<EPA Registration Division contact: Sidney Jackson<PHONE_NUMBER>>

Interregional Research Project Number 4 (IR-4)

<PP 7E7183>

<	EPA has received a pesticide petition (PP) [7E7183] from IR-4, 500
College road East, Suite 201 W, Princeton, NJ 08540 proposing, pursuant
to section 408(d) of the Federal Food, Drug, and Cosmetic Act (FFDCA),
21 U.S.C. 346a(d), to amend 40 CFR part 180.476>

<	by establishing a tolerance for combined residues of the fungicide
triflumizole,
1-(1-((4-chloro-2-(trifluoromethyl)phenyl)imino)-2-propoxyethyl)-1 H
-imidazole, and its metabolites containing the
4-chloro-2-trifluoromethylaniline moiety, calculated as the parent
compound, >

<	in or on the raw agricultural commodity leafy brassica (subgroup 5B)
at 20 parts per million (ppm).  EPA has determined that the petition
contains data or information regarding the elements set forth in section
408 (d)(2) of the FDDCA; however, EPA has not fully evaluated the
sufficiency of the submitted data at this time or whether the data
support granting of the petition. Additional data may be needed before
EPA rules on the petition.>

<A. Residue Chemistry>

<	1. Plant metabolism. In crops, the metabolism of  [14C]-Phenyl]
triflumizole was investigated in cucumber, pears, grapes and apples. The
major metabolites were:
N-(4-chloro-2-trifluoromethylphenyl)-n-propoxyacetamidine  (FM-6-1),
N-(4-chloro-2-trifluoromethyphenyl)-n-propoxyacetanilide  (FD-1-1) and
the free or conjugated products of
N-(4-chloro-2-trifluoromethylphenyl)-hydroxyacetamidine (the
O-dealkylation product of FM-6-1),
N-(4-chloro-2-trifluoromethylphenyl)-hydroxyacetanilide (FD-2-1)  and
the triflumizole aniline (FA-1-1).

>

<	2. Analytical method. The analytical method is suitable for analyzing
crops for residues of triflumizole and its aniline containing
metabolites at the proposed tolerance levels.  The analytical method has
been independently validated.  Residue levels of triflumizole are
converted to FA-1-1 by acidic and alkaline reflux, followed by
distillation.  Residues are then extracted and subjected to SPE
purification.  Detection and quantitation are conducted by a gas
chromatograph equipped with nitrogen phosphorus detector, electron
capture detector or mass spectrometry detection.  The limit of
quantitation of the method has been determined at 0.05 ppm for the
combined residues of triflumizole and FA-1-1 in mustard greens.  The
enforcement methodology has been submitted to the Food & Drug
Administration for publication in the Pesticide Analytical Manual, Vol.
II (PAM II).>

<	3. Magnitude of residues. Section 3 registrations for triflumizole is
currently exist for several commodities (e.g., apple, cherry, filbert,
grape, pear, strawberry, cucurbits, and meat, milk, poultry and eggs)
and feed items.  The subject of the August 23, 2006, Federal Register
notice regarding triflumizole was the establishment and/or extension of
emergency exemption tolerances on several crops in Texas (i.e., parsley
leaves, dandelion leaves, swiss chard, collards, kale, kohlrabi, mustard
greens, Chinese napa cabbage, broccoli, coriander leaves and turnip
greens).   Many of these crops are in subgroup 5B, so the purpose of
this dietary assessment is to expand the uses of triflumizole to all
crops in 5B.  The proposed group tolerance for leafy brassica vegetables
(subgroup 5B) is 20 ppm.>

<B. Toxicological Profile>

<	1. Acute toxicity. The database includes the following studies for
triflumizole technical: a rat acute oral study with a LD50 of 2.23 g/kg;
a rabbit acute dermal study with a LD50 >2 g/kg; a rat acute inhalation
study with a LC50 >5.3 mg/l; a rabbit primary ocular irritation study
which showed moderate irritation; a rabbit primary dermal irritation
study which showed no irritation; a guinea pig dermal sensitization
study which showed slight dermal sensitization potential.  The database
also includes the following studies for Procure 480SC:  a rat acute oral
study with a LD50 of > 2 g/kg; a rabbit acute dermal study with a LD50
>5 g/kg; a rat acute inhalation study with a LC50 >3.7 mg/l; a rabbit
primary ocular irritation study which showed slight irritation; a rabbit
primary dermal irritation study which showed no irritation; a guinea pig
dermal sensitization study which was negative for skin sensitization.
Acute neurotoxicity study of triflumizole in rats.  Male and Female rats
were administered a single dose of triflumizole by oral gavage at levels
of 0, 25, 100, 200 (female) and 400 (male) mg/kg and observed for 15
days.  Decreased motor activity was noted 3 to 6 hours post exposure in
male and female rats at 100 mg/kg and above.  Functional Observational
Battery (FOB) effects included a decrease rearing counts in females,
decreases in forelimb and hind limb grip strength in males and forelimb
grip strength in females at 100 mg/kg and above.  The NOAEL was
considered to be 25 mg/kg based on clinical findings and functional
observational battery evaluations at 100 mg/kg.>

<	2. Genotoxicty. Triflumizole was negative in all genotoxicity assays
including: Ames assay in S. typhimurium, gene conversion assay in yeast
strain D4, REC assay in B. subtilis, unscheduled DNA synthesis (UDS)
assay in cultured rat hepatocytes, chromosome aberration assay in
cultured Chinese hamster ovary (CHO) cells and a mouse micronucleus
assay.>

<	3. Reproductive and developmental toxicity. In a developmental
toxicity study, triflumizole was administered by oral gavage to
pregnant, female Sprague Dawley rats at dosage levels of 0, 10, 35 or
120 mg/kg/day.  Maternal toxicity, as evidenced by a substantial
reduction in body weight gain, was seen at 35 and 120 mg/kg/day. At
these dosage levels there was a decrease in fetal viability in the form
of late resorptions. There were no teratogenic effects.  The no observed
adverse effect level (NOAEL) for maternal and developmental toxicity was
10 mg/kg/day. Triflumizole was also administered by oral gavage to
pregnant, female New Zealand White rabbits at dosage levels of 0, 5, 25,
or 50 mg/kg/day.  At a dose level of 50 mg/kg/day there was a reduction
in body weight gain in kits. There were no developmental or teratogenic
effects. The NOAEL for maternal toxicity was 25 mg/kg/day and the NOAEL
for developmental toxicity was greater than 50 mg/kg/day. The
reproductive toxicity of triflumizole was evaluated in a rat
reproduction study, conducted on three generations, at dietary
concentrations of 0, 30, 70 and 170 ppm .  Fertility was not affected by
treatment.  There was an increase in placental weight in the F1b, F2b
and F3b litters and a statistically significant increase in gestation
length in the high dose group at the F1a interval and at all three dose
levels at the F3a interval.  The NOEL for reproductive effects in this
study is 70 ppm, which was the original conclusion of the study director
at Life Science Research.  This is based on the increase in gestation
length seen at 170 ppm in two of six matings.  In addition, the NOEL for
systemic parental toxicity was greater than 170 ppm and the NOEL for
developmental toxicity was 70 ppm based upon increased incidences of
hydroureter and space between the body wall and organs.]>

<	4. Subchronic toxicity. To assess sub-acute dermal toxicity,
triflumizole was applied to the backs of male and female Sprague Dawley
rats for three weeks.  High dose female rats exposed to 1,000 mg/kg/day
exhibited mild fatty vacuolation in the liver, which was within the
range of normal biological variation.  Therefore, the NOAEL for
sub-acute dermal toxicity in rats was greater than 1,000 mg/kg/day.  90
Day Neurotoxicity Study of Triflumizole in Rats.  Male and female rats
were administered triflumizole in the diet at levels of 70, 700 or 2000
ppm (4.1, 40.9, 117.3 mg/kg/day male and 4.9, 47.8 and 133.3 mg/kg/day
females) for a period of 90 days.  The NOAEL for general toxicity was 70
ppm (4.1, 4.9 mg/kg/day males and females respectively) based on body
weight (significantly higher in males at 700 ppm and significantly lower
in females at 2000 ppm), food consumption (lower in females at 2000
ppm), hematology (Hb, Hct and/or rbc values were slightly lower in males
and females at 2000 ppm and at week 4 in the 700 ppm dose group) and
pathology evaluations (higher mean and relative liver weights in males
and females at 700 and 2000 ppm, hepatocellular hypertrophy in males and
females at 700 and 2000 ppm).  The NOAEL for neurotoxicity was 2000 ppm
(117.3, 133.3 mg/kg/day males and females respectively).>

<	5. Chronic toxicity. Triflumizole was fed to male and female Beagle
dogs for one year at dietary concentrations of 0, 100, 300 and 1,000 ppm
to assess chronic toxicity.  At a dosage level of 1,000 ppm there was an
increase in serum liver enzymes and a decrease in RBC concentration. The
NOAEL for chronic toxicity in dogs was 300 ppm (7.5 mg/kg/day).
Triflumizole was fed to male and female Sprague Dawley rats for two
years at dietary concentrations of  0, 100, 400 and 1,600 ppm to assess
chronic toxicity. At the high dose level there was a substantial
reduction in body weight gain in males and females. At the mid and high
dose levels there was an increase in liver weight. Ovary weight was
increased in high dose female rats, and kidney weights were elevated in
high dose animals.  Alanine amino-transferase and lactose dehydrogenase
were elevated in high dose males and females, respectively.  High dose
females had an increased incidence of ovarian follicular cysts, while
high dose males exhibited pancreatic acinar cell atrophy. Fatty
vacuolization of the liver was seen at all dose levels and hepatocytic
hypertrophy was seen in high and mid-dose males and females. Female rats
given 400 or 1,600 ppm had an increased incidence of basophilic
foci/areas of hepatocytic alteration. Effects at 100 ppm were confined
to hepatocytic fatty vacuolation and hypertrophy in females. These
changes were less severe than those seen in rats given 400 or 1,600 ppm
and were considered by the laboratory to be indicative of adaptive
metabolic change. The  dietary level of 100 ppm (5 mg/kg/day) is
considered to be a NOAEL.>

