
[Federal Register Volume 76, Number 83 (Friday, April 29, 2011)]
[Rules and Regulations]
[Pages 23891-23898]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2011-10435]


-----------------------------------------------------------------------

ENVIRONMENTAL PROTECTION AGENCY

40 CFR Part 180

 [EPA-HQ-OPP-2010-0266; FRL-8869-5]


Pyrasulfotole; Pesticide Tolerances

AGENCY: Environmental Protection Agency (EPA).

ACTION: Final rule.

-----------------------------------------------------------------------

SUMMARY: This regulation establishes or revises tolerances for residues 
of pyrasulfotole in or on grain sorghum, grass, and livestock 
commodities. Bayer CropScience LLC requested these tolerances under the 
Federal Food, Drug, and Cosmetic Act (FFDCA).

DATES: This regulation is effective April 29, 2011. Objections and 
requests for hearings must be received on or before June 28, 2011, and 
must be filed in accordance with the instructions provided in 40 CFR 
part 178 (see also Unit I.C. of the SUPPLEMENTARY INFORMATION).

ADDRESSES: EPA has established a docket for this action under docket 
identification (ID) number EPA-HQ-OPP-2010-0266. All documents in the 
docket are listed in the docket index available at http://www.regulations.gov. Although listed in the index, some information is 
not publicly available,

[[Page 23892]]

e.g., Confidential Business Information (CBI) or other information 
whose disclosure is restricted by statute. Certain other material, such 
as copyrighted material, is not placed on the Internet and will be 
publicly available only in hard copy form. Publicly available docket 
materials are available in the electronic docket at http://www.regulations.gov, or, if only available in hard copy, at the OPP 
Regulatory Public Docket in Rm. S-4400, One Potomac Yard (South Bldg.), 
2777 S. Crystal Dr., Arlington, VA. The Docket Facility is open from 
8:30 a.m. to 4 p.m., Monday through Friday, excluding legal holidays. 
The Docket Facility telephone number is (703) 305-5805.

FOR FURTHER INFORMATION CONTACT: Susan Stanton, Registration Division 
(7505P), Office of Pesticide Programs, Environmental Protection Agency, 
1200 Pennsylvania Ave., NW., Washington, DC 20460-0001; telephone 
number: (703) 305-5218; e-mail address: stanton.susan@epa.gov.

SUPPLEMENTARY INFORMATION:

I. General Information

A. Does this action apply to me?

    You may be potentially affected by this action if you are an 
agricultural producer, food manufacturer, or pesticide manufacturer. 
Potentially affected entities may include, but are not limited to those 
engaged in the following activities:
     Crop production (NAICS code 111).
     Animal production (NAICS code 112).
     Food manufacturing (NAICS code 311).
     Pesticide manufacturing (NAICS code 32532).
    This listing is not intended to be exhaustive, but rather to 
provide a guide for readers regarding entities likely to be affected by 
this action. Other types of entities not listed in this unit could also 
be affected. The North American Industrial Classification System 
(NAICS) codes have been provided to assist you and others in 
determining whether this action might apply to certain entities. If you 
have any questions regarding the applicability of this action to a 
particular entity, consult the person listed under FOR FURTHER 
INFORMATION CONTACT.

B. How can I get electronic access to other related information?

    You may access a frequently updated electronic version of EPA's 
tolerance regulations at 40 CFR part 180 through the Government 
Printing Office's e-CFR site at http://www.gpoaccess.gov/ecfr.

C. How can I file an objection or hearing request?

    Under FFDCA section 408(g), 21 U.S.C. 346a, any person may file an 
objection to any aspect of this regulation and may also request a 
hearing on those objections. You must file your objection or request a 
hearing on this regulation in accordance with the instructions provided 
in 40 CFR part 178. To ensure proper receipt by EPA, you must identify 
docket ID number EPA-HQ-OPP-2010-0266 in the subject line on the first 
page of your submission. All objections and requests for a hearing must 
be in writing, and must be received by the Hearing Clerk on or before 
June 28, 2011. Addresses for mail and hand delivery of objections and 
hearing requests are provided in 40 CFR 178.25(b).
    In addition to filing an objection or hearing request with the 
Hearing Clerk as described in 40 CFR part 178, please submit a copy of 
the filing that does not contain any CBI for inclusion in the public 
docket. Information not marked confidential pursuant to 40 CFR part 2 
may be disclosed publicly by EPA without prior notice. Submit a copy of 
your non-CBI objection or hearing request, identified by docket ID 
number EPA-HQ-OPP-2010-0266, by one of the following methods:
     Federal eRulemaking Portal: http://www.regulations.gov. 
Follow the on-line instructions for submitting comments.
     Mail: Office of Pesticide Programs (OPP) Regulatory Public 
Docket (7502P), Environmental Protection Agency, 1200 Pennsylvania 
Ave., NW., Washington, DC 20460-0001.
     Delivery: OPP Regulatory Public Docket (7502P), 
Environmental Protection Agency, Rm. S-4400, One Potomac Yard (South 
Bldg.), 2777 S. Crystal Dr., Arlington, VA. Deliveries are only 
accepted during the Docket Facility's normal hours of operation (8:30 
a.m. to 4 p.m., Monday through Friday, excluding legal holidays). 
Special arrangements should be made for deliveries of boxed 
information. The Docket Facility telephone number is (703) 305-5805.

