[Congressional Record Volume 140, Number 34 (Wednesday, March 23, 1994)]
[Senate]
[Page S]
From the Congressional Record Online through the Government Printing Office [www.gpo.gov]


[Congressional Record: March 23, 1994]
From the Congressional Record Online via GPO Access [wais.access.gpo.gov]

 
             FIBERGLASS AND THE NATIONAL TOXICOLOGY PROGRAM

  Mr. DOLE. Mr. President, I wanted to make my colleagues aware of a 
situation that has developed at the Department of Health and Human 
Services that may have an enormous impact on over 1,300 employees in my 
State of Kansas at three fiberglass insulation production facilities in 
McPherson and Kansas City, KS.
  Under the National Toxicology Program, the Department will soon issue 
the seventh annual report on carcinogens. The recommendation of the 
interagency working group of the NTP was to include glass wool, 
respirable size, on the list of substances reasonably anticipated to be 
a carcinogen.
  However, Mr. President, the working group also voted to recommend 
that a review was needed of the criteria by which ARC decisions are 
made generally, and in particular, to review whether the existing 
criteria are appropriate for assessing fiber carcinogenicity.
  Basically, Mr. President, the question is this: Why should this 
substance be officially listed as a possible cancer hazard under the 
old criteria when a recommended criteria review has yet to be 
completed? It is my understanding there is a considerable body of 
evidence recently completed in Canada that supports the industry 
contention that inclusion on the list is not warranted.
  Mr. President, I would ask unanimous consent that a letter I have 
sent to Secretary Shalala and supporting materials be printed in the 
Record.

                                                  U.S. Senate,

                                   Washington, DC, March 23, 1994.
     Hon. Donna E. Shalala,
     Secretary of Health and Human Services,
     Washington, DC.
       Dear Secretary Shalala: I am writing to you regarding a 
     recent request by my constituents Owens-Corning Fiberglass, 
     Schuller International and Certain Teed Corporation.
       The information which I have received relates to the 
     National Toxicology Program (NTP) administered by the 
     Department of Health and Human Services. These constituents 
     are asking that the review of their product under the NTP be 
     delayed in light of the recent decision by the Interagency 
     Working Group that the criteria used for evaluation of 
     substances should be reviewed.
       I am pleased to forward this information to you for your 
     review prior to your final decision.
           Sincerely,
                                                         Bob Dole,
                                                      U.S. Senate.
                                  ____

  There being no objection, the material was ordered to be printed in 
the Record, as follows:


                                                        NAIMA,

                                               September 30, 1993.
     Donald Ainslie Henderson, M.D., M.P.H.,
     Deputy Assistant Secretary for Health-Science, Department of 
         Health and Human Services, Washington, DC.
     Re: Proposed Listing of Glass Wool (Respirable Size) On 7th 
       Annual Report on Carcinogens.

