QENTER FQR DRUG EYALIJATIQN AND RESEARQ :fl
`
`AP
`
`ATI
`
`MBER: NDA 20845
`
`
`
`

`

`ENVIRONMENTAL ASSESSMENT
`
`AND
`
`' FINDING OF NO SIGNIFICANT IMPACT
`
`FOR
`
`NITRIC OXIDE FOR INHALATION
`(400 ppm in Nitrogen)
`
`NDA 29:845.
`
`FOOD AND DRUG ADMINISTRATION
`CENTER FOR DRUG EVALUATION AND RESEARCH
`‘ DIVISION OF CARDIO-RENAL DRUG PRODUCTS
`(HFD-IIO)
`Ar
`
`NDA 20-845
`
`

`

`
`
`{I
`
`u
`
`FINDING OF NO SIGNIFICANT IMPACT
`
`NDA 20-845
`
`NITRIC OXIDE FOR INHALATION
`
`The National Environmental Policy Act of 1969 (NEPA) reguires all Federal agendas to assess the
`environmental
`impact of their actions.
`FDA is required under NEPA to consider the
`environmental impact of approving certain drug product applications as an integral part of its
`regulatory process.
`R
`
`will not have a significant effect on the quality of the human environment and that an
`environmental impact statement therefore will not be prepared.
`
`‘In support of their. new orphan drug application for Nitric Oxide for Inhalation, Ohmeda ‘
`Pharmaceutical Products Division Inc (Ohmeda PPD), Liberty Comer, New jersey 07938-0804
`prepared an environmental assessment (attached) which evaluates the potential environmental
`impacts of the manufacture, use and disposal of the product. The format for the environmental
`assessment for an orphan drug NDA, defined in 21 CPR 2531a (b) (3), is the same as the Tier 0
`format.
`
`The combustion of fossil fuels results in the emission of millions of tors of nitric oxide into the
`atmosphere. The quantities used for medical purposes are very small by comparison.
`Furthermore, precautions used in manufacturing and administration to patients are designed to
`minimize atmospheric emissions related to this NDA.
`
`Nitric oxide is a synthetic gaseous drug substance. It is diluted in nitrogen, specifically, 400 ppm
`NO in nitrogen. It is administered to term and near term infants in conjunction with mechanical
`ventilation for the treatment of respiratory hypoxia. The drug substance, nitric oxide, and the'
`drug product, Nitric Oxide for Inhalation, are manufactured, packaged, tested and labeled by
`(BOC Gases, Port Allen, LA 70767.J Both Ohmeda PPD andrBOC Cases are operating divisions of
`l:I'he BOC Group Inc. JChemical waste is collected and shipped frofi‘i Port Allendbyr
`Ator
`_:a licensed chemical
`waste disposal company. All facilities are certified to operate in accord with applicable
`environmental regulations.
`
`The drug product, Nitric Oxide for Inhalation, will be used primarily in hospitals and
`secondarily, in ambulatory transport.
`.
`
`Nitric oxide must be administered through the I-NOvent (or equivalent) delivery device to
`n'iinimize escape of nitrogen oxides into the environment. The amount of inhaled nitric oxide that
`is absorbed by a patient is variable, however some nitric oxide rapidly diffuses into the vascular
`bed where it
`induces vasodilatation and undergoes rapid inactivation by reaction with
`
`Acid waste from the drug substance manufacturing operations is neutralized to pH 7, analyzed
`and disposed into the municipal storm sewers.
`
`INDA 204545
`
`

`

`2|
`
`It
`
`-" Residual nitric oxide (drug substance) contained in reusable aluminum alloy compressed gas
`cylinders with a stainless steel valve withr'l'eflon O-Ringa is disposed by‘BOC Gases at the Port__1
`[Mien site;1The contents of compressed gas cylinders containing less than 10% nitric oxide may
`vented to the atmosphere according to the Small Source Exemption for Air Emission issued by the
`State of Louisiana tot-80C Gases” on'Dec'ember 14, 1994. Alternatively, the cylinders may be
`shipped to a licensed chemical waste disposal company. lhis includes all rejected, used (empty),
`unused (partially full) or expired drug product cylinders.
`-
`
`The contents of compressed gas cylinders containing more-[than 10% nitric oxide are treate with
`oxygen to form higher oxides of nitrogen, scrubbed with caustic solution and disposed b
`
`Adverse effects are not anticipated upon endangered or threatened species or upon property
`listed in or eligible for listing in the National Register of Historic Places.
`-
`
`luly 21,192?
`Date
`
`a
`
`PREPARED BY: Florian Zielinski, Review Chemist
`Division of New Drug Chemistry I
`
`
`
` ON CONCURRENCE: Robert Wolters
`
`D'
`
`ision of New Drug Chemistry I
`A
`
`
`
`142' glfi-
`ate
`APPROVED: Nan
`. Sager, Team ader
`Environmental Assessment Team
`. Center for Drug Evaluation and Research
`
`'
`
`Attachments:
`
`Environmental Assessment, pages 332 to 356
`Material Safety Data Sheets -
`a) Nitric Oxide, pages 344 to 350
`b) Nitric Oxide in Nitrogen, 0.00001% to 1%, pages 351 to 356
`
`Original; NDA 20-845;
`HFD-357 FONSI File [NDA 20-845]
`RFD-357 Docket File
`HFD-ZOS POI COPY
`HFD-l 10 Division File
`HFD-110 C50, Zelda McDonald
`RFD-110 Review Chemist, Florian Zielinski
`
`-
`
`~
`
`NDA 20-845
`
`

