[Federal Register Volume 86, Number 215 (Wednesday, November 10, 2021)]
[Notices]
[Pages 62529-62530]
[FR Doc No: 2021-24555]

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

ENVIRONMENTAL PROTECTION AGENCY

[EPA-HQ-OLEM-2018-0105, FRL-9087-01-OLEM]

Proposed Information Collection Request; Comment Request;
Information Collection Request Submitted to OMB for Review and
Approval; Implementation of the Oil Pollution Act Facility Response
Plan Requirements (Renewal), EPA ICR No. 1630.13, OMB Control No. 2050-
0135

AGENCY: Environmental Protection Agency (EPA).

ACTION: Notice.

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

SUMMARY: The Environmental Protection Agency (EPA) is planning to
submit an information collection request (ICR), Oil Pollution Act
Facility Response Plans (Renewal) (EPA ICR No. 1630.13, OMB Control No.
2050-0135) to the Office of Management and Budget (OMB) for review and
approval in accordance with the Paperwork Reduction Act. Before doing
so, EPA is soliciting public comments on specific aspects of the
proposed information collection as described in Supplementary
Information. This is a proposed extension of the ICR, which is
currently approved through July 31, 2022. 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: Comments must be submitted on or before January 10, 2022.

ADDRESSES: Submit your comments, referencing Docket ID No. EPA-HQ-OLEM-
2018-0105, to: (1) EPA online using www.regulations.gov (our preferred
method) or by mail to: EPA Docket Center, Environmental Protection
Agency, Mail Code 28221T, 1200 Pennsylvania Ave. NW, Washington, DC
20460, and (2) OMB via email to [email protected]. Address
comments to OMB Desk Officer for EPA.
    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 Proprietary Business Information (PBI) or other
information whose disclosure is restricted by statute.

FOR FURTHER INFORMATION CONTACT: J. Troy Swackhammer, Office of
Emergency Management, Mail Code 5104A, Environmental Protection Agency,
1200 Pennsylvania Ave. NW, Washington, DC 20460; telephone number:
(202) 564-1966; email address: [email protected].

SUPPLEMENTARY INFORMATION: Supporting documents, which explain in
detail the information that EPA will be collecting, are available in
the public docket for this ICR. The docket can be viewed online at
www.regulations.gov. Out of an abundance of caution for members of the
public and our staff, the EPA Docket Center and Reading Room is closed
to the public, with limited exceptions, to reduce the risk of
transmitting COVID-19. Our Docket Center staff will continue to provide
remote customer service via email, phone and webform. For further
information about the EPA's public docket, Docket Center services and
the current status, please visit us online at https://www.epa.gov/dockets. The telephone number for the Docket Center is<PHONE_NUMBER>.
    Pursuant to section 3506(c)(2)(A) of the PRA, EPA is soliciting
comments and information to enable it to: (i) Evaluate whether the
proposed collection of information is necessary for the proper
performance of the functions of the Agency, including whether the
information will have practical utility; (ii) evaluate the accuracy of
the Agency's estimate of the burden of the proposed collection of
information, including the validity of the methodology and assumptions
used; (iii) enhance the quality, utility, and clarity of the
information to be collected; and (iv) minimize the burden of the
collection of information on those who are to respond, including
through the use of appropriate automated electronic, mechanical, or
other technological collection techniques or other forms of information
technology, e.g., permitting electronic submission of responses. EPA
will consider the comments received and amend the ICR as appropriate.
The final ICR package will then be submitted to OMB for review and
approval. At that time, EPA will issue another Federal Register notice
to announce the submission of the ICR to OMB and the opportunity to
submit additional comments to OMB.
    Abstract: The authority for EPA's facility response plan (FRP)
requirements is derived from section 311(j)(5) of the Clean Water Act,
as amended by the Oil Pollution Act of 1990. EPA's regulation is
codified at 40 CFR 112.20 and 112.21 and related appendices. The owner
or operator of a facility subject to 40 CFR 112.20 must prepare and
submit an FRP to EPA based on the following applicability criteria: (1)
The facility transfers oil over water to or from a vessel and has a
total

storage capacity of greater than or equal to 42,000 gallons; or (2) the
facility's total oil storage capacity is greater than or equal to one
million gallons and one or more of the following harm factors are met:
Insufficient secondary containment for aboveground storage tanks at the
facility; a discharge of oil could cause injury to fish and wildlife
and sensitive environments; a discharge of oil could shut down a
drinking water intake; the facility has experienced a reportable oil
discharge of 10,000 gallons or more in the last 5 years; or other
factors considered by the Regional Administrator (see 40 CFR
112.20(a)(2), (b)(1), (f)(1) and (f)(2) for further information).
    The purpose of an FRP is to help an owner or operator identify the
necessary resources to respond to an oil discharge in a timely manner.
If implemented effectively, the FRP will reduce the impact and severity
of oil discharges and may prevent discharges because of the
identification of risks at the facility. Although the owner or operator
is the primary data user, EPA also uses the data in certain situations
to ensure that facilities comply with the regulation and to help
allocate response resources. State and local governments may use the
data, which are not generally available elsewhere, and can greatly
assist local emergency preparedness planning efforts. The EPA reviews
all submitted FRPs and must approve FRPs for those facilities whose
discharges may cause significant and substantial harm to the
environment to ensure that facilities believed to pose the highest risk
have planned for adequate resources and procedures to respond to oil
discharges (See 40 CFR 112.20(f)(3) for further information about the
criteria for significant and substantial harm.). No information
collected under the FRP rule is expected to be confidential. One of the
criteria necessary for information to be classified as ``proprietary
business information'' (40 CFR 2.208) is that a business must show that
it has previously taken reasonable measures to protect the
confidentiality of the information and that it intends to continue to
take such measures. EPA provides no assurances of confidentiality to
facility owners or operators when they file their FRPs.
    The burden estimates, numbers and types of respondents, wage rates
and unit and total costs for this ICR renewal will be revised and
updated, if needed, during the 60-day comment period while the ICR
Supporting Statement is undergoing review at OMB.
    Form Numbers: None.
    Respondents/affected entities: Owners or operators of facilities
required to have Spill Prevention, Control, and Countermeasure (SPCC)
plans under the Oil Pollution Prevention regulation (40 CFR part 112)
and that, because of their location, could reasonably be expected to
cause substantial harm to the environment.
    Respondent's obligation to respond: Mandatory under section
311(j)(5) of the Clean Water Act, as amended by the Oil Pollution Act
of 1990.
    Estimated number of respondents: 16,027 (total).
    Frequency of response: Annual.
    Total estimated burden: 385,784 hours (per year). Burden is defined
at 5 CFR 1320.03(b).
    Total estimated cost: $17,728,836 (per year), includes $3,355
annualized capital or operation and maintenance costs.
    Changes in Estimates: Total estimated costs reflect U.S. Bureau of
Labor Statistics labor rates as of May 2020. This estimate is based on
EPA's current inventory of facilities that have submitted and are
maintaining an FRP. Any change in burden or cost resulting from the 60-
day OMB review period will be described and explained in this section
when the updated ICR Supporting Statement is completed.

    Dated: October 28, 2021.
Donna Salyer,
Director, Office of Emergency Management.
[FR Doc. 2021-24555 Filed 11-9-21; 8:45 am]
BILLING CODE 6560-50-P


[Federal Register Volume 81, Number 98 (Friday, May 20, 2016)]
[Rules and Regulations]
[Pages 31854-31855]
[FR Doc No: 2016-11817]

=======================================================================
-----------------------------------------------------------------------

DEPARTMENT OF LABOR

Occupational Safety and Health Administration

29 CFR Parts 1904 and 1902

[Docket No. OSHA-2013-0023]
RIN 1218-AC49

Improve Tracking of Workplace Injuries and Illnesses; Correction

AGENCY: Occupational Safety and Health Administration (OSHA), DOL.

ACTION: Final rule; correction.

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

SUMMARY: OSHA published in the Federal Register of May 12, 2016, a
final rule revising its Recording and Reporting Occupational Injuries
and Illnesses Regulation. In the rule, a paragraph was inadvertently
removed. This document reinserts that paragraph.

DATES: Effective: August 10, 2016.

FOR FURTHER INFORMATION CONTACT: For press inquiries: Frank Meilinger,
Office of Communications, Room N-3647, OSHA, U.S. Department of Labor,
200 Constitution Avenue NW., Washington, DC 20210; telephone (202) 693-
1999; email<EMAIL_ADDRESS>    For general and technical information: Miriam Schoenbaum, Office of
Statistical Analysis, Room N-3507, OSHA, U.S. Department of Labor, 200
Constitution Avenue NW., Washington, DC 20210; telephone<PHONE_NUMBER>;
email<EMAIL_ADDRESS>
SUPPLEMENTARY INFORMATION: OSHA published in the Federal Register of
May 12, 2016, a final rule revising its Recording and Reporting
Occupational Injuries and Illnesses regulation (92 FR 29624).
    This document was prepared under the direction of David Michaels,
Ph.D., MPH, Assistant Secretary of Labor for Occupational Safety and
Health. It is issued under Sections 8 and 24 of the Occupational Safety
and Health Act (29 U.S.C. 657, 673), Section 553 of the Administrative
Procedure Act (5 U.S.C. 553), and Secretary of Labor's Order No. 41-
2012 (77 FR 3912 (Jan. 25, 2012)).

Need for Correction

    Inadvertently Sec.  1904.35(b)(2) was designated as reserved. This
document reinserts that paragraph.
    In FR Rule Doc. No. 2016-10443 beginning on page 29624 in the issue
of May 12, 2016, make the following correction:
    On page 29692, in the first column, after the second paragraph,
remove ``(2) [Reserved].'' and add the following in its place:
    ``(2) Do I have to give my employees and their representatives
access to the OSHA injury and illness records? Yes, your employees,
former employees, their personal representatives, and their authorized
employee representatives have the right to access the OSHA injury and
illness records, with some limitations, as discussed below.
    (i) Who is an authorized employee representative? An authorized
employee representative is an authorized collective bargaining agent of
employees.
    (ii) Who is a ``personal representative'' of an employee or former
employee? A personal representative is:
    (A) Any person that the employee or former employee designates as
such, in writing; or
    (B) The legal representative of a deceased or legally incapacitated
employee or former employee.
    (iii) If an employee or representative asks for access to the OSHA
300 Log, when do I have to provide it? When an employee, former
employee, personal representative, or authorized employee
representative asks for copies of your current or stored OSHA 300
Log(s) for an establishment the employee or former employee has worked
in, you must give the requester a copy of the relevant OSHA 300 Log(s)
by the end of the next business day.
    (iv) May I remove the names of the employees or any other
information from the OSHA 300 Log before I give copies to an employee,
former employee, or employee representative? No, you must leave the
names on the 300 Log. However, to protect the privacy of injured and
ill employees, you may not record the employee's name on the OSHA 300
Log for certain ``privacy concern cases,'' as specified in Sec.
1904.29(b)(6) through (9).
    (v) If an employee or representative asks for access to the OSHA
301 Incident Report, when do I have to provide it? (A) When an
employee, former employee, or personal representative asks for a copy
of the OSHA 301 Incident Report describing an injury or illness to that
employee or former employee, you must give the requester a copy of the
OSHA 301 Incident Report containing that information by the end of the
next business day.
    (B) When an authorized employee representative asks for copies of
the OSHA 301 Incident Reports for an establishment where the agent
represents employees under a collective bargaining agreement, you must
give copies of those forms to the authorized employee representative
within 7 calendar days. You are only required to give the authorized
employee

representative information from the OSHA 301 Incident Report section
titled ``Tell us about the case.'' You must remove all other
information from the copy of the OSHA 301 Incident Report or the
equivalent substitute form that you give to the authorized employee
representative.
    (vi) May I charge for the copies? No, you may not charge for these
copies the first time they are provided. However, if one of the
designated persons asks for additional copies, you may assess a
reasonable charge for retrieving and copying the records.''