       Dear Dr. Henderson: Thank you for your letter of August 17. 
     I am disappointed that we will not have the opportunity to 
     meet with you at this time. However, I do appreciate that the 
     Department and the National Toxicology Program (NTP) are 
     considering the issues raised in our petition, and I respect 
     your decision that this is not the right time for a meeting.
       NAIMA remains very concerned that the issues raised in the 
     petition regarding the Annual Report on Carcinogens (ARC) 
     listing criteria, as well as the underlying science on glass 
     wool, receive a detailed, expert and objective review by 
     scientists familiar with fiber toxicology and occupational 
     epidemiology issues. We believe that the criteria used by the 
     NTP, at least as NTP now interprets them, are outside the 
     scientific mainstream and scientifically indefensible. 
     Because of this, the NTP should not proceed with the listing 
     of glass wool until this review is completed and the criteria 
     revised. Proceeding to evaluate glass wool under the existing 
     criteria (or NTP's interpretation of those criteria) risks an 
     erroneous, arbitrary and capricious result.
       Along those lines, NAIMA is concerned that your memorandum 
     of July 15, 1993 to Dr. Olden may be misunderstood. This 
     memorandum was telecopied to us for comment by a reporter for 
     the Bureau of National Affairs (BNA); the reporter indicated 
     he had received the memorandum from members of Dr. Olden's 
     staff. Your August 17 letter states that the Department is in 
     the midst of considering the issues raised by the petition 
     including, presumably, the ARC listing criteria and NTP's 
     interpretation of those criteria. However, your July 15 
     memorandum describes a review process in which both the NTP 
     Scientific Review Committee and the NTP Working Group will 
     review ``the strength of the evidence for glass wool's 
     carcinogenicity according to ARC criteria.''
       Meaningful consideration of the NAIMA petition's arguments 
     that the NTP listing criteria require reevaluation would 
     entail a review of the existing ``strength of the evidence'' 
     approach to carcinogen classification. Under that ``strength 
     of the evidence approach,'' a substance must be classified as 
     a carcinogen if it produces tumors in laboratory animals--
     regardless of any other evidence. Under a ``weight of the 
     evidence'' approach, by contrast, the totality of 
     scientific evidence may be considered in making human 
     carcinogen hazard identification judgments [including 
     negative animal studies, the relevance of the routes of 
     animal and human exposure, other mechanistic information 
     and epidemiological (mortality and morbidity) data]. NAIMA 
     is concerned that NTP may consider your memorandum to Dr. 
     Olden warrant for the evaluation of the glass wool science 
     under the existing criteria.
       The Department's decisions to review the NTP carcinogen 
     hazard classification criteria and the application of those 
     criteria to glass wool are of obvious importance to the 
     industry, the industry's employees, the public and the NTP. 
     These reviews provide a unique opportunity to assess 
     important scientific issues both generically and with regard 
     to a particular, important substance--glass wool. NAIMA 
     believes these reviews should be as well informed, as fair 
     and impartial and as comprehensive as practicable. To that 
     end, NAIMA formally requests that a number of procedures be 
     followed.
       First, we believe, it is imperative that these decisions be 
     made on the basis of an open, publicly available record that 
     contains all relevant documents to be considered. Over the 
     past several weeks, NAIMA has repeatedly been questioned by 
     reporters in possession of external letters written to the 
     Department as well as internal Departmental and NTP 
     memoranda, and has been asked to comment or respond. We 
     believe that the public record should reflect what 
     representations have been made to the Department so that 
     NAIMA and others can bring relevant information supporting or 
     refuting those representations to the Department's attention.
       Second, NAIMA requests that the Working Group meeting(s) be 
     open to the public. There has been considerable confusion 
     regarding the proceedings to date including precisely what 
     occurred at the closed October 1992 Working Group meeting and 
     precisely what information was transmitted to Dr. Olden 
     thereafter regarding the views of the various NTP Working 
     Group constituent agencies. NAIMA also believes that secrecy 
     regarding these important questions of science and science 
     policy serves no purpose. Openness is more consistent with 
     and promotes fairness and full discussion. It should be the 
     policy of the Department to provide the public the fullest 
     information practicable regarding these important decision-
     making processes.
       Third, NAIMA requests the opportunity to make full, expert 
     scientific presentations to the Working Group regarding glass 
     wool toxicology, the epidemiology studies of glass wool 
     workers and the NTP carcinogen hazard identification 
     criteria. NAIMA anticipates that a number of eminent, 
     independent toxicologists with fibers, occupational 
     epidemiologists and carcinogen classification experts would 
     be available to make such presentations. This would doubtless 
