Documentation of Environmental Contamination 

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.      

"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.

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.

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.  

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.

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.

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."

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.

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.

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.

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.

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

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.

1. Peelen S, Roeleveld N et al. Toxic effects on reproduction in hospital personnel. Netherlands: Elsevier; 1999. (Translation by Interverbum, Gothenburg Sweden from original Dutch)

The study suggests an increased risk of spontaneous abortion and low birth weight associated with exposure to cytostatic agents.

The results were found particularly in nurses working in outpatient clinics and/or involved in the preparation of cytostatic agents and handling waste.

This paper reviews the literature concerning possible health risks for 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.

The study suggests a statistically significant increase in the risk of miscarriage in women handling cytostatic agents prior to or during pregnancy.

These findings indicate that biological intake (positive urine mutagenicity tests) can occur among healthcare workers who handle cytostatic drugs.

This study establishes a minimal level of acceptable extra cancer risks per one million. The Netherlands propose that a target of one extra cancer case per million is acceptable and greater than 100 per million is totally unacceptable. Any risk between 1 and 100 should be dealt with aggressively. Increased cancer risks of healthcare staff exposed to cyclophosphamide are theoretically shown to be 17-100 extra cases per million employees, with regard to leukemia in women. Cases of bladder cancer in men and women exposed to CP increased to 15-76 extra cases per million.

The study evaluated the increased risk of cancer in 9,499 active and retired female pharmacy staff licensed as of January 1, 1970 or later. The study indicated an increased risk of non-Hodgkin’s lymphoma among the long-term pharmacy staff. In addition, there was a 53% significantly higher risk for non-melanoma skin cancer than amongst the general population.

This study involved a group of Dutch and Czech healthcare workers handling antineoplastic drugs. The study compared the results from a method detecting cyclophosphamide in urine with the results from an analysis of chromosomal aberrations in peripheral blood lymphocytes.

This study shows that hospital workers have an increase in chromosome aberrations if they work with at least one antineoplastic agent.

Stucker I, Caillard J-F, Collin R et al. Risk of spontaneous abortion among nurses handling antineoplastic drugs. Scand J Work Environ Health. 1990; 16: 102-107.

Selevan SG, Lindbohm M-L, Hornug RW et al. A study of occupational exposure to antineoplastic drugs and fetal loss in nurses. N Engl J Med. 1985; 313: 1173-1178.

These three studies report higher rates of spontaneous abortion or ectopic pregnancies in women exposed to cytostatic drugs during pregnancy.   

The paper describes the mass spectrometry method of testing urine for traces of cyclophosphamide. The method is deemed appropriate for the routine analysis of urine for antineoplastic agents in healthcare workers.

The findings of this study are that skin contact is the best predictor of acute symptoms in nurses working with chemotherapy. Symptoms shown to increase with skin exposure to chemo or patient excreta (those receiving chemotherapy) included loss of appetite, nausea, vomiting, diarrhea, coughing, shortness of breath, irregular heart beat, increased blood pressure, hair loss, pain during urination, etc.

The findings of this study are that skin contact is the best predictor of acute symptoms in nurses working with chemotherapy. Symptoms shown to increase with skin exposure to chemo or patient excreta (those receiving chemotherapy) included loss of appetite, nausea, vomiting, diarrhea, coughing, shortness of breath, irregular heart beat, increased blood pressure, hair loss, pain during urination, etc.

Reports show an increased frequency of leukemia cases in nurses exposed to cytostatic drugs.

Hemminki K Kyyronen P, Lindlohm ML. Spontaneous abortions and malformations in the offspring of nurses exposed to anaesthetic gases, cytostatic drugs, and other potential hazards in hospitals, based on registered information of outcome. J Epidemiol Community Health. 1985; 39: 141-147.

These studies report findings of malformations in the offspring of women exposed to cytostatic drugs.

This study describes liver damage in three oncology nurses hypothesized to result from several years’ occupational exposure to cytostatic drugs.