    Signed at Washington, DC, on May 13, 2016.
David Michaels,
Assistant Secretary of Labor for Occupational Safety and Health.
[FR Doc. 2016-11817 Filed 5-19-16; 8:45 am]
 BILLING CODE 4510-26-P


[Federal Register Volume 74, Number 115 (Wednesday, June 17, 2009)]
[Notices]
[Pages 28684-28686]
[FR Doc No: E9-14207]

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

DEPARTMENT OF ENERGY

Federal Energy Regulatory Commission

Combined Notice of Filings 1

June 09, 2009.
    Take notice that the Commission received the following exempt
wholesale generator filings:

    Docket Numbers: EG09-49-000.
    Applicants: Blackstone Wind Farm, LLC.
    Description: Notice of Self-Certification of Exempt Wholesale
Generator Status of Blackstone Wind Farm, LLC.
    Filed Date: 06/08/2009.
    Accession Number: 20090608-5043.
    Comment Date: 5 p.m. Eastern Time on Monday, June 29, 2009.

    Take notice that the Commission received the following electric
rate filings:

    Docket Numbers: ER98-1643-013.
    Applicants: Portland General Electric Company.

    Description: Notice on Non-Material Change in Status of Portland
General Electric Company.
    Filed Date: 06/08/2009.
    Accession Number: 20090608-5091.
    Comment Date: 5 p.m. Eastern Time on Monday, June 29, 2009.

    Docket Numbers: ER01-596-008; ER01-560-014; ER01-2690-012; ER02-
963-012; ER02-2509-009; ER02-1942-011; ER01-559-014; ER01-557-014;
ER01-2641-014; ER00-1780-010; ER00-840-011; ER01-137-009; ER02-77-012;
ER05-524-007; ER94-389-032; ER98-1767-017; ER99-2992-010; ER99-3165-
011.
    Applicants: Alabama Electric Marketing, LLC, Big Sandy Peaker
Plant, LLC, California Electric Marketing, LLC, Crete Energy Venture,
LLC, High Desert Power Project, LLC, Kiowa Power Partners, LLC, Lincoln
Generating Facility, LLC, New Mexico Electric Marketing, LLC, Tenaska
Alabama Partners, L.P., Tenaska Alabama II Partners, L.P., Tenaska
Frontier Partners, Ltd., Tenaska Gateway Partners, Ltd., Tenaska
Georgia Partners, L.P., Tenaska Power Services Co., Tenaska Virginia
Partners, L.P., Texas Electric Marketing, LLC, University Park Energy,
LLC, Wolf Hills Energy, LLC.
    Description: Alabama Electric Marketing, LLC et al. submits revised
tariff sheets removing references to Replacement Reserves, Non-Spinning
Reserves, and Automatic Generation Control from the third party
provider provisions.
    Filed Date: 06/05/2009.
    Accession Number: 20090609-0027.
    Comment Date: 5 p.m. Eastern Time on Friday, June 26, 2009.

    Docket Numbers: ER01-1527-013; ER01-1529-013.
    Applicants: Sierra Pacific Power Company; Nevada Power Company.
    Description: Nevada Power Company and Sierra Pacific Power Company,
Non-Material Change In Status Filing for Nevada Power Company and
Sierra Pacific Power Company.
    Filed Date: 06/08/2009.
    Accession Number: 20090608-5023.
    Comment Date: 5 p.m. Eastern Time on Monday, June 29, 2009.

    Docket Numbers: ER08-1404-001.
    Applicants: Midwest Independent Transmission System Operator, Inc.
    Description: Midwest Independent Transmission System Operator, Inc
submits termination of the Independent Market Monitor-Balancing
Authority Agreement, Rate Schedule 7, etc.
    Filed Date: 06/05/2009.
    Accession Number: 20090605-0306.
    Comment Date: 5 p.m. Eastern Time on Friday, June 26, 2009.

    Docket Numbers: ER09-823-000.
    Applicants: MidAmerican Energy Company.
    Description: MidAmerican Energy Company submits Answer filed 6/3/09
to the Deficiency Letter issued on 5/4/09.
    Filed Date: 06/04/2009.
    Accession Number: 20090608-0101.
    Comment Date: 5 p.m. Eastern Time on Thursday, June 25, 2009.

    Docket Numbers: ER09-988-001; ER09-989-001; ER09-990-001.
    Applicants: NextEra Energy Duane Arnold, LLC.
    Description: NextEra Energy Duane Arnold, LLC et al. submits an
amendment to the market based rate tariff.
    Filed Date: 06/05/2009.
    Accession Number: 20090609-0031.
    Comment Date: 5 p.m. Eastern Time on Friday, June 26, 2009.

    Docket Numbers: ER09-1206-000.
    Applicants: PacifiCorp.
    Description: PacifiCorp submits Transmission Interconnection
Agreement for Points of Delivery dated 5/12/09 between Price City and
PacifiCorp, to be designated as PacifiCorp Rate Schedule FERC 642.
    Filed Date: 05/26/2009.
    Accession Number: 20090528-0151.
    Comment Date: 5 p.m. Eastern Time on Tuesday, June 16, 2009.

    Docket Numbers: ER09-1247-001.
    Applicants: California Independent System Operator Corp.
    Description: California Independent System Operator Corp submits a
corrected version of its 6/1/09 filing of proposed amendments re
implement acceleration of the payment timeline.
    Filed Date: 06/04/2009.
    Accession Number: 20090605-0287.
    Comment Date: 5 p.m. Eastern Time on Thursday, June 25, 2009.

    Docket Numbers: ER09-1265-001.
    Applicants: PacifiCorp.
    Description: PacifiCorp submits corrected First Revised Sheet 1 et
al. to Original Rate Schedule FERC 615.
    Filed Date: 06/08/2009.
    Accession Number: 20090609-0085.
    Comment Date: 5 p.m. Eastern Time on Monday, June 29, 2009.

    Docket Numbers: ER09-1277-000.
    Applicants: PJM Interconnection LLC.
    Description: PJM Interconnection, LLC submits an executed
interconnection service agreement with NAEA Ocean Peaking Power, LLC et
al.
    Filed Date: 06/04/2009.
    Accession Number: 20090605-0286.
    Comment Date: 5 p.m. Eastern Time on Thursday, June 25, 2009.

    Docket Numbers: ER09-1279-000.
    Applicants: American Electric Power Service Corporation.
    Description: American Electric Power Service Corporation submits
Original Sheet 1 et al. to its First Revised Rate Schedule FERC No 34.
    Filed Date: 06/05/2009.
    Accession Number: 20090605-0305.
    Comment Date: 5 p.m. Eastern Time on Friday, June 26, 2009.

    Docket Numbers: ER09-1281-000.
    Applicants: California Independent System Operator Corporation.
    Description: California Independent System Operator Corp submits an
amendment to its tariff re designation of references bus in day-ahead
price calculations.
    Filed Date: 06/05/2009.
    Accession Number: 20090609-0028.
    Comment Date: 5 p.m. Eastern Time on Friday, June 26, 2009.

    Docket Numbers: ER09-1282-000.
    Applicants: ISO New England Inc.
    Description: ISO New England Inc., Informational Filing of the
Internal Market Monitoring Unit's Report Analyzing the Operations and
Effectiveness of the Forward Capacity Market.
    Filed Date: 06/05/2009.
    Accession Number: 20090605-5160.
    Comment Date: 5 p.m. Eastern Time on Friday, June 26, 2009.

    Take notice that the Commission received the following open access
transmission tariff filings:

    Docket Numbers: OA09-22-001.
    Applicants: Florida Power & Light Company.
    Description: Penalty Distribution Compliance Filing of Florida
Power & Light Company.
    Filed Date: 06/05/2009.
    Accession Number: 20090605-5105.
    Comment Date: 5 p.m. Eastern Time on Friday, June 26, 2009.

    Any person desiring to intervene or to protest in any of the above
proceedings must file in accordance with Rules 211 and 214 of the
Commission's Rules of Practice and Procedure (18 CFR 385.211 and
385.214) on or before 5 p.m. Eastern time on the specified Comment
Date. It is not necessary to separately intervene again in a subdocket
related to a compliance filing if you have previously intervened in the
same docket. Protests will be considered by the Commission in
determining the appropriate action to be taken, but will not serve to
make protestants parties to the proceeding. Anyone filing a motion to
intervene or protest must serve a copy of that document on the
Applicant. In reference to filings initiating a new proceeding,
interventions or protests submitted on or before the comment deadline
need

not be served on persons other than the Applicant.
    The Commission encourages electronic submission of protests and
interventions in lieu of paper, using the FERC Online links at http://www.ferc.gov. To facilitate electronic service, persons with Internet
access who will eFile a document and/or be listed as a contact for an
intervenor must create and validate an eRegistration account using the
eRegistration link. Select the eFiling link to log on and submit the
intervention or protests.
    Persons unable to file electronically should submit an original and
14 copies of the intervention or protest to the Federal Energy
Regulatory Commission, 888 First St. NE., Washington, DC 20426.
    The filings in the above proceedings are accessible in the
Commission's eLibrary system by clicking on the appropriate link in the
above list. They are also available for review in the Commission's
Public Reference Room in Washington, DC. There is an eSubscription link
on the Web site that enables subscribers to receive e-mail notification
when a document is added to a subscribed dockets(s). For assistance
with any FERC Online service, please e-mail<EMAIL_ADDRESS>or call<PHONE_NUMBER> (toll free). For TTY, call<PHONE_NUMBER>.