<	6. Animal metabolism. Triflumizole, [14C-Phenyl]
1-(1-((4-chloro-2-trifluoromethylphenyl)imino)-2-propoxyethyl)-1H-imidaz
ole, was found to be rapidly absorbed and excreted in rats. Two days
after oral dosing, 78% was found to be excreted in the urine and 20% in
the feces.  No sex difference was noted. It appears that the loss of the
imidazole ring was the basic step in the metabolic pathway of this
fungicide in mammals. The elimination of the imidazole ring yielded
initially N-(4-chloro-2-trifluoromethylphenyl)-n-propoxyacetamidine
(FM-6-1), and N-(4-chloro-2-trifluoromethylphenyl)-n-propoxyacetanilide
(FD-1-1). Other hydroxylated metabolites identified (free, or as
sulfate/glucuronide conjugates) included, among others,
N-(4-chloro-2-trifluoromethylphenyl)-hydroxyacetamidine (FM- 8-1);
4-chloro-2-trifluoromethyl-hydroxyacetanilide (FD-2-1); and 4-chloro-2-
trifluoromethyl-6-hydroxyaniline (FA-1-5).>

<	7. Metabolite toxicology. Both plant and animals produce the same
metabolites that were identified in the metabolism studies; therefore,
the toxicity of the metabolites has essentially been evaluated in the
rat toxicology studies.>

<	8. Endocrine disruption. In the rat reproduction study there was an
increase in placental weight in females at the high dose level of 170
ppm.  There was also a biologically significant increase in gestation
length in high dose F0 and F2 females (F1a and F3a intervals).  The NOEL
for endocrine effects is 70 ppm (3.5 mg/kg/day)>

<C. Aggregate Exposure>

<	1. Dietary exposure. Based on dietary, drinking water and
non-occupational exposure assessments, there is reasonable certainty of
no harm to the US population, any population subgroup, or infants and
children from chronic exposure to triflumizole.>

<	i. Food. Chronic dietary exposures were estimated utilizing the
Dietary Exposure Evaluation Model software with Food Commodity Intake
Database (DEEM-FCID), version 2.16.  EPA’s most recent estimate of
chronic estimated dietary exposures for triflumizole are reported in the
August 23, 2006, Federal Register notice which established emergency
exemption tolerances on a variety of crops.  In that assessment, EPA
used a mixture of anticipated residues (i.e., mean residues from field
trials) and tolerances for the different crops.  EPA included percent
crop treated information from the Biological and Economic Analysis
Division (BEAD) for apples, grapes and pears, while all others were
assumed to be 100% treated.  EPA used modified processing factors for
apples and grapes based on previously submitted studies, while default
processing factors were used for all other foods.  EPA also included an
estimated concentration in drinking water of 40 ppb, which is the
chronic (annual average) concentration in surface water generated by the
FIRST model, in the residue file for the August 23, 2006, assessment.
Estimated chronic dietary exposures (including drinking water) in the
August 23, 2006, notice are reported as 17% of the cPAD for the general
U.S. population, 24% of the cPAD for all infants less than 1 year old,
and 31% of the cPAD for children aged 1-2 years old.  The cPAD used in
the August 23, 2006, notice is 0.015 mg/kg/d, so it is possible to
estimate the chronic exposures in terms of mg/kg/d by multiplying the %
cPAD estimates by the cPAD itself (0.015 mg/kg/d), as shown in Table 1.
These exposure estimates form the baseline for the current assessment.
The only the member of subgroup 5B not included in EPA’s assessment
were added to this risk assessment (cabbage (Chinese, bok choy) and rape
greens).  These crops were included in the current incremental chronic
exposure assessment using tolerance level residues and default
processing factors and assuming 100% crop treated.  Estimated chronic
exposure associated with these two additional subgroup 5B crops are
quite low:  0.000044 mg/kg/d for the general U.S. population, no
exposure for all infants, and 0.000030 mg/kg/d for children aged 1-2
years.  Finally, the resulting total chronic dietary exposures is
expressed as a percent of the revised cPAD (0.035 mg/kg/d).  Thus, the
total chronic dietary exposures are estimated to be 7.4% of the cPAD
(0.035 mg/kg/d) for the general U.S. population, 10% for all infants,
and 13% for children aged 1-2 years old.  Chronic dietary exposures
below 100% of the cPAD are reasonably anticipated to result in no harm
to exposed populations.

For the acute assessment, EPA’s August 23, 2006, assessment assumed
tolerance-level residues, and 100% crop treated for all crops.  EPA used
modified processing factors for apples and grapes based on previously
submitted studies, while default processing factors were used for all
other foods.  Drinking water was included directly into the dietary
assessment using the acute (peak) concentration for surface water (191
ppb) estimated by the FIRST model.  For this updated assessment, an
acute residue file was created using all the information and assumptions
from the EPA assessment and then adding the remaining subgroup 5B crops
assuming tolerance-level residues, 100% crop treated and default
processing factors.  Acute exposures were calculated using DEEM-FCID
version 2.16.  The acute population adjusted dose (aPAD) for
triflumizole is 0.25 mg/kg/d for the general population and 0.1 mg/kg/d
for females aged 13-49.  At the 95th percentile, which is the
appropriate point of comparison for this conservative Tier 1 acute
dietary assessment, the estimated acute exposures range from 9.3% of the
aPAD for the general U.S. population to 25% of the aPAD for children
aged 1-2 years old.  For females aged 13-49 years old,  the 95th
percentile acute dietary exposure is 17% of the subpopulation-specific
aPAD (0.1 mg/kg/d).  Acute dietary exposures below 100% of the aPAD are
reasonably anticipated to result in no harm to exposed populations.>

<	ii. Drinking Food. Tier I screen models FIRST (First Index Reservoir
Screening Tool) and SCI-GRO (Screening Concentrations in Ground Water)
were used to predict estimates of triflumizole concentrations in surface
and groundwater, respectively.  Drinking water levels of comparison
(DWLOCs) were estimated and compared to drinking water estimated
concentrations (DWECs) using EPA standard operating procedures.  DWECs
were obtained from the August 23, 2006, EPA assessment.  The DWECs are
40 ppb for chronic exposures, and 191 ppb for acute exposures.  The
chronic DWLOCs are 98 ppb for toddlers, 324 ppb for adult females and
369 ppb for all adults.  The chronic and acute DWECs are below the
chronic and acute DWLOCs, respectively, for all population groups and
exposure durations.>

<	2. Non-dietary exposure.There are no registered or proposed uses for
application by homeowners. For the proposed residential uses, only
professional handlers would apply triflumizole to woody ornamentals
(trees, shrubs, vines). Triflumizole is not used or proposed for use on
lawns or turf. Therefore, residential exposure is not likely.>

<D. Cumulative Effects>

<	The potential for cumulative effects of triflumizole, an imidazole,
and other substances that have a common mechanism of toxicity was
considered.  The mammalian toxicity of triflumizole is well defined.  No
reliable information exists to indicate that toxic effects produced by
triflumizole would be cumulative with those of any other chemical
compounds.  Therefore, consideration of a common mechanism of toxicity
with other compounds is not appropriate.  Thus, only the potential risks
of triflumizole are considered in the aggregate exposure assessment.>

<E. Safety Determination>

<	1. U.S. population. i. Short-Term Risk.  The acute Population Adjusted
Dose (aPAD) of 0.0233 mg/kg/day and was 9.3% of the aPAD.  Acute dietary
exposure to children (1-2 yrs) was 0.0630 mg/kg/day and was 25.21% of
the aPAD.  Acute dietary exposure to females 13-49 yrs was
0.0167/kg/day, and was 16.7% of the aPAD.  The acute drinking water
level of concern (DWLOC) was calculated to be 658 ppb, and the
model-predicted acute EECs of 191 ppb for surface water and 0.12 ppb for
groundwater are less than this DWLOC.  Therefore, acute aggregate
exposure from triflumizole is not expected to exceed the aPAD.

ii. Chronic Risk.  The chronic Population Adjusted Dose (cPAD) of  0.035
mg/kg bw/day was based on the NOAEL of 3.5 mg/kg/day from the rat
reproduction study,  a 100x uncertainty factor, and a 1x FQPA safety
factor. The chronic dietary exposure to the general U.S. population was
0.002594 mg/kg/day and was 7.4% of the cPAD.  The chronic dietary
exposure to children (1-2 yrs) was 0.0036 mg/kg/day and 10% of the cPAD.
 The chronic DWLOC was calculated  to be 160 ppb, and the
model-predicted chronic EECs of 40 ppb for surface water and 0.12 ppb
for groundwater are less than this DWLOC.  Therefore, chronic aggregate
exposure from triflumizole is not expected to exceed the cPAD.>

<	2. Infants and children. Acute dietary exposure to children (1-2 yrs)
was 0.0630 mg/kg/day and was 25.21% of the aPAD.  The chronic dietary
exposure to children (1-2 yrs) was 0.0036 mg/kg/day and 10% of the
cPAD.>

<F. International Tolerances>

<	Maximum Residue Limits have been established for Chinese cabbage, kale
and turnip greens in Japan at 1.0 ppm.>


Form for Compliance with E. O. 12866 Docket Requirements Title of Regulation: National Emission Standards for Hazardous Air Pollutants for Primary Magnesium Refining Facilities; Final Rule Contact person: Lula Melton, OAQPS/ ESD/ MG ( C439 02)

Phone number: ( 919) 541 2910 Was this regulation reviewed by OMB under Executive Order 12866  Regulatory Planning and Review?

Yes  No.

If you checked " no", you are done with this form. Simply place it in the docket for your regulation. If you checked " yes", please fill out the remainder of the form before placing it in the docket. Also docket any relevant documents referenced in the form.

For regulations that are checked " Yes" above:

This regulation was reviewed by OMB under Executive Order 12866  Regulatory Planning and Review.

Attached is the draft regulation and any other documents sent to OMB for review, such as analyses and assessments. E. O. 12866 requires agencies to make these publicly available.

E. O. 12866 also requires agencies to identify the substantive changes between the draft regulation sent to OMB for review and the regulation subsequently announced [ Please check the appropriate box below:]

EPA made substantive changes to this regulation ( includes changes initiated by EPA or OMB). Attached is a document which: ( 1) identifies all the substantive changes made, and ( 2) notes those changes OMB suggested or recommended.

 No substantive changes were made to this regulation Therefore, no further attachments are required..

If you have questions about this regulation, please call the EPA contact person listed above.


[Federal Register: August 17, 2010 (Volume 75, Number 158)]
[Notices]
[Page 50797-50799]
[DOCID:fr17au10-96]

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DEPARTMENT OF TRANSPORTATION

Federal Motor Carrier Safety Administration

[FMCSA Docket No. FMCSA-2010-0162]

Qualification of Drivers; Exemption Applications; Diabetes
Mellitus

AGENCY: Federal Motor Carrier Safety Administration (FMCSA), DOT.

