Comparative studies onin vivocarcinogenesis in rats andin vitromutagenesis of mutagenic coal fly ash

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Abstract
Polycarbonate filter packets containing either mutagenic coal fly ash or beeswax pellets with 210 μg 7,12‐dimethylbenz[a]anthracene (DMBA) were placed in the lumina of heterotopic rat trachea/ transplants for 1, 2, 4, and 6 mo to test for carcinogenicity. Release of DMBA, as calculated from spectrophotometric determination of residual DMBA in removed beeswax pellets, was found to approach first‐order kinetics. The release rate was estimated to be 45.02% per month of the amount remaining in the pellets. Histopathological examination demonstrated in DMBA‐exposed tracheas consistent hyperplastic, metaplastic, and neoplastic changes (squamous‐celt carcinoma) by 2 mo post‐transplantation, when only 20.5% of total DMBA remained in pellets. These histopathological changes were not found in tracheas exposed to packeted coal fly ash or other control samples including loose coal fly ash, packeted heat‐inactivated fly ash, packeted glass beads, or empty tracheas. Mutagenicity tests with Salmonella typhimurium TA1538 showed that DMBA had a specific mutagenic activity of 10 revertants/μg upon metabolic activation. Coal fly ash had an activity of 236 revertants/mg when rat liver S9 was not incorporated and of 163.6 revertants/mg when the S9 was incorporated. The mutagenicity studies also showed that rapid release of ash mutagens in tracheal lumina occurred within 1 mo post‐transplantation. A t that time and thereafter, only about 25–40% of total mutagenic activity remained on the surface of ash particulates. An attempt was made to explain the failure to demonstrate carcinogenicity (in terms of neoplastic changes in tracheas) of coal fly ash. Results obtained from histopathological examinations of DMBA‐ or coal‐fly‐ash‐exposed tracheas, from specific mutagenicities, and from the rate of release of DMBA and coal fly ash into tracheal lumina were analyzed. Although coal fly ash produced 2.7 times more mutations (in terms of non‐histidine‐requiring revertant colonies) than DMBA at 2 mo post‐transplantation, it failed to induce any neoplastic changes in exposed tracheas. It is thus concluded that the critical factor is not the number of mutations produced per se, but rather the nature of the mutagen(s) responsible for carcinogenesis.