title: Chemical synthesis of a novel aromatic amine mutagen isolated from water of the Nishitakase River in Kyoto and a possible route of its formation.
abstract: Among five mutagenic compounds isolated from water samples, taken at sites below the sewage plants of the Nishitakase River in Kyoto, Japan, the structure of compound I has been determined to be 2-[2-(acetylamino)-4-[bis(2-methoxyethyl)amino]-5-methoxyphenyl]-5-am ino-7-bromo-4-chloro-2H-benzotriazole (PBTA-1). Since this novel aromatic amine mutagen has characteristic substituents in its molecule, it is postulated that the azo dye, 2-[(2-bromo-4, 6-dinitrophenyl)azo]-4-methoxy-5-[bis(2-methoxyethyl)amino]acetoanili de (AZO DYE-1), used as an industrial material, is converted to the corresponding 2-phenylbenzotriazole derivative with a reducing reagent and subsequently to PBTA-1 by chlorination. In fact, AZO DYE-1 changed to the dechlorinated derivative of PBTA-1 (deClPBTA-1) on treatment with sodium hydrosulfite, and this reacted with sodium hypochlorite to produce PBTA-1. Moreover, the presence of deClPBTA-1 was confirmed in a river water sample, along with PBTA-1. PBTA-1 showed potent mutagenic activities in Salmonella typhimurium TA98 and YG1024, inducing 88 000 and 3 000 000 revertants, respectively, per microg, with S9 mix. deClPBTA-1 was also mutagenic, but less potent. From these observations, it is suggested that PBTA-1 is produced from AZO DYE-1 through deClPBTA-1, during industrial processes at dyeing factories and the treatment of wastewater at sewage plants.
authors.affiliation: Graduate School of Nutritional and Environmental Sciences and School of Pharmaceutical Science, University of Shizuoka, 52-1, Yada, Shizuoka 422, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Shiozawa
authors.forename: K
authors.initials: K
authors.lastname: Muraoka
authors.forename: H
authors.initials: H
authors.lastname: Nukaya
authors.forename: T
authors.initials: T
authors.lastname: Ohe
authors.forename: H
authors.initials: H
authors.lastname: Sawanishi
authors.forename: A
authors.initials: A
authors.lastname: Oguri
authors.forename: K
authors.initials: K
authors.lastname: Wakabayashi
authors.forename: T
authors.initials: T
authors.lastname: Sugimura
authors.forename: Y
authors.initials: Y
authors.lastname: Terao
mesh_terms: D007564:Japan; D009153:Mutagens / Q000138:chemical synthesis*; D014230:Triazoles / Q000138:chemical synthesis*; D014874:Water Pollutants, Chemical / Q000138:chemical synthesis*
chemical_list: C112866:2-(2-(acetylamino)-4-(bis(2-methoxyethyl)amino)-5-methoxyphenyl)-5-amino-7-bromo-4-chloro-2H-benzotriazole; D009153:Mutagens; D014230:Triazoles; D014874:Water Pollutants, Chemical