Sunday, July 31, 2005

Diesel v. Cigarettes

Okay, BrooklynDodger concedes this paper comes from the "Phillip Morris Research Center." Nevertheless, it illustrates how toxic diesel particulate is, compared to a premier substance which at low exposure levels [0.05 mg/m3 or less] is known to be a human carcinogen.

Inhalation Toxicology is not available to BrooklynDodger in full text, so this blog is abstract based, which may include distortions the editor and reviewers were too distracted to find.

Exposures were 3 and 10 mg/M3. In the rat, 10 mg/M3 for mainstream smoke is probably not an effect level for lung tumors. For diesel, it is an effect level.

For the final endpoint "the tumor incidence (predominantly bronchiolo-alveolar adenomas) was 2% in the sham-exposed groups, 5% in the high RASS [cigarette] groups, and 46% in the high DEE [diesel] groups (sexes combined)."

[It would be nice to see NTP style mortality adjusted statistics. This would determine whether the high sidestream smoke group was elevated or not, and would permit a comparison to the direct smoke study from Lovelace. Except Lovelace only does the mortality adjusted [more sensitive and more specific] method when it's contracting to NTP.]

The other biochemical measures all were positive with diesel and marginal to negative with cigarette smoke.

Diesel at these exposure levels in the rat is about equally potent with washed carbon black. There's a camp which argues diesel carcinogenicity at these levels is a particle effect, not an effect of the goo on the outside of the particle. Traditionally cigarette carcinogenesis research focuses on the genotoxic goo on the outside of the smoke particle, not the particle itself. But the cigarette particle is way less potent than the diesel particle.

It will certainly be difficult to get the cigarette toxicology guys to refocus on particles, having spent so much time with the goo.

If we allow for the particle effect in these rat bioassays [mice and hamsters are more resistent and don't get much], for both agents, what does that say for human exposures? Is there a threshold for the particle effect? Community air pollution research suggests no, at least down to 15 micrograms.

Inhalation Toxicology
Volume 17, Number 11 / October 2005
549 - 576

Chronic Nose-only Inhalation Study in Rats, comparing Room-aged Sidestream Cigarette Smoke and Diesel Engine Exhaust

Walter Stinn A1, Ashok Teredesai A1, Erwin Anskeit A1, Klaus Rustemeier A1, Georg Schepers A1, Peter Schnell A1, Hans-Juergen Haussmann A1, Richard A. Carchman A2, Christopher R. E. Coggins A3, Wolf Reininghaus A1
A1 Philip Morris Research Laboratories GmbH, Cologne, GermanyA2 Philip Morris USA Research Center, Richmond, Virginia, USAA3 Carson Watts Consulting, King, North Carolina, USA

Nose-only exposure of male and female Wistar rats to a surrogate for environmental tobacco smoke, termed room-aged sidestream smoke (RASS), to diesel engine exhaust (DEE), or to filtered, fresh air (sham) was performed 6 hours/day, 7 days/week for 2 years, followed by a 6-month post-exposure period. The particulate concentrations were 3 and 10 mg/m3. Markers of inflammation in bronchoalveolar lavage showed that DEE (but not RASS) produced a dose-related and persistent inflammatory response. Lung weights were increased markedly in the DEE (but not RASS) groups and did not decrease during the 6-month post-exposure period. Bulky lung DNA adducts increased in the RASS groups, but not in the DEE groups. Cell proliferation in the lungs was unaffected by either experimental treatment. Histopathological responses in the RASS groups were minimal and almost completely reversible; lung tumors were similar in number to those seen in the sham-exposed groups. Rats exposed to DEE showed a panoply of dose-related histopathological responses: largely irreversible and in some cases progressive. Malignant and multiple tumors were seen only in the DEE groups; after 30 months, the tumor incidence (predominantly bronchiolo-alveolar adenomas) was 2% in the sham-exposed groups, 5%in the high RASS groups, and 46% in the high DEE groups (sexes combined). Our results suggest that in rats exposed to DEE, but not to RASS, the following series of events occurs: particle deposition in lungs → lung “overload” → pulmonary inflammation → tumorigenesis, without a significant modifying role of cell proliferation or DNA adduct formation.

No comments: