1. Conner T, Anderson R, Sessink PJM et al. Surface contamination with antineoplastic agents in six cancer centers in Canada and the United States. Am J Health-System Pharm. 1999; 56: 1427-1432.

Significant surface contamination of cyclophosphamide, ifosfamide and 5-fluorouracil were found outside biological safety cabinets on floors and cabinets both in preparation areas and administration areas at six cancer treatment centers in the US and Canada.      

2. Conner T, Shults M, Fraser M. Determination of the vaporization of solutions of mutagenic antineoplastic agents at 23 and 37°C using a desiccator technique. Hosp Pharm. 1999; 34(11): 85-92.

"This study found that vaporization of standard solutions of some antineoplastic agents is possible at room temperature and increases as the temperature increases." Carmustine (BCNU™), cyclophosphamide (Cytoxan™), ifosfamide (Ifex™), thiotepa, and nitrogen mustard (Mustargen™) demonstrated vaporization at 37°C. Carmustine and nitrogen mustard demonstrated significant vaporization at 23°C (room temperature); cyclophosphamide demonstrated a 50% increase in revertants at this temperature.

3. Sessink PJM, Bos RP. Drugs hazardous to healthcare workers (evaluation of methods for monitoring occupational exposure to cytostatic drugs). A Review Article. Drug Safety. 1999; 20(4): 347-359.

This article reviews the literature concerning the possible health risks of individuals occupationally exposed to cytostatic drugs.

In the Netherlands, a limit has been set on the number of new cases of cancer to one extra case per million employees per year. This risk increase should be monitored and risks greater than 100 cases per million employees per year should be not accepted.

The value of new sensitive monitoring methods has been demonstrated by the detection of cyclophosphamide in the urine of healthcare workers who are not directly involved in the preparation and administration of cyclophosphamide, such as pharmacist checks after preparation.

A possible reason for this is suggested to be the inhalation of cytostatics in gas form.

4. Minioia C, Turci R, Sotannie C et al. Application of high performance liquid chromatography/tandem mass spectrometry in the environmental and biological monitoring of healthcare personnel occupationally exposed to cyclophosphamide and ifosfamide. Rapid Commun Mass Spectrom. 1998; 12: 1485-1493.

The study reports that environmental contamination of cyclophosphamide (CF) and ifosfamide (IF) was detected outside of BSCs, under latex and vinyl gloves and under protective gowns.

Clinical reports of urine excretion of CP and IF in study group. Further safety guidelines should be established for use of BSCs and improved personal protective equipment. Establishes that both CP and IF are permeable through latex and vinyl.  

5. Opiolka M, et al. Umgang mit Zytostatika: Besteht ein ausreichender Personenschutz bei der Zytostatika-Zubereitung? Krankenhaus Technik. 1998; 56-58.

This study indicates that safety cabinets equipped with high performance HEPA filters can protect against hazardous particles but not substances in gas form. Variables such as open doors, ventilation air pressure, size of room, etc. can effect the functionality of air-cleaning systems and therefore result in hazardous vapors entering the preparation room, where they can be inhaled by staff. The study further suggests that staff are not adequately protected against cytostatics in gas form.

6. Opiolka S, Molter W, Goldschmidt R et al. Evaporation of cytostatic drugs during preparation. Gefahrstoffe-Reinhaltung der Luft. 1998; 58.

The study establishes the vapor pressure of cyclophosphamide and 5-fluorouracil and concludes that both agents vaporize at room temperature and can escape the HEPA filter and penetrate the environment where healthcare workers reside.

7. Baker E, Connor T. Monitoring occupational exposure to cancer chemotherapy drugs. A Review Article. Am J Health-System Pharm. 1996; 53: 2713-2723.

This report is a general overview of literature published to support the need for improved handling practices of chemotherapeutic drugs. The report stresses the need for education and compliance with better techniques. "One must conclude intuitively that exposure to even small quantities of mutagenic, teratogenic, or carcinogenic substances should be avoided to the utmost extent."

8. Sessink PJM, Friemel NSS, Anzion RBM et al. Biological and environmental monitoring of occupational exposure of pharmaceutical plant workers to methotrexate. Int Arch Environ Health. 1994; 65: 401-403.

Pharmaceutical plant workers were studied for contamination of methotrexate (MTX). All air samples were positive for MTX as were all urine samples from the workers.

9. Sessink PJM, Timmermans JL et al. Assessment of occupational exposure of pharmaceutical plant workers to 5-fluorouracil. Determination of a-fluoro-b-alanine in urine. J Occup Med. 1994; 36: 79-83.

Pharmaceutical plant workers were studied for contamination of 5-fluorouracil during manufacturing. Contamination was found in air samples and wipe studies and the main metabolite a-fluoro-b-alanine was discovered in the urine of the workers.

10. Sessink PJM, Wittenhorst BCJ et al. Exposure of pharmacy technicians to antineoplastic agents; reevaluation after additional protective measures. Department of Toxicology, Faculty of Medical Sciences, University of Nijmegen, The Netherlands. Submitted 1994.

The study indicates that–after additional measures to protect staff by double gloving, replacement of ampoules with vials as well as using special masks–contamination still resulted. The reason for continued contamination remains unknown in this study.

11. Sessink PJM, Joost HC et al. Occupational exposure of animal keepers to cyclophosphamide. Journal of Occupational Medicine. 1993; 35: 47-52.

This study shows environmental contamination in facilities that utilize animals for cytotoxic agent (cyclophosphamide, "CP") experimentation. Air samples, wipe samples and staff urine samples were found to be positive for CP.

12. Sessink PJM, Anzion RBM et al. Detection of contamination with antineoplastic agents in a hospital pharmacy department. Pharmaceutisch Weekblad Scientific Edition. 1992; 14: 16-22.

This study showed contamination of fluorouracil, cyclophosphamide and methotrexate in air samples both in front of and below the vertical laminar airflow safety hood.

13. Sessink PJM, Boer KA, Scheefhals APH et al. Occupational exposure to antineoplastic agents at several departments in a hospital. Int Arch Occup Environ Health. 1992; 64: 105-112.

Twenty-five pharmacy technicians and nurses from four departments of a hospital were analyzed in a study for contamination of cyclophosphamide (CP), ifosfamide (IF), 5-fluorouracil (5FU) and methotrexate (MTX.) Contamination was detected on the work surfaces in the safety cabinets, on the floors, workbenches, sinks, vial and ampoules.

Traces of CP and IF were detected in the urine of eight members of the study group.