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ACS (American Chemical Society)

ACS Water, Reagent (CAS Number 7732-18-5)

Title – Reagent Chemicals: American Chemical Society specifications, official from January 1, 2000
Web Address – http://www.acs.org
Price – Approximately $165 (bookstores)
Reagent Solutions: Preparation – "Throughout the specifications for reagent chemicals, the term 'water' means distilled water or deionized water that meets the requirements of Water, Reagent, page 686. However, for specific applications – such as UV determinations or liquid and ion chromatography – ASTM Type I reagent water (ASTM, 1999) or water for which the suitability has been determined should be used. In tests for nitrogen compounds, water should be 'ammonia-free' or 'nitrogen-free'. Water for use in analysis of ultratrace metals must meet the requirements on page 688. For some tests, freshly boiled water must be used to ensure freedom from materials absorbed from the air, such as ammonia, carbon dioxide, or oxygen."

Discussion

It is curious that ACS recommends ASTM International Type I water for UV determinations or liquid and ion chromatography. Type I water is inadequately specified (see ASTM International below) and there is no reason to believe that Type I water would necessarily make a better choice for UV determinations or liquid chromatography than ACS Reagent Water.

ACS Reagent Water is specified as having a 2 megohms-cm (referenced to 25° C) limit for resistivity, a silicate (as SIO₂) limit of 0.01 ppm, a heavy metals (as Pb) limit of 0.01 ppm, chloride limit of 0.4 ppm, a nitrate limit of 0.4 ppm, a phosphate limit of 1.0 ppm, and a sulfate limit of 1.0 ppm. ACS Reagent Water must also pass a permanganate test for organics. In addition, ACS Reagent Water must pass a UV test or absorbance and gradient elution tests, if it is to be used for ultraviolet spectrophotometry or liquid chromatography. Brief methods for performing all of the measurements are provided. Most laboratories are likely to find the measurement of specific inorganicontaminants of little practical value when ion exchange is a convenient option. Furthermore, ACS Reagent Water will not be adequate for many sensitive bioscientific applications.

ANSI (American National Standards Institute)

No Standards (See Comments)

Web Address – http://www.ANSI.org
Comment – ANSI has accredited the American Society for Testing Materials International (ASTM International) and the National Committee for Clinical Laboratory Standards (CLSI), which means that these standards developer organizations (SDOs) can submit their standards to ANSI for processing as proposed American National Standards, provided these SDOs comply with ANSI requirements for openness, due process, and consensus by a balanced group of materially affected interests. Once standards are submitted to ANSI, they are published in the ANSI publication, Standards Action, and any persons or groups with an interest have sixty days to comment to the ANSI Board of Standards (Board of Standards, ANSI, 11 West 42nd Street, New York City, NY 10036 [psa@ansi.org]) and the SDO developer.

ANSI is also the sole US representative to the International Organization for Standardization (ISO). For information about ANSI's ISO activities refer to the following ANSI Web information: www.ansi.org/public/ansi_info/ansi_iso.html. ANSI accredits Technical Advisory Groups (TAGs) to formulate US positions and TAG administrators may be SDOs. TAG votes/positions on all proposed international standards/policy issues are cast and/or communicated through ANSI to the international secretariat of the appropriate ISO Technical Committee (TC)/Subcommittee (SC), or other ISO Council/Committee. A listing of all US TAGs is available as an ANSI PDF document: www.ansi.org/public/db_list/usico.pdf.

Discussion

Insofar as High-Q editors are aware, ANSI has not developed any standards for reagent-grade water internally. Of the standards discussed in this Web page, the following are being considered for approval by ANSI:

None

Of the standards discussed in this Web page, the following have been approved by ANSI:

None

ASTM International (American Society for Testing and Materials International)

Relevant Legal Issue

ASTM International is listed as a defendant in a suit before the United States District Court, Northern District of Ohio, Eastern Division. The plaintiffs in the case, 1:98CV 2584, allege in part:

"This action involves Defendants' wilful and unlawful manipulation of a purportedly impartial standard setting organization, ASTM, in order to mislead federal and state environmental protection agencies, the owners of underground storage tanks ("USTs"), and the general public about the environmental protection afforded by Defendant Corrpro's and Defendant WRA/Rogers' method for assessing USTs to create a monopoly in favor of Defendant Corrpro and Defendant WRA/Rogers in the UST assessment upgrade market. Defendant ASTM is responsible for failing to enforce adequate measures to prevent antitrust anti-competitive manipulation of the ASTM standard setting system. . . ."

