DATE: October 11, 2005 MEMORANDUM SUBJECT: TRIETHYLENE GLYCOL: Revised Toxicology Chapter in Support of Issuance of the Reregistration Eligibility Decision ( RED) Document. PC Code: 083501 Reregistration Case Number: 3145. CAS Registry Number: 112 27 6. DP#: 325786 FROM: Michelle M. Centra, Pharmacologist Regulatory Management Branch II Antimicrobials Division ( 7510C)

THRU: Timothy F. McMahon, Ph. D. Division Senior Toxicologist Antimicrobials Division ( 7510C)

TO: Heather Garvie, Chemical Review Manager Ben Chambliss, Team Leader Mark Hartman, Branch Chief Regulatory Management Branch II Antimicrobials Division ( 7510C)

Attached is the revised Triethylene Glycol toxicology chapter for incorporation into the risk assessment document and the Reregistration Eligibility Decision ( RED) document.

Supporting documentation used to generate the toxicology chapter are listed below:

1. TRIETHYLENE GLYCOL  Revised Report of the Antimicrobials Division Toxicology Endpoint Selection Committee ( Memorandum: T. McMahon, 11/ 21/ 05). 2 2. EPA ID# 083501: Triethylene glycol. Review of Phase IV Response Submissions in Support of FIFRA 88. ( Memorandum: G. Reddy, 12/ 12/ 93).

3. TRIETHYLENE GLYCOL: Antimicrobials Division Review of Toxicity Studies Submitted to the Agency's Office of Pollution, Prevention and Toxics. PC Code: 083501. Reregistration Case Number: 3145. CAS Registry Number: 112 27 6. DP#: 305169 ( Memorandum: M. Centra, 10/ 11/ 05). 3 TRIETHYLENE GLYCOL PC Code: 083501 Revised Toxicology Disciplinary Chapter for the Reregistration Eligibility Decision ( RED) Document Antimicrobials Division Office of Pesticide Programs U. S. Environmental Protection Agency Prepared by: Michelle M. Centra, Pharmacologist Revised Date: October 11, 2005 4 INTRODUCTION The active ingredient, triethylene glycol, was first registered by the FDA for use in hospitals as an air disinfectant on August 3, 1948 ( James Varley & Sons' Glyco Mist, EPA Reg. No. 421 21). As an active ingredient, triethylene glycol is formulated primarily as a pressurized liquid and is used in two types of applications: air sanitizers/ hospital disinfectants, and pest ( mites and red lice) control on caged birds. As an inert ingredient, triethylene glycol facilitates delivery of formulated pesticide chemical products that are used as herbicides, fungicides, insecticides, growth regulators and attractants on a wide variety of agricultural commodities.

The majority of the producers of triethylene glycol formulated pesticide products are represented by a consortium called the CSPA ( Consumer Specialty Products Association) Glycols Joint Venture ( formerly known as the CMSA Glycol Joint Venture). The member companies currently represented by this consortium are: Amrep, Inc., Medo Industries, Inc., S. C. Johnson & Son, and Waterbury Companies, Incl.

In 1997, the Office of Pesticide Programs, Health Effects Division conducted an evaluation of the toxicity of the active ingredient, triethylene glycol as required by law under FIFRA for the reregistration of pesticidal chemicals.

The triethylene glycol mammalian toxicity database consists of published literature studies and monographs submitted by the Glycols Joint Venture consortium as a result of the Phase IV review of triethylene glycol for reregistration under FIFRA. These submitted data were reviewed by the Agency and classified as acceptable or waived as indicated below in Table 2. At that time, these data were determined to satisfy the Subdivision F guideline test guideline requirements and no additional data requirements were identified for the non food use of triethylene glycol. 1 Table 2. Data Requirements for Non Food Use of Triethylene Glycol ( 1997)

Guideline Number Study Type Required Satisfied § 81 1 Acute Oral  Rat Yes Yes § 81 2 Acute Dermal  Rabbit Yes Waived § 81 3 Acute Inhalation  Rat Yes Yes § 81 4 Primary Eye Irritation Yes Yes § 81 5 Primary Dermal Irritation Yes Yes § 81 6 Skin Sensitization Yes Yes § 82 1a Subchronic Oral  Rodent No No § 82 1b Subchronic Oral  Non Rodent Yes Yes Table 2. Data Requirements for Non Food Use of Triethylene Glycol ( 1997)

5 § 82 2 21 Day Dermal Yes Yes § 82 4 90 Day Inhalation Yes Yes § 83 3a Developmental Toxicity  Rodent Yes Yes § 83 3b Developmental Toxicity  Non Rodent Yes Yes § 83 4 Reproductive Toxicity  Rodent Yes Yes § 83 1b Chronic Toxicity  Non Rodent Yes Yes § 83 1a Carcinogenicity  Rodent Yes Yes § 84 2 Gene Mutation  Ames Yes Waiveda § 84 2 Cytogenetics  Structural Chromosomal Aberration Yes Waiveda § 85 1 General Metabolism Yes Yes aThe data waivers granted by the Agency in 1997 for the triethylene glycol mutagenicity assays are no longer applicable to this chemical. Several mutagenicity assays submitted to the Agency's Office of Toxic Substances were reviewed by OPP's Antimicrobials Division and determined to be acceptable/ non guideline studies. These four mutagenicity studies have been incorporated into the toxicity data base for triethylene glycol.