`

`mo “(nitric oxide) for inhalation
`NDA CMC Submission
`V. Enviromnental Assess-nan:
`
`1. Date of preparation
`
`February 21, 1997. ,7
`
`2. Name of Applicant/Petitioner
`
`Ohmeda Pharmaceutical Products Division (PPD) Inc
`The BOC Group of Companies
`"
`
`3. Address
`
`110AllenRoad
`
`I
`
`"
`
`Liberty Corner, NJ 07933, USA
`
`’ 4. Description ofProgosed Action
`
`:1. Requested Approval
`
`Pursuant to section 505 (b)(2) ofthe Act, OhmedaPPDIS submitting an NBA for an
`.orphan drug, I-NO" (Nitric Oxide) for Inhalation, 400 ppm (in nitrogen), packagedin
`a seamless aluminum compressed gas cylinder with a stainless steel valve and Teflon
`gasket. An environmental assessment
`(EA), prepared according to the Tier 0
`approach,
`is being submitted pursuant to 21 CFR 25.25a(b)(5) and the FDA EA
`
`guideline.
`
`I). Need For Action
`
`, "‘
`
`(RDS), meconium aspiration,
`distress‘ syndrome
`respiratory
`hypertension,
`pneumonia/sepsis, and congenital diaphragmatic hernia. This15 a new therapy for the
`
`
`
`

`

`LNG "(nitric oxide) for inhalation
`N‘DA CMC Sutmissian
`". Enviromnenlal Assessmmt
`
`_
`
`treatment of respiratory hypoxia in infants and can provide significant advantages
`
`over the existing therapies.
`!
`
`c'. Production Location
`_
`.
`.
`Both Ohmeda PPD Inc, the NDA holder, and ECG Gases," the manufacturer of the
`drug substance/product (listed below), are operating divisionslsubsidiaries of The
`
`BOC Group Inc.
`
`The drug substance (NO) and drug product (Nitric Oxide for Inhalation) will be
`
`manufactured, packaged, tested, and labeled at the facility listed below (also known as
`
`the Port Allen site).
`
`(I
`
`BOC Gases
`
`1075 Cinclare Drive
`
`Port Allen, LA 70767, USA
`
`Port Allen is a suburb of Baton Rouge, Louisiana and is locatedon the opposite bank
`
`ofthe Mississippi River (within about 2 miles.) The BOC Gases facility1s located in-
`an induStrial zone. The region is flat and the climatets temperate.
`
`d. Locations 01‘ Use
`
`Nitric Oxide for Inhalation Will be used primarily in hospitals and secondarily in
`
`ambulatmy transport;
`
`Page 3114
`ml...“I -.:¢_\......,-.\_n\.u-:nnaln\a-nvnwunl‘chnrdnn.doc
`
`0334"
`
`

`

`l-NO "(nitric oxide) for inhalation
`NBA cue Submission
`V. Enviromncnlal W]!
`
`e. Disposal Sites
`
`.
`i. DISPOSAL or 511m315 BY-PRODUCTS
`Nitric oxide (NO) is synthesized in a one step process according to the chemical
`
`reaction listed below.
`
`2H20 + 3 SO; + ZI'D‘I03 ‘9 2N0 + 3H2$04
`(sulfur dioxide) (nfin'c acid)
`(nitric oxide) (sulfuric acid)
`
`The by-products of the drug synthesis are sulfuric acid, a reaction by—product, and
`
`nitric acid, which is reacted in excess.
`
`Rrior to disposal, sulfuric and nitric acids are neutralized with caustic solution to
`pH 7, in accordance with the regulations of the City of Port Allen.
`[The neutralized
`waste is analyzed by an independent laboratoryf
`L/Icontracted by BOC Gases, in order to monitor long-term sulfate
`and nitrate salt output] The neutralized solution then is released into the municipal
`
`storm sewers-as permitted by the City of Port Allen (BOC Gases Waste Generators
`
`I.
`
`' Permit No. LAD094178050).
`
`Any residual SO; is scrubbed with a caustic solution, and the exhausted scrubber
`
`solution is collected and shipped from the Port Allen site by(
`
`disposal companyr
`
`J to a licensed chemical waste
`
`. _J
`
`ii. DISPOSAL OF NITRIC OXIDE DRUG SUBSTANCE AND DRUG PRODUCT
`
`As the drug product, which is packaged in a reusable aluminum alloy compressed gas
`
`cylinder with a stainless steel valve and Teflon O-ring is ‘loaned' to the health care
`
`provider, all used, unused or expired drug product cylinders are expected to be
`
`returned from the user to Port Allen for disposal as described below. If any supplies
`
`V
`
`.
`
`0335
`
`Page4!!4
`
`gzlregulaulcmeunolorigndaknvasmnlbonfdnll .doc
`
`
`
`a
`E
`
`

`

`l-Nommitric oxide) for inhalation
`' NDA CMC Submisicn
`V. FAWN Asml
`
`" are not returned by US hOSpitals, pharmacies or clinics, they will be disposed of
`according to hospital, pharmacy or clinic procedures.
`
`Returned, expired, drug product or rejected drug substance and/or. drug product will
`be disposed of either by BOC Gases at the Po
`rt Allen site, or shipped to a licensed
`chemical waste disposal company.
`i
`'
`
`Thecontents of compressed gas cylinders containing nitric oxide
`
`greater than 1
`
`5.
`
`a.
`
`i.
`
`Identification of Chemical Substances that are the Subiec ofthe Preposed 7
`Action
`_
`.
`
`Nomenclature
`
`' ESTABLISHED NAMEQJS ADOPTED NAME - 055m
`
`none
`
`ii.
`
`BRAND/PROPRIETARY NAME '
`I-No'” (nitric oxide) for Inhalation
`
`033B
`
`
`
`

