[Federal Register Volume 87, Number 78 (Friday, April 22, 2022)]
[Notices]
[Pages 24175-24181]
[FR Doc No: 2022-08571]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2004-N-0451]

Food and Drug Administration Modernization Act of 1997:
Modifications to the List of Recognized Standards, Recognition List
Number: 057

AGENCY: Food and Drug Administration, Health and Human Services (HHS).

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA or Agency) is announcing
a publication containing modifications the Agency is making to the list
of standards FDA recognizes for use in premarket reviews (FDA
Recognized Consensus Standards). This publication, entitled
``Modifications to the List of Recognized Standards, Recognition List
Number: 057'' (Recognition List Number: 057), will assist manufacturers
who elect to declare conformity with consensus standards to meet
certain requirements for medical devices.

DATES: Submit either electronic or written comments on the notice at
any time. These modifications to the list of recognized standards are
applicable April 22, 2022.

ADDRESSES: You may submit comments on the current list of FDA
Recognized Consensus Standards at any time as follows:

Electronic Submissions

    Submit electronic comments in the following way:
     Federal eRulemaking Portal: https://www.regulations.gov.
Follow the instructions for submitting comments. Comments submitted
electronically, including attachments, to https://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 https://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): Dockets Management Staff (HFA-305), Food and Drug
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
     For written/paper comments submitted to the Dockets
Management Staff, 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-2004-N-0451 for ``Food and Drug Administration Modernization Act of
1997: Modifications to the List of Recognized Standards, Recognition
List Number: 057.'' Received comments will be placed in the docket and,
except for those submitted as ``Confidential Submissions,'' publicly
viewable at https://www.regulations.gov or at the Dockets Management
Staff between 9 a.m. and 4 p.m., Monday through Friday,<PHONE_NUMBER>.
FDA will consider any comments received in determining whether to amend
the current listing of modifications to the list of recognized
standards, Recognition List Number: 057.
     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 https://www.regulations.gov.
Submit both copies to the Dockets Management Staff. 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: https://www.govinfo.gov/content/pkg/FR-2015-09-18/pdf/2015-23389.pdf.
    Docket: For access to the docket to read background documents or
the electronic and written/paper comments received, go to https://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 Dockets Management Staff, 5630 Fishers Lane,
Rm. 1061, Rockville, MD 20852,<PHONE_NUMBER>.
    An electronic copy of Recognition List Number: 057 is available on
the internet at https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/Standards/ucm123792.htm. See section IV for
electronic access to the searchable database for the current list of
FDA-recognized consensus standards, including Recognition List Number:
057 modifications and other standards-related information. Submit
written requests for a single hard copy of the document entitled
``Modifications to the List of Recognized Standards, Recognition List
Number: 057'' to Scott Colburn, Center for Devices and Radiological
Health, Food and Drug Administration, 10903 New Hampshire Ave., Bldg.
66, Rm. 5606, Silver Spring, MD 20993,<PHONE_NUMBER>. Send one self-
addressed adhesive label to assist that office in processing your
request, or Fax your request to<PHONE_NUMBER>.

FOR FURTHER INFORMATION CONTACT: Scott Colburn, Center for Devices and
Radiological Health, Food and Drug Administration, 10903 New Hampshire
Ave., Bldg. 66, Rm. 5606, Silver Spring, MD 20993,<PHONE_NUMBER>,
[email protected].

SUPPLEMENTARY INFORMATION:

I. Background

    Section 204 of the Food and Drug Administration Modernization Act
of 1997 (Pub. L. 105-115) amended section 514 of the Federal Food,
Drug, and Cosmetic Act (FD&C Act) (21 U.S.C. 360d). Amended section 514
allows FDA to recognize consensus standards developed by international
and national organizations for use in satisfying portions of device
premarket review submissions or other requirements.
    In the Federal Register of September 14, 2018 (83 FR 46738), FDA
announced the availability of a guidance entitled ``Appropriate Use of
Voluntary Consensus Standards in Premarket Submissions for Medical
Devices.'' The guidance describes how FDA has implemented its standards
recognition

program and is available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/appropriate-use-voluntary-consensus-standards-premarket-submissions-medical-devices. Modifications to the
initial list of recognized standards, as published in the Federal
Register, can be accessed at https://www.fda.gov/medical-devices/standards-and-conformity-assessment-program/federal-register-documents.
    These notices describe the addition, withdrawal, and revision of
certain standards recognized by FDA. The Agency maintains on its
website hypertext markup language (HTML) and portable document format
(PDF) versions of the list of FDA Recognized Consensus Standards,
available at https://www.fda.gov/medical-devices/standards-and-conformity-assessment-program/federal-register-documents. Additional
information on the Agency's Standards and Conformity Assessment Program
is available at https://www.fda.gov/medical-devices/device-advice-comprehensive-regulatory-assistance/standards-and-conformity-assessment-program.

II. Modifications to the List of Recognized Standards, Recognition List
Number: 057

    FDA is announcing the addition, withdrawal, correction, and
revision of certain consensus standards the Agency is recognizing for
use in premarket submissions and other requirements for devices. FDA is
incorporating these modifications to the list of FDA Recognized
Consensus Standards in the Agency's searchable database. FDA is using
the term ``Recognition List Number: 057'' to identify the current
modifications.
    In table 1, FDA describes the following modifications: (1) The
withdrawal of standards and their replacement by others, if applicable;
(2) the correction of errors made by FDA in listing previously
recognized standards; and (3) the changes to the supplementary
information sheets of recognized standards that describe revisions to
the applicability of the standards.
    In section III, FDA lists modifications the Agency is making that
involve new entries and consensus standards added as modifications to
the list of recognized standards under Recognition List Number: 057.

       Table 1--Modifications to the List of Recognized Standards
------------------------------------------------------------------------
                   Replacement
Old recognition    recognition   Title of standard \1\       Change
      No.              No.
------------------------------------------------------------------------
                            A. Anesthesiology
------------------------------------------------------------------------
                      No new entries at this time.
------------------------------------------------------------------------
                           B. Biocompatibility
------------------------------------------------------------------------
2-275..........  ..............  ISO 10993-7 Second     Title change.
                                  edition 2008-10-15
                                  Biological
                                  evaluation of
                                  medical devices--
                                  Part 7: Ethylene
                                  oxide sterilization
                                  residuals
                                  [Including:
                                  Technical
                                  Corrigendum 1
                                  (2009), AMENDMENT 1:
                                  Applicability of
                                  allowable limits for
                                  neonates and infants
                                  (2019)].
2-284..........           2-292  USP-NF M98833_01_01    Withdrawn and
                                  <87> Biological        replaced with
                                  Reactivity Test, In    newer version.
                                  Vitro--Direct
                                  Contact Test.
2-285..........           2-293  USP-NF M98833_01_01    Withdrawn and
                                  <87> Biological        replaced with
                                  Reactivity Test, In    newer version.
                                  Vitro--Elution Test.
2-286..........           2-294  USP-NF M98834_01_01    Withdrawn and
                                  <88> Biological        replaced with
                                  Reactivity Tests, In   newer version.
                                  Vivo.
2-287..........           2-295  USP-NF M98900_01_01    Withdrawn and
                                  <151> Pyrogen Test     replaced with
                                  (USP Rabbit Test)..    newer version.
------------------------------------------------------------------------
                            C. Cardiovascular
------------------------------------------------------------------------
3-88...........           3-171  ASTM F2514-21          Withdrawn and
                                  Standard Guide for     replaced with
                                  Finite Element         newer version.
                                  Analysis (FEA) of
                                  Metallic Vascular
                                  Stents Subjected to
                                  Uniform Radial
                                  Loading.
3-99...........           3-172  AAMI TIR42:2021        Withdrawn and
                                  Evaluation of          replaced with
                                  particulate            newer version.
                                  associated with
                                  vascular medical
                                  devices.
3-133..........           3-173  ISO 5840-3 Second      Withdrawn and
                                  edition 2021-01        replaced with
                                  Cardiovascular         newer version.
                                  implants--Cardiac
                                  valve prostheses--
                                  Part 3: Heart valve
                                  substitutes
                                  implanted by
                                  transcatheter
                                  techniques.
3-145..........           3-174  ISO 5840-1 Second      Withdrawn and
                                  edition 2021-01        replaced with
                                  Cardiovascular         newer version.
                                  implants--Cardiac
                                  valve prostheses--
                                  Part 1: General
                                  requirements.
3-147..........           3-175  ISO 5840-2 Second      Withdrawn and
                                  edition 2021-01        replaced with
                                  Cardiovascular         newer version.
                                  implants--Cardiac
                                  valve prostheses--
                                  Part 2: Surgically
                                  implanted heart
                                  valve substitutes.
------------------------------------------------------------------------
                  D. Dental/Ear, Nose, and Throat (ENT)
------------------------------------------------------------------------
4-89...........  ..............  ANSI/ADA Standard No.  Withdrawn.
                                  53--2008 (R2013)
                                  Polymer-Based Crown
                                  and Bridge Materials.
------------------------------------------------------------------------
4-282..........           4-284  ISO 10873 Second       Withdrawn and
                                  edition 2021-07        replaced with
                                  Dentistry--Denture     newer version.
                                  adhesives.
------------------------------------------------------------------------