HAZARD PROFILE Acute Toxicity Published literature studies submitted by the Glycols Joint Venture consortium show low toxicity ( Toxicity Categories III and IV) following acute exposures ( Table 3). The acute oral and dermal toxicity of the chemical appears to be low, with reported oral LD 50 values ranging from 15 22 g/ kg compiled from monographs and review articles. The data available on acute dermal toxicity were insufficient to establish a dermal LD 50 , but the data requirement was waived based on the low order of toxicity observed in other studies with triethylene glycol. Data on inhalation toxicity showed a maximum tolerated level of 800 mg/ m3 in rats, but intratracheal instillation of 0.25 cc undiluted chemical caused marked pulmonary irritation, edema, and later, fibrosis and abcess formation in these animals ( intratracheal instillation is not an accepted route of administration for the Agency's toxicity testing guidelines). Published literature data on the skin and eye irritation as well as skin sensitization showed triethylene glycol to be non irritating to the skin and eye ( when tested at the limit doses established by the Agency for acute toxicity testing) and not a dermal sensitizer. 2 5 Triethylene glycol was evaluated for acute inhalation toxicity in male and female Sprague Dawley albino rats in a study submitted to the Agency's Office of Toxic Substances. A review of this study by the Antimicrobials Division established a four hour LC 50 greater than 5.2 mg/ L, and 6 places acute inhalation in Toxicity Category IV. Based on these results, this study was determined to be adequate for regulatory purposes and it now replaces the earlier submitted acute inhalation information. 6 Table 3. Acute Toxicity Profile of Triethylene Glycol Guideline Study Type MRID No. Results Toxicity Category 870.1100 Acute Oral  Rat 42814404 LD50 = 15 22 g/ kg IV 870.1200 Acute Dermal  Rabbit 42814404 LD50 not determined Study requirement waived 870.1300 Acute Inhalation  Rat OTS0527779 2 LC50 > 5.2 mg/ L IV 870.2400 Acute Eye Irritation  Rat 42814404 mild irritant III 870.2500 Acute Skin Irritation  Rabbit 42814404 slight irritant IV 870.2600 Skin Sensitization 42814404 non sensitizer N/ A N/ A = Not applicable Subchronic Toxicity Repeat oral dosing studies conducted in rats to determine triethylene glycol toxicity showed in general, that the chemical was either without any adverse effects or produced toxicities only at doses at or greater than the limit doses established for EPA guideline test requirements. Triethylene glycol administered in the drinking water to rats at concentrations of 3% and 5% by volume for 30 days showed signs of toxicity ( weight loss, alopecia and poor grooming) at the lower concentration with one animal dying on day 25 of the study. All rats in the 3% test group survived to study completion with no signs of toxicities. 7 In a 14 day oral toxicity study, Fischer 344 rats receiving triethylene glycol in the feed ( doses equivalent to 1132, 2311, or 3916 mg/ kg/ day for males and 1177, 2411, or 6209 mg/ kg/ day for females ) showed only changes in urinalysis ( increased urine volume, decreased urine pH, and decreased urine triple phosphate crystals) at the highest respective doses tested in male and female rats. 8 In a third oral toxicity study conducted for 90 days in rats, triethylene glycol was administered in the diet at doses of 748, 1522, or 3849 mg/ kg/ day ( males), and 848, 1699, or 4360 mg/ kg ( females). Although toxicities were noted at the high dose in male and female rats ( decreases in body weight, slight decreases in hemoglobin and hematocrit, slight increases in mean corpuscular volume, and increased relative kidney and brain weights), these effects were noted at dose levels that exceed the established limit dose of 1000 mg/ kg/ day for such studies. 9 In a 21 day dermal toxicity study, there was no evidence of dermal or systemic toxicity from repeated dermal applications of 2ml ( approximately 600 mg/ kg) triethylene glycol applied to the skin of rabbits. These results are supported by triethylene glycols' low dermal irritancy a negative response as a skin sensitizer. 10 11 7 Sprague Dawley rats exposed ( whole body) to triethylene glycol in an aerosol inhalation study at concentrations of 494, 2011, or 4842 mg/ m3 ( 0.5, 2.0, or 5.0 mg/ L/ day), for six hours a day, nine times over a two week period showed the following toxicities at the highest concentration level tested: ataxia, prostration, unkept fur, labored respiration ( males only), ocular discharge, swollen periocular tissue, perinasal and perioral encrustation, blepharospasm and reduced body weight Necropies revealed hyperinflation of the lungs, ocular opacity, congestion and hemorrhage in many organs and tissues ( pituitary gland, brain, nasal mucosa, kidney, thymus and lungs). All of the rats in the high dose group died or were sacrificed moribund by day 5 of the study. Clinical signs of toxicity observed at the low and mid dose of 0.5 and 2.0 mg/ L/ day, respectively, were limited to swollen periocular tissues and perinasal encrustations. Treatment related changes in organ weights in mid dose males included an increase in liver and kidney weights relative to body weight; mid dose females showed increases in absolute and relative ( to body and brain weights) liver and kidney weights. Statistically significant clinical chemistry findings for males treated with 2.0 mg/ L/ day triethylene glycol included an increase in ALT activity and a decrease in serum creatinine levels. Mid dose females showed increases in urea nitrogen, inorganic phosphorus, ALT and ALK activity, and decreases in glucose, creatinine, and chloride. However, the changes in organ weights and clinical chemistry findings were not correlated with any histopathological observations. 13 Rats exposed to the test material via a whole body inhalation protocol are also receiving the chemical via the oral and dermal routes. These additional routes of exposure may have increased the total dose received and contributed to the toxicities observed in the whole body exposure inhalation study. Therefore, a second study was conducted using a nose only exposure for 6 hours a day, 9 consecutive days. In this second inhalation toxicity study, mean exposure concentrations of 102, 517, or 1036 mg/ m3 ( approximately 0.1, 0.5, 1.0 mg/ L/ day) triethylene glycol produced no treatment related toxicities at any dose tested. 12 Monkeys exposed by inhalation to approximately 1 ppm vapor from two weeks to 13 months and human volunteers exposed to air saturated with vapor ( approximately 0.5 to 1 ppm) showed no adverse reactions or histopathological changes suggestive of toxicity from prolonged exposure to triethylene glycol. 14 Dogs given daily intravenous injections ( 0.1 or 0.5 ml/ kg) of triethylene glycol for four weeks showed no mortality or toxicity with the exception of flattened epithelial cells in the urine and phlebitis at the site of injection. 15 Chronic Toxicity and Carcinogenicity Published literature sources examining the chronic toxicity and carcinogenic potential of triethylene glycol have shown the chemical to be non toxic/ negative in rodent species.

In a 12 month study, monkeys receiving triethylene glycol ( 0.25 mL to 0.5 mL) orally in egg nog ( approximately 50 to 100 times the quantity an animal could absorb by breathing air saturated 8 with glycol) were without any adverse effects in physiological functions or organ histopathology. 14 Triethylene glycol administered in feed at levels of 0, 1, 2 or 4% to Osborn Mendel rats for 2 years showed that the body weight gains, hematological parameters and clinical chemistries were not affected by treatment. Under the conditions of this study, triethylene glycol was not carcinogenic in rats. The dosages tested in rats are equivalent to as much as 3 to 4 g/ kg/ day which are well above the upper limit dose of 1 g/ kg/ day ( 1000 mg/ kg/ day) for testing pesticides via the oral route in subchronic and chronic toxicity studies. 16 Mutagenicity Triethylene glycol was tested for mutagenic or genotoxic potential and found to be negative in a battery of studies: a bacterial gene mutation assay using Salmonela typhimurium, an in vitro Chinese hamster ovary ( CHO) mutation assay, an in vitro Chinese hamster ovary ( CHO) chromosomal aberration assay and an in vitro sister chromatid exchange assay. 17 20 Dermal Absorption No studies have been reported dealing with the skin absorption of triethylene glycol. Although it is possible that, under conditions of very severe prolonged exposures to this chemical, absorption through the skin, it is doubtful any appreciable systemic/ dermal injury would occur because triethylene glycol has ( 1) a low order of dermal irritancy, ( 2) is not a skin sensitizer, and ( 3) showed no evidence of dermal or systemic toxicity following repeated dermal applications of 2ml ( approximately 600 mg/ kg) triethylene glycol applied to the skin of rabbits in a 21 day dermal toxicity study.

Metabolism and Excretion The fate of 14C labeled triethylene glycol in rats and of unlabeled material in rabbits was recently studied. Following oral dosing, the rat and rabbit excreted most of the triethylene glycol in both unchanged and/ or oxidized forms ( mono and dicarboxylic acid derivatives of triethylene glycol). In rabbits dosed with 200 or 2000 mg/ kg triethylene glycol respectively excreted 34.3% or 28%, of the administered dose in the urine as unchanged triethylene glycol and 35.2% as a hydroxyacid form of this chemical. In the studies with rats, little if any C14 oxalate or C14 triethylene glycol in conjugated form was found in the urine. Trace amounts of orally administered 14C triethylene glycol were excreted in expired air as carbon dioxide (< 1%) and in detectable amounts in feces ( 2 to 5 %). The total elimination of radioactivity ( urine, feces and CO 2 ) during the five day period following an oral dose of labeled compound ( 22.5 mg) ranged from 91 to 98%. The majority of the radioactivity appeared in the urine. 21 Developmental and Reproductive Toxicity 9 Triethylene glycol was administered orally at doses of 0, 0.5, 5.6, and 11.27 g/ kg/ day in timed pregnant CD 1 mice from gestation Days 6 through 15. There were no treatment related maternal deaths and no abortions. Hyperactivity and rapid respiration were observed at the highest dose level. No effects were observed on maternal weight gain or food consumption at any dose level. Pregnancy outcome was unaffected at any dose level tested. There were no treatment related effects on external or visceral malformations in offspring. Some evidence of delayed ossification was observed at the high dose level. 22 In a second study, pregnant Sprague Dawley rats were administered triethylene glycol by gavage on gestation days 6 through 15 at dose levels of 0, 1.0, 5.6, and 11.27 g/ kg/ day. There were no effects on maternal mortality and there were no abortions. Clinical toxicity was observed in maternal rats at the high dose and consisted of audible respiration, periocular encrustation, and perioral wetness. Decreased body weight and food consumption was observed in maternal rats at the 5.6 g/ kg/ day dose. No effects were observed at the 1.0 g/ kg/ day dose. In offspring, mean fetal body weight was decreased at the 11.27 g/ kg/ day dose level, but there were no treatmentrelated increases in external, visceral, or skeletal malformations. 23 Published literature examined the effect of triethylene glycol on reproduction in Swiss CD 1 mice. Doses of 0, 0.3, 1.5, and 3% were administered in drinking water using a continuous breeding protocol. No effects on reproductive function were observed at any dose level tested ( up to the high dose of 6.78 g/ kg) including sperm concentration, morphology, and motility. Reduced pup weight was observed at the 1.5 and 3% doses of triethylene glycol. 24 25 In a study submitted to the Agency, rats were exposed to an atmosphere saturated with triethylene glycol ( approx. 1 ppm) for 12 18 months with no adverse reproductive effects noted. 14,26 The available developmental and reproductive studies conducted with triethylene glycol are from published sources or from studies submitted to the Office of Toxic Substances and do not report all the data that are normally reported under the OPPTS 870 toxicity test guidelines. However, it is apparent that the toxicities observed in these studies are consistently manifested only at doses of triethylene glycol that exceed the established limit doses for animal studies and are of a non specific nature. Therefore, there is no concern for the developmental or reproductive toxicity of triethylene glycol.

