Relationships between coumarin, its derivatives, and dicumarol

FIGURE VI-1 Relationships between coumarin, its derivatives, and dicumarol. 

In previous metabolic studies, it had been reported that coumarin was not a precursor of dicumarol (II) (6A03, 6AI5) or of o-coumaric acid [3-(2-hydroxyphenyI)-2-prope-noic acid] III (6A21). Ill was known to be a precursor of dicumarol via 4-hydroxycoumarin IV. Laboratory animals (rats, rabbits) fed coumarin excreted 4-hydroxycoumarin IV (6A04). Between 70% and 90% of coumarin administered to humans resulted in excretion of 7-hydroxycoumarin V (6A17), a coumarin derivative never indicted as dangerous to any species or proposed as a dicumarol precursor. 

Newell reported in 1963 that (1) inclusion in cigarette tobacco of 3- C-coumarin 1 gave no dicumarol II in either the MSS or the sidestream smoke (SSS) and (2) inclusion in cigarette tobacco of unlabeled dicumarol gave no dicumarol 11 in either the MSS or the SSS (2757). Of the 

3- C-coumarin applied to the tobacco blend, Newell reported that 60% appeared unchanged in the MSS and SSS. 

Despite the controversies over the tumorigenicity of coumarin, its use in tobacco flavor formulations was subsequently discontinued throughout the tobacco industry worldwide. 

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