Nathaniel J. Davis, Sr.,
Deputy Secretary.
[FR Doc. E9-14207 Filed 6-16-09; 8:45 am]
BILLING CODE 6717-01-P


[Federal Register Volume 87, Number 93 (Friday, May 13, 2022)]
[Notices]
[Pages 29420-29421]
[FR Doc No: 2022-10258]

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

SECURITIES AND EXCHANGE COMMISSION

[Release No. 34-94874; File No. SR-MIAX-2022-16]

Self-Regulatory Organizations; Miami International Securities
Exchange, LLC; Notice of Withdrawal of Proposed Rule Change To Amend
the MIAX Fee Schedule To Adopt a Tiered-Pricing Structure for
Additional Limited Service MIAX Express Interface Ports

May 9, 2022.
    On April 1, 2022, Miami International Securities Exchange, LLC
(``MIAX'' or

``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 amend the Exchange's Fee Schedule to adopt a
tiered-pricing structure for additional limited service express
interface ports.
---------------------------------------------------------------------------

    \1\ 15 U.S.C. 78s(b)(1).
    \2\ 17 CFR 240.19b-4.
    \3\ 15 U.S.C. 78s(b)(3)(A). A proposed rule change may take
effect upon filing with the Commission if it is designated by the
exchange as ``establishing or changing a due, fee, or other charge
imposed by the self-regulatory organization on any person, whether
or not the person is a member of the self-regulatory organization.''
15 U.S.C. 78s(b)(3)(A)(ii).
    \4\ 15 U.S.C. 78s(b)(3)(C).
    \5\ 15 U.S.C. 78s(b)(2)(B).
    \6\ See Securities Exchange Act Release No. 94720 (April 14,
2022), 87 FR 23586.
---------------------------------------------------------------------------

    The proposed rule change was immediately effective upon filing with
the Commission pursuant to Section 19(b)(3)(A) of the Act.\3\ On April
20, 2022, the proposed rule change was published for comment in the
Federal Register and, pursuant to Section 19(b)(3)(C) of the Act,\4\
the Commission: (1) Temporarily suspended the proposed rule change; and
(2) instituted proceedings under Section 19(b)(2)(B) of the Act \5\ to
determine whether to approve or disapprove the proposed rule change.\6\
On May 2, 2022, the Exchange withdrew the proposed rule change (SR-
MIAX-2022-16).

    For the Commission, by the Division of Trading and Markets,
pursuant to delegated authority.\7\
---------------------------------------------------------------------------

    \7\ 17 CFR 200.30-3(a)(12).
---------------------------------------------------------------------------

J. Matthew DeLesDernier,
Assistant Secretary.
[FR Doc. 2022-10258 Filed 5-12-22; 8:45 am]
BILLING CODE 8011-01-P


[Federal Register Volume 81, Number 48 (Friday, March 11, 2016)]
[Notices]
[Pages 12910-12912]
[FR Doc No: 2016-05478]

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

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2009-N-0221]

Agency Information Collection Activities; Proposed Collection;
Comment Request; Food Labeling; Notification Procedures for Statements
on Dietary Supplements

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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

SUMMARY: The Food and Drug Administration (FDA or we) 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 invites comments on the information collection
provisions of the regulation requiring the manufacturer, packer, or
distributor of a dietary supplement to notify us that it is marketing a
dietary supplement product that bears on its label or in its labeling a
statement provided for in the Federal Food, Drug, and Cosmetic Act (the
FD&C Act). The notice also invites comment on a new electronic form
that allows manufacturers, packers, and distributors of dietary
supplements to notify us via FDA's Unified Registration and Listing
System (FURLS).

DATES: Submit either electronic or written comments on the collection
of information by May 10, 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-2009-N-0221 for ``Agency Information Collection Activities;
Proposed Collection; Comment Request; Food Labeling; Notification
Procedures for Statements on Dietary Supplements.'' 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.

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, we are publishing notice of the proposed collection
of information set forth in this document.
    With respect to the following collection of information, we invite
comments on these topics: (1) Whether the proposed collection of
information is necessary for the proper performance of our functions,
including whether the information will have practical utility; (2) the
accuracy of our 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.

Food Labeling; Notification Procedures for Statements on Dietary
Supplements--21 CFR 101.93

OMB Control Number 0910-0331--Extension

    Section 403(r)(6) of the FD&C Act (21 U.S.C. 343(r)(6)) and its
implementing regulation, 21 CFR 101.93, require that we be notified by
the manufacturer, packer, or distributor of a dietary supplement that
it is marketing a dietary supplement product that bears on its label or
in its labeling a statement provided for in section 403(r)(6) of the
FD&C Act. These provisions require that we be notified, with a
submission about such statements, no later than 30 days after the first
marketing of the dietary supplement. Information that is required in
the submission includes: (1) The name and address of the manufacturer,
packer, or distributor of the dietary supplement product; (2) the text
of the statement that is being made; (3) the name of the dietary
ingredient or supplement that is the subject of the statement; (4) the
name of the dietary supplement (including the brand name); and (5) the
signature of a responsible individual or the person who can certify the
accuracy of the information presented, and who must certify that the
information contained in the notice is complete and accurate, and that
the notifying firm has substantiation that the statement is truthful
and not misleading.
    We have developed an electronic form (Form FDA 3955) that
interested persons will be able to use to electronically submit their
notifications to FDA via FURLS. Firms that prefer to submit a paper
notification in a format of their own choosing will still have the
option to do so, however. Form FDA 3955 prompts a respondent to include
certain elements in their structure/function claim notification (SFCN)
described in Sec.  101.93 in a standard format electronically and helps
the respondent organize their SFCN to include only the information
needed for our review of the claim. Note that the SFCN, whether
electronic or paper, is used for all claims made pursuant to section
403(r)(6) of the FD&C Act, including nutrient deficiency claims and
general well-being claims in addition to structure/function claims. The
electronic form, and any optional elements that would be prepared as
attachments to the form (e.g., label), can be submitted in electronic
format via FURLS. Submissions of SFCNs will continue to be allowed in
paper format. We use this information to evaluate whether statements
made for dietary ingredients or dietary supplements are permissible
under section 403(r)(6) of the FD&C Act. Draft screenshots of Form FDA
3955 and instructions are available for comment at http://www.fda.gov/Food/DietarySupplements/IndustryInfo/ucm485532.htm.
    Description of Respondents: Respondents to this collection of
information include manufacturers, packers, or distributors of dietary
supplements that bear section 403(r)(6) of the FD&C Act statements on
their labels or labeling.
    We estimate the burden of this collection of information as
follows:

                                 Table 1--Estimated Annual Reporting Burden \1\
----------------------------------------------------------------------------------------------------------------
                                                   Number of
        21 CFR section             Number of     responses per   Total annual    Average burden     Total hours
                                  respondents     respondent       responses      per response
----------------------------------------------------------------------------------------------------------------
101.93........................           2,200               1           2,200  0.75 (45                   1,650
                                                                                minutes).
----------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of
  information.

    We believe that there will be minimal burden on the industry to
generate information to meet the notification requirements of section
403(r)(6) of the FD&C Act by submitting information regarding section
403(r)(6) of the FD&C Act statements on labels or in labeling of
dietary supplements. We also believe that submission via FURLS will not
affect the burden estimates. We are requesting only information that is
immediately available to the manufacturer, packer, or distributor of
the dietary supplement that bears such a statement on its label or in
its labeling. We estimate that, each year, approximately 2,200 firms
will submit the information required by section 403(r)(6) of the FD&C
Act. This estimate is based on the average number of notification
submissions received by us in the preceding 3 years. We estimate that a
firm will require 0.75 hours to gather the information needed and
prepare a communication to us, for a total of 1,650 hours (2,200 x
0.75).

    Dated: March 7, 2016.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2016-05478 Filed 3-10-16; 8:45 am]
 BILLING CODE 4164-01-P


Purity: Not Reported NOEL: < 50 mg/ kg/ d LOEL: 50 mg/ kg/ d based on alterations of several enzymes indicative of liver and kidney damage Page 48 of 62 Table A 1 Toxicity Profile of Alkylbenzene Sulfonates Guideline No./ Study Type MRID No./ Reference Information/ Study Classification Dosing and Animal Information Results 870.3100 Oral Subchronic ( rodent) MRID No. 43498402 Oser et al. ( 1965) Toxicologic Studies with Branched and Linear Alkyl Benzene Sulfonates in the Rat. Toxicol. Appl. Pharmacol. 7: 819 825. ( HERA) Acceptable Guideline LAS and ABS were administered at dietary levels of 0, 50, or 250 mg/ kg/ day, adjusted for bw and fc, for 90 days FDRL Strain ( Wistar derived) Rat ( 15/ sex/ dose)

Purity: Not Reported NOEL: 50 mg/ kg/ d LEL: 250 mg/ kg/ d for increased absolute and relative liver weight in both sexes ( 21%) and increased relative cecal weight ( 21%) in males 870.3100 Oral Subchronic ( rodent) Watari et al. ( 1977) Ultrastructural Observations of the Protective Effect of Glycyrrhizin for Mouse Liver Injury Caused by Oral Administration of Detergent Ingredients ( LAS), J. Clin. Electron. Microscopy ( Nihon Rinsho Denshikenbikyo Kaishi) 10 ( 1 2): 121 139.

Open Literature Benzenesulfonic acid, C10 13 alkyl derivatives, sodium salt was administered in the drinking water for 6 months at 0 and 100 ppm with 2 months recovery ( M: 0 and 17 mg/ kg bw, F: 0 and 20 mg/ kg bw)

M/ F ddy Mouse Purity: Not Reported Liver effects were observed at the only dose tested ( 17 20 mg/ kg/ d), but they disappeared following the 2 month recovery period.

870.3100 Oral Subchronic ( rodent) Yoneyama & Hiraga ( 1977) Effect of Linear Alkylbenzene Sulfonate on Serum Lipid in Rats, J Ann Rep Tokyo Metrop Res Lab, Public Health 28( 2): 109 111. ( HERA)

Open Literature LAS was administered in the diet at concentrations of 180, 360, or 540 mg/ kg bw/ d for two and four weeks M Wistar Rat ( 5/ group)

Purity: 60% a. i. Body weight gain was suppressed in the group receiving 540 mg/ kg bw/ d at four weeks, and the relative liver weight was increased at two weeks and thereafter in the groups receiving 360 mg/ kg bw/ d and 540 mg/ kg bw/ d. The levels of triglyceride and total lipids in the serum had decreased markedly at two weeks in all the experimental groups, and the levels of phospholipids and cholesterol in the serum had decreased significantly at two weeks in the groups given 360 and 540 mg/ kg bw/ d. These changes were less apparent at four weeks, but triglyceride, phospholipid, and cholesterol levels in serum were significantly decreased in the group given 540 mg/ kg bw. Significant increases in triglyceride levels were seen in the liver after two weeks in the groups receiving 180 and 540 mg/ kg bw/ d, and in cholesterol levels in the group given 180 mg/ kg bw.

870.3100 Oral Subchronic ( rodent) Yoneyama et al. ( 1978) Effects of LAS on Incorporation of Acetate 1 14C in Liver Lipids in Rats. J Ann Rep Tokyo Metrop Res Lab Public Health, 29 ( 2): 55 57.

Open Literature LAS was administered at a concentration of 200 mg/ kg bw/ d in the diet or in drinking water ( 560 mg/ kg bw/ d) for two weeks to determine the effect on the synthesis of lipids in the liver M Wistar Rat ( 5/ group)

Purity: Not Reported Uptake of acetate 1 14C by lipids in the liver was increased in both groups; uptake of phospholipids and triglycerides tended to increase, and that of phospholipids increased significantly in rats given LAS in the diet.