         E. General I (Quality Systems/Risk Management) (QS/RM)
------------------------------------------------------------------------
5-117..........           5-134  ISO 15223-1 Fourth     Withdrawn and
                                  edition 2021-07        replaced with
                                  Medical devices--      newer version.
                                  Symbols to be used
                                  with medical device
                                  labels, labelling,
                                  and information to
                                  be supplied--Part 1:
                                  General requirements.
------------------------------------------------------------------------
F. General II (Electrical Safety/Electromagnetic Compatibility) (ES/EMC)
------------------------------------------------------------------------
19-34..........           19-41  ANSI/UL 61010-1 3rd    Withdrawn and
                                  Ed, dated May 12,      replaced with
                                  2012 with revision     newer version.
                                  through July 19,
                                  2019 Standard for
                                  Safety for
                                  Electrical Equipment
                                  For Measurement,
                                  Control and
                                  Laboratory Use; Part
                                  1: General
                                  Requirements.
------------------------------------------------------------------------
          G. General Hospital/General Plastic Surgery (GH/GPS)
------------------------------------------------------------------------
6-365..........           6-464  ISO 11040-4 Third      Withdrawn and
                                  edition 2015-04-01     replaced with
                                  Prefilled syringes--   newer version.
                                  Part 4: Glass
                                  barrels for
                                  injectables and
                                  sterilized
                                  subassembled
                                  syringes ready for
                                  filling [Including
                                  AMENDMENT 1 (2020)].
6-451..........           6-465  USP-NF M76090_03_01    Withdrawn and
                                  Sodium Chloride        replaced with
                                  Irrigation.            newer version.
6-452..........           6-466  USP-NF M76070_03_01    Withdrawn and
                                  Sodium Chloride        replaced with
                                  Injection.             newer version.
6-453..........           6-467  USP-NF M80200_04_01    Withdrawn and
                                  Nonabsorbable          replaced with
                                  Surgical Suture.       newer version.
6-454..........           6-468  USP-NF M99670_02_01    Withdrawn and
                                  <881> Tensile          replaced with
                                  Strength.              newer version.
6-455..........           6-469  USP-NF M99650_02_01    Withdrawn and
                                  <861> Sutures--        replaced with
                                  Diameter.              newer version.
6-456..........           6-470  USP-NF M99660_03_01    Withdrawn and
                                  <871> Sutures--        replaced with
                                  Needle Attachment.     newer version.
6-457..........           6-471  USP-NF M88880_05_01    Withdrawn and
                                  Sterile Water for      replaced with
                                  Irrigation.            newer version.
6-458..........           6-472  USP-NF M36660_04_01    Withdrawn and
                                  Heparin Lock Flush     replaced with
                                  Solution..             newer version.
6-459..........           6-473  USP-NF M80190_04_01    Withdrawn and
                                  Absorbable Surgical    replaced with
                                  Suture.                newer version.
------------------------------------------------------------------------
                      H. In Vitro Diagnostics (IVD)
------------------------------------------------------------------------
                      No new entries at this time.
------------------------------------------------------------------------
                              I. Materials
------------------------------------------------------------------------
8-103..........           8-563  ASTM F1801-20          Withdrawn and
                                  Standard Practice      replaced with
                                  for Corrosion          newer version.
                                  Fatigue Testing of
                                  Metallic Implant
                                  Materials.
8-121..........           8-564  ASTM F2005-21          Withdrawn and
                                  Standard Terminology   replaced with
                                  for Nickel-Titanium    newer version.
                                  Shape Memory Alloys.
8-193..........           8-565  ASTM F2754/F2754M-21   Withdrawn and
                                  Standard Test Method   replaced with
                                  for Measurement of     newer version.
                                  Camber Cast Helix
                                  and Direction of
                                  Helix of Coiled Wire.
8-346..........           8-566  ASTM F1813-21          Withdrawn and
                                  Standard               replaced with
                                  Specification for      newer version.
                                  Wrought Titanium--12
                                  Molybdenum--6
                                  Zirconium--2 Iron
                                  Alloy for Surgical
                                  Implant (UNS R58120).
8-353..........           8-567  ASTM F86-21 Standard   Withdrawn and
                                  Practice for Surface   replaced with
                                  Preparation and        newer version.
                                  Marking of Metallic
                                  Surgical Implants.
8-355..........           8-568  ASTM F1586-21          Withdrawn and
                                  Standard               replaced with
                                  Specification for      newer version.
                                  Wrought Nitrogen
                                  Strengthened 21
                                  Chromium-10 Nickel-3
                                  Manganese-2.5
                                  Molybdenum Stainless
                                  Steel Bar for
                                  Surgical Implants
                                  (UNS S31675).
8-385..........           8-569  ASTM F648-21 Standard  Withdrawn and
                                  Specification for      replaced with
                                  Ultra-High-Molecular-  newer version.
                                  Weight Polyethylene
                                  Powder and
                                  Fabricated Form for
                                  Surgical Implants.
8-398..........           8-570  ASTM F1108-21          Withdrawn and
                                  Standard               replaced with
                                  Specification for      newer version.
                                  Titanium-6Aluminum-
                                  4Vanadium Alloy
                                  Castings for
                                  Surgical Implants.
8-422..........           8-571  ASTM F2052-21          Withdrawn and
                                  Standard Test Method   replaced with
                                  for Measurement of     newer version.
                                  Magnetically Induced
                                  Displacement Force
                                  on Medical Devices
                                  in the Magnetic
                                  Resonance
                                  Environment.
8-423..........           8-572  ASTM F2565-21          Withdrawn and
                                  Standard Guide for     replaced with
                                  Extensively            newer version.
                                  Irradiation-
                                  Crosslinked Ultra-
                                  High Molecular
                                  Weight Polyethylene
                                  Fabricated Forms for
                                  Surgical Implant
                                  Applications.
8-424..........           8-573  ASTM F2695-12(2020)    Withdrawn and
                                  Standard               replaced with
                                  Specification for      newer version.
                                  Ultra-High Molecular
                                  Weight Polyethylene
                                  Powder Blended With
                                  Alpha-Tocopherol
                                  (Vitamin E) and
                                  Fabricated Forms for
                                  Surgical Implant
                                  Applications.