II. Summary of Petitioned-for Tolerance

    In the Federal Register of June 23, 2010 (75 FR 35801) (FRL-8831-
3), EPA issued a notice pursuant to section 408(d)(3) of FFDCA, 21 
U.S.C. 346a(d)(3), announcing the filing of a pesticide petition (PP 
9F7680) by Bayer CropScience LLC, 2 T. W. Alexander Drive, Research 
Triangle Park, NC 27709. The petition requested that 40 CFR part 180 be 
amended by establishing tolerances for residues of the herbicide 
pyrasulfotole, (5-hydroxy-1,3-dimethyl-1H-pyrazol-4-yl)[2-
(methylsulfonyl)-4-(trifluoromethyl)phenyl]methanone, in or on sorghum, 
grain at 0.8 parts per million (ppm); sorghum, forage at 1.2 ppm; 
sorghum, stover at 0.35 ppm; grass, hay at 2.5 ppm; and grass, forage 
at 10 ppm. The petition also requested that established tolerances in 
40 CFR 180.631 for residues of pyrasulfotole on livestock commodities 
be increased to the following levels: Cattle, goat, hog, sheep, horse, 
meat at 0.04 ppm; cattle, goat, hog, sheep, horse, fat at 0.04 ppm; 
cattle, goat, hog, sheep, horse, meat byproducts, except liver at 2 
ppm; and cattle, goat, hog, sheep, horse, liver at 8 ppm. The petition 
requested that the new and revised tolerances be established for 
residues of pyrasulfotole, including its metabolites and degradates, 
but that compliance with the specified tolerance levels be determined 
by measuring only residues of pyrasulfotole, (5-hydroxy-1,3-dimethyl-
1H-pyrazol-4-yl)-[2-(methylsulfonyl)-4-(trifluoromethyl)-phenyl]-
methanone, and its desmethyl metabolite, (5-Hydroxy-3-methyl-1H-
pyrazol-4-yl)-[2-(methylsulfonyl)-4-(trifluoromethyl)phenyl] methanone, 
calculated as the stoichiometric equivalent of pyrasulfotole, in or on 
the commodities. That notice referenced a summary of the petition 
prepared by Bayer CropScience LLC, the registrant, which is available 
in the docket, http://www.regulations.gov. There were no comments 
received in response to the notice of filing.
    Based upon review of the data supporting the petition, EPA has 
revised the sorghum commodity terms and the proposed tolerances levels 
for sorghum, grass; and livestock commodities. The reasons for these 
changes are explained in Unit IV.C.

III. Aggregate Risk Assessment and Determination of Safety

    Section 408(b)(2)(A)(i) of FFDCA allows EPA to establish a 
tolerance (the legal limit for a pesticide chemical residue in or on a 
food) only if EPA determines that the tolerance is ``safe.'' Section 
408(b)(2)(A)(ii) of FFDCA defines ``safe'' to mean that ``there is a 
reasonable certainty that no harm will result from aggregate exposure 
to the pesticide chemical residue, including all anticipated dietary 
exposures and all other exposures for which there is reliable 
information.'' This includes exposure through drinking water and in 
residential settings, but does not include occupational exposure. 
Section 408(b)(2)(C) of FFDCA requires EPA to give special 
consideration to exposure

[[Page 23893]]

of infants and children to the pesticide chemical residue in 
establishing a tolerance and to ``ensure that there is a reasonable 
certainty that no harm will result to infants and children from 
aggregate exposure to the pesticide chemical residue. * * *''
    Consistent with section 408(b)(2)(D) of FFDCA, and the factors 
specified in section 408(b)(2)(D) of FFDCA, EPA has reviewed the 
available scientific data and other relevant information in support of 
this action. EPA has sufficient data to assess the hazards of and to 
make a determination on aggregate exposure for pyrasulfotole including 
exposure resulting from the tolerances established by this action. 
EPA's assessment of exposures and risks associated with pyrasulfotole 
follows.