`

`l-NO “(nitric oxide) for wanna.
`NDA cue Submission
`V. Environmental Amaneru
`
`_7
`
`iii. CHE CAL
`
`s
`
`.-
`
`(1) Chemical Abstracts-Service (CA8) Name
`
`nitric oxide
`
`_
`(2) Systematic Chemical Name
`nitric oxide; nitrogenal) oxide; mononitrogen monoxide; nitrogen monoxide
`—v
`
`b. Chemical Abstracts Service (CAS) Registration Number
`
`[10102-434]
`
`'
`
`c. Molecular Formula
`
`NO
`
`(1. Molecular Weight
`
`30.01
`
`c.
`
`Structural Formula
`
`f.
`
`Physical Descriptio'ri
`
`Nitric oxide is a colorless gas at room temperature.
`
`g. Additives
`
`The drug substance nitric oxide contains no additives of any kind.
`
`'io—
`
`The drug product Nitric Oxide for Inhalation contains nitrogen (N;) as the sole.
`inactive ingredient. The CAS number for nitrogen'IS [7727-37-9]. Since nitrogen is
`0337
`
`2
`
`Page 6!I 4
`
`
`
`

`

`1.No""(niuic oxide) for inhalation
`NDA CMC Submission
`. V. Enviromnenu] Amen-mm;
`
`'
`
`1
`
`
`
`greater than 1%.
`
`6.1ntroduction of Substances intothe'EnVironment
`
`y
`
`_
`
`b.
`
`.Control Exercised
`
`Information on the control/treatment of emitted substan
`item 4.1: “‘Disposal Sites”.
`
`.0
`
`C.
`
`Citation OfAnd Statement 01' Compliance With Applicable Emission‘
`
`Requirements
`
`
`
`

`

`mo "(nitric oxide) for mum
`N'DA CMC Submission
`v, Envimnmmtsl Assn-11m!
`
`'
`
`_
`
`.
`
`A Waste Generators Permit from the State ofLouisiana, No. LAD094178050.
`
`The Material Safety Data Sheet, for both drug substance and drug product,
`
`is
`
`included in non-confidential Appendix 15.a
`
`d. Discussion 01' Thai-Effect 0f Approval 0n _Compliance With
`Current Emission Requirements
`-
`
`Based upon the estimated sales volume in the fifth year of marketing after approval of
`
`_the Nitric Oxide NDA, pgoduction of nitric oxide at the Port Allen facility will not
`
`adversely affect compliance with applicable environmental regulations, permits, and
`requirements. i
`
`Expected Introduction Concentrations From Use And Disposal
`
`The potential concentration of nitric oxide introduced into the atmosphere as a result
`
`of manufacture, use, and disposal is expected to be less than 1 ppb. as explained in
`
`:
`
`confidential appendix 15b.
`
`7. Fate OfEmitted Substances In The Environment
`
`8. Environmental Effects Of Emitted Substances
`9. Use of Resources and Energy
`
`10. Mitigation Measures
`
`11. Alternatives To The Proposed 'Action
`EA format items 7-1] listed“above are omitted, since nitric oxide is an Orphan Drug
`
`(Application No. 93-744, approved 6/2193) and the EA follows the Tier 0 approach.
`
`The justification for the 'l‘ier 0 approach is provided in confidential Appendix 15.b.
`
`Page am -
`KNEE“ktc‘ancfinobdgrudaknvastnnlloonl‘dnt Ldoc
`
`G 3 3 9
`
`
`
`

`

`l-NO "(mic oxide) for human
`NDA CMC Submission
`V. HAW Amen!
`
`V =:
`
`r
`
`i
`
`_12. List ofPreQarers
`Brian E. Wildstein, Associate Drug Regulatory Affairs
`B.S. Chemistry, State University ofNew York, Stony Brook, NY
`M.S. Chemistry, The Pennsylvania State University, College Park, PA
`Four years experience in the pharmaceutical
`industry including medicinal
`* chemistry and regulatory affairs (CMC).
`.
`
`David L. Ziening, PhD: Assistant Director Drug Regulatory Affairs (cm) -
`B.S. Chemistry, Seton Hall University, South Orange, NJ
`MA. Chemistry, Princeton University, Princeton, NJ
`.PhD. Chemistry, Princeton University, Princeton, NJ
`'Thirteen years experience in the pharmaceutical
`industry including analytical
`chemistry and regulatory affairs (CMC).
`
`
`
`a:
`
`H
`
`.'
`
`0340‘
`
`
`
`

`

`I-NO “(m-5c oxide) for inhalujon
`NDA CMC Submision
`V. Enwumnmul Anus-me“!
`
`Ronald Burkett
`
`Director Environmental Afl‘airs. Ohmeda Inc.
`
`
`
`0341
`
`

`

`(
`
`
`
`NDAQMCSubmission
`i-MJ '"' ("1111C oxide) [or inhalation
`V. Enhmnmmul Assumed .
`
`.
`
`.; Andersen, A. T.
`
`_ 0573(94)
`
`, 1995, DE/EIA
`
`Butler, J. D , Arr Pollution Chemistry Academic: New York, 1979, pp.‘ 37-38,
`
`76-78, 273-275
`
`=Brown, T. L.; Lemay, H. E., Jr.; Bursten, B E. “Th Chemistry ofAtmosphenc
`Pollutants" m Chemmry, 77%: Central Scrence Prentice Hall: Englcwood Clifi‘s
`1991
`
`.
`
`.
`
`‘
`‘
`
`h
`Id
`
`0
`
`Office of Air Pollution. “Air Quaint
`
`Technical Information Services, 1995.
`
`vironmental Protection Agency: National
`
`
`
`