8-425..........           8-574  ASTM F2820-12(2021)e1  Withdrawn and
                                  Standard               replaced with
                                  Specification for      newer version.
                                  Polyetherketoneketon
                                  e (PEKK) Polymers
                                  for Surgical Implant
                                  Applications.
8-443..........           8-575  ASTM F3160-21          Withdrawn and
                                  Standard Guide for     replaced with
                                  Metallurgical          newer version.
                                  Characterization of
                                  Absorbable Metallic
                                  Materials for
                                  Medical Implants.
8-450..........           8-576  ASTM F451-21 Standard  Withdrawn and
                                  Specification for      replaced with
                                  Acrylic Bone Cement.   newer version.
8-456..........           8-577  ISO 13179-1 Second     Withdrawn and
                                  Edition 2021-09        replaced with
                                  Implants for           newer version.
                                  surgery--Coatings on   Title change.
                                  metallic surgical
                                  implants--Part 1:
                                  Plasma-sprayed
                                  coatings derived
                                  from titanium or
                                  titanium-6 aluminum-
                                  4 vanadium alloy
                                  powders.
8-460..........           8-578  ASTM F2848-21          Withdrawn and
                                  Standard               replaced with
                                  Specification for      newer version.
                                  Medical-Grade Ultra-
                                  High-Molecular-
                                  Weight Polyethylene
                                  Yarns.
8-515..........           8-579  ISO 13779-3 Second     Withdrawn and
                                  Edition 2018-12        replaced with
                                  Implants for           newer version.
                                  surgery--Hydroxyapat
                                  ite--Part 3:
                                  Chemical analysis
                                  and characterization
                                  of crystallinity
                                  ratio and phase
                                  purity [Including
                                  AMENDMENT 1 (2021)].
------------------------------------------------------------------------
                            J. Nanotechnology
------------------------------------------------------------------------
                      No new entries at this time.
------------------------------------------------------------------------
                              K. Neurology
------------------------------------------------------------------------
                      No new entries at this time.
------------------------------------------------------------------------
  L. Obstetrics-Gynecology/Gastroenterology/Urology (OB-Gyn/G/Urology)
------------------------------------------------------------------------
                      No new entries at this time.
------------------------------------------------------------------------
                              M. Ophthalmic
------------------------------------------------------------------------
10-73..........          10-127  ANSI Z80.21-2020       Withdrawn and
                                  American National      replaced with
                                  Standard for           newer version.
                                  Ophthalmics--Instrum
                                  ents--General-
                                  Purpose Clinical
                                  Visual Acuity Charts.
10-87..........          10-128  ASTM D882-18 Standard  Withdrawn and
                                  Test Method for        replaced with
                                  Tensile Properties     newer version.
                                  of Thin Plastic
                                  Sheeting.
10-88..........          10-129  ASTM D790-17 Standard  Withdrawn and
                                  Test Methods for       replaced with
                                  Flexural Properties    newer version.
                                  of Unreinforced and
                                  Reinforced Plastics
                                  and Electrical
                                  Insulating Materials.
10-102.........          10-130  ANSI Z80.36-2021       Withdrawn and
                                  American National      replaced with
                                  Standard for           newer version.
                                  Ophthalmics--Light
                                  Hazard Protection
                                  for Ophthalmic
                                  Instruments.
------------------------------------------------------------------------
                              N. Orthopedic
------------------------------------------------------------------------
11-239.........          11-385  ASTM F2345-21          Withdrawn and
                                  Standard Test          replaced with
                                  Methods for            newer version.
                                  Determination of
                                  Cyclic Fatigue
                                  Strength of Ceramic
                                  Modular Femoral
                                  Heads.
11-266.........          11-386  ASTM F2665-21          Withdrawn and
                                  Standard               replaced with
                                  Specification for      newer version.
                                  Total Ankle
                                  Replacement
                                  Prosthesis.
11-305.........          11-387  ASTM F1781-21          Withdrawn and
                                  Standard               replaced with
                                  Specification for      newer version.
                                  Elastomeric Flexible
                                  Hinge Finger Total
                                  Joint Implants.
11-345.........          11-388  ASTM F1717-21          Withdrawn and
                                  Standard Test          replaced with
                                  Methods for Spinal     newer version.
                                  Implant Constructs
                                  in a Vertebrectomy
                                  Model.
11-359.........          11-389  ISO 7206-10 Second     Withdrawn and
                                  edition 2018-08        replaced with
                                  Implants for           newer version.
                                  surgery--Partial and
                                  total hip-joint
                                  prostheses--Part 10:
                                  Determination of
                                  resistance to static
                                  load of modular
                                  femoral heads
                                  [Including AMENDMENT
                                  1 (2021)].
------------------------------------------------------------------------
                          O. Physical Medicine
------------------------------------------------------------------------
                      No new entries at this time.
------------------------------------------------------------------------
                              P. Radiology
------------------------------------------------------------------------
12-299.........          12-341  IEC 62563-1 Edition    Withdrawn and
                                  1.2 2021-07            replaced with
                                  CONSOLIDATED VERSION   newer version.
                                  Medical electrical
                                  equipment--Medical
                                  image display
                                  systems--Part 1:
                                  Evaluation methods.
12-300.........          12-342  NEMA DICOM PS 3.1--    Withdrawn and
                                  3.20 2021e Digital     replaced with
                                  Imaging and            newer version.
                                  Communications in
                                  Medicine (DICOM) Set.
------------------------------------------------------------------------

                         Q. Software/Informatics
------------------------------------------------------------------------
13-46..........  ..............  ASTM F2761-09 (2013)   Withdrawn. See
                                  Medical Devices and    13-120.
                                  Medical Systems--
                                  Essential safety
                                  requirements for
                                  equipment comprising
                                  the patient-centric
                                  integrated clinical
                                  environment (ICE)--
                                  Part 1: General
                                  requirements and
                                  conceptual model.
------------------------------------------------------------------------
                              R. Sterility
------------------------------------------------------------------------
14-424.........          14-563  ISO 13408-6 Second     Withdrawn and
                                  edition 2021-04        replaced with
                                  Aseptic processing     newer version.
                                  of health care
                                  products--Part 6:
                                  Isolator systems.
14-555.........          14-564  USP-NF M98910_01_01    Withdrawn and
                                  <161> Medical          replaced with
                                  Devices-Bacterial      newer version.
                                  Endotoxin and
                                  Pyrogen Tests.
14-556.........          14-565  USP-NF M98802_01_01    Withdrawn and
                                  <62> Microbiological   replaced with
                                  Examination of         newer version.
                                  Nonsterile Products:
                                  Tests for Specified
                                  Microorganisms.
14-557.........          14-566  USP-NF M98795_02_01    Withdrawn and
                                  <55> Biological        replaced with
                                  Indicators--Resistan   newer version.
                                  ce Performance Tests.
14-558.........          14-567  USP-NF M7414_01_01     Withdrawn and
                                  <1229.5> Biological    replaced with
                                  Indicators for         newer version.
                                  Sterilization.
14-559.........          14-568  USP-NF M98800_01_01    Withdrawn and
                                  <61> Microbiological   replaced with
                                  Examination of         newer version.
                                  Nonsterile Products:
                                  Microbial
                                  Enumeration Tests.
14-560.........          14-569  USP-NF M98810_01_01    Withdrawn and
                                  <71> Sterility Tests.  replaced with
                                                         newer version.
14-561.........          14-570  USP-NF M98830_02_01    Withdrawn and
                                  <85> Bacterial         replaced with
                                  Endotoxins Test.       newer version.
------------------------------------------------------------------------
                          S. Tissue Engineering
------------------------------------------------------------------------
15-29..........  ..............  ASTM F2259-10          Withdrawn.
                                  (Reapproved 2012)e1
                                  Standard Test Method
                                  for Determining the
                                  Chemical Composition
                                  and Sequence in
                                  Alginate by Proton
                                  Nuclear Magnetic
                                  Resonance (1H NMR)
                                  Spectroscopy.
------------------------------------------------------------------------
\1\ All standard titles in this table conform to the style requirements
  of the respective organizations.

III. Listing of New Entries

    In table 2, FDA provides the listing of new entries and consensus
standards added as modifications to the list of recognized standards
under Recognition List Number: 057. These entries are of standards not
previously recognized by FDA.

        Table 2--New Entries to the List of Recognized Standards
------------------------------------------------------------------------
                                                     Reference No. and
   Recognition No.        Title of standard \1\             date
------------------------------------------------------------------------
                            A. Anesthesiology
------------------------------------------------------------------------
                      No new entries at this time.
------------------------------------------------------------------------
                           B. Biocompatibility
------------------------------------------------------------------------
                      No new entries at this time.
------------------------------------------------------------------------
                            C. Cardiovascular
------------------------------------------------------------------------
3-176................  Cardiovascular implants     ISO 18193 First
                        and artificial organs--     edition 2021-08.
                        Cannulae for
                        extracorporeal
                        circulation.
3-177................  Standard Guide for Three-   ASTM F2606-08
                        Point Bending of Balloon-   (Reapproved 2021).
                        Expandable Vascular
                        Stents and Stent Systems.
3-178................  Standard Guide for Radial   ASTM F3067-14
                        Loading of Balloon-         (Reapproved 2021).
                        Expandable and Self-
                        Expanding Vascular Stents.
3-179................  Standard Guide for Design   ASTM F3172-15
                        Verification Device Size    (Reapproved 2021).
                        and Sample Size Selection
                        for Endovascular Devices.
3-180................  Standard Test Method for    ASTM F3505-21.
                        Stent and Endovascular
                        Prosthesis Kink
                        Resistance.
------------------------------------------------------------------------
                  D. Dental/Ear, Nose, and Throat (ENT)
------------------------------------------------------------------------
4-285................  Dental Abrasive Powders...  ANSI/ADA Standard No.
                                                    37--1986 (R2020).
4-286................  Dental Impression Trays...  ANSI/ADA Standard No.
                                                    87--1995 (R2014).

