[Federal Register: June 1, 2010 (Volume 75, Number 104)]
[Rules and Regulations]
[Page 30282-30284]
[DOCID:fr01jn10-8]

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DEPARTMENT OF TRANSPORTATION

Federal Aviation Administration

14 CFR Part 39

[Docket No. FAA-2010-0261; Directorate Identifier 2010-CE-008-AD;
Amendment 39-16312; AD 2010-11-07]
RIN 2120-AA64

Airworthiness Directives; Quartz Mountain Aerospace, Inc. Model
11E Airplanes

AGENCY: Federal Aviation Administration (FAA), Department of
Transportation (DOT).

ACTION: Final rule.

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SUMMARY: We are adopting a new airworthiness directive (AD) for all
Quartz Mountain Aerospace, Inc. Model 11E airplanes. This AD requires
you to clean and lubricate the aileron pushrod bearings. This AD
results from reports of the aileron control stick force increasing and
of the controls being very noisy. We are issuing this AD to detect and
correct insufficient lubrication and residual metallic paint particles
in the pushrod end ball joints, which could result in difficulty
actuating aileron controls sometime during flight after takeoff. This
condition could lead to difficulty controlling the airplane in flight.

DATES: This AD becomes effective on July 6, 2010.
    On July 6, 2010, the Director of the Federal Register approved the
incorporation by reference of certain publications listed in this AD.

ADDRESSES: Quartz Mountain Aerospace, Inc. is in liquidation. For
service/or continued airworthiness information identified in this AD,
contact Manager, Fort Worth Aircraft Certification Office, FAA, ATTN:
Garry D. Sills, Aerospace Engineer, Rotorcraft Directorate--Airplane
Certification Office, ASW-150, 2601 Meacham Blvd, Fort Worth, Texas
76193; telephone:<PHONE_NUMBER>; facsimile:<PHONE_NUMBER>.

    To view the AD docket, go to U.S. Department of Transportation,
Docket Operations, M-30, West Building Ground Floor, Room W12-140, 1200
New Jersey Avenue, SE., Washington, DC 20590, or on the Internet at
http://www.regulations.gov. The docket number is FAA-2010-0261;
Directorate Identifier 2010-CE-008-AD.

FOR FURTHER INFORMATION CONTACT: Garry D. Sills, Aerospace Engineer,
Rotorcraft Directorate--Airplane Certification Office, ASW-150, 2601
Meacham Blvd, Fort Worth, Texas 76193; telephone:<PHONE_NUMBER>;
facsimile:<PHONE_NUMBER>.

SUPPLEMENTARY INFORMATION:

Discussion

    On March 9, 2010, we issued a proposal to amend part 39 of the
Federal Aviation Regulations (14 CFR part 39) to include an AD that
would apply to all Quartz Mountain Aerospace, Inc. Model 11E airplanes.
This proposal was published in the Federal Register as a notice of
proposed rulemaking (NPRM) on March 16, 2010 (75 FR 12468). The NPRM
proposed to require you to clean and lubricate the aileron pushrod
bearings.

Comments

    We provided the public the opportunity to participate in developing
this AD. We received no comments on the proposal or on the
determination of the cost to the public.

Conclusion

    We have carefully reviewed the available data and determined that
air safety and the public interest require adopting the AD as proposed
except for minor editorial corrections. We have determined that these
minor corrections:
     Are consistent with the intent that was proposed in the
NPRM for correcting the unsafe condition; and
     Do not add any additional burden upon the public than was
already proposed in the NPRM.

Costs of Compliance

    We estimate that this proposed AD would affect 12 airplanes in the
U.S. registry.
    We estimate the following costs to do the proposed cleaning and
lubrication:

------------------------------------------------------------------------
                                                 Total cost   Total cost
            Labor cost              Parts cost      per        on U.S.
                                                  airplane    operators
------------------------------------------------------------------------
1 work-hour x $85 per hour = $85.          $10          $95       $1,140
------------------------------------------------------------------------

Authority for This Rulemaking

    Title 49 of the United States Code specifies the FAA's authority to
issue rules on aviation safety. Subtitle I, section 106 describes the
authority of the FAA Administrator. Subtitle VII, Aviation Programs,
describes in more detail the scope of the agency's authority.
    We are issuing this rulemaking under the authority described in
subtitle VII, part A, subpart III, section 44701, ``General
requirements.'' Under that section, Congress charges the FAA with
promoting safe flight of civil aircraft in air commerce by prescribing
regulations for practices, methods, and procedures the Administrator
finds necessary for safety in air commerce. This regulation is within
the scope of that authority because it addresses an unsafe condition
that is likely to exist or develop on products identified in this AD.

Regulatory Findings

    We have determined that this AD will not have federalism
implications under Executive Order 13132. This AD will not have a
substantial direct effect on the States, on the relationship between
the national government and the States, or on the distribution of power
and responsibilities among the various levels of government.
    For the reasons discussed above, I certify that this AD:
    1. Is not a ``significant regulatory action'' under Executive Order
12866;
    2. Is not a ``significant rule'' under the DOT Regulatory Policies
and Procedures (44 FR 11034, February 26, 1979); and
    3. Will not have a significant economic impact, positive or
negative, on a substantial number of small entities under the criteria
of the Regulatory Flexibility Act.
    We prepared a summary of the costs to comply with this AD (and
other information as included in the Regulatory Evaluation) and placed
it in the AD Docket. You may get a copy of this summary by sending a
request to us at the address listed under ADDRESSES. Include ``Docket
No. FAA-2010-0261; Directorate Identifier 2010-CE-008-AD'' in your
request.

List of Subjects in 14 CFR Part 39

    Air transportation, Aircraft, Aviation safety, Incorporation by
reference, Safety.

