Carcinogenicity

Phenoxybenzamine hydrochloride is reasonably anticipated to be a human carcinogen based on sufficient evidence of carcinogenicity from studies in experimental animals.

Properties

Phenoxybenzamine hydrochloride is the hydrochloride salt of a haloalkylamine (closely related chemically to the nitrogen mustards) that exists as a white crystalline powder at room temperature (Akron 2009). It is sparingly soluble in water, soluble in ethanol, chloroform, and propylene glycol, and insoluble in diethyl ether (IARC 1980). It is unstable in neutral and alkaline solutions and is sensitive to oxidation and photodegradation. Physical and chemical properties of phenoxybenzamine hydrochloride are listed in Table 1.

Table 1

Properties of Phenoxybenzamine Hydrochloride.

Use

Phenoxybenzamine hydrochloride is an α-adrenergic receptor blocking agent that was used in the past to treat peripheral vascular disorders such as Raynaud disease, to control hypertension, and to treat phlebitis, phlebothrombosis, diabetic gangrene, causalgia, chronic skin ulcers, and shock (IARC 1980; NCI 1978). It is now used primarily to treat hypertension and sweating caused by pheochromocytoma (MedlinePlus 2009). It may also be used to treat urinary-bladder problems such as urgency and frequency of urination and inability to control urination in patients with neurogenic bladder, functional outlet obstruction, or partial prostatic obstruction.

Production

Phenoxybenzamine hydrochloride has been produced commercially in the United States by one company since 1953 (IARC 1980). In 2009, it was available from 11 U.S. suppliers (ChemSources 2009). No data on amounts of U.S. production, imports, or exports of phenoxybenzamine hydrochloride were found.

Exposure

The only potential route of human exposure to phenoxybenzamine hydrochloride is ingestion during its medical use. The usual adult dosage is 10 mg twice a day, increasing to 20 to 40 mg two or three times a day, as long as there are no adverse effects on blood pressure (Mayo Clinic 2009). For children, the dose is based on body weight and typically begins at 0.2 mg/kg of body weight once a day, but may increase to 0.4 to 1.2 mg/kg given daily in three or four divided doses. The National Occupational Exposure Survey (conducted from 1981 to 1983) estimated that 797 workers, including 406 women, potentially were exposed to phenoxybenzamine hydrochloride (NIOSH 1990).

Regulations

Guidelines

References

1. Akron. 2009. The Chemical Database. The Department of Chemistry at the University of Akron; Last accessed: 8/4/09. http://ull​.chemistry.uakron.edu/erd/ and search on CAS number.
2. ChemIDplus. 2009. ChemIDplus Advanced. National Library of Medicine; Last accessed: 8/4/09. https://chem​.nlm.nih​.gov/chemidplus/chemidheavy.jsp and select Registry Number and search on CAS number.
3. ChemSources. 2009. Chem Sources - Chemical Search. Chemical Sources International; Last accessed: 8/4/09. http://www​.chemsources​.com/chemonline.html and search on phenoxybenzamine hydrochloride.
4. IARC. 1980. Phenoxybenzamine and phenoxybenzamine hydrochloride. In Some Pharmaceutical Drugs. IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Humans, vol. 24. Lyon, France: International Agency for Research on Cancer. pp. 185–194.
5. Mayo Clinic. 2009. Phenoxybenzamine (Oral Route). Mayo Foundation for Medical Education and Research; Last accessed: 8/4/09. http://www​.mayoclinic​.com/health/drug-information/DR601107
6. MedlinePlus. 2009. Phenoxybenzamine. National Library of Medicine; Last accessed: 8/4/09. https://www​.nlm.nih.gov​/medlineplus/druginfo/meds/a682059​.html
7. NCI. 1978. Bioassay of Phenoxybenzamine Hydrochloride for Possible Carcinogenicity. Bethesda, MD: U.S. Department of Health and Human Services, National Institutes of Health, National Cancer Institute. Technical Report Series no. 72. DHEW Publication No. (NIH) 78-1322. [PubMed: 12830225]
8. Nettesheim O, Höffken G, Gahr M, Breidert M. 2003. [Haematemesis and dysphagia in a 20-year-old woman with congenital spine malformation and situs inversus partialis]. Z Gastroenterol. 41(4):319–324. 10.1055/s-2003-38636 [PubMed: 12695937] [CrossRef]
9. NIOSH. 1990. National Occupational Exposure Survey (1981-83). National Institute for Occupational Safety and Health; https://www​.cdc.gov/noes/
10. Vaidyanathan S, Mansour P, Soni BM, Hughes PL, Singh G. 2006. Chronic lymphocytic leukaemia, synchronous small cell carcinoma and squamous neoplasia of the urinary bladder in a paraplegic man following long-term phenoxybenzamine therapy. Spinal Cord. 44(3):188–191. 10.1038/sj.sc.3101789 [PubMed: 16130025] [CrossRef]