870.3100 Oral Subchronic ( rodent) MRID No. 43498413 Heywood et al. ( 1978) Toxicology Studies of Linear Alkyl Sulphonate LAS was given to four groups of three males and three females at doses of 30, 150, 300 mg/ kg bw/ day At 300 ( po) and 1.0 ( sc) mg/ kg bw/ day, the monkeys vomited frequently and usually within 3 hours of administration. An increased frequency of loose or liquid faeces was recorded for animals receiving 150 Page 49 of 62 Table A 1 Toxicity Profile of Alkylbenzene Sulfonates Guideline No./ Study Type MRID No./ Reference Information/ Study Classification Dosing and Animal Information Results ( LAS) in Rhesus Monkeys I. Simultaneous Oral and Subcutaneous Administration for 28 Days. Toxicol. Appl. Pharmacol. 11: 245 250. ( HERA)

Acceptable Guideline per gavage ( po) and simultaneously with 0.1, 0.5, or 1.0 mg/ kg bw/ day subcutaneously ( sc). Control groups were used.

Rhesus Monkey ( 3/ sex/ dose), 18 36 months old Purity: Not Reported ( po) and 0.5 ( sc) mg/ kg bw/ day. These effects are probably related to the inherent irritative effects of LAS rather than to its systemic toxicity. Fibrosis of the injection sites was found among the entire test group, the incidence and severity being dose related. Ophthalmoscopy, laboratory examination of blood and urine, organ weight analysis and histopathological investigation did not detect any further treatment related responses.

The LOAEL is 150 mg/ kg bw/ day ( po) + 0.5 mg/ kg bw/ day ( sc) based on an increase in liquid feces and the NOAEL is 30 mg/ kg/ d 870.3200 21 Day Dermal Mathur et al. ( 1992) Effect of Dermal Exposure to LAS Detergent and HCH Pesticide in Guinea Pigs: Biochemical and Histopathologic Changes in Liver and Kidney. J Toxicol Cutan Ocular Toxicol, 11( 1): 3 13. ( WHO 1996)

Open Literature A solution of LAS in distilled water equivalent to 60 mg/ kg bw was applied to a 4 cm2 area of clipped dorsal skin daily for 30 days 12 Guinea Pigs Purity: Not Reported The activities of B glucuronidase, gamma glutamyl transpeptidase, 5 nucleotidase, and sorbitol dehydrogenase were increased in liver and kidney. Lipid peroxidation was increased in the kidney but not in liver, and the glutathione content was unchanged in both organs. Extensive fatty changes were found in hepatic lobules, with dilation of sinusoids; tubular lesions were found in the kidney, predominantly in the proximal and distal portions.

870.3200 21 Day Dermal Tox Record No. 003441 Subchronic ( 28 day) Percutaneous Toxicity ( Rabbit) of Compound: B0002.01, ( Bio/ dynamics Inc., Project No. 4717 77, March 17, 1978, submitted by Procter and Gambel Company, May 10, 1978).

Unacceptable Core Minimum Data SDDBS ( end use product Comet Cleanser) was applied to the skin of rabbits for 28 days at 200 mg/ kg/ d. The hair of each rabbit was clipped from its trunk, so as to expose approximately 25% of the total body surface area and the skin was abraded daily just prior to treatment.

20 M/ F Albino New Zealand White Rabbits ( 5/ sex/ group)

Purity: 10% NOEL: > 200 mg/ kg/ d 870.3465 90 Day Inhalation MRID No. 43498403 Coate et al. ( 1978) Respiratory Toxicity of Enzyme Detergent Dust. Toxicol. Appl. Pharmacol., 45: 477 496.

Acceptable Guideline SDDBS was administered a SDDBS mixture at levels of 0, 100( detergent), and [ .001, .01, 0.1 and 1 ( enzyme)] together with [+ 0, 1, 10, and 100 ( detergent)] mg/ m3 for 6 hours daily, 5 days a week, for 6 months 12 groups of 5 M/ 4 F Cynomolgus Monkeys Purity: 13% NOEL: 1 mg/ m3 detergent dust combined with up to 0.1 mg/ m3 enzyme dust.

The detergent dust alone at 100 mg/ m3 caused gross signs of respiratory distress, pulmonary histopathological effects, and pulmonary function impairment indicative of constricted bronchioles. Exposure to 10 or 100 mg/ m3 together with 0.01 and 0.1 mg/ m3 enzyme dust produced the same effects along with weight loss and decreased weight gain.

Developmental Toxicity Page 50 of 62 Table A 1 Toxicity Profile of Alkylbenzene Sulfonates Guideline No./ Study Type MRID No./ Reference Information/ Study Classification Dosing and Animal Information Results 870.3700a Developmental Toxicity ( rodent) Daly et al. ( 1980) A Teratology Study of Topically Applied LAS in Rats, Fd. Cosmet. Toxicol. 18: 55 58. ( HERA)

Open Literature LAS was applied to the skin on days 0 through 21 of gestation at doses of 20, 100, and 400 mg/ kg bw/ d Rat Purity: Not Reported NOAEL ( maternal): 20 mg/ kg bw/ d NOAEL ( fetuses): 400 mg/ kg bw/ d Maternal toxicity: the dams treated with 400 mg/ kg bw/ day and 100 mg/ kg bw/ day showed inhibition of body weight gain and llocal skin effects that compromised the integrity of the skin and caused overt toxicity, like inhibition of the body weight gain. Teratogenicity: there were no findings indicative of effects of LAS on the foetal parameters evaluated. There were no indications of teratogenic or embryotoxic effects.

870.3700a Developmental Toxicity ( rodent) Endo et al. ( 1980) Studies of the Chronic Toxicity and Teratogenicity of Synthetic Surfactants, Ann. Rep. Tokyo Metrop. Res. Inst. Environ. Prot. ( Tokyo Kogai Kenkyujo Nempo), 236 246. ( HERA)

Open Literature LAS was administered in the drinking water at 0.1%, corresponding to 383 mg/ kg bw/ d for rats and up to 3030 mg/ kg bw/ d for rabits from day 6 to 15 ( rats) and day 6 to 18 ( rabbits) of pregnancy.

F Rat and Rabbit Purity: Not Reported NOAEL ( maternal): 383 mg/ kg bw/ d ( rat) LOAEL ( maternal): 3030 mg/ kg bw/ d ( rabbit) NOAEL ( fetuses): 383 mg/ kg bw/ d ( rat) LOAEL ( fetuses): 3030 mg/ kg bw/ d ( rabbit)

The effect on the dams was a slight inhibition of body weight gain in the rabbits. The litter parameters of both species did not show any significant differences from those of the controls. Delayed ossification was observed in rabbits, but there was no increase in malformations in either the rabbits or the rats. 870.3700a Developmental Toxicity ( rodent) Imahori et al. ( 1976) Effects of LAS Applied Dermally to Pregnant Mice on the Pregnant Mice and their Fetuses, J. Jpn. J. Public Health ( Nihon Koshueisei Zasshi) 23( 2): 68 72. ( HERA)

Open Literature LAS was applied daily at dermal doses of 15, 150, and 1500 mg/ kg bw/ d on days 6 through day 15 of pregnancy F Mouse Purity: Not Reported NOAEL ( maternal): 150 mg/ kg bw/ d NOAEL ( fetuses): 1500 mg/ kg bw/ d The 1500 mg/ kg bw/ day group showed a clear decrease in the pregnancy rate ( 67.9%) when compared with a rate of 96.3% in the controls. However, there were no decreases in the litter size, and no changes in the litter parameters with the exception of a slight decrease in foetal body weight. There were no significant increases in the incidence of malformations in the foetuses.

870.3700a Developmental Toxicity ( rodent) MRID No. 43498423 Masuda et al. ( 1974) Effects of LAS Applied Dermally to Pregnant Mice on the Development of their Fetuses. 15: 349 355.

Acceptable Guideline LAS was applied dermally at a level of 0.5 ml. The ICR JCL strain received doses of 0, 0.85, 1.7, 2.55, and 3.4% solutions daily from days 1 to 13 of gestation and the ddY strain received doses of 0, 0.017, 0.17, and 1.7% solutions daily from days 2 to 14 of gestation.

Mouse ( ICR JCL strain and ddY strain)

Purity: Not Reported NOEL ( maternal and developmental toxicity  ddY): 1.7% ( HDT) NOEL ( maternal toxicity  ICR JCL): 2.55% NOEL ( developmental toxicity  ICR JCL): 1.7%

At 3.4% LAS, maternal body weight and the absolute weight of liver, kidney, spleen were significantly increased over control.. Pregnancy rates were significantly less ( 33.35) compared to controls ( 69%). The number of implantations, live fetuses, sex ratio, dead or resorbed fetuses, placenta weight and external malformations were comparable with control. Fetal body weights of 2.55% and 3.4% LAS treated groups were significantly less than controls.

870.3700a Developmental MRID 43498424 and 43498425 LAS ( 0.1 ml ) was applied at a concentration of 20% Development was retarded and cleavage of eggs was interrupted. Significantly higher numbers of embryos Page 51 of 62 Table A 1 Toxicity Profile of Alkylbenzene Sulfonates Guideline No./ Study Type MRID No./ Reference Information/ Study Classification Dosing and Animal Information Results Toxicity ( rodent) Nomura, T et al. ( 1980) The Synthetic Surfactants AS and LAS Interrupt Pregnancy in Mice. Life Sciences, 26: 49 54. ( HERA)

Nomura, T. et al. ( 1987) Killing of Preimplantation Mouse Embryos by AS and LAS. Mutation Research 190: 25 29. ( HERA)

Acceptable Guideline to the dorsal skin of pregnant mice during the pre implantation period twice a day from day 0 to day 3 of pregnancy Female ICR/ Jcl Mouse,

9 10 weeks old Purity: 20% were found to be deformed in the LAS group in comparison to controls, and most of these embryos were in the morula stage, whereas they were mostly in the last blastocyst stage in controls.

Some dead, deformed, and growth retarded embryos were observed in the treated group. Although the authors stated that these effects were not due to maternal toxicity since no maternal organs were affected, this statement is probably not correct in view of the high concentration of LAS and its irritation effects. A secondary effect due to maternal toxicity appears much more likely.

870.3700a Developmental Toxicity ( rodent) MRID 43498426 Palmer et al. ( 1975) Assessment of the Teratogenic Potential of Surfactants, ( Part I), Toxicology 3: 91 106.