Adoption of the Amendment

0
Accordingly, under the authority delegated to me by the Administrator,
the Federal Aviation Administration amends part 39 of the Federal
Aviation Regulations (14 CFR part 39) as follows:

PART 39--AIRWORTHINESS DIRECTIVES

0
1. The authority citation for part 39 continues to read as follows:

    Authority:  49 U.S.C. 106(g), 40113, 44701.

Sec.  39.13  [Amended]

0
2. FAA amends Sec.  39.13 by adding the following new AD:

2010-11-07 Quartz Mountain Aerospace, Inc.: Amendment 39-16312;
Docket No. FAA-2010-0261; Directorate Identifier 2010-CE-008-AD.

Effective Date

    (a) This AD becomes effective on July 6, 2010.

Affected ADs

    (b) None.

Applicability

    (c) This AD applies to Model 11E airplanes, all serial numbers,
that are certificated in any category.

Subject

    (d) Air Transport Association of America (ATA) Code 27: Flight
Controls.

Unsafe Condition

    (e) This AD results from reports of the aileron control stick
force increasing and of the controls being very noisy. We are
issuing this AD to detect and correct insufficient lubrication and
residual metallic paint particles in the rod end ball joints, which
could result in difficulty actuating aileron controls sometime
during flight after takeoff. This failure could lead to difficulty
controlling the airplane in flight.

Compliance

    (f) To address this problem, you must do the following, unless
already done:

------------------------------------------------------------------------
           Actions                 Compliance            Procedures
------------------------------------------------------------------------
(1) Clean and lubricate the   Within the next 10    Follow Quartz
 aileron pushrod bearings.     hours time-in-        Mountain Aerospace
                               service (TIS) after   Mandatory Service
                               July 6, 2010 (the     Bulletin No. SB 09-
                               effective date of     02, dated May 5,
                               this AD).             2009.
(2) Lubricate the aileron     Within 50 hours TIS   Follow Quartz
 pushrod bearings.             after the cleaning    Mountain Aerospace
                               and lubrication       Mandatory Service
                               required by           Bulletin No. SB 09-
                               paragraph (f)(1) of   02, dated May 5,
                               this AD.              2009.
                               Repetitively
                               thereafter at
                               intervals not to
                               exceed 50 hours TIS.
------------------------------------------------------------------------

Special Flight Permit

    (g) Under 14 CFR part 39.23, a special flight is not permitted
for this AD.

Alternative Methods of Compliance (AMOCs)

    (h) The Manager, Fort Worth Aircraft Certification Office, FAA,
has the authority to approve AMOCs for this AD, if requested using
the procedures found in 14 CFR 39.19. Send information to ATTN:
Garry D. Sills, Aerospace Engineer, Rotorcraft Directorate--Airplane
Certification Office, ASW-150, 2601 Meacham Blvd, Fort Worth, Texas
76193; telephone:<PHONE_NUMBER>; facsimile:<PHONE_NUMBER>. Before
using any approved AMOC on any airplane to which the AMOC applies,
notify your appropriate principal inspector (PI) in the FAA Flight
Standards District Office (FSDO), or lacking a PI, your local FSDO.

Material Incorporated by Reference

    (i) You must use Quartz Mountain Aerospace Mandatory Service
Bulletin No. SB 09-02, dated May 5, 2009, to do the actions required
by this AD, unless the AD specifies otherwise.
    (1) The Director of the Federal Register approved the
incorporation by reference of this service information under 5
U.S.C. 552(a) and 1 CFR part 51.
    (2) Quartz Mountain Aerospace, Inc. is in liquidation. For
service information identified in this AD, contact Manager, Fort
Worth Aircraft Certification Office, FAA, ATTN: Garry D. Sills,
Aerospace Engineer, Rotorcraft Directorate--Airplane Certification
Office, ASW-150, 2601 Meacham Blvd, Fort Worth, Texas 76193;
telephone:<PHONE_NUMBER>; fax:<PHONE_NUMBER>.
    (3) You may review copies of the service information
incorporated by reference for this AD at the FAA, Central Region,
Office of the Regional Counsel, 901 Locust, Kansas City, Missouri
64106. For information on the availability of this material at the
Central Region, call<PHONE_NUMBER>.
    (4) You may also review copies of the service information
incorporated by reference for this AD at the National Archives and
Records Administration (NARA). For information on the availability
of this material at NARA, call<PHONE_NUMBER>, or go to: http://
www.archives.gov/federal_register/code_of_federal_regulations/
ibr_locations.html.

    Issued in Kansas City, Missouri, on May 14, 2010.
Kim Smith,
Manager, Small Airplane Directorate, Aircraft Certification Service.
[FR Doc. 2010-12302 Filed 5-28-10; 8:45 am]
BILLING CODE 4910-13-P


[Federal Register Volume 82, Number 126 (Monday, July 3, 2017)]
[Notices]
[Pages 30850-30851]
[FR Doc No: 2017-13954]

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DEPARTMENT OF ENERGY

Federal Energy Regulatory Commission

[Docket No. RC11-6-005]

North American Electric Reliability Corporation; Notice Of Staff
Review Of Compliance Programs

    Commission staff coordinated with the staff of the North American
Electric Reliability Corporation (NERC) to conduct the annual oversight
of the Find, Fix, Track and Report (FFT) program, as outlined in the
March 15, 2012 Order,\1\ and the Compliance Exception (CE) Program, as
proposed by NERC's September 18, 2015 annual Compliance Filing.\2\ The
Commission supported NERC's plan to coordinate with Commission staff to
review the same sample of possible violations, thereby reducing the
burden on the Regional Entities of providing evidence for two different
samples. Commission staff reviewed a sample of 23 FFT possible
violations out of 46 FFT possible violations posted by NERC between
October 2015 and September 2016 and a sample of 100 CE instances of
noncompliance out of 470 CE instances of noncompliance posted by NERC
between October 2015 and September 2016.
---------------------------------------------------------------------------

