[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.
____________________