[Federal Register Volume 73, Number 200 (Wednesday, October 15, 2008)]
[Rules and Regulations]
[Pages 60969-60974]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E8-24034]


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ENVIRONMENTAL PROTECTION AGENCY

40 CFR Part 180

[EPA-HQ-OPP-2008-0042; FRL-8377-4]


Cyprosulfamide; Pesticide Tolerances

AGENCY: Environmental Protection Agency (EPA).

ACTION: Final rule.

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SUMMARY: This regulation establishes tolerances for residues of the 
herbicide safener cyprosulfamide in or on corn, field, forage; corn, 
field, grain; corn, field, stover; corn, pop, grain; corn, pop, stover; 
corn, sweet, forage; corn, sweet, kernel plus cob with husks removed; 
and corn, sweet, stover; and for combined residues of cyprosulfamide 
and its metabolite 4-(aminosulfonyl)-N-cyclopropylbenzamide, calculated 
as cyprosulfamide, in or on cattle, meat byproducts; goat, meat 
byproducts; horse, meat byproducts and sheep, meat byproducts. Bayer 
CropScience requested these tolerances under the Federal Food, Drug, 
and Cosmetic Act (FFDCA).

DATES: This regulation is effective October 15, 2008. Objections and 
requests for hearings must be received on or before December 15, 2008, 
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-2008-0042. To access the 
electronic docket, go to http://www.regulations.gov, select ``Advanced 
Search,'' then ``Docket Search.'' Insert the docket ID number where 
indicated and select the ``Submit'' button. Follow the instructions on 
the regulations.gov website to view the docket index or access 
available documents. All documents in the docket are listed in the 
docket index available in regulations.gov. Although listed in the 
index, some information is not publicly available, 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: <a href="/cdn-cgi/l/email-protection#780b0c19160c1716560b0d0b1916381d0819561f170e"><span class="__cf_email__" data-cfemail="b4c7c0d5dac0dbda9ac7c1c7d5daf4d1c4d59ad3dbc2">[email protected]</span></a>.

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:
    <bullet> Crop production (NAICS code 111).
    <bullet> Animal production (NAICS code 112).
    <bullet> Food manufacturing (NAICS code 311).
    <bullet> 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 Access Electronic Copies of this Document?

    In addition to accessing an electronic copy of this Federal 
Register document through the electronic docket at http://www.regulations.gov, you may access this Federal Register document 
electronically through the EPA Internet under the ``Federal Register'' 
listings at http://www.epa.gov/fedrgstr. You may also access a 
frequently updated electronic version of EPA's tolerance regulations at 
40 CFR part 180 through the Government Printing Office's pilot e-CFR 
site at http://www.gpoaccess.gov/ecfr.

C. Can I File an Objection or Hearing Request?

    Under section 408(g) of FFDCA, 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-2008-0042 in the subject line on the first page of 
your submission. All requests must be in writing, and must be mailed or 
delivered to the Hearing Clerk as required by 40 CFR part 178 on or 
before December 15, 2008.
    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 that is described in ADDRESSES. Information not marked 
confidential pursuant to 40 CFR part 2 may be disclosed publicly by EPA 
without prior notice. Submit this copy, identified by docket ID number 
EPA-HQ-OPP-2008-0042, by one of the following methods:
    <bullet> Federal eRulemaking Portal: http://www.regulations.gov. 
Follow the on-line instructions for submitting comments.
    <bullet> Mail: Office of Pesticide Programs (OPP) Regulatory Public 
Docket (7502P), Environmental Protection Agency, 1200 Pennsylvania 
Ave., NW., Washington, DC 20460-0001.

[[Page 60970]]

    <bullet> 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'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. Petition for Tolerance