4-287................  Oral Rinses (Modified       ANSI/ADA Standard No.
                        adoption of ISO             116--2020.
                        16408:2015, Dentistry
                        Oral Care Products--Oral
                        Rinses).
4-288................  Dentistry--Mixing machines  ISO 7488 Second
                        for dental amalgam.         edition 2018-04.
4-289................  Dentistry--Intraoral        ISO 18556 First
                        spatulas.                   edition 2016-04.
4-290................  Dentistry--Integrated       ISO 28158 Second
                        dental floss and handles.   edition 2018-09.
4-291................  Dentistry--Products for     ISO 28399 First
                        external tooth bleaching.   edition 2011-01.
4-292................  Dentistry--Screening        ISO 28888 First
                        method for erosion          edition 2013-10.
                        potential of oral rinses
                        on dental hard tissues.
------------------------------------------------------------------------
         E. General I (Quality Systems/Risk Management) (QS/RM)
------------------------------------------------------------------------
                      No new entries at this time.
------------------------------------------------------------------------
F. General II (Electrical Safety/Electromagnetic Compatibility) (ES/EMC)
------------------------------------------------------------------------
19-42................  Electrical equipment for    IEC 61326-1 Edition
                        measurement, control and    3.0 2020-10.
                        laboratory use--EMC
                        requirements--Part 1:
                        General requirements.
19-43................  Electrical equipment for    IEC 61326-2-6 Edition
                        measurement, control and    3.0 2020-10.
                        laboratory use--EMC
                        requirements--Part 2-6:
                        Particular requirements--
                        In vitro diagnostic (IVD)
                        medical equipment.
19-44................  American National           ANSI/IEEE C63.24-
                        Standard--Recommended       2021.
                        Practice for In Situ RF
                        Immunity Evaluation of
                        Electronic Devices and
                        Systems.
------------------------------------------------------------------------
          G. General Hospital/General Plastic Surgery (GH/GPS)
------------------------------------------------------------------------
6-474................  Standard Specification for  ASTM F3352-19.
                        Isolation Gowns Intended
                        for Use in Healthcare
                        Facilities.
                      H. In Vitro Diagnostics (IVD)
------------------------------------------------------------------------
7-309................  Radiological protection--   ISO 17099 First
                        Performance criteria for    edition 2014-11-15.
                        laboratories using the
                        cytokinesis block
                        micronucleus (CBMN) assay
                        in peripheral blood
                        lymphocytes for
                        biological dosimetry.
7-310................  Radiological protection--   ISO 19238 Second
                        Performance criteria for    edition 2014-02-01.
                        service laboratories
                        performing biological
                        dosimetry by cytogenetics.
7-311................  A Hierarchical Approach to  CLSI EP39, 1st
                        Selecting Surrogate         Edition
                        Samples for the
                        Evaluation of In Vitro
                        Medical Laboratory Tests.
------------------------------------------------------------------------
                              I. Materials
------------------------------------------------------------------------
8-580................  Eyewear display--Part 20-   IEC 63145-20-10
                        10: Fundamental             Edition 1.0 2019-08.
                        measurement methods--
                        Optical properties.
8-581................  Eyewear display--Part 20-   IEC 63145-20-20
                        20: Fundamental             Edition 1.0 2019-09.
                        measurement methods--
                        Image quality.
8-582................  Eyewear display--Part 22-   IEC 63145-22-10
                        10: Specific measurement    Edition 1.0 2020-01.
                        methods for AR type--
                        Optical properties.
------------------------------------------------------------------------
                            J. Nanotechnology
------------------------------------------------------------------------
18-19................  Nanotechnologies--Measurem  ISO 19749 First
                        ents of particle size and   edition 2021-07.
                        shape distributions by
                        scanning electron
                        microscopy.
18-20................  Standard Guide for          ASTM E3275-21.
                        Visualization and
                        Identification of
                        Nanomaterials in
                        Biological and
                        Nonbiological Matrices
                        Using Darkfield
                        Microscopy/Hyperspectral
                        Imaging (DFM/HSI)
                        Analysis.
------------------------------------------------------------------------
                              K. Neurology
------------------------------------------------------------------------
                      No new entries at this time.
------------------------------------------------------------------------
  L. Obstetrics-Gynecology/Gastroenterology/Urology (OB-Gyn/G/Urology)
------------------------------------------------------------------------
                      No new entries at this time.
------------------------------------------------------------------------
                              M. Ophthalmic
------------------------------------------------------------------------
                      No new entries at this time.
------------------------------------------------------------------------
                              N. Orthopedic
------------------------------------------------------------------------
11-390...............  Implants for surgery--Pre-  ISO 23089-2 First
                        clinical mechanical         edition 2021-05.
                        assessment of spinal
                        implants and particular
                        requirements--Part 2:
                        Spinal intervertebral
                        body fusion devices.
11-391...............  Standard Practice for       ASTM F2722-21.
                        Evaluating Mobile Bearing
                        Knee Tibial Baseplate
                        Rotational Stops.
11-392...............  Standard Test Method for    ASTM F2723-21.
                        Evaluating Mobile Bearing
                        Knee Tibial Baseplate/
                        Bearing Resistance to
                        Dynamic Disassociation.

11-393...............  Standard Test Method for    ASTM F2724-21.
                        Evaluating Mobile Bearing
                        Knee Dislocation.
------------------------------------------------------------------------
                          O. Physical Medicine
------------------------------------------------------------------------
16-232...............  Medical electrical          IEC 80601-2-78
                        equipment--Part 2-78:       Edition 1.0 2019-07.
                        Particular requirements
                        for basic safety and
                        essential performance of
                        medical robots for
                        rehabilitation,
                        assessment, compensation
                        or alleviation.
------------------------------------------------------------------------
                              P. Radiology
------------------------------------------------------------------------
                      No new entries at this time.
------------------------------------------------------------------------
                         Q. Software/Informatics
------------------------------------------------------------------------
13-120...............  Medical Devices and         ANSI/AAMI 2700-
                        Medical Systems--           1:2019.
                        Essential safety
                        requirements for
                        equipment comprising the
                        patient-centric
                        integrated clinical
                        environment (ICE)--Part
                        1: General requirements
                        and conceptual model.
------------------------------------------------------------------------
                              R. Sterility
------------------------------------------------------------------------
14-571...............  Sterilization of health     ISO 11138-8 First
                        care products--Biological   edition 2021-07.
                        indicators--Part 8:
                        Method for validation of
                        a reduced incubation time
                        for a biological
                        indicator.
------------------------------------------------------------------------
                          S. Tissue Engineering
------------------------------------------------------------------------
                      No new entries at this time.
------------------------------------------------------------------------
\1\ All standard titles in this table conform to the style requirements
  of the respective organizations.

IV. List of Recognized Standards

    FDA maintains the current list of FDA Recognized Consensus
Standards in a searchable database that may be accessed at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfStandards/search.cfm. Such
standards are those that FDA has recognized by notice published in the
Federal Register or that FDA has decided to recognize but for which
recognition is pending (because a periodic notice has not yet appeared
in the Federal Register). FDA will announce additional modifications
and revisions to the list of recognized consensus standards, as needed,
in the Federal Register once a year, or more often if necessary.

V. Recommendation of Standards for Recognition by FDA

    Any person may recommend consensus standards as candidates for
recognition under section 514 of the FD&C Act by submitting such
recommendations, with reasons for the recommendation, to
[email protected]. To be considered, such recommendations
should contain, at a minimum, the information available at https://www.fda.gov/medical-devices/device-advice-comprehensive-regulatory-assistance/standards-and-conformity-assessment-program#process.