    \1\ North American Electric Reliability Corp., 138 FERC 61,193,
at P 73 (2012) (discussing Commission plans to survey a random
sample of FFTs submitted each year to gather information on how the
FFT program is working).
    \2\ North American Electric Reliability Corp., Docket No. RC11-
6-004, at 1 (Nov. 13, 2015) (delegated letter order) (stating NERC's
intention to combine the evaluation of Compliance Exceptions with
the annual sampling of FFTs to further streamline oversight of the
FFT and compliance exception programs).
---------------------------------------------------------------------------

    Commission staff believes that the FFT and CE programs are meeting
expectations with limited exceptions. Sampling for the 2016 program
year indicated that the Regional Entities appropriately included 97.5
percent of the sampled possible violations in the FFT and CE programs
and that all 123 possible violations have been adequately remediated.
Commission staff's sample analysis indicated a decreasing number of
documentation concerns, particularly with regard to the quality of the
information contained in the FFT and/or CE postings. For example,
Commission staff found that a few FFT or CE issues still lacked some of
the information requested in NERC's Guidance for Self Reports document
and necessary for the posted FFT or CE.\3\ This includes information
such as start

or end dates, or root cause. Specifically, the identification of root
cause has improved significantly over the past three years, moving from
38 percent missing an identification of root cause to less than 2
percent. Commission staff subsequently reviewed the supporting
information for these FFTs or CEs, which provided a majority of the
missing information. Commission staff ultimately agreed with the final
risk determinations for 120 of the 123 samples. Commission staff also
noted a significant improvement in the clear identification of factors
affecting the risk prior to mitigation (such as potential and actual
risk), and actual harm, which was identified in all samples. In
addition, Commission staff noted that the FFTs and CEs sampled did not
contain any material misrepresentations by the registered entities.
---------------------------------------------------------------------------

    \3\ North American Electric Reliability Corp., 138 FERC 61,193,
at P 60 (2012).

    Dated: June 27, 2017.
Kimberly D. Bose,
Secretary.
[FR Doc. 2017-13954 Filed 6-30-17; 8:45 am]
BILLING CODE 6717-01-P


MEMORANDUM

To:	Margaret Sheppard

From:	Kara Altshuler, Reva Rubenstein, Charlotte Coultrap-Bagg, Mark
Wagner

Date:	March 28, 2006

Re:	Revised Memorandum regarding RTI Metabolism Study on nPB (EPA
Contract Number EP-W-06-008, Task Order 3 Task 06).

Attached please find a revised version of ICF’s review of RTI’s
Final Study Report on 1-Bromopropane, previously delivered under EPA
Contract Number 68-D-00-266, Work Assignment 4-04, Task 02 on November
30, 2005.

RTI’s investigations were conducted to improve the knowledge base on
the metabolism of nPB in animal models.  RTI analyzed the following:

The uptake, distribution and clearance of nPB in rats and mice following
intravenous (i.v.) exposure;

The metabolism of nPB in rats and mice;

Sex differences in the metabolism of inhaled nPB in rats; and

The dermal uptake, distribution and metabolism of nPB in rats.

The data collected by RTI contrast with previous data regarding the role
of CYP enzymes in mice and rats and the role of glutathione in the
metabolism of nPB in rats.  In addition, female rats may be more
susceptible to the adverse effects of nPB at higher concentrations than
males, but metabolize nPB similarly to male rats at lower
concentrations.

Please contact Mark Wagner at<PHONE_NUMBER> with any questions or
comments.Pharmacokinetic Studies with nPB prepared by RTI

RTI has conducted a number of studies in rats and mice to determine the
uptake, distribution, clearance, and pharmacokinetics of nPB via
intravenous (iv), inhalation, and dermal uptake.  These experiments were
conducted primarily because metabolism data on nPB in animal models was
incomplete, and much of it was dated (Barnsley, 1966; Jones and Walsh,
1979; Tachizawa et al., 1982; Ishidao et al., 2002).  Based on the data,
RTI presented the following conclusions:

nPB that is administered via injection or inhalation is eliminated
mainly via volatiles in the breath or as exhaled CO2, with excretion in
the urine as a secondary path.

Distribution and metabolism are similar across intravenous (iv) doses
spanning two orders of magnitude (up to 100 mg/kg).

Male rats and mice are similar in the distribution and clearance of
systemic nPB.

The tissue:blood ratio of 3.15 indicates that nPB preferentially
partitions into tissues and organs following exposure, and should not
remain in the bloodstream.

Metabolism of nPB appears to be primarily carried out by cytochrome P450
(CYP450) isozymes.

Rats have two systems that metabolize nPB; at low doses, oxidation
predominates, but at higher doses, metabolites shift to those indicative
of glutathione conjugation, indicating that metabolism is dose-dependent
in this species.

Mice appear to metabolize nPB differently than rats (metabolism is
almost exclusively via oxidation by P450 enzymes and is not
dose-dependent).

Female rats may have a decreased capacity to metabolize nPB compared to
male rats;

Rodents have a decreased ability to metabolize and excrete inhaled nPB
when initial exposure concentrations are greater than 800 ppm (e.g.,
metabolism is saturated).

nPB is not appreciably absorbed in rats following dermal application.

More detailed descriptions of the experiments conducted by RTI are
provided in the sections that follow.  There are a few limitations to
the RTI studies: 1) the document does not provide any raw data from the
experiments, which prevents an independent validation of presented
results and conclusions; and 2) metabolism studies, in general, involve
very few animals (4-5 per dose in this study), which often results in
standard deviations around the mean values that overlap for many
endpoints and time points.