    In the Federal Register of June 13, 2008 (73 FR 33814) (FRL-8367-
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 
7E7206) by Bayer CropScience, 2 TW Alexander Drive, P.O. Box 12014, 
Research Triangle Park, NC 27709. The petition requested that 40 CFR 
part 180 be amended by adding a section for the herbicide safener 
cyprosulfamide and establishing tolerances therein for residues of 
cyprosulfamide (parent) in or on the raw agricultural commodities field 
corn grain at 0.01 parts per million (ppm); sweet corn kernels at 0.01 
ppm; sweet corn (k+cwhr) at 0.01 ppm; pop corn grain at 0.01 ppm; milk 
at 0.01ppm; cattle, meat at 0.01 ppm; cattle, fat at 0.01 ppm; cattle, 
liver at 0.02 ppm; cattle, kidney at 0.05 ppm; goat, meat at 0.01 ppm; 
goat, fat at 0.01 ppm; goat, liver at 0.02 ppm; goat, kidney at 0.05 
ppm; hog, meat at 0.01 ppm; hog, fat at 0.01 ppm; hog, liver at 0.02 
ppm; hog, kidney at 0.05 ppm; horse, meat at 0.01 ppm; horse, fat at 
0.01 ppm; horse, liver at 0.02 ppm; horse, kidney at 0.05 ppm; sheep, 
meat at 0.01 ppm; sheep, fat at 0.01 ppm; sheep, liver at 0.02 ppm; and 
sheep, kidney at 0.05 ppm; and for residues of parent cyprosulfamide 
and its metabolites AE 0001789-sulfonamide-alanine, AE 0001789-
sulfonamide-lactate, and AE 0001789-N-cyclopropyl-4-sulfamoylbenzamide 
in or on the raw agricultural commodity field corn forage at 0.15 ppm, 
sweet corn forage at 0.40 ppm, field corn stover at 0.60 ppm, sweet 
corn stover at 0.60 ppm, and pop corn stover at 0.60 ppm. That notice 
referenced a summary of the petition prepared by Bayer CropScience, the 
registrant, which is available to the public 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 
modified the metabolites to be included in the tolerance expression for 
livestock, corn forage and corn stover commodities; modified tolerance 
levels for corn stover commodities and field corn forage; and revised 
the livestock commodities for which tolerances are needed as well as 
the livestock commodity tolerance levels. 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 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 the petitioned-for 
tolerances for residues of the herbicide safener cyprosulfamide in or 
on corn, field, forage at 0.20 ppm; corn, field, grain at 0.01 ppm; 
corn, field, stover at 0.20 ppm; corn, pop, grain at 0.01 ppm; corn, 
pop, stover at 0.20 ppm; corn, sweet, forage at 0.40 ppm; corn, sweet, 
kernel plus cob with husks removed at 0.01 ppm; and corn, sweet, stover 
at 0.35 ppm; and for combined residues of cyprosulfamide and its 
metabolite 4-(aminosulfonyl)-N-cyclopropylbenzamide, calculated as 
cyprosulfamide, in or on cattle, meat byproducts at 0.02 ppm; goat, 
meat byproducts at 0.02 ppm; horse, meat byproducts at 0.02 ppm; and 
sheep, meat byproducts at 0.02 ppm. EPA's assessment of exposures and 
risks associated with establishing tolerances 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.
    Cyprosulfamide has low toxicity in acute toxicity and irritation 
studies and is not a skin sensitizer. In subchronic and chronic oral 
toxicity studies, the critical target organ for cyprosulfamide is the 
urinary tract including the kidney, bladder and ureters. Toxic effects 
in these organs include inflammation and irritation resulting from the 
formation of calculi caused by deposition of the parent compound at 
high doses.
    In the rat chronic toxicity/carcinogenicity study, at doses 
associated with mortality due to nephropathy, there were treatment-
related transitional cell carcinomas in the kidney of one male and a 
transitional cell carcinoma in the urinary bladder of one female. In 
mice, at a dose where there was formation of calculi in the urothelial 
system, cyprosulfamide was associated with two incidents of 
transitional cell papilloma in the urinary bladder. Since the neoplasms 
occurred only at high doses that also demonstrated calculi formation, 
cyprosulfamide was classified as ``Not likely to be a Carcinogen to 
Humans at doses that do not cause urothelial cytotoxicity.'' None of 
the battery of mutagenicity or genetic toxicity studies indicated a 
positive result for cyprosulfamide.
    There is no evidence of developmental toxicity in the prenatal 
developmental toxicity studies in the rat and rabbit and no evidence of 
increased qualitative or quantitative susceptibility of fetuses in 
these studies or of offspring in the 2-generation reproduction study in 
rats. Specific neurotoxicity was not identified in the rat, mouse or 
dog subchronic or chronic studies or in the rat acute and subchronic 
neurotoxicity screen studies.
     Specific information on the studies received and the nature of the 
adverse effects caused by cyprosulfamide as well as the no-observed-
adverse-effect-level (NOAEL) and the lowest-observed-adverse-effect-
level (LOAEL) from the toxicity studies can be found at http://www.regulations.gov in the document Cyprosulfamide: Human Health Risk 
Assessment for Proposed Uses on Corn (Field, Sweet, and Pop), Sorghum 
(Seed Treatment), Residential Turf and

[[Page 60971]]

Ornamentals, page 55 in docket ID number EPA-HQ-OPP-2008-0042.