Neurotoxicity From the available repeat dose toxicity studies, there was no evidence of neurotoxicity of triethylene glycol, however, the toxicology data are inadequate to characterize repeated dose toxicity. Therefore, neurotoxicity testing could be required if additional data are needed for future uses of triethylene glycol. 10 REFERENCES 1. Davis, K.( 1993) Compilation of Toxicology Data References for Triethylene Glycol: Lab Project Number: TEGTOX. Unpublished study prepared by RegWest Co. 131 p. MRID No. 42814404.

2. Safety Assessment of Triethylene Glycol and PEG 4: Final Report of the Cosmetic Ingredient Review Expert Panel, Fegruary 7, 2003.

3. Budavari, S., M. J. O'Neill, A. Smith, and P. E. Heckelman ( eds.) 1989. The Merck Index: An Encyclopedia of Chemicals, Drugs, and Biologicals. Rahway ( eleventh edition), NJ: Merck & Co., Inc.

4. Clayton, G. D. and F. E. Clayton ( eds.). Patty's Industrial Hygiene and Toxicology: Volume 2A, 2B, 2C: Toxicology. 3rd ed. New York: John Wiley Sons, 1981 1982. 3839.

5. Smyth, H. F. et al ( 1941) The single dose toxicity of some glycol derivatives. J. Ind. Hyg. Toxicol. 23( 6): 259 268.

6. Nachreiner, D. J. ( 1991) Triethylene Glycol ( TEG) Acute Aerosol Inhalation Toxicity Test in Rats. Bushy Run Research Center; Project Report 53 139 ( BRCC No. 90 22 40272), March 4, 1991; NTIS Report No. OTS0527779 1. Unpublished.

7. Lauter, W. M. and V. L. Vria ( 1940) Toxicity of Triethylene Glycol and the Effect of Paraamino benzene Sulfonamide Upon the Toxicity of this Glycol. J. Am. Pharmaceutical Assoc. 29: 5 8.

8. Union Carbide ( 1989) Triethylene Glycol: Fourteen day Dietary Toxicity Study in Fischer 344 Rats. NTIS Report No. OTS0527779 1. Unpublished.

9. Union Carbide ( 1990) Triethylene Glycol: Ninety day Dietary Toxicity Study in Fischer 344 Rats. NTIS Report No. OTS0527779 1. Unpublished.

10. Monographs on Fragrance Raw Materials: Special Issue V ( 1979). Food and Cosmetic Toxicology., 17( suppl): 913.

11. Guillot, J. P., et al. ( 1982) Safety Evaluation of Some Humectants and Moisturizers Used in Cosmetic Formulations. International J. Cosmetic Sci., 4: 67.

12. Norris, J. and W. Kintigh ( 1994) Triethylene Glycol: Nine day Aerosol Inhalation ( Noseonly Exposure) toxicity study in Rats. Bushy Run Research Center, Union Carbide 11 Corporation, Inc., Export, PA. Laboratory Project ID: 93U1293, October 26, 1994. NTIS Report No. OTS0537563 1. Unpublished.

13. Sun, J. and W. Kintigh ( 1992) Triethylene Glycol: Nine day Aerosol Inhalation study in Rats. Bushy Run Research Center, Union Carbide Chemicals and Plastics Company, Inc., Export, PA. Laboratory Project ID: 91U0027, December 14, 1992. NTIS Report No. OTS0537563 1 with cover letter dated 010693 ( 1992). Unpublished.

14. Robertson, O. H., et al. ( 1947) Tests for the Chronic Toxicity of Propylene Glycol and Triethylene Glycol on Monkeys and Rats by vapor inhalation and Oral Administration. J. Pharm. Exp. Ther., 91: 52.

15. Stenger, E. G., er al. ( 1968) Zur Toxikologie des Triathylenglkol. Arzneimittel Forsch, 18: 1536.

16. Fitzhugh, O. G. and Nelson, A. A. ( 1946) Comparison of the Chronic Toxicity of Triethylene Glycol with that of Diethylene Glycol. J. Ind. Hyg. Toxicol. 28( 2): 40 43.

17. Guzzie, P., Slesinski, F. Frank, et al. ( 1986) Triethylene Glycol Salmonella/ Microsome ( Ames) Bacterial Mutagenicity Assay. Bushy Run Research Center, Export, PA. Project Report 49 58. April 29, 1986. NTIS Report No. OTS0527779 1. Unpublished.

18. Slensinski, R., F. Frank, and P. Guzzie ( 1986) Triethylene Glycol: In vitro Genotoxicity Studies: CHO/ HGPRT Mutation Test; Sister Chromatid Exchange Assay. Bushy Run Research Center, Export, PA. Project Report 49 83. June 26, 1986. NTIS Report No. OTS0527779 1. Unpublished.

19. Guzzie, P., Slesinski, F. Frank, et al. ( 1986) Triethylene Glycol: In vitro Chromosome Aberration Study. Bushy Run Research Center, Export, PA. Project Report 49 82. July 1, 1986. NTIS Report No. OTS0527779 1. Unpublished.

20. Slensinski, R., F. Frank, and P. Guzzie ( 1986) Triethylene Glycol: In vitro Mammalian Cell Gene Mutation Assay in CHO Cells. Bushy Run Research Center, Export, PA. Project Report 49 82. June 26, 1986. NTIS Report No. OTS0527779 1. Unpublished.

21. McKennis, Jr., et al. ( 1962) The Excretion and Metabolism of Triethylene Glycol. Toxic. Appl. Pharmacol., 91: 52.

22. Union Carbide ( 1990) Developmental Toxicity Study of Triethylene Glycol Administered by Gavage to CD 1 Mice. NTIS Report No. OTS0527779 1. Unpublished. 12 23. Union Carbide ( 1991) Developmental Toxicity Study of Triethylene Glycol Administered by Gavage to CD ( Sprague Dawley) Rats. NTIS Report No. OTS0527779 4. Unpublished.

24. Bossert, N. L., et al. ( 1992) Reproductive Toxicity of Triethylene Glycol and its Diacetate and Dimethyl ether Derivatives in a Continuous Breeding Protocol in Swiss CD 1 mice. Fund. Appl. Pharmacol. 18: 602 608.

25. Lamb, I. V. et al. ( 1997) Triethylene Glycol. Environ. Health Perspectives, 105( Suppl 1): 235 236. Also available as an NTP Report No. PB85 137073.

