

tyrosinemia and ocular discharge.

NOAEL not established.

Dermal

Short-Term (1-30 

days), 

Intermediate-Term 

(1-6 months) and 

Long-Term (>6 

months)

LOAEL= 

2.1 mg/kg/day

UFA = 10X

UFH = 10X

FQPA SF/UFL = 3X

Residential LOC for 

MOE = 300

Reproduction Study (mouse) 

Offspring LOAEL = 2.1/2.4 

mg/kg/day (M/F) based on 

tyrosinemia and ocular discharge 

NOAEL not established

Inhalation

Short-Term (1-30 

days), 

Intermediate-term 

(1-6 months) and 

Long-Term (>6 

months)

LOAEL= 

2.1 mg/kg/day

UFA= 10X

UFH = 10X

FQPA SF/UFL = 3X

Residential LOC for 

MOE = 300

Reproduction Study (mouse) 

Offspring LOAEL = 2.1/2.4 

mg/kg/day (M/F) based on 

tyrosinemia and ocular discharge.

NOAEL not established.

Cancer (oral, 

dermal, inhalation)

Classified as “not likely to be carcinogenic to humans” based upon lack of evidence of carcinogenicity in 

rats and mice.

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

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

LOAEL = lowest-observed adverse-effect level. UF = uncertainty factor. UFA = extrapolation from animal to human (interspecies). UFH = 

potential variation in sensitivity among members of the human population (intraspecies). UFL = use of a LOAEL to extrapolate a NOAEL. 

FQPA SF = FQPA Safety Factor. PAD = population-adjusted dose (a = acute, c = chronic). RfD = reference dose. MOE = margin of exposure. 

LOC = level of concern. 
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Table 3.2. Summary of Toxicological Doses and Endpoints for Mesotrione for Use in Occupational HumanHealth Risk Assessments.

Exposure/ 

Scenario

Point of 

Departure Uncertainty Factors LOC for Risk Assessment Study and Toxicological Effects

Dermal

Short-Term (1-30 

days), 

Intermediate-Term 

(1-6 months) and 

Long-Term (>6 

months)

LOAEL = 

2.1 mg/kg/day

UFA = 10X

UFH = 10X

UFL = 3X

Occupational LOC 

for MOE = 300

Reproduction Study (mouse) 

Offspring LOAEL = 2.1/2.4 

mg/kg/day (M/F) based on 

tyrosinemia and ocular discharge.

NOAEL not established.

Inhalation

Short-Term (1-30 

days), 

Intermediate-term 

(1-6 months) and 

Long-Term (>6 

months)

LOAEL = 

2.1 mg/kg/day

UFA = 10X

UFH = 10X

UFL = 3X

Occupational LOC 

for MOE = 300

Reproduction Study (mouse) 

Offspring LOAEL = 2.1/2.4 

mg/kg/day (M/F) based on 

tyrosinemia and ocular discharge.

NOAEL not established.

Cancer (oral, 

dermal, inhalation)

Classified as “not likely to be carcinogenic to humans” based upon lack of evidence of carcinogenicity in 

rats and mice

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

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

LOAEL = lowest-observed adverse-effect level. UF = uncertainty factor. UFA = extrapolation from animal to human (interspecies). UFH = 

potential variation in sensitivity among members of the human population (intraspecies). UFL = use of a LOAEL to extrapolate a NOAEL. MOE 

= margin of exposure. LOC = level of concern. 
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Attachment 4: Summary of Registered Uses.

Crop/Use Site Formulation Application 

method Maximum App Rate (lb ai/A) REI

Asparagus Liquid

Aerial, 

Groundboom, 

Chemigation

Preemergence: 0.24 lb aiA; 

Postemergence: 0.09 lb ai/A 12 hr

Bush and Caneberries Liquid

Aerial, 

Groundboom, 

Chemigation

Pre-bloom post-directed spray: 0.19 lb 

aiA 12 hr

Low-bush Blueberry (SLN) Liquid

Groundboom and 

chemigation (Aerial 

prohibited)

Preemergence and early postemergence: 

0.125 lb ai/A 12 hr

Corn

Liquid

Aerial, 

Groundboom, 

Chemigation

Preemergence: 0.24 lb ai/A and 

Postemergence: 0.078 - 0.23 lb ai/A 

(depends on timing)

12 -

24 hr

Dry 

Flowable

Groundboom 

(Aerial and 

Chemigation 

prohibited)

Preemergence: 0.18 - 0.24 lb ai/A and 

Postemergence: 0.078 - 0.24 lb ai/A 

(depends on timing)

12 hr

Corn (SLN) Dry 

Flowable

Allows for Aerial 

application 0.078 lb ai/A 12 hr

Cranberries Liquid

Aerial, 

Groundboom, 

Chemigation

0.25 lb ai/A 12 hr

Cuphea (ornamental; SLN) Liquid Groundboom and 

Handheld

Postemergence: 0.094 lb ai/A or 0.0098 lb 

ai/gal 12 hr

Flax Liquid

Aerial, 

Groundboom, 

Chemigation

Preemergence only: 0.19 lb aiA 12 hr

Golf courses

Granular Groundboom and 

Handheld 0.25 lb ai/A

12 hr

Liquid

Groundboom 

(Aerial and 

Chemigation 

prohibited)

