Mesotrione - Registration of a Major Change in ... - Cornell University

New York State Department of Environmental Conservation
Division of Solid and Hazardous Materials
Bureau of Pesticides Management, 11 th Floor
625 Broadway, Albany, New York 12233-7257
Phone: (518) 402-8768 • Fax: (518) 402-9024
Website: www.dec.ny.gov/chemical/298.html
E-mail: ppr@gw.dec.state.ny.us
CERTIFIED MAIL (Co. No. 100)
Ms. Susan Person
Syngenta Crop Protection, Inc.
P.O. Box 18300
Greensboro, NC 27419-8300
Dear Ms. Person:
February 3, 2010
Alexander B. Grannis
Commissioner
Re: Registration of a Major Change in Labeled (MCL) Use Pattern for the Active Ingredient
Mesotrione Contained in the Pesticide Product Tenacity (EPA Reg. No. 100-1267;
Chemical Code 122990)
The New York State Department of Environmental Conservation (Department) has completed
review of your application and data package received on July 15, 2008 regarding registration of the
above-referenced pesticide product. The subject application and data package were deemed complete
for purposes of technical review on September 8, 2009. Pursuant to the review time frame specified in
Environmental Conservation Law (ECL) §33-0704.2, a registration decision date of February 5, 2010
was established.
Tenacity contains 40.0% of the active ingredient mesotrione (Chemical Code 122990) and is
labeled as a preemergence and post-emergence herbicide for the selective contact and residual control of
weeds in ornamental turfgrasses. Mesotrione was initially registered by the Department on June 10,
2002 for control of annual broadleaf weeds in field corn, production seed corn, and corn grown for
silage. The maximum application rate was 0.34 pounds mesotrione per acre per season. A Major Change
in Labeling was registered on September 4, 2008, adding control of weeds in turfgrasses on golf courses
and sodfarms. The maximum application rate was 0.5 pounds mesotrione per acre per season. The new
proposed uses of mesotrione for application to athletic fields, parks, residential and commercial
properties, cemeteries, airports, and lawns represent a major change in use pattern for this active
ingredient in New York State.
Tenacity is formulated as a flowable concentrate and is intended for broadcast application. The
maximum labeled use rates are 8 fluid ounces of product (0.25 pounds of active ingredient) per acre per
application and 16 fluid ounces of product (0.5 pounds of active ingredient) per acre per year.
A human health risk assessment was conducted for mesotrione and the formulated
product Tenacity. An environmental fate risk assessment was not performed because previous
reviews of the product indicate that it is not likely to leach significantly to groundwater on sandy

Ms. Susan Person 2.
Long Island soils when used as labeled because of the short half-life and low application rate.
An ecological effects risk assessment was not performed because previous reviews of the active
ingredient indicate that it is not likely to impact fish or wildlife resources when used as labeled
because mesotrione degrades fairly rapidly in the environment, making extended exposures
unlikely.
HUMAN HEALTH EFFECTS
The New York State Department of Health (NYSDOH) previously reviewed mesotrione and the
formulated products Tenacity in 2008 and Callisto Herbicide (EPA Reg. No. 100-1131) in 2002;
Tenacity is a repackaging of the Callisto Herbicide product for turf use. Neither mesotrione nor the
formulated product Tenacity was very toxic in acute oral, dermal or inhalation exposure studies in
laboratory animals. Mesotrione was a moderate eye irritant, but not a skin irritant or sensitizer, whereas
Tenacity was slightly irritating to both skin and eyes and a mild skin sensitizer. Mesotrione caused
some toxicity in subchronic and chronic animal feeding studies, including ocular lesions, liver and
kidney toxicity and increased plasma tyrosine levels. In addition, this chemical caused delayed
ossification in offspring of rats, mice and rabbits in developmental toxicity studies and was associated
with significantly increased plasma tyrosine levels in multi-generation reproduction studies in rats and
mice. Mesotrione did not cause oncogenic effects in rat or mouse chronic feeding studies and was
negative in a number of genotoxicity studies. Based on this, the U.S. Environmental Protection Agency
(U.S. EPA) classified mesotrione as “not likely to be carcinogenic to humans.” The U.S. EPA Office of
Pesticide Programs established a reference dose (RfD) of 0.007 milligrams per kilogram body weight
per day (mg/kg/day) based on a lowest-observed-effect level (LOEL) of 2.1 mg/kg/day in the mouse
multi-generation reproduction study (tyrosinemia and ocular discharge) and an uncertainty factor of 300.
An uncertainty factor of 100 was used to account for inter-species extrapolation and human variability
and an additional uncertainty factor of 3 to account for using a LOEL instead of a no-observed-effect
level (NOEL). This RfD has not yet been adopted by the U.S. EPA’s Integrated Risk Information
System (IRIS). A current search of the toxicological literature did not find any significant new
information on the toxicity of mesotrione.
The U.S. EPA conducted an occupational risk assessment for combined short- (1-30 days) and
intermediate-term (1-6 months) dermal and inhalation exposures for several occupational handler
scenarios of liquid and granular formulations of Tenacity (only the liquid formulation was submitted for
registration in New York State). These handler scenarios included mixer/loaders (aerial and tractor
drawn spreader applications), applicators (aerial, groundboom equipment and tractor drawn spreader
applications), flaggers and mixer/loader/applicators (low-pressure handwand, handgun sprayer,
backpack sprayer and push-type spreader). For determining margins of exposure (MOEs), the U.S. EPA
compared estimated dermal and inhalation exposures to the LOEL of 2.1 mg/kg/day from the multigeneration
reproduction study in the mouse and used a one percent dermal absorption (based on data
from in vivo experiments) and one hundred percent inhalation absorption. For mixer/loaders, the MOEs
for dermal exposures were estimated to be between 6,300 and 75,000; MOEs for inhalation exposures
were between 57,000 and 180,000. For commercial applicators, the MOEs for dermal exposures were
estimated to be between 16,000 and 90,000, and between 63,000 and 1,000,000 for inhalation exposures,
assuming an enclosed cockpit for aerial applications. The dermal and inhalation MOEs for flaggers
supporting aerial applications were estimated to be 13,000 and 200,000, respectively. For

