EVIDENCE ON THE CARCINOGENICITY OF QUINOLINE AND ITS STRONG ACID SALTS Reproductive and Cancer Hazard Assessment Section Office of Environmental Health Hazard Assessment California Environmental Protection Agency

PREFACE The Safe Drinking Water and Toxic Enforcement Act of 1986 (Proposition 65, California Health and Safety Code 25249.5 et seq.) requires that the Governor cause to be published a list of those chemicals " known to the state " to cause cancer or reproductive toxicity. The Act specifies that " a chemical is known to the state to cause cancer or reproductive toxicity...if in the opinion of the state's qualified experts the chemical has been clearly shown through scientifically valid testing according to generally accepted principles to cause cancer or reproductive toxicity. " The lead agency for implementing Proposition 65 is the Office of Environmental Health Hazard Assessment (OEHHA) of the California Environmental Protection Agency. The " state's qualified experts " regarding findings of carcinogenicity are identified as the members of the Carcinogen Identification Committee of the OEHHA Science Advisory Board (22 CCR 12301). Quinoline was discussed as a high priority candidate for Committee review during a public committee meeting held in Sacramento, California on July 22, 1996 and at a public workshop held November 15, 1996. Public input was solicited on the priority of this chemical in two public comment periods, each of 60 days duration. Once the chemical was selected for Committee review, a public request for pertinent information was made. This draft document Evidence on the Carcinogenicity of Quinoline and Its Strong Acid Salts was developed to provide the Committee with relevant information for use in its deliberations, and reviews the available scientific evidence on the carcinogenic potential of quinoline and its strong acid salts. 1 EXECUTIVE SUMMARY Quinoline is a naturally occurring heterocyclic aromatic chemical found in creosote and other products produced from fossil fuels. It is produced by combustion of a variety of substances including tobacco and is used in the chemical industry. Strong acid salts of quinoline, including the hydrochloride, can be expected to exist in a dissociated state in solution and in vivo, and thus are considered toxicologically equivalent to the free or protonated base forms. Administration of quinoline in feed to male rats produced a significant increase in the incidence of vascular tumors (hemangiomas or hemangio­ sarcomas) of the liver in three studies. Quinoline in the diet produced a high incidence of hepatocellular tumors and hemangioendotheliomas in male and female mice in one study that lacked untreated controls. It did not produce a significant increase in the incidence of tumors in …