The slope of the first regression line was fitted to the study data. The second slope was varied in such a way MK-2206 datasheet that the test statistics just reached statistical significance (p < 0.05). The difference between both slopes, expressed as percent, was taken as MDD. For an estimate of the lung tumor size, the number of consecutive cross sections showing the same individual lung tumor or precancerous lesion was multiplied with the 300 μm distance of consecutive step serial sections. The proportion between adenomas and carcinomas within the different exposure groups was calculated by the quotient of carcinomas and

the sum of adenomas and carcinomas on an individual animal basis. Animals were included in this type of evaluation, if at least one lung adenoma or carcinoma BMS-907351 clinical trial was present. These data were compared statistically by ANOVA followed by pairwise comparison using the Tukey test (Zar, 1984). All tests were considered statistically significant at p ≤ 0.05. No correction for multiple testing was performed. All test atmospheres were reproducibly generated throughout the 18-month inhalation period at the MS target concentrations of 75, 150, and 300 mg TPM/m3 (Table 1). This resulted in proportional concentrations of other aerosol constituents such as carbon

monoxide, nicotine, acetaldehyde and acrolein. An exception for this linear dilution was seen for formaldehyde. The concentrations in the current study (Study 2) corresponded well to those previously observed in the Study 1 (Stinn et al., 2012). Inhalation exposure to MS was monitored by determining carboxyhemoglobin proportions, which were 0.3 ± 0.1, 10.7 ± 0.5, 19.3 ± 0.7, and 36.5 ± 1.1% for males and 0.3 ± 0.1, 10.3 ± 0.3, 19.8 ± 0.5, and 37.0 ± 1.3% for females in the sham, MS-75, MS-150, and MS-300 groups, respectively (mean ± SE; N = 8 per group at two time points during the study). The carboxyhemoglobin proportions correlated Edoxaban with the carbon monoxide concentrations in the test atmospheres and were similar to those reported in Study 1. In the groups scheduled for 18 months of inhalation,

mortality rates of 58, 48, 34, and 45% for males and of 39, 39, 28, and 20% for females were observed in sham, MS-75, MS-150, and MS-300 groups, respectively. The trend to higher mortality in the sham-exposed compared to MS-exposed mice was also observed in Study 1. However, the overall mortality in Study 2 was higher than in Study 1. This may have been at least partly due to a dilated cardiomyopathy which occurred mainly during the first months of the study and was more pronounced in male than in female mice. In affected mice, the hearts were enlarged and displayed a grey-white discoloration. Microscopically, an infiltration of neutrophilic granulocytes and lymphocytes was observed as well as a calcification and necrosis of heart muscle cells.