Sunday, July 03, 2005

Of Mice and Men and Fine Particles

[apologies to Steinbeck]

Mort Lippman remains an active leader in industrial hygiene and environmental health sciences, starting with an MS in IH in 1955. This project uses all kinds of advances unknown to BrooklynDodger at career start two decades later: particle concentrators, knockout mice, and even a reason to examine ambient particles at close to ambient levels.

The abstract summarized below continues the explosion of data on health effects of ambient particles. Inhalation Tox is not available to BrooklynDodger in full text, so the number of animals per group, the magnetude of significant effects, and any unquoted effects in the regular mice can't be figured into an equation for a level of concern for this exposure. The size of the test group establishes a statistical limit of detection for health effects; this limit of detection is an artifact of study design and feasibility.

The EPA annual average limit for PM2.5 is 15 mcg/m3, it's probably the best comparison for the exposure below. Actually there's not much stuff in the air with a MMD of 2.5, most of the mass in this fraction is in particles which are 1.0 and below, agglomeration of combustion generated ultrafine particles. Tuxedo is off in the country, so these particles are the effluent of killer trees, motor vehicles, and drift from elsewhere. If 100 mcg/m3 is an effect level, then 10 mcg/m3 approximates the benchmark dose, which is itself a 1/10 attack rate and therefore projects an unreasonable risk to public health.

But, these are mice genetically engineered to be less resistent to the exposure. Industry advocates have advocated that rats are an inappropriate model for particulate carcinogenesis, since they get lung tumors from particulate exposure [for example, tobacco smoke], while mice do not [including tobacco smoke.]

...normal mice (C57) and knockout mice that develop atherosclerotic plaque [were exposed] for 6 h/day, 5 days/wk for 5 or 6 mo ... to either filtered air or 10-fold concentrated ambient particles (CAPs) in Tuxedo, NY (average PM2.5 concentration during exposure = 110 microg/m3). [For those who don't know, Tuxedo borders the Catskills, it's where summer camps for NY kids were established before the middle class got rich enough to send the kids further away. Tuxedo is Rockefeller country, not the inner city.] ...

the daily variations in CAPs were significantly associated, in ApoE-/- mice, with daily variations in cardiac functions;

there were significant differences between CAPs and sham-exposed ApoE-/- mice in terms of cardiac function after the end of exposure period, as well as small differences in atherosclerotic plaque density, coronary artery disease, and cell density in the substantia nigra in the brain in the ApoE-/- mice;

there are suggestive indications of gene expression changes for genes associated with the control of circadian rhythm in the ApoE-/- LDLr-/- double knockout (DK) mice.

These various CAPs-related effects on cardiac function and the development of histological evidence of increased risk of clinically significant disease at the end of exposures in animal models of atherosclerosis provide biological plausibility for the premature mortality associated with PM2.5 exposure in human subjects and provide suggestive evidence for neurogenic disease as well.

Inhal Toxicol. 2005 Apr;17(4-5):255-61.

Effects of subchronic exposures to concentrated ambient particles in mice. IX. Integral assessment and human health implications of subchronic exposures of mice to CAPs.

Lippmann M, Gordon T, Chen LC.

Department of Environmental Medicine, Nelson Institute of Environmental Medicine, New York University School of Medicine, Tuxedo, New York 10987, USA.

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