B. Toxicological Endpoints

    For hazards that have a threshold below which there is no 
appreciable risk, a toxicological point of departure (POD) is 
identified as the basis for derivation of reference values for risk 
assessment. The POD may be defined as the NOAEL in the toxicology study 
identified as appropriate for use in risk assessment. However, if a 
NOAEL cannot be determined, the LOAEL or a Benchmark Dose (BMD) 
approach is sometimes used for risk assessment. Uncertainty/safety 
factors (UFs) are used in conjunction with the POD to take into account 
uncertainties inherent in the extrapolation from laboratory animal data 
to humans and in the variations in sensitivity among members of the 
human population as well as other unknowns. Safety is assessed for 
acute and chronic dietary risks by comparing aggregate food and water 
exposure to the pesticide to the acute population adjusted dose (aPAD) 
and chronic population adjusted dose (cPAD). The aPAD and cPAD are 
calculated by dividing the POD by all applicable UFs. Aggregate short-
term, intermediate-term, and chronic-term risks are evaluated by 
comparing food, water, and residential exposure to the POD to ensure 
that the margin of exposure (MOE) called for by the product of all 
applicable UFs is not exceeded. This latter value is referred to as the 
Level of Concern (LOC).
    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 
greater than that 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 cyprosulfamide used 
for human risk assessment can be found at http://www.regulations.gov in 
the document Cyprosulfamide: Human Health Risk Assessment for Proposed 
Uses on Corn (Field, Sweet, and Pop), Sorghum (Seed Treatment), 
Residential Turf and Ornamentals in docket ID number EPA-HQ-OPP-2008-
0042.

C. Exposure Assessment

    1. Dietary exposure from food and feed uses. In evaluating dietary 
exposure to cyprosulfamide, EPA considered exposure under the 
petitioned-for tolerances. No other tolerances have been established 
for cyprosulfamide. EPA assessed dietary exposures from cyprosulfamide 
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. No such effects were 
identified in the toxicological studies for cyprosulfamide; therefore, 
a quantitative acute dietary exposure assessment is unnecessary.
    ii. Chronic exposure. In conducting the chronic dietary exposure 
assessment EPA used the food consumption data from the United States 
Department of Agriculture (USDA) 1994-1996 and 1998 Continuing Surveys 
of Food Intakes by Individuals (CSFII). As to residue levels in food, 
EPA assumed that 100% of crops with requested uses of cyprosulfamide 
are treated and that all treated crops contain residues at the 
tolerance level.
    iii. Cancer. Based on the results of carcinogenicity studies in 
rats and mice, EPA classified cyprosulfamide as ``Not likely to be a 
Carcinogen to Humans at doses that do not cause urothelial cytotoxicity 
''; therefore, a cancer exposure assessment is unnecessary for this 
chemical.
    iv. Anticipated residue and percent crop treated (PCT) information. 
EPA did not use anticipated residue or PCT information in the dietary 
assessment for cyprosulfamide. Tolerance level residues and 100 PCT 
were assumed for all food commodities.
    2. Dietary exposure from drinking water. The Agency used screening 
level water exposure models in the dietary exposure analysis and risk 
assessment for cyprosulfamide in drinking water. These simulation 
models take into account data on the physical, chemical, and fate/
transport characteristics of cyprosulfamide. 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 cyprosulfamide for 
chronic exposures for non-cancer assessments are estimated to be 2.4 
parts per billion (ppb) for surface water and 0.14 ppb for ground 
water.
    Modeled estimates of drinking water concentrations were directly 
entered into the dietary exposure model. For chronic dietary risk 
assessment, the water concentration of value 2.4 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).
    Cyprosulfamide is proposed for registration on the following use 
sites that could result in residential exposures: Residential 
turfgrass, ornamentals and recreational sites. EPA assessed residential 
exposure using the following assumptions: Homeowners who apply 
cyprosulfamide to ornamentals and turfgrass may be exposed for short-
term durations via the dermal and inhalation routes. Short-term dermal 
and inhalation exposures were assessed for residential handlers who 
mix, load and apply liquid cyprosulfamide products using low-pressure 
hand wands and garden hose-end sprayers.
    There is also potential for short-term postapplication dermal 
exposure of adults and children and incidental oral exposure of 
children following application of cyprosulfamide to turf (e.g. home 
lawns). EPA assessed adult and toddler postapplication dermal exposures 
as well as incidental oral exposure of toddlers from hand-to-mouth, 
object-to-mouth and incidental soil ingestion activities.
    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.''
    Although cyprosulfamide has in common with other sulfonamide 
chemicals the ability to cause urinary tract calculi and in some cases 
tumors in the urinary tract at high doses, EPA has not made a common 
mechanism finding for cyprosulfamide such that cumulative risk 
assessment based on chemicals with a common mechanism is necessary for 
cyprosulfamide and other sulfonamides. With cyprosulfamide, the 
formation of calculi in the urinary tract results from the 
precipitation of cyprosulfamide once it reaches saturation in the 
animal's system. Precipitation of cyprosulfamide is a physical/chemical 
process and not a mechanism of toxicity. Exposures to cyprosulfamide 
and other sulfonamides, such as thiencarbazone-methyl, are not

