PROPOSAL BY NIEHS TO LIST TALC NOT CONTAINING ASBESTIFORM FIBERS AS A "REASONABLY ANTICIPATED" HUMAN CARCINOGEN IN THE UPCOMING TENTH REPORT ON CARCINOGENS;

FAILURE TO CONSIDER THE VIEWS OF, AND ADEQUATELY
COORDINATE WITH, THE PRIMARY REGULATORY AGENCY, FDA

• Congress intended the Reports on Carcinogens ("RoC"s) to provide information to the general public on exposures that should be avoided. Responsibility for preparing the RoCs was given to the Secretary of Health and Human Services, who was supposed to consult with other interested federal agencies, particularly FDA, NCI, and NIEHS.
  
  
• NIEHS has proposed two separate RoC listings for talc, one for talc containing asbestiform (i.e., asbestos or asbestos-like) fibers, and one for talc not containing such fibers.
  
  
• Talc which is free of asbestiform fibers is widely used in consumer products, particularly in the cosmetics industry (e.g., baby powder and anti-fungal treatments), and the proposed listing would likely have a severe impact on such products if ultimately accepted by the Director of NTP and the Secretary.
  
  
• An NIEHS review group and an NTP review group have proposed that talc not containing asbestiform fibers be listed as "reasonably anticipated" to cause cancer in humans in the upcoming 10^th Report on Carcinogens. The basis for their recommendations is contained in a document called a "Draft Background Document" ("DBD").
  
  
• Any listing in the RoCs must meet the specific evidentiary criteria established by the Secretary.
  
  
• The next step in the RoC review process will be a public review of the evidence pertaining to the proposed listing, and seven others, by the RoC Subcommittee of the NTP Board of Scientific Counselors in Washington, DC on December 13-15, 2000. In an ordinary review, the next step after this would be review of all preceding recommendations by the NTP Executive Committee and forwarding of its recommendations and all others to the Director of the NTP/NIEHS for final decision, then final confirmation by the Secretary.
  
  
• The FDA is the only federal agency with legislative authority to regulate directly cosmetic products containing talc.

• The formal RoC listing criteria require that listings be based on "evidence".
  
  
• The recommendations of the NIEHS and NTP review groups to list talc not containing asbestiform fibers as "reasonably anticipated" to cause cancer in humans are supposedly based on a combination of evidence from (a) studies in humans suggesting an association between hygienic/cosmetic use of "talc" and ovarian cancer, and (b) a single experimental animal study.
  
  
• However, the DBD admits explicitly that the studies in humans using cosmetic "talc" for hygienic/cosmetic purposes are all inadequate because none "provide any characterization of talc mineralogy or morphology that could be used to determine the effects of different kinds of talc." (At 28.)
  
  
• At the same time, the DBD admits that cosmetic talc used today could be free of asbestiform fibers because industry adopted new purity standards towards the end of the 1970s.
  
  
• Nevertheless, based on reports of "widespread" contamination of talc with asbestiform fibers during the 1960s and 1970s, the DBD takes the position that the listing is appropriate because it is "prudent" to assume that all talc may be contaminated with asbestiform fibers (and therefore there is essentially no such thing as talc not containing asbestiform fibers). Id.
  
  
• Assumptions are not "evidence", as required by the listing criteria, and the nomination requires a listing decision on talc not containing asbestiform fibers. The DBD effectively concludes that the evidence from studies in humans is inadequate for use in supporting a listing decision for talc not containing asbestiform fibers.
  
  
• Since the human evidence is admittedly inadequate for a listing decision, the proposed listing must, under the listing criteria, at least be supported by "sufficient" evidence from experimental animal studies.¹
  
  
• Under the criteria, an animal study is not "sufficient", as the meaning of that term has become established, if there are "unresolved questions regarding the adequacy of the design, conduct or interpretation of the study".
  
  
• In 1994, shortly after the release of the 1993 NTP bioassay results, FDA co-sponsored an expert workshop to review, and try to reach consensus, on the significance of the NTP animal study findings. Twenty FDA experts participated, along with more than eighty other scientists from academia, cancer research institutions, and industry. At the end of the workshop a consensus was reached, and published, that the NTP bioassay results were "the likely experimental artifact and nonspecific generic response of dust overload of the lungs and not a reflection of a direct activity of talc" and that the results "cannot be considered as relevant predictors of human risk."²
  
  
• This published 1994 consensus appraisal of the 1993 NTP animal study has not been referenced or discussed in the DBD. However, the DBD does admit that several non-governmental experts have questioned the adequacy and relevancy of the study.
  
  
• What it comes down to is that the listing proposal rests on a single 1993 NTP animal study concerning which there are certainly "unresolved questions regarding the adequacy of the design, conduct or interpretation of the study" – on the part of both FDA and distinguished members of the non-governmental scientific community.
  
  
• In the RoC review proceedings to date, there has been only one FDA scientist involved, Dr. William Allaben of NCTR. It is not known how Dr. Allaben voted as a member of the RG2 review group, or whether he consulted with other scientists at FDA who are familiar with the talc database and the results of the 1994 workshop.
  
  
• There is thus an unresolved inter-agency conflict over the proposed listing that should be resolved before the review goes forwards.

• The evidence set out in the DBD is, on its face, not adequate to meet the criteria for listing talc not containing asbestiform fibers as "reasonably anticipated" to cause cancer in humans.
  
  
  • The evidence from studies of ovarian cancer in humans is admitted in the DBD to be inadequate because it is not known whether the exposures studied were to talc not containing asbestiform fibers. Assumptions cannot take the place of the required evidence.
    
    
  • The evidence from the single animal study relied on in the DBD for the proposed listing cannot be considered "sufficient" because there clearly are unresolved questions, including on the part of FDA, concerning its adequacy and relevancy to human exposures.
    
    
• There clearly has not been adequate consultation with FDA, as Congress intended, because the published results of the 1994 workshop have not been discussed or even cited, and only one FDA scientist has so far participated in the review process.
  
  
• Since the evidence was clearly not sufficient to support the listing proposal at the time of the RG1 review, the nomination should have been rejected at the end of that review, as would have been done, according to published RoC procedures, with a nomination received from an entity outside the government.
  
  
• The proposal to list talc not containing asbestiform fibers should be withdrawn, and NIEHS should consult with FDA scientists knowledgeable concerning the talc database as to whether new research should be conducted that would be pertinent to today’s cosmetic-grade talc products which are free of asbestiform fibers. Such consultation should be conducted in an open forum after notice in the Federal Register.

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