Saturday, July 23, 2005

Money Tox - Fine Particle Environmental Exposure Standard

BrooklynDodger follows Regulatory Toxicology and Pharmacology, otherwise known as the Journal of Corporate Risk Reviews and Briefs.
Well, that's not totally fair, there's some scholarship published there as well. However, the impact of the journal is that some meta-analyses [arguably new scholarship] and other reviews appear with the imprint of peer review to be included in reviews at IARC and NTP.
So, here comes, in advance of the new EPA review on particle limits, something which falls rhetorically outside the lines. The abstract begins "I review the rationale for the Environmental Protection Agency's 1996 fine particle standard..." This review was sponsored by the American Petroleum Institute. It's not clear from what regulatory venue it's recycled.
Suresh Moolgavkar may actually have the weight to start a scholarly paper with "I," since he has a carcinogenesis extrapolation model named for him, the "two-stage clonal expansion model." [Actually, the two-stage model has more parameters than the "linearized multi-stage model."] Even so, the convention of scholarly writing is that there is no "I" in expert.
Moolgavkar is correct that in 1996, there was little toxicological support for the finding of increased cardiovascular mortality associated with particulate exposure. The lynch pin epidemiology appeared only in 1993. However, it's not totally balanced to invoke epidemiology since 1996 to evaluate the staff paper, and ignore the wealth of toxicology since 1996. Toxicology, spurred by epidemiology, has provided biological plausibility to the epidemiological findings.
Moogavkar's problems with the epidemiology boil down to not believing the statistical methods, which for those of us who don't do that kind of work, are black boxes. The two-stage model is another black box.
A nice quote about human data was extracted from the full text:

Another striking example of the limitations of observational epidemiological studies is provided by the experiencewith anti-oxidants and cancer and heart disease. Based on observational epidemiology studies, experimental evidence and biological plausibility, anti-oxidants were widely considered to be promising chemo-preventiveagents for both cancer and heart disease (Blocket al., 1992; Omenn, 1998; Omenn et al., 1996). Yet large randomized clinical trials of a combination of anti-oxidants,b-carotene and retinol, indicated that these supplementsconferred no protection against lung cancer among high risk groups (Omenn et al., 1996). Theauthors concluded, ‘‘. . . the combination of beta caroteneand vitamin A had no benefit and may have had anadverse effect on the incidence of lung cancer and onthe risk of death from lung cancer, cardiovascular disease,and any cause in smokers and workers exposed to asbestos.’’ Very recently a meta-analysis (Miller et al.,2005) of randomized clinical trials of another anti-oxidant,vitamin E, concluded that high doses of this vitamin ‘‘may increase all-cause mortality and should be avoided.’’
Regulatory Toxicology and Pharmacology 42 (2005) 123–144

A review and critique of the EPA's rationale for a fine
particle standard
Suresh H. Moolgavkar
Sciences International, Inc., King Street Station, 1800 Diagonal Road, Suite 500, Alexandria, VA 22314, USA

I review the rationale for the Environmental Protection Agency's 1996 fine particle standard, which was based almost entirely on the epidemiological data with neither support from Toxicology nor understanding of mechanism. While many epidemiological papers available in 1996 reported associations between ambient particles and adverse effects on human health, many others did not and the evidence fell far short of supporting a causal association between particle mass concentration and human health.

The literature appearing after 1996 further complicates the picture. The large studies that have appeared after 1996, such as National Mortality Morbidity and Air Pollution Study, and the reanalyses of the American Cancer Society II study, report risks that are substantially smaller than the risks reported in the 1996 Criteria Document and Staff Paper. Moreover, concerns about confounding by weather, temporal trends and co-pollutants remain unresolved. Other issues having to do with model choice have resurfaced as a
result of reanalyses of critical data to address a glitch in a widely used software package for time-series epidemiology studies of air pollution.
Finally, contemporary examples show that the results of observational epidemiology studies can be seriously biased, particularly when estimated risks are small, as is the case with studies of air pollution. The Agency has largely ignored these issues. I conclude that a particle mass standard is not defensible on the basis of a causal association between ambient particle mass and adverse effects on human health. Such a standard may be justifiable on the basis of the precautionary principle, however.
The Agency could argue that the Science raises concerns about current levels of air pollution, and that reduction of ambient fine particulate matter mass, if it could be achieved without an increase in the level of the ultrafines, could have positive effects on human health. If the Agency justifies a particulate matter mass standard on these grounds then the debate over the form and level of the standard will, for all practical purposes, belong strictly in the Policy arena.

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