     be useful input to the Working Group members.
       Fourth, we request that the Department and/or the Working 
     Group convene an independent, peer review panel of preeminent 
     fiber toxicologists and occupational epidemiologists, as well 
     as carcinogen classification experts, to assist the 
     Department and/or the Working Group in evaluating all the 
     scientific evidence including the evidence presented 
     pursuant to NAIMA's previous (third) request.
       We would point out that Department action granting this 
     request would be consistent with the consensus of the NTP 
     Working Group, as reflected in the publicly available minutes 
     of the October 8, 1992 Working Group meeting:
       ``The general consensus was that the review by the Working 
     Group for the ARC could be considered as a partial peer 
     review but that it should be willing to take some scientific 
     issues which need further definition to some body of 
     scientists deemed expert on the issue.''
       NTP Working Group Minutes, October 8, 1992 Meeting, p.6. 
     Specifically, regarding the new glass wool toxicology data, 
     again according to the October 8 meeting minutes, ``Dr. 
     Allaben then stated that he did not feel it was in the 
     charter of the Working Group for the ARC to serve as a peer 
     review group for this type of submission and felt that an ad 
     hoc group of experts would better serve to review this data 
     for the NTP.'' Id. at 8-9. If NIH grant proposals and NTP 
     bioassays deserve external peer review, then critical 
     carcinogen hazard identification information intended for 
     general public dissemination surely deserves no less review.
       Fifth, NAIMA requests that the NTP/NIEHS, taken together, 
     be allowed only one vote at the next Working Group meeting. 
     The minutes of the October 8 meeting reflect a series of 
     ballots in which nine votes were cast although only eight 
     agencies were represented. Although the NTP and NIEHS 
     representatives are identified separately as if they 
     represent distinct entities, both representatives work for 
     and report to the NIEHS/NTP Director and are NIEHS employees. 
     Indeed, the cover page of the October 8, 1992 Working Group 
     minutes specifically identifies two voting members as NIEHS 
     representatives (copy attached as Attachment 1). Given the 
     significance of the issues to be discussed and the closeness 
     of the October 8 votes, it would be more representative if 
     NTP/NIEHS were treated as are other agencies and allowed only 
     one vote. This would also eliminate any questions about the 
     appropriateness of such double counting.
       There is no doubt that the Department is legally required, 
     having decided to review its criteria and the glass wool 
     decision, to follow procedures fair to all interested parties 
     and adequate to develop a full and fair record. We believe 
     the procedures requested above are essential to achieving 
     that end.
       We are, in similar vein, concerned that these important 
     scientific issues be debated within this decisional process--
     and not in the press. In recent weeks, we have been called by 
     a number of reporters and informed by them that they had 
     received information from NTP employees about the decisional 
     process--information about which we were totally unaware. 
     As you know, that information has led to several press 
     stories in recent weeks.
       We believe it essential that the scientific issues be 
     considered fully and fairly by each of the participants in 
     the NTP process. The process will inevitably be infected if 
     such publicity continues. Creating an open, publicly 
     available record, opening up the Working Group meeting, 
     allowing expert input, requiring independent expert peer 
     review and addressing the voting process--as we request 
     above--is an appropriate means of assuring a full and fair 
     process.
       Finally, even if the NTP criteria were to remain unchanged, 
     we do not believe that a rigorous, impartial and even-handed 
     review of the science supporting the proposed listing of 
     glass wool has yet taken place. Specifically, even under the 
     extant criteria, NTP must consider questions of study design, 
     conduct and the meaning of the results in its evaluation of 
     the scientific evidence which allegedly supports the listing. 
     See Introduction, Sixth (1991) Annual Report on Carcinogens, 
     Summary, p. 6 (``As an alternative.  . . . epidemiologic 
     studies  . . ., scientists can use well-designed animal 
     studies'') (emphasis added). Any positive studies must be 
     found to meet a certain threshold of quality in order for 
     them to be considered to be ``sufficient'' to warrant a 
     finding of carcinogenic hazard.
       NTP staff has been at great pains to identify any weakness 
     in the RCC glass wool inhalation studies and to question 
     their value in the carcinogen hazard identification process. 
     NAIMA welcomes this detailed scrutiny and analysis of the 
     design and conduct of this study, conducted according to Good 
     Laboratory Practices and now published in two peer-reviewed 
     journals. Similar scrutiny is welcomed of the seven other 
     consistent, negative animal inhalation studies involving 
     glass wool exposure to a variety of species.
       By contrast, with respect to the glass wool injection/
     implantation studies, NTP staff has set forth no criteria 