26. Goldstein, I., et al. ( 1970) Toxicity of Glycol Derivatives. Igenia, 19: 209.


[Federal Register Volume 81, Number 98 (Friday, May 20, 2016)]
[Notices]
[Pages 31994-31996]
[FR Doc No: 2016-11877]

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SECURITIES AND EXCHANGE COMMISSION

[Release No. 34-77836; File No. SR-NYSEMKT-2016-53]

Self-Regulatory Organizations; NYSE MKT LLC; Notice of Filing and
Immediate Effectiveness of Proposed Rule Change To Amend the Definition
of Professional Customer in Rule 900.2NY(18A)

May 16, 2016.
    Pursuant to Section 19(b)(1) \1\ of the Securities Exchange Act of
1934 (the ``Act'') \2\ and Rule 19b-4 thereunder,\3\ notice is hereby
given that on May 3, 2016, NYSE MKT LLC (the ``Exchange'' or ``NYSE
MKT'') filed with the Securities and Exchange Commission (the
``Commission'') the proposed rule change as described in Items I and II
below, which Items have been prepared by the self-regulatory
organization. The Commission is publishing this notice to solicit
comments on the proposed rule change from interested persons.
---------------------------------------------------------------------------

    \1\ 15 U.S.C. 78s(b)(1).
    \2\ 15 U.S.C. 78a.
    \3\ 17 CFR 240.19b-4.
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I. Self-Regulatory Organization's Statement of the Terms of the
Substance of the Proposed Rule Change

    The Exchange proposes to amend the definition of Professional
Customer in Rule 900.2NY(18A) to specify the manner in which the
Exchange calculates average daily order submissions for purposes of
counting Professional Customer orders. The proposed rule change is
available on the Exchange's Web site at www.nyse.com, at the principal
office of the Exchange, and at the Commission's Public Reference Room.

II. Self-Regulatory Organization's Statement of the Purpose of, and
Statutory Basis for, the Proposed Rule Change

    In its filing with the Commission, the self-regulatory organization
included statements concerning the purpose of, and basis for, the
proposed rule change and discussed any comments it received on the
proposed rule change. The text of those statements may be examined at
the places specified in Item IV below. The Exchange has prepared
summaries, set forth in sections A, B, and C below, of the most
significant parts of such statements.

A. Self-Regulatory Organization's Statement of the Purpose of, and
Statutory Basis for, the Proposed Rule Change

1. Purpose
    The Exchange proposes to amend the definition of Professional
Customer in Rule 900.2NY(18A) to adopt a methodology for counting
average daily order submissions in listed options to determine whether
a person or entity meets the definition of a Professional Customer
(``Professional Customer order counting''). The proposed rule change is
designed to harmonize Professional Customer order counting with the
recently adopted rules of competing options exchanges--specifically the
Chicago Board of Options Exchange, Inc. (``CBOE'') and NASDAQ OMX PHLX
LLC (``PHLX'').\4\
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    \4\ See Securities Exchange Act Release Nos. 77450 (March 25,
2016), 81 FR 18668, (March 31, 2016) (SR-CBOE-2016-005); 77449
(March 25, 2016), 81 FR 18665, (March 31, 2016) (SR-Phlx-2016-10)
(approval orders). The Exchange notes that it recently issued
guidance regarding Professional Customer order counting. See e.g.,
NYSE Arca, Inc.'s and NYSE MKT LLC's Joint Regulatory Bulletin (RBO-
15-03 and RBO-15-06, respectively) dated September 9, 2015. This
proposal codifies that guidance in a manner that is consistent with
CBOE and PHLX's approved rules.
---------------------------------------------------------------------------

    Rule 900.2NY(18A) defines Professional Customer ``as an individual
or organization that (i) is not a Broker/Dealer in securities, and (ii)
places more than 390 orders in listed options per day on average during
a calendar month for its own beneficial account(s).'' The Exchange
believes that identifying Professional Customer accounts based upon the
average number of orders entered in qualified accounts is an
appropriate, objective approach that will reasonably distinguish such
persons and entities from non-professional, retail investors or market
participants.\5\ In order to properly represent orders entered on the
Exchange, ATP Holders are required to indicate whether Customer orders
are ``Professional Customer'' orders.\6\ To comply with this
requirement, member organizations are required to review their
Customers' activity on at least a quarterly basis to determine whether
orders that are not for the account of a broker-dealer should be
represented as Customer orders or Professional Customer orders.\7\
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    \5\ See, e.g., Securities Exchange Act Release No. 73665
(November 21, 2014), 79 FR 70907, 70908 (November 21, 2014) (SR-
NYSEArca-2014-133) (adopting professional customer definition on
immediately effective basis, citing rules of various exchanges,
including Rule 900.2NY(18A)).
    \6\ See e.g., Rule 957NY (Reporting Duties), Commentary .02
(requiring that manual orders submitted be marked with an origin
code ``PC.'').
    \7\ Orders for any customer that had an average of more than 390
orders per day during any month of a calendar quarter must be
represented as Professional Customer orders for the next calendar
quarter. ATP Holders would be required to conduct a quarterly review
and make any appropriate changes to the way in which they are
representing orders within five business days after the end of each
calendar quarter. While members only would be required to review
their accounts on a quarterly basis, if during a quarter the
Exchange identifies a customer for which orders are being
represented as Customer orders but that has averaged more than 390
orders per day during a month, the Exchange would notify the ATP
Holder would be required to change the manner in which it is
representing the customer's orders within five business days.
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    The advent of new multi-leg spread products and the proliferation
of the use of complex orders and algorithmic execution strategies by
both institutional and retail market participants has raised questions
as to what should be counted as an ``order'' for Professional Customer
order counting purposes. The proposed changes would specifically
address the counting of multi-leg spread products, algorithm generated
orders, and complex orders for purposes of determining Professional
Customer status. In addition, the proposal is intended to provide
guidance regarding the methodology used by the Exchange when
calculating average daily orders for Professional order counting
purposes.\8\
---------------------------------------------------------------------------

    \8\ This proposal is consistent with CBOE and PHLX's approved
rules. See supra n. 4.
---------------------------------------------------------------------------

    As proposed, the rule would provide that an order would count as
one order for Professional Customer counting purposes, unless one of
the exceptions enumerated in the proposed rule stipulates otherwise
(each an ``Exception''). The first Exception relates to the treatment
of complex orders for purposes of computing orders for Professional
order counting purposes. Specifically, the proposed rule provides that
a complex order of eight legs or less would count as one order, whereas
a complex order comprised of nine (9) option legs or more counts as
multiple orders with each option leg counting as

its own separate order.\9\ The Exchange believes the distinction
between complex orders with up to eight legs from those with nine or
more legs is appropriate in light of the purposes for which Rule
900.2NY(18A) was adopted. In particular, the Exchange notes that multi-
leg complex order strategies with nine or more legs are more complex in
nature and thus, more likely to be used by professional traders than
traditional two, three, and four leg complex order strategies such as
the strangle, straddle, butterfly, collar, and condor strategies, and
combinations thereof with eight legs or fewer, which are generally not
algorithmically generated and are frequently used by non-professional,
retail investors. Thus, the types of complex orders traditionally
placed by retail investors would continue to count as only one order
while the more complex strategy orders that are typically used by
professional traders would count as multiple orders for Professional
Customer order counting purposes.\10\
---------------------------------------------------------------------------

    \9\ See proposed Rule 900.2NY(18A)(A)(1)(i)-(ii).
    \10\ See also supra n. 4.
---------------------------------------------------------------------------

    The second Exception relates to calculations for parent/child
orders. As proposed, if a parent order submitted for the beneficial
account(s) of a person or entity other than a broker or dealer is
subsequently broken up into multiple child orders on the same side
(buy/sell) and series by a broker or dealer, or by an algorithm housed
at the broker or dealer, or by an algorithm licensed from the broker or
dealer but housed with the customer, then the order would count as one
order even if the child orders are routed across several exchanges.\11\
The Exchange believes this proposed change would allow the orders of
public customers to be ``worked'' by a broker (or a broker's algorithm)
in order to achieve best execution without counting the multiple child
orders as separate orders for Professional Customer order counting
purposes. Conversely, if a parent order, including a strategy
order,\12\ is broken into multiple child orders on both sides (buy/
sell) of a series and/or multiple series, then each child order would
count as a separate new order per side and series.\13\ This proposed
change would allow the Exchange, for Professional Customer order
counting purposes, to count as multiple orders those ``child'' orders
of ``parent'' orders generated by algorithms that are typically used by
sophisticated traders to continuously update their orders in concert
with market updates in order to keep their overall trading strategies
in balance.
---------------------------------------------------------------------------

