Phenacetin

ROC STATUS: Reasonably anticipated human carcinogen since 1980

ALSO KNOWN AS: Saridon, Acetophenetidin

RELATED CANCERS: Urothelial neoplasms, especially transitional cell carcinoma of the renal pelvis and bladder

DEFINITION: Phenacetin is an analgesic and antipyretic introduced in 1887. It was linked to urothelial neoplasms, especially transitional cell carcinoma of the renal pelvis and bladder, as well as interstitial nephritis in combination with renal papillary necrosis, and was removed from the market in 1983.

Exposure routes: Oral ingestion

Where found: Sold as an analgesic and antipyretic (fever-reducing) medication; in illicit drugs

At risk: All who have taken medications containing phenacetin; people with substance abuse disorder

ETIOLOGY AND SYMPTOMS OF ASSOCIATED CANCERS: The cause and mechanism of the nephropathic change due to phenacetin in humans is unknown, but the renal lesion sometimes seen was interstitial nephritis in combination with renal papillary necrosis.

When administered in the diet, phenacetin caused benign and malignant tumors of the urinary tract in mice and rats of both sexes and of the nasal cavity in rats of both sexes, according to studies by the International Agency for Research on Cancer (IARC). There is limited evidence for the carcinogenicity of phenacetin in humans because this medication was usually taken mixed with other drugs.

History: Phenacetin was first introduced in 1887 and used principally as an analgesic and fever reducer. Its analgesic effects are reportedly because of its actions on the sensory tracts of the spinal cord. In addition, phenacetin acts as a negative inotrope on the heart, weakening the heart’s muscular action. Phenacetin also was once used as a stabilizer for hydrogen peroxide in hair-bleaching preparations. Many case reports provided evidence that abuse of analgesic mixtures containing phenacetin resulted in kidney cancer (cancer of the renal pelvis). It was implicated in kidney disease (nephropathy) and renal papillary necrosis due to abuse of analgesics, and it was withdrawn from the US market in 1983.

Phenacetin was first listed in the First Annual Report on Carcinogens (RoC; 1980), and analgesic mixtures containing phenacetin were first listed in the Fourth Annual Report on Carcinogens (1985).

In the early twenty-first century, phenacetin was discovered to be used as a common adulterant in illegal street drugs, especially cocaine. This was part of a larger trend that saw toxic substances added to street drugs, making them even more dangerous to ingest.

Bibliography

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"Phenacetin." IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, vol. 100A, 2012, pp. 377–398.

“Phenacetin: A Toxic Adulterant Found in Illicit Street Drugs.” The Center for Forensic Science Research & Education, 20 Apr. 2021, www.cfsre.org/nps-discovery/public-alerts/phenacetin-a-toxic-adulterant-found-in-illicit-street-drugs. Accessed 17 June 2024.

“Phenacetin - Pharmaceuticals.” NCBI, 2012, www.ncbi.nlm.nih.gov/books/NBK304337. Accessed 17 June 2024.

Singh, Vanila M., et al. "The Emerging Role of Toxic Adulterants in Street Drugs in the US Illicit Opioid Crisis." Public Health Reports, vol. 135, no. 1, 2020, pp. 6-10, doi.org/10.1177/0033354919887741. Accessed 17 June 2024.

Tan, Giok Hwa, Michael D. Rabbino, and James Hopper, Jr. "Is Phenacetin a Nephrotoxin?" California Medicine, vol. 101.2, 1964, pp. 73–77.

United States. Dept. of Health and Human Services. Natl. Toxicology Program. Report on Carcinogens. 12th ed. Research Triangle Park: Dept. of Health and Human Services, 2011.