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2,6-Xylidine is a chemical intermediate used principally in the production of dyes. It is also a component of tobacco smoke, a degradation product of aniline-based pesticides, and a metabolite of certain drugs, particularly the xylide group of local anesthetics.


2,6-Xylidine is easily absorbed from the gastro-intestinal tract and excreted unchanged or metabolized via the urine in experimental animals. 2,6-xylidine produces only weak methaemoglobin formation.


2,6-Xylidine is absorbed from the small intestine in rats, the half life periods for this process being 14.4 minutes (no further details; Pla' Delfina, et al., 1972). Further studies dealing specifically with absorption of the xylidines are not available. Proof of absorption following oral application of 2,6-xylidine in rats, and following oral application of 2,6-xylidine in dogs, has been furnished by the detection of the xylidines and their corresponding metabolites in the urine (Hardy et al., Short et al).

Poisoning symptoms, which have been described following corresponding applications, suggest that absorption via the skin and the respiratory tract may take place.


No studies or results are available for tissue distribution in animals.



The results of studies on the metabolism of the xylidines following oral application are given in shortened form in the following table. In general, investigations with different species show the same main metabolites after hydroxylation of 2,6-xylidine.




Conjugate of the metabolite



2,6-xylidine unchanged


2-amino-3-methyl benzoic acid

not specified

Lindstromet al.(1963)


2,6-xylidine unchanged


N,2,5-trimethyl aniline

glucuronide, sulphate

glucuronide, sulphate

Shortet al.(1989)


2,6-xylidine unchanged


2-amino-3-methyl benzoic acid





Shortet al.(1989)


In the study by Lindstromet al.(1963) 2,6-xylidine was given to male Osborne-Mendel rats at a dose of 20 mg/kg body weight in water by gavage. Apart from the initial substance and non-specified conjugates, the urine analysis resulted in mainly the 4-hydroxy-2,6-xylidine and, in lower concentration, the 2-amino-3-methyl benzoic acid as excretion products.

Shortet al.(1989a) examined the metabolism of rats. 16 male (12 week-old) Fischer-344 rats were treated with 2,6-xylidine (purity > 99%) in corn oil by gavage at a dose of 262.5 mg/kg body weight (1/4 of the LD50) for 10 days. 3 further groups, each consisting of 16 male Fischer-344 rats, were given intraperitoneal injections of either 80 mg phenobarbital/kg body weight, 15 mg methylcholanthrene/kg body weight or 50 mg SKF-525A/kg body weight daily for 10 days, in addition to the 2,6-xylidine treatment. Pooled 24-hour urine samples were analysed from day 1 and day 10. Analysis of the urine gave, apart from the initial substance, 4-hydroxy-2,6-xylidine and the sulphate and glucuronic conjugates of both substances. N,2,6-trimethylaniline was found in low concentration. The duration of treatment had no qualitative or significant quantitative effect on the metabolism. In the same study, following administration of 2,6-xylidine to dogs, apart from the initial substance, 4-hydroxy-2,6-xylidine was mainly found and, in lower quantities, 2-amino-3-methyl benzoic acid and its glycine conjugate, N,2,6-trimnethylaniline, 2,6-dimetbylnitrosabenzene and 4-imino-3,5-dimethylquinone. The quantity of different metabolites was subject to considerable individual variations. The longer treatment had no effect.


In all the investigations on metabolism of the xylidines following oral application mentioned in this section, the possibility of excretion of the xylidines or their metabolites through breathing or through the faeces was not examined.