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

Abstract

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.

Mosquito coil smoke inhalation toxicity. Part II: Subchronic nose-only inhalation study in rats

“…The irritant-related changes of the respiratory epithelium at the site of initial deposition (anterior nasal passages, larynx) are commonly viewed as adaptive, non-progressive and reversible (Stinn et al, 2005). This high-level exposure was not associated with particle-related adverse effects in the airways or lower respiratory tract.…”

Concentrations of the Carcinogen 4-(Methylnitrosamino)-1-(3-Pyridyl)-1-Butanone in Sidestream Cigarette Smoke Increase after Release into Indoor Air: Results from Unpublished Tobacco Industry Research

“…It is known that the concentration of NNK in sidestream cigarette smoke is higher than that in mainstream cigarette smoke (7,44). Previous publications have also reported that the concentration of NNK in freshly generated sidestream cigarette smoke and in secondhand cigarette smoke in test chambers may be higher than the concentration of other TSNAs (39,40). However, we believe that this is the first publication to disclose data showing that the concentration of NNK in sidestream cigarette smoke can increase after the smoke is released into a room.…”

“…The precedent established in previous toxicologic experiments on sidestream cigarette smoke, by the tobacco industry (39,40,(51)(52)(53) and by independent scientists (54-61), of aging smoke in a controlled manner before testing biological effects is sound. It would be useful for these researchers to validate their experimental proxies for SHS by comparing proxy NNK concentrations to those found in the real world.…”

“…Philip Morris did, however, present and publish work that emphasized the rapid loss of SHS components from room air by adsorption and ventilation (34)(35)(36)(37)(38). Publications in 1998 and 2005 from Philip Morris on the toxicity of experimentally aged sidestream cigarette smoke do provide TSNA concentration data and show that NNK concentrations are elevated 10-to 20-fold relative to other TSNAs (39,40). However, unless the readers of these publications were aware that the concentration of NNK was only slightly higher than that of other TSNAs in fresh sidestream smoke, the fact that NNK forms as sidestream smoke ages will not be evident.…”

Secondhand Tobacco Smoke

“…Lung tumours were not significantly increased in rats exposed for 24 months and kept until 30 months of age (Stinn et al, 2005b).…”