    Dated: April 18, 2022.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2022-08571 Filed 4-21-22; 8:45 am]
BILLING CODE 4164-01-P


>>> "Mary Bachynsky/FPC Environmental Dept."<EMAIL_ADDRESS>1/14/2008 1:41 PM >>>

Hello Greg, Below is our response to your questions. Upon your review, please let us know of any additional questions or comments.

Q1. Are VI members working on assembling the information for #5 (i.e., mass balance information around reactors, strippers and control devices), or did you want us to provide feedback before that got underway?

A1. The VI Members were hoping for EPA feedback before getting underway with mass balance estimates.

Our approach at this point would be to use generic process flow diagrams and generic process descriptions for each PVC production process, and provide range estimates of Lb/hr, T/Yr and Lb/MMlb/yr. The Members would like to identify HAP emissions sources that have a minimal potential for emissions from the operation, which would allow both EPA and the VI Members to focus on the more significant potential HAP sources. In our experience, mass balances for small quantities of pollutants do not typically work well when actual data does not exist. Regarding mass balance information, for the more significant HAP emission sources (reactors, strippers and control devices), our plan is to provide an aggregated mass balance, based on available information, and would include range estimates. Would you please provide feedback as to whether this approach is acceptable to EPA?

Q.2 The facility list shows a Dow plant in Texas City, TX.  Dow's website doesn't mention that this plant manufactures PVC products, but does mention some products that fall under the MON, so we wanted to verify their inclusion here is correct.  If so, will they be participating through the VI or on their own behalf?

A.2 Dow is not a member of the VI. However, the Dow representative working with the VI on another environmental matter was contacted and your question was provided to the contact. The Dow contact is routing the information to the correct Dow representative and will provide information shortly.

Q3. Of the three process diagrams only the second one is labeled.  Can you label the other two?

A3. Attached, please find a copy of the labeled flow diagrams, which were included in EPA’s February 1982 "Vinyl Chloride- A Review of National Emission Standard" document (EPA-450/3-82-003).

Q.4 In the second process diagram, there is no stripper identified, but notes on the left side of the page indicate that stripping is part of the process.  Is the reactor used as the stripper?  Is that typical for the bulk process?

A.4 We believe that the stripping activity occurs within the Post-polymerization reactor (number 4 on Figure 3-4). We have requested confirmation of our understanding from a Bulk PVC producer and will advise the agency if our understanding is not correct.

Q.5. The 3rd process diagram does not mention stripping of any kind.  I don’t recall this being discussed in October, so if that can be described it would be helpful.

A.5. The 3rd process flow diagram addresses the Solution PVC production process. We believe, as per EPA’s 1982 review document, that there is only one Solution PVC Plant in the US. It appears that the plant may be Dow’s in Texas City, TX. Dow may be better able to address this question. Again, this will be confirmed, once Dow determines who its PVC MACT contact will be. A process description will be included, as per our response in A.1.

Q6. Some streams going to water strippers are identified on the diagrams.  Can you provide information about the presence/absence of VCM or any other compounds in those streams?

A.6. VI Members may have estimated data on some HAPs into the wastewater strippers and some measured data on wastewater stripper discharges (namely VCM). We will address wastewater streams on the generic flow diagrams to the best of our ability.

We appreciate the agency’s willingness to guide us through the data development phase, and look forward to your feedback.

Regards, Mary

Mary P. Bachynsky  Formosa Plastics Corp. U.S. A.  9 Peach Tree Hill Road  Livingston, New Jersey  07039  Phone:<PHONE_NUMBER>   Cell:<PHONE_NUMBER>  <EMAIL_ADDRESS><EMAIL_ADDRESS> -----Original Message----- From<EMAIL_ADDRESS><EMAIL_ADDRESS>Sent: Monday, January 07, 2008 1:24 PM To: Mary Bachynsky/FPC Environmental Dept<EMAIL_ADDRESS>Cc<EMAIL_ADDRESS>Subject: Re: VI PVC MACT Submittal

Hi Mary and Peter,   Hope you enjoyed the holidays, but now it's back to PVC. . .   We have looked over the submittal that Frank sent in December and it looks to be heading in the right direction.  About a month before our October meeting, I sent Frank an email with a summary of our overall informational needs.  Here is the list from that email:   1.  Confirm that our PVC facility inventory is complete; 2.  Identify which emission point data are PVC, VCM, EDC, chlor-alkali (C/A), or other (provide description); [we provided a column for them to do this in each spreadsheet] 3.  Key the records to a process diagram or flowsheet so that we may easily identify which parts of the process these emissions are coming from [there is a comments field where they may include this];  The process diagram would be generated by each company. 4.  Provide descriptions for emission unit and control device where these are left blank or left unspecified; 5.  In addition, we would like industry to provide mass balance information around the reactors, strippers and control devices (list all inputs and outputs, including vent stream composition and flowrate on a per production rate).

From the information just received it looks like items 1, 3 and 4 are close to being satisfied, with #5 being the main item to address.  I think by going the process diagram route #2 is no longer being pursued.  Are VI members working on assembling the information for #5, or did you want us to provide feedback before that got underway? The recent submittal also raised a couple questions that are listed below:   - The facility list shows a Dow plant in Texas City, TX.  Dow's website doesn't mention that this plant manufactures PVC products, but does mention some products that fall under the MON, so we wanted to verify their inclusion here is correct.  If so, will they be participating through the VI or on their own behalf?    - Of the three process diagrams only the second one is labeled.  Can you label the other two?  In the second process diagram, there is no stripper identified, but notes on the left side of the page indicate that stripping is part of the process.  Is the reactor used as the stripper?  Is that typical for the bulk process?    - The 3rd process diagram does not mention stripping of any kind.  I dont' recall this being discussed in October, so if that can be described it would be helpful.   - Some streams going to water strippers are identified on the diagrams.  Can you provide information about the presence/absence of VCM or any other compounds in those streams?   Let me know if you need to discuss further.  Thanks.  Greg.   Greg Nizich, OAQPS, Sector Policy and Programs Div. Coatings and Chemicals Group 919-469-6687.

  -----"Borrelli, Frank"<EMAIL_ADDRESS>wrote: -----

To: Greg Nizich/RTP/USEPA/US@EPA From: "Borrelli, Frank"<EMAIL_ADDRESS>Date: 12/21/2007 03:31PM cc<EMAIL_ADDRESS><EMAIL_ADDRESS><EMAIL_ADDRESS>"de la Cruz, Peter"<EMAIL_ADDRESS><EMAIL_ADDRESS>"Givonetti, Raymond"<EMAIL_ADDRESS><EMAIL_ADDRESS>"John Yonge"<EMAIL_ADDRESS><EMAIL_ADDRESS>"Sheridan, Kevin"<EMAIL_ADDRESS>"Sistrunk, Otis J. (PED)"<EMAIL_ADDRESS>"Tinsley, Wendell"<EMAIL_ADDRESS>"TOM BERGER"<EMAIL_ADDRESS><EMAIL_ADDRESS><EMAIL_ADDRESS>Subject: VI PVC MACT Submittal

Dear Greg,

As discussed at our meeting, enclosed please find four documents.  The first is an updated list of PVC production facilities, their nameplate capacities and current operators based on data from CMAI.  I have also included generic process flow sheets that we intend to enhance as we develop the additional information on HAPs associated with the PVC process.  We think that the flow sheets accurately describe the boundary of the PVC process as they were part of the docket on the original NESHAP back in the 1970’s.

The third document is a list of potential HAPs that may be associated with PVC production.  Substances are listed based on responses to a survey of VI member companies.  Please note that we have included substances in the list even if they were reported by only one facility.  In addition, we listed materials without regard to the amount involved or potential for emissions.  Our goal was to define the universe of potential HAPs that might fall under the PVC MACT rule with the understanding that both the need for inclusion in the rule or the need to develop a surrogacy analysis would come at a later date.  The inclusion of a substance on this list does not reflect any agreement by the VI or its members that the substance merits regulation under the PVC MACT.  We have not included vinyl chloride monomer on the list because we understand that the agency will certainly include that HAP in the regulation.  We have attempted to identify the possible source and noted expected fate of these HAPS following the polymerization step of the PVC process.   A number of these HAPs are identified as VCM impurities.  These HAPS normally exist at trace levels in commercial monomer grade vinyl chloride. They remain in the vinyl chloride monomer following the purification steps in a vinyl chloride process as a result of having  similar physical properties, (volatility and solubility), as vinyl chloride but normally exist at part per million (ppm) levels.  In some cases, certain HAPs would undergo free radical polymerization similarly to the vinyl chloride and become part of the PVC polymer molecule.  In other cases they may remain and concentrate in the recovered vinyl chloride until they enter the vinyl chloride process vent gas control system.   I have also included a vinyl chloride specification sheet that provides expected maximum levels of these impurities in normal commercial grade vinyl chloride.  Actual levels are expected to be much lower.

