2- Toluidine toxicity

Toxic effects due to 4-chloro-ort/20-toluidine result from inhalation or skin contact (Stasik, 1991). The first symptom of 4-chloro-orl/20-toluidine toxicity is macroscopic or microscopic haematuria. Further symptoms include dysuria, reduced bladder capacity and generalized pain in the lower abdomen. Haemorrhagic cystitis is the leading symptom of acute toxicity. 

Several methods including spectrophotometric or chromatographic techniques have been proposed for the determination of furans such as HMF or furfural, or developed to determine both furan compounds simultaneously. The spectrophotometric methods do not differentiate between HMF and furfural without the need of a previous separation procedure. The commonly employed colorimetric method for HMF is Winkler s 38), which is based on the use of barbituric acid and p-toluidine. Toxicity of p-toluidine, instability of the color complex formed, and interference of sulfurous acid and possibly other compounds present in the fruit juice 40) are known to be problems. Unlike HMF, the colorimetric method for furfural was based on a previous distillation of juice and the colorimetric analysis of distillate for furfural based on colorimetric reaction with aniline acetic acid in juices 41). However, distillation procedure with poor recovery (about 34%) and long reaction time for color development (approximately 1 h), and requirement of hazardous chemical aniline 20) are known to be the drawbacks of the colorimetric method for furfural. Also, colorimetric method generally requires strict control of reaction time and temperature to achieve stable and reproducible color development. 

This dmg is synthesized like cinchophen, method one, above. The only difference is the starting material is p-toluidine instead of aniline. It is used for the same purpose as cinchophen, but is claimed to be much less toxic, even though the dosage is to be stopped after three days, just like cinchophen. The mp is 74° and the dosage is 300 to 600 mg, with baking soda and water taken in conjunction. 

Toxicology. ort/ o-Toluidine causes anoxia due to the formation of methemoglobin and hematuria xA-toluidine hydrochloride is carcinogenic in experimental animals. The meta-and para-isomers are assumed to produce comparable toxic effects however, meta-tolrriAine seems to have no carcinogenic activity. 

Rats survived an 8-hour exposure to concentrated vapor. Animals exposed to from 6 to 23 ppm for several hours developed mild methemoglobinemia. In the eye of a rabbit, the liquid caused a severe burn. Excessive drying of the skin may result from repeated or prolonged contact. The meta- and para-isomers of toluidine show the same toxicity profile and dose range as ort/jo-toluidine similar effects from exposure are expected, although these isomers have not been tested as extensively as o-toluidine. ... 

According to the Toxics Release Inventory (Environmental Protection Agency, 1997), air emissions of ori/zo-toluidine from 23 industrial facilities were approximately 5260 kg in 1995 in the United States. 

Environmental Protection Agency (1984) Chemical Hazard Information Profile ortho-Toluidine, ortho-Toluidine Hydrochloride, Washington DC, Office of Pesticide Program and Toxic Substances... 

In humans, 4-chloro-ort/2o-toluidine induces acute toxicity in the urinary bladder and causes methaemoglobinaemia. In rodents, 4-chloro-ort/zo-toluidine and/or its metabolites bind to macromolecules in liver cells. 

Bentley, R, Waechter, E, Bieri, E, Staubli, W. Muecke, W. (1986a) Species differences in the covalent binding of p-chloro-o-toluidine to DNA. Arch. Toxicol., Suppl. 9, 163-166 Bendey, R, Bieri, E, Muecke, W., Waechter, E. Staubli, W. (1986b) Species differences in the toxicity of p-chloro-o-toluidine to rats and mice. Covalent binding to hepatic macromolecules and hepatic non-parenchymal cell DNA and an investigation of effects upon the incorporation of [ Hjthymidine into capillary endothelial cells. Chem.-biol. Interact., 57, 27-40... 

Prilocaine is an amide-type LA with a rapid onset and an intermediate duration of action associated with a low toxicity. However, metabolism to ortho-toluidine can cause oxidation of the ferric form of hemoglobin to the ferrous form, creating methemoglobin. In most cases the methemoglobuniemia is benign, but sometimes tissue hypoxia is observed (Eriksson, 1966). 

Prilocaine, which is equal in potency to lidocaine, has a longer duration of action. It is metabolized to o-toluidine, which in toxic doses may cause methemoglobinemia. 

Toxicity O-Toluidine is highly toxic to animals and humans and is rapidly absorbed by oral, dermal, and inhalation routes. The acute oral LD50 in rats ranges from 900 to 940 mg/kg.78,83 The compound is known to cause adverse effects in workers that include headache, irritation of skin, eye, kidneys, and bladder, and hematuria. O-Toluidine has caused hepatocellular adenomas and carcinomas in experimental mice and rats. 

DOT CLASSIFICATION 6.1 Label KEEP AWAY FROM FOOD SAFETY PROFILE Poison by ingestion. Mutation data reported. When heated to decomposition it emits toxic fumes of Cl and NOx. See also other chloro toluidine entries. 

DFG MAK Confirmed Animal Carcinogen with Unknown Relevance to Humans DOT CLASSIFICATION 6.1 Label Poison SAFETY PROFILE Confirmed carcinogen. Poison by ingestion and intraperitoneal routes. Mutation data reported. A severe skin and eye irritant. Flammable when exposed to heat, flame, or oxidizers. Can react vigorously on contact with oxidizing materials. To fight fire, use foam, CO2, dry chemical. When heated to decomposition it emits highly toxic fumes of NOx. See also o-TOLUIDINE and ANILINE. 

SAFETY PROFILE Poison by intraperitoneal route. Moderately toxic by ingestion. Questionable carcinogen with experimental carcinogenic and tumorigenic data. When heated to decomposition it emits very toxic fumes of NOx and HCl. See also p-TOLUIDINE. 

Caution p-Toluidine, like many aromatic amines, is highly toxic. o-Toluidine is not only highly toxic but also a cancer suspect agent. 

Caution p-Toluidine is toxic. Handle with care. 

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