Friday, March 25, 2005

Don’t Stop Thinking About Tomorrow … But Think Less about Yesterday [an essay with no references]

Back in the day – mid ‘70’s – it seemed like there were maybe 4 lung carcinogens: cigarette smoke, asbestos, radon, and coke oven emissions. Notably, all of these made the list based on studies in people, with little or no laboratory toxicology to back it up.

Based on the distribution of exposures to this gang of only 4, Peto and Doll issued a canonical statement that only 2% of cancers were due to “pollution” or industrial chemicals. Additionally, the only hints of airborne contaminants causing heart disease were carbon monoxide, or fibrotic exposures stressing the heart.

The Peto-Doll estimate was faulty even with what was known then. Cigarette smoke was then known to potentiate other lung carcinogens, asbestos and radon, yet all the cancers were attributed to the demon leaf. Hold this thought for later.

BrooklynDodger remembers when many devoted their research efforts to explaining why asbestos caused fibrosis and lung cancer, while silica caused only fibrosis and not lung cancer.

Many in the IH community are still stuck in yesterday. Here’s where we are today. These comments track a parallelogram whose sides are: health effects in animals from exposures known to be carcinogenic in people; and, health effects in people of exposures known to be carcinogenic in animals.
The first idol to fall was silica. Silica was tested in animals, first as a non-cancer but fibrogenic control for oil shale dust, and then as part of an assay of Mt. St. Helen’s dust. All the carcinogenesis of oil shale was due to Silica. Silica was carcinogenic in the rat. This provided biological plausibility to the more than 50 studies showing silica to cause excess cancer in workers. Finally, a study in Vermont granite workers put silica over the top as a known human carcinogen.

Diesel particulate matter should have altered another paradigm. DPM was initially a concern as a tobacco or coke oven emissions surrogate – carbon-containing particles with heavy organic carcinogens adsorbed onto the surface. Extracts from DPM particles were mutagenic in bacterial bioassays. Simultaneously, EPA and industry money started laboratory bioassays and mortality studies in workers exposed in trucking and on the railroads. DPM turned out to about 100 times as potent a carcinogen in the rat as cigarette smoke [which is barely carcinogenic at all in the lab.] Meanwhile, about two dozen studies in railroad, trucking and some miners found excess lung cancer, including studies taking smoking into account. [Smoking is never the cause of increased lung cancer in an occupational cohort.] Then a bioassay of carbon black – diesel with the gooey carcinogens washed away – was positive as well.

Non asbestos [baby grade] talc proved carcinogenic in a laboratory bioassay in the rat.

A series of community studies found increase mortality from respiratory illness [no biological surprise] and cardiac diagnoses [a big surprise] with increases in particulate pollution. This sparked a wave of laboratory studies showing that fine particles – 0.3 micron – penetrated the lung into systemic circulation. Which means that remote site tumors from cigarette smoke and coke oven emissions may be a direct particle effect rather than a surface carcinogen desorbed and absorbed effect.

Radon’s human carcinogenic effect was observed in miners. At the time these studies were done, silica was not yet a carcinogen, so silica exposure was not taken into account. Almost certainly, the cancers in the miners were a joint effect of radon [daughters] and silica, so radon potency is overstated, and the fraction of cancers due to radon is also overstated.

Environmental tobacco smoke was declared a known human carcinogen, based on household studies comparing non smoking spouses of smokers to non smoking spouses on non smokers.

How do these dots connect?

Everyone, everywhere, inhales mineral and carbon particles constantly, even without specific occupational exposures. These previously inert particles are much more potent than tobacco smoke, but for smokers there’s a lot more tobacco smoke. For ETS exposed people, potency differences mean that ETS is likely the tail wagging the particle dog. The same goes for radon, where ignoring particle toxicity [in the mines] leads to recommendations that people move out or tear down their houses.

For us old dog industrial hygienists, the earth needs to move from 5000 micrograms of “nuisance” dust being nearly ok, to worrying about 50 micrograms of particles NOS as a cancer risk.

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