Acceptable Guideline LAS was administered by gavage on days 6 15 of pregnancy in rats and mice and days 6 18 of pregnancy in rabbits at doses of 0.2, 2, 300, and 600 mg/ kg bw/ d 20 CD Rats, 20 CD 1 Mice, and 13 New Zealand White Rabbits Purity: 17% NOAEL ( rat  maternal): 300 mg/ kg bw/ d NOAEL ( mouse  maternal): 2.0 mg/ kg bw/ d ( However, there is a large difference between this dose and the next highest dose of 300 mg/ kg bw/ d, this study does not allow determination of a reliable maternal NOAEL for mice)

NOAEL ( rabbit  maternal): 2.0 mg/ kg b/ d ( However, the study does not allow determination of reliable NOAELs, given the large difference between the maternal no effects doses of 2 mg/ kg bw/ d and the maternal LOAEL dose ( 300 mg/ kg bw/ d) that is also the dose for which effects on litters could not be determined due to the high mortality rate in parent animals)

NOAEL ( rat  developmental): 300 mg/ kg bw/ d NOAEL ( mouse  developmental): 2.0 mg/ kg bw/ d NOAEL ( rabbit  developmental): 2.0 mg/ kg bw/ d NOAEL ( rat  fetal): 600 mg/ kg bw/ d NOAEL ( mouse  fetal): 300 mg/ kg bw/ d ( Due to a high mortality rate of parent animals, no assessment was possible at 600 mg/ kg bw/ d) NOAEL ( rabbit  fetal): could not be determined 870.3700a Developmental Toxicity ( rodent) MRID 43511403 Palmer, et al. ( 1975) Assessment of the Teratogenic Potential of Surfactants, ( Part III)  Dermal Application of LAS and Soap. Huntingdon Research Centre, Huntingdon, Great Britain. Study No. DDBSA JV RP4 029. Toxicology 4: 171 181.

Acceptable Guideline LAS was administered percutaneously to shaved skin at solutions of 0.03%, 0.3%, and 3% during pregnancy on days 2 13 in mice, 2 15 in rats, and 1 16 in rabbits. Dosages employed were 0.5 ml/ rat or mouse/ day and 10 ml/ rabbit/ day CD 1 Mice ( 20/ group), CD Rats ( 20/ group), N2W Rabbits ( 13/ group)

Purity: 0.03%, 0.3%, and 3% LOEL ( maternal toxicity, mice): 0.3% ( 50 mg/ kg/ d) LOEL ( maternal toxicity, rats): 3.0% ( 60 mg/ kg/ d) LOEL ( maternal toxicity, rabbits): 0.3% ( 9.0 mg/ kg/ d)

NOEL ( maternal toxicity, mice): 0.03% ( 5.0 mg/ kg/ d) NOEL ( maternal toxicity, rats): 0.3% ( 6.0 mg/ kg/ d) NOEL ( maternal toxicity, rabbits): 0.03% (( 0.9 mg/ kg/ d)

LOEL ( developmental toxicity): 0.3% ( 50 mg/ kg/ d) LOEL ( developmental toxicity): 3.0% ( 60 mg/ kg/ d) LOEL ( developmental toxicity): 3.0% ( 90 mg/ kg/ d)

NOEL ( developmental toxicity): 0.03% ( 5.0 mg/ kg/ d) NOEL ( developmental toxicity): 0.3% ( 6.0 mg/ kg/ d) NOEL ( developmental toxicity): 0.3% ( 9.0 mg/ kg/ d)

Marked local skin reaction, irritability, weight loss and failure to maintain or establish pregnancy was evident in mice treated with LAS 3% soap, 3 or 30%: marked local Page 52 of 62 Table A 1 Toxicity Profile of Alkylbenzene Sulfonates Guideline No./ Study Type MRID No./ Reference Information/ Study Classification Dosing and Animal Information Results reaction and weight loss also occurred in rabbits receiving LAS 3%. Moderate maternal toxicity was observed among mice treated with LAS, 0.3% and mild maternal toxicity in rats receiving LAS 3% or soap 30% and rabbits receiving LAS 0.3%. Effects on litter parameters were dose dependent, causing marked maternal toxicity in mice, the principal higher fetal loss, reduction in viable litter size. LAS at 3% showed marked maternal toxicity in the rabbit The moderate maternal toxicity of LAS, 0.3% in the mouse correlated with a higher incidence of embryonic deaths and lower litter size but only the former differed significantly from the corresponding control value.

870.3700a Developmental Toxicity ( rodent) Sato et al. ( 1972) Studies on the Toxicity of Synthetic Detergents: ( III), Examination of Teratogenic Effects of Alkylbenzene Sulfonates Spread on the Skin of Mice. Ann. Rep. Tokyo Metrop. Res. Lab. Public Health 24: 441 448. ( HERA)

Open Literature LAS was applied to the skin of female mice daily on days 0 through 13 of pregnancy with a single LAS dose of 110 mg/ kg bw/ d. Control group not specified.

F Mouse Purity: Not Reported NOAEL ( maternal): 110 mg/ kg bw/ d No abnormalities were seen in the dam or foetuses.

870.3700a Developmental Toxicity ( rodent) Shiobara S., Imahori A. ( 1976) Effects of LAS Orally Administered to Pregnant Mice on the Pregnant Mice and their Fetuses. J. Food Hyg. Soc. Jpn. ( Shokuhin Eiseigaku Zasshi) 17( 4): 295 301.

Open Literature LAS was administered by gavage at doses of 10, 100, and 300 mg/ kg bw/ d at day 6 through 15 of gestation ICR SLC Mouse ( 25 33/ dose)

Purity: Not Reported LOAEL ( maternal): 10 mg/ kg bw/ d NOAEL ( fetuses): 300 mg/ kg bw/ d 1. Marked maternal and embryonic toxicities, such as maternal death, premature delivery, total litter loss and high fetal death rate, were observed at 300 mg/ kg group.

2. Slight suppression of maternal body weight gain and slight body weight suppression of live fetuses were observed in each treated group.

3. External malformations such as cleft palate and exencephaly were observed sporadically both in the control and the treated groups. However, the incidence of these malformations was not significant, and considered to be within the spontaneous incidence of ICR mice.

870.3700a Developmental Toxicity ( rodent) Takahashi et al. ( 1975) Teratogenicity of Some Synthetic Detergent and LAS. Ann. Rep. Tokyo Metrop. Res. Lab. Public Health 26( 2): 67 78. ( HERA)

Open Literature LAS doses of 40, and 400 mg/ kg bw/ d were administered daily from day 0 to day 6 of pregnancy or from day 7 to 13 of pregnancy by gavage Mouse ( 13 14/ group)

Purity: not reported NOAEL ( maternal): 40 mg/ kg bw/ d NOAEL ( fetuses): 400 mg/ kg bw/ d At 400 mg/ kg bw/ day, the pregnancy rate was 46.2% compared to 92.9% in the controls. There was no increase in malformations. Although no information on maternal toxicity is available, it appears likely that maternal toxicity was present at the high dose group.

870.3700a Developmental Toxicity Tiba et al. ( 1976) Effects of LAS on Dam, Fetus, and Newborn Rat. J. Food Hyg. Soc. Jpn. LAS was administered in the diet at doses of 80 and 780 mg/ kg bw/ d from day 0 NOAEL ( maternal): 780 mg/ kg bw/ d NOAEL ( fetuses): 780 mg/ kg bw/ d At 780 mg/ kg bw/ day there were no abnormalities in the body weight gains of the dams, or in the occurrence and Page 53 of 62 Table A 1 Toxicity Profile of Alkylbenzene Sulfonates Guideline No./ Study Type MRID No./ Reference Information/ Study Classification Dosing and Animal Information Results ( rodent) ( Shokuhin Eiseigaku Zassh) 17( 1): 66 71. ( HERA)

Open Literature to 20 of gestation F Rat ( 16/ dose)

Purity: Not Reported maintenance of pregnancy. The values of the litter parameters did not differ from those of the controls and there was no evidence of teratogenicity. The number of offsprings was rather low in the highest dose group, and the weaning rate of 78.3% was lower than the 100% rate observed in the controls. However, there were no abnormalities in body weight gain, organ weights or functions in the offsprings. Reproduction Toxicity 870.3800 Reproduction MRID 43498416 Buehler, E., Newmann, E., and King, W. ( 1971) Two Year Feeding and Reproduction Study in Rats with Linear Alkylbenzene Sulfonate ( LAS). Tox. Appl. Pharm. 18: 83 91. ( HERA)

Acceptable Guideline LAS was administered in the diet at doses of 0, 0.02, 0.1, and 0.5% , equivalent to ( 0, 10, 50, 250 mg/ kg bw/ day) for 84 days.

Weanling Charles River CD Rat ( 20/ sex/ dose)

Purity: 98.1% NOAEL Parental: 250 mg/ kg bw/ day NOAEL Offspring: 50 mg/ kg/ d.

The LOAEL of 250 mg/ kg/ day in the offspring is due to slight ( non significant) changes in hematology and histopathology and slight decrease in day 21 body weights.

870.3800 Reproduction Endo et al. ( 1980) Studies of the Chronic Toxicity and Teratogenicity of Synthetic Surfactants, Ann. Rep. Tokyo Metrop. Res. Inst. Environ. Prot. ( Tokyo Kogai Kenkyujo Nempo), 236 246. ( HERA)

Open Literature LAS was administered at 70 mg/ kg bw/ day in the drinking water in a four generation rat study.

M/ F Wistar Rat Purity: Not Reported NOAEL: > 70 mg/ kg ( only dose tested)

No effects of LAS administration were observed 870.3800 Reproduction Palmer et al. ( 1974) Effect of CLD Reproductive Function of Multiple Generations in the Rat, Report LFO10/ 731029, Unpublished results. ( HERA)

Open Literature A commercial light duty liquid detergent of LAS ( 17%) and alkyl ethoxylate sulphate ( 7%) was continuously administered in the diet for three generations 60 days prior to mating at concentrations of 0, 40, 200, and 1000 mg/ kg bw/ d. The corresonding administration of LAS was of 0, 6.8, 34, and 170 mg/ kg bw/ d.

Rat Purity: 17% NOAEL: 170 mg/ kg bw/ d Among parental animals over the three generations there were no signs of adverse effects of treatment. Food consumption and bodyweight changes showed no consistent relationship to dosage. Necroscopy revealed no changes due to treatment. The mating performance, the pregnancy rate and the duration of gestation were unaffected. Among litter parameters, organ weight analysis, histopathology and skeletal staining of representative young from the F3b generation revealed no changes that could be conclusively related to treatment.

Chronic Toxicity 870.4100a Chronic Toxicity Taniguchi et al. ( 1978) Results of Studies on Synthetic Detergents. LAS were applied to the dorsal skin of rats three times per week at doses of Treatment had no effect on organ weights or histopathological appearance, and there was no evidence of toxicity or carcinogenicity. Page 54 of 62 Table A 1 Toxicity Profile of Alkylbenzene Sulfonates Guideline No./ Study Type MRID No./ Reference Information/ Study Classification Dosing and Animal Information Results ( rodent) Tokyo, Science and Technology Agency, Research and Coordination Bureau, pp. 18 54. ( WHO 1996)

Open Literature 1, 5, or 25 mg/ rat for 24 months. Each application was washed from the skin with warm water after 24 hours.

SLC Wistar Rats Purity: 19.7% a. i.