ACTION: Notice of final disposition.

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

SUMMARY: FMCSA announces its decision to exempt twenty individuals from
its rule prohibiting persons with insulin-treated diabetes mellitus
(ITDM) from operating commercial motor vehicles (CMVs) in interstate
commerce. The exemptions will enable these individuals to operate CMVs
in interstate commerce.

DATES: The exemptions are effective August 17, 2010. The exemptions
expire on August 17, 2012.

FOR FURTHER INFORMATION CONTACT: Dr. Mary D. Gunnels, Director, Medical
Programs,<PHONE_NUMBER><EMAIL_ADDRESS>FMCSA, Room W64-224,
Department of Transportation, 1200 New Jersey Avenue, SE., Washington,
DC 20590-0001. Office hours are from 8:30 a.m. to 5 p.m., Monday
through Friday, except Federal holidays.

SUPPLEMENTARY INFORMATION:

Electronic Access

    You may see all the comments online through the Federal Document
Management System (FDMS) at: http://www.regulations.gov.
    Docket: For access to the docket to read background documents or
comments, go to http://www.regulations.gov and/or Room W12-140 on the
ground level of the West Building, 1200 New Jersey Avenue, SE.,
Washington, DC, between 9 a.m. and 5 p.m., Monday through Friday,
except Federal holidays.
    Privacy Act: Anyone may search the electronic form of all comments
received into any of DOT's dockets by the name of the individual
submitting the comment (or of the person signing the comment, if
submitted on behalf of an association, business, labor union, or other
entity). You may review DOT's Privacy Act Statement for the Federal
Docket Management System published in the Federal Register on January
17, 2008 (73 FR 3316), or you may visit http://edocket.access.gpo.gov/
2008/pdf/E8-785.pdf.

Background

    On June 28, 2010, FMCSA published a Notice of receipt of Federal
diabetes exemption applications from twenty individuals and requested
comments from the public (75 FR 36775). The public comment period
closed on July 28, 2010 and one comment was received.
    FMCSA has evaluated the eligibility of the twenty applicants and
determined that granting the exemptions to these individuals would
achieve a level of safety equivalent to, or greater than, the level
that would be achieved by complying with the current regulation 49 CFR
391.41(b)(3).

Diabetes Mellitus and Driving Experience of the Applicants

    The Agency established the current standard for diabetes in 1970
because several risk studies indicated that drivers with diabetes had a
higher rate of crash involvement than the general population. The
diabetes rule provides that ``A person is physically qualified to drive
a commercial motor vehicle if that person has no established medical
history or clinical diagnosis of diabetes mellitus currently requiring
insulin for control'' (49 CFR 391.41(b)(3)).
    FMCSA established its diabetes exemption program, based on the
Agency's July 2000 study entitled ``A Report to Congress on the
Feasibility of a Program to Qualify Individuals with Insulin-Treated
Diabetes Mellitus to Operate in Interstate Commerce as Directed by the
Transportation Act for the 21st Century.'' The report concluded that a
safe and practicable protocol to allow some drivers with ITDM to
operate CMVs is feasible. The September 3, 2003 (68 FR 52441) Federal
Register Notice in conjunction with the November 8, 2005 (70 FR 67777)
Federal Register Notice provides the current protocol for allowing such
drivers to operate CMVs in interstate commerce.
    These twenty applicants have had ITDM over a range of 1 to 23
years. These applicants report no hypoglycemic reaction that resulted
in loss of consciousness or seizure, that required the assistance of
another person, or resulted in impaired cognitive function without
warning symptoms in the past 5 years (with one year of stability
following any such episode). In each case, an endocrinologist verified
that the driver has demonstrated a willingness to properly monitor and
manage his/her diabetes mellitus, received education related to
diabetes management, and is on a stable insulin regimen. These drivers
report no other disqualifying conditions, including diabetes-related
complications. Each meets the vision standard at 49 CFR 391.41(b)(10).
    The qualifications and medical condition of each applicant were
stated and discussed in detail in the June 28, 2010, Federal Register
Notice and they will not be repeated in this Notice.

Basis for Exemption Determination

    Under 49 U.S.C. 31136(e) and 31315, FMCSA may grant an exemption
from the diabetes standard in 49 CFR 391.41(b)(3) if the exemption is
likely to achieve an equivalent or greater level of safety than would
be achieved without the exemption. The exemption allows the applicants
to operate CMVs in interstate commerce.
    To evaluate the effect of these exemptions on safety, FMCSA
considered medical reports about the applicants' ITDM and vision, and
reviewed the treating endocrinologists' medical opinion related to the
ability of the driver to safely operate a CMV while using insulin.
    Consequently, FMCSA finds that in each case exempting these
applicants from the diabetes standard in 49 CFR 391.41(b)(3) is likely
to achieve a level of safety equal to that existing without the
exemption.

Conditions and Requirements

    The terms and conditions of the exemption will be provided to the
applicants in the exemption document and they include the following:
(1) That each individual submit a quarterly monitoring checklist
completed by the treating endocrinologist as well as an annual
checklist with a comprehensive medical evaluation; (2) that each
individual reports within 2 business days of occurrence, all episodes
of severe hypoglycemia, significant complications, or inability to
manage diabetes; also, any involvement in an accident or any other
adverse event in a CMV or personal vehicle, whether or not it is
related to an episode of hypoglycemia; (3) that each individual provide
a copy of the ophthalmologist's or optometrist's report to the medical
examiner at the time of the annual medical examination; and (4) that
each individual provide a copy of the annual medical certification to
the employer for retention in the driver's qualification file, or keep
a copy in his/her driver's qualification file if he/she is self-
employed. The driver must also have a copy of the certification when
driving, for presentation to a duly authorized Federal, State, or local
enforcement official.

Discussion of Comments

    FMCSA received one comment in this proceeding. The comment was
considered and discussed below.
    The Pennsylvania Department of Transportation stated that it had
reviewed the driving records for Pradip B. Desai, Chad C. Gittings, and
Gerald J. Scheeler and was in favor of granting a Federal diabetes
exemption to these individuals.

Conclusion

    Based upon its evaluation of the twenty exemption applications,
FMCSA exempts, Gary L. Alexander, Michael J. Baron, Daniel E.
Bergstresser, Neil H. Buchner, Charles L. Cheeseboro, Sr., Stephen F.
Clendenin, Donald P. Dean, Pradip B. Desai, Howard M. Galton, Chad C.
Gittings, Steve Gumienny, Richard L. Harding, Mark D. Huffine, Brian M.
Katayama, Rajendra Narine, James M. Parr, Hubert S. Paxton, Gerald J.
Scheeler, Daniel L. Smith and Steven C. Vanscoyoc from the ITDM
standard

in 49 CFR 391.41(b)(3), subject to the conditions listed under
``Conditions and Requirements'' above.
    In accordance with 49 U.S.C. 31136(e) and 31315 each exemption will
be valid for two years unless revoked earlier by FMCSA. The exemption
will be revoked if: (1) The person fails to comply with the terms and
conditions of the exemption; (2) the exemption has resulted in a lower
level of safety than was maintained before it was granted; or (3)
continuation of the exemption would not be consistent with the goals
and objectives of 49 U.S.C. 31136(e) and 31315. If the exemption is
still effective at the end of the 2-year period, the person may apply
to FMCSA for a renewal under procedures in effect at that time.

    Issued on: August 9, 2010.
Larry W. Minor,
Associate Administrator for Policy and Program Development.
[FR Doc. 2010-20216 Filed 8-16-10; 8:45 am]
BILLING CODE 4910-EX-P


[Federal Register Volume 83, Number 88 (Monday, May 7, 2018)]
[Rules and Regulations]
[Pages 19968-19972]
[FR Doc No: 2018-09647]

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ENVIRONMENTAL PROTECTION AGENCY

40 CFR Part 180

[EPA-HQ-OPP-2017-0294; FRL-9977-31]

Duddingtonia flagrans strain IAH 1297; Exemption from the
Requirement of a Tolerance

AGENCY: Environmental Protection Agency (EPA).

ACTION: Final rule.

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SUMMARY: This regulation establishes an exemption from the requirement
of a tolerance for residues of Duddingtonia flagrans strain IAH 1297 in
or on all food commodities when used in accordance with label
directions and good agricultural practices. International Animal Health
Products Pty. Ltd. submitted a petition to EPA under the Federal Food,
Drug, and Cosmetic Act (FFDCA), requesting an exemption from the
requirement of a tolerance. This regulation eliminates the need to
establish a maximum permissible level for residues of Duddingtonia
flagrans strain IAH 1297 under FFDCA.

DATES: This regulation is effective May 7, 2018. Objections and
requests for hearings must be received on or before July 6, 2018, 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: The docket for this action, identified by docket
identification (ID) number EPA-HQ-OPP-2017-0294, is available at http://www.regulations.gov or at the Office of Pesticide Programs Regulatory
Public Docket (OPP Docket) in the Environmental Protection Agency
Docket Center (EPA/DC), West William Jefferson Clinton Bldg., Rm. 3334,
1301 Constitution Ave. NW, Washington, DC 20460-0001. The Public
Reading Room is open from 8:30 a.m. to 4:30 p.m., Monday through
Friday, excluding legal holidays. The telephone number for the Public
Reading Room is<PHONE_NUMBER>, and the telephone number for the OPP
Docket is<PHONE_NUMBER>. Please review the visitor instructions and
additional information about the docket available at http://www.epa.gov/dockets.

FOR FURTHER INFORMATION CONTACT: Robert McNally, Director,
Biopesticides and Pollution Prevention Division (7511P), Office of
Pesticide Programs, Environmental Protection Agency, 1200 Pennsylvania
Ave. NW, Washington, DC 20460-0001; main telephone number: (703) 305-
7090; email address: [email protected].

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.
The following list of North American Industrial Classification System
(NAICS) codes is not intended to be exhaustive, but rather provides a
guide to help readers determine whether this document applies to them.
Potentially affected entities may include:
     Crop production (NAICS code 111).
     Animal production (NAICS code 112).
     Food manufacturing (NAICS code 311).
     Pesticide manufacturing (NAICS code 32532).

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

    You may access a frequently updated electronic version of 40 CFR
part 180 through the Government Printing Office's e-CFR site at http://www.ecfr.gov/cgi-bin/text-idx?&c=ecfr&tpl=/ecfrbrowse/Title40/40tab_02.tpl.