    \11\ See proposed Rule 900.2NY(18A)(A)(2)(i).
    \12\ The term ``strategy order'' refers to an execution
strategy, trading instruction, or algorithm whereby multiple
``child'' orders on both sides of a series and/or multiple series
are generated prior to being sent to an options exchange(s).
    \13\ See proposed Rule 900.2NY(18A)(A)(2)(ii).
---------------------------------------------------------------------------

    The third Exception would govern the counting methodology for
cancel/replace orders. As proposed, any order that cancels and replaces
an existing order would count as a separate order (or multiple orders
in the case of complex orders of nine legs or more) for Professional
Customer order counting purposes.\14\ However, the Exchange proposes
that an order to cancel and replace a child order would not count as a
new order if the parent order that was placed for the beneficial
account(s) of a non-broker or dealer had been subsequently broken into
multiple child orders on the same side and series as the parent order
by a broker or dealer, algorithm at a broker or dealer, or algorithm
licensed from a broker or dealer but housed at the customer.\15\ By
contrast, the Exchange proposes that an order that cancels and replaces
a child order resulting from a parent order, including a strategy
order, that generated child orders on both sides (buy/sell) of a series
and/or in multiple series would count as a new order per side and
series (``Both Sides/Multiple Series'').\16\ Finally, the Exchange
proposes that, notwithstanding the treatment of a cancel/replace
relating to Both Sides/Multiple Series orders, an order that cancels
and replaces any child order resulting from a parent order being pegged
to the Exchange's best bid or offer (``BBO'') or the national best bid
or offer (``NBBO'') or that cancels and replaces any child order
pursuant to an algorithm that uses the BBO or NBBO in the calculation
of child orders and attempts to move with or follow the BBO or NBBO of
a particular options series would count as a new order each time the
order cancels and replaces in order to attempt to move with or follow
the BBO or NBBO.\17\
---------------------------------------------------------------------------

    \14\ See proposed Rule 900.2NY(18A)(A)(3)(i).
    \15\ See proposed Rule 900.2NY(18A)(A)(3)(ii).
    \16\ See proposed Rule 900.2NY(18A)(A)(3)(iii).
    \17\ See proposed Rule 900.2NY(18A)(A)(3)(iv).
---------------------------------------------------------------------------

Implementation
    The Exchange proposes to implement the rule on July 1, 2016, which
would be announced via Trader Update.
2. Statutory Basis
    The Exchange believes that the proposed change is consistent with
Section 6(b) of the Act,\18\ in general, and furthers the objectives of
Section 6(b)(5),\19\ in particular, in that it is designed to promote
just and equitable principles of trade, to foster cooperation and
coordination with persons engaged in regulating, clearing, settling,
processing information with respect to, and facilitation transactions
in securities, to remove impediments to, and perfect the mechanism of a
free and open market and, in general, to protect investors and the
public interest.
---------------------------------------------------------------------------

    \18\ 15 U.S.C. 78f(b).
    \19\ 15 U.S.C. 78f(b)(5).
---------------------------------------------------------------------------

    Specifically, the Exchange believes that the proposal is designed
to adopt a reasonable and objective approach to determine Professional
Customer status that is consistent with the approach being utilized on
other options exchanges, which benefits market participants by
providing consistency across exchanges regarding the Professional
Customer order counting.\20\ In this regard, the Exchange believes that
codifying the manner in which the Exchange would conduct Professional
Customer order counting would provide ATP Holders with certainty and
provide them with insight as they conduct their own quarterly reviews
for purposes of designating orders.
---------------------------------------------------------------------------

    \20\ See supra n. 4.
---------------------------------------------------------------------------

    The Exchange notes that it is not amending the threshold of 390
orders in listed options per day but, consisting with other exchanges
is revising the method for counting Professional Customer orders in the
context of multi-part orders and cancel/replace activity. In short, the
proposal addresses how to account for complex orders, parent/child
orders, and cancel/replace orders. The Exchange believes that
distinguishing between complex orders with 9 or more options legs and
those orders with 8 or fewer options legs is a reasonable and objective
approach. In addition, the Exchange believes the proposal appropriately
distinguishes between parent/child orders that are generated by a
broker's efforts to obtain an execution on a larger size order while
minimizing market impact and multi-part orders that used by more
sophisticated market participants. Similarly, the Exchange believes
that the proposal that cancel/replace orders would count as separate
orders with limited exceptions is a reasonable and objective approach
to distinguish the orders of retail customers that are ``worked'' by a
broker from orders generated by algorithms used by more sophisticated
market participants.
    Thus, the Exchange believes the proposal, which establishes an
objective methodology for counting average daily order submissions for
Professional

Customer order counting purposes, is consistent with the Act.

B. Self-Regulatory Organization's Statement on Burden on Competition

    The Exchange does not believe that this proposed rule change would
impose any burden on competition not necessary or appropriate in
furtherance of the purposes of the Act. To the contrary, the proposed
rule change is a competitive change that is substantially similar to
recent rule changes filed by the CBOE and PHLX.\21\
---------------------------------------------------------------------------

    \21\ See id.
---------------------------------------------------------------------------

    The Exchange notes that one of the purposes of the Professional
Customer designation is to help ensure fairness in the marketplace and
promote competition among all market participants. The Exchange
believes that this proposal would help establish more competition among
market participants and promote the purposes for which the Exchange's
Professional Customer rule was originally adopted. Moreover, the
proposal would stem ensure consistency and stem potential confusion as
to the manner in which options exchanges compute the Professional
Customer order volume.

C. Self-Regulatory Organization's Statement on Comments on the Proposed
Rule Change Received From Members, Participants, or Others

    No written comments were solicited or received with respect to the
proposed rule change.

III. Date of Effectiveness of the Proposed Rule Change and Timing for
Commission Action

    The Exchange has filed the proposed rule change pursuant to Section
19(b)(3)(A)(iii) of the Act \22\ and Rule 19b-4(f)(6) thereunder.\23\
Because the proposed rule change does not: (i) Significantly affect the
protection of investors or the public interest; (ii) impose any
significant burden on competition; and (iii) become operative prior to
30 days from the date on which it was filed, or such shorter time as
the Commission may designate, if consistent with the protection of
investors and the public interest, the proposed rule change has become
effective pursuant to Section 19(b)(3)(A) of the Act and Rule 19b-
4(f)(6)(iii) thereunder.
---------------------------------------------------------------------------

    \22\ 15 U.S.C. 78s(b)(3)(A)(iii).
    \23\ 17 CFR 240.19b-4(f)(6).
---------------------------------------------------------------------------

    At any time within 60 days of the filing of such proposed rule
change, the Commission summarily may temporarily suspend such rule
change if it appears to the Commission that such action is necessary or
appropriate in the public interest, for the protection of investors, or
otherwise in furtherance of the purposes of the Act. If the Commission
takes such action, the Commission shall institute proceedings under
Section 19(b)(2)(B) \24\ of the Act to determine whether the proposed
rule change should be approved or disapproved.
---------------------------------------------------------------------------

    \24\ 15 U.S.C. 78s(b)(2)(B).
---------------------------------------------------------------------------

IV. Solicitation of Comments

    Interested persons are invited to submit written data, views, and
arguments concerning the foregoing, including whether the proposed rule
change is consistent with the Act. Comments may be submitted by any of
the following methods:

Electronic Comments

     Use the Commission's Internet comment form (http://www.sec.gov/rules/sro.shtml); or
     Send an email to<EMAIL_ADDRESS>Please include
File No. SR-NYSEMKT-2016-53 on the subject line.