All parties to this suit agreed to a sealed settlement early in 2002.

D1193

Title – D1193-99^e1 Standard Specification for Reagent Water (Reapproved in 1999 and changed March of 2002 – see Discussion below)
Web Address – http://www.astm.org
Price – $25 US
Scope – "This specification covers requirements for water suitable for use in methods of chemical analysis and physical testing. Four grades are specified: Type I, Type II, Type III, and Type IV."
Adopted – According to ASTM International, D1193 is referenced by over 1000 ASTM standards and has been adopted by the American Institute of Aeronautics and Astronautics (AIAA), the Department of Defense (DOD) [Federal Test Method 7916], the International Organization for Standardization (ISO) and the National Aeronautics and Space Administration (NASA).
ANSI Acceptance – D1193 was published in ANSI Standards Action and the comment period ended 04/23/01. Numerous negative comments were received and must be addressed before this standard can be accepted by ANSI. Reference was made to the negative comments at the ASTM International D19 (Water) Committee Winter Meetings, January 21-24, 2002 in Cocoa Beach, FL, and the decision was made to withdraw D1193 from ANSI consideration without responding to the negative comments. The minutes of the June 2002 Meeting of the D1193 Task Group elaborate, "It was agreed at that meeting [January], that there was no longer any benefit to D19 or ASTM to have ANSI recognize and publish D19 standards as ANSI standards."

Discussion
	D1193 may be the classic antithesis of a standard for reagent-grade water, if the purpose of such a standard is to improve quality control and to facilitate the accumulation and exchange of knowledge relating to the impact of water purity on laboratory applications. The ASTM D19 (Water) Committee is currently debating the fate of D1193 and everyone is encouraged to read the following critique and to join in the debate (ASTM membership is not a prerequisite).
	*A Critique of ASTM International Standard D1193, Standard Specification for Reagent Water; (Edition 2.6) [11/01/03]* View / Print >> Printer-quality version [95 Kb] Summary — The Critique describes D1193 as an example of The Emperor’s New Clothes in an allusion to Hans Christian Andersen’s allegorical tale. D1193 has been ASTM International’s only specification for reagent water for nearly 50 years and is reported to be the most widely referenced reagent water specification in the world. Informal surveys suggest that most scientists believe Type I Water, a term coined by D1193, to be the accepted standard of purity for virtually every discipline. In fact, most laboratory water purification systems may have been purchased on the strength of their Type I ratings. But D1193 appears to be a surprisingly vague, poorly edited, error-filled, and internally inconsistent process specification (not a reagent water specification), which does not require any maintenance of the specified purification systems or monitoring of the water they produce, and Type I Water is likely to be an inconsistent unknown. Comment — This Critique was first submitted to ASTM in June of 1999 and has been repeatedly brought to the attention of ASTM since that time. On April 8, 2002, the ASTM D-19 (Water) Committee distributed the Critique to its full roster of members and asked that specific suggestions for repairing D1193 be sent to the D-19 Staff Manager for distribution to the D1193 Task Group. The minutes of the June 2002 D1193 Task Group Meeting, published in January of 2003, state that the five (5) persons in attendance agreed "that there was no longer any benefit to D19 or ASTM to have ANSI recognize and publish D19 standards as ANSI standards." The minutes also state that the D1193 Task Group "has acknowledged repeatedly [verbally] that D1193 has flaws and stands ready to make revisions to improve it." It is laudable that formal efforts are finally under way to rewrite D1193.¹ However, the minutes of the January 2003 D1193 Task Group indicate that the individual, who volunteered "to do a complete editorial revision of the Standard", anticipates that it make take many years to achieve a consensus. Meanwhile, the flawed version of D1193 may remain on the books for many more years. At the June, 2003 D19 Meetings (Louisville, TN), the nine persons present for the D1193 Task Group Meeting concluded that all the significant negatives contained in the Critique were "not persuasive". They categorically rejected the assertion that D1193 was so fundamentally flawed that it should be abandoned in favor of a more modern standard. They confirmed that D19 officers are unwilling to consider the replacement of D1193, because it is "a sound Specification that has stood the test of time." It would appear that change will come very slowly.
	¹ *Gibbs, E.L. Standards – A progress report on standards for laboratory reagent-grade water.* Ultrapure Water 20:18-23 (Feb 2003)** View / Print >> Printer-quality version [55 Kb]

