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The evidence that different smoking regimes have varied influences on both nicotine and TSNA levels in smoke (i.e., the International Organization of Standardization (ISO) protocol generates less nicotine and TSNAs compared to the Canadian Intense (CI) protocol) 27 implies these influences significantly alter the transfer of nicotine to the smoke, and may indicate why we do not observe a correlation between NNK/NNN and nicotine levels