Paper Comments

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

All submissions should refer to File No. SR-NYSEMKT-2016-53. This file
number should be included on the subject line if email is used. To help
the Commission process and review your comments more efficiently,
please use only one method. The Commission will post all comments on
the Commission's Internet Web site (http://www.sec.gov/rules/sro.shtml). Copies of the submission, all subsequent amendments, all
written statements with respect to the proposed rule change that are
filed with the Commission, and all written communications relating to
the proposed rule change between the Commission and any person, other
than those that may be withheld from the public in accordance with the
provisions of 5 U.S.C. 552, will be available for Web site viewing and
printing in the Commission's Public Reference Room, 100 F Street NE.,
Washington, DC 20549 on official business days between the hours of
10:00 a.m. and 3:00 p.m. Copies of such filing also will be available
for inspection and copying at the principal office of the Exchange. All
comments received will be posted without change; the Commission does
not edit personal identifying information from submissions. You should
submit only information that you wish to make available publicly. All
submissions should refer to File No. SR-NYSEMKT-2016-53, and should be
submitted on or before June 10, 2016.

    For the Commission, by the Division of Trading and Markets,
pursuant to delegated authority.\25\
Robert W. Errett,
Deputy Secretary.
---------------------------------------------------------------------------

    \25\ 17 CFR 200.30-3(a)(12).
---------------------------------------------------------------------------

[FR Doc. 2016-11877 Filed 5-19-16; 8:45 am]
 BILLING CODE 8011-01-P


[Federal Register Volume 81, Number 143 (Tuesday, July 26, 2016)]
[Notices]
[Pages 48809-48813]
[FR Doc No: 2016-17570]

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

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: 044

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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

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: 044 (Recognition List Number: 044), will assist manufacturers
who elect to declare conformity with consensus standards to meet
certain requirements for medical devices.

DATES: Submit electronic or written comments concerning this document
at any time. These modifications to the list of recognized standards
are effective July 26, 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-2004-N-0451 for ``Food and Drug Administration Modernization Act of
1997: Modifications to the List of Recognized Standards, Recognition
List Number: 044.'' 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. 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: 043.
     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.
    An electronic copy of Recognition List Number: 044 is available on
the Internet at http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/Standards/ucm123792.htm. See section VI of
this document for electronic access to the searchable database for the
current list of FDA recognized consensus standards, including
Recognition List Number: 044 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: 044'' to Scott A. Colburn, Center for Devices
and Radiological Health, Food and Drug Administration, 10903 New
Hampshire Ave., Bldg. 66, Rm. 5514, Silver Spring, MD 20993. 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 A. Colburn, Center for Devices
and Radiological Health, Food and Drug Administration, 10903 New
Hampshire Ave., Bldg. 66, Rm. 5514, Silver Spring, MD 20993, 301-796-
6287<EMAIL_ADDRESS>
SUPPLEMENTARY INFORMATION:

I. Background

    Section 204 of the Food and Drug Administration Modernization Act
of 1997 (FDAMA) (Pub. L. 105-115) amended section 514 of the Federal
Food, Drug, and Cosmetic Act (the 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 a notice published in the Federal Register of February 25, 1998
(63 FR 9561), FDA announced the availability of a guidance entitled
``Recognition and Use of Consensus Standards.'' The

notice described how FDA would implement its standard recognition
program and provided the initial list of recognized standards.
    Modifications to the initial list of recognized standards, as
published in the Federal Register, can be accessed at http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/Standards/ucm123792.htm.
    These notices describe the addition, withdrawal, and revision of
certain standards recognized by FDA. The Agency maintains hypertext
markup language (HTML) and portable document format (PDF) versions of
the list of FDA Recognized Consensus Standards. Both versions are
publicly accessible at the Agency's Internet site. See section VI of
this document for electronic access information. Interested persons
should review the supplementary information sheet for the standard to
understand fully the extent to which FDA recognizes the standard.

II. Modifications to the List of Recognized Standards, Recognition List
Number: 044

    FDA is announcing the addition, withdrawal, correction, and
revision of certain consensus standards the Agency will recognize for
use in premarket submissions and other requirements for devices. FDA
will incorporate these modifications in the list of FDA Recognized
Consensus Standards in the Agency's searchable database. FDA will use
the term ``Recognition List Number: 044'' to identify these 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 the initial addition of standards not previously recognized by
FDA.

                           Table 1--Modifications to the List of Recognized Standards
----------------------------------------------------------------------------------------------------------------
                                          Replacement
          Old recognition No.             recognition        Title of standard \1\               Change
                                              No.
----------------------------------------------------------------------------------------------------------------
                                               A. Biocompatibility
----------------------------------------------------------------------------------------------------------------
2-93..................................  ..............  ASTM F763-04 (Reapproved 2010)  Extent of recognition,
                                                         Standard Practice for Short-    Relevant guidance.
                                                         Term Screening of Implant
                                                         Materials.
2-94..................................  ..............  ASTM F981-04 (Reapproved 2010)  Extent of recognition,
                                                         Standard Practice for           Relevant guidance.
                                                         Assessment of Compatibility
                                                         of Biomaterials for Surgical
                                                         Implants with Respect to
                                                         Effect of Materials on Muscle
                                                         and Bone.
2-114.................................  ..............  ASTM F1877-05 (Reapproved       Extent of recognition,
                                                         2010) Standard Practice for     Relevant guidance.
                                                         Characterization of Particles.
2-117.................................           2-226  ANSI/AAMI/ISO 10993-3:2014      Withdrawn and replaced
                                                         Biological evaluation of        with newer version.
                                                         medical devices--Part 3:
                                                         Tests for genotoxicity,
                                                         carcinogenicity, and
                                                         reproductive toxicity.
2-118.................................  ..............  ANSI/AAMI/ISO 10993-11:2006/    Reaffirmation, Extent of
                                                         (R) 2014 Biological             recognition, Relevant
                                                         evaluation of medical           guidance.
                                                         devices--Part 11: Tests for
                                                         systemic toxicity.
2-119.................................  ..............  ASTM F813-07 (Reapproved 2012)  Extent of recognition,
                                                         Standard Practice for Direct    Relevant guidance.
                                                         Contact Cell Culture
                                                         Evaluation of Materials for
                                                         Medical Devices.
2-120.................................  ..............  ANSI/AAMI/ISO 10993-6:2007/(R)  Reaffirmation, Extent of
                                                         2014 Biological evaluation of   recognition, Relevant
                                                         medical devices--Part 6:        guidance.
                                                         Tests for local effects after
                                                         implantation.
2-122.................................  ..............  ASTM F719-81 (Reapproved 2012)  Extent of recognition,
                                                         Standard Practice for Testing   Relevant guidance.
                                                         Biomaterials in Rabbits for
                                                         Primary Skin Irritation.
2-124.................................  ..............  ASTM F750-87 (Reapproved 2012)  Extent of recognition,
                                                         Standard Practice for           Relevant guidance.
                                                         Evaluating Material Extracts
                                                         By Systemic Injection in the
                                                         Mouse.
2-126.................................  ..............  ASTM F748-06 (Reapproved 2010)  Extent of recognition,
                                                         Standard Practice for           Relevant guidance.
                                                         Selecting Generic Biological
                                                         Test Methods for Materials
                                                         and Devices.
2-133.................................  ..............  ASTM F1408-97 (Reapproved       Extent of recognition,
                                                         2013) Standard Practice for     Relevant guidance.
                                                         Subcutaneous Screening Test
                                                         for Implant Materials.
2-134.................................  ..............  ASTM F2065-00 (Reapproved       Extent of recognition,
                                                         2010) Standard Practice for     Relevant guidance.
                                                         Testing for Alternative
                                                         Pathway Complement Activation
                                                         in Serum by Solid Materials.
2-136.................................  ..............  ASTM E1262-88 (Reapproved       Extent of recognition,
                                                         2013) Standard Guide for        Relevant guidance.
                                                         Performance of Chinese
                                                         Hamster Ovary Cell/
                                                         Hypoxanthine Guanine
                                                         Phosphoribosyl Transferase
                                                         Gene Mutation Assay.
2-141.................................  ..............  ASTM F1984-99 (Reapproved       Extent of recognition,
                                                         2013) Standard Practice for     Relevant guidance.
                                                         Testing for Whole Complement
                                                         Activation in Serum by Solid
                                                         Materials.
2-142.................................           2-227  ASTM F1983-14 Standard          Withdrawn and replaced
                                                         Practice for Assessment of      with newer version.
                                                         Selected Tissue Effects of
                                                         Absorbable Biomaterials for
                                                         Implant Applications.
2-145.................................  ..............  ASTM F1439-03 (Reapproved       Extent of recognition,
                                                         2013) Standard Guide for        Relevant guidance.
                                                         Performance of Lifetime
                                                         Bioassay for the Tumorigenic
                                                         Potential of Implant
                                                         Materials.
2-153.................................  ..............  ANSI/AAMI/ISO 10993-5:2009/(R)  Extent of recognition,
                                                         2014 Biological evaluation of   Relevant guidance.
                                                         medical devices--Part 5:
                                                         Tests for in vitro
                                                         cytotoxicity.
2-155.................................  ..............  ASTM F2147-01 (Reapproved       Extent of recognition,
                                                         2010) Standard Practice for     Relevant guidance.
                                                         Guinea Pig: Split Adjuvant
                                                         and Closed Patch Testing for
                                                         Contact Allergens.
2-156.................................  ..............  ANSI/AAMI 10993-1:2009/(R)      Extent of recognition,
                                                         2013 Biological evaluation of   Relevant guidance.
                                                         medical devices--Part 1:
                                                         Evaluation and testing within
                                                         a risk management process
                                                         [Including: Technical
                                                         Corrigendum 1 (2010)].
2-162.................................  ..............  ASTM F1903-10 Standard          Extent of recognition,
                                                         Practice for Testing For        Relevant guidance.
                                                         Biological Responses to
                                                         Particles In Vitro.