D5196

Title – D5196-91 (1999) Standard Guide for Biomedical Grade Water (Reapproved in 1999)
Web Address – http://astm.org
Price – $25 US
Scope – "This guide is intended to describe the physical and chemical characteristics of water to be used whenever critical purity is essential to the use intended in clinical, pharmaceutical, biophysical, biomedical, chemical, physical research applications, or a combination of these. This guide is not intended for use in preparing water for injectables. Generally, the appropriate use of this guide may include experiments involving tissue culture, chromatography, mass spectroscopy, or analysis where molecular quantities of impurities may be important."
Adopted – According to ASTM International, D5196 is referenced by only one ASTM standard and has not been adopted by other organizations.
ANSI Acceptance – D5196 was published in ANSI Standards Action and the comment period ended 05/08/01. Numerous negative comments were received and must be addressed before this standard can be accepted by ASNI. Reference was made to the negative comments at the ASTM International D19 (Water) Committee Winter Meetings, January 21-24, 2002 in Cocoa Beach, FL, and the decision was made to withdraw D5196 from ANSI consideration without responding to the negative comments. The minutes of the June 2002 Meeting of the D1193 Task Group elaborate, "It was agreed at that meeting [January], that there was no longer any benefit to D19 or ASTM to have ANSI recognize and publish D19 standards as ANSI standards."

Discussion
	D5196 has languished in obscurity for years; however, as controversy surrounding D1193 has increased, D5196 has become the focus of considerable attention and concern. Though D5196 is titled as a guide, its structure suggests that it might be confused for a specification and this possiblity is disturbing to many interested parties. The ASTM D19 (Water) Committee is currently debating the fate of D5196 and anyone with an interest in laboratory water standards, especially water for biomedical applications, is encouraged to read the following critique and to join in the debate (ASTM membership is not a prerequisite).
	*A Critique of ASTM International Standard D5196, Standard Guide for Biomedical Grade Water; (Edition 2.2) [04/23/02]* View / Print >> Printer-quality version [93 Kb] Summary — This critique of D5196 describes a standard overflowing with errors, internal contradictions, and vague, confusing, and misleading language. 5196 is titled a guide; however, it tells the reader virtually nothing about how to prepare what it defines as biomedical-grade water and it makes no attempt to justify the need for this grade of water. D5196 lists limits for 29 substances in biomedical-grade water, but indicates that these limits are based primarily on the detection limits of suggested methods rather than on the requirements of biomedical applications. And, without supporting evidence or discussion, D5196 declares that the 29 limits should be met, if water is produced according to procedures described in a few confusing paragraphs found in an appendix. Comment — This Critique was first submitted to ASTM in June of 1999 and has been repeatedly brought to the attention of ASTM since that time. The minutes of the January 2003 D5196 Task Group Meeting state that D5196 will be re-titled, "Bio-application Grade Water" and re-written – apparently only the identification number will remain unchanged. ASTM has yet to provide a specific rebuttal to the Critique of D5196 or to explain why D5196 should not have been abandoned long ago.¹ At the June, 2003 D19 Meetings (Louisville, TN), the six persons present for the D5196 Task Group Meeting were presented with the conclusion of an informal survey of laboratories that might use BioMedical Grade water: "Almost all did not feel that they would approach their water needs with an analysis of bio-med water for the extensive list of analytes in the current draft." As of March 2006, a draft of the revised D5196 has a new title and bears essentially no resemblance to the currently published version; however, the D5196 designation is being maintained, probably to avoid difficulties associated with introducing a new standard.
	¹ *Gibbs, E.L. Standards – A progress report on standards for laboratory reagent-grade water.* Ultrapure Water 20:18-23 (Feb 2003)** View / Print >> Printer-quality version [55 Kb]