`

`1440 T” (mac oxide) for irduluinn
`NDA cue Submissim
`V. Eavimmuml Astana-nun
`
`15. Appendix
`
`3. Non-Confidentiallnfannation
`
`:-~—
`
`The Material Safety Data Sheet, for both nitric oxide drug substance and dmg
`product, is provided on the pages which‘follow.
`
`
`
`
`

`

`WBOC GASES
`
`MATERIAL SAFETY DATA SHEET
`
` - BRODUCTNAMEIENITRICEE'GXIDE'?:'
`
`1. Chemical Product and Company Identification
`
`-
`
`BOC Gases,
`Division of,
`The BOC Group, Inc
`575 Mountain Avenue
`Murray Hill, NJ 07974
`
`'
`
`TELEPHONE NUMBER: (908) 464-810Q
`24-HOUR EMERGENCY TELEPHONE
`NUMBER: CI-IEMTREC (800) 424-9300
`
`.
`
`'
`
`BOC Gases
`Division of,
`BOC Canada Ltd.
`5975 Falbourne Street, Unit 2
`Mis'sissauga, Ontario LSR 3W6
`
`TELEPHONE NUMBER: (905) 501-1700
`24-HOUR EMERGENCY TELEPHONE
`NUMBER:- (905) 949-3777 -
`-
`EMERGENCY RESPONSE PLAN NO: 20101
`
`PRODUCT NAME; NITRIC OXIDE
`CHEMICAL NAME: Nitric Oxide
`
`COMMON NAMESISYNONYMS: Nitrogen Monoxide
`TDG (Cainada) CLASSIFICATION: 2.3 (5.1. 8)
`WHMIS CLASSIFICATION: A, C. DlA, E. DZB
`
`PREPARED BY: Loss Control (908)464-8lOOI(9OS)273-7700
`PREPARATION DATE: 6/1195
`REVIEW DATES: 6/7196
`
`2. Composition, Information on Ingredients
`
`
`
`FORMULA: no
`CAS: 10102-439
`RTECSfl: oxoszsooo
`;Assutedinl9 CFR 1910 Subpan2.(revised Julyl. 1993)
`2A: stated'1:: the ACGIH 1994-95 Threshold Umit Valor: for Chemical Substance. and Physical Agents
`
`,-
`
`i
`
`‘
`
`_
`:1
`
`3. Hazards Identification
`
`‘
`
`'
`
`:-
`
`
`EMERGENCY-F OVERVIEW
`
`es:and.resniratoly= system“Efleclsmay be delayed for.sever'al
`y _m 0 _ng 0-
`
`ng
`lo
`7
`grepCorrosive. Inhalation mayr'esdltfIn chemical pneumonitis and pulmonary
`
`
`
`edema Nonflammable,Oxidizerh Thispreduct accelera'les the combustion of combdsiible-material..
`
`
`
`E
`
`I
`
`.;_
`
`'
`
`'
`
`MSDS: 6-60
`
`Revised: GIT/96
`
`‘
`
`‘
`
`.0
`
`.
`
`0344
`
`Page 1 of 7
`
`
`
`

`

`
`
` ' PRODUCTrNAME:NITRICOXIDE
`
`: " ROUTE OF ENTRY:
`
`
`
`
`
`
`
`HEALTH EFFECTS:
`MM '
`Yes
`‘ Teratogen
`No
`—
`
`Synergistic Effects
`None Re . - fled
`
`
`
`
`_
`
`-
`
`.
`
`-
`
`‘
`
`
`
`Yes
`Reproductive Hazard
`'
`No
`
`
`
`No
`Mutagen
`No
`
`
`
`
`Carcinogenicity:—NTP: No
`
`IARC: No OSHA: No
`
`EYE EFFECTS:
`
`Severely irritating to the eyes.
`
`SKIN EFFECTS:
`
`Severely‘irritating to dermal tissues.
`
`INGESTION EFFECTS:
`
`None. This product is a gas and cannot be ingested.
`
`INHALATION EFFECTS:
`
`Nitric oxide vapors are a strong irritant to the pulmonary tract. At high concentrations initial symptoms of
`inhalation may be moderate and include irritation to thethroat. tightness of the chest. headache. nausea and
`gradual loss of strength. Severe symptoms may be delayed (possible for several hours) and include cyanosis.
`increased difficulty in breathing. irregular reSpiration, lassitude and possible eventual death due to pulmonary
`edema in untreated cases.
`'
`
`NFPA HAZARD CODES
`
`HMIS HAZARD CODES
`
`RATINGS SYSTEM
`
`0 = No Hazard
`l = Slight Hazard
`2 = Moderate Hazard
`3 = Serious Hazard"
`4 = Severe Hazard ‘
`
`3
`Health:
`Flammability: 0
`Reactivity:
`0
`
`'
`
`-
`
`3
`Health:
`Flammability: 0
`Reactivity:
`0
`OXIDIZER
`
`tt i iI
`
`4. First Aid Measures-
`
`EYES:
`
`Immediately flush with tepid water in large quantities. or with a sterile saline solution. Seek medical attention
`as soon as possible.
`
`\
`
`SKIN:
`
`Immediately flush with tepid water in large quantities. or with a sterile saline solution. Seek medical attention.
`if blisters or other reactions develoP.
`
`INGESTION:
`
`Not required.
`
`MSDS: G-60
`Revised: 6/7/96
`
`-
`
`0345
`
`Page 2 of ‘7
`
`
`
`