Uptake, Distribution and Clearance of nPB in Male Mice and Rats
Following i.v. Exposure

RTI conducted a series of experiments in male B6C3F1 mice and Fisher 344
rats using radiolabeled nPB (at the 1-carbon position) that was
administered as a single bolus iv dose.  Doses of 5, 20, or 100 mg/kg
were used.  The doses were cleared from the body in the mice primarily
as uncharacterized volatile organic compounds (VOCs) in the breath
(~39-49% of the radiolabeled dose after 48 hours), via CO2 in the breath
(~19-28% of the dose at 48 hours), and in the urine (~16-26% of the dose
after 48 hours).  Very little (<4% of the dose) was eliminated via
feces.  Approximately 2% of the dose was retained in the tissues and
carcass, with distribution primarily to the liver, muscle, skin, small
intestine, and residual carcass.  Distribution and excretion of the
radiolabel was independent of the dose.  Similar results were obtained
in Fischer 344 male rats administered 5- and 20-mg/kg dosages,
indicating that male mice and rats distribute and clear injected nPB in
a similar fashion.  Analysis of the urine revealed no bromine,
indicating that it had been reabsorbed within the time frame of the
analysis (48 hours post-dosing).  Bromine is passively reabsorbed in the
kidneys as a negatively charged ion associated with sodium that is
reabsorbed in this organ.  It has an extended half-life in the body,
which increases its bioavailability (Pavelka et al., 2005).    REF
_Ref121131986 \h  \* MERGEFORMAT  Table 1  presents the results of the
experiments in mice.

Table   SEQ Table \* ARABIC  1 .  Recovery of Radioactivity Following a
Single iv Dose of 5 mg/kg

[14C]-nPB to Male B6C3F1 Mice at 48 hours Post-Dosinga

Route	Cumulative Percent Dose Excreted or Absorbed

Tissue Absorption

	     Liver	   0.432±0.491

     Muscle	   0.415±0.079

     Skin	   0.332±0.046

     Small Intestine	   0.112±0.026

     Carcass	   0.33±0.13

Subtotal for tissues	2.03

Urine	25.5±5.8

Feces	2.9±1.1

VOCs	44.7±9.6

CO2	27.5±3.5

aExcerpted from Table 5.2, RTI (2005), p. 23.

In a separate set of experiments, the researchers analyzed the clearance
of nPB as a function of dose in male rats and mice.  They showed that at
5 mg/kg (iv dose), mice excreted slightly more of the
radioactively-labeled nPB in the urine than rats, the same amount as
CO2, and less as VOCs in the breath, than rats.  When the dose was
increased to 20 mg/kg, and further to 100 mg/kg, the amount excreted in
the urine and as CO2 decreased for both animals but more dramatically
for rats, and the percentage of label in exhaled VOCs increased from 50
to 70% in the rat, but did not change appreciably in the mouse.  These
data suggested that the mouse had a greater ability to metabolize nPB
completely to CO2 compared to the rat as exposure doses increased.

RTI focused on the P450 and glutathione enzyme systems because these two
enzyme groups are primarily responsible for clearing environmental
toxicants from the body and because previous metabolism studies (Jones
and Walsh, 1979; Kim et al., 1999; Ichihara et al., 2000) implicated
these enzymes in the metabolism of nPB. The difference in metabolism of
nPB between species appears to be that in rats, metabolism is begun as
oxidation by CYP450 enzymes, with glutathione conjugation still playing
an important role.  In mice, oxidation appears to be the only
significant pathway.  This hypothesis is supported by two sets of
independent data.  The first is the change in distribution of
radioactivity in urine, VOCs, CO2, and liver following iv dosing.  For
example, nPB tends to distribute in the livers of rats more than that of
mice, even at the lowest dose of 5 mg/kg.  At this low dose, compared to
the rat, the mouse showed slightly increased excretion in urine, lower
exhalation as VOCs in breath, and equal exhalation as CO2.  However, at
this dose (and at 20 mg/kg), nPB deposition in the liver (measured as
ng-equivalents/g liver) was 7 to ~10 times higher in rats.  It is
RTI’s supposition that the first step of metabolism must be oxidation
(rather than glutathione conjugation) to make a more bio-reactive
molecule; if glutathione conjugation were the first step, the increased
water solubility of the compound would lead it to be excreted, and it
would not be further retained in the tissue otherwise the compound would
not preferentially be absorbed into tissue.  This is shown by the
decrease of radiolabeled compounds in the liver following nPB exposure
when rats are pretreated with 1-aminobenzotriazole (1-ABT), a chemical
that blocks CYP450 enzymes and prevents them from metabolizing toxicants
within the cells.  The second set of data comprises the different series
of metabolites that are found in rat and mouse urine following nPB
exposure (explained in more detail below).  Although there appear to be
species-specific differences in primary pathways for metabolism in mice
and rats, additional experiments in male and female mice and rats
indicated that both sexes of each species can metabolize an inhaled dose
of nPB at 800 ppm, with metabolism saturating only at concentrations
≥800 ppm.  It is not possible to extrapolate to the human experience
from these data except to note that cytochrome oxidation may be the
principal pathway in nPB metabolism, and that like rodents, human
metabolic pathways are likely to be saturable at high concentrations.