     against which such studies are to be evaluated and judged to 
     be valid, well designed and well conducted. This apparently 
     uncritical acceptance of the positive injection/implantation 
     studies is especially troubling in light of the growing 
     national and international consensus that the sole value of 
     these non-physiological route of exposure studies is as 
     screening tests to determine what fibers should be subject to 
     inhalation testing, the exposure route relevant to humans. 
     The NAIMA petition of June 29, 1993 discusses in detail the 
     nearly identical conclusions of the Chemical Industry 
     Institute of Toxicology (CIIT) (1992) and World Health 
     Organization (WHO) (1992) expert panels on this point. So as 
     not to prolong this letter, NAIMA here merely enumerates 
     certain of the importing failings of the glass wool 
     injection/implantation studies. These studies:
       1. Employ excessive or overload doses;
       2. Use non-physiologic routes of administration by normal, 
     respiratory system defense mechanisms:
       3. Have produced results that have not been demonstrated to 
     correspond to results in either animal inhalation or human 
     epidemiology studies;
       4. Have not been conducted in accordance with established, 
     accepted repeatable scientific protocols following Good 
     Laboratory Practices:
       5. Allow little or no opportunity for natural clearance of 
     fiber from the injection/implantation site;
       6. Entail abnormal anatomical localization of fibers;
       7. Permit little or no interaction with cell types common 
     in the terminal bronchioles and alveoli; and
       8. Result in a high incidence (approximately 10%) of 
     neoplasms in saline control animals.
       Such criticisms are abundant in the peer-review literature, 
     and yet they apparently have received little or no 
     consideration by NIP as part of its evaluation. Instead, NPT 
     has relied totally upon these studies as the basis for 
     recommending that glass fibers be listed as a reasonably 
     anticipated human carcinogen. Rather than elaborate these 
     criticisms here, NAIMA respectfully refers you to Attachment 
     2, where some of these criticisms and failings are discussed 
     in more detail. NAIMA shares the concerns reflected in the 
     October 8, 1992 Working Group meeting minutes that the 
     Working Group may not have the highly specialized expertise 
     to conduct a full evaluation of these studies. As such, NAIMA 
     requests that if the review of glass wool is to proceed under 
     the existing criteria, that this evaluation be referred to an 
     independent panel of fiber toxicology experts.
       A final note is in order. Some individuals have attempted 
     to minimize the significance of the proposed listing of glass 
     wool as reasonably anticipated to be a human carcinogen. 
     These individuals have argued that NAIMA should not be 
     concerned because this is merely the ``First step in hazard 
     identification'' and further that ``reasonably anticipated'' 
     in fact means only ``may possibly.'' Others have questioned 
     industry's good faith in filing the petition and pursuing the 
     options provided to it by law under the Administrative 
     Procedure Act.
       Two points need to be made. Let us momentarily put to one 
     side any economic harm to the industry or the jobs of its 
     employees. Let us also momentarily put to one side the 
     concrete and empirically verifiable losses in the area of 
     energy conservation, recycling and air pollution prevention 
     if the market place substitutes other, untested products for 
     glass wool or uses less insulation as a result of an 
     unwarranted classification of glass wool as reasonably 
     anticipated to be a human carcinogen. Putting all that aside, 
     NAIMA, its member companies and their many thousands of 
     employees and customers have a right to a full, fair and 
     open hearing before being needlessly stigmatized by the 
     United States Government as working with or selling a 
     product that has been classified as a reasonably 
     anticipated human carcinogen. NAIMA does not choose to 
     waive that right.
       Second, the public has a right to a full and fair 
     evaluation from its Government of these important questions 
     of science and public policy. It has been observed that 
     ``once the government condemns a substance as inherently 
     dangerous, that denouncement may well be tantamount to an 
     economic death knell.'' The ability of the public to make 
     fine distinctions between ``reasonably anticipated'' and 
     ``may possibly,'' and between ``first step in hazard 
     identification'' and ``actual risk that I will get cancer'' 
     is difficult to estimate. However, one point is clear: the 
     public will be harmed if substances are classified 
     provisionally as carcinogens on the basis of flawed criteria. 
     The public is also keenly interested in not being falsely 
     alarmed by government agencies about the carcinogenicity of 
     particular substances.
       NAIMA respectfully requests that this letter and its two 
     attachments be made part of the administrative record that 
     the Department preserves for this proceeding.
       Thank you for your consideration of this important matter.
           Sincerely yours,
                                                    William Black,
                                                        President.
                                  ____


