- Evidence of carcinogenesis in humans (phenacetin only; Sufficient for phenacetin analgesic mixtures)
Renal pelvis and other urothelial neoplasms have been reported in patients who have taken a large number of Phenacetin analgesics. Case-control studies have consistently shown that renal pelvis cancer and bladder cancer are positively associated with the use of painkillers containing phenacetin, with relative risks ranging from 2.4 to more than 6; These associations were not explained by confusion with other causes of urothelial carcinoma, and a positive dose-response relationship was evident when sought. In one study, the use of painkillers without Phenacetin appeared to increase the risk of renal pelvis cancer by the same amount as painkillers with Phenacetin. This result has not been seen in other studies.
- evidence of carcinogenesis in animals (sufficient for phenacetin; Limited to analgesic compounds containing phenacetin)
Phenacetin oral administration can induce benign and malignant tumors of urinary tract in mice and rats and benign tumors of nasal cavity in rats. When given in combination with aspirin and caffeine in rats or mice, no significant association was found between compound administration and tumor incidence. In rats, phenacetin alone or in combination with phenacetin slightly increased the incidence of renal cell and renal pelvic tumors; Hepatocellular tumor occurred in rats treated with phenacetin, Phenacetin, and caffeine. In rats, phenacetin increases the incidence of n-nitrobutyl-n -(4-hydroxybutyl-amine) -induced bladder tumors and protects against hepatocellular carcinoma induced by 2-acetylaminofluorene.
- Other relevant data
There are no data on genetic and related effects of phenacetin in humans.
Studies on inducing chromosomal aberrations sister chromatid exchange and micronucleus in Phenacetin treated rodents in vivo have been equivocal. Phenacetin induced chromosomal aberrations in Chinese hamster cells in vitro, but no DNA strand breaks were observed in rat liver cells. It does not induce sexually related recessive lethal mutations in fruit flies. Phenacetin was mutagenic to bacteria when tested in the presence of metabolic systems derived from hamsters rather than mouse or rat livers. Phenacetin treated Chinese hamster urine, but not rat urine, was mutagenic to bacteria.