A. Toxicological Profile

    EPA has evaluated the available toxicity data and considered its 
validity, completeness, and reliability as well as the relationship of 
the results of the studies to human risk. EPA has also considered 
available information concerning the variability of the sensitivities 
of major identifiable subgroups of consumers, including infants and 
children.
    Pyrasulfotole has low to moderate acute toxicity via the oral, 
dermal, and inhalation routes of exposure. It is not a dermal 
sensitizer or skin irritant but has been shown to be a moderate eye 
irritant.
    Chronic oral exposure of rats to pyrasulfotole resulted in 
extensive eye toxicity at almost all doses tested. Eye effects included 
corneal opacity, neovascularization of the cornea, inflammation of the 
cornea, regenerative corneal hyperplasia, corneal atrophy, and/or 
retinal atrophy. Ocular toxicity is believed to be an indirect result 
of tyrosinemia caused by inhibition of hepatic HPPD (4-
hydroxyphenylpyruvate dioxygenase). In mice, ocular toxicity was not 
observed at any dose, thereby reflecting accepted differences in 
effects among rodent species for HPPD inhibitors. Long-term exposure of 
mice to pyrasulfotole did cause toxicity of the urinary system, 
including the kidney, urinary bladder, and ureters at the highest dose 
tested (HDT), as well as gallstone formation at all doses tested. Dogs 
treated with pyrasulfotole for 1 year exhibited toxicity of the urinary 
system (kidneys and bladder) at mid and high doses, as well as 
cataracts at a very low incidence at the HDT.
    In the combined chronic/carcinogenicity study in rats, two male 
rats had rare treatment-related corneal tumors at the HDT (104/140 
milligrams/kilograms/day (mg/kg/day), M/F)), a dose associated with 
widespread corneal inflammation, hyperplasia, metaplasia, 
neurovascularization and atrophy. In the mouse carcinogenicity study, 
treatment-related urinary bladder transitional cell tumors were seen in 
males and females only at the HDT (560/713 mg/kg/day, M/F). The 
evidence from animal data is suggestive of carcinogenicity, which 
raises a concern for carcinogenic effects but is judged not sufficient 
for quantification of cancer risk in humans. In the case of 
pyrasulfotole, cancer risk from dietary exposure is less of a concern 
based on the following weight of evidence considerations:
     The incidence of ocular tumors was low (2/55), seen only 
at the high dose, and was associated with widespread corneal 
inflammation, hyperplasia, metaplasia, neurovascularization, and 
atrophy;
     It is biologically plausible for corneal tumors to result 
from a nongenotoxic mode of action that is secondary to corneal 
inflammation and regenerative hyperplasia caused by tyrosine;
     The urinary bladder tumors in mice were seen only at the 
high dose (one-half of the Limit Dose), which was determined to be an 
excessive dose due to occurrence of death, bladder stones, and bladder 
hyperplasia;
     Data from available toxicity studies showed dose and 
temporal concordance among putative key events for the biological 
plausibility for a nongenotoxic proliferative mechanism for the bladder 
tumors. This was evidenced by the concurrent presence of secondary 
inflammation and hyperplastic lesions in the urinary bladder induced by 
the urinary stones;
     In both species tumors were observed only at the highest 
dose tested (i.e., lack of dose-response);
     Pyrasulfotole and its benzoic metabolite, AE B197555, do 
not pose a mutagenic concern; and
     The NOAEL of 1.0 mg/kg/day used for deriving the chronic 
RfD is approximately 100- to 500-fold lower than the doses that induced 
ocular tumors in rats (104 mg/kg/day) and urinary bladder tumors in 
mice (560 mg/kg/day).
    Thus, for all these reasons, the Agency has determined that a non-
linear approach is adequate for assessing cancer risk and that the 
chronic PAD (0.01 mg/kg/day) will adequately account for all chronic 
effects, including carcinogenicity, likely to result from exposure to 
the pyrasulfotole.
    Signs of potential neurotoxicity were observed in the acute 
neurotoxicity study in rats (decreased locomotor activity on the day of 
treatment), as well as in the rat subchronic neurotoxicity study (urine 
staining in the high dose females during the Functional Observational 
Battery) and rat developmental neurotoxicity (DNT) study (decreased 
brain weights, learning deficits, and the changes in brain 
morphometry).
    In the prenatal developmental toxicity study in rats, an increased 
incidence of skeletal variations was observed in fetal offspring at the 
mid dose, as was decreased fetal body weight in male offspring. Both 
effects were observed in the presence of maternal toxicity (decreased 
body weight gain, enlarged placenta, clinical signs) at the same dose. 
In the DNT study in rats, ocular toxicity as well as several adverse 
developmental effects (delayed preputial separation, morphometric 
changes, and delays in learning/memory) were observed at the mid dose. 
Ocular toxicity was also observed at this dose in maternal animals; an 
identical NOAEL was established in both dams and offspring. In the 
prenatal developmental toxicity study in rabbits, an increased 
incidence of skeletal variations was observed in fetal offspring at the 
mid dose. However, maternal toxicity (decreased body weight gain and 
food consumption) was observed only at the next highest dose tested. 
Therefore, increased quantitative susceptibility of offspring was 
observed in the rabbit developmental toxicity study, but not in the 
developmental toxicity or DNT studies in rats.
    In the 2-generation reproductive toxicity study in rats, ocular 
toxicity (keratitis, corneal opacity and/or corneal 
neovascularization), was observed at the mid and high doses in the 
adults and offspring of 2-generations. Thyroid (colloid alteration, 
pigment deposition) and kidney (tubular dilation) toxicity were 
observed in adult animals of each generation. Colloid alteration and 
pigment deposition were also observed in rats following short-term 
dermal and chronic oral exposure of rats, although they were attributed 
to aging in the latter case. At the highest dose tested, decreased 
viability and decreased body weight were observed in offspring of both 
generations. At the mid and/or high doses, delays in balanopreputial 
separation (males) and vaginal patency (females) were observed in 
first-generation offspring.
    Specific information on the studies received and the nature of the 
adverse effects caused by pyrasulfotole as well as the NOAEL and the 
lowest-observed-

[[Page 23894]]

adverse-effect-level (LOAEL) from the toxicity studies can be found at 
http://www.regulations.gov in the document ``Pyrasulfotole: Human-
Health Risk Assessment for Proposed Section 3 Uses on Grain Sorghum and 
Grass Grown for Seed,'' p. 30 in docket ID number EPA-HQ-OPP-2010-0266.

