Chemical Synthesis of a Novel Aromatic Amine Mutagen Isolated from Water of the Nishitakase River in Kyoto and a Possible Route of Its Formation

• Published in: Chemical research in toxicology 1998-04, Vol.11 (4), p.375-380
• Main Authors: Shiozawa, Tatsushi, Muraoka, Koichi, Nukaya, Haruo, Ohe, Takeshi, Sawanishi, Hiroyuki, Oguri, Atsuko, Wakabayashi, Keiji, Sugimura, Takashi, Terao, Yoshiyasu
• Format: Article
• Language: English
• Subjects: Japan; Mutagens - chemical synthesis; Triazoles - chemical synthesis; Water Pollutants, Chemical - chemical synthesis
• ISSN: 0893-228X; 1520-5010
• DOI: 10.1021/tx970222j

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-amino-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]acetoanilide (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 μg, 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.