870.3100 Chronic Toxicity ( rodent) Yoneyama et al. ( 1976) Subacute Toxicity of LAS, Ann. Rep. Tokyo Metrop. Res. Lab. Public Health27( 2): 105 112, See: IPCS, 1996. ( HERA)

Open Literature LAS was administered in the diet at concentrations of 500 and 1000 mg/ kg bw/ d and in drinking water at concentrations of 100, 250, 600 mg/ kg bw/ d for males and 100, 250, 900 mg/ kg bw/ d for females for 9 months Mouse ( 8 or 9/ sex/ dose)

Purity: Not Reported LOAEL: 500 mg/ kg bw/ d ( in diet) NOAEL: 250 mg/ kg bw/ d ( in water)

LAS in diet: in the mice given 500 mg/ kg bw/ day, body weight gain was not suppressed, but the weight of the liver increased in male and female mice. Enzymatic examinations revealed significant decreases in LDH of the liver and in acid phosphatase of the kidneys in the male mice.

LAS in drinking water: body weight was depressed at the highest dose for male and females, increase in liver weight in females, significant decreases in renal Na, K ATPase.

870.3100 Chronic Toxicity ( rodent) Yoneyama et al. ( 1976) Subacute Toxicity of LAS, Ann. Rep. Tokyo Metrop. Res. Lab. Public Health27( 2): 105 112, See: IPCS, 1996. ( HERA)

Open Literature LAS was administered for 9 months in the drinking water at doses of 85, 145, 430 mg/ kg bw/ day M/ F Wistar Rat Purity: Not Reported NOAEL: 85 mg/ kg bw/ d LOAEL: 145 mg/ kg bw/ d Haematological examination revealed no significant changes in any experimental group and no organ weight changes were observed. Body weight gain was suppressed in the males of the highest dose group and also serum biochemical and enzymatic parameters of the liver and kidney were affected. A significant decrease in renal Na, K ATPase was seen in the group given 145 mg/ kg bw/ day of LAS.

870.4100a Chronic Toxicity ( rodent) Yoneyama et al. ( 1972) Studies on the Toxicity of Synthetic Detergents. ( II) Subacute Toxicity of Linear and Branched Alkyl Benzene Sulfonates in Rats. Ann Rep Tokyo Metrop Res Lab Public Health, 24: 409 440.

Open Literature Technical grade LAS was administered in the feed for 6 months at a concentration of 0, 0.07, 0.2, 0.6, or 1.8%

Wistar SLC Strain Rat ( 10/ sex/ dose)

Purity: Not Reported NOAEL: 0.07% ( 40 mg/ kg bw/ day)

At 1.8%, diarrhea, decrease in body weight gain and tissue damage in caecum liver and kidney were observed. The damage to the kidney was especially remarkable.

At 0.6% of the LAS or ABS, the adverse effects observed were a slight decrease of body weight, increase of ceacum weight, increased activity of alkaline phosphatase, decrease of total protein in blood, and the tissue damage in the kidney.

At 0.2% of the LAS or ABS, an increase of caecum weight and a slight damage to the kidney were observed.

Carcinogenicity 870.4200a Oncogenicity ( Rat) MRID 43498416 Buehler, E., Newmann, E., and King, W. ( 1971) Two Year Feeding and Reproduction Study in Rats with Linear Alkylbenzene Sulfonate ( LAS). Tox. Appl. Pharm. 18: 83 91. LAS was administered in the diet at doses of 10, 50, and 250 mg/ kg/ day for 2 years Weanling Charles River CD Rats ( 50/ sex/ group)

Purity: Not Reported Negative at 250 mg/ kg/ day ( HDT) Page 55 of 62 Table A 1 Toxicity Profile of Alkylbenzene Sulfonates Guideline No./ Study Type MRID No./ Reference Information/ Study Classification Dosing and Animal Information Results ( HERA)

Acceptable Guideline 870.4200a Oncogenicity ( Rat) Endo et al. ( 1980) Studies of the Chronic Toxicity and Teratogenicity of Synthetic Surfactants, Ann. Rep. Tokyo Metrop. Res. Inst. Environ. Prot. ( Tokyo Kogai Kenkyujo Nempo), 236 246. ( HERA) Open Literature LAS was administered in the drinking water at the dose of 200 mg/ kg bw/ d 62 M/ F Wistar Rat Purity: 38.74% a. i. The administration of LAS had no effect on the intake of water, mortality, body weight gain, or general condition. In pathological examinations, looseness, atrophy, and fatty change of the hepatic cells in the liver were found in the experimental control group at 6 months, together with significant increases in GOT, GTP and bilirubin. In hematological examinations no effects due to LAS were observed.

870.4200a Oncogenicity ( Rat) Fujii et al. ( 1977) Pathological Examination of Rats Fed with LAS for their Lifespan, Ann. Rep. Tokyo Metrop. Res. Lab. Public Health 28( 2): 85 108. ( HERA)

Yoneyama et al. ( 1977) Toxicity of LAS by Dietary Administration for Life Span to Rats, Ann. Rep. Tokyo Metrop. Res. Lab. Public Health 28( 2): 73 84. ( HERA)

Open Literature LAS was administered in the feed at a concentration of 0.04, 0.16, and 0.60% for 24 months or lifespan Wistar Weanling Rat ( 15/ sex/ dose)

Purity: Not Reported Histopathological examination revealed that there was no evidence of a treatment related effect on any tissue examined. Whereas a variety of tumors were observed in both linear alkylbenzene sulfonate treated and control rats, none was attributed for the exposure to linear alkylbenzene sulfonate. There was no relationship among the dosage groups, sex, type of tumor, or the site of occurrence.

870.4200a Oncogenicity ( Rat) MRID 43498420 Takahasi et al. ( 1969) Effect of Alkylbenzenesulfonate as a Vehicle for 4 Nitroquinoline 1 Oxid e on Gastric Carcinogenesis in Rats. GANN: 8, 241 261.

Acceptable Guideline For 560 days; Group I ( 79 rats): 1 mg 4 NQO and 80 mg SDDBS 2 3x per week for 18 weeks; Group I' ( 17 rats): same as Group 1, but fasted for 12 hours prior to dosing,; Group II ( 37 rats): 1 mg 4 NQO only; Group III ( 28 rats): 80 mg SDDBS only 97 M Wistar Rats Purity: Not Reported In Groups I and I', the presence of SDDBS shifts the incidence of benign papillomas to malignant papillomas of the forestomach and the incidence of adenocarcinoma and sarcoma of the stomach were increased in comparison to Group II with only 4 NQO. The administration of SDDBS by itself has no effect on gastric tumors ( Group III). The study authors concluded that the increased carcinogenicity produced by SDDBS was due to the better uptake of 4 NQO via LAS's surfactive/ detersive effects on the protective mucous barrier which is normally found in the glandular stomach and other gastric compartments of the rat. The effect of SDDBS was physical rather than chemical in promoting the increased tumorigenicity.

870.4200a Oncogenicity ( Rat) MRID 43498419 Takahasi et al. ( 1970) Effect of 4 Nitroquinoline 1 Oxid e with Alkylbenzenesulfonate on Gastric Carcinogenesis in Rats. GANN: 61, 27 33.

Acceptable Rats were divided into three groups and gavaged with the following regimen for 560 days: Group I ( 37 rats)  1 mg 4 NQO + 80 mg SDDBS + 20 mg ethanol in a 1 ml gavage for 18 weeks; Group II ( 13 rats)  4 NQO and ethanol for 18 weeks; Group III ( 13 rats)  SDDBS + ethanol for Survival: Mortality was 59% in Group I, 31% in Group II, and 23% in Group III Tumors: Group III  no gastric tumors; Group II  9 benign papillomas of forestomach; Group I  8 benign papillomas of forestomach, 2 malignant papillomas of forestomach, 1 hemangiosarcoma of forestomach. In glandular stomach, 2 adenocarcinomas, 1 hemangiosarcoma, 1 hemangioma, 5 squamous cell carcinomas, and 2 rats exhibited atrophic gastritis. Page 56 of 62 Table A 1 Toxicity Profile of Alkylbenzene Sulfonates Guideline No./ Study Type MRID No./ Reference Information/ Study Classification Dosing and Animal Information Results Guideline 18 weeks 64 M Motoyama Strain Rat Purity: Not Reported The increased toxicity in Group I produced increased mortality and increased numbers of malignant tumors. The role of SDDBS in the tumorigenesis of 4 NQO was to promote increased absorption of 4 NQO through the forestomach and glandular stomach.

870.4200a Oncogenicity ( Rat) MRID 43498421,  22 Takahasi et al. ( 1973) Carcinogenic Effect of N Methyl N' Nitro N N itrosoguanidine with Various Kinds of Surfactant in the Glandular Stomach of Rats.

Acceptable Guideline SDDBS was administered to 5 groups of rats: ( I) 13 rats received 0.1g of MNNG + 4000 mg Tween 60 per L of drinking water for 36 weeks; ( II) 16 rats received 0.1 g MNNG + 2000 mg nonipol per L of drinking water for 36 weeks; ( III) 15 rats received 0.1 g of MNNG + 1000 mg branched (" hard") SDDBS per L of drinking water for 63 weeks; ( IV) 10 rats received 0.1 g MNNG + 1000 mg of linear (" soft") SDDBS per L of drinking water for 63 weeks; ( V) 14 rats received o. 1 g MNNG per L of drinking water for 63 weeks M Wistar Rats Purity: Not Reported Survivial was 100% in Groups I, III, and IV, and 93% and 94% in Groups V and II, respectively.

The Group I and II rats had more tumors than the controls ( Group V), whereas, the rats in Group III, (" hard" SDDBS, and particularly, Group IV ( linear " soft" SDDBS) had the fewest tumors in comparison to controls.

870.4200a Oncogenicity ( Rat) Tiba S ( 1972) Studies on the Acute and Chronic Toxicity of LAS, J. Food Hyg. Soc. Jpn. ( Shokuhin Eiseigaku Zasshi) 13( 6): 509 516. ( HERA)

Open Literature LAS was administered in drinking water for 2 years at doses of 20, 100, and 200 mg/ kg bw/ d M Wistar Rat ( 20/ group)

Purity: Not Reported There were no changes due to the administration of LAS in regard to growth, mortality, the weight of major organs, or histopathological findings Mutagenicity 870.5100 Bacterial reverse mutation test Huls, Report No. AM 93/ 12, Unpublished data, 1993. ( As cited in HERA 2004)

Open Literature LAS was tested at 8 5000 ug/ plate with and without metabolic activation. The cytotoxicity concentration was > 5000 ug/ plate.

Salmonella typhimurium, strains TA 98, TA 100, TA 1535, TA 1537, and TA 1538 Purity: Not Reported Negative results 870.5100 Bacterial reverse mutation test MRID 43498429 Inoue et al. ( 1980) Studies of In Vitro Cell Transformation and Mutagenicity by Surfactants and other Compounds, Food. SDDBS was tested at cytotoxic levels or limit concentrations of 2,000 30,000 ug/ plate for 2 days ( Salmonella) or 8 days ( SHE) Negative ( both with and without S 9 metabolic activation) Page 57 of 62 Table A 1 Toxicity Profile of Alkylbenzene Sulfonates Guideline No./ Study Type MRID No./ Reference Information/ Study Classification Dosing and Animal Information Results Cosmet. Toxicol 18: 289 296. ( HERA)

Acceptable Guideline Strain: Salmonella typhimurium  TA 98 and TA 100 cells and Embryonic Syrian Golden Hamster cells ( SHE)

Purity: Not Reported 870.5100 Bacterial reverse mutation test Sunakawa et al. ( 1981) Studies on the Mutagenicity of Surfactants Following Activation with Various Liver Homogenates ( S 9) and Mutagenicity in the Presence of Norharman, Hyg. Chem. ( Eisei Kagaku) 27( 4): 204 211, See: WHO, 1996.