We had looked into you concerns on compounding operations and offer the following.   Under the Miscellaneous Organic NESHAP (Part 63 Subpart FFFF), EPA determined at 40 CFR 63.2435(a), (b) and (c), that a Unit which is located at, or is part of, a major source of hazardous air pollutants (HAP) engaged in compounding purchased plastic resin is exempt from the MACT Standard.  This is due to the minimal potential for emissions from such an operation.  For the same reason, EPA determined that a Unit which is located at, or is part of, a major source of HAPs, engaged in compounding its own resin is also exempt from the MACT Standard, as long as the compounding operation does not involve processing with HAP solvent or the intended purpose of the operation is to remove residual HAP monomer.

After you have an opportunity to review this information, we would like to discuss the next steps, which we believe would involve the quantification of potential HAPS and information regarding surrogacy.  If you have any immediate questions, please do not hesitate to contact us.   As you know I will be retiring at year end and in the interim ask that you contact   Peter de la Cruz of Keller and Heckman and Mary Bachynsky of Formosa Plastics regarding this program.  It has been a pleasure working with you, good luck with your efforts and have a wonderful holiday season.

Regards

Frank Borrelli

Mary P. Bachynsky  Formosa Plastics Corp. U.S. A.  9 Peach Tree Hill Road  Livingston , New Jersey   07039  Phone:<PHONE_NUMBER>   Cell:<PHONE_NUMBER>  m<EMAIL_ADDRESS><EMAIL_ADDRESS>>

Peter L. de la Cruz  Partner Keller and Heckman

1001 G Street, N.W., Suite 500 West | Washington , D.C. 20001  Tel:<PHONE_NUMBER> | fax<PHONE_NUMBER> |<EMAIL_ADDRESS>

____________________________________________________________ This communication is solely for use by the intended recipient and may contain information that is privileged, confidential or copyrighted under applicable law. If you are not the intended recipient, you are hereby formally notified that any use, copying or distribution of this communication, in whole or in part, is strictly prohibited. Unless explicitly stated, this communication does not constitute a contract offer, a contract amendment, or an acceptance of a contract offer. This communication also does not constitute consent to the use of sender's contact information for direct marketing purposes or for transfers of data to third parties.


EPA REGISTRATION DIVISION COMPANY NOTICE OF FILING FOR PESTICIDE PETITIONS PUBLISHED IN THE FEDERAL REGISTER

EPA Registration Division contact: [Jennifer Gaines --<PHONE_NUMBER>]

INSTRUCTIONS:  Please utilize this outline in preparing the pesticide petition.  In cases where the outline element does not apply, please insert "NA-Remove" and maintain the outline. Please do not change the margins, font, or format in your pesticide petition. Simply replace the instructions that appear in green, i.e., "[insert company name]," with the information specific to your action.

TEMPLATE:

Makhteshim Agan of North America, Inc.

5F3865

	EPA has received a pesticide petition ([5F3865]) from Makhteshim Agan of North America, Inc (d/b/a ADAMA), 3120 Highwoods Blvd, Suite 100, Raleigh, NC 27604 requesting, pursuant to section 408(d) of the Federal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 346a(d), to amend 40 CFR part 180

   	By establishing a tolerance for residues of

	Fluensulfone (to be measured by residues of 3,4,4-trifluoro-but-3-end-1-sulfonic acid, expressed as the stoichiometric equivalent of fluensulfone) in or on tomato, paste at 1 ppm.  EPA has determined that the petition contains data or information regarding the elements set forth in section 408 (d)(2) of  FDDCA; however, EPA has not fully evaluated the sufficiency of the submitted data at this time or whether the data supports granting of the petition. Additional data may be needed before EPA rules on the petition.

A. Residue Chemistry

      1. Plant metabolism.  Fluensulfone is supported by a complete plant metabolism data package based on the uses in fruiting vegetables (crop group 8) and cucurbit vegetables (crop group 9).  In all plant matrices, whether from a primary or rotational crop, a clear pattern was observed with TSA (M-3625) and BSA (M-3627) forming the majority of the residues following the cleavage of fluensulfone.  Neither compound has acute oral toxicity greater than parent fluensulfone or shows any genotoxic potential in a range of mutagenicity studies.  The residues definition for both monitoring and risk assessment should therefore be the sum of TSA and BSA, expressed as fluensulfone equivalents.

	2. Analytical method. Adequate analytical methods for determining fluensulfone in/on appropriate raw agricultural commodities and processed commodities have been developed and validated, including LC-MS/MS methods.  The analytical procedures have been successfully validated in terms of specificity, linearity, precision, accuracy and LOQ.

      The MRM study demonstrates that the FDA multiresidue methods (MRMs) are not suitable for detection and enforcement of fluensulfone residues as sulfonic acid metabolites in non-fatty matrices.

	3. Magnitude of residues. Fluensulfone is proposed for use on processing tomatoes. To support these uses ADAMA sponsored a tomato processing study involving two (2) field trial locations in the United States; one trial in California and one trial in Florida.  Fluensulfone and M-3627 (BSA) were sought in all samples. The LOQ is 0.01 mg/kg. EPA removed the fluensulfone metabolite methyl sulfone (M- 3626) and thiazole sulfonic acid (TSA, M-3625) from the residue definition therefore these were not included in the residue analysis.

Adequate data are available to propose this tolerance (MRL) and there is no unacceptable risk to consumers from the consumption of processing tomatoes treated with formulations containing fluensulfone.

B. Toxicological Profile

      1. Acute toxicity.  The acute oral LD50 is 671 mg/kg bw in rats.  The acute dermal LD50 of fluensulfone is >2000 mg/kg bw.  The acute inhalation LD50 in rats is >5.1 mg/L.  Fluensulfone displayed no eye irritation in rabbits.  Fluensulfone is not irritating to the skin and is a skin sensitizer.

      2. Genotoxicty. A complete data package of in vitro and in vivo mutagenicity studies is available for fluensulfone.  A full summary of the genotoxicity database is provided in the OECD Dossier.  On the basis of the robust in vitro and in vivo mutagenicity data, it is concluded that fluensulfone does not possess any genotoxic potential.

      3. Reproductive and developmental toxicity. The reproductive toxicity of fluensulfone was evaluated in a 2-generation reproduction study in rats. Developmental toxicity was assessed in rats and rabbits.

      Reproductive toxicity.  A 2-generation reproduction study in rats was conducted at dose levels of 0, 30, 250 and 1800 ppm (2.0, 16.2, and 122.0 mg/kg/day in males and 2.8, 23.0 and 169.1 mg/kg/day in females).  Treatment with fluensulfone up to and including 1800 ppm, the highest tested dose level, showed no effects on reproductive function, including gonadal function, mating behavior, fertility, viability of offspring, breeding, conception, gestation and parturition.               Parental systemic toxicity was evident however, with effects on body weight development throughout the study observed at 1800 ppm (the LOAEL); hence the NOAEL was set at 250 ppm (equivalent to approximately 16.2 mg/kg/day in males and 23.0 mg/kg /day in females). A NOAEL for general toxicity in F1 and F2 pups was established at 250 ppm, based on reduced pup weight noted at 1800 ppm.              Developmental toxicity.  Fluensulfone was not teratogenic or fetotoxic either in rats or rabbits.               A pre-natal developmental study in rats included dose groups of 0, 7.7, 48.6, and 292.0 mg/kg/day.  Maternal toxicity, manifested as decreased body weight gain and food consumption in rats, resulted in a lower body weight of female pups; the maternal and developmental NOAEL was set at 48.6 mg/kg/day.              A pre-natal developmental study in rabbits included dose groups of 0, 2.5, 10 and 40 mg/kg/day.  Similarly, as with the study in rats, treatment of rabbits at 40 mg/kg/day resulted in slight maternal toxicity consisting of reduction in food consumption at the onset of the treatment and between days 18 and 24, and reduced mean body weight gain at the beginning of the treatment only. As the lower fetal weights recorded at this dose level were within the range of the historical control data, the NOAEL for maternal and developmental toxicity was considered to be 40 mg/kg/day, the highest dose tested.