B. Toxicological Points of Departure/Levels of Concern

    Once a pesticide's toxicological profile is determined, EPA 
identifies toxicological points of departure (POD) and levels of 
concern to use in evaluating the risk posed by human exposure to the 
pesticide. For hazards that have a threshold below which there is no 
appreciable risk, the toxicological POD is used as the basis for 
derivation of reference values for risk assessment. PODs are developed 
based on a careful analysis of the doses in each toxicological study to 
determine the dose at which no adverse effects are observed (the NOAEL) 
and the lowest dose at which adverse effects of concern are identified 
(the LOAEL). Uncertainty/safety factors are used in conjunction with 
the POD to calculate a safe exposure level--generally referred to as a 
population-adjusted dose (PAD) or a reference dose (RfD)--and a safe 
margin of exposure (MOE). For non-threshold risks, the Agency assumes 
that any amount of exposure will lead to some degree of risk. Thus, the 
Agency estimates risk in terms of the probability of an occurrence of 
the adverse effect expected in a lifetime. For more information on the 
general principles EPA uses in risk characterization and a complete 
description of the risk assessment process, see http://www.epa.gov/pesticides/factsheets/riskassess.htm.
    A summary of the toxicological endpoints for pyrasulfotole used for 
human risk assessment is shown in the following Table:

  Table--Summary of Toxicological Doses and Endpoints for Pyrasulfotole for Use in Human Health Risk Assessment
----------------------------------------------------------------------------------------------------------------
                                        Point of departure and
          Exposure/scenario               uncertainty/safety     RfD, PAD, LOC for risk  Study and toxicological
                                               factors                 assessment                effects
----------------------------------------------------------------------------------------------------------------
Acute dietary (All populations)......  NOAEL = 3.8 milligrams/  Acute RfD = 0.038 mg/kg/ Developmental
                                        kilograms/day (mg/kg/    day.                     neurotoxicity (rat;
                                        day).                   aPAD = 0.038 mg/kg/day.   dietary).
                                       UFA = 10x..............                           LOAEL = 37 mg/kg/day
                                       UFH = 10x..............                            based on delayed
                                       FQPA SF = 1x...........                            preputial separation
                                                                                          (males), decreased
                                                                                          cerebrum length (PND
                                                                                          21 females), and
                                                                                          decreased cerebellum
                                                                                          height (PND 21 males).
Chronic dietary (All populations)....  NOAEL= 1.0 mg/kg/day...  Chronic RfD = 0.01 mg/   Combined chronic
                                       UFA = 10x..............   kg/day.                  toxicity/
                                       UFH = 10x..............  cPAD = 0.01 mg/kg/day..   carcinogenicity (rat;
                                       FQPA SF = 1x...........                            dietary).
                                                                                         LOAEL = 10/14 mg/kg/day
                                                                                          (M/F) based on corneal
                                                                                          opacity,
                                                                                          neovascularization of
                                                                                          the cornea,
                                                                                          inflammation of the
                                                                                          cornea, regenerative
                                                                                          corneal hyperplasia,
                                                                                          corneal atrophy, and/
                                                                                          or retinal atrophy
                                                                                          (both sexes), and
                                                                                          hepatocellular
                                                                                          hypertrophy along with
                                                                                          increased serum
                                                                                          cholesterol (males).
                                      --------------------------------------------------------------------------
Cancer (Oral, dermal, inhalation)....  Classification: ``Suggestive Evidence of Carcinogenic Potential'' based
                                        on increased incidences of corneal tumors in male rats (oral
                                        carcinogenicity study) and urinary bladder tumors in male and female
                                        mice (oral carcinogenicity study).
----------------------------------------------------------------------------------------------------------------
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. UFS = use of a short-term
  study for long-term risk assessment. UFDB = to account for the absence of data or other data deficiency. FQPA
  SF = Food Quality Protection Act Safety Factor. PAD = population adjusted dose (a = acute, c = chronic). RfD =
  reference dose. MOE = margin of exposure. LOC = level of concern.

C. Exposure Assessment

    1. Dietary exposure from food and feed uses. In evaluating dietary 
exposure to pyrasulfotole, EPA considered exposure under the 
petitioned-for tolerances as well as all existing pyrasulfotole 
tolerances in 40 CFR 180.631. EPA assessed dietary exposures from 
pyrasulfotole in food as follows:
    i. Acute exposure. Quantitative acute dietary exposure and risk 
assessments are performed for a food-use pesticide, if a toxicological 
study has indicated the possibility of an effect of concern occurring 
as a result of a 1-day or single exposure. Such effects were identified 
for pyrasulfotole. In estimating acute dietary exposure, EPA used food 
consumption information from the United States Department of 
Agriculture (USDA) 1994-1996 and 1998 Nationwide Continuing Surveys of 
Food Intake by Individuals (CSFII). As to residue levels in food, EPA 
assumed that residues are present in all commodities at the tolerance 
level and that 100% of commodities are treated with pyrasulfotole. 
Dietary Exposure Evaluation Model (DEEM) \TM\ 7.81 default 
concentration factors were used to estimate residues of pyrasulfotole 
in processed commodities.
    ii. Chronic exposure. In conducting the chronic dietary exposure 
assessment EPA used the food consumption data from the USDA 1994-1996 
and 1998 CSFII. As to residue levels in food, EPA assumed tolerance-
level residues and 100 percent crop treated (PCT) and used 
DEEMTM 7.81 default concentration factors to estimate 
residues of pyrasulfotole in processed commodities.
    iii. Cancer. EPA determines whether quantitative cancer exposure 
and risk assessments are appropriate for a food-use pesticide based on 
the weight of the evidence from cancer studies and other relevant data. 
Cancer risk is quantified using a linear or nonlinear approach. If

