Chemotherapy Drug 

Exposures at an 

Oncology Clinic – 

Florida

James Couch, CIH, MS, REHS/RS

Christine West, RN, MSN/MPH

Health Hazard Evaluation Report

HETA 2009-0148-3158

June 2012 

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Centers for Disease Control and Prevention

Workplace

Safety and Health

 National Institute for Occupational 

Safety and Health
The employer shall post a copy of this report 

for a period of 30 calendar days at or near 

the workplace(s) of affected employees. The 

employer shall take steps to insure that the 

posted determinations are not altered, defaced, 

or covered by other material during such 

period. [37 FR 23640, November 7, 1972, as 

amended at 45 FR 2653, January 14, 1980].
Health Hazard Evaluation Report 2009-0148-3158 Page i

Report Abbreviations................................................................................................ii

Highlights of the NIOSH Health Hazard Evaluation........................iii

Summary .........................................................................................................v

Introduction ...................................................................................................1

Assessment.....................................................................................................3

Results..............................................................................................................5

Discussion.......................................................................................................8

Conclusions................................................................................................. 10

Recommendations.................................................................................... 10

References.................................................................................................... 15

Contents

Acknowledgments Acknowledgments and Availability of Report................................ 27

Appendix A Methods........................................................................................................ 17

Appendix C Tables............................................................................................................. 24

Appendix B Occupational Exposure Limits and Health Effects......................... 18
Page ii Health Hazard Evaluation Report 2009-0148-3158

Abbreviations

ACGIH® American Conference of Governmental Industrial Hygienists

ASHP American Society of Health-System Pharmacists

BSC Biological safety cabinet

BVNA Bureau Veritas North America

CDC Centers for Disease Control and Prevention

CFR Code of Federal Regulations

cm Centimeter

cm2 Centimeter squared

HEPA High-efficiency particulate air

HHE Health hazard evaluation

IARC International Agency for Research on Cancer

IV Intravenous

LOD Limit of detection

LOQ Limit of quantitation

NAICS North American Industry Classification System

NIOSH National Institute for Occupational Safety and Health

ng Nanogram

ng/100 cm2 Nanograms per 100 square centimeters

OEL Occupational exposure limit

OSHA Occupational Safety and Health Administration

PEL Permissible exposure limit

PPE Personal protective equipment

REL Recommended exposure limit

STEL Short-term exposure limit

TLV® Threshold limit value

TWA Time-weighted average

WEELTM Workplace environmental exposure level

USP United States Pharmacopeia
Health Hazard Evaluation Report 2009-0148-3158 Page iii

The National Institute for 

Occupational Safety and 

Health (NIOSH) received 

a confidential employee 

request for a health 

hazard evaluation (HHE) 

at an oncology clinic 

in Florida. Employees 

submitting the HHE 

request were concerned 

with work-related upper 

respiratory irritation, 

headache, fainting, 

diarrhea, loss of appetite, 

and other health effects.

Highlights of the

NIOSH Health

Hazard Evaluation

What NIOSH Did

● We evaluated the clinic in September 2009 and November 2010.

● We took surface wipe samples for platinum-containing 

chemotherapy drugs during the first and second visits. 

During the second visit we also tested for cyclophosphamide, 

ifosfamide, and doxorubicin.

● We took hand wipe samples for platinum-containing 

chemotherapy drugs during the first site visit. The samples 

were from two nurses who had recently handled these drugs.

● We checked the air flow of the biological safety cabinet.

● We talked with employees about their health and safety concerns.

● We reviewed work-related injuries and illnesses for 2006 

through 2008.

What NIOSH Found

● Platinum-containing chemotherapy drugs were found in 

most of the surface wipe samples.

● No platinum-containing chemotherapy drugs were found in 

the hand wipe samples.

● Cyclophosphamide and ifosfamide were found in some 

surface wipe samples.

● The biological safety cabinet operated properly and was 

checked annually.

● The most commonly reported health concerns were upper 

respiratory symptoms.

● Employees reported inconsistent use of personal protective 

equipment. They also reported that training on the 

occupational hazards of chemotherapy drugs was not sufficient.

What Managers Can Do

● Review the cleaning procedures with the staff on how 

chemotherapy drugs should be handled.

● Observe employee and patient activities in the checkout area to 

find where chemotherapy drug cross-contamination may occur.

