Safrole

Regarding the toxicity of safrole, animal studies showed that administration led to the induction of tumors, e.g., in mice and rats [98]. In the early 1960s, the first data were published indicating that safrole causes carcinogenic effects in rat liver [99]. In the

following years, results of different animal studies (e.g., in rat and mice) confirmed that safrole is a carcinogen in the liver and other tissues, such as the lung [100,101]. Moreover, it was demonstrated that this carcinogenic effect was—at least in parts—mediated via active metabolites, such as 1- -hydroxysafrole or, rather, 1- -sulfoxysafrole [80,98,101–103]. The mutagenic effect of safrole and its metabolites was also verified in vitro and in vivo [7,104]. The toxicological relevance of the genotoxic 1- -sulfoxysafrole is underlined by the finding that co-administration of the SULT-inhibitor PCP drastically reduced the carcinogenic activity of safrole in rodents [80]. Therefore, the Scientific Committee on Food (SCF) of the European Commission (EC) considered safrole as a genotoxic carcinogen in 2002 [98]. In line with this, International Agency for Research on Cancer (IARC) also classified safrole as "possibly carcinogenic to humans" (Group 2B) [105].