Ms. Susan Person 3.
mixer/loader/applicator scenarios, the dermal MOEs were estimated to be between 500 and 22,000;
MOEs for inhalation exposures were between 760,000 and 3,200,000. These estimates assumed that all
workers wore long-sleeved shirt and long pants, chemical-resistant gloves, and shoes plus socks (except
for the low-pressure handwand sprayer and granular push-type spreader scenarios, where no glove use
was assumed) as per label requirements. MOEs for post-application activities (e.g., mowing, weeding,
transplanting) on Day 0 of the application were estimated to be between 1,700 and 3,300 with a 12-hour
restricted entry interval (REI). The U.S. EPA considered MOEs of 300-fold or greater to provide
adequate worker protection from mesotrione.
The U.S. EPA also conducted a risk assessment for post-application residential exposures to
mesotrione from use on lawns. For determining MOEs, the U.S. EPA compared estimated short-term
dermal and ingestion exposures to a LOEL of 2.1 mg/kg/day from the multi-generation reproduction
study in the mouse (tyrosinemia and ocular discharge). The estimated dermal MOEs for adult postapplication
exposures of high-contact activities, mowing and golfing were 3,100; 13,000 and 45,000,
respectively. The estimated dermal MOEs for youth post-application exposures of mowing and golfing
were 8,600 and 29,000, respectively. The estimated dermal post-application risk for a 3-year old toddler
was 2,200 for high contact activities. The U.S. EPA also estimated post-application risks for toddlers to
mesotrione from applications to lawns via exposure from hand-to-mouth activity, object-to-mouth
activity and incidental soil ingestion. The estimated MOEs for these exposure scenarios were 560;
3,100 and 170,000, respectively. The MOE for total residential toddler exposure across all pathways
was 390. In addition, the U.S. EPA estimated short- and intermediate-term aggregate risks for
residential dietary and non-dietary exposures to mesotrione from all registered uses. The short-term
aggregate MOEs for toddlers, youths and adults were estimated to be 370; 6,000 and 2,600, respectively.
The intermediate-term MOE for toddlers was estimated to be 9,000; no other age category was believed
to have intermediate exposures from turf. The U.S. EPA considered a target MOE of 300 to be
adequately protective of human health for these exposure scenarios.
There are no chemical specific federal or New York State drinking water/groundwater standards
for mesotrione or its degradates. Based on their chemical structures, mesotrione and its degradates fall
under the 50 microgram per liter (µg/L) New York State drinking water standard for “unspecified
organic contaminants” (10 NYCRR Part 5, Public Water Systems). The New York State drinking water
standard for the sum of “unspecified organic contaminants” and “principal organic contaminants” is 100
µg/L. If one uses the RfD (0.007 mg/kg/day) and procedures for deriving ambient water quality
standards and guidelines based on non-oncogenic effects (6 NYCRR Part 702.5), a value of 49 µg/L can
be calculated. This value could be used to derive a screening value for comparison to estimated impacts
to groundwater and surface water.
The available information on mesotrione and Tenacity indicates that they are not very acutely
toxic in laboratory animal studies. While the Tenacity product has some skin sensitizing properties, the
label cautions users of this potential and requires adequate personal protective equipment. Data from
animal developmental and reproductive studies indicate that mesotrione affects offspring through
delayed ossification and ocular effects. These effects, as well as those in the liver and kidney, are
believed to be secondary to tyrosinemia that in part results from the inhibition of the enzyme phydroxyphenylpyruvate
dioxygenase (HPPD), which, in mammals, is involved in the catabolism of the
amino acid tyrosine. However, as we noted in our previous reviews of mesotrione, humans have a
considerable capacity to regulate tyrosine levels due to a relatively high activity level of another enzyme

Ms. Susan Person 4.
involved in tyrosine catabolism, tyrosine aminotransferase (TAT). In addition, the estimated risk to the
general public and workers from the labeled use of Tenacity on turf is within the range that is generally
considered acceptable.
REGISTRATION SUMMARY
Based on previous reviews, an environmental fate review and an ecological effects review were
not performed by the Department. A human health review of the submitted information indicated no
significant impact to human health is expected upon labeled use of Tenacity. Therefore, the
Department has registered Tenacity (EPA Reg. No. 100-1267) for use in New York State.
Enclosed is a copy of the stamped “Accepted For Registration” label and the New York State
Certificate of Pesticide Registration for Tenacity. Please note that a proposal by Syngenta Crop
Protection or any other registrant to register a product that contains mesotrione, and whose labeled uses
are likely to increase the potential for significant impact on humans, nontarget organisms, or the
environment, would constitute a major change in labeled (MCL) use pattern. Such an application must
be accompanied by a new application fee and meet the requirements listed in Appendix 1.B. of “New
York State Pesticide Product Registration Procedures” (April 2009). Such information, as well as forms,
can be accessed at our website as listed in our letterhead. Please be aware that any unregistered product
may not be sold, offered for sale, distributed, or used in New York State.
If you have any questions regarding this matter, please contact our Pesticide Product Registration
Section, at (518)-402-8768
Enclosures
ecc: w/enc. - R. Mungari - NYS Dept. of Ag. & Markets
- A. Grey/E. Horn - NYS Dept. of Health
- W. Smith - Cornell University, PSUR
Sincerely,
Maureen P. Serafini
Director
Bureau of Pesticides Management