● Instruct employees and cleaning staff to clean work surfaces 

after chemotherapy drugs are used and at the end of each day.
Page iv Health Hazard Evaluation Report 2009-0148-3158

Highlights of the

NIOSH Health

Hazard Evaluation

 (continued)

 

● Start a health and safety committee that includes managers 

and employees to routinely discuss health and safety concerns.

● Start a medical surveillance program, and provide annual 

training for staff who handle chemotherapy drugs.

● Require that employees wear gowns, goggles, and double 

chemotherapy protective gloves when preparing and 

administering chemotherapy drugs.

What Employees Can Do

● Wear all required personal protective equipment when 

preparing and handling chemotherapy drugs.

● Carry chemotherapy drugs in a sealed outer container to 

prevent spills.

● Clean up any chemotherapy drugs spills quickly using the 

proper spill kit.

● Dispose of chemotherapy drugs and any disposable 

administration equipment in yellow chemotherapy waste bags.

● Report all symptoms that you think are related to work. 

Follow-up with a healthcare provider who is knowledgeable 

about occupational diseases.

● Report any workplace safety or health concerns to your 

supervisor. 
Health Hazard Evaluation Report 2009-0148-3158 Page v

NIOSH investigators 

evaluated potential 

occupational exposures 

to chemotherapy drugs 

at an oncology clinic. We 

sampled for platinumcontaining chemotherapy 

drugs, cyclophosphamide, 

ifosfamide, and 

doxorubicin on 

surfaces. We found 

platinum-containing 

chemotherapy drugs 

and cyclophosphamide 

and ifosfamide. We 

recommend that the clinic 

review cleaning practices 

and PPE use to reduce 

employee exposures to 

chemotherapy drugs.

Summary

On May 1, 2009, NIOSH received a confidential employee 

request for an HHE at an oncology clinic in Florida. The request 

concerned potential exposures to chemotherapy drugs and adverse 

health effects such as upper respiratory symptoms, rash, diarrhea, 

migraine, and headache. During our first site visit in September 

2009, we measured the face velocity of the Class 2 BSC where 

chemotherapy drugs were mixed and collected surface and hand 

wipe samples for platinum-containing chemotherapy drugs. We 

also conducted health interviews with 14 of 54 employees and 

reviewed the OSHA Form 300 Log of Work-Related Injuries and 

Illnesses for 2006 through 2008.

In November 2010, during our second evaluation, we collected 

surface wipe samples (but no hand wipe samples) for platinumcontaining chemotherapy drugs in similar locations as in the 

2009 evaluation. We also collected surface wipe samples for 

cyclophosphamide, ifosfamide, and doxorubicin at the beginning 

of the work day before the chemotherapy drugs were unpacked and 

at the end of the work day after the last chemotherapy treatment 

was completed. We did this to evaluate the clinic’s cleaning 

procedures and employee work practices.

Platinum-containing chemotherapy drugs were detected in 

most surface wipe samples during both evaluations but not on 

the two hand wipes collected in 2009 from nurses who had 

recently handled platinum-containing chemotherapy drugs. 

Cyclophosphamide and ifosfamide were detected on surface wipe 

samples collected throughout the clinic, suggesting inadequate work 

practices and housekeeping. Doxorubicin was not detected on any 

surface wipe samples but its recovery may have been poor because 

these wipe samples had been frozen for approximately 7 months 

awaiting development of an analytical method [Burr 2011a].

The Class 2 BSC was certified biannually. The sash alarm that 

was malfunctioning during our first visit had been repaired by our 

second visit. The average BSC face velocity we measured was 275 

feet per minute, which met the CDC recommendation of at least 

100 feet per minute [CDC 2007].

Of the 14 employees we interviewed, 4 reported health symptoms 

consisting of runny nose, sneezing, eye irritation, and headache 

that improved on their days off work. One of these four 

reported a recurring “burning” rash on his nose after handling 

chemotherapy drug waste. All interviewed employees reported 
Page vi Health Hazard Evaluation Report 2009-0148-3158

Keywords: NAICS 621111 Office of Physicians (Except Mental Health 

Specialists), anti-neoplastic drugs, cisplatin, cyclophosphamide, 

ifosfamide, doxorubicin, healthcare personnel, chemotherapy drugs, 

housekeeping

Summary

 (continued) adequate training about the safe preparation, administration, 

and disposal of chemotherapy drugs. However, three employees 

reported inadequate training on the potential short- and longterm health effects of chemotherapy drug exposure. When 

preparing chemotherapy drugs, all employees reported using 

double gloves, goggles, and chemotherapy protective gowns. 