0.25 lb ai/A; 0.0058 lb ai/1000 ft2; 0.0116 

lb ai/gal

Grass grown for seed Liquid

Aerial, 

Groundboom, 

Chemigation

Preemergence and Postemergence: 0.19 lb 

aiA 12 hr

Oats Liquid

Aerial, 

Groundboom, 

Chemigation

Preemergence: 0.19 lb aiA; 

Postemergence: 0.09 lb ai/A 12 hr

Okra Liquid

Aerial, 

Groundboom, 

Chemigation

Preemergence: 0.19 lb aiA; 

Postemergence: 0.09 lb ai/A 12 hr

Pearl Millet Liquid

Aerial, 

Groundboom, 

Chemigation

Preemergence only: 0.19 lb aiA 12 hr

Residential 

lawns/Recreational 

areas/Athletic Fields

Granular Handheld 0.25 lb ai/A 12 hr

Liquid Handheld 0.25 lb ai/A; 0.0058 lb ai/1000 ft2; 0.0116 

lb ai/gal None

Non-residential turf areas 

(airports, cemeteries, 

commercial buildings, and 

similar sites)

Liquid

Groundboom or 

Handheld (Aerial 

and Chemigation 

prohibited)

0.25 lb ai/A; 0.0058 lb ai/1000 ft2; 0.0116 

lb ai/gal None

Rhubarb Liquid

Aerial, 

Groundboom, 

Chemigation

Preemergence only: 0.19 lb aiA 12 hr
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Crop/Use Site Formulation Application 

method Maximum App Rate (lb ai/A) REI

Sod farms

Granular Groundboom and 

Handheld 0.25 lb ai/A

12 hr

Liquid

Groundboom 

(Aerial and 

Chemigation 

prohibited)

Broadcast: 0.25 lb ai/A

Sorghum Liquid

Aerial, 

Groundboom, 

Chemigation

0.2 lb ai/A 12-24 

hr

Soybean Liquid

Aerial, 

Groundboom, 

Chemigation

Preemergence: 0.2 lb ai/A; 

Postemergence: 0.11 lb ai/A 12 hr

Sugarcane Liquid

Aerial, 

Groundboom, 

Chemigation

Preemergence: 0.24 lb aiA; 

Postemergence: 0.09 lb ai/A 12 hr

Wildflowers (SLN) Liquid Groundboom or 

Handheld

Preemergence (applied after seeding in 

fall): 0.125 lb ai/A in 30 gal water/A = 

0.0042 lb ai/gal; Postemergence (in March 

or April the year following fall wildflower 

seeding): 0.094 lb ai/A or 0.0031 lb ai/gal

12 hr
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Attachment 5: Mesotrione IRLS Sheet.

Summary of US and International Tolerances and Maximum Residue Limits.

Residue Definition:

US Canada Mexico1 Codex

40 CFR 180.571:

Plant: Mesotrione (2-[4-(methylsulfonyl)-2-

nitrobenzoyl]-1,3-cyclohexanedione), 

including its metabolites and degradates.

Livestock: None

2-[4-(methylsulfonyl)-2-

nitrobenzoyl]-1,3-

cyclohexanedione

None

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

US Canada Mexico1 Codex

Asparagus 0.01 0.01

Berry, group 13 0.01

0.01 aronia berries, buffalo 

currants, Chilean guavas, 

cranberries,currants, 

elderberries, European 

barberries, gooseberries, 

highbush blueberries, highbush 

cranberries honeysuckle, 

huckleberries, jostaberries, 

lingonberries, lowbush 

blueberries, native currants, 

salal berries, saskatoon berries 

(juneberries), sea buckthorn

Corn, field, forage 0.01

Corn, field, grain 0.01 0.01

Corn, field, stover 0.01

Corn, pop, grain 0.01 0.01

Corn, pop, stover 0.01

Corn, sweet, forage 0.5

Corn, sweet, kernel plus cob with 

husks removed 0.01 0.01

Corn, sweet, stover 1.5

Cranberry 0.02 0.01

Flax, seed 0.01 0.01

Grass, forage 0.01

Grass, hay 0.01

Grass, seed screenings 0.10

Grass, straw 0.10

Lingonberry 0.01 0.01

Millet, forage 0.01

Millet, grain 0.01 0.01 pearl millet, proso millet

Millet, hay 0.02

Millet, straw 0.02

Oat, forage 0.01

Oat, grain 0.01 0.01

Oat, hay 0.01

Oat, straw 0.01

Okra 0.01

Rhubarb 0.01 0.01

Sorghum, grain, forage 0.01

Sorghum, grain, grain 0.01 0.01 sorghum

Sorghum, grain, stover 0.01
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Sorghum, sweet 0.01 0.01 sorghum

Sorghum, seed 0.01

Sugarcane, cane 0.01 0.01

MRLs With NO US Equivalent

Dry soybeans 0.01

Eggs 0.01

Meat byproducts of cattle 0.01

Meat byproducts of goats 0.01

Meat byproducts of hogs 0.01

Meat byproducts of horses 0.01

Meat byproducts of poultry 0.01

Meat byproducts of sheep 0.01

Meat of cattle 0.01

Meat of goats 0.01

Meat of hogs 0.01

Meat of horses 0.01

Meat of poultry 0.01

Meat of sheep 0.01

Milk 0.01

Completed: M. Negussie; 02/06/14

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