[[Page 23895]]

sufficient information on the carcinogenic mode of action is available, 
a threshold or non-linear approach is used and a cancer RfD is 
calculated based on an earlier noncancer key event. If carcinogenic 
mode of action data are not available, or if the mode of action data 
determines a mutagenic mode of action, a default linear cancer slope 
factor approach is utilized. Based on the data summarized in Unit 
III.A., EPA has concluded that a nonlinear RfD approach is appropriate 
for assessing cancer risk to pyrasulfotole. Cancer risk was assessed 
using the same exposure estimates as discussed in Unit III.C.1.ii., 
chronic exposure.
    2. Dietary exposure from drinking water. The Agency used screening 
level water exposure models in the dietary exposure analysis and risk 
assessment for pyrasulfotole in drinking water. These simulation models 
take into account data on the physical, chemical, and fate/transport 
characteristics of pyrasulfotole. Further information regarding EPA 
drinking water models used in pesticide exposure assessment can be 
found at http://www.epa.gov/oppefed1/models/water/index.htm.
    Based on the First Index Reservoir Screening Tool (FIRST) and 
Screening Concentration in Ground Water (SCI-GROW) models, the 
estimated drinking water concentrations (EDWCs) of pyrasulfotole for 
acute exposures are estimated to be 6.9 parts per billion (ppb) for 
surface water and 2.4 ppb for ground water. For chronic exposures for 
non-cancer assessments the EDWCs are estimated to be 4.8 ppb for 
surface water and 2.4 ppb for ground water.
    Modeled estimates of drinking water concentrations were directly 
entered into the dietary exposure model. For acute dietary risk 
assessment, the water concentration value of 6.9 ppb was used to assess 
the contribution to drinking water. For chronic dietary risk 
assessment, the water concentration of value 4.8 ppb was used to assess 
the contribution to drinking water.
    3. From non-dietary exposure. The term ``residential exposure'' is 
used in this document to refer to non-occupational, non-dietary 
exposure (e.g., for lawn and garden pest control, indoor pest control, 
termiticides, and flea and tick control on pets). Pyrasulfotole is not 
registered for any specific use patterns that would result in 
residential exposure.
    4. Cumulative effects from substances with a common mechanism of 
toxicity. Section 408(b)(2)(D)(v) of FFDCA requires that, when 
considering whether to establish, modify, or revoke a tolerance, the 
Agency consider ``available information'' concerning the cumulative 
effects of a particular pesticide's residues and ``other substances 
that have a common mechanism of toxicity.''
    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, it is 
the ocular effect (corneal opacity) that 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 effective 
therapeutic agents to treat patients suffering from rare genetic 
diseases of tyrosine catabolism. Treatment starts in childhood but is 
often sustained throughout the 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 and of itself 
cannot easily overwhelm the tyrosine-clearance mechanism in humans.
    Therefore, due to an efficient metabolic process to handle excess 
tyrosine, exposure to environmental residues of HPPD-inhibiting 
herbicides is unlikely to result in high blood levels of tyrosine and 
ocular toxicity in humans; and EPA has concluded that a cumulative risk 
assessment with other HPPD inhibitors is unnecessary. For information 
regarding EPA's efforts to determine which chemicals have a common 
mechanism of toxicity and to evaluate the cumulative effects of such 
chemicals, see EPA's Web site at http://www.epa.gov/pesticides/cumulative.

D. Safety Factor for Infants and Children

    1. In general. Section 408(b)(2)(C) of FFDCA provides that EPA 
shall apply an additional tenfold (10X) margin of safety for infants 
and children in the case of threshold effects to account for prenatal 
and postnatal toxicity and the completeness of the database on toxicity 
and exposure unless EPA determines based on reliable data that a 
different margin of safety will be safe for infants and children. This 
additional margin of safety is commonly referred to as the Food Quality 
Protection Act (FQPA) Safety Factor (SF). In applying this provision, 
EPA either retains the default value of 10X, or uses a different 
additional safety factor when reliable data available to EPA support 
the choice of a different factor.
    2. Prenatal and postnatal sensitivity. The prenatal and postnatal 
toxicity database for pyrasulfotole includes developmental toxicity 
studies in rats and rabbits, a DNT study in rats and a 2-generation 
reproductive toxicity study in rats. As discussed in unit III.A, there 
was quantitative evidence of increased susceptibility of fetal 
offspring in the developmental toxicity study in rabbits. In this 
study, an increased incidence of skeletal variations was observed in 
fetal offspring at the mid dose; whereas maternal toxicity (decreased 
body weight gain and food consumption) was observed only at the next 
highest dose tested.
    The concern for increased susceptibility seen in the rabbit 
developmental toxicity study is low because a) there is well 
established developmental NOAEL in this study, b) the increased 
susceptibility was not seen in the rat developmental toxicity study, 
the DNT study in rats, or the 2-generation reproduction study in rats,

