EVIDENCE ON THE CARCINOGENICITY OF 2,4,5-TRIMETHYLANILINE 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 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). 2,4,5-Trimethylaniline 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 2,4,5­ Trimethylaniline 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 2,4,5­ trimethylaniline and its strong acid salts. A public meeting of the Committee to discuss this evidence is tentatively scheduled for September 25, 1997. Written public comment on the document should be submitted to OEHHA by August 20, 1997, in order to be considered by the Committee in advance of the meeting. During the September meeting, the public will have an opportunity to present verbal comments to the Committee. 1 EXECUTIVE SUMMARY 2,4,5-Trimethylaniline (CAS number 137-17-7) has been used as an intermediate for dye manufacture. The hydrochloride (CAS number 21436­ 97-5) and other strong acid salts are expected exist in a dissociated state in solution and in vivo, and thus are considered toxicologically equivalent to the free or protonated amine form. 2,4,5-Trimethylaniline has been demonstrated to induce liver carcinoma in male and female Fischer 344 rats and female B6C3F 1 mice in studies by the National Cancer …