[[Page 60972]]

additive with regard to the formation of urinary tract calculi at 
anticipated exposure levels. At higher doses, each sulfonamide will 
form calculi independently of the other by a separate physical/chemical 
process. At lower doses, near the anticipated exposure levels, calculi 
will not form even if there is exposure to multiple sulfonamides 
because sulfonamides will not influence the formation of precipitates 
by each other. It would be appropriate to add exposures in assessing 
precipitate formation only if the sulfonamides interacted somehow 
during crystal formation. For information regarding EPA's efforts to 
determine which chemicals have a common mechanism of toxicity and to 
evaluate the cumulative effects of such chemicals, see the policy 
statements released by EPA's Office of Pesticide Programs concerning 
common mechanism determinations and procedures for cumulating effects 
from substances found to have a common mechanism on EPA's website at 
http://www.epa.gov/pesticides/cumulative/.

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 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 cyprosulfamide includes rat and rabbit 
developmental toxicity studies and a 2-generation reproduction toxicity 
study in rats. There was no evidence of increased susceptibility of in 
utero rats or rabbits in the prenatal developmental studies or of young 
rats in the 2-generation reproduction study.
    No fetal effects were seen in the rat developmental toxicity study 
at doses that produced maternal toxicity (weight gain effects and 
indications of kidney effects in one animal). There are two rabbit 
developmental studies available for cyprosulfamide. A second study was 
conducted due to excess maternal toxicity (including deaths) in the 
first study. As in the rat study, no fetal effects were seen in either 
rabbit study at doses that resulted in maternal toxicity (body weight 
decrease, reduced food consumption, and kidney effects in both studies; 
as well as deaths in the first study).
    In the rat reproduction study, effects in the pups occurred at 
doses that also resulted in maternal toxicity. Mid-dose effects 
included organ weight changes in the spleen and urinary tract in the 
dams and body weight changes in the pups. At the high dose, there was 
mortality among the dams associated with poor physical condition and 
severe renal lesion; effects in pups at the high dose included 
decreased pup weight, delayed vaginal opening (apparently related to 
the decreased pup weight), reduced viability (3 total litter loss in 
the F1 generation), reduced lactation index and clinical findings 
(paleness, cold to touch, missing milk spot and thin appearance). No 
increase in sensitivity of the pups was indicated.
    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 cyprosulfamide is complete, except for 
immunotoxicity studies. EPA began requiring functional immunotoxicity 
testing of all food and non-food use pesticides on December 26, 2007. 
Since the requirement went into effect well after this tolerance 
petition was submitted, these studies are not yet available for 
cyprosulfamide. In the absence of specific immunotoxicity studies, EPA 
has evaluated the available toxicity data for cyprosulfamide and 
determined that an additional database uncertainty factor is not needed 
to account for potential immunotoxicity. EPA's determination is based 
on the following considerations.
    a. There was some indication of possible immunotoxicity in the form 
of increased severity of lymphocytolysis in the subchronic mouse study 
in females, but only at a high dose of about 1,300 mg/kg/day. Although 
minimal lymphocytolysis was seen in the control animals, 
lymphocytolysis to a slightly greater degree was observed in some of 
the high dose animals. This minor difference in severity is not of 
concern because:
    (1) The marginal change in severity between control and dosed 
animals was only noted at a very high dose and may not constitute an 
adverse effect.
    (2) No similar effect was seen in the carcinogenicity study in the 
mouse at about 600 mg/kg/day or in other species.
    b. EPA considered the entire toxicity database for cyprosulfamide 
for potential adverse effects on the thymus and spleen as indications 
of potential immunotoxicity. Although changes in thymus weight and 
shape and brown pigment in the spleen were noted, these were determined 
to be non-specific changes not indicative of immunotoxicity.
    c. Cyprosulfamide does not belong to a class of chemicals that 
would be expected to be immunotoxic.
    Therefore, based the considerations in this Unit, EPA does not 
believe that conducting immunotoxicity testing will result in a NOAEL 