[[Page 23896]]

and c) the NOAEL of the study chosen for the chronic RfD (1 mg/kg/day) 
is 10-fold lower than the NOAEL observed in the rabbit developmental 
toxicity study.
    3. Conclusion. EPA has determined that reliable data show the 
safety of infants and children would be adequately protected if the 
FQPA SF were reduced to 1X. That decision is based on the following 
findings:
    i. The toxicity database for pyrasulfotole is largely complete, 
lacking only an immunotoxicity study. There is no evidence of potential 
immunotoxicity (such as effects on the spleen or thymus, or increased 
globulins) in the available toxicity studies for pyrasulfotole; and EPA 
is using critical studies for the chronic and acute RfDs that have the 
lowest NOAELs in the database for those exposure durations. Therefore, 
EPA does not believe that conducting a functional immunotoxicity study 
will result in a lower POD than that currently used for overall risk 
assessment, and a database uncertainty factor (UFDB) is not 
needed to account for lack of this study.
    ii. Although there were signs of neurotoxicity observed in the 
acute, subchronic and developmental neurotoxicity studies, EPA's 
concern for these effects is low. The critical study (developmental 
neurotoxicity study in rats) chosen for the acute RfD has a well-
defined NOAEL that is 54-fold lower than the dose at which effects 
(decreased locomotor activity on day 0) were seen in the acute 
neurotoxicity study. The critical study (chronic toxicity/
carcinogenicity study in the rat) chosen for the chronic RfD also has a 
well-defined NOAEL that is 42- and 37-fold lower than the doses at 
which effects were observed in the subchronic and developmental 
neurotoxicity studies, respectively. Therefore, EPA does not believe 
that an additional uncertainty factor is needed to account for 
neurotoxicity.
    iii. Although there is evidence of increased quantitative 
susceptibility of in utero rabbits in the prenatal developmental 
toxicity study, the degree of concern for developmental effects is low, 
and EPA did not identify any residual uncertainties after establishing 
toxicity endpoints and traditional UFs to be used in the risk 
assessment of pyrasulfotole.
    iv. There are no residual uncertainties identified in the exposure 
databases. The dietary food exposure assessments were performed based 
on 100 PCT and tolerance-level residues. EPA made conservative 
(protective) assumptions in the ground and surface water modeling used 
to assess exposure to pyrasulfotole in drinking water. These 
assessments will not underestimate the exposure and risks posed by 
pyrasulfotole.

E. Aggregate Risks and Determination of Safety

    EPA determines whether acute and chronic dietary pesticide 
exposures are safe by comparing aggregate exposure estimates to the 
acute PAD (aPAD) and chronic PAD (cPAD). For linear cancer risks, EPA 
calculates the lifetime probability of acquiring cancer given the 
estimated aggregate exposure. Short-, intermediate-, and chronic-term 
risks are evaluated by comparing the estimated aggregate food, water, 
and residential exposure to the appropriate PODs to ensure that an 
adequate MOE exists.
    1. Acute risk. An acute aggregate risk assessment takes into 
account acute exposure estimates from dietary consumption of food and 
drinking water. Using the exposure assumptions discussed in this unit 
for acute exposure, the acute dietary exposure from food and water to 
pyrasulfotole will occupy 9% of the aPAD for children 1 to 2 years old, 
the population group receiving the greatest exposure.
    2. Chronic risk. Using the exposure assumptions described in this 
unit for chronic exposure, EPA has concluded that chronic exposure to 
pyrasulfotole from food and water will utilize 16% of the cPAD for 
children 1 to 2 years old, the population group receiving the greatest 
exposure. There are no residential uses for pyrasulfotole.
    3. Short-term risk. Short-term aggregate exposure takes into 
account short-term residential exposure plus chronic exposure to food 
and water (considered to be a background exposure level). A short-term 
adverse effect was identified; however, pyrasulfotole is not registered 
for any use patterns that would result in short-term residential 
exposure. Short-term risk is assessed based on short-term residential 
exposure plus chronic dietary exposure. Because there is no short-term 
residential exposure and chronic dietary exposure has already been 
assessed under the appropriately protective cPAD (which is at least as 
protective as the POD used to assess short-term risk), no further 
assessment of short-term risk is necessary, and EPA relies on the 
chronic dietary risk assessment for evaluating short-term risk for 
pyrasulfotole.
    4. Intermediate-term risk. Intermediate-term aggregate exposure 
takes into account intermediate-term residential exposure plus chronic 
exposure to food and water (considered to be a background exposure 
level). An intermediate-term adverse effect was identified; however, 
pyrasulfotole is not registered for any use patterns that would result 
in intermediate-term residential exposure. Intermediate-term risk is 
assessed based on intermediate-term residential exposure plus chronic 
dietary exposure. Because there is no intermediate-term residential 
exposure and chronic dietary exposure has already been assessed under 
the appropriately protective cPAD (which is at least as protective as 
the POD used to assess intermediate-term risk), no further assessment 
of intermediate-term risk is necessary, and EPA relies on the chronic 
dietary risk assessment for evaluating intermediate-term risk for 
pyrasulfotole.
    5. Aggregate cancer risk for U.S. population. As explained in Unit 
III.A, risk assessments based on the endpoint selected for chronic risk 
assessment are considered to be protective of any potential 
carcinogenic risk from exposure to pyrasulfotole. Based on the results 
of the chronic risk assessment discussed above in Unit III.E.2, EPA 
concludes that pyrasulfotole is not expected to pose a cancer risk.
    6. Determination of safety. Based on these risk assessments, EPA 
concludes that there is a reasonable certainty that no harm will result 
to the general population, or to infants and children from aggregate 
exposure to pyrasulfotole residues.

IV. Other Considerations

A. Analytical Enforcement Methodology

    Adequate enforcement methodology is available to enforce the 
tolerance expression. Bayer Method AI-001-P04-02 (a high-performance 
liquid chromatography (HPLC)/mass spectrometry (MS)/MS method) is 
available to enforce pyrasulfotole tolerances in plants. Bayer Method 
AI-006-A08-01 (an HPLC-MS/MS method) is suitable as an enforcement 
method for livestock commodities. The methods may be requested from: 
Chief, Analytical Chemistry Branch, Environmental Science Center, 701 
Mapes Rd., Ft. Meade, MD 20755-5350; telephone number: (410) 305-2905; 
e-mail address: residuemethods@epa.gov.

