Light Yellow Liquid O Toluidine C7H9N With Mpurity Reference Substance

Light Yellow Liquid O-Toluidine With Mpurity Reference Substance

O-Toluidine, the isomer produced in greatest volume, has found many commercial applications. By far the single largest use for O-Toluidine is in the preparation of 6-ethyl-o-Toluidine, an intermediate in the manufacture of two very large-volume herbicides, metolachlor and acetochlor. Another important use of o-Toluidine is in rubber chemicals, where it could be used in the manufacture of a rubber antioxidant, and of di-ortho-tolylguanidine, a nonstaining rubber accelerator. Acetoacet[1]o-Toluidine, 3-hydroxy-2-o-Toluidine, 2-toluidine-5-sulfonic acid, and ortho-aminoazotoluene are four of the more important dye and pigment intermediates manufactured from o-Toluidine. In addition, o-Toluidine is used to manufacture epoxy resin hardeners such as methylene-bis-2-methylcyclohexylamine, fungicide inter[1]mediates such as 2-amino-4-methylbenzothiazole, and ortho-fluorobenzoyl chloride. Certain pharmaceutical intermediates are also prepared starting with o-Toluidine (Bowers, 2000). Other minor uses of o-Toluidine and its hydrochloride salt are as intermediates in organic synthesis and as ingredients in a clinical laboratory reagent for glucose analysis (HSDB, 2009).

Occupational exposure to o-Toluidine can occur during its production, or during the production of dyes, pigments and rubber chemicals manufactured from this compound. Laboratory and medical personnel may be exposed when using o-Toluidine for staining tissues.

(a) Production of o-Toluidine

In the former USSR (Khlebnikova et al., 1970), air samples at a plant manufacturing o-Toluidine from ortho-nitrotoluene (215 samples) generally exceeded the maximum permissible concentrations of 3 mg/m3 (IARC 1982) by 2–7 times. The highest airborne exposure concentrations were observed during distillation and extraction processes (25– 28.6 mg/m3 ). Concurrently, in 80–90% of the air samples ortho-nitrotoluene levels exceeded the maximum permissible concentration of 1 mg/m3 : values up to approximately 5 mg/m3 were reported. Dermal deposition of o-Toluidine at 0.01– 0.03 mg/dm2 of skin was measured by collecting 1% acetic acid washes from the wrists, chest and back of individuals at the end of work-shifts (n = 168). After post-shift showers, o-Toluidine 411 dermal levels of o-Toluidine had decreased by a factor of 10. Patches of cloth placed on the workers’ overalls collected about 0.10 mg/dm2 (n = 46).

(b) Use of o-Toluidine in dye production

Measurements in the 1940s in a dye-production plant in the United States indicated that the concentration of o-Toluidine was below 0.5 ppm (2.19 mg/m3 ) in the workroom air (breathing zone and area samples) and ranged from < 0.3 ppm to 1.7 ppm in the urine of workers engaged in the production of thioindigo. In addition to inhalatory exposure, exposure from ingestion and skin contact may have occurred (Ott & Langner, 1983). Exposure to o-Toluidine was reported to occur in an Italian plant producing fuchsin (magenta) and safranine T-based dyes (Rubino et al., 1982), in a German plant producing 4-chloro-o-Toluidine (Stasik, 1988), and in a plant producing azo-dyes in New Jersey, USA (Delzell et al., 1989). No data on exposure levels were provided.

(c) Production and use of rubber antioxidant

O-Toluidine, aniline, hydroquinone and toluene were used to synthesize a rubber antioxidant in a chemical plant in the United States. Despite low air concentrations (< 1 ppm; 4.38 mg/m3 ), elevated pre-shift urinary o-Toluidine levels of 18 ± 27 μg/L (n = 46) and post-shift levels of 104 ± 111 μg/L were detected. The average concentration of o-Toluidine in the pre-shift samples was 17 times higher than that in urine samples of unexposed workers (Ward et al., 1991; Teass et al., 1993). Sorahan et al. (2000) reported worker exposure to o-Toluidine in a plant that produced rubber chemicals in the United Kingdom, but no data on exposure concentrations were provided. Korinth et al. (2006) reported on four workers involved in vulcanising hydraulic rubber articles, who were exposed to o-Toluidine contained in di-ortho-tolylguanidine (used as an accelerator for the vulcanization of rubber products) by dermal absorption. The concentrations of o-Toluidine in the air at the workplace ranged between 26.6– 93.9 μg/m3 and o-Toluidine concentrations in urine were between 54.7–242.9 μg/L.

(d) Demolition workers of an SO2 plant polluted with o-toluidine

Labat et al. (2006) measured urinary o-Toluidine levels in workers employed in the demolition of a liquid-SO2 plant polluted with o-Toluidine. The plant had stopped production 20 years earlier. For unexposed workers, urinary concentrations of ortho[1]toluidine ranged between 0.17 and 2.46 μg/g creatinine. Post-shift urinary concentrations for exposed workers ranged between 26.1 and 462 μg/g creatinine. After protective measures were taken, this decreased to 2.4–20.1 μg/g creatinine. 412 IARC MONOGRAPHS VOLUME 99

(e) Laboratory workers

Although medical and laboratory personnel represent a significant population of workers potentially exposed to o-Toluidine, air concentrations have been determined to be below 22 µg/l (Environmental Protection Agency, 1984). Kauppinen et al. (2003) reported that in 1988 in Finland, five of 26 pathological laboratories used o-Toluidine for staining tissues with a median use of 10 g/year, three of 30 clinical laboratories used it with a median use of 180 g/year, and six of 20 other laboratories with a median use of 10 g/year.