less than the NOAEL of 39 mg/kg/day already established for 
cyprosulfamide, and an additional factor (UFDB) for database 
uncertainties is not needed to account for potential immunotoxicity.
    ii. There is no indication that cyprosulfamide is a neurotoxic 
chemical and there is no need for a developmental neurotoxicity study 
or additional UFs to account for neurotoxicity.
    iii. There is no evidence that cyprosulfamide results in increased 
susceptibility in in utero rats or rabbits in the prenatal 
developmental studies or in young rats in the 2-generation reproduction 
study.
    iv. There are no residual uncertainties identified in the exposure 
databases. The dietary food exposure assessments were performed 
assuming 100 PCT and tolerance-level residues. EPA made conservative 
(protective) assumptions in the ground and surface water modeling used 
to assess exposure to cyprosulfamide in drinking water. EPA used 
similarly conservative assumptions to assess postapplication exposure 
of children as well as incidental oral exposure of toddlers. These 
assessments will not underestimate the exposure and risks posed by 
cyprosulfamide.

E. Aggregate Risks and Determination of Safety

    EPA determines whether acute and chronic pesticide exposures are 
safe by comparing aggregate exposure estimates to the aPAD and cPAD. 
The aPAD and cPAD represent the highest safe exposures, taking into 
account all appropriate SFs. EPA calculates the aPAD and cPAD by 
dividing the POD by all applicable UFs. For linear cancer risks, EPA 
calculates the probability of additional cancer cases given the 
estimated aggregate exposure. Short-term, intermediate-term, and 
chronic-term risks are evaluated by comparing the estimated aggregate 
food, water, and residential exposure to the POD to ensure that the MOE 
called for by the

[[Page 60973]]

product of all applicable UFs is not exceeded.
    1. Acute risk. An acute aggregate risk assessment takes into 
account exposure estimates from acute dietary consumption of food and 
drinking water. No adverse effect resulting from a single oral exposure 
was identified in the toxicology studies for cyprosulfamide and no 
acute dietary endpoint was selected. Therefore, cyprosulfamide is not 
expected to pose an acute risk.
    2. Chronic risk. Using the exposure assumptions described in this 
unit for chronic exposure, EPA has concluded that chronic exposure to 
cyprosulfamide from food and water will utilize less than 1% of the 
cPAD for the U.S. population and all population subgroups, including 
infants and children. Based on the explanation in Unit III.C.3., 
regarding residential use patterns, chronic residential exposure to 
residues of cyprosulfamide is not expected.
    3. Short-term risk. Short-term aggregate exposure takes into 
account short-term residential exposure plus chronic exposure through 
food and water (considered to be a background exposure level).
    Cyprosulfamide is currently registered for uses that could result 
in short-term residential exposure, and the Agency has determined that 
it is appropriate to aggregate chronic exposure through food and water 
with short-term residential exposures to cyprosulfamide. Using the 
exposure assumptions described in this unit for short-term exposures, 
EPA has concluded the combined short-term food, water, and residential 
exposures aggregated result in aggregate MOEs of 6,900 for adults and 
5,300 for children (toddlers). The aggregate MOE for adults is based on 
the residential turf scenario and includes combined food, drinking 
water, dermal and inhalation exposures for residential handlers as well 
as post-application dermal exposures from activities on treated turf. 
The aggregate MOE for children includes food, drinking water and post-
application dermal and incidental oral exposures (hand-to-mouth, 
object-to-mouth and soil ingestion) from activities on turf areas 
previously treated with cyprosulfamide.
    4. Intermediate-term risk. Intermediate-term aggregate exposure 
takes into account intermediate-term residential exposure plus chronic 
exposure through food and water (considered to be a background exposure 
level). Cyprosulfamide is not registered for any use patterns that 
would result in intermediate-term residential exposure. Therefore, the 
intermediate-term aggregate risk is the sum of the risk from exposure 
to cyprosulfamide through food and water, which has already been 
addressed, and will not be greater than the chronic aggregate risk.
    5. Aggregate cancer risk for U.S. population. EPA classified 
cyprosulfamide as ``Not likely to be a Carcinogen to Humans at doses 
that do not cause urothelial cytotoxicity. '' Cyprosulfamide 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 cyprosulfamide residues.