`

`
`
`
`
`pRoouanAME':Sige-Nrrths'oxroe.;;I;-'-:-;.}‘
`
`'- 2 INHALATION:
`
`-
`
`PROMPT MEDICAL ATTENTION IS MANDATORY IN ALL CASES OF OVEREXPOSURE. RESCUE
`PERSONNEL SHOULD BE EQUIPPED WITH SELF-CONTAINED BREATHING APPARATUS.
`Conscious victims should be CARRIED (not assisted) to an uncontaminated area and inhale fresh air with
`supplemental oxygen. Quick removal from the contaminated area is most important. .Keep the patient warm,
`(quiet and under competent medical observation until the danger of delayed pulmonary edema has passed (at
`least 72 hours). Any physical exertion during this period should be discouraged as it may increase the severity
`of the pulmonary edema or chemical pneumonitis. Bed rest is indicated. Unconscious persons should be
`moved to an uncontaminated area, and ifbreathing has stepped. administer artificial resuscitation and
`supplemental oxygen: Once respiration has been restored they should be treated as above.
`
`5. Fire Fighting Measures
`
`—.
`
` .1
` Ii"l
`
`U'EL(%}: None
`
`
`
` Conditions of Flammabili
`
`: Not flammable. Oxidizer
`
`Flash point:
`Method:
`Autoignition
`None
`Not A - - licable
`Tern: rature: None
`‘
`LEL(%): None
`Hazardous combustion uroducts: Oxides of nitro en
`
`
`Sensitivity to mechanical shock: None
`
`
`Sensitivi
`to static dischar,e: None
`
`
`
`
`FIRE AND EXPLOSION HAZARDS:
`Nitric oxide is nonflammable but will support combustion. As examples:
`13.5% and an UEL of 49% Methane 942% and Butane 7.5-12.s%.
`
`In NO, hydrogen has a LEL of
`
`EXTINGUISHING MEDIA:
`Not Applicable. Use media appropriate for surrounding—materials. Nitric oxide hydrolizes to nitric acid in the
`presence of moisture.
`
`FIRE FIGHTING INSTRUCTIONS:
`Cut off the flow of gas if possible.
`
`6. Accidental Release Measures '
`
`Evacuate all personnel from afl'ected area. Use appropriate protective equipment. If leak is in userfs
`equipment, be certain to purge piping with inert gas prior to attempting repairs. Ifleak is in container or
`container valve, contact the appropriate emergency telephone number listed in Section I or call your closest
`BOC location.
`-
`'
`-
`
`7. Handling and Storage
`
`Electrical Classification:
`Nonhazardous.
`
`-\
`
`Nitric oxide is' noncorrosive and may be used with most common structural materials. However. in the
`presence of moisture and oxygen~ corrosive conditions will develop as a result of the formation of nitric and
`nitrous acids. Prior to use, systems to contain nitric oxide must first be purged with an inert gas. Where air
`contamination cannot be eliminated. stainless steel materials should be used.
`
`MSDS: 6-60
`Revised: 6/7196
`
`0346
`
`Page 3' of ‘7
`
`
`
`

`

`
`
`'l
`
` FRODUCENAME: i-"NITRinDXIDE.,., ‘ 71'
`
`3
`-' Use only in well-ventilated areas. Valve protection caps must remain in place unless container is secured with
`valve outlet piped to use point. Do not drag, slide or roll cylinders. Use a suitable hand truck for cylinder
`movement. Use a pressure reducing regulator when connecting cylinder to lower pressure (<3000 psig) piping
`or systems. Do not heat cylinder by any means to increase the discharge rate ofproduct from the cylinder.
`Use a check valve or trap in the discharge line to prevent hazardous back flow into the system.
`'
`
`8. Exposure Controls, Personal Protection
`
`EXPOSURE LIMITS':
`
`{NGREDIENTL;:;
`.TE' 11% VOLUME
`
`Nitric Oxide
`
`FORMULA: NO
`
`
`CAS:10102-43-9 '
`
`RTECS #: OXOSZSOOO
`
`
`
`
`98.0 to 99.995
`
`
`" Referlo individual state ofprovincial regulations. as applicable, for limits which may he more miragertt than
`those listed here.
`2:?
`' As stated in 29 CFR 1910. 8:1me Z.(revised July 1. 1993)
`’ As stated in the ACGIH 19944995 'I‘hreshold Limit Values for Chemical Substances and Physical Agents.
`
`
`
`25 ppm TWA
`
`25 ppm TWA
`
`LDso of LC”
`.Routels . -eies '
`
`
`
`
`
`
`
`
`
`IDLH (Nitric Oxide): 100 ppm
`
`ENGINEERING CONTROLS:
`Local exhaust to prevent accumulation of NO above the exposure limit.
`
`EYEIFACE PROTECTION: ‘
`Gas-tight safety goggles or full-face respirator.
`
`_
`SKIN PROTECTION:
`Protective gloves of Rubber or Teflon 0.
`
`RESPIRATORY PROTECTION:
`Positive pressure airline with hill-face mask and escape bottle or self-contained breathing apparatus should be
`available for emergency use.
`'
`
`OTHER/GENERAL PROTECTION:
`Safety shoes and eyewash.
`
`
`
`MSDS: 0-60
`Revised:' err/95
`
`_
`
`\
`
`'
`
`h
`
`.
`
`0 3 4 7
`Page 4 of 7
`
`
`
`