Open Literature LAS was tested at up to 500 ug/ plate Salmonella typhimurium Purity: Not Reported Negative Results 870.5300 In Vitro mammalian cell gene mutation test Inoue, K. et al. ( 1977) Osaka furitsu Koshu Eisei Kenkyusho Kenkyu Hokoku, Shokuhin Eisei Hen 8: 25 8. ( HERA)

Open Literature Sodium alkylbenzenesulfonate was added to culture at 62.5 ug/ ml and 125 ug/ l Hamster Lung Cell Purity: Not Reported At 62.5 ug/ ml: induced cell mutation, no effect on sister chromatid exchange At 125 ug/ ml: destroyed the cells completely 870.5300 In Vitro cell transformation MRID No. 43498427 K. Inoue et al ( 1980) Food Cosmetic Toxicol. 18: 289 296 Acceptable Open Literature Duplicate primary cultures of embryonic SHE and Salmonella typhimurium strain TA 98 and TA 100 cells were exposed to SDDBS and positive and negative controls for 8 days. SDDBS was negative for transformation up to cytotoxic levels and did not induce mutation in either strains of Salmonalla when allplied up to cytotoxic levels or limit concentration of 2000 3000 ug/ plate. SDDBS was tested negative at cytotoxic levels or limit concentrations ( both with and without S 9 metabolic activation) of 2,000 30,000 ug/ plate for 2 days ( Salmonella) or 8 days ( SHE)

870.5385 Mammalian bone marrow chomosomal aberration test Inoue K, et al. ( 1979) In vivo Cytogenetic Tests of Some Synthetic Detergents in Mice, Ann. Rep. Osaka Perfect. Inst. Public Health 8: 17 24 ( in Japanese), See: IPCS, 1996. ( HERA)

Open Literature LAS was administered at doses of 200, 400, and 800 mg/ kg bw/ d by gavage for 1 and 5 days M Mouse Purity: Not Reported There was no significant difference in the incidence of chromosomal aberrations between any of the groups 870.5385 Mammalian bone marrow chomosomal aberration test Inoue, K. et al. ( 1977) In Vivo Cytogenetic Tests of Some Synthetic Detergents in Mice. Ann Rep Osaka Prefect Inst Public Health, 8: 17 24. ( HERA)

Open Literature LAS was administered at a dose of 200, 400, and 800 mg/ kg bw/ d by gavage for 5 days. One commercial preparation containing 19.0% LAS was also given, at a dose of 800, 1600, or 3200 mg/ kg bw, and another containing 17.1% LAS at a dose of 1000, 2000, or 4000 mg/ kg bw once only by gavage. There was no significant difference between any of the groups given LAS and the negative control group in the incidence of chromosomal aberrations Page 58 of 62 Table A 1 Toxicity Profile of Alkylbenzene Sulfonates Guideline No./ Study Type MRID No./ Reference Information/ Study Classification Dosing and Animal Information Results M ICR: JCL Mouse Purity: Not Reported 870.5385 Mammalian bone marrow chomosomal aberration test MRID 43498428 J. Hope ( 1977) Absence of Chromosome Damage in the Bone Marrow of Rats Fed Detergent Actives for 90 Days. Mutation Research, 56: 47 50.

Acceptable Guideline SDDBS was administered in the diet for 90 days at 0, 280, and 565 mg/ kg bw/ d Colworth/ Wistar Weanling Rat ( 6/ sex/ dose)

Purity: Not Reported All test preparations were negative for increased chromosomal damage over controls.

870.5385 Mammalian bone marrow chomosomal aberration test Masabuchi et al. ( 1976) Cytogenetic Studies and Dominant Lethal Tests with Long Term Administration of Butylated Hydroxytoluene ( BHT) and LAS in Mice and Rats, Ann. Rep. Tokyo Metrop. Res. Lab. Public Health 27( 2): 100 104. ( HERA)

Open Literature LAS was administered in the diet for 9 months at a dose of 0.9% in rats ( 450 mg/ kg bw/ d) and in mice ( 1170 mg/ kg bw/ d)

Male Rat and Male Mouse Purity: Not Reported There were no significant differences in the incidences of chromosomal aberrations between the experimental and control groups 870.5395 Mammalian erthrocyte micronucleus test Kishi et al. ( 1984) Effects of Surfactants on Bone Marrow Cells, Bull. Kanagawa Public Health Lab. 14: 57 58. ( HERA)

Open Literature LAS was administered as a single intraperitoneal injection at a dose of 100 mg/ kg bw 3 M ddY Mice Purity: Not Reported There were no differences in the incidences of polychromatic erythrocytes with micronuclei in the bone marrow cells between the treated group and the control group 870.5395 Mammalian erthrocyte micronucleus test Koizumi et al. ( 1985) Implantation Disturbance Studies with LAS in Mice, Arch. Environ. Contam. Toxicol. 14: 73 81. ( HERA)

Open Literature LAS were administered as a single oral dose of 2 mg to pregnant mice on day 3 of gestation. On day 17 of gestation, each animal received a subcutaneous dose of 1, 2, or 10 mg and were killed 24 h later.

Pregnant ICR Mice Purity: Not Reported There was no difference among treated groups in the incidence of polychromatic erythrocytes with micronuclei in maternal bone marrow or fetal liver or blood. No mutagenetic effect was found in any of the groups.

870.5450 Rodent dominant lethal assay Masubuchi MA et al. ( 1976) Cytogenetic Studies and Dominant Lethal Tests with Long Term Administration of Butylated Hydroxytoluene ( BHT) and Linear A diet containing 0.6% LAS at 300 mg/ kg bw/ d was administered to mice for 9 months. Each of the male mice was then mated with two female mice that had not been given LAS, and 11 of the 14 females There were no significant differences in fertility, mortality of ova and embryos, the number of surviving fetuses, or the index of dominant lethal induction ( Roehrborn) between the experimental and control groups. Page 59 of 62 Table A 1 Toxicity Profile of Alkylbenzene Sulfonates Guideline No./ Study Type MRID No./ Reference Information/ Study Classification Dosing and Animal Information Results Alkylbenzene Sulfonate ( LAS) in Mice and Rats. Ann Rep Tokyo Metrop Res Lab Public Heath, 27( 2): 100 104.

( HERA)

Open Literature became pregnant. The pregnant mice were laparotomized on day 13 of gestation 7 M ICR: JCL Mice Purity: Not Reported Metabolism 870.7485 General Metabolism MRID 43498410 Creswell et al. ( 1978) Toxicology Studies of Linear Alkylbenzene Sulphonate ( LAS) in Rhesus Monkeys II. The Disposition of C14 LAS After Oral or Subcutaneous Administration. Toxicology, 11: 5 17.

Acceptable Guideline Single oral doses of C14 LAS ( SDDBS; 25 ucuries) were administered to each animal, following 2 3 weeks between dose levels, at levels of 30, 150, and 300 mg/ kg. Following 2 3 weeks after the last single oral dose, each monkey received 7 consecutive daily oral doses of 30 mg/ kg/ d of C14 LAS.

2 M/ 2 F Rhesus Monkeys Purity: Not Reported After single 30 mg/ kg doses the radioactivity was rapidly excreted, mostly during the first 24 hours. Feces and urine contained 23.1% and 71.2%, respectively, in the first 5 days after oral dosing. Plasma concentrations were comparable after the oral doses and averaged 34, 41, and 36 u/ ml, respectively. Peak plasma concentrations increased proportional to the dose and were 0.16, 0.72, 1.13 u/ ml, respectively. In urine samples analyzed for metabolites, there was no unchanged SDDBS and the 5 metabolites detected were polar, but were not sulphate or glucuronide conjugates.

870.7485 General Metabolism Lay JP, et al. ( 1983) Toxicol. Letters 17 ( 1 2): 187 192 Open Literature ( 14) C labeled sodium dodecylbenzenesulfonate was administered daily in the diet at a concentration of 1.4 mg/ kg for 5 weeks M Rat Purity: not reported From a total uptake of 1.213 + or  0.08 mg/ animal of DBS, 81.8% was excreted during the dosing period: 52.4% in feces and 29.4% in urine. Low levels of ( 14) C DBS derived residues were detected in all tissues analyzed on day 35 of the study. Following 1 week on a normal diet, only 7.8% of the nominally stored amount of ( 14) C was found in the excreta.

870.7485 General Metabolism Sunakawa et al. ( 1979) Yakuzaigaku 39 ( 2): 59 68 Open Literature Sodium para dodecylbenze nesulfonate Rat Purity: Not Reported Blood levels were max at 2 hr, negligible at 48 hr Excretion rate of radioactive label was 99.4% after 48 hr 870.7485 General Metabolism The Royal Society of Chemistry. ( 1981) Foreign Compound Metabolism in Mammals. Volume 6: A Review of the Literature Published during 1978 and 1979. London: The Royal Society of Chemistry, p. 354.

Open Literature ( 35) S labeled sodium dodecylbenzenesulfonate was administered as a single oral dose Rat Purity: Not Reported Rats excreted 64% and 24% of the dose in urine and feces, respectively 870.7485 General Metabolism The Royal Society of Chemistry. ( 1981) Foreign Compound Metabolism in Mammals. Volume 6: A Repeated doses of ( 14) C labeled alkylbenzenesulfonate were orally administered Radioactivity did not accumulate in the tissues Page 60 of 62 Table A 1 Toxicity Profile of Alkylbenzene Sulfonates Guideline No./ Study Type MRID No./ Reference Information/ Study Classification Dosing and Animal Information Results Review of the Literature Published during 1978 and 1979. London: The Royal Society of Chemistry, p. 354. Rhesus Monkey Purity: Not Reported 870.7485 General Metabolism MRID 43498431 W. Michael ( 1968) Metabolism of Linear Alkylate Sulfonate and Alkyl Benzene Sulfonate. Toxicol. Appl. Pharmacol. 12: 473 485.

Acceptable Guideline LAS S35 was administered orally to fasted rats at doses of 0.6, 1.2, 8, and 40 mg Charles River CD M Rat Purity: Not Reported The rate and distribution of the excreted dose was independent of concentration.

Similar levels of radioactivity were found in urine and feces and within 3 days, 85.2%  96.6% of the label was recovered.

In the high dose rats, no detectable radioactivity was found in the carcasses after 3 days.

Following methylation, one urinary metabolite was identified as 4( 4' methylsulfophenyl) pentanoate. LAS S35 in the feces remained unmetabolized.