      4. Subchronic toxicity. Repeated dose, oral (dietary) toxicity studies with fluensulfone are available for rats, mice and dogs.  The studies conducted include 28-day and 90-day studies in the rat, mouse, and dog.  In addition, a 1-year oral toxicity study in dogs and a 28-day dermal toxicity study in rats were performed.

The rat 28-day study was conducted at dose levels of 0, 125, 500, and 2000 ppm (0, 10.4, 42.5, and 152 mg/kg/day in males and 0, 12.2, 37.2, and 165.9 mg/kg/day in females).  The NOAEL was 125 ppm (10.4 and 12.2 mg/kg day in males and females respectively), based on results at the LOAEL of functional effects in the liver and kidney effects, which were considered adverse as a precaution but likely of no toxicological relevance.

The mouse 28-day study was conducted at dose levels of 0, 100, 500, and 2000 ppm (0, 30.33, 101.31, and 374.5 mg/kg/day in males and 0, 41.32, 155.12, and 353.0 mg/kg/day in females).  The NOAEL was 100 ppm (30.33 and 41.32 mg/kg/day in males and females respectively), based on results at the LOAEL of decreased food consumption and liver toxicity (increased relative weight, histopathological findings).

The dog 28-day study was conducted at dose levels of 0, 50, 200, and 900 ppm (1.9, 7.3, and 30.9 mg/kg/day in males and 2.0, 7.9, and 29.7 mg/kg/day in females).  The NOAEL was 200 ppm (7.3 and 7.9 mg/kg/day in males and females respectively), based on results at the LOAEL of slight changes in food consumption, body weight and organ weight (liver and thyroid) and on hepatic tissue enzyme activities.

The rat subchronic 90-day study was conducted at dose levels of 0, 60, 120, 500 and 2000 ppm (4.31, 8.26, 34.86, and 139.01 mg/kg/day in males and 4.85, 11.68, 53.10 and 148.73 mg/kg/day in females).  The NOAEL was 120 ppm (8.3 and 11.7 mg/kg/day in males and females respectively), based on results at the LOAEL of decreased body weight/body weight gain in males, increased water consumption in males and increased triglycerides in females.

The mouse subchronic 90-day study was conducted at dose levels of 0, 60, 300, and 1500 ppm (11.06, 50.85, and 228.53 mg/kg/day in males and 18.33, 68.47 and 252.49 mg/kg/day in females).  The NOAEL was 60 ppm (11.06 and 18.33 mg/kg/day in males and females, respectively), based on results at the LOAEL of decreased food consumption in females and marginal effects in liver and hematological findings in males.

The dog subchronic 90-day study was conducted at dose levels of 0, 5, 50, and 500 ppm (0.2, 1.6 and 17.1 mg/kg/day in males and 0.2, 1.8 and 18.0 mg/kg/day in females).  The NOAEL was 500 ppm (17.1 and 18.0 mg/kg/day in males and females, respectively), based on only slight and reversible liver effects at the top dose tested.

The rat 28-day dermal study was conducted at dose levels of 0, 80, 400, and 2000 mg/kg/day in males and females.  Only a minimal increase in the incidence of acanthosis/hyperkeratosis was observed at the limit dose of 2000 mg/kg/day.  However, because of the moderate degree recorded in comparison to the vehicle control, the finding was considered adaptive and likely to be reversible after cessation of treatment and on this basis not adverse. The NOAEL was 2000 mg/kg/day, the highest dose tested, based on no systemic or adverse dermal effects at the highest dose level tested.

In all species the liver appears to be the main target organ, although often the observed effects were limited to adaptive changes (e.g. hepatocyte hypertrophy concomitant to increased weight, induction of mainly phase II activities). Investigations on liver enzyme activities in all species revealed that fluensulfone administration does not result in significant induction of (activating) phase I cytochrome P450 subfamilies, but that the (conjugating) phase II enzymes were induced. Frank hepatotoxicity was observed only at very high doses, and only in mice.

The NOAEL for oral subchronic toxicity is 8.3 mg/kg bw/day based on decreased body weights in males (and supported by increased triglycerides in females at the same dietary dose) in the 90 day rat study. The NOAEL for dermal subchronic toxicity is 2000 mg/kg bw/day, based on absence of adverse effects at the highest test dose in the rat 28-day dermal toxicity study.

      5. Chronic toxicity. The long-term toxicity and carcinogenicity potential of fluensulfone was evaluated in dogs (one year study), rats (combined study for chronic toxicity and carcinogenicity), and mice (carcinogenicity).         In a 1-year oral toxicity study in dogs, fluensulfone was administered in the diet at 0, 5, 50 100 and 500 ppm (0.1, 1.5, 3.1, and 19 mg/kg/day in males and 0.1, 1.5, 3.3, and 16.2 mg/kg/day in females) to purebred Beagle dogs for a period of 52 weeks with selected animals retained for an 8-week recovery period.  The NOAEL was considered to be 100 ppm (3.1 mg/kg bw/day in males and 3.3 mg/kg bw/day in females), based on decreased body weight and body weight gains, decreased hemoglobin, MCH, MCHC and increased kidney weights at 500 ppm (16.0 and 16.2 mg/kg/day in males and females respectively) in the diet. A combined chronic dietary toxicity and carcinogenicity study in rats was conducted with 0, 30, 200, and 1200 ppm dose groups (1.6, 11 and 66.3 mg/kg/day after 52 weeks and 1.4, 9.6 and 57.7 mg/kg/day after 104 weeks in males; 1.9, 13.1 and 75.2 mg/kg/day after 52 weeks and 1.7, 11.6 and 69.3 mg/kg/day after 104 weeks in females). Fluensulfone showed no carcinogenic potential in this study, and the NOAEL for lifespan treatment (2-years) was set at 30 ppm (1.4 mg/kg/day in males and 1.7 mg/kg/day in females) on the basis of chronic interstitial inflammation in the lungs of females, decreased body weight and body weight gain in males, and decreased hemoglobin concentration and hemoglobin concentration distribution width in females receiving 200 ppm.        A 78-week dietary carcinogenicity study in mice was conducted with 0, 30, 200, and 1200 ppm dose groups (4.2, 27.6 and 152.3 mg/kg/day in males and 6.4, 39.0, and 188.4 in females).  The overall NOEL in mice following lifespan treatment was set at 30 ppm (4.2 and 6.4 mg/kg/day in males and females, respectively). In mice, treatment with fluensulfone for 78 weeks resulted in an increased incidence of alveolar/bronchiolar adenomas in females receiving 200 and 1200 ppm. Mechanistic studies were carried out to determine the relevance for humans of this finding. Tumors were found to be a species-specific effect in mice due to activation of fluensulfone by mouse lung Clara cells, leading to local cytotoxicity, cell proliferation and finally formation of benign tumors.  Rats have lower metabolic activity in the lungs compared to mice (below the threshold needed to cause lung tumors upon lifetime exposure) and activity in humans is orders of magnitude lower than rats.  Fluensulfone was found to be extensively metabolized by mouse lung microsomes, whereas no metabolic activity was seen in human lung microsomes.    In accordance with the International Programme on Chemical Safety (IPCS) mode of action and human relevance framework, it is concluded that fluensulfone leads to species-specific tumors via a non-genotoxic threshold mode of action in the mouse lung, and that these tumors are not relevant to human hazard or risk.

The NOAEL for lifespan treatment was set at 1.4 mg/kg/day on the basis of decreased body weight and body weight gain in males (supported by chronic interstitial inflammation in the lungs and decreased hemoglobin concentration and hemoglobin concentration distribution width in females).

