VOL.: 77 (2000) (p. 503)
CAS No.:
5. Summary of Data Reported and Evaluation
5.1 Exposure data
Pyridine is an organic liquid of disagreeable odour, produced from coal-tar or by chemical synthesis. It is widely used as a solvent and intermediate in the production of piperidine, agricultural chemicals, drugs, dyestuffs, paints, rubber products, polycarbonate resins and textile water-repellents, as well as in laboratories. Occupational exposure may occur through inhalation and dermal contact during its production and its various uses as well as during the processing of oil-shale and at coke-oven works. It is rarely detected in ambient air or drinking water but is frequently found in indoor air. It is present in cigarette smoke and in the volatile components of certain foodstuffs.
5.2 Human carcinogenicity data
One mortality study of workers at a 4,4¢-bipyridyl manufacturing plant using pyridine as a starting material showed a small non-significant excess of lung cancer mortality. This excess could not be attributed to specific chemical exposures within the plant, and it was not clear if the risk associated with pyridine exposure was specifically assessed.
5.3 Animal carcinogenicity data
Pyridine was tested for carcinogenicity by oral administration in the drinking-water in one experiment in mice and in two experiments in rats and by subcutaneous injection in one experiment in rats. In male and female mice, it increased incidences of hepatocellular carcinomas and hepatoblastomas. In male Fischer 344 rats, it increased the incidence of renal tubule adenomas but not in male Wistar rats. No increase in tumour incidence at any site was observed in rats following subcutaneous injection of pyridine for one year and a subsequent observation period of six months.
In two studies with genetically modified mice, there was no treatment-related increase in the incidence of tumours.
5.4 Other relevant data
Pyridine is well absorbed from the gastrointestinal tract in mammals, and undergoes extensive metabolism by C- and N-oxidation and by N-methylation, giving the quaternary ion N-methylpyridinium.
In humans, acute pyridine intoxication affects the central nervous system, leading to dizziness, headache, nausea and anorexia. There is one case report of lethality after a high dose. Further symptoms include abdominal pain and pulmonary congestion. Pyridine was hepatotoxic in Fischer 344 and Wistar rats and caused an increase in granular casts and renal tubule hyaline degeneration in male Fischer 344 rats. Inhalation of pyridine can cause necrotic damage of the nasal epithelium. In rats and rabbits, pyridine is an inducer of CYP2E1 in the liver and kidney.
No data on reproductive and developmental effects in humans were available.
Exposure to pyridine in drinking-water led to reduction of sperm motility at all dose levels in mice and increased estrous cycle length at the highest dose level in rats.
Apart from positive responses in the sex-linked recessive lethal assay in Drosophila melanogaster and for aneuploidy in a fungal system, all tests, covering a range of end-points, for genetic toxicology of pyridine gave negative results.
5.5 Evaluation
There is inadequate evidence in humans for the carcinogenicity of pyridine.
There is limited evidence in experimental animals for the carcinogenicity of pyridine.
Overall evaluation
Pyridine is not classifiable as to its carcinogenicity to humans (Group 3).
For definition of the italicized terms, see Preamble Evaluation.
Synonyms
See Also:
Toxicological Abbreviations
Pyridine (ICSC)