95-53-4 Orthotoluidine Organic Chemical Raw Materials For Pest Killers

Organic chemical raw materials O-Toluidine For Pest Killers

o-Toluidine, also named ortho-toluidine is a synthetic, light sensitive, light yellow liquid that is slightly soluble in water and miscible, carbon tetrachloride and ethanol. The hydrochloride is a synthetic, light sensitive, white crystalline powder that is soluble in ethanol and dimethylsulfoxide. o-Toluidine and o-toluidine hydrochloride are used primarily as intermediates in the manufacture of pigments and dyes. When heated to decomposition, o-toluidine emits toxic fumes of nitrogen oxides in process of the hydrochloride also producing hydrochloric acid. Four studies of workers exposed to o-toluidine reported an excess of bladder cancers. o-Toluidine and o-toluidine hydrochloride are reasonably anticipated to be human carcinogens.

A general Section on “Aromatic amines: metabolism, genotoxicity, and cancer susceptibility” appears as Section 4.1 in the Monograph on 4-aminobiphenyl in this volume.

O-Toluidine is a constituent of tobacco smoke and it is excreted in larger amounts in the urine of smokers than of non-smokers (Riedel et al., 2006). O-Toluidine induced urinary bladder and mammary gland tumours in rats and liver tumours and haemangiosarcomas in mice. The cancer risk of the urinary bladder was elevated in workers exposed to o-Toluidine. This substance has been evaluated in a huge number of genetic toxicology studies (IARC, 2010); But, there has been much inconsistency in the results reported.

The metabolism of o-Toluidine has not yet been totally characterized, however the available data indicate a preferential ring-oxidation or N-acetylation rather than N-oxidation (Son et al., 1980). Meanwhile, cancers of the urinary bladder associated with occupational exposure to o-Toluidine may result from peroxidative activation of the chemical, catalysed by prostaglandin H synthase in the epithelium of the urinary bladder. o-Toluidine-haemoglobin adduct levels were increased in patients treated with the anaesthetic prilocaine (Gaber et al., 2007) and in workers employed in the rubber chemicals manufacturing area of a chemical plant (Ward et al., 1996). Metabolites are excreted primarily as sulfate or glucuronide conjugates, since o-Toluidine is not a substrate for human NAT1-mediated acetylation (Zhang et al., 2006).

O-Toluidine induces tumours in rodents and DNA lesions in multiple organs. Most studies reported that o-Toluidine was not mutagenic in S. typhimurium, some other studies reported positive responses in the same strains. The N-oxidized metabolite of o-Toluidine, N-hydroxy-o-Toluidine, was mutagenic in S. typhimurium strain TA100 (Gupta et al., 1987). O-Toluidine, induced intrachromosomal recombination, in Saccharomyces cerevisiae in an assay that is responsive to the induction of DNA deletions (Carls & Schiestl, 1994); this result was reduced in the presence of an antioxidant. Others reported effects of o-Toluidine (Danford, 1991) include the induction of sister chromatid exchange, aneuploidy, unscheduled DNA synthesis, DNA strand breaks, and cell transformation in vitro, and the induction of micronuclei in peripheral blood of rats treated in vivo (Suzuki et al., 2005). The formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine in calf thymus DNA incubated in vitro with 4-amino-3-methylphenol, a metabolite of o-Toluidine, suggests a potential role of reactive oxygen species in the DNA-damaging effects of this aromatic amine (Ohkuma et al., 1999). O-Toluidine induced DNA lesions – measured by means of the comet assay – in multiple organs of exposed rats and mice (Sekihashi et al., 2002): increased DNA migration was observed in the liver, bladder, lung, and stomach of mice, and in the liver, bladder, and brain of rats.