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

    Under FFDCA section 408(g), 21 U.S.C. 346a(g), 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-2017-0294 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
July 6, 2018. 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 (excluding any Confidential Business Information (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 the non-CBI copy of your objection or hearing
request, identified by docket ID number EPA-HQ-OPP-2017-0294, by one of
the following methods:
     Federal eRulemaking Portal: http://www.regulations.gov.
Follow the online instructions for submitting comments. Do not submit
electronically any information you consider to be CBI or other
information whose disclosure is restricted by statute.
     Mail: OPP Docket, Environmental Protection Agency Docket
Center (EPA/DC), (28221T), 1200 Pennsylvania Ave. NW, Washington, DC
20460-0001.
     Hand Delivery: To make special arrangements for hand
delivery or delivery of boxed information, please follow the
instructions at http://www.epa.gov/dockets/contacts.html. Additional
instructions on commenting or visiting the docket, along with more
information about dockets generally, is available at http://www.epa.gov/dockets.

II. Background and Statutory Findings

    In the Federal Register of October 23, 2017 (82 FR 49022) (FRL-
9967-37), EPA issued a document pursuant to FFDCA section 408(d)(3), 21
U.S.C. 346a(d)(3), announcing the filing of a pesticide tolerance
petition (PP 6F8531) by International Animal Health Products Pty. Ltd.,
18 Healey Circuit, Huntingwood, New South Wales 2148, Australia (in
care of SciReg. Inc., 12733 Director's Loop, Woodbridge, VA 22192). The
petition requested that 40 CFR part 180 be amended by establishing an
exemption from the requirement of a tolerance for residues of
Duddingtonia flagrans strain IAH 1297 in or on all raw and processed
agricultural commodities. That document referenced a summary of the
petition prepared by the petitioner International Animal Health
Products Pty. Ltd., which is available in the docket via http://www.regulations.gov.

There were no comments received in response to the notice of filing.
    EPA changed the commodity to be reflected in the tolerance
expression from ``in or on all raw and processed agricultural
commodities'' to ``in or on all food commodities.'' The reason for this
change is explained in Unit VII.B.
    Section 408(c)(2)(A)(i) of FFDCA allows EPA to establish an
exemption from the requirement for a tolerance (the legal limit for a
pesticide chemical residue in or on a food) only if EPA determines that
the exemption is ``safe.'' Section 408(c)(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. Pursuant to FFDCA section 408(c)(2)(B), in
establishing or maintaining in effect an exemption from the requirement
of a tolerance, EPA must take into account the factors set forth in
FFDCA section 408(b)(2)(C), which require EPA to give special
consideration to exposure of infants and children to the pesticide
chemical residue in establishing a tolerance or tolerance exemption 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 . . . .'' Additionally, FFDCA section 408(b)(2)(D)
requires that EPA consider ``available information concerning the
cumulative effects of [a particular pesticide's] . . . residues and
other substances that have a common mechanism of toxicity.''
    EPA performs a number of analyses to determine the risks from
aggregate exposure to pesticide residues. First, for microbial
pesticides, EPA determines the pathogenicity and toxicity of the
pesticide. Second, EPA examines exposure to the pesticide through food,
drinking water, and other exposures that occur as a result of pesticide
use in residential settings, as well as other non-occupational exposure
to the substance.

III. Toxicological Profile

    Consistent with FFDCA section 408(b)(2)(D), EPA reviewed the
available scientific data and other relevant information on
Duddingtonia flagrans strain IAH 1297 and considered their validity,
completeness, and reliability, as well as the relationship of this
information to human risk. EPA also considered available information
concerning the variability of the sensitivities of major identifiable
subgroups of consumers, including infants and children.

A. Overview of Duddingtonia flagrans Strain IAH 1297 (Refs. 1 and 2)

    Duddingtonia flagrans is a fungus commonly found worldwide in
soils, various plant materials, and animal feces that, in the presence
of nematodes, forms looped adhesive network traps in animal feces in
pasture when the diet of grazing animals is supplemented with the
fungus' chlamydospores or the chlamydospores are acquired naturally
from soil or plant material while the animals graze. Duddingtonia
flagrans strain IAH 1297 chlamydospores can survive passage through the
rumen and gastrointestinal tract after ingestion by grazing animals and
then germinate on pasture (i.e., the chlamydospores do not germinate in
animals and cannot grow at normal body temperature or under anaerobic
conditions). Nematode eggs excreted by pastured or wild animals hatch
in the presence of Duddingtonia flagrans strain IAH 1297. Thereafter,
Duddingtonia flagrans strain IAH 1297 passively traps nematodes,
penetrates the nematode cuticle and kills them within 4-8 hours,
occupies the nematode body with hyphae within 20-36 hours, and consumes
nematodes within 48 hours, thus breaking the infection excretion and
reinfection cycle of nematodes. Duddingtonia flagrans strain IAH 1297's
use as a feed-through nematicide comes as growing anthelmintic
(antiparasitic drug) resistance and general lack of new drug options to
treat affected animals is becoming a concern.

B. Microbial Pesticide Toxicology Data Requirements

    All applicable mammalian toxicology data requirements supporting
the request for an exemption from the requirement of a tolerance for
residues of Duddingtonia flagrans strain IAH 1297 in or on all food
commodities have been fulfilled with data submitted by the petitioner
or data waiver requests that have been granted by EPA. The toxicity
tests (acute oral and dermal) and the primary dermal irritation test
that address potential routes of exposure to the active ingredient are
all classified in Toxicity Category IV (see section II of Ref. 3) and
reveal no toxicity or irritation attributed to Duddingtonia flagrans
strain IAH 1297. Moreover, during typical toxicity/pathogenicity
testing done with microbial pesticides, Duddingtonia flagrans strain
IAH 1297 showed no toxicity, pathogenicity, or infectivity via the
pulmonary route of exposure. The conclusions and classifications from
all toxicological information associated with the active ingredient and
submitted by the petitioner are briefly described below.
    1. Acute oral toxicity--rat (Harmonized Guideline 870.1100; Master
Record Identification Number (MRID) No. 503887-01). An acceptable acute
oral toxicity study demonstrated that Duddingtonia flagrans strain IAH
1297 is not toxic to female rats when dosed via the oral route at 5,000
milligrams per kilogram (mg/kg) of bodyweight. The oral median lethal
dose (LD50), which is a statistically derived single dose
that can be expected to cause death in 50% of test animals, was greater
than 5,000 mg/kg of bodyweight for female rats (Toxicity Category IV).
(Refs. 1 and 2).
    2. Acute oral toxicity/pathogenicity (Harmonized Guideline
885.3050; MRID Nos. 501117-14 and 501117-27). An acceptable scientific
rationale was submitted by the petitioner; therefore, EPA waived acute
oral toxicity/pathogenicity testing for Duddingtonia flagrans strain
IAH 1297. An acute oral toxicity study conducted on female rats (MRID
No. 503887-01) demonstrated that Duddingtonia flagrans strain IAH 1297
was not toxic (LD50 greater than 5,000 mg/kg; Toxicity
Category IV). Further, field studies were conducted on animal groups in
Australia under direction of veterinarians. A 56-day study using young
cattle demonstrated that a test substance containing Duddingtonia
flagrans strain IAH 1297 had no discernible health effects when given
with feed at 125 grams per 100 kilograms of bodyweight per day
(representing 10X the label use rate). A 42-day study using Merino ewes
had no findings attributable to treatment with a test substance
containing Duddingtonia flagrans strain IAH 1297, and both groups had
statistically similar weight gains throughout at 1 kilogram per group
per day (representing 5X the label use rate). A 56-day study using
horses demonstrated that a test substance containing Duddingtonia
flagrans strain IAH 1297 had no discernible health effects when given
with feed at 1 gram per kilogram bodyweight per day (representing 10X
the label use rate). No signs of any infection were observed during
these lengthy studies. EPA believes these data, when taken together,
indicate that this fungus would not be toxic, infective, and/or
pathogenic through the oral route of exposure and that further testing
is not necessary. (Refs. 1 and 2).
    3. Acute pulmonary toxicity/pathogenicity--rat (Harmonized
Guideline 885.3150; MRID Nos. 501117-

15, 501117-16, 505317-00, and 505318-00). An acceptable acute pulmonary
toxicity/pathogenicity study performed with Duddingtonia flagrans
strain IAH 1297 did not induce signs of toxicity, infectivity, or
pathogenicity when administered to rats as a single, intratracheal dose
of 5.8 x 10\4\ spores per animal. Additionally, clearance was
established by day 42 of the test. (Refs. 1, 2, and 4).
    4. Acute injection toxicity/pathogenicity (Harmonized Guideline
885.3200; MRID No. 501117-17). An acceptable scientific rationale was
submitted by the petitioner; therefore, EPA waived acute injection
toxicity/pathogenicity testing for Duddingtonia flagrans strain IAH
1297. Intratracheal pulmonary administration of the highest possible
dose of Duddingtonia flagrans strain IAH 1297 did not show any sign of
infection or pathogenicity (MRID No. 501117-16). Lengthy oral dosing of
cattle, sheep, and horses demonstrated no effects at doses of 5-10X the
label use rates (MRID No. 501117-27), and an oral dose of 5,000 mg/kg
of bodyweight to female rats also demonstrated no effects (MRID No.
503887-01). Further, injection is expected to result in minimal
breakdown of spores, and the relatively large size of the spores makes
injection testing impractical. The lack of growth when Duddingtonia
flagrans strain IAH 1297 was tested at 37[deg]C (oral dosing) also
allays the need to test infectivity and pathogenicity by the injection
route. Duddingtonia flagrans strain IAH 1297 has not shown any ability
to germinate or grow when mammals were exposed by various other routes,
and injection of these large spores is not expected to result in
infection even if possible to perform the test. Thus, EPA believes
these data and information, when taken together, indicate that this
fungus would not be toxic, infective, and/or pathogenic through the
injection route of exposure and that further testing is not necessary.
(Refs. 1 and 2).
    5. Acute dermal toxicity--rat (Harmonized Guideline 870.1200; MRID
No. 501113-05). An acceptable acute dermal toxicity study conducted
using a test substance containing Duddingtonia flagrans strain IAH 1297
demonstrated that the fungus was not toxic to rats when dosed at 5,000
mg/kg of bodyweight for 24 hours to a body surface area of
approximately 10 percent. Following exposure, animals were observed for
14 days. All animals survived, gained weight, appeared active and
healthy, and had no signs of dermal irritation throughout the study. No
observable abnormalities were found in any animal at necropsy. The
dermal LD50 for male and female rats combined was greater
than 5,000 mg/kg of bodyweight (Toxicity Category IV). (Refs. 1 and 2).
    6. Primary dermal irritation--rabbit (Harmonized Guideline
870.2500; MRID No. 501113-07). An acceptable primary dermal irritation
study conducted using a test substance containing Duddingtonia flagrans
strain IAH 1297 demonstrated that the fungus was non-irritating to the
skin of rabbits. No dermal erythema, edema, or irritation was noted on
any animal during the study. The primary irritation index was 0.0, and
all animals gained weight normally during the study (Toxicity Category
IV). (Refs. 1 and 2).