      6. Neurotoxicity. Acute and subchronic specific neurotoxicity studies (i.e. inclusive of neuropathology) were carried out, and functional observation batteries (FOBs) and motor activity assessments were included in the repeated dose/chronic studies with fluensulfone.  The FOBs and motor activity assessments conducted within the repeated dose/chronic toxicity studies revealed no effects.        In an acute oral neurotoxicity study in rats, groups of 10 male and 10 female Wistar rats were administered single oral doses of 0 (control), 100, 400 and 1200 mg/kg bw of fluensulfone by oral gavage  and observed for 14 days.  No test item-related effects on absolute and relative brain weights were evident, and there were no findings in the nervous system during macroscopic and microscopic pathology examinations.  The LOAEL for general toxicity is 100 mg/kg bw in males and females, based on the general systemic toxicity due to the bolus dose.  The NOAEL for neurotoxicity is 100 mg/kg bw in males and females, based on reduced activity in the functional observation battery and decreased motor activity at 400 mg/kg in absence of any neuropathological finding at any dose level.        In a subchronic dietary neurotoxicity study, groups of 12 male and 12 female RccHan:WIST (SPF) rats received fluensulfone in their diet at concentrations of 0 (control), 100, 500 and 2500 ppm (0, 6, 31, and 153 mg/kg/day in males and 0, 7, 34, and 162 mg/kg/day in females) for at least 90 days.  Treatment-related effects were confined to lower food consumption, body weight and body weight gain in males and females at 2500 ppm. These treatment-related effects were attributed to systemic toxicity, and not to neurotoxicity.  No effects on functional parameters or neurohistopathology were observed. Therefore, the high dose level of 2500 ppm was the `no-observed-effect level' (NOEL) for neurotoxicity associated with dietary exposure, equivalent to 153 mg/kg bw/day in males and 162 mg/kg bw/ day in females.  The no-observed-adverse-effect level (NOAEL) for systemic toxicity was 500 ppm equivalent to 31 mg/kg bw/day for males and 34 mg/kg bw/day for females.         As developmental studies did not indicate that the offspring are more sensitive than the adult, and neuropathological effects were not observed in any of the performed neurotoxicity studies, a developmental neurotoxicity study was considered not necessary.

      7. Immunotoxicity.  Although immunotoxicity endpoints were already included in the 28-day dietary study in rats and mice, fluensulfone was tested also in mice in the 28-day sheep red blood cell assay, to evaluate its immunotoxicity potential. In addition, the entire available data set was examined to check immunotoxicity-related endpoints.  It is concluded that fluensulfone is not an immunotoxic substance.              8. Animal metabolism. Fluensulfone (labeled at the thiazole and the butene-moieties of the molecule) administered orally to rats at nominal single doses of either 5 mg/kg or 500 mg/kg is rapidly metabolized. The recovery of radioactivity was essentially complete for all groups of rats. The disposition and excretion of radiolabel for males and females were generally similar. There was no indication that the metabolic elimination processes were saturated by the 100-fold increase in dose level, as levels of radiolabel in urine, cage wash, feces, carcass, and gastro-intestinal (GI tract) were similar.

Urine was the major route of excretion and the only source of metabolites at >=5% of the applied radiolabel.  The cage wash contained relatively high levels of radiolabeled metabolites and analysis showed that those metabolites in cage wash and urine were similar.  Low amounts of thiazole sulfonic acid were found in feces, but no other fecal metabolites were >=5% of the applied dose.  Fluensulfone is not a significant residue in either urine or feces.

In addition to investigating metabolism after a single dose, the tissue distribution was studied when the dosing of radioactivity was preceded by 14 days administration of unlabelled material.  The results indicate that distribution is comparable in both cases.

	7. Metabolite toxicology. The acute oral LD50 of fluensulfone metabolite M-3625 was greater than 2000 mg/kg(less than that of the parent fluensulfone).

Metabolite M-3625 was tested for its genotoxic potential in a bacterial reverse gene mutation assay, an in vitro chromosome aberration assay in mammalian cells, and an in vivo micronucleus assay in the bone marrow of rat. No genotoxic properties were identified.

      The acute oral LD50 of fluensulfone metabolite M-3627 (BSA) was greater than 2000 mg/kg bw (less than that of the parent fluensulfone).

Metabolite M-3627 was tested for its genotoxic potential in a bacterial reverse gene mutation assay, an in vitro chromosome aberration assay in mammalian cells, and an in vivo micronucleus assay in the bone marrow of rat. No genotoxic properties were identified.

	8. Endocrine disruption. Evidence from the large available toxicological data set demonstrates that fluensulfone does not exert any adverse effects on thyroid gland, reproductive system and related endocrine organs and adrenal glands.  Therefore, it is concluded that fluensulfone does not possess any endocrine disrupting potential.

C. Aggregate Exposure

	1. Dietary exposure. Acute and chronic dietary (food + water) exposures to fluensulfone have been recently conducted and this proposed use is not likely to significantly impact the previous conclusions. The recent drinking water modeling conducted by EPA (2014) is still relevant and results were incorporated into the assessment. Based on livestock metabolism studies, no residues of concern (parent fluensulfone) are expected in milk or any animal tissue. A Tier 1 acute dietary exposure assessment was conducted assuming tolerance-level residues, 100% crop treated and default processing factors. Exposure was assessed using the acute and chronic toxicological endpoints determined by EPA (2014), which are an aPAD of 0.16 mg/kg bw/day derived from a NOAEL of 16.2 mg/kg bw/day from a 2-generation reproduction rat study and a cPAD of 0.03 mg/kg bw/day derived from a NOAEL of 3.1 mg/kg bw/day from co-critical 90-day dog and chronic dog studies. EPA has determined that the level of concern for fluensulfone for acute and chronic exposures is 100 (EPA, 2014).

      Acute Dietary Exposure.  Acute dietary (food + water) exposures to fluensulfone, which were calculated using DEEM- FCID version 4.02, for a recent 2014 submission. The reported exposures correspond to the 95th percentile of the exposure distributions, as is appropriate for a Tier 1 acute dietary exposure assessment. The 95th percentile acute dietary (food + water) exposures are well below the aPAD (0.16 mg/kg/d). For all infants, the most highly exposed subpopulation, 95th percentile acute dietary exposures correspond to 9.13% of the aPAD. For the general U.S. Population, 95th percentile acute dietary exposures correspond to 2.79% of the aPAD. Acute dietary exposures below 100% of the aPAD are reasonably anticipated to result in no harm to exposed populations.              Chronic Dietary Exposure.  Chronic dietary exposures to fluensulfone, which were calculated using DEEM-FCID version 4.02, was also recently conducted. Chronic dietary exposures are less than the cPAD (0.03 mg/kg/d). For infants, the most highly exposed subpopulation, chronic dietary exposures correspond to 15.1% of the cPAD. For the general U.S. Population, chronic dietary exposures correspond to 4.0% of the cPAD. Chronic dietary exposures below 100% of the cPAD are reasonably anticipated to result in no harm to exposed populations.        	i. Food. Exposure to fluensulfone through food is included in the dietary assessment section above.

	ii. Drinking water. Exposure to fluensulfone through water is included in the dietary assessment section above.

	2. Non-dietary exposure. Fluensulfone is currently not registered for use on any residential non-food site.  Therefore, residential exposure to fluensulfone residues will be through dietary exposure only.

D. Cumulative Effects

	Fluensulfone is a member of a new chemical class of nematicides with a specific toxicological profile. It does not share a known toxicological mode of action with other pesticides. Thus, no cumulative effects are foreseen.

E. Safety Determination

	1. U.S. population. Using the conservative exposure assumptions described above and based on the completeness of the toxicity data, it can be concluded that total food and drinking water exposure to fluensulfone from all proposed crop uses will be 2.79% of the aPAD and 4.0% of the cPAD for the overall US population.

    2. Infants and children. Using the conservative exposure assumptions described above and based on the completeness of the toxicity data, it can be concluded that the total acute food and drinking water exposure to fluensulfone from all proposed crop uses will be 9.13% (all infants), 4.21% (children 1-2 yrs), 3.53% (children 3-5 yrs), and 2.46% (6-12 yrs) of the aPAD. It can be concluded that the total chronic food and drinking water exposure to fluensulfone from all proposed crop uses will be 15.1% (all infants), 6.2% (children 1-2 yrs), 4.9% (children 3-5 yrs), and 3.5% (children 6-12 yrs) of the cPAD.

F. International Tolerances

	No Codex Maximum Residue Levels (MRLs) have been established for residues of fluensulfone on any crops.  MRL's have been set by Canada for Import Tolerance purposes. There are no established tolerances for fluensulfone in Mexico.