Metabolism of nPB in Rats and Mice

In order to determine which enzyme systems were primarily responsible
for metabolizing nPB, RTI exposed male rats to iv nPB after exposing the
rats to an oral dose of a glutathione inhibitor (buthionine sulfoximine,
BSO) or a cytochrome P450 inhibitor (1-aminobenzotriazole, 1-ABT).  When
compared to naïve rats (i.e., rats that were not pre-exposed to BSO or
1-ABT) treated only with nPB, 1-ABT exposure decreased the amount of
radioactive label found in CO2 by ~80%, and decreased the amount of
radioactive label in urine by ~40%, while BSO only decreased the amount
of label in CO2 and urine by ~10 and 4%, respectively.  These data
suggested that CYP450 enzymes, and not glutathione, were primarily
responsible for the metabolism of nPB in rats, because the CYP450
inhibitor was associated with a much greater decrease in metabolized
nPB.  Further, tissue:blood ratios of nPB decreased from a control value
of 3.12 in male rats treated only with nPB to 2.64 in BSO-pretreated
rats, and a low of 1.00 in 1-ABT-pretreated rats.  A lower tissue to
blood ratio occurs where more of the nPB is cleared from the body and
less is absorbed into body tissue.  The results suggest that reactive
metabolites, which should be absorbed more by the liver, were formed
primarily by CYP450 rather than glutathione.

The researchers performed a series of HPLC analyses of thawed breath and
urine samples taken at different time points from the rats injected with
bolus doses of radiolabeled nPB at 5, 20, and 100 mg, rats pretreated
with either 1-ABT or BSO and rats exposed to nPB via inhalation at 800
ppm.  Parent nPB was not detected in any urine sample at any dose.
After a 20-mg/kg dose, radioactivity was associated with 8 major and 2
minor metabolites; 20% of the label co-eluted with a spike of
N-acetyl-S-propylcysteine.  At 100 mg/kg (4 hours post-dosing),
approximately 80-90% of the radiolabel is N-acetyl-S-propylcysteine,
although the other metabolite peaks evident at the lower dose are also
present.  The urinary profile of a rat at 8 hours following a 100-mg
dose resembles that of a 20-mg dose. The proportion of urinary
metabolites in the rat 6 hours following inhalation of 800 ppm nPB is
similar to that 8 hours following iv dosing with 100 mg/kg, indicating
the similarity of metabolism across exposure routes.  When male rats
were pretreated with 1-ABT, the majority of metabolites diminished,
except for N-acetyl-S-propylcysteine, which accounted for >90% of the
radioactivity.  With BSO pretreatment, the N-acetyl-S-propylcysteine
decreased slightly, but the other metabolites increased.  Taken
together, these data indicate that cytochrome oxidation of nPB is the
primary metabolic route in rats, accounting for perhaps as much as 70%
of the metabolism of the compound at lower doses (20 mg/kg) and that
when the dose is increased, metabolism via this pathway is saturated,
and glutathione conjugation becomes more important.

13C-NMR and mass spectrum analyses were performed on urine samples from
two male rats exposed to nPB via iv injection (two 100-mg/kg doses of
13C-nPB, labeled at the 1-carbon position, given 4 hours apart) and from
two rats exposed to 800 ppm [1,2,3-13C] nPB (labeled at all carbons) in
an inhalation chamber.  Additional inhalation metabolism experiments
were performed with wild-type mice and mice deficient in CYP 2E1 (4
males per group) also exposed to 800 ppm radiolabeled nPB.  Studies were
also done using liver homogenate from one male rat to try to elucidate
intermediate metabolites that were not detected in urine from exposed
rats.  The similarity of HPLC traces of urinary metabolites for rats
exposed via iv or inhalation indicated that qualitatively, the
metabolism of nPB is not route-dependent.  NMR spectra of urine from the
rats given nPB alone via iv injection revealed several 13C multiplets
(or peaks).  When 1-ABT was given to the rats administered nPB via iv,
the NMR spectrum was simplified to two compounds,
N-acetyl-S-propylcysteine and N-acetyl-S-propylcysteine-S-oxide
(determined by comparing to NMR spectra of synthetic standards of these
compounds).  This result indicated that cytochrome P450 inhibition
eliminates all metabolites of nPB save the ones listed above. The latter
compound was detected following 100 mg/kg injections and inhalation
exposures, but was minor at the low (20 mg/kg) iv dose.  Inspection of
NMR scans of mouse urine indicated that there were one major multiplet,
and two minor multiplets, that accounted for >90% of the 13C multiplets
present above the natural background.  Comparison of the spectra to rat
urinary metabolites confirmed the major metabolite to be
N-acetyl-S-(2-hydroxypropyl)cysteine, and the minor ones were
N-acetyl-S-propylcysteine and 1-bromo-2-propanol-O-glucuronide.
Evaluation of the NMR data from CYP 2E1 (-/-) mice indicated that fewer
2-hydroxylated metabolites were present in urine.  The data for
metabolites in rats and mice are presented in   REF _Ref130719776 \h  \*
MERGEFORMAT  Table 2  below, and those data showing differences in
wild-type and CYP 2E1 null mice are shown in   REF _Ref130719784 \h  \*
MERGEFORMAT  Table 3 .

Table   SEQ Table \* ARABIC  2 : Primary Metabolites of nPB in Rats and
Mice

Metabolitea	Acronym	Relative Abundanceb

Rat

(% of administered dose)	Mouse

N-acetyl-S-propylcysteine	APC	37%	Minor

N-acetyl-S-(2-hydroxypropyl)cysteine	AHPC	16%	Major

N-acetyl-S-propylcysteine S-oxide	APCO	5%	Secondary

1-bromo-2-propanol-O-glucuronide	BPG	9%	Minor

N-acetyl-S-(2-oxopropyl)cysteine	APS	12%	Secondary

N-acetyl-S-(2-oxopropyl)cysteine-S-oxide

Minor

	aThree additional trace metabolites were detected in rats, but not
identified by RTI (2005).

bAs measured in urine following 6 hour nPB inhalation at 800 ppm.

Source: RTI (2005), Stelljes (2005).

