Monday, January 17, 2005

Is Diesel Particulate 100 Times as Carcinogenic as Cigarette Smoke?

It seems bizarre that in 2004 a paper would be published showing that cigarette smoke causes cancer. But this publication actually provides a critical anchor for use of risk assessment from laboratory studies of cancer causing chemicals.

Risk assessment methods debates come back to three questions: Does carcinogenicity at high doses predict risk at lower doses? Does carcinogenicity in laboratory animal studies [usually rats and mice] predict cancer risk in people? And, do high dose studies showing carcinogenicity in laboratory animals [which often cause other physiological changes] predict low dose risk in people?

Critical to the knowledge base supporting risk assessment is examining the behavior of agents known to cause cancer in people, in relation to the results of laboratory bioassays of these chemicals, often bioassays done after the fact of epidemiology.

Most recently, NIOSH asked for comments on whether lab studies of large particle titanium dioxide [found in most white paints] which produced a significant increase in lung tumors in rats at 250 mg/M3 predicted human cancer risk as lower levels. The industry side, predictably, denounced the high exposure levels as being irrelevant to people. A similar debate followed bioassays showing carcinogenicity of diesel particulate matter at much lower levels, 2.5 mg/M3. [Pay attention to the numbers, they are important.] In the case of diesel, the bioassay exposure levels were a small multiple of what workers in indoor settings with diesel engines get, although DPM in the outdoors is closer to 0.005 mg/M3.

The recent paper on cigarette smoke is actually the first bioassay showing clear evidence for carcinogenicity of cigarette smoke in the rat. The investigators reported that male and female F344 rats (n = 81 to 178/gender) [much larger groups than the standard cancer bioassay] were exposed whole-body smoke from 1R3 research cigarettes diluted to 100 mg/M3 (LS) or 250 mg/M3 (HS). There was only a slight reduction of survival at the HS level. Cigarette smoke exposure significantly increased the incidences of non cancer and cancer related proliferative lung lesions in females, while nonsignificant increases were observed in males. The combined incidence of bronchioloalveolar adenomas (benign) and carcinomas (malignant tumors) in females were: HS = 14%; LS = 6%; and C = 0%. The incidence of neoplasia of the nasal cavity was significantly increased at the HS, but not the LS level in both males and females (HS = 6%, LS = 0.3%, C = 0.4% for combined genders).

BrooklynDodger, were we reviewing the papers listed below for publication, would have argued strongly that the abstracts minimize the strength and importance of the findings, to the degree that naive readers will miss their point entirely. BrooklynDodger notes that the lead author has generally argued that risks of DPM to people are low. By contrast, BrooklynDodger points out that simply dividing the effect level for cigarette smoke by the effect level of DPM yields a potency ratio of 100. The lung cancer yield of in people smoking a pack a day is somewhere around 5 to 10%, pretty much the same observed for 250 mg/M3 of cigarette smoke, or 2.5 mg/M3 for diesel particulate matter in the rat.

Toxicol Sci. 2004 Oct;81(2):280-92.

Chronic inhalation exposure to mainstream cigarette smoke increases lung and nasal tumor incidence in rats.

Mauderly JL, Gigliotti AP, Barr EB, Bechtold WE, Belinsky SA, Hahn FF, Hobbs CA, March TH, Seilkop SK, Finch GL.Lovelace Respiratory Research Institute, Albuquerque, New Mexico 87108, USA. jmauderl@lrri.orgA

Fundam Appl Toxicol. 1995 Apr;25(1):80-94.

Comparative pulmonary toxicities and carcinogenicities of chronically inhaled diesel exhaust and carbon black in F344 rats.

Nikula KJ, Snipes MB, Barr EB, Griffith WC, Henderson RF, Mauderly JL.Inhalation Toxicology Research Institute, Lovelace Biomedical and Environmental Research Institute, Albuquerque, New Mexico 87185, USA.

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