CAP (College of American Pathologists)

No Standards (See Discussion)

Title – Laboratory General Checklists (September 2001)
Web Address – ftp://ftp.cap.org/lapchecklist/cfklst01_0901.pdf
Comment – CAP does not offer water standards, but only cites references for illustrative purposes.
Checklist Commissioner – Dr. Albert Rabinovitch, M.D.

Discussion

CAP Laboratory General Checklists repeatedly reference the CLSI approved guideline, Preparation and Testing of Reagent Water in the Clinical Laboratory - Third Edition (C3-A3 / 1997) (See CLSI below) and clinical laboratories may be forgiven if they conclude that by doing so CAP has converted a private guideline into government regulation. In the past, this interpretation resulted in threatened litigation and an article in the Wall Street Journal (Marketplace), He ran up against latest business foe: Private regulators (09/22/95). Among other things, this article discussed whether the prior edition of the CLSI guideline (C3-A2 / 1991) may have been biased by the presence of an executive of the Barnstead Thermolyne Corporation (a manufacturer of water purification equipment) on the seven member CLSI committee in charge of the guideline.

In communications to High-Q, the CAP Commission on Laboratory Accreditation explained that CAP does not set standards for water quality and that references cited in Checklists, whether they are from government regulations, scientific organizations, industry, textbooks, peer-reviewed scientific literature, etc., do not constitute de facto "endorsement" by CAP. Rather, such citations are intended to direct laboratories towards illustrative literature, which is not necessarily all-encompassing. The Commission stressed that is was important for clinical laboratories to consult the CAP Checklists directly, so there would be no confusion.

A copy of a critical review of C3-A3 (see CLSI below) was submitted to the CAP Laboratory Accreditation Program, which referred it to the "appropriate Resource Committees for their review and recommendations" on February 7, 2002. CAP has yet to respond. Anyone with an interest in laboratory water standards, especially clinical laboratory water standards, is encouraged to become involved in the discussion.

CLSI (Clinical and Laboratory Standards Institute) [formerly NCCLS]

C3-A4 / 2006

Title – Preparation and Testing of Reagent Water in the Clinical Laboratory; Approved Guidline -Fourth Edition; Volume 26 Number 22 2006 (ISBN 1-56238-610-7 ISSN 0273-3099)
Web Address – http://www.clsi.org
Price – $120.00 US non-member $60.00 US member
Abstract – "The document provides information on water purity requirements for clinical laboratory testing, validation of specifications, technology available for water purification, and test procedures to monitor and trend water purity parameters."
Chairholder – W. Gregory Miller, PhD, Virginia Commonwealth University

Discussion
	The C3-A4 edition of the CLSI Guideline, Preparation and Testing of Reagent Water in the Clinical Laboratory, represents a dramatic break with past editions and with most other guidelines and standards for reagent water.^1,2 Gone is the implication that water purification equipment can be thought of as a specifiable, perhaps even certifiable, black box. The C3-A4 Guideline acknowledges the reality that purifying water and achieving effective control of its purity requires an effective, ongoing maintenance and monitoring program as well as a working knowledge of purification and monitoring technologies. The Guideline provides excellent discussion of the strengths and weaknesses of the discrete purification technologies; describes global (i.e., colligative) tests for monitoring purified water for contaminating ions, organics, and microorganisms; and emphasizes the trending of monitoring data as the most effective means of achieving control. Specifications for six types of purified water are defined: Clinical Laboratory Reagent Water (CLRW); Special Reagent Water (SRW); Instrument Feed Water; Water Supplied by a Method Manufacturer for Use as a Diluent or Reagent; and Commercially Bottled, Purified Water. It is noteworthy that the Guideline includes a caveat that no summary of the parameter limits for a C3-A4 water specification has significance outside the context of the entire Guideline. This caveat addresses the fact that there is much more to a water specification than a misleadingly simplified table of limits. It is necessary to know how the parameters are measured, at what point in the purification process they are measured, how frequently they are measured, etc. The specifications are practical, and provisions for the systematic extension of the SRW specification make it possible for laboratories to describe reagent water purity in a meaningful way. Surely, better documentation and communication will result in greater understanding of how water purity impacts laboratory applications at a time when they are becoming increasingly sensitive and water contaminants are becoming ever more numerous and challenging. The C3-A4 Guideline is important reading and a valuable reference for every laboratory that uses water, even if it uses commercially bottled, purified water.

	¹ *A Critique of CLSI Approved Guideline C3-A3, Preparation and Testing of Reagent Water in the Clinical Laboratory -Third Edition; Approved Guideline C3-A3 / 1997 (ISBN 1-56238-336-1)* [02/02/02] View / Print >> Printer-quality version** [120 Kb]
	² *Gibbs, E.L. Standards – A progress report on standards for laboratory reagent-grade water.* Ultrapure Water 20:18-23 (Feb 2003)** View / Print >> Printer-quality version [55 Kb]

ISO (International Organization for Standardization) [ISO from the greek word meaning equal.]

ISO 3696:1987

Title – Water for analytical laboratory use – Specification and test methods
Web Address – http://www.iso.ch/
Price – $44 Swiss francs
Scope – "This International Standard specifies the requirements and corresponding test methods for three grades of water for laboratory use for the analysis of inorganic chemicals.

It is not applicable to water for organic trace analysis, to water for the analysis of surface active agents, or to water for biological or medical analysis."
Technical committee/subcommittee – TC 47
ICS – 71.040.30
Stage – 90.60
Stage date – 1997-07-17
Comment – ANSI is not a member of ISO Technical Committee 47 (TC 47) and it would appear that this TC is not undertaking any work on the development of reagent-grade water.

Discussion

This Standard requires a minimum resistivity of 10 megohms-cm (referenced to 25° C); a maximum silicate of 10 ppb; and a maximum absorbance of 0.001 a 254 nm with 1 cm path for Grade 1 water. It is suggested that the water might be produced by multiple steps of distillation, reverse osmosis, or deionization, followed by filtration through a membrane filter of pore size 0.2 micron or redistillation in a quartz still. The standard is rather vague. A brief discussion of the test methods is provided, but there is no discussion of purification methods. As the authors of this standard state in the scope, water meeting the Grade 1 requirements would most likely not be suitable for many bioscientific applications.

USP (United States Phamacopeial Convention, Inc.)

USP-25 (Effective January 2002) Specifies Nine Types of Water

Title – USP-25
Web Address – http://www.usp.org

Book –
Item Number: 830405
ISBN: 1-889788-10-4
Price: $ 589.00

CD ROM –
Item Number: 852601
Price: $ 799.00

Discussion

It has been the experience of High-Q that it is very difficult to obtain copies of the USP standards from most science libraries. Photocopies of the pages related to the water standards may be available from USP for about $100 to $150; however, USP does not appear to have a routine procedure for handling such a request.