IV. Other Considerations

A. Analytical Enforcement Methodology

    Adequate enforcement methodology is available to enforce the 
tolerance expression in plants (High Pressure Liquid Chromatography/
Mass Spectrometry/Mass Spectromety (HPLC/MS/MS) Method UB-008-P06-01) 
and livestock commodities (HPLC/MS/MS Method UB-008-P06-01/02). 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: 
<a href="/cdn-cgi/l/email-protection#60120513090415050d0514080f0413200510014e070f16"><span class="__cf_email__" data-cfemail="8cfee9ffe5e8f9e9e1e9f8e4e3e8ffcce9fceda2ebe3fa">[email protected]</span></a>.

B. International Residue Limits

    There are no Codex, Canadian or Mexican maximum residue limits 
(MRLs) established for residues of cyprosulfamide in crop or livestock 
commodities. However, the U.S. is working with Canada and the United 
Kingdom to achieve MRL harmonization for corn grain.

C. Revisions to Petitioned-For Tolerances

    Based upon review of the data supporting the petition, EPA has 
modified the metabolites to be included in the tolerance expression for 
livestock, corn forage and corn stover commodities; modified tolerance 
levels for corn stover commodities and field corn forage; and revised 
the livestock commodities for which tolerances are needed as well as 
the livestock commodity tolerance levels.
    The petitioner proposed tolerances for residues of cyprosulfamide 
and three metabolites (AE 0001789-sulfonamide-alanine, AE 0001789-
sulfonamide-lactate, and AE 0001789-N-cyclopropyl-4-sulfamoylbenzamide) 
on corn forage and stover commodities as follows: Field corn forage at 
0.15 ppm; field corn stover at 0.60 ppm; pop corn stover at 0.60 ppm; 
sweet corn forage at 0.40 ppm; and sweet corn stover at 0.60 ppm. Based 
on limited toxicity data for AE 0001789-N-cyclopropyl-4-
sulfamoylbenzamide, this metabolite cannot be excluded as a residue of 
concern based on hazard considerations. The other two metabolites (AE 
0001789-sulfonamide-alanine, AE 0001789-sulfonamide-lactate) are 
expected to be less toxic than the parent compound based on structure 
activity relationship (SAR) analysis and can thus be excluded as 
residues of concern based on hazard considerations. In corn field 
trials, residues of all four compounds were low (most below the limit 
of quantitation of 0.01 ppm), with parent cyprosulfamide levels being 
the highest of the four. Based on the lack of hazard concern for two of 
the metabolites and the low levels of all three, EPA concluded that 
parent cyprosulfamide is the residue of concern to be included in the 
tolerance expression for corn commodities, including forage and stover. 
The results of the field trials support tolerances for residues of 
cyprosulfamide, per se, of 0.20 ppm in/on field corn forage and stover; 
0.20 ppm in/on popcorn stover; 0.40 ppm in/on sweet corn forage; and 
0.35 ppm in/on sweet corn stover.
    The petitioner proposed tolerances for residues of cyprosulfamide, 
per se, on meat (0.01 ppm), fat (0.01 ppm), liver (0.02 ppm) and kidney 
(0.05 ppm) of cattle, goat, hog, horse and sheep; and milk (0.01 ppm). 
As noted in this Unit, EPA concluded that the metabolite AE 0001789-N-
cyclopropyl-4-sulfamoylbenzamide (4-(aminosulfonyl)-N-
cyclopropylbenzamide) cannot be excluded as a residue of concern based 
on hazard considerations. The data from the submitted cattle feeding 
study indicate that no quantifiable residues of cyprosulfamide or this 
metabolite are expected in milk, meat or fat. However, quantifiable 
residues of cyprosulfamide and its metabolite may occur in meat 
byproducts (kidney and liver) of cattle, goat, horse and sheep. Based 
on the calculated dietary burden of swine, there is no reasonable 
expectation of residues of cyprosulfamide or its metabolite in swine 
(hog) commodities. Therefore, EPA determined that tolerances are needed 
only for residues of cyprosulfamide and its metabolite (4-
(aminosulfonyl)-N-cyclopropylbenzamide) in/on the meat byproducts of 
cattle, goat, horse and sheep. The submitted data and calculated 
dietary burden for ruminants