IV. Aggregate Exposure

    In examining aggregate exposure, FFDCA section 408 directs EPA to
consider available information concerning exposures from the pesticide
residue in food and all other non-occupational exposures, including
drinking water from ground water or surface water and exposure through
pesticide use in gardens, lawns, or buildings (residential and other
indoor uses).

A. Dietary Exposure (Refs. 1 and 2)

    1. Food exposure. The proposed use of Duddingtonia flagrans strain
IAH 1297 is as a feed-through product for grazing animals such as
sheep, goats, cattle, horses, deer, alpacas and zoo animals. As
Duddingtonia flagrans is naturally present in soils and commonly found
in various plant materials, it is likely that grazing animals have
natural background exposure to the fungus. No adverse effects have been
reported as a result of these types of exposures. Studies performed
with Duddingtonia flagrans strain IAH 1297 have not shown that this
strain has the ability to germinate or grow when mammals are exposed by
various routes, including the oral route. Further, no foodborne disease
outbreaks or cases of mammalian toxin production from Duddingtonia
flagrans have been reported. As a result, dietary exposure to
Duddingtonia flagrans strain IAH 1297 through agricultural commodities
is not anticipated from use of the pesticide products as the spores
and/or components of the spores are unlikely to remain in the treated
animals. Should Duddingtonia flagrans strain IAH 1297 be present in
food, however, supporting toxicological data and information indicate
that no toxicity, pathogenicity, or infectivity is likely to occur with
this type of exposure resulting from the use of this microbial
pesticide when applied in accordance with label directions and good
agricultural practices.
    2. Drinking water exposure. Since Duddingtonia flagrans is
naturally present in the environment and Duddingtonia flagrans strain
IAH 1297 will be present in the feces of treated animals, exposure to
surface and possibly groundwater can be expected. Water treatment
processes should remove any Duddingtonia flagrans or Duddingtonia
flagrans strain IAH 1297 present in these water sources, and no adverse
effects have been reported from exposure to Duddingtonia flagrans
through drinking water. As a result, dietary exposure to Duddingtonia
flagrans strain IAH 1297 through drinking water is not anticipated from
use of the pesticide products as the spores and/or components of the
spores are unlikely to survive the water treatment process. Should
Duddingtonia flagrans strain IAH 1297 be present in water, however,
supporting toxicological data and information indicate that no
toxicity, pathogenicity, or infectivity is likely to occur with this
type of exposure resulting from the use of this microbial pesticide
when applied in accordance with label directions and good agricultural
practices.

B. Other Non-Occupational Exposure

    The pesticide products containing Duddingtonia flagrans strain IAH
1297 are proposed for agricultural use sites and zoos. As a result,
residential exposures resulting from use of these products are not
anticipated. Nevertheless, Duddingtonia flagrans strain IAH 1297 was
not toxic or irritating by dermal exposure and was not toxic,
infective, or pathogenic by pulmonary exposure. Further, the products
are mixed into feed ingredients at 2-34.6% so it is not in pure form,
and the spore size is at the upper end of the respirable range so human
exposures to Duddingtonia flagrans strain IAH 1297 by inhalation from
contact with animal feed supplements is unlikely.

V. 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, EPA consider
``available information concerning the cumulative effects of [a
particular pesticide's] . . . residues and other substances that have a
common mechanism of toxicity.''
    Duddingtonia flagrans strain IAH 1297 is not toxic and does not
have a common mechanism of toxicity with other substances.
Consequently, FFDCA section 408(b)(2)(D)(v) does not apply.

VI. Determination of Safety for U.S. Population, Infants and Children

A. U.S. Population

    For all of the reasons discussed previously, EPA concludes that
there is reasonable certainty that no harm will result to the U.S.
population, including infants and children, from aggregate exposure to
residues of Duddingtonia flagrans strain IAH 1297. This includes all
anticipated dietary exposures and all other exposures for which there
is reliable information.

B. Infants and Children

    FFDCA section 408(b)(2)(C) 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
Safety Factor. 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. As discussed above, EPA has concluded that Duddingtonia
flagrans strain IAH 1297 is not toxic, pathogenic, or infective to
mammals, including infants and children. Because there are no threshold
levels of concern to infants, children, and adults when Duddingtonia
flagrans strain IAH 1297 is used in accordance with label directions
and good agricultural practices, EPA concludes that no additional
margin of safety is necessary to protect infants and children.

VII. Other Considerations

A. Analytical Enforcement Methodology

    An analytical method is not required for enforcement purposes
because EPA is establishing an exemption from the requirement of a
tolerance without any numerical limitation.

B. Revisions to Requested Tolerance Exemption

    One modification has been made to the requested tolerance
exemption. EPA is changing ``in or on all raw and processed
agricultural commodities'' to ``in or on all food commodities'' to
align with the terminology the Agency currently uses when establishing
tolerance exemptions for residues of other like active ingredients.

VIII. Conclusions

    EPA concludes that there is a reasonable certainty that no harm
will result to the U.S. population, including infants and children,
from aggregate exposure to residues of Duddingtonia flagrans strain IAH
1297. Therefore, an exemption from the requirement of a tolerance is
established for residues of Duddingtonia flagrans strain IAH 1297 in or
on all food commodities when used in accordance with label directions
and good agricultural practices.

IX. References

1. U.S. EPA. 2017. Duddingtonia flagrans strain IAH 1297. Memorandum
from J.V. Gagliardi, Ph.D. through M.J. Perry to M. Glikes, dated
October 17, 2017 (available as a ``Supporting Document'' within
Docket ID Number EPA-HQ-OPP-2017-0296 at http://www.regulations.gov).
2. U.S. EPA. 2018. Duddingtonia flagrans strain IAH-1297 (PC Code
033000)--Human Health Risk Assessment Summary. Memorandum from M.
Perry through J. Kough, Ph.D. to C. Kendrick, dated March 26, 2018
(available as a ``Supporting Document'' within Docket ID Number EPA-
HQ-OPP-2017-0296 at http://www.regulations.gov).
3. U.S. EPA. 2014. Chapter 7 of the Label Review Manual
(Precautionary Statements) (Revised July 2014). Available from
https://www.epa.gov/sites/production/files/2015-03/documents/chap-07-jul-2014.pdf.
4. U.S. EPA. 2018. Duddingtonia flagrans strain IAH-1297. Memorandum
from J.V. Gagliardi, Ph.D. through J.L. Kough, Ph.D. to C. Kendrick,
dated March 27, 2018 (available as a ``Supporting Document'' within
Docket ID Number EPA-HQ-OPP-2017-0296 at http://www.regulations.gov).

X. Statutory and Executive Order Reviews

    This action establishes a tolerance exemption under FFDCA section
408(d) in response to a petition submitted to EPA. 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 action has been
exempted from review under Executive Order 12866, this action 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 action 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 FFDCA section 408(d), such as the tolerance
exemption in this action, 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 action directly regulates growers, food processors, food
handlers, and food retailers, not States or tribes. As a result, this
action does not alter the relationships or distribution of power and
responsibilities established by Congress in the preemption provisions
of FFDCA section 408(n)(4). As such, EPA 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, EPA 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 action. In addition, this action does not
impose any enforceable duty or contain any unfunded mandate as
described under Title II of the Unfunded Mandates Reform Act (UMRA) (2
U.S.C. 1501 et seq.).
    This action does not involve any technical standards that would
require EPA's consideration of voluntary consensus standards pursuant
to section 12(d) of the National Technology Transfer and Advancement
Act (NTTAA) (15 U.S.C. 272 note).

XI. Congressional Review Act

    Pursuant to the Congressional Review Act (5 U.S.C. 801 et seq.),
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
the rule in the Federal Register. This action 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 26, 2018.
Wynne Miller,
Acting Director, Office of Pesticide Programs.
    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. Add Sec.  180.1355 to subpart D to read as follows:

Sec.  180.1355   Duddingtonia flagrans strain IAH 1297; exemption from
the requirement of a tolerance.

    An exemption from the requirement of a tolerance is established for
residues of Duddingtonia flagrans strain IAH 1297 in or on all food
commodities when used in accordance with label directions and good
agricultural practices.

[FR Doc. 2018-09647 Filed 5-4-18; 8:45 am]
 BILLING CODE 6560-50-P


[Federal Register: June 23, 2008 (Volume 73, Number 121)]
[Notices]
[Page 35432]
[DOCID:fr23jn08-90]

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SECURITIES AND EXCHANGE COMMISSION

[File No. 500-1]In the Matter of:

Kafus Industries, Ltd., Kevco, Inc., andKings Road Entertainment,
Inc.; Order of Suspension of Trading

June 19, 2008.
    It appears to the Securities and Exchange Commission that there is
a lack of current and accurate information concerning the securities of
Kafus Industries, Ltd. because it has not filed any periodic reports
since the period ended December 31, 1999.
    It appears to the Securities and Exchange Commission that there is
a lack of current and accurate information concerning the securities of
Kevco, Inc. because it has not filed any periodic reports since the
period ended September 30, 2000.
    It appears to the Securities and Exchange Commission that there is
a lack of current and accurate information concerning the securities of
Kings Road Entertainment, Inc. because it has not filed any periodic
reports since the period ended April 30, 2005.
    The Commission is of the opinion that the public interest and the
protection of investors require a suspension of trading in the
securities of the above-listed companies.
    Therefore, it is ordered, pursuant to Section 12(k) of the
Securities Exchange Act of 1934, that trading in the above-listed
companies is suspended for the period from 9:30 a.m. EDT on June 19,
2008, through 11:59 p.m. EDT on July 2, 2008.

