Hepatocarcinogenicity of estragole (1-allyl-4-methoxybenzene) and 1'-hydroxyestragole in the mouse and mutagenicity of 1'-acetoxyestragole in bacteria.
Approximately 20% of a dose of estragole, a naturally occurring flavoring agent, was excreted in the urine of outbred male CD -1 mice as a conjuage (presumably the glucuronide) of 1'-hydroxyestragole, Estragole and its 1'-hydroxy metabolite caused significant increases in the incidences of hepatocellular carcinomas in male CD-1 mice that received the compounds by sc injection at 1-22 days of age. Estragole induced hepatocellular carcinomas by 15 months in 23 and 39% of the mice that received total doses of 4.4 and 5.2 mumoles, respectively, and lived to an age of 12 months or more. Of the 12-month survivors given a total dose of 4.4 mumoles of 1'-hydroxyestragole, 70% developed hepatocellular carcinomas; the incidence in mice that received only the vehicle (trioctanoin) was 12%. Multiple tumors ocurred in 5, 28, 64, and 0%, respectively, of the mice in each of these 4 groups. Of the mice given a total dose of 4.4 mumoles of 1'-hydroxysafrole, 59developed hepatocellular carcinomas; 39% of the mice bore multiple liver tumors. As previsously demonstrated for 1'-acetoxysafrole, 1'-acetoxyestragole and 1'-acetoxy-1-allyl-4-methoxynaphthalene reacted nonenzymatically with guanosine and inosine to form adducts. These electrophilic esters were strongly mutagenic for the Salmonella typhimurium missense mutant TA100. 1'-Acetoxyallybenzene had little or no activity in either of these tests. Attempts to demonstrate liver-mediated mutagenicty for 1'-hydroxysafrole and 1'-hydroxyestragole in the bacterial test system were unsuccessful.
D000081248:Allylbenzene Derivatives; D000818:Animals; D000831:Animals, Newborn; D000840:Anisoles / Q000378:metabolism / Q000633:toxicity*; D002273:Carcinogens; D006528:Carcinoma, Hepatocellular / Q000139:chemically induced* / Q000473:pathology; D005421:Flavoring Agents / Q000378:metabolism / Q000633:toxicity*; D005965:Glucuronates / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008113:Liver Neoplasms / Q000139:chemically induced* / Q000473:pathology; D008297:Male; D051379:Mice; D009153:Mutagens; D009374:Neoplasms, Experimental / Q000139:chemically induced / Q000473:pathology; D009705:Nucleosides / Q000378:metabolism; D012486:Salmonella typhimurium / Q000187:drug effects
D000081248:Allylbenzene Derivatives; D000840:Anisoles; D002273:Carcinogens; D005421:Flavoring Agents; D005965:Glucuronates; D009153:Mutagens; D009705:Nucleosides; C014037:1'-hydroxyestragole; C007633:estragole