Table   SEQ Table \* ARABIC  3 . Recovery of Metabolites from Wild-Type
and CYP 2E1 (-/-) Mice Following Inhalation Exposure to 800 ppm [13C]
nPB

Metabolite	Wild-Type	CYP 2E1 (-/-)	% Change (Approximate)

	(mmol recovered)

	N-acetyl-S-(2-hydroxypropyl)cysteine	0.034	0.021	-38

1-bromo-2-propanol-O-glucuronide	0.005	0.002	-64

N-acetyl-S-propylcysteine	0.008	0.024	190

Ratio 2-hydroxylated:directly conjugated	4.77	0.97

	Source: RTI (2005), Table 6.3.

The data indicate that mice with no capacity for CYP 2E1 metabolism of
nPB have a ~60% decrease in the 1-bromo-2-propanol-O-glucuronide and a
190% increase in the directly conjugated metabolite of nPB,
N-acetyl-S-propylcysteine, when compared to wild-type mice.  Thus, it
appears that wild-type mice metabolize nPB primarily via a P450
mechanism that begins with hydroxylation at the 2-position carbon.

These analyses indicate that following inhalation in the rat, the
primary pathway of oxidation is the hydroxylation of nPB at the 2
position to form 1-bromo-2-propanol.  This compound was not detected in
urine following nPB exposure, but the data discussed above indicate that
a majority (>50%) of urinary compounds following low-level iv or
inhalation exposures are metabolized from this compound.  The
1-bromo-2-propanol is then either metabolized further or conjugated.
When higher doses are administered, the CYP 2E1 system becomes
saturated, cannot metabolize the nPB, and the glutathione-dependent
pathway becomes critical for elimination of the compound.  In mice, at
all administered doses, glutathione conjugation was a very minor
contributor to nPB metabolism; the major metabolite was the mercapturic
acid of the P450 oxidation product, 1-bromo-2-propanol.  Therefore, the
metabolism of nPB differs in mice compared to rats.

Sex Differences in Metabolism of Inhaled nPB

ant (λz), and elimination half-lives (t1/2).  The researchers
determined that in general, males were able to metabolize nPB more
rapidly than females as the estimated half-lives for nPB in female rats
were roughly twice those of the male rats (in mice, however, the speed
of metabolism was not consistently different between the sexes and was
only different at 70 and 2700 ppm).  However, both male and female rats
metabolized comparable amounts of nPB when measured 6.5 hours following
exposure.  The authors estimated Vmax values (a measure of the maximum
initial rate of an enzyme-catalysed reaction) for male and female rats
of 0.227 and 0.143, respectively. In mice, the Vmax values were 0.329
for male mice and 0.234 for female mice.  Taken together, these data do
suggest the possibility that there may be sex-related differences in
metabolism in nPB.  The small numbers of animals and the exposure
methodology used do not allow strong conclusions to be drawn regarding
whether sex-based differences are expected at lower concentrations
administered over a sub-chronic or chronic duration.  Further, the fact
that both male and female animals were able to metabolize comparable
amounts of nPB (up to 2700 ppm) indicates that sex-based differences may
not be observed when exposures are limited to the concentrations and
exposure durations more typical of occupational environments.

Dermal Uptake, Distribution and Metabolism of nPB in Rats

Six male rats were administered approximately 96 mg [14C]-nPB/kg
bodyweight dermally to a shaved portion of the back (scapular area)
using a device equipped with a charcoal filter that did not prevent the
nPB from evaporating.  The rats were exposed within a metabolism chamber
for at least 48 hours.  This device thus allowed the researchers to
simulate an environment similar to that of an occupational worker.  If
the experiment had been conducted as a typical dermal toxicity
investigation, the treated area would have been occluded with plastic or
some similar non-permeable material, and the compound would not have
been able to evaporate.  The charcoal filter was intended to trap nPB;
however, concentrations of the compound in the chamber were measured at
4 and 10 ppm, at 1 and 6 hours post-dosing, respectively, thus
indicating the potential for exposure via inhalation of the volatilized
nPB.

Radioactivity levels were measured in the following media at 48 hours:
urine, feces, air in the chamber, tissues at the dose site, carcass,
other tissues, and in the application devices, skin washes, and other
sinks.  Approximately 37% of the dose was obtained in volatiles derived
from the breathing of the rats, while 35.7% of the dose was located on
the application devices and skin washings.  A minimal 1.2% of the dose
was located in urine, and 1.7% was exhaled as [14C]-CO2.  Radioactivity
in tissues measured 0.28% of the administered dose, of which skin and
ears (0.103%) and liver (0.102%) had the highest percentages.  The study
authors measured free bromide in the plasma of the dermally-exposed rats
at 48 hours post-dosing and noted that the values were comparable to
those measured at 7 hours following iv exposure to 20 mg/kg nPB.  Using
this free bromide level, and the terminal rate constant for elimination,
the authors calculated that the free bromide concentrations reached in
plasma following dermal exposure were 27% of those following iv
exposure.  Therefore, they hypothesized that only 3-27% of the dermal
dose was absorbed relative to the iv dose and the impact of inhaling
volatilized nPB could not be quantified.

ICF Conclusions

Based on the data from the metabolism studies, it appears that CYP
enzymes may be responsible for the majority of metabolism of nPB in mice
and also in rats.  However, in rats, glutathione conjugation is an
important clearance pathway that is susceptible to depletion even at low
exposure doses (5 mg/kg).  This finding is in contrast to what previous
researchers concluded (Jones and Walsh, 1979).  Nevertheless, the
results indicate that both CYP and glutathione conjugation are necessary
pathways for clearance, and decreasing hepatic levels of one leads to a
shift toward the other enzyme for metabolism.

The data indicate that at very high concentrations (2700 ppm and
greater), females may be more susceptible to the adverse effects of nPB,
based on lower metabolism of the compound in female rats. But at lower
concentrations, females and males seem equally capable of clearing the
compound.