`

` 'PRODUCTFNAMEECif"‘NiTRlC OXIDE
`9. Physical and Chemical Properties
`
`H
`
`.
`
`.
`
`_
`
`=
`
`-
`
`PARAMETER
`Physical stale (gas, liquid, solid)
`Vapor presmre
`_
`Vapor density at 81? (Air = l)
`Evaporation point
`Boiling point
`
`.
`
`’
`
`Freezing point
`-
`
`pH
`Specific gravity
`Oflfuater partition coefl'tcient
`Solubility (HZO)
`Odor threshold
`Odor and appearance
`
`10. Stability and Reactivity
`
`STABILITY:
`Stable
`
`UNITS
`
`-
`
`.
`
`.
`
`VALUE
`: Gas
`: above critical temp.
`: 1.04
`: Not Available
`: -24l.2
`: -15i.9
`: -262.5
`: -163.6
`: Not Applicable.
`: Not Available
`: Not Available
`: Negligible
`: Not Applicable
`: Colorless gas with sufl‘oeating odor. reddish brown
`m atr
`
`.
`
`°F -
`oc:
`°F -
`“C
`
`
`
`
`INCOMPATIBLE MATERIALS:
`Oxidizing agents, halides. hydrocarbons and oxygen. Reacts vigorously with fluorine, fluorine oxides and
`chlorine in the presence of moisture.
`
`HAZARDOUS DECOMPOSITION PRODUCTS:
`Oxidizes in air to form nitrogen dioxide, which is extremely reactive and a strong oxidizer. Upon contact ivith
`moisture and oxygen, it produces nitrous and nitric acids.
`'
`
`HAZARDOUS POLYMERIZATION:
`Will not occur.
`
`11, Toxicological Information
`
`MUTAGENIC:
`There is unspecified mutagenic data for nitric oxide (SAX/RTECS).
`
`OTHER:
`Chronic or repeated‘exposure may cause pemtanent decrements in pulmonary function (Silo Filler's Disease).
`The absence ofmarked acute irritation of nitric oxide limits its warning properties.
`\
`
`12. Ecological Information
`
`No data given.
`
`MSDS: 6-60
`Revised; 6/7/96
`
`,
`
`'
`
`'
`
`0 3 4 8
`page's of‘7
`
`
`
`

`

`PRODUCT'N'AME': .'iNlTR|C OXIDE'
`
`
`
`13. Disposal Considerations
`
`Do not attempt to dispose of residual waste or unused quantities. Return in the shipping container
`PROPERLY LABELED, WITH ANY VALVE OUTLET PLUGS OR CAPS SECURED AND VALVE
`PROTECTION CAP IN PLACE to BOC Gases or authorized distributor for proper disposal.
`
`14. Transport Information
`
`
`
`
`PARAMETER“"la-.14."
`_.
`"
`‘é.5.United-'States-DOT-----~'-‘-'-.'--'-"-."."
`
`
`'
`.:
`
`ennnnnnnnnliIliillnnannllllll
`
`InannaalllllIlllllllalllllll
`
`rennannunallllllllnnslllllll
`
`seasonal-IIIIleanaaanananaunl
`'wmweawmeewemws
`Additional Marl-ting Requirement: “Inhalation Hazard“
`Additional Shipping Paper Description Requirement: “Poison-Inhalation Hazard. Zone B"
`
`
`
`
`
`"'Canada'TDG" “'3
`
`15. Regulatory Information-
`Nitric oxide is listed under the accident prevention provisions of section 112(r) of the Clean Air Act (CAA)
`with a threshold quantity (TQ) of 10.000 pounds.
`
`SARA TITLE [[1 NOTIFICATIONS AND INFORMATION
`Nitric oxide is listed as an extremely hamrdous subsumce (EH8) subject to state and local reporting under
`Section 304 of SARA Title II] (EPCRA).
`
`The presence of nitric oxide in quantities in excess of the threshold planning quantity ('I'PQ) of 100 pounds
`requires cenain emergency planning activities to be conducted.
`
`Releases of nitric oxide in quantities equal to or greater than the reportable quantity (RQ) of 10 pounds are
`subject to reporting to the National Response Center under CERCLA. Section 304 SARA Title III.
`
`SARA TITLE III - HAZARD CLASSES:
`Acute Health Hazard
`Chronic Health Hazard
`
`Sudden Release of Pressure Hazard
`Reactivity Hazard
`
`
`
`
`
`MSDS: 6-60
`Revised: 6/7/96
`
`‘
`
`.
`
`0349
`
`Pageéof?
`
`
`
`

`

`
`
`
`
` PRODUCT‘NAMEfEEéNITRIC'OXIDE‘
`
`_-_'
`
`.1
`
`“16. Other Information
`
`DISCLAIMER OF EXPRESSED AND mum WARRANTIES: .
`
`
`
`.MSDS: 0-60
`Revised: 6/7/96
`
`.
`
`'A
`
`A
`
`.
`
`0350
`Page 7 of7
`
`
`
`

