Fibrous glass insulation and cancer: response and rebuttal.

In response to our commentary on fibrous glass and cancer [Infante et al., 1994], three letters have been received by the journal. The arguments put forth in these letters do not lead us to alter our scientific view that fibrous glass insulation is carcinogenic. No information is given in the letters that has not previously been stated. Even though these letters raise the same diaphanous arguments, we believe that to preserve occupational and public health we must respond in detail to ensure that the contentions of the fibrous glass industry do not gain further acceptance. Thus, we respond to each letter in turn: The first by Weiss questions and distorts epidemiologic findings, the second by McConnell attempts to recant his past views on the carcinogenicity of fibrous glass and on the value of rodent bioassays in general, and the third by Hesterberg and Chase impugns our analyses demonstrating a positive cancer response in their study. Lastly, we have not debated every issue raised in these three letters because of space limitations, and have centered our responses on what we consider the major incongruities and falsities in each letter. Likewise, we have been selective in citing only relevant literature, or those reports used by the industry or its consultants to support their views.

Fibrous glass and cancer.

Some argue that fibrous glass (glass wool) should not be considered as a likely human carcinogen and hence should not be listed in the Seventh Annual Report on Carcinogens (ARC) prepared by the National Toxicology Program (NTP) and mandated by the U.S. Congress. In examining this issue, data from both laboratory experiments (animal studies) and epidemiologic studies (human data) are reviewed with the results evaluated according to the criteria established by the International Agency for Research on Cancer (IARC) and adopted in slightly modified form by the NTP for classifying substances as human carcinogens or likely human carcinogens. From our comprehensive review of the available information, we conclude that fibrous glass materials are carcinogenic, and in view of the NTP and IARC definitions should be listed in the ARC. Our review then examines the carcinogenic potency of glass fibers to humans in comparison with asbestos fibers and concludes that on a fiber-per-fiber basis, glass fibers may be as potent or even more potent than asbestos. The implications of these findings are then presented for regulatory purposes in the occupational setting.

Effect of the ornithine decarboxylase inhibitor alpha, alpha-difluoromethylornithine on phorbol diester-induced inhibition of murine B lymphocyte differentiation.

The tumor-promoting agent 12-O-tetradecanoylphorbol-13-acetate (TPA) inhibits the differentiation of murine B lymphocytes to antibody-producing plasma cells, in unfractionated spleen cell cultures or enriched B lymphocyte cultures. To determine the role of polyamines in TPA-induced inhibition, unfractionated splenic lymphocytes, in culture with antigen, were incubated with alpha, alpha-difluoromethylornithine (DFMO, 0.10 mM), an irreversible inhibitor of ornithine decarboxylase (ODC). DFMO prevented the TPA-induced inhibition of antibody forming cell number in a 5-day in vitro immunization procedure as measured by a hemolytic plaque assay. In enriched B lymphocyte cultures, however, DFMO had no comparable effect. DFMO did not prevent TPA-induced inhibition of antibody production in unfractionated spleen cell cultures but itself inhibited the amount of antibody produced. Putrescine (0.1 mM), added on day 4 of immunization, reversed DFMO inhibition of antibody production but did not enable DFMO to prevent the TPA-induced inhibition. These findings suggest that TPA-induced inhibition of plasma cell number can be mediated indirectly through effects on T lymphocytes and/or macrophages or directly through effect on B lymphocytes.

Direct inhibition of murine B lymphocyte differentiation by 12-O-tetradecanoylphorbol-13-acetate.

The tumor-promoting agent, 12-O-tetradecanoylphorbol-13-acetate (TPA) inhibits the humoral immune response of lymphocytes to antigen. To test the hypothesis that this inhibition is due to a direct effect upon B lymphocytes, splenic lymphocytes or murine B lymphocytes, enriched by 'panning' splenic lymphocytes onto anti-IgM-coated petri dishes, were immunized in vitro with the thymus/accessory cell-independent antigen trinitrophenyl lipopolysaccharide (TNP-LPS) with or without TPA. The number of anti-TNP antibody-forming cells present in both lymphocyte populations after 5 days was almost completely inhibited to the same degree by TPA. These data unambiguously show that TPA can directly inhibit the differentiation of B lymphocytes to antibody-forming cells.