 Department of Health and Human Services--U.S. Public Health Service, 
                      National Toxicology Program


                           members/alternates

       Dr. Jameson, NIEHS, Chairman; Dr. Allaben, NCTR/FDA; Dr. 
     Cameron, NCI; Dr. Fouts, NIEHS; Dr. Parker, EPA; Dr. Schuman, 
     OSHA; Dr. Siegel, NLM; Ms. Stevens, ATSDR; Dr. Wind, CPSC 
     (absent); Dr. Zumwaide, NIOSH.


                               observers

       Dr. Greenman, NCTR/FDA Dr. Sheridan, NEIHS.

 The Limitations of Animal Injection/Implantation Studies in Assessing 
                          Human Cancer Hazards

       Numerous governmental agencies and scientific groups have 
     questioned the relevance of animal injection and implantation 
     studies in assessing the hazard to humans of fibers. The 
     World Health Organization and the International Programme on 
     Chemical Safety and, in the United States, the National 
     Institute on Occupational Safety and Health, the 
     Environmental Protection Agency (EPA), the Consumer Product 
     Safety Commission, and a symposium co-sponsored by EPA and 
     the National Institute of Environmental Health Sciences have 
     all in recent years issued reports that, while finding value 
     in such studies to screen fibers for further testing by 
     physiological (inhalation) routes of exposure, also find they 
     should not be used to assess whether the same fibers, when 
     inhaled by humans, pose cancer hazards.
       These reviews question the relevance of injection/
     implantation studies based on fundamental failings of such 
     studies. Injection/implantation studies:
       (1) Employ non-physiologic routes of administration that 
     bypass normal respiratory system defense mechanisms;
       (2) Have produced results that have not been demonstrated 
     to correspond to results in either animal inhalation or human 
     epidemiology studies; and
       (3) Have not been conducted in accordance with established, 
     accepted protocols following Good Laboratory Practice (GLP) 
     methodology.
       We describe each failing below.
       (1) Non-Physiologic Routes of Administration: When humans 
     inhale fibers, five levels of defense protect against adverse 
     effects: (a) aerodynamic filtration of the respiratory tract; 
     (b) ciliated mucous transport of fibers deposited on the 
     bronchial tree; (c) phagocytosis by macrophages of fibers 
     that reach the terminal bronchioles; (d) solubilization of 
     fibers that may remain in this region; and (e) additional 
     filtration of fibers in moving to the lung pleura. Injection/
     implantation studies bypass all of these defense mechanisms 
     and thus do not reflect the reality that:
       ``If the lung is able to prevent the fiber from reaching or 
     removes the fiber from the critical site for producing a 
     pathological response, the fiber will not be pathogenic.''
       D.M. Bernstein, ``An Evaluation of the Use of an Inhalation 
     Model versus Intraperitoneal Injection Model for 
     the Assessment in Rats of the Carcinogenicity of Natural 
     and Man-Made Vitreous Fibers,'' 43 Zbl Arbeitzsmed [Main 
     Journal of Occupational Medicine] 120, 126 (1993).
       Moreover, these defense mechanisms, even if they do not 
     totally prevent fibers from reaching target tissues, may 
     substantially change the size, shape, surface area, surface 
     charge and chemical composition of the fibers--each of which 
     factors may affect fiber toxicity. Indeed, the intra-
     peritoneal test has shown coarse fibers to be more 
     carcinogenic than finer fibers--in contrast to the accepted 
     toxicological wisdom that precisely the opposite is true. 
     C.E. Rossiter, ``Fiber Carcinogenesis: Intro-Cavitary Studies 
     Cannot Assess Risk to Man,'' 567, 575 Mechanisms in Fiber 
     Carcinogenesis (1991).
       In addition, the typical bolus dose employed injection/
     implantation studies (up to 100 million times the typical 
     human dose) will often produce a massive inflammatory 
     response totally untypical of human reactions. Indeed, 