`

`
`
`WBOC GASES
`
`MATERIAL SAFETY DATA SHEETm
`
`
`: pROD‘UCEr-gis-NKMEr-NITRIC OXIDE IN'NITROGEN 0.00001 %TO1%
`1. Chemical Product and Company Identification
`
`_
`:
`3
`
`BOC Gases.
`Division of.
`The BOC Group, Inc
`575 Mountain Avenue
`_
`Murray Hill, NJ 07974
`TELEPHONE NUMBER: (908) 464-8100 7.
`24-HOUR EMERGENCY TELEPHONE
`NUMBER: CHEMTREC (800) 424-9300
`
`I
`
`_
`
`BOC Gases
`Division of.
`BOC Canada Ltd.
`*5975 Falbourne Street. Unit 2
`__ . .. Mississauga, Ontario 15}! 3W6
`TELEPHONE NUMBER: (905) 501-1700
`24-HO‘UR EMERGENCY TELEPHONE
`NUMBER:
`(905) 949-3777
`EMERGENCY RESPONSE PLAN N0: 2010'!
`
`PRODUCT NAME: NITRIC OXIDE IN NITROGEN 0.00001% TO 1%
`CHEMICAL NAME: Nitric Oxide'm Nitrogen
`COMMON NAMEsIstONvMS: Not Applicable
`TDG (Canada) CLASSIFICATION. 2 2
`WHMIS CLASSIFICATION A. 023
`
`PREPARED BY: Loss Control (908)464-8]OO/(905)273-7700
`PREPARATION DATE: 6/1/95
`REVIEW DATES: 6/7/96
`
`2. Composition, Information on Ingredients
`
`
`
`NOREOIeNr
`-
`__ %VOLUME
`1.0.. one” ..
`.'
`Routels- cies ‘
`
`Nitn’c Oxide
`
`0.00001 to ‘l O
`LC”
`FORMULA: N0
`
`
`CA8: 10102-43—9
`1068 mgurn’
`
`
`RTECS #r OXOSZSOOO
`(m!)
`
`
`
`Nitrogen
` Not Avallable
`FORMULA: N;
`
`
`CAS: 7727-37-9
`
`RTECSII: OWBTOOOOO
`
`
`:As statedin 29 CFR1910.SubpanZ(revised July I 1993)
`
`2A5stand':11the ACGIH 1994-95 Threshold Limit Values forChemical Substancesand Physical Agents
`
`3. Hazards Identification
`
`
` 1:: MERGENCY OVERVIEW
`I
`‘_
`_andrespiratorySysttam. Effects maybe delayed forseveral
`
`
`
`__Igh=concentralionsmayr‘eS'u'ltInchemical pneumomus and
`
`
`irogemsaSimple'aspfiyxiant.
`
`
`
`MSDS: 6-153
`Revised: 6/7/96
`
`‘
`
`'
`
`'
`
`0381
`
`
`
`
`25 ppm TWA
`
`25 ppm TWA
`
`
`
`
`
`
`
`

`

`
`
`
`
`
`
`
`
`
`Yes
`
`No
`Synergistic Effects
`Olhcrajntsthatinitatethere .irato -
`
`
`
`_
`
`Yes
`
`No
`
`stemmv.
`
`..
`
`-
`
`'-
`
`-
`
`_
`
`'
`
`
`
`
`'
`
`’
`
`No
`
`Unknown
`
`Carcinogenicityz—N‘I'P: No mac: No" OSHA: No
`
`EYE EFFECTS:
`
`Irritation of the eyes in moderate concentrations.
`
`SKIN EFFECTS:
`None.
`
`‘-
`
`mcasrron EFFECTS: -
`None. This product is a gas and cannot be ingested.
`
`INHALATION EFFECTS:
`Efl'ects of oxygen deficiency resulting from simple asphyxiants may include: rapid breathing. diminished
`mental alertness. impaired muscular coordination. faulty judgement. depression of all sensations. emotional
`instability. and fatigue. As asphyxiation progresses. nausea. vomiting. prostration. and loss of consciousness
`may result. eventually leading to convulsions. coma, and death.
`
`Oxygen deficiency during pregnancy has produced developmental abnormalities in humans and experimental
`animals.
`3
`'
`
`Nitric oxide vapors are a strong im'tant to the pulmonary tract. At high concentrations initial symptoms of
`inhalation may be moderate and include irritation to the throat, tightness of the chest. headache. nausea and
`gradual loss of strength. Severe symptoms may be delayed (possibly for several hours) and include cyanosis,
`increased difiiculty in breathing. irregular respiration. lassitude and possible eventual death due to pulmonary
`edema in untreated cases.
`‘
`NFPA HAZARD CODES
`RATINGS SYSTEM
`
`HMIS HAZARD CODES
`
`.
`
`1
`Health:
`Flammability: 0
`Reactivity:
`0
`
`'
`
`'
`
`1
`Health:
`Flammability: 0
`Reactivity:
`0
`
`o = ‘No Hazard
`l = Slight Hazard
`2 = Moderate Hazard
`3 = Serious Hazard
`4 = Severe Hazard
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`4. First Aid Measures
`
`EYES:
`Immediately flush with tepid water in large
`as soon as possible.
`
`quantities. or with a sterile saline solution. Seek medical attention
`
`.
`MSDS:
`(3-153
`Revised: GNI96
`
`.
`
`'
`
`.
`
`-
`
`-
`
`0352
`
`Page: of 6
`
`
`
`
`
`
`
`