[[Page 60974]]

indicate that a tolerance level of 0.02 ppm in these commodities is 
appropriate.

V. Conclusion

    Therefore, tolerances are established for residues of the herbicide 
safener cyprosulfamide (N-[[4-[(cyclopropylamino)carbonyl] 
phenyl]sulfonyl]-2-methoxybenzamide) in or on corn, field, forage at 
0.20 ppm; corn, field, grain at 0.01 ppm; corn, field, stover at 0.20 
ppm; corn, pop, grain at 0.01 ppm; corn, pop, stover at 0.20 ppm; corn, 
sweet, forage at 0.40 ppm; corn, sweet, kernel plus cob with husks 
removed at 0.01 ppm; and corn, sweet, stover at 0.35 ppm; and for 
combined residues of cyprosulfamide and its metabolite, 4-
(aminosulfonyl)-N-cyclopropylbenzamide, calculated as cyprosulfamide, 
in or on cattle, meat byproducts at 0.02 ppm; goat, meat byproducts at 
0.02 ppm; horse, meat byproducts at 0.02 ppm; and sheep, meat 
byproducts at 0.02 ppm.

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, 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) (Public Law 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: September 29, 2008.
Debra Edwards,
Director, Office of Pesticide Programs.

0
Therefore, 40 CFR chapter I is amended as follows:

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 180.644 is added to read as follows:


Sec.  180.644  Cyprosulfamide; tolerances for residues.

    (a) General. (1) Tolerances are established for residues of the 
herbicide safener cyprosulfamide, N-[[4-[(cyclopropylamino)carbonyl] 
phenyl]sulfonyl]-2-methoxybenzamide, in or on the following raw 
agricultural commodities:

------------------------------------------------------------------------
                      Commodity                        Parts per million
------------------------------------------------------------------------
Corn, field, forage..................................               0.20
Corn, field, grain...................................               0.01
Corn, field, stover..................................               0.20
Corn, pop, grain.....................................               0.01
Corn, pop, stover....................................               0.20
Corn, sweet, forage..................................               0.40
Corn, sweet, kernel plus cob with husks removed......               0.01
Corn, sweet, stover..................................               0.35
------------------------------------------------------------------------

    (2) Tolerances are established for residues of the herbicide 
safener cyprosulfamide, N-[[4-[(cyclopropylamino)carbonyl] 
phenyl]sulfonyl]-2-methoxybenzamide, and its metabolite 4-
(aminosulfonyl)-N-cyclopropylbenzamide, calculated as cyprosulfamide, 
in or on the following raw agricultural commodities:

------------------------------------------------------------------------
                      Commodity                        Parts per million
------------------------------------------------------------------------
Cattle, meat byproducts..............................               0.02
Goat, meat byproducts................................               0.02
Horse, meat byproducts...............................               0.02
Sheep, meat byproducts...............................               0.02
------------------------------------------------------------------------

    (b) Section 18 emergency exemptions. [Reserved]
    (c) Tolerances with regional registrations. [Reserved]
    (d) Indirect or inadvertant residues. [Reserved]
[FR Doc. E8-24034 Filed 10-14-08; 8:45 am]
BILLING CODE 6560-50-S


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