2-163.................................  ..............  ANSI/AAMI/ISO 10993-9: 2009/    Reaffirmation, Extent of
                                                         (R) 2014 Biological             recognition, Relevant
                                                         evaluation of medical           guidance.
                                                         devices--Part 9: Framework
                                                         for identification and
                                                         quantification of potential
                                                         degradation products.
2-165.................................  ..............  ANSI/AMMI/ISO 10993-14:2001/    Relevant guidance.
                                                         (R) 2011, Biological
                                                         evaluation of medical
                                                         devices--Part 14:
                                                         Identification and
                                                         quantification of degradation
                                                         products form ceramics.
2-167.................................  ..............  ISO TS 10993-19 First edition   Extent of recognition,
                                                         2006-06-01 Biological           Relevant guidance.
                                                         evaluation of medical
                                                         devices--Part 19: Physio-
                                                         chemical, morphological and
                                                         topographical
                                                         characterization of materials.
2-168.................................  ..............  ISO 10993-9 Second edition      Extent of recognition,
                                                         2009-12-15 Biological           Relevant guidance.
                                                         evaluation of medical
                                                         devices--Part 9: Framework
                                                         for identification and
                                                         quantification of potential
                                                         degradation products.
2-169.................................  ..............  ISO 10993-13 Second edition     Extent of recognition,
                                                         2010-06-15, Biological          Relevant guidance.
                                                         evaluation of medical
                                                         devices--Part 13:
                                                         Identification and
                                                         quantification of degradation
                                                         products from polymeric
                                                         medical devices.
2-170.................................  ..............  ISO 10993-14 First edition      Relevant guidance.
                                                         2001-11-15, Biological
                                                         evaluation of medical
                                                         devices--Part 14:
                                                         Identification and
                                                         quantification of degradation
                                                         products from ceramics.
2-171.................................  ..............  ISO 10993-16 Second edition     Relevant guidance.
                                                         2010-02-15, Biological
                                                         evaluation of medical
                                                         devices--Part 16:
                                                         Toxicokinetic study design
                                                         for degradation products and
                                                         leachables.
2-172.................................  ..............  ANSI/AAMI/ISO TIR 10993-        Extent of recognition,
                                                         19:2006 Biological evaluation   Relevant guidance.
                                                         of medical devices--Part 19:
                                                         Physicochemical,
                                                         morphological, and
                                                         topographical
                                                         characterization of materials.
2-173.................................  ..............  ANSI/AAMI/ISO 10993-10:2010/    Reaffirmation, Extent of
                                                         (R) 2014 Biological             recognition, Relevant
                                                         evaluation of medical           guidance.
                                                         devices--Part 10: Tests for
                                                         irritation and skin
                                                         sensitization.
2-174.................................  ..............  ISO 10993-10 Third Edition      Extent of recognition,
                                                         2010-08-01 Biological           Relevant guidance.
                                                         evaluation of medical
                                                         devices--Part 10: Tests for
                                                         irritation and skin
                                                         sensitization.
2-175.................................           2-228  ISO 10993-3:2014 Third edition  Withdrawn and replaced
                                                         2014-10-1 Biological            with newer version.
                                                         evaluation of medical
                                                         devices--Part 3: Tests for
                                                         genotoxicity,
                                                         carcinogenicity, and
                                                         reproductive toxicity.
2-176.................................  ..............  ISO 10993-11 Second edition     Extent of recognition,
                                                         2006-08-15 Biological           Relevant guidance.
                                                         evaluation of medical
                                                         devices--Part 11: Tests for
                                                         systemic toxicity.
2-177.................................  ..............  ISO 10993-06 Second edition     Extent of recognition,
                                                         2007-04-15 Biological           Relevant guidance.
                                                         evaluation of medical
                                                         devices--Part 6: Tests for
                                                         local effects after
                                                         implantation.
2-180.................................  ..............  ANSI/AAMI/ISO 10993-16:2010/    Relevant guidance.
                                                         (R) 2014, Biological
                                                         evaluation of medical
                                                         devices--Part 16:
                                                         Toxicokinetic study design
                                                         for degradation products and
                                                         leachables from medical
                                                         devices.
2-189.................................  ..............  ASTM F895-11 Standard Test      Extent of recognition,
                                                         Method for Agar Diffusion       Relevant guidance.
                                                         Cell Culture Screening for
                                                         Cytotoxicity.
2-190.................................  ..............  ANSI/AAMI/ISO 10993-13:2010/    Reaffirmation, Extent of
                                                         (R) 2014 Biological             recognition, Relevant
                                                         evaluation of medical           guidance.
                                                         devices--Part 13:
                                                         Identification and
                                                         quantification of degradation
                                                         products from polymeric
                                                         medical devices.
2-191.................................  ..............  ISO 10993-12 Fourth edition     Extent of recognition,
                                                         2012-07-01 Biological           Relevant guidance.
                                                         evaluation of medical
                                                         devices--Part 12: Sample
                                                         preparation and reference
                                                         materials.
2-197.................................  ..............  ASTM F749-13 Standard Practice  Extent of recognition,
                                                         for Evaluating Material         Relevant guidance.
                                                         Extracts by Intracutaneous
                                                         Injection in the Rabbit.
2-198.................................  ..............  ANSI/AAMI/ISO 10993-12:2012     Extent of recognition,
                                                         Biological evaluation of        Relevant guidance.
                                                         medical devices--Part 12:
                                                         Sample preparation and
                                                         reference materials.
2-204.................................  ..............  ASTM F720-13 Standard Practice  Extent of recognition,
                                                         for Testing Guinea Pigs for     Relevant guidance.
                                                         Contact Allergens: Guinea Pig
                                                         Maximization Test.
2-206.................................  ..............  ASTM F2148-13 Standard          Extent of recognition,
                                                         Practice for Evaluation of      Relevant guidance.
                                                         Delayed Contact
                                                         Hypersensitivity Using the
                                                         Murine Local Lymph Node Assay
                                                         (LLNA).
2-207.................................  ..............  ASTM F756-13 Standard Practice  Extent of recognition,
                                                         for Assessment of Hemolytic     Relevant guidance.
                                                         Properties of Materials.
2-213.................................  ..............  ASTM F1904-14 Standard          Extent of recognition,
                                                         Practice for Testing the        Relevant guidance.
                                                         Biological Responses to
                                                         Particles In Vivo.
2-214.................................  ..............  ASTM F619-14 Standard Practice  Extent of recognition,
                                                         for Extraction of Medical       Relevant guidance.
                                                         Plastics.
2-215.................................           2-229  USP 39-NF34:2016 <87>           Withdrawn and replaced
                                                         Biological Reactivity test,     with a newer version.
                                                         In Vitro--Direct Contact Test.
2-216.................................           2-230  USP 39-NF34:2016 <87>           Withdrawn and replaced
                                                         Biological Reactivity Test,     with a newer version.
                                                         In Vitro--Elution Test.
2-217.................................           2-231  USP 39-NF34: 2016 <88>          Change in title,
                                                         Biological Reactivity Tests,    Withdrawn and replaced
                                                         In Vivo.                        with a newer version.
2-218.................................  ..............  USP 39-NF34: 2016 <88>          Withdrawn; See 2-231.
                                                         Biological Reactivity Tests
                                                         In Vivo, Classification of
                                                         Plastics--Intracutaneous Test.
2-219.................................  ..............  USP 39-NF34: 2016 <88>          Withdrawn; See 2-231.
                                                         Biological Reactivity Tests
                                                         In Vivo, Classification of
                                                         Plastics--Systemic Injection
                                                         Test.