It would be useful to make conclusions regarding human metabolism of nPB
based on these studies.  One could speculate that women might not be
able to metabolize nPB as quickly as men; it is not unusual for there to
be sex-related differences in the amount of detoxification enzymes
(e.g., lesser amounts of alcohol dehydrogenase).  Case studies appear to
involve more women than men, but this is likely to be the result of more
women carrying out the work of spraying nPB-containing adhesives in
foam-cushion manufacturing facilities (Majersik et al., 2004).  These
case reports cannot be used to make broad generalizations about which
sex is more susceptible.  Data from the NTP (2003) 13-week inhalation
studies do not strongly support a finding of increased susceptibility in
female rodents.

posure period.  Therefore, it is impossible to extrapolate the results
following a one-time acute exposure at ≥ 240 ppm to potentially
chronic exposures.

It is reasonable to suspect that repeated dosing may result in the
depletion of cellular glutathione levels, based on reported findings in
the RTI studies, as well as the published literature on nPB.  It may
also result in saturation of an oxidative system (P450).  However,
despite the animal evidence, it is not possible to know how quickly
enzyme depletion would occur following repeat exposure, how extensive
the depletion would be, and how quickly an alternative pathway of
metabolism would be activated.  This study indicates that 80% decreases
in GSH enzyme were observed even at the lowest exposure concentrations.

The authors of the RTI report only speculate that rats may be more
susceptible to the toxicity of nPB than mice, based on the different
metabolic pathways.  They do not comment on what the results might mean
for human exposure to nPB.

References

Barnsley EA, Grenby TH, Young L.  1966.  Biochemical Studies of Toxic
Agents.  The Metabolism of 1- and 2-Bromopropane in Rats.  Biochem. J.
100: 282-288.

Ichihara G, Yu X, Kitoh J, Asaeda N, et al.  2000.  Reproductive
Toxicity of 1-Bromopropane, a Newly Introduced Alternative to Ozone
Layer Depleting Solvents, in Male Rats.  Toxicol Sci 54: 416-423.

Ishidao T, Kunugita N, Fueta Y, Arashidani K, Hori H.  2002.  Effects of
inhaled 1-bromopropane vapor on rat metabolism.  Toxicol Lett
134:237-243.

Jones AR, Walsh DA.  1979.  The oxidative metabolism of 1-bromopropane
in the rat.  Xenobiotica.  9:763-772.

Kim Y, Park J, Moon Y.  1999.   Hematopoietic and Reproductive
Toxicity of 2-Bromopropane, a Recently Introduced Substitute for
Chlorofluorocarbons.  Toxicol. Lett. 108:309-313.

Majersik JJ, Steffans JD, Caravati EM.  2004.  Chronic Exposure to
1-Bromopropane Associated with Spastic Paraparesis and Distal
Neuropathy: A Report of Six Foam Cushion Gluers. Salt Lake City, Utah.
A study presented October 5, 2004, at the 129th annual meeting of the
American Neurological Association in Toronto.

National Toxicology Program (NTP). 2003.  National Toxicology Program
Database Search Application.  Search criteria for 1-bromopropane.
Available at
<http://ntp-apps.niehs.nih.gov/ntp_tox/index.cfm?fuseaction=shorttermbio
assaydata.datasearch&study_no=C20011&cas_no=106-94-5&chemical_name=1-bro
mopropane&study_length=13%20Weeks&test_type=Short-Term>.

Pavelka S, Babicky A, Vobecky M.  2005.  Biological half-life of bromide
in the rat depends primarily on the magnitude of sodium intake.  Physiol
Res.  (Epub ahead of print).

#

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al Memorandum to EnviroTech International.  7 September.

Tachizawa H, MacDonald TL, Neal RA.  1982.  Rat liver microsomal
metabolism of propyl halides.  Mol Pharmacol 22:745-751.

  Cytochrome P450 (CYP450) isozymes are similar varieties of the CYP450
enzymes.  These enzymes play an important role in the metabolism of
compounds in many organs/tissues.

 Glutathione (g-glutamylcysteinylglycine, GSH) is a sulfhydryl (-SH)
water soluble antioxidant and antitoxin. It is found in animals, plants,
and microorganisms.  Glutathione conjugation is the process by which
enzymes called glutathione S-transferases bind glutathione to compounds
in the body to increase their water solubility so that they may be
excreted.

-  PAGE  8 -


Kawasaki Motors Corp., U. S. A.

° International Consortium on Fire Safety and EPA Workshop Fire and Burn Performance of Catalytic Converters on Outdoor Power Equipment October 5, 2005 Kawasaki Motors Corp., U. S. A.

° International Consortium on Fire Safety and EPA Workshop Fire and Burn Performance of Catalytic Converters on Outdoor Power Equipment October 5, 2005 ° CARB Tier III Compliance Plan   Class I and II engines Kawasaki Motors Corp., U. S. A.

° International Consortium on Fire Safety and EPA Workshop Fire and Burn Performance of Catalytic Converters on Outdoor Power Equipment October 5, 2005 ° CARB Tier III Compliance Plan   Class I and II engines ° Technology: Catalysts Kawasaki Motors Corp., U. S. A.

° International Consortium on Fire Safety and EPA Workshop Fire and Burn Performance of Catalytic Converters on Outdoor Power Equipment October 5, 2005 ° CARB Tier III Compliance Plan   Class I and II engines ° Technology: Catalysts ° Current findings: Moderate but manageable increase in exhaust gas and muffler surface temperatures Kawasaki Motors Corp., U. S. A.