    By the Commission.
Jill M. Peterson,
Assistant Secretary.
[FR Doc. 08-1376 Filed 6-19-08; 9:53 am]

BILLING CODE 8010-01-P


[Federal Register Volume 80, Number 153 (Monday, August 10, 2015)]
[Notices]
[Pages 47978-47980]
[FR Doc No: 2015-19536]

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SECURITIES AND EXCHANGE COMMISSION

[Release No. 34-75599; File No. SR-NYSE-2015-02]

Self-Regulatory Organizations; New York Stock Exchange LLC; Order
Instituting Proceedings To Determine Whether To Disapprove Proposed
Rule Change Amending Sections 312.03(b) and 312.04 of the NYSE Listed
Company Manual To Exempt Early Stage Companies From Having To Obtain
Shareholder Approval Before Issuing Shares for Cash to Related Parties,
Affiliates of Related Parties or Entities in Which a Related Party Has
a Substantial Interest

August 4, 2015.

I. Introduction

    On April 16, 2015, New York Stock Exchange LLC (``NYSE'' or the
``Exchange'') filed with the Securities and Exchange Commission
(``Commission''), pursuant to Section 19(b)(1) of the Securities
Exchange Act of 1934 (``Act'') \1\ and Rule 19b-4 thereunder,\2\ a
proposed rule change to exempt early stage companies from having to
obtain shareholder approval before issuing shares to related parties,
affiliates of related parties or entities in which a related party has
a substantial interest. The proposed rule change was published for
comment in the Federal Register on May 6, 2015.\3\ The Commission
received no comment letters on the proposal. On June 18, 2015, the
Commission designated a longer period for Commission action on the
proposed rule change, until August 4, 2015.\4\ This order institutes
proceedings under Section 19(b)(2)(B) of the Act \5\ to determine
whether to disapprove the proposed rule change.
---------------------------------------------------------------------------

    \1\ 15 U.S.C. 78s(b)(1).
    \2\ 17 CFR 240.19b-4.
    \3\ See Securities Exchange Act Release No. 74849 (April 30,
2015), 80 FR 26118 (``Notice'').
    \4\ See Securities Exchange Act Release No. 75248 (June 18,
2015), 80 FR 36385 (June 24, 2015).
    \5\ 15 U.S.C. 78s(b)(2)(B).
---------------------------------------------------------------------------

II. Description of the Proposal

    The Exchange proposes to amend Sections 312.03(b) and 312.04 of the
NYSE Listed Company Manual (``Manual'') to provide an exemption to an
``early stage company'' listed on the Exchange from having to obtain
shareholder approval, under certain circumstances, before issuing
shares of common stock, or securities convertible into or exercisable
for common stock, to a (1) director, officer \6\ or substantial
security holder \7\ of the company (``Related Party'' or ``Related
Parties''), (2) subsidiary, affiliate or closely-related person of a
Related Party or (3) company or entity in which a Related Party has a
substantial direct or indirect interest (together, a ``Proposed
Exempted Party'' or '' Proposed Exempted Parties'').\8\ In particular,
shareholder approval would no longer be required for an ``early stage
company,'' \9\ before the issuance of shares for cash to a Proposed
Exempted Party, provided that the company's audit committee or a
comparable committee comprised solely of independent directors reviews
and approves of all such transactions prior to their completion. Today,
shareholder approval would be required prior to the issuance of shares,
among other things, where the number of shares to be issued to the
Proposed Exempted Party exceeds either 1% of the number of shares of
common stock or 1% of the voting power outstanding before the issuance
(or 5% of the number of shares or voting power, if the Related Party is
classified as such solely because it is a substantial security holder,
and the issuance relates to a sale of stock for cash, at a price at
least as great as each of the book and market value of the company's
common stock).\10\
---------------------------------------------------------------------------

    \6\ Section 312.04(h) of the Manual states that the term
``officer'' has the same meaning as defined by the Commission in
Rule 16a-1(f) under the Act.
    \7\ Section 312.04(e) of the Manual states that an interest
consisting of less than either 5% percent of the number of shares of
common stock or 5% of the voting power outstanding of a company or
entity shall not be considered a substantial interest or cause the
holder of such an interest to be regarded as a substantial security
holder.
    \8\ The Commission notes that there is an inconsistency between
the proposed rule text in Exhibit 5 and the proposed shareholder
approval exception discussed in the Notice. The proposed rule text
in Exhibit 5 states that the exception only applies to Related
Parties, which is defined in Section 312.03(b)(1) of the Manual.
However, the Notice clearly states that the proposed rule change is
meant to apply to all Proposed Exempted Parties, as set forth in
Sections 312.03(b)(1), (2), and (3) of the Manual, not just Related
Parties under Section 312.03(b)(1) of the Manual. See Notice, supra
note 3, at 26119.
    \9\ See supra notes 11 through 13 and accompanying text.
    \10\ The Exchange states that neither The NASDAQ Stock Market
LLC (``NASDAQ'') nor NYSE MKT LLC has a rule comparable to Section
312.03(b) requiring listed companies to obtain shareholder approval
prior to 1% (or in certain cases 5%) share issuances in cash sales
to a Proposed Exempted Party. See Notice, supra note 3, at 26120.
Thus, the Exchange believes the proposed rule change is necessary to
enable the Exchange to compete with NASDAQ for the listing of early
stage companies. See id.

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

    The Exchange also proposes to amend Section 312.04 to include a
definition of the term ``early stage company.'' \11\ The Exchange
proposes to define an early stage company as a company that has not
reported revenues greater than $20 million in any two consecutive
fiscal years since its incorporation. Further, an early stage company
would lose that designation at any time after listing on the Exchange
that the company files an annual report with the Commission in which
the company reports two consecutive fiscal years with revenues greater
than $20 million in each year.\12\ The Exchange represents that a
company's annual financial statements prior to listing on the Exchange
would also be considered when determining if the company should lose
its early stage company designation.\13\
---------------------------------------------------------------------------

    \11\ See proposed Section 312.04(k) of the Manual.
    \12\ The Exchange believes that only a small number of currently
listed companies would qualify under the proposed exemption from
shareholder approval. See Notice, supra note 3, at 26120.
    \13\ See Notice, supra note 3, at 26119, n.6. As an example, the
Exchanges states that if a company files an annual report with the
Commission one year after listing on the Exchange and such annual
report shows that the company has had revenues greater than $20
million in each of two consecutive years (even if one of those years
was prior to listing on the Exchange), the company would lose its
early stage company designation at that time. See id. Moreover, once
the early stage company designation is lost, it cannot be regained
if the subject company later reports reduced revenues. See id. at
26120.
---------------------------------------------------------------------------

    The Exchange also states that any issuance of shares that is not a
sale for cash, including any issuance in connection with the
acquisition of stock or assets of another company, would remain subject
to the shareholder approval provisions of Section 312.03(b) of the
Manual.\14\ Additionally, the Exchange highlights that under Section
312.04(a) of the Manual, an exemption from one provision of Section
312.03 is not a general exemption from all of Section 312.03.
Therefore, notwithstanding that a transaction by an early stage company
may have an exemption under the proposed amendments to Sections
312.03(b) of the Manual, the Exchange states that shareholder approval
requirements of Sections 312.03(c) \15\ and 312.03(d) \16\ would still
be applicable.\17\
---------------------------------------------------------------------------

    \14\ See Notice, supra note 3, at 26119.
    \15\ Section 312.03(c) of the Manual, with certain exceptions,
requires shareholder approval of any issuance of securities in any
transaction or related transactions relating to 20% of more of a
listed company's stock before the issuance. When applying Section
312.03(c), the Exchange states that it reviews issuances to
determine whether they are related and should be aggregated for
purposes of the rule. See Notice, supra note 3, at 26120. The
Exchange analyzes the relationship between separate stock issuances
if they occur within a short period of time, are made to the same or
related parties, or if there is a common use of proceeds. See id.
The Exchange represents that it would engage in this analysis with
respect to any series of sales made by an early stage company to a
Related Party. See id. Moreover, should the Exchange determine that
it is necessary to aggregate the series of sales and, as aggregated,
the total number of shares sold exceeds 19.9% of the shares
outstanding, shareholder approval would be required pursuant to
Section 312.03(c). See id.
    \16\ Section 312.03(d) of the Manual requires shareholder
approval prior to an issuance giving rise to a change of control.
    \17\ See Notice, supra note 3, at 26119-20. The Commission
notes, however, that Section 312.03(c)(2) of the Manual contains an
exception for sales of common stock (or securities convertible into
common stock) for cash in a ``bona fide private financing,'' as
defined in Section 312.04(g), if certain requirements are met.
---------------------------------------------------------------------------

    Lastly, the Exchange also proposes to delete obsolete text from
Section 312.03 of the Manual related to a limited transition period
that is no longer relevant.

III. Proceedings To Determine Whether To Approve or Disapprove SR-NYSE-
2015-02 and Grounds for Disapproval Under Consideration

    The Commission is instituting proceedings pursuant to Section
19(b)(2)(B) of the Act \18\ to determine whether the proposed rule
change should be disapproved. Institution of such proceedings appears
appropriate at this time in view of the legal and policy issues raised
by the proposal, as discussed below. Institution of disapproval
proceedings does not indicate that the Commission has reached any
conclusions with respect to any of the issues involved. Rather, as
described in greater detail below, the Commission seeks and encourages
interested persons to comment on the proposed rule change to inform the
Commission's analysis whether to approve or disapprove the proposed
rule change.
---------------------------------------------------------------------------

    \18\ 15 U.S.C. 78s(b)(2)(B). Section 19(b)(2) of the Act also
provides that proceedings to determine whether to disapprove a
proposed rule change must be concluded within 180 days of the date
of publication of notice of the filing of the proposed rule change.
See id. The time for conclusion of the proceedings may be extended
for up to 60 days if the Commission finds good cause for such
extension and publishes its reasons for so finding. See id.
---------------------------------------------------------------------------

    Pursuant to Section 19(b)(2)(B) of the Act,\19\ the Commission is
providing notice of the grounds for disapproval under consideration.
The Commission is instituting proceedings to allow for additional
analysis of, and input from commenters with respect to, the consistency
of the proposed rule change with Section 6(b)(5) of the Act,\20\ which
requires that the rules of a national securities exchange be designed,
among other things, to prevent fraudulent and manipulative acts and
practices, to promote just and equitable principles of trade, to remove
impediments to and perfect the mechanism of a free and open market and
a national market system and, in general, to protect investors and the
public interest.
---------------------------------------------------------------------------

    \19\ Id.
    \20\ 15 U.S.C. 78f(b)(5).
---------------------------------------------------------------------------