2-220.................................  ..............  ISO 10993-1 Fourth edition      Extent of recognition,
                                                         2009-10-15 Biological           Relevant guidance.
                                                         evaluation of medical
                                                         devices--Part 1: Evaluation
                                                         and testing within a risk
                                                         management process
                                                         [Including: Technical
                                                         Corrigendum 1 (2010)].
2-221.................................  ..............  ANSI/AAMI/ISO 10993-2:2006/(R)  Extent of recognition,
                                                         2014 Biological evaluation of   Relevant guidance.
                                                         medical devices--Part 2:
                                                         Animal welfare requirements.
2-222.................................  ..............  ISO 10993-2 Second edition      Extent of recognition,
                                                         2006-07-15 Biological           Relevant guidance.
                                                         evaluation of medical
                                                         devices--Part 2: Animal
                                                         welfare requirements.
2-223.................................  ..............  ASTM F2901-13, Standard guide   Relevant guidance.
                                                         for selecting tests to
                                                         evaluate potential
                                                         neurotoxicity of medical
                                                         devices.
2-225.................................  ..............  ASTM F2567-06 (Reapproved       Relevant guidance.
                                                         2010), Standard practice for
                                                         testing for classical
                                                         complement activation in
                                                         serum by solid materials.
----------------------------------------------------------------------------------------------------------------
                                                  B. Sterility
----------------------------------------------------------------------------------------------------------------
14-477................................           2-232  USP 39-NF34:2016 <151> Pyrogen  Transferred to
                                                         Test.                           Biocompatibility;
                                                                                Relevant guidance.
----------------------------------------------------------------------------------------------------------------
\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: 044.

        Table 2--New Entries to the List of Recognized Standards
------------------------------------------------------------------------
                                                          Reference No.
        Recognition No.          Title of standard \1\      and Date
------------------------------------------------------------------------
                           A. Biocompatibility
------------------------------------------------------------------------
2-233.........................  Standard Test Method    F2382-04
                                 for Assessment of       (Reapproved
                                 Intravascular Medical   2010).
                                 Device Materials on
                                 Partial
                                 Thromboplastin Time
                                 (PTT).
2-234.........................  Biological Evaluation   ANSI/AAMI/ISO
                                 of Medical Devices--    10993-4:2002/
                                 Part 4: Selection of    (R)2013 &
                                 tests for interaction   A1:2006/
                                 with blood [Including   (R)2013.
                                 Amendment 1(2006)].
2-235.........................  Biological Evaluation   ISO 10994-4
                                 of Medical Devices--    Second edition
                                 Part 4: Selection of    2002-10-15
                                 tests for interaction   Amendment 1
                                 with blood [Including   2006-07-15.
                                 Amendment 1(2006)].
2-236.........................  Biological evaluation   ANSI/AAMI/ISO
                                 of medical devices--    10993-17:2002/
                                 Part 17:                (R)2012.
                                 Establishment of
                                 allowable limits for
                                 leachable substances.
2-237.........................  Biological evaluation   ISO 10993-17
                                 of medical devices--    First edition
                                 Part 17:                2002-12-01.
                                 Establishment of
                                 allowable limits for
                                 leachable substances.
2-238.........................  Biological evaluation   ANSI/AAMI BE 83:
                                 of medical devices--    2006/(R)2011.
                                 Part 18: Chemical
                                 characterization of
                                 materials.
2-239.........................  Biological evaluation   ANSI/AAMI/ISO
                                 of medical devices--    TIR 10993-
                                 Part 20: Principles     20:2006.
                                 and methods for
                                 immunotoxicology
                                 testing of medical
                                 devices.
2-240.........................  Biological evaluation   ISO/TS 10993-20
                                 of medical devices--    First edition
                                 Part 20: Principles     2006-08-01.
                                 and methods for
                                 immunotoxicology
                                 testing of medical
                                 devices.
2-241.........................  Cardiovascular          ISO/TR 37137
                                 biological evaluation   First edition
                                 of medical devices--    2014-05-15.
                                 Guidance for
                                 absorbable implants.
2-242.........................  Cardiovascular          ANSI/AAMI/ISO TR
                                 biological evaluation   37137: 2014.
                                 of medical devices--
                                 Guidance for
                                 absorbable implants.
2-243.........................  Biological evaluation   ISO/TR 10993-
                                 of medical devices--    33:2015 First
                                 Part 33: Guidance on    edition 2015-03-
                                 tests to evaluate       01.
                                 genotoxicity.
------------------------------------------------------------------------
\1\ All standard titles in this table conform to the style requirements
  of the respective organizations.

IV. List of Recognized Standards

    FDA maintains the Agency's current list of FDA Recognized Consensus
Standards in a searchable database that may be accessed directly at
FDA's Internet site at http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfStandards/search.cfm. FDA will incorporate the modifications
and revisions described in this notice into the database and, upon
publication in the Federal Register, this recognition of consensus
standards will be effective. 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.
Beginning with Recognition List 033, FDA no longer announces minor
revisions to the list of recognized consensus standards such as
technical contact person, devices affected, processes affected, Code of
Federal Regulations citations, and product codes.

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_ADDRESS>To be properly considered,

such recommendations should contain, at a minimum, the following
information: (1) Title of the standard, (2) any reference number and
date, (3) name and address of the national or international standards
development organization, (4) a proposed list of devices for which a
declaration of conformity to this standard should routinely apply, and
(5) a brief identification of the testing or performance or other
characteristics of the device(s) that would be addressed by a
declaration of conformity.

VI. Electronic Access

    You may obtain a copy of ``Guidance on the Recognition and Use of
Consensus Standards'' by using the Internet. The Center for Devices and
Radiological Health (CDRH) maintains a site on the Internet for easy
access to information including text, graphics, and files that you may
download to a personal computer with access to the Internet. Updated on
a regular basis, the CDRH home page, http://www.fda.gov/MedicalDevices,
includes a link to standards-related documents including the guidance
and the current list of recognized standards. After publication in the
Federal Register, this notice announcing ``Modification to the List of
Recognized Standards, Recognition List Number: 044'' will be available
at http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/Standards/ucm123792.htm. You may access ``Guidance on the Recognition
and Use of Consensus Standards,'' and the searchable database for ``FDA
Recognized Consensus Standards'' at http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/Standards.

    Dated: July 19, 2016.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2016-17570 Filed 7-25-16; 8:45 am]
 BILLING CODE 4164-01-P