No abstract

In rodents, the larynx is a major site of histopathologic alteration following inhalation exposure to particulates, vapors, and aerosols. Specifically, the epithelial lining of a narrowly delineated region on the ventral floor of the larynges of rats and mice appears to be especially vulnerable to inhaled materials, and is recognized as a preferred site for histopathological evaluation in inhalation studies. This site is located at the base of the epiglottis, cranial to the ventral laryngeal diverticulum (ventral pouch (Fig. 1). The cranial half of the larynx is then embedded in paraffin (cut side down). The block of tissue is then slowly faced caudad to craniad until the ventral laryngeal diverticulum appears ventrally, and the arytenoid and &dquo;U&dquo; cartilages appear laterally (Fig. 2). Proceeding more

Sprague-Dawley rats were exposed nose-only for 1 h/day on weekdays for 13 weeks to the smoke from test and reference cigarettes. The test cigarette was a new prototype: the tobacco is heated rather than burned. The University of Kentucky lR4F cigarette was used as a reference. The exposures used were around 25% higher than those used in earlier studies, and for the test cigarette the resulting blood carboxyhemoglobin concentrations approached those associated with death (62 + %). The smoke from the reference cigarette produced substantial reductions in breathing frequency, whereas the smoke from the test cigarette did not. The availability of nicotine from test and reference cigarettes was very similar. The histopathology seen (mucus-secreting cells; nasal, laryngeal, and bronchial hyperplasia and squamous metaplasia, pulmonary macrophages) indicated that most of the changes observed in the reference animals were absent in the test animals. When changes were seen in the test groups (primarily in the larynx), they were substantially reduced when compared with the reference groups and were completely reversible.The authors thank

Male Sprague-Dawley rats were exposed 6 hr/day, 5 dayslweek for up to 13 weeks to aged and diluted sidestream smoke (ADSS), used as a surrogate for environmental tobacco smoke (ETS), at concentrations of 0.1 ("typical'?, I ("extreme"), or 70 ("exaggerated) mg of particulates/m3. Subgroups of animals were killed after 1 and 4 weeks of exposure. Animals were exposed nose-only, inside whole-body chambers, to ADSS from the 1R4F reference cigarette. End points included histopathology, CO oximetv plasma nicotine and cotinine, clinical pathology, and organ and body weights. The target particulate concentrations were achieved; at the exaggerated exposure they resulted in CO concentrations in excess of 50 ppm. Particle size distributions showed that the aerosols were completely respirable: the mass median diameter values were less than 1 pm. The only pathological response observed was slight to mild epithelial hyperplasia in the rostra1 nasal cavity, in the exaggerated exposure group only. No effects were noted a t low (typical of measured real-world ETS concentrations) or extreme exposures. The changes were similar in animals killed after 4'28, or 90 days, and were also similar to those noted in an earlier experiment with only 14 days duration, indicating that the change does not progress with increased exposure duration from 4 to 90 days. The nasal change was absent in a subgroup of animals kept without further smoke exposure for an additional 90 days, indicating complete reversibility. Overall, the end points used in the study demonstrated that (7) there was no detectable biological activity of ADSS at typical or even ?&fold ETS concentrations, and (2) the activity was only minimal at exaggerated concentrations in one region of one organ only Based on the nasal histopathology, the NOEL for the 9@day study is > 1 mg/m3.

Eight groups of 30 male and 30 female rats were exposed 1 hr per day, 5 days per week for 13 weeks, to smoke from reference (tobacco burned) or test (tobacco only heated) cigarettes, at nicotine concentrations of 5, 15, or 30μ/liter, of air. Similar smoke concentrations of wet total particulate matter and carbon monoxide were produced in each of the test/reference comparisons. There was a pronounced depression of minute ventilation of animals in the reference groups, but not in the test animals. Blood carboxyhemoglobin concentrations were similar in animals exposed to smoke from test and reference cigarettes. Plasma concentrations of nicotine and cotinine in the test groups were higher than in the reference groups. There were no differences between the smoke-exposed groups in terms of body weight or feed consumption. At necropsy, an increase in heart weight was noted in both high exposure groups. There were notable differences in histopathology, with fewer and less-pronounced changes in the test groups than in the reference groups. Many of the histopathological responses induced in the reference groups were absent in the test groups. Overall, the study demonstrated a substantial reduction in the biological activity of smoke from the test cigarette when compared with the reference.