`

`
`
`PRODUCt»NAME:-.=NITRIC OXIDE -lN NITROGEN 'O.DOOD1% TO 1%
`
`
`
`
`
`: SKIN:
`
`None normally required.
`
`INGESTION:
`
`None normally required.
`
`.
`INHALATION:
`PROMPT MEDICAL ATTENTION IS MANDATORY IN ALL CASES OF OVEREJCPOSURE. RESCUE
`PERSONNEL SHOULD BE EQUIPPED WITH SELF-CONTAINED BREATHING APPARATUS.
`Conscious victims should be CARRIED (not assisted) to an uncontaminated area and inhale fresh air with
`supplemental oxygen. Quicknmovalfrom—the contaminated areais-tnost-important. Keep the patient warm, -- ..
`quiet and under competent medical observation until the danger of delayed pulmonary edema has passed (at
`least 72 hours). Any physical exertion durin’g'ihis period should be discouraged as it may increase the severity
`of the pulmonary edema or chemical pneumonitis. Bed rest is indicated. Unconscious persons should be
`moved to an uncontaminated area, and if breathing has stopped. administer artificial resuscitation and
`supplemental oxygen. Once respiration has been restored they should be treated as above.
`
`5. Fire Fighting=Measures
`
`J
`
`
`
`
` Conditions of Flammabili
`
`: Not flammable
`Flash point:
`Method:
`Autoignition
`None
`Temrrature: None
`
`-
`LEL(%: None
`UEL(%): None
`
`Hazardous combustion -roducts: Oxides of nitro-en
`
`Sensitivi
`to mechanical shock: None
`
`
`Sensitivi
`to static dischare: None
`
`
`
`
`
`
`
`FIRE AND EXPLOSION HAZARDS:
`Nitric oxide is nonflamrnable but will supportficombustion.
`
`EXTINGUISHING MEDIA:
`Not Applimble. Nonflarnamble product.
`
`FIRE FIGHTING INSTRUCTIONS:
`Not Applicable.
`
`6.. Accidental Release Measures
`
`Evacuate all personnel from affected area. Use apprOpn'ate protective equipment. If leak is in user's
`equipment. be certain to purge piping with inert gas prior to attempting repairs. Ifleak is in container or
`container valve. contact the appropriate emergency telephone number listed in Section 1 or call your closest
`BOC [cation
`
`7. Handling and Storage
`
`Electrical Classification:
`Nonharardous.
`
`.
`MSDS: G-ISB
`Revised: 61"7/96
`
`SJ
`
`‘
`
`-
`
`8353
`
`Page 3 of6
`
`

`

`
`Nitric oxide and nitrogen is non-corrosive and may be used with any common structural material. Corrosive
`. conditions can exist in the presence of moisture, i.e. Nitric Acid.
`-
`
`Use only in well-ventilated areas. Valve protection caps must remain in place unless container is secured with
`valve outlet piped to use point. Do not drag, slide or roll cylinders. Use a suitable hand truck for'cylinder
`movement. Use a pressme reducing regulator when connecting cylinder to lower pressure (<3000 psig) piping ‘
`or systems. Do not heat cylinder by any. means to increase the discharge rate of product from the cylinder.
`Use a check valve or trap in the discharge line to prevent hazardous back flow into the system.
`
`Protect cylinders from physical damage. Store in cool, dry, well-ventilated area away from heavily trafficked
`. areas and emergency Exits. Do not allow the temperature where cylinders are stored to exceed 130°F (54°C).
`Cylinders should be stored upright and-firmlysecured to-prevent falling or being knocked over;”Full‘and" "
`empty cylinders should be segregated. Use a “first inlfirst out” inventory system to prevent full cylinders being
`stored for excessive periods of time.
`“
`
`Never carry a compressed gas cylinder or a container ofa gas in cryogenic liquid form in an enclosed space
`such as a car trunk, van or station wagon. A leak can result in a fire, explosion. asphyxiation or a toxic
`exposure.
`--
`
`8. Exposure Controls. Personal Protection
`
`fiVOLUME
`7
`0.00001 to 1.0
`
`Pat-05m:2
`25 ppm TWA'
`
`..
`'-
`
`TLV-ACGIHi
`.
`25 ppm TWA
`
`.,
`
`Lo... “TLC”
`Routers
`
`Balance
`
`EXPOSURE LIMITS‘:
`
`
`
`"
`'
`mcRsoiENr_-__ -
`.‘
`
`
`Nitric Oxide
`
`.
`
`FORMULA: N0
`CA5: 10102-43-9
`
`
`
`
`
`RTECS #: QXOSZSOOO
`
`
`Nitrogen
`Simple Asphwiant
`Simple Asphyxiant
`Not Available
`
`
`
`FORMULA: N;
`
`
`CAS: 7727-37-9
`RTECS #: QWBTOOOOO
`
` As stated in 29 CFR 1910. Subpart Z (revised July 1. 1993)
`1 Refer to individual state ofprovineial regulations. as applicable. for limits which may be more stringent than
`those listed here.
`-
`’ A:m in the ACGIH 1994-1995 Threshold Limit Values for Chemical Substances and Physical Agean.
`
`
`
`
`' aimed: 6/7/96
`
`IDLH (Nitric Oxide): 100 ppm
`
`ENGINEERING CONTROLS:
`Local exhaust to prevent accumulation of high concentrations so as to reduce the oxygen level in the air to less
`than 19.5% and to prevent N0 accumulation above the exposure limit.
`
`EYEIFACE PROTECTION:
`Safety goggles or glasses and face shield.
`
`SKIN PROTECTION:
`Protective gloves of any material, (Rubber or teflon).
`
`RESPIRATORY rad-monom-
`Posmve pressure air line with full-face mask and escape bottle or self-contained breathing apparatus should be
`available for emergency use.
`-
`
`MSDS: 6-153
`
`
`
`

`

`
`
`“3
`
`
`
`
`
`
`
`
` PRODUCTs'NAME: NITRIC OXIDE lN NITROGEN 0.00001% T01%
`
`OWERJGENERAL PROTECTION:
`Safety shoes and eyewash.
`
`9. Physical and Chemical Properties
`
`PARAMETER
`Physical s