Section 1231, Water for Pharmaceutical Purposes, discusses approaches to design, maintenance, and validation of water purification systems. This Section is noteworthy, because it mentions concerns about water purification technologies that are ignored by many other laboratory water standards:

Activated carbon beds – "The chief operating concerns regarding activated carbon beds include the propensity to support bacterial growth, the potential for hydraulic channeling, the inability to be regenerated in situ, and the shedding of bacteria, endotoxins, organic chemicals, and fine carbon particles."
Macroreticular Resins– "Operating concerns are associated with scavenging capacity and shedding of resin fragments."
Deionization – " Concerns for all forms of deionization units [including electrodeionization] include microbial and endotoxin control, chemical additive impact on resins and membranes, and loss, degradation, and fouling of resin. Issues of concern specific to DI units include regeneration frequency, channeling, complete resin separation for mixed bed regeneration, and mixing air contamination (mixed beds). . . Rechargeable canisters can be the source of contamination and should be carefully monitored. Full knowledge of previous resin use, minimum storage time between regeneration and appropriate sanitizing procedures are critical factors ensuring proper performance."
Reverse Osmosis– "Concerns associated with the design and operation of RO units include membrane material sensitivity to bacteria and sanitizing agents, membrane fouling, membrane integrity, seal integrity, and the volume of wastewater."
Ultrafiltration– "Issues of concern include compatibility of membrane material with sanitizing agents, membrane integrity, fouling by particles and microorganisms, cartridge contamination retention, and seal integrity."
Microbial Retentive Filters– "The potential exists for the release of microorganisms should the membrane filter rupture or as the result of microbial grow-through."
Distillation– "Areas of concern include carry-over of impurities, evaporator flooding, stagnant water, pump and compressor seal design, and conductivity (quality) variations during start-up and operation."
Distribution– "The distribution system should permit sanitization for microorganism control. The system may be continuously operated at sanitizing conditions or sanitized periodically."

There is no reason to doubt that the nine types of water described by USP are sufficiently pure for their intended purpose; however, they do not appear to be sufficiently pure for many, if not most, bioscientific applications. The title, Water for Injection, suggests a high level of purity and many bioscientific laboratories have used this water as a source of bottled reagent-grade water. However, a TOC limit of 500 ppb and an endotoxin limit of 0.25 EU/ml, which amounts to approximately 2500-25,000 gram negative bacteria, or their cell walls, per ml are well above generally accepted levels for reagent-grade water.

High-Purity Water is described within section 661. This grade of water appears intended primarily for testing containers for aqueous solutions and requires a minimum resistivity of 6.7 megohms-cm (referenced to 25° C). The method of preparation may be distillation followed by deionization (nuclear-grade resins) and ultrafiltration (cellulose ester membrane with 0.45 micron pore size). Since the only limit on this water is a modest resistivity, this water could contain significant concentrations of non-ionic impurities; however, because of the method of preparation, it has the potential to be the most pure (in a broad spectrum sense) of the USP waters.
Note: Because distillation can produce water of the required resistivity, there is no need for the deionization step, which is likely to increase organic and microbial contamination in routine use.
Conductivity Water is described within section 645. This water must pass at least one of three tests: 1) The water has a resistivity of not less than 0.769 megohms-cm (referenced to 25° C); 2) The water has a resistivity of not less than 0.476 megohms-cm (referenced to 25° C) after being equilibrated with air; and 3) The resistivity of the water must be above certain limits as a function of the pH of the water. This water is intended for use in measuring the conductivity of Purified Water and Water for Injection and is not necessarily high purity water.
Purified Water that is produced on site is described in the Official Monographs and is required to meet the requirements for Conductivity Water with an additional maximum limit of 500 ppb of total organic carbon.
Sterile Purified Water is described in the Official Monographs as Purified Water that has been sterilized and suitably packaged.
Water for Injection is described in the Official Monographs as water that is finally purified by distillation or reverse osmosis and meets all the requirements for Purified Water. In addition, Water for Injection must not have more than 0.25 USP EU/ml.
Sterile Water for Injection is described in the Official Monographs as Water for Injection that has been sterilized and suitably packaged.
Bacteriostatic Water for Injection is described in the Official Monographs as Sterile Water for Injection to which one or more antimicrobial preservatives have been added.
Sterile Water for Irrigation is described in the Official Monographs as Water for Injection which has been sterilized and packaged for rapid delivery of moderate volumes
Sterile Water for Inhalation is described in the Official Monographs as Water for Injection which has been sterilized and packaged for use in the preparation of inhalation solutions.