    As discussed above, the Exchange proposes to amend Sections
312.03(b) and 312.04 of the Manual, in order to exempt early stage
companies from having to obtain shareholder approval before issuing a
substantial amount of shares for cash, even at a discount from book and
market value, to Related Parties, namely officers, directors and
substantial security holders, as well as the other Proposed Exempted
Parties.\21\ Although the Exchange conditions its proposed exemption on
the company obtaining the approval of the transaction by its audit
committee (or comparable committee comprised solely of independent
directors), the Commission is concerned that audit committee approval
may not be an effective substitute for the approval of shareholders,
whose interests would be directly impacted by the potentially dilutive
effect of such a transaction. In addition, while the Exchange believes
that the proposal would benefit shareholders of early stage companies
because it could allow those companies to raise additional capital
quickly and inexpensively, any such benefit must be weighed against the
potentially detrimental impact of a dilutive transaction on
shareholders who would no longer have the right to approve it.\22\
---------------------------------------------------------------------------

    \21\ See supra notes 6 and 7.
    \22\ The Commission also notes that the Exchange has not
addressed how the proposal is consistent with the shareholder
approval requirements of Section 303A.08 of the Manual that
generally requires that shareholders must be given the opportunity
to vote on all equity-compensation plans and material revisions
thereto, with limited exemptions. Under Section 303A.08, an equity-
compensation plan is defined as a plan or other arrangement that
provides for the delivery of equity securities of the listed company
to any employee, director or other service provider as compensation
for services. The definition specifically states ``[E]ven a
compensatory grant of options or other equity securities that is not
made under a plan is, nonetheless, an `equity-compensation plan'''
for purposes of the rule. Section 303A.08 also lists certain plans
that would not be considered equity compensation plans under its
definition, for example, plans that are made available to
shareholders generally, such as a typical dividend reinvestment
plan, and plans that merely allow employees, directors or other
service providers to elect to buy shares on the open market or from
the listed company for their current fair market value. The
Commission notes that, in approving the equity compensation rules,
it stated that the rules should have the effect of safeguarding the
interests of shareholders, while placing certain restrictions on
listed companies, and provide shareholders with greater protection
from the potential dilutive effect of equity compensation plans. See
Securities Exchange Act Release No. 48108 (June 30, 2003), 68 FR
39995 (July 3, 2003) (SR-NYSE-2002-46 and SR-NASD-2002-140).

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

    The Commission therefore believes that questions are raised as to
whether the proposed rule change is consistent with the requirements of
Section 6(b)(5) of the Act, including whether it would be designed to
promote just and equitable principles of trade, and protect investors
and the public interest.

IV. Procedure: Request for Written Comments

    The Commission requests that interested persons provide written
submissions of their views, data, and arguments with respect to the
concerns identified above, as well as any others they may have with the
proposal. In particular, the Commission invites the written views of
interested persons concerning whether the proposed rule change is
inconsistent with Section 6(b)(5) \23\ or any other provision of the
Act, or the rules and regulation thereunder. Although there do not
appear to be any issues relevant to approval or disapproval which would
be facilitated by an oral presentation of views, data, and arguments,
the Commission will consider, pursuant to Rule 19b-4, any request for
an opportunity to make an oral presentation.\24\
---------------------------------------------------------------------------

    \23\ 15 U.S.C. 78f(b)(5).
    \24\ Section 19(b)(2) of the Act, as amended by the Securities
Act Amendments of 1975, Pub. L. 94-29 (June 4, 1975), grants the
Commission flexibility to determine what type of proceeding--either
oral or notice and opportunity for written comments--is appropriate
for consideration of a particular proposal by a self-regulatory
organization. See Securities Act Amendments of 1975, Senate Comm. on
Banking, Housing & Urban Affairs, S. Rep. No. 75, 94th Cong., 1st
Sess. 30 (1975).
---------------------------------------------------------------------------

    Interested persons are invited to submit written data, views, and
arguments regarding whether the proposed rule change should be
disapproved by August 31, 2015. Any person who wishes to file a
rebuttal to any other person's submission must file that rebuttal by
September 14, 2015. The Commission asks that commenters address the
sufficiency and merit of the Exchange's statements in support of the
proposed rule change, in addition to any other comments they may wish
to submit about the proposed rule change. In particular, the Commission
seeks comment on the statements of the Exchange contained in the
Notice,\25\ and any other issues raised by the proposed rule change.
---------------------------------------------------------------------------

    \25\ See Notice, supra note 3.
---------------------------------------------------------------------------

    Comments may be submitted by any of the following methods:

Electronic Comments

     Use the Commission's Internet comment form (http://www.sec.gov/rules/sro.shtml); or
     Send an email to<EMAIL_ADDRESS>Please include
File Number SR-NYSE-2015-02 on the subject line.

Paper Comments

     Send paper comments in triplicate to Brent J. Fields,
Secretary, Securities and Exchange Commission, 100 F Street NE.,
Washington, DC 20549-1090.

All submissions should refer to File Number SR-NYSE-2015-02. This file
number should be included on the subject line if email is used. To help
the Commission process and review your comments more efficiently,
please use only one method. The Commission will post all comments on
the Commission's Internet Web site (http://www.sec.gov/rules/sro.shtml). Copies of the submission, all subsequent amendments, all
written statements with respect to the proposed rule change that are
filed with the Commission, and all written communications relating to
the proposed rule change between the Commission and any person, other
than those that may be withheld from the public in accordance with the
provisions of 5 U.S.C. 552, will be available for Web site viewing and
printing in the Commission's Public Reference Room, 100 F Street NE.,
Washington, DC 20549, on official business days between the hours of
10:00 a.m. and 3:00 p.m. Copies of such filing also will be available
for inspection and copying at the principal office of the Exchange. All
comments received will be posted without change; the Commission does
not edit personal identifying information from submissions. You should
submit only information that you wish to make available publicly. All
submissions should refer to File Number SR-NYSE-2015-02 and should be
submitted on or before August 31, 2015. Rebuttal comments should be
submitted by September 14, 2015.

    For the Commission, by the Division of Trading and Markets,
pursuant to delegated authority.\26\
Robert W. Errett,
Deputy Secretary.
---------------------------------------------------------------------------

    \26\ 17 CFR 200.30-3(a)(57).
---------------------------------------------------------------------------

[FR Doc. 2015-19536 Filed 8-7-15; 8:45 am]
 BILLING CODE 8011-01-P


[Federal Register Volume 88, Number 152 (Wednesday, August 9, 2023)]
[Notices]
[Pages 53944-53945]
[FR Doc No: 2023-16992]

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SECURITIES AND EXCHANGE COMMISSION

[SEC File No. 270-154, OMB Control No. 3235-0122]

Proposed Collection; Comment Request; Extension: Rule 17a-10

Upon Written Request, Copies Available From: Securities and Exchange
Commission, Office of FOIA Services, 100 F Street NE, Washington, DC
20549-2736.

    Notice is hereby given that pursuant to the Paperwork Reduction Act
of 1995 (``PRA'') (44 U.S.C. 3501 et seq.), the Securities and Exchange
Commission (``Commission'') is soliciting comments on the existing
collection of information provided for in Rule 17a-10 (17 CFR 240.17a-
10), under the Securities Exchange Act of 1934 (15 U.S.C. 78a et seq.)
(``Exchange Act''). The Commission plans to submit this existing
collection of information to the Office of Management and Budget
(``OMB'') for extension and approval.
    The primary purpose of Rule 17a-10 is to obtain the economic and
statistical data necessary for an ongoing analysis of the securities
industry. Paragraph (a)(1) of Rule 17a-10 generally requires broker-
dealers that are exempted from the requirement to file monthly and
quarterly reports pursuant to paragraph (a) of Exchange Act Rule 17a-5
(17 CFR 240.17a-5) to file with the Commission the Facing Page, a
Statement of Income (Loss), and balance sheet from Part IIA of Form X-
17A-5 \1\ (17 CFR 249.617), and Schedule I of Form X-17A-5 not later
than 17 business days after the end of each calendar year.
---------------------------------------------------------------------------

    \1\ Form X-17A-5 is the Financial and Operational Combined
Uniform Single Report (``FOCUS Report''), which is used by broker-
dealers to provide certain required information to the Commission.
---------------------------------------------------------------------------

    Paragraph (a)(2) of Rule 17a-10 requires a broker-dealer subject to
Rule 17a-5(a) to submit Schedule I of Form X-17A-5 with its Form X-17A-
5 for the calendar quarter ending December 31 of each year.
    Paragraph (b) of Rule 17a-10 provides that the provisions of
paragraph (a) do not apply to members of national securities exchanges
or registered national securities associations that maintain records
containing the information required by Form X-17A-5 and which transmit
to the Commission copies of the records pursuant to a plan which has
been declared effective by the Commission.
    The Commission staff estimates that the current hour burden under
Rule 17a-10 is approximately 44,892 hours per year and the current cost
burden is $0.
    Written comments are invited on: (a) whether the proposed
collection of information is necessary for the proper performance of
the functions of the Commission, including whether the information
shall have practical utility; (b) the accuracy of the Commission's
estimates of the burden of the proposed collection of information; (c)
ways to enhance the quality, utility, and clarity of the information
collected; and (d) ways to minimize the burden of the collection of
information on respondents, including through the use of automated
collection techniques or other forms of information technology.
Consideration will be given to comments and suggestions submitted by
October 10, 2023.
    An agency may not conduct or sponsor, and a person is not required
to respond to, a collection of information unless it displays a
currently valid OMB control number.
    Please direct your written comments to: David Bottom, Director/
Chief

Information Officer, Securities and Exchange Commission, c/o John
Pezzullo, 100 F Street NE, Washington, DC 20549, or send an email to:
[email protected].

    Dated: August 3, 2023.
Sherry R. Haywood,
Assistant Secretary.
[FR Doc. 2023-16992 Filed 8-8-23; 8:45 am]
BILLING CODE 8011-01-P


[Federal Register Volume 81, Number 34 (Monday, February 22, 2016)]
[Notices]
[Pages 8726-8728]
[FR Doc No: 2016-03543]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2010-N-0117]

Agency Information Collection Activities; Proposed Collection;
Comment Request; Guidance for Industry on Hypertension Indication: Drug
Labeling for Cardiovascular Outcome Claims

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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

SUMMARY: The Food and Drug Administration (FDA) is announcing an
opportunity for public comment on the proposed collection of certain
information by the Agency. Under the Paperwork Reduction Act of 1995
(the PRA), Federal Agencies are required to publish notice in the
Federal Register concerning each proposed collection of information
including each proposed extension of an existing collection of
information and to allow 60 days for public comment in response to the
notice. This notice solicits comments on the information collection
associated with the guidance ``Hypertension Indication: Drug Labeling
for Cardiovascular Outcome Claims,'' which is intended to assist
applicants in developing labeling for outcome claims for drugs that are
indicated to treat hypertension.