B. International Residue Limits

    In making its tolerance decisions, EPA seeks to harmonize U.S. 
tolerances with international standards whenever possible, consistent 
with U.S. food safety standards and agricultural practices. EPA 
considers the international maximum residue limits (MRLs) established 
by the Codex Alimentarius Commission (Codex), as required by FFDCA 
section 408(b)(4).

[[Page 23897]]

The Codex Alimentarius is a joint U.N. Food and Agriculture 
Organization/World Health Organization food standards program, and it 
is recognized as an international food safety standards-setting 
organization in trade agreements to which the United States is a party. 
EPA may establish a tolerance that is different from a Codex MRL; 
however, FFDCA section 408(b)(4) requires that EPA explain the reasons 
for departing from the Codex level.
    The Codex has not established a MRL for pyrasulfotole on grain 
sorghum, grass, or livestock commodities.

C. Revisions to Petitioned-For Tolerances

    EPA has revised the sorghum commodity terms and the tolerance 
levels for both sorghum and grass commodities. The sorghum commodity 
terms have been revised (from ``sorghum, grain;'' sorghum, forage;'' 
and sorghum, stover'' to ``sorghum, grain, grain;'' ``sorghum, grain, 
forage;'' and ``sorghum, grain, stover'') to agree with the accepted 
terminology in the Agency's Food and Feed Vocabulary. The tolerance 
levels for sorghum and grass commodities have been revised as follows 
based on analysis of the field trial data using the Agency's NAFTA-
harmonized tolerance/MRL calculator in accordance with the Guidance for 
Setting Pesticide Tolerances Based on Field Trial Data: Sorghum, grain, 
grain from 0.8 ppm to 0.70 ppm; sorghum, grain, forage from 1.2 ppm to 
1.5 ppm; sorghum, grain, stover from 0.35 ppm to 0.80 ppm; grass, 
forage from 10 ppm to 25 ppm; and grass, hay from 2.5 ppm to 3.5 ppm.
    Based on the results of the cattle feeding study and the calculated 
maximum reasonable dietary burden (MRDB) for cattle, EPA determined 
that the existing tolerance of 0.02 ppm in or on the meat of cattle, 
goat, horse, and sheep is adequate and need not be raised to 0.04 ppm, 
as proposed; but that tolerances should be established for residues of 
pyrasulfotole and its desmethyl metabolite in or on milk at 0.03 ppm 
(no increase in the established tolerance of 0.01 ppm was proposed); 
fat of cattle, goat, horse and sheep at 0.03 ppm (proposed at 0.04 
ppm); liver of cattle, goat, horse, and sheep at 3.0 ppm (proposed at 8 
ppm); and meat byproducts, except liver, of cattle, goat, horse, and 
sheep at 0.70 ppm (proposed at 2 ppm).
    Based upon a MRDB for hogs, there is no reasonable expectation of 
finding quantifiable residues of pyrasulfotole or its desmethyl 
metabolite in hog muscle and fat; thus, the current tolerances of 0.02 
ppm are adequate (proposed at 0.04 ppm). There is a reasonable 
expectation of residues of pyrasulfotole and/or its desmethyl 
metabolite in hog liver and kidney, and EPA has determined that 
tolerances for these commodities should be set at the following levels: 
hog, meat byproducts, except liver at 0.05 ppm (proposed at 2 ppm); and 
hog, liver at 0.30 ppm (proposed at 8 ppm).
    The petitioner did not propose changes to the existing poultry 
tolerances for pyrasulfotole; however, based on the results of the 
poultry metabolism study and the calculated MRDB for poultry, EPA has 
determined that the existing tolerance for residues of pyrasulfotole 
and its desmethyl metabolite in or on poultry, meat byproducts should 
be increased from 0.02 ppm to 0.20 ppm.

V. Conclusion

    Therefore, tolerances are established for residues of 
pyrasulfotole, including its metabolites and degradates as set forth in 
the regulatory text.

