Pyridine

Carcinogenicity

Description of key information

Pyridine and pyridine derivatives are not able to classified as human carcinogens, according to IARC.

Key value for chemical safety assessment

Carcinogenicity: via oral route

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

NOAEL

7 mg/kg bw/day

Study duration:

chronic

Species:

rat

Quality of whole database:

adequate

Carcinogenicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Carcinogenicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

A bioassay of pyridine resulted in some tumour development in rats and mice, but IARC determined that pyridine was not able to be classified as a human carcinogen.

The U.S. National Toxicology Program's (NTP) results of the chronic bioassay on 3 -methylpyridine in rats and mice is still in draft status. The increased incidences of lung tumours give rise to questions about whether the route of exposure was solely oral, or if inhalation effects could have occurred. The test substance is corrosive and irritation effects may have impacted the results. The tumours observed occur at high background frequencies and are not highly relevant for human risk assessment. There was no increase in alveolar/bronchiolar tumours in rats or mice exposed to pyridine.

There is insufficient evidence to classify pyridine and methylpyridine derivatives as carcinogens.

Additional information

Carcinogencity was examined in a chronic bioassay with pyridine in the drinking water of F344 and Wistar rats, and B6C3F1 mice. Tumors were observed in each strain of rat and mouse, but none were consistent over the 3 species. The NTP concluded that there was some evidence of carcinogenic activity of pyridine in F344 and Wistar rats, and in C3H6F1 mice. The International Agency for Cancer Research (IARC) reviewed this data and epidemiologic evidence and concluded that pyridine was not able to be classified as a human carcinogen.

A two-year cancer bioassay in rats and mice was also undertaken with 3-methylpyridine in drinking water. The conclusions of a draft report are available, with findings of “clear evidence” of carcinogenic activity in female mice based on increased incidences of alveolar/bronchiolar adenoma or carcinoma (combined) in the lung and hepatocellular carcinoma and hepatoblastoma (liver). The NOAEL is the low dose of 312.5 mg/L, equivalent to 26 mg/kg bw/d in males and 18 mg/kg bw/day in females. There was “equivocal evidence” of carcinogenic activity in male mice based on increased incidences of lung adenoma and/or carcinoma (combined).  There was “some evidence” of carcinogenic activity based on lung tumours in female rats at a rate slightly above the historical control levels, with a statistically significant trend test.

Justification for selection of carcinogenicity via oral route endpoint:
experimental result according to a guideline protocol

Carcinogenicity: via oral route (target organ): urogenital: kidneys