DATES: Submit either electronic or written comments on the collection
of information by April 22, 2016.

ADDRESSES: You may submit comments as follows:

Electronic Submissions

    Submit electronic comments in the following way:
     Federal eRulemaking Portal: http://www.regulations.gov.
Follow the instructions for submitting comments. Comments submitted
electronically, including attachments, to http://www.regulations.gov
will be posted to the docket unchanged. Because your comment will be
made public, you are solely responsible for ensuring that your comment
does not include any confidential information that you or a third party
may not wish to be posted, such as medical information, your or anyone
else's Social Security number, or confidential business information,
such as a manufacturing process. Please note that if you include your
name, contact information, or other information that identifies you in
the body of your comments, that information will be posted on http://www.regulations.gov.
     If you want to submit a comment with confidential
information that you do not wish to be made available to the public,
submit the comment as a written/paper submission and in the manner
detailed (see ``Written/Paper Submissions'' and ``Instructions'').

Written/Paper Submissions

    Submit written/paper submissions as follows:
     Mail/Hand delivery/Courier (for written/paper
submissions): Division of Dockets Management (HFA-305), Food and Drug
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
     For written/paper comments submitted to the Division of
Dockets Management, FDA will post your comment, as well as any
attachments, except for information submitted, marked and identified,
as confidential, if submitted as detailed in ``Instructions.''
    Instructions: All submissions received must include the Docket No.
FDA-2010-N-0117 for ``Agency Information Collection Activities;
Proposed Collection; Comment Request; Guidance for Industry on
Hypertension Indication: Drug Labeling for Cardiovascular Outcome
Claims.'' Received comments will be placed in the docket and, except
for those submitted as ``Confidential Submissions,'' publicly viewable
at http://www.regulations.gov or at the Division of Dockets Management
between 9 a.m. and 4 p.m., Monday through Friday.
     Confidential Submissions--To submit a comment with
confidential information that you do not wish to be made publicly
available, submit your comments only as a written/paper submission. You
should submit two copies total. One copy will include the information
you claim to be confidential with a heading or cover note that states
``THIS DOCUMENT CONTAINS CONFIDENTIAL INFORMATION.'' The Agency will
review this copy, including the claimed confidential information, in
its consideration of comments. The second copy, which will have the
claimed confidential information redacted/blacked out, will be
available for public viewing and posted on http://www.regulations.gov.
Submit both copies to the Division of Dockets Management. If you do not
wish your name and contact information to be

made publicly available, you can provide this information on the cover
sheet and not in the body of your comments and you must identify this
information as ``confidential.'' Any information marked as
``confidential'' will not be disclosed except in accordance with 21 CFR
10.20 and other applicable disclosure law. For more information about
FDA's posting of comments to public dockets, see 80 FR 56469, September
18, 2015, or access the information at: http://www.fda.gov/regulatoryinformation/dockets/default.htm.
    Docket: For access to the docket to read background documents or
the electronic and written/paper comments received, go to http://www.regulations.gov and insert the docket number, found in brackets in
the heading of this document, into the ``Search'' box and follow the
prompts and/or go to the Division of Dockets Management, 5630 Fishers
Lane, Rm. 1061, Rockville, MD 20852.

FOR FURTHER INFORMATION CONTACT: FDA PRA Staff, Office of Operations,
Food and Drug Administration, 8455 Colesville Rd., COLE-14526, Silver
Spring, MD 20993-0002<EMAIL_ADDRESS>
SUPPLEMENTARY INFORMATION: Under the PRA (44 U.S.C. 3501-3520), Federal
Agencies must obtain approval from the Office of Management and Budget
(OMB) for each collection of information they conduct or sponsor.
``Collection of information'' is defined in 44 U.S.C. 3502(3) and 5 CFR
1320.3(c) and includes Agency requests or requirements that members of
the public submit reports, keep records, or provide information to a
third party. Section 3506(c)(2)(A) of the PRA (44 U.S.C. 3506(c)(2)(A))
requires Federal Agencies to provide a 60-day notice in the Federal
Register concerning each proposed collection of information, including
each proposed extension of an existing collection of information,
before submitting the collection to OMB for approval. To comply with
this requirement, FDA is publishing notice of the proposed collection
of information set forth in this document.
    With respect to the following collection of information, FDA
invites comments on these topics: (1) Whether the proposed collection
of information is necessary for the proper performance of FDA's
functions, including whether the information will have practical
utility; (2) the accuracy of FDA's estimate of the burden of the
proposed collection of information, including the validity of the
methodology and assumptions used; (3) ways to enhance the quality,
utility, and clarity of the information to be collected; and (4) ways
to minimize the burden of the collection of information on respondents,
including through the use of automated collection techniques, when
appropriate, and other forms of information technology.

Guidance for Industry on Hypertension Indication: Drug Labeling for
Cardiovascular Outcome Claims; OMB Control Number 0910-0670--Extension

    This guidance is intended to assist applicants in developing
labeling for outcome claims for drugs that are indicated to treat
hypertension. With few exceptions, current labeling for
antihypertensive drugs includes only the information that these drugs
are indicated to reduce blood pressure; the labeling does not include
information on the clinical benefits related to cardiovascular outcomes
expected from such blood pressure reduction. However, blood pressure
control is well established as beneficial in preventing serious
cardiovascular events, and inadequate treatment of hypertension is
acknowledged as a significant public health problem. FDA believes that
the appropriate use of these drugs can be encouraged by making the
connection between lower blood pressure and improved cardiovascular
outcomes more explicit in labeling. The intent of the guidance is to
provide common labeling for antihypertensive drugs except where
differences are clearly supported by clinical data. The guidance
encourages applicants to submit labeling supplements containing the new
language.
    The guidance contains two provisions that are subject to OMB review
and approval under the PRA and one provision that would be exempt from
OMB review:
    1. Section IV.C of the guidance requests that the CLINICAL STUDIES
section of the Full Prescribing Information of the labeling should
include a summary of placebo or active-controlled trials showing
evidence of the specific drug's effectiveness in lowering blood
pressure. If trials demonstrating cardiovascular outcome benefits
exist, those trials also should be summarized in this section. Table 1
in Section V of the guidance contains the specific drugs for which FDA
has concluded that such trials exist. If there are no cardiovascular
outcome data to cite, one of the following two paragraphs should
appear:
    ``There are no trials of [DRUGNAME] or members of the [name of
pharmacologic class] pharmacologic class demonstrating reductions in
cardiovascular risk in patients with hypertension,'' or ``There are no
trials of [DRUGNAME] demonstrating reductions in cardiovascular risk in
patients with hypertension, but at least one pharmacologically similar
drug has demonstrated such benefits.''
    In the latter case, the applicant's submission generally should
refer to table 1 in section V of the guidance. If the applicant
believes that table 1 is incomplete, it should submit the clinical
evidence for the additional information to Docket No. FDA-2008-D-0150.
The labeling submission should reference the submission to the docket.
FDA estimates that no more than one submission to the docket will be
made annually from one company, and that each submission will take
approximately 10 hours to prepare and submit. Concerning the
recommendations for the CLINICAL STUDIES section of the Full
Prescribing Information of the labeling, FDA regulations at Sec. Sec.
201.56 and 201.57 (21 CFR 201.56 and 201.57) require such labeling, and
the information collection associated with these regulations is
approved by OMB under OMB control number 0910-0572.
    2. Section VI.B of the guidance requests that the format of
cardiovascular outcome claim prior approval supplements submitted to
FDA under the guidance should include the following information:
     A statement that the submission is a cardiovascular
outcome claim supplement, with reference to the guidance and related
Docket No. FDA-2008-D-0150.
     Applicable FDA forms (e.g., 356h, 3397).
     Detailed table of contents.
     Revised labeling to:
    [cir] Include draft revised labeling conforming to the requirements
in Sec. Sec.  201.56 and 201.57 and
    [cir] include marked-up copy of the latest approved labeling,
showing all additions and deletions, with annotations of where
supporting data (if applicable) are located in the submission.
    FDA estimates that approximately 1 cardiovascular outcome claim
supplement will be submitted annually from approximately 1 different
companies, and that each supplement will take approximately 20 hours to
prepare and submit. The guidance also recommends that other labeling
changes (e.g., the addition of adverse event data) should be minimized
and provided in separate supplements, and that the revision of labeling
to conform to Sec. Sec.  201.56 and 201.57 may require

substantial revision to the ADVERSE REACTIONS or other labeling
sections.
    3. Section VI.C of the guidance states that applicants are
encouraged to include the following statement in promotional materials
for the drug.
    ``[DRUGNAME] reduces blood pressure, which reduces the risk of
fatal and nonfatal cardiovascular events, primarily strokes and
myocardial infarctions. Control of high blood pressure should be part
of comprehensive cardiovascular risk management, including, as
appropriate, lipid control, diabetes management, antithrombotic
therapy, smoking cessation, exercise, and limited sodium intake. Many
patients will require more than one drug to achieve blood pressure
goals.''
    The inclusion of this statement in the promotional materials for
the drug would be exempt from OMB review based on 5 CFR 1320.3(c)(2),
which states that the public disclosure of information originally
supplied by the Federal government to the recipient for the purpose of
disclosure to the public is not included within the definition of
collection of information.
    FDA requests public comments on the information collection
provisions described set forth in the following table:

                                 Table 1--Estimated Annual Reporting Burden \1\
----------------------------------------------------------------------------------------------------------------
                                                     Number of
            Activity                 Number of     responses per   Total annual      Hours per      Total hours
                                    respondents     respondent       responses       response
----------------------------------------------------------------------------------------------------------------
Submission to Docket No. FDA-                  1               1               1              10              10
 2008-D-0150....................
Cardiovascular Outcome Claim                   1               1               1              20              20
 Supplement Submission..........
rrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrr
    Total.......................  ..............  ..............  ..............  ..............              30
----------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of
  information.

    Dated: February 16, 2016.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2016-03543 Filed 2-19-16; 8:45 am]
 BILLING CODE 4164-01-P