VI. Statutory and Executive Order Reviews

    This final rule establishes tolerances under section 408(d) of 
FFDCA in response to a petition submitted to the Agency. The Office of 
Management and Budget (OMB) has exempted these types of actions from 
review under Executive Order 12866, entitled Regulatory Planning and 
Review (58 FR 51735, October 4, 1993). Because this final rule has been 
exempted from review under Executive Order 12866, this final rule is 
not subject to Executive Order 13211, entitled Actions Concerning 
Regulations That Significantly Affect Energy Supply, Distribution, or 
Use (66 FR 28355, May 22, 2001) or Executive Order 13045, entitled 
Protection of Children from Environmental Health Risks and Safety Risks 
(62 FR 19885, April 23, 1997). This final rule does not contain any 
information collections subject to OMB approval under the Paperwork 
Reduction Act (PRA), 44 U.S.C. 3501 et seq., nor does it require any 
special considerations under Executive Order 12898, entitled Federal 
Actions to Address Environmental Justice in Minority Populations and 
Low-Income Populations (59 FR 7629, February 16, 1994).
    Since tolerances and exemptions that are established on the basis 
of a petition under section 408(d) of FFDCA, such as the tolerance in 
this final rule, do not require the issuance of a proposed rule, the 
requirements of the Regulatory Flexibility Act (RFA) (5 U.S.C. 601 et 
seq.) do not apply.
    This final rule directly regulates growers, food processors, food 
handlers, and food retailers, not States or tribes, nor does this 
action alter the relationships or distribution of power and 
responsibilities established by Congress in the preemption provisions 
of section 408(n)(4) of FFDCA. As such, the Agency has determined that 
this action will not have a substantial direct effect on States or 
tribal governments, on the relationship between the national government 
and the States or tribal governments, or on the distribution of power 
and responsibilities among the various levels of government or between 
the Federal Government and Indian tribes. Thus, the Agency has 
determined that Executive Order 13132, entitled Federalism (64 FR 
43255, August 10, 1999) and Executive Order 13175, entitled 
Consultation and Coordination with Indian Tribal Governments (65 FR 
67249, November 9, 2000) do not apply to this final rule. In addition, 
this final rule does not impose any enforceable duty or contain any 
unfunded mandate as described under Title II of the Unfunded Mandates 
Reform Act of 1995 (UMRA) (Pub. L. 104-4).
    This action does not involve any technical standards that would 
require Agency consideration of voluntary consensus standards pursuant 
to section 12(d) of the National Technology Transfer and Advancement 
Act of 1995 (NTTAA), Public Law 104-113, section 12(d) (15 U.S.C. 272 
note).

VII. Congressional Review Act

    The Congressional Review Act, 5 U.S.C. 801 et seq., generally 
provides that before a rule may take effect, the agency promulgating 
the rule must submit a rule report to each House of the Congress and to 
the Comptroller General of the United States. EPA will submit a report 
containing this rule and other required information to the U.S. Senate, 
the U.S. House of Representatives, and the Comptroller General of the 
United States prior to publication of this final rule in the Federal 
Register. This final rule is not a ``major rule'' as defined by 5 
U.S.C. 804(2).

List of Subjects in 40 CFR Part 180

    Environmental protection, Administrative practice and procedure, 
Agricultural commodities, Pesticides and pests, Reporting and 
recordkeeping requirements.

    Dated: April 21, 2011.
Lois Rossi,
Director, Registration Division, Office of Pesticide Programs.
    Therefore, 40 CFR chapter I is amended as follows:

[[Page 23898]]

PART 180--[AMENDED]

0
1. The authority citation for part 180 continues to read as follows:

    Authority: 21 U.S.C. 321(q), 346a and 371.


0
2. Section 180.631 is amended by revising the introductory text and 
table in paragraph (a) to read as follows:


Sec.  180.631  Pyrasulfotole; tolerances for residues.

    (a) General. Tolerances are established for residues of the 
herbicide pyrasulfotole, including its metabolites and degradates, in 
or on the commodities in the table below. Compliance with the tolerance 
levels specified below is to be determined by measuring only the sum of 
pyrasulfotole ((5-hydroxy-1,3-dimethyl-1H-pyrazol-4-yl)[2-
(methylsulfonyl)-4-(trifluoromethyl)phenyl]methanone) and its desmethyl 
metabolite (5-hydroxy-3-methyl-1H-pyrazol-4-yl)[2-(methylsulfonyl)-4-
(trifluoromethyl)phenyl]methanone), calculated as the stoichiometric 
equivalent of pyrasulfotole, in or on the commodities:

------------------------------------------------------------------------
                                                              Parts per
                         Commodity                             million
------------------------------------------------------------------------
Aspirated grain fractions..................................         0.40
Barley, grain..............................................         0.02
Barley, hay................................................         0.30
Barley, straw..............................................         0.20
Cattle, fat................................................         0.03
Cattle, liver..............................................         3.0
Cattle, meat...............................................         0.02
Cattle, meat byproducts, except liver......................         0.70
Eggs.......................................................         0.02
Goat, fat..................................................         0.03
Goat, liver................................................         3.0
Goat, meat.................................................         0.02
Goat, meat byproducts, except liver........................         0.70
Grass, forage..............................................        25
Grass, hay.................................................         3.5
Hog, fat...................................................         0.02
Hog, liver.................................................         0.30
Hog, meat..................................................         0.02
Hog, meat byproducts, except liver.........................         0.05
Horse, fat.................................................         0.03
Horse, liver...............................................         3.0
Horse, meat................................................         0.02
Horse, meat byproducts, except liver.......................         0.70
Milk.......................................................         0.03
Oat, forage................................................         0.10
Oat, grain.................................................         0.08
Oat, hay...................................................         0.50
Oat, straw.................................................         0.20
Poultry, fat...............................................         0.02
Poultry, meat..............................................         0.02
Poultry, meat byproducts...................................         0.20
Rye, forage................................................         0.20
Rye, grain.................................................         0.02
Rye, straw.................................................         0.20
Sheep, fat.................................................         0.03
Sheep, liver...............................................         3.0
Sheep, meat................................................         0.02
Sheep, meat byproducts, except liver.......................         0.70
Sorghum, grain, forage.....................................         1.5
Sorghum, grain, grain......................................         0.70
Sorghum, grain, stover.....................................         0.80
Wheat, forage..............................................         0.20
Wheat, grain...............................................         0.02
Wheat, hay.................................................         0.80
Wheat, straw...............................................         0.20
------------------------------------------------------------------------

* * * * *
[FR Doc. 2011-10435 Filed 4-28-11; 8:45 am]
BILLING CODE 6560-50-P


