Evaluation of changes in biomarkers of exposure in adult smokers switching to a tobacco pouch product.

A71

Background: There is an abundance of epidemiological evidence, from Sweden, demonstrating that low-nitrosamine oral tobacco products significantly reduce the overall smoking related disease risk. Few studies in the US have systematically characterized changes in exposure to some of the cigarette smoke constituents in adult smokers exclusively switching to such products.
 >Purpose: The goal of this study was to evaluate changes in exposure to nicotine, nitrosamines and potential mutagenic substances (as measured by urine mutagenicity) in adult smokers switching to tobacco pouch products .
 >Methods: Adult male (n=21) and female (n=6) smokers (20-40 cigarettes/day), were enrolled in a single center switching study. Upon entering the clinic, the subjects smoked their own cigarettes at Baseline (Day -1). From Day 1 through Day 7, the subjects stopped smoking and switched to exclusive, unrestricted pouch usage. Twenty-four hour urinary excretion of nicotine and five of its major metabolites (reported as nicotine equivalents, NE), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) metabolites (4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol, total NNAL) as well as urine mutagenicity were measured at Baseline (Day -1) and Post-Baseline (Day 7). Plasma nicotine was measured three times on Days -1, 1, 4 and 7. Residual nicotine, NNK and NNN were measured in the pouches after the subjects completed usage.
 >Results: The number of cigarettes smoked at Baseline was 17.7 ±3.1 (Mean ± SD). After switching to pouch, daily pouch consumption varied among Days 1-7, and ranged from 0 to 14 pouches per day. Pouch usage did not correlate with number of cigarettes smoked at Baseline. Statistically significant reductions in NE (-77.6%), total NNAL (-67.9 %) and urine mutagenicity (-82.6 %) were observed on Day 7 during pouch consumption compared to Baseline while smoking. Total NNAL levels observed from pouch consumption (146 ± 17.7 ng/24hr, Mean ± SE) were comparable to those observed in previous studies (158 ± 14.2 ng/24hr, n =109) in smokers who had stopped smoking for a similar period . Plasma nicotine levels, during pouch consumption, were 4.70 ± 1.11 ng/ml on evening of Day 7, compared to 24.8 ± 1.83 ng/ml in the evening at Baseline while smoking. The residual amounts of nicotine, NNK and NNN remaining in the pouch after usage (n=110) were 3.10 ± 0.07mg (original content 4.4 mg), 10.7 ± 0.3 ng (original content 16.9 ng) and 137 ± 3.0 ng (original content 188 ng) respectively.Conclusion:When adult smokers stopped smoking and switched to pouch use, significant reductions in exposure to potential mutagenic and carcinogenic substances were observed, as measured by urine mutagenicity and total NNAL. Based on residual amounts of nicotine, NNK and NNN remaining, it appears that only small fractions of nicotine and nitrosamines are extracted and probably absorbed from the pouch. Despite the opportunity for unrestricted pouch usage upon stopping smoking, adult smokers consumed much lower numbers of pouches than the number of cigarettes smoked and sustained much lower plasma nicotine levels from pouches, relative to that from cigarette smoking.