° International Consortium on Fire Safety and EPA Workshop Fire and Burn Performance of Catalytic Converters on Outdoor Power Equipment October 5, 2005 ° CARB Tier III Compliance Plan   Class I and II engines ° Technology: Catalysts ° Current findings: Moderate but manageable increase in exhaust gas and muffler surface temperatures ° Conclusion   no increased risk to public safety


[Federal Register Volume 85, Number 148 (Friday, July 31, 2020)]
[Notices]
[Page 46091]
[FR Doc No: 2020-16581]

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

ENVIRONMENTAL PROTECTION AGENCY

[EPA HQ-OPPT-2020-0078; FRL-10012-06-OMS]

Information Collection Request Submitted to OMB for Review and
Approval; Comment Request; Toxic Chemical Release Reporting (Renewal)

AGENCY: Environmental Protection Agency (EPA).

ACTION: Notice.

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

SUMMARY: The Environmental Protection Agency (EPA) has submitted an
information collection request (ICR), Toxic Chemical Release Reporting
(EPA ICR Number 2613.02, OMB Control Number 2070-0212) to the Office of
Management and Budget (OMB) for review and approval in accordance with
the Paperwork Reduction Act. This is a proposed extension of the ICR,
which is currently approved through July 31, 2020. This notice allows
for an additional 30 days for public comments. A fuller description of
the ICR is given below, including its estimated burden and cost to the
public. 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.

DATES: Additional comments may be submitted on or before August 31,
2020.

ADDRESSES: Submit your comments to EPA, referencing Docket ID No. EPA-
HQ-OPPT-2020-0078, online using www.regulations.gov (our preferred
method), by email to<EMAIL_ADDRESS>or by mail to: EPA Docket
Center, Environmental Protection Agency, Mail Code 28221T, 1200
Pennsylvania Ave. NW, Washington, DC 20460. EPA's policy is that all
comments received will be included in the public docket without change
including any personal information provided, unless the comment
includes profanity, threats, information claimed to be Confidential
Business Information (CBI), or other information whose disclosure is
restricted by statute.
    Submit written comments and recommendations to OMB for the proposed
information collection within 30 days of publication of this notice to
www.reginfo.gov/public/do/PRAMain. Find this particular information
collection by selecting ``Currently under 30-day Review--Open for
Public Comments'' or by using the search function.

FOR FURTHER INFORMATION CONTACT: Cassandra Vail, Toxic Release
Inventory Division, Office of Pollution Prevention and Toxics,
Environmental Protection Agency, 1200 Pennsylvania Ave. NW, Washington,
DC 20460; telephone number:<PHONE_NUMBER>; email address:
<EMAIL_ADDRESS>
SUPPLEMENTARY INFORMATION: Supporting documents, which explain in
detail the information that the EPA will be collecting, are available
in the public docket for this ICR. The docket can be viewed online at
www.regulations.gov or in person at the EPA Docket Center, WJC West,
Room 3334, 1301 Constitution Ave. NW, Washington, DC. The telephone
number for the Docket Center is<PHONE_NUMBER>. For additional
information about EPA's public docket, visit http://www.epa.gov/dockets.
    Abstract: Pursuant to section 313 of the Emergency Planning and
Community Right-to-Know Act (EPCRA, 42 U.S.C. 11001 et seq.), certain
facilities that manufacture, process, or otherwise use specified toxic
chemicals in amounts above reporting threshold levels as provided in 40
CFR 372.25 must submit annually to EPA and to their designated state or
Indian country officials toxic chemical release forms containing
information specified by EPA; see 42 U.S.C. 11023. In addition,
pursuant to section 6607 of the Pollution Prevention Act (PPA, 42
U.S.C. 13101 et seq.), facilities reporting under section 313 of EPCRA
must also report pollution prevention and waste management data,
including recycling information, for such chemicals; see 42 U.S.C.
13106. EPA compiles and stores these reports in a publicly accessible
database known as the Toxics Release Inventory (TRI). Regulations at 40
CFR part 372, subpart B, require facilities that meet the above
criteria to report annually.
    This ICR consolidates the ICR for TRI Reporting currently approved
by OMB under OMB Control No. 2025-0009, with the currently approved
version of this ICR covering the TRI Reporting of additional chemicals.
Upon OMB approval of this ICR, EPA intends to discontinue OMB Control
No. 2025-0009.
    Form Numbers: EPA Form 9350-1, EPA Form 9350-2, and EPA Form 9350-
3.
    Respondents/Affected Entities: Regulations at 40 CFR part 372,
subpart B, require facilities that meet all the following criteria to
report:
    1. The facility has 10 or more full-time employee equivalents
(i.e., a total of 20,000 hours worked per year or greater; see 40 CFR
372.3); and
    2. The facility is included in a North American Industry
Classification System (NAICS) Code listed at 40 CFR 372.23 or under
Executive Order 13148, Federal facilities regardless of their industry
classification; and
    3. The facility manufactures (defined to include importing),
processes, or otherwise uses any EPCRA section 313 (TRI) chemical in
quantities greater than the established thresholds for the specific
chemical in the course of a calendar year.
    Respondent's obligation to respond: Mandatory (40 CFR 372).
    Estimated number respondents: 76,534.
    Frequency of response: Annual.
    Total estimated burden: 3,615,128 hours (per year). Burden is
defined at 5 CFR 1320.03(b).
    Total estimated cost: $200,205,764 (per year), includes $0
annualized capital or operation & maintenance costs.
    Changes in the Estimates: There is an increase of 3,597,275 hours.
This ICR submittal merges the existing ICR (2025-0009, approved by OMB
on October 15, 2018) into this ICR number (2070-0212), created to cover
the expanded list of toxic chemicals subject to reporting under the
NDAA for Fiscal Year 2020, to provide for a single control number. The
burden levels already approved under the collections being consolidated
in this ICR remain unchanged.

Courtney Kerwin,
Director, Regulatory Support Division.
[FR Doc. 2020-16581 Filed 7-30-20; 8:45 am]
BILLING CODE 6560-50-P