     certain often-employed intra-peritoneal test systems produce 
     about 10% neoplasms from injection of saline in controls. 
     Such results should be viewed as artifactual of the test 
     system, rather than as evidence of animal or human hazard or 
     risk. Rossiter, supra, at 573-75. See also R.O. McClellan, 
     ``Approaches to Evaluating the Toxicity and Carinogenicity of 
     Man-Made Fibers: Summary of a Workshop Held November 11-13, 
     1991, Durham, North Carolina,'' 16 Reg. Toxicol. & Pharmacol. 
     321, 335 (1992).
       (2) Lack of Correspondence to Inhalation Results: 
     Injection/implantation studies of fibers have never been 
     validated as relevant to human, or even animal, inhalation. 
     Marked discrepancies exist between human and animal 
     inhalation results and results achieved in injection/
     implantation studies of the same fibers.
       Chrysotile asbestos, for example, very rarely causes 
     mesotheliomas in humans, and fiber glass has never been 
     associated with mesotheliomas in humans or in animals 
     inhalation studies. Yet, intra-cavitary studies have produced 
     significant mesothelioma rates with both fibers. On the other 
     hand, animal inhalation studies, when properly performed 
     using fibers of the relevant dimensions, have been found to 
     correlate well with human results.
       Studies that have not been validated as demonstrating 
     results that are similar to real-life results should not be 
     relied upon in human health hazard assessment.
       (3) Absence of Accepted Protocols: No accepted protocols 
     have been adopted by governmental scientific bodies for 
     injection/implantation studies, Nor have such studies been 
     conducted according to Good Laboratory Practice methodologies 
     as are required for inhalation studies relied on by 
     Governmental bodies.
       Animal inhalation study protocols have been developed with 
     great care over the years by NTP, EPA, the European Economic 
     Community and many other groups. Regulators have insisted on 
     compliance with these protocols in order to rely on study 
     results. No such established protocols exist for injection/
     implantaton studies.
       Nor have injection/implantation studies been performed 
     according to Good Laboratory Practices regulations. Such 
     rules assure that all aspects of the study were performed as 
     specified in the protocols and that all data were properly 
     recorded and reported. Such guarantees of proper study design 
     and implementation have not been employed in injection/
     implantation research.
       Because of the absence of established protocols and GLP 
     methodology, injection/implantation studies typically fail to 
     include important research techniques and/or report very 
     important information. For example, such studies:
       Typically do not report the full range of fiber dimensions 
     administered;
       Do not include microscopic recovery tests to determine 
     which of the administered fibers actually reached the target 
     tissues;
       Fail to report on the viral status of the animals;
       Do not include microscopic histopathological 
     examinations of control animals;
       Do not include evaluations of the origins of the tumors 
     produced;
       Do not include any peer review reading of the slides.
       These failings all indicate an absence of information 
     critical to assessment of injection/implantation studies. 
     Without such information, for example, it is impossible to 
     know whether lesions have been missed in examination of 
     controls, or to determine which tumors in which organs are or 
     are not related to the administered fiber, or whether 
     important issues in pathology diagnosis exist as interpreted 
     by different pathologists.
       Given all the failings in the typical conduct of injection/
     implantation studies, reports of such studies fall short of 
     providing the information necessary for appropriate review.

                          ____________________