Special Studies 870.3700a Developmental Toxicity ( rodent) Koizumi et al. ( 1985) Implantation Disturbance Studies with LAS in Mice, Arch. Environ. Contam. Toxicol. 14: 73 81. ( HERA)

Open Literature LAS was administered as a single oral dose of 350 mg/ kg bw on day 3 of gestation Pregnant ICR Mice Purity: Not Reported LAS was not detected in the uterus Other Inoue K, T Sunakawa. ( 1979) Mutagenicity Tests of Surfactants, Jpn. Fragr. J. 38: 67 75, ( in Japanese), See: IPCS, 1996. ( HERA)

Open Literature LAS tested in a recombination assay at concentrations up to 50 ug/ plate Bacillus subtilis Purity: 99.5% Negative results with and without metabolic activation Other Fujise, H. and Aoyama, M. ( 1984) Nagoya Med J, 28 ( 3 4): 211 5 Open Literature The proliferation rate of the connective tissue was examined by measuring the activity of proline hydroxylase. The dorsal neck skin of rats was coated with sodium laurylbenzenesulfonate for 4 days, and on the 5th day, the enzyme activity in the skin was measured.

Rat Purity: Not Reported The proline hydroxylase in the part of the skin coated with the irritants showed clearly higher activity than normal skin, although it was still lower than the injured skin region prepared as a positive control.

Other MRID 43498430 and 43498408 Kimura et al. ( 1982) Mechanisms of Toxicities of Some Detergents Added to a Diet and the Ringer's bicarbonate ( containing sodium lauryl benzene sulfonate) at 0.5 ml/ min was used to perfuse a 10 cm length of jejunal segment for 150 minutes; equilibrated for 30 minutes and then the perfusates Alkaline phosphatase was released by an increase of 15 fold in comparison to Ringer's alone ( controls without added sodium lauryl benzene sulfonate) and 3 7 times greater than other surfactants tested in Ringer's. The authors conclude that SDDBS has an exfoliative effect on the intestinal brush border Page 61 of 62 Table A 1 Toxicity Profile of Alkylbenzene Sulfonates Guideline No./ Study Type MRID No./ Reference Information/ Study Classification Dosing and Animal Information Results Ameliorating Effects of Dietary Fiber in the Rat. J. Nutrit. Science and Science and Vitaminology, 28: 483 489.

Kimura et al. ( 1982) Toxicity for Detergent Feeding and Effect of the Concurrent Feeding of Dietary Fiber in the Rat. Nutrition Reports International, 26( 2): 271 279.

Acceptable Guideline were collected in 30 minute aliqouts for 120 minutes M Wistar Rat Purity: 0.5%

Other Oba et al. ( 1968) Biochemical Studies of n alpha olefin sulfonates: ( II) Acute Toxicity, Skin and Eye Irritation, and Some Other Physiological Properties. J Jpn Oil Chem Soc, 17 ( 11): 628 634. ( EHC 169)

Open Literature Solutions of various concentrations of LAS were mixed with red blood cells from rabbits at room temperature for 3 hours Rabbit Red Blood Cell Purity: Not Reported The 50% haemolytic concentration of LAS was 9 mg/ litre Other Samejima Y ( 1991) Effects of Synthetic Surfactants and Natural Soap on the Development of Mouse Embryos In Vitro and the Fertilizing Capacity of Mouse and Human Sperm. J Osaka Univ Med Sch, 3 ( 12): 675 682. ( EHC 169)

Open Literature Eggs were fertilized in vitro and incubated in culture medium containing LAS at concentrations between 0.015 and 0.03%.

F B6C3F1 Mouse Egg Purity: Not Reported Concentrations of LAS less than 0.025%: Eggs exposed for 1 hr, washed, and then cultured for 5 days developed normally to the blastocyst stage Concentrations of LAS higher than 0.03%: The eggs did not develop beyond the one cell stage With continuous exposure to LAS for five days, a concentration of 0.01% slightly impaired development to the blastocyst stage, and 0.025% prevented development to the one cell stage Other Takahashi et al. ( 1974) Inhibition of Thrombin by Linear Alkylbenzene Sulfonate ( LAS). Ann Rep Tokyo Metrop Res Lab Public Health, 25: 637 645. ( HERA)

Open Literature Purified LAS at various concentrations were added to 10 ul of plasma from rats and prothrombin time was determined M Rat Purity: Not Reported Prothrombin time was prolonged; the 50% inhibitory concentration was about 0.6 mmol/ litre. When LAS at various concentrations were added to a mixture of 1% fibrinogen and thrombin, the time of formation of a mass of fibrin was prolonged by inhibition of thrombin activity. The 50% inhibitory concentration was about 0.05 mmol/ litre.

Other Yanagisawa et al. ( 1964) Biochemical Studies of Dodecylbenzene Sulfonates; Differences Between Soft and Hard Detergents. Jpn. J Public Health, 11( 13): The haemolytic action of LAS was investigated by mixing red blood cells from rabbits with solutions of LAS at concentrations of 1 1000 mg/ litre at 38 C for 30 min Haemolysis occurred at concentrations >= 5 mg/ litre. Page 62 of 62 Table A 1 Toxicity Profile of Alkylbenzene Sulfonates Guideline No./ Study Type MRID No./ Reference Information/ Study Classification Dosing and Animal Information Results 859 864. ( EHC 169)

Open Literature Rabbit Red Blood Cell Purity: Not Reported


[Federal Register Volume 88, Number 30 (Tuesday, February 14, 2023)]
[Notices]
[Pages 9589-9590]
[FR Doc No: 2023-03098]

=======================================================================
-----------------------------------------------------------------------

DEPARTMENT OF TRANSPORTATION

Federal Aviation Administration

[Docket No. FAA-2023-0305]

Notice of Public Meeting: Input to Changed Product Rule (CPR)
International Authorities Working Group (IAWG) Recommendations

AGENCY: Federal Aviation Administration (FAA), DOT.

ACTION: Notice of public meeting.

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

SUMMARY: This notice announces a public meeting for input to Changed
Product Rule (CPR) International Authorities Working Group (IAWG)
recommendations. The purpose of the public meeting is for the FAA to
present information on and receive public input on the CPR IAWG
recommendations.

DATES: The meeting will be held on Tuesday, February 28, 2023, from
9:00 a.m. to 4:00 p.m. Eastern Time. Requests to attend the meeting
must be received by Monday, February 20, 2023. Requests for
accommodations to a disability must be received by Monday, February 20,
2023. Materials to be presented during the meeting must be received no
later than Monday, February 20, 2023. The FAA will accept input on the
IAWG recommendations until March 17, 2023.

ADDRESSES: The meeting will be held at The General Aviation
Manufacturers Association, 1400 K Street NW, Suite 801, Washington, DC
20005 and virtually. Members of the public who wish to participate in
the meeting must RSVP by emailing [email protected].
    Meeting minutes, transcripts, and other information will be
available in the public docket at Regulations.gov, unless certain
information is protected from disclosure.
    Docket: Send comments identified by Docket No. FAA-2023-0137 using
any of the following methods:
     Federal eRegulations Portal: Go to https://www.regulations.gov/ and follow the online instructions for sending
your comments electronically.
     Mail: Send comments to Docket Operations, M-30, U.S.
Department of

Transportation (DOT), 1200 New Jersey Avenue SE, Room W12-140, West
Building Ground Floor, Washington, DC 20590-0001.
     Hand Delivery or Courier: Take comments to Docket
Operations in Room W12-140 of the West Building Ground Floor at 1200
New Jersey Avenue SE, Washington, DC, between 9 a.m. and 5 p.m., Monday
through Friday, except Federal holidays.
     Fax: Fax comments to Docket Operations at<PHONE_NUMBER>
    Privacy: In addition to the presentations, the FAA will post all
comments it receives, without change, to https://www.regulations.gov/,
including any personal information provided by the commenter. DOT's
complete Privacy Act Statement can be found in the Federal Register
published on April 11, 2000 (65 FR 19477-19478).

FOR FURTHER INFORMATION CONTACT: Sue McCormick, Manager, Strategic
Policy for Systems Standards, AIR-619, Strategic Policy Management
Branch, Policy and Innovation Division, Aircraft Certification Service,
Federal Aviation Administration, 26805 East 68th Avenue, Denver, CO
80249, telephone<PHONE_NUMBER>, email [email protected].

SUPPLEMENTARY INFORMATION:

I. Background

    The FAA issued a notice in the Federal Register (87 FR 77671,
December 19, 2022), announcing the availability of recommendations from
the CPR IAWG, encouraged industry review of the CPR IAWG
recommendations, and informed the public on the intent to seek input
and comments during a forthcoming public meeting.
    A copy of the International Authorities Working Group (IAWG)
Changed Product Rule (CPR) Recommendations can be downloaded at:
https://www.faa.gov/aircraft/air_cert/design_approvals/dah/iawg_cpr_recs.

II. Agenda

    At the meeting, the agenda will solicit input on each of the
recommendations from the IAWG report in the following manner:

Morning Session

    Recommendations applicable to Sec.  21.101 of title 14, Code of
Federal Regulations (14 CFR), significant changes to include
eliminating impractical exceptions, combining impractical and does not
contribute materially to the level of safety exceptions, additional
design requirements and conditions, definition of baseline product,
cumulative effect and related changes, proposed revisions to Sec.
21.101, and removing secondary changes.

Afternoon Session

    Continue discussion on recommendations applicable to Sec.  21.101
significant changes to include the use of system safety methodologies,
documentation of certification basis on certificates and
recommendations applicable to Sec.  21.19: Substantial Changes. Input
that is supported by data, especially quantifiable data, on use of the
CPR process is highly encouraged.
    The final meeting agenda will be posted on the FAA website https://www.faa.gov/aircraft/air_cert/design_approvals/dah.

III. Purpose

    The purpose of the public meeting is for the FAA to hear the
public's views and obtain information relevant to the CPR IAWG
recommendations. The FAA will consider comments made at the public
meeting as well as comments submitted to the docket.

IV. Public Participation

    The meeting will be open to the public on a first-come, first
served basis, as space is limited. The FAA will make every effort to
accommodate all persons wishing to attend. Persons wishing to attend
this one-time meeting in person are requested to register in advance,
due to limited space. Please confirm your attendance with the person
listed in the FOR FURTHER INFORMATION CONTACT section. Please provide
the following information: full legal name, country of citizenship,
name of your industry association or applicable affiliation, your
intention to attend in person or virtually, and if you intend to
present information at the meeting. There will be 10 minutes allotted
for oral comments from each member of the public joining the meeting.
To accommodate as many speakers as possible, the time for each
commenter may be limited. Additionally, the FAA may end sessions early,
per the discretion of the facilitator. The FAA will email virtual
registrants the meeting access information in a timely manner prior to
the meeting.
    Members of the press, in addition to registering for this event,
must also RSVP by emailing [email protected] by February 20, 2023.
    The U.S. Department of Transportation is committed to providing
equal access to this meeting for all participants. If you need
alternative formats or services because of a disability, such as sign
language, interpretation, or other ancillary aids, please contact the
person listed in the FOR FURTHER INFORMATION CONTACT section.

    Issued in Washington, DC, on February 9, 2023.
Victor Wicklund,
Acting Director, Policy & Innovation Division, Aircraft Certification
Service.
[FR Doc. 2023-03098 Filed 2-13-23; 8:45 am]
BILLING CODE 4910-13-P