Some employees stated they voluntarily wore disposable filtering 

facepiece respirators and/or surgical masks to avoid contaminating 

the chemotherapy drugs and/or to protect the patients. Four 

employees reported not consistently double gloving or using 

chemotherapy protective gowns when administering chemotherapy 

drugs to patients. Some employees also reported reusing disposable 

surgical masks.

Considering the inconsistent use of PPE and presence of 

chemotherapy drug residue in the clinic work area, employees are 

at risk of both acute and chronic health effects from exposure to 

chemotherapy drugs. We recommend the clinic improve employee 

work practices and housekeeping, start a medical surveillance 

program for employees, provide annual training, and require the 

use of appropriate PPE when handling chemotherapy drugs.
Health Hazard Evaluation Report 2009-0148-3158 Page 1

Introduction

In May 2009, NIOSH received a confidential employee request 

for an HHE at an oncology clinic (“clinic”) in Florida. The HHE 

request was submitted because of concerns about potential 

exposures to chemotherapy drugs and suspected associated adverse 

health effects such as upper respiratory symptoms, rash, diarrhea, 

migraine, and headache.

NIOSH investigators conducted a site visit on September 21–22, 

2009. We held an opening meeting with clinic managers and 

employee representatives to discuss the HHE request, health 

concerns, and the scope of the evaluation. We collected surface 

and hand wipe samples for platinum-containing chemotherapy 

drugs (such as cisplatin, a chemotherapy drug frequently 

administered at the clinic). Employees also participated in 

confidential health interviews. A closing meeting was held on 

September 22, 2009, with employer and employee representatives 

to summarize our site visit activities and provide preliminary 

findings. On the basis of initial sample results we visited the clinic 

again on November 15–18, 2010, to collect additional surface 

wipe samples (but no hand wipe samples) for platinum-containing 

chemotherapy drugs and for cyclophosphamide, ifosfamide, and 

doxorubicin (other chemotherapy drugs used at the clinic).

In an interim letter to employer and employee representatives dated 

April 8, 2010, we provided our preliminary recommendations 

and reported the hand and surface wipe sample results collected 

in September 2009. Because we had described these results 

as measurements of cisplatin in a February 11, 2011 letter, we 

recalculated and reported the wipe sample results as platinum. 

Several platinum-containing chemotherapy drugs (not just 

cisplatin) were used at the clinic. Our surface wipe samples were 

analyzed only for total platinum, not for any specific platinumcontaining chemotherapy drug. In this final report all hand and 

surface wipe samples that were collected for platinum-containing 

chemotherapy drugs are reported as platinum. Results of the 

surface wipe sample results we collected in November 2010 for 

cyclophosphamide, ifosfamide, and doxorubicin were not available 

at the time of the February 2011 letter because these analyses were 

delayed by the need to develop an analytical method.
Page 2 Health Hazard Evaluation Report 2009-0148-3158

Introduction

 (continued) Work Process

Chemotherapy drugs were delivered to the clinic in coolers from 

a local pharmacy and received by the clinic’s pharmacy (Figure 

1). These chemotherapy drugs were double-bagged, and the 

descriptions of the contents were clearly visible without opening 

the bag. Some of these drugs were mixed in the clinic pharmacy 

because of the drug’s short half-life.

A clinic pharmacy employee emptied the coolers and arranged 

the bagged drugs chronologically on a countertop according to 

the patient’s appointment (Figure 2). All employees handling 

chemotherapy drugs were required to wear two pairs of 

chemotherapy protective gloves (double-gloving), and some tasks 

also required wearing a chemotherapy protective apron. Some 

employees stated they voluntarily wore disposable surgical masks 

to avoid contaminating the chemotherapy drugs and/or to protect 

the patients. Upon patient arrival, nurses retrieved the appropriate 

chemotherapy bag from the pharmacy and transported it to one of 

two treatment rooms.

After verifying the chemotherapy drug treatment with the patient’s 

medical record, a nurse began administration via an IV bag hung 

from a stand adjacent to the patient chair. The chemotherapy drug 

administration time varied from minutes to hours depending on 

the treatment protocol (Figure 3).

After completing the chemotherapy treatment the nurse removed 

the IV from the patient and disposed of all the chemotherapy 

drug–contaminated materials in a chemotherapy waste container. 

The nurse then removed both pairs of chemotherapy protective 

gloves and placed them in the chemotherapy waste container. The 

patient was then escorted to the checkout area for discharge.

Figure 1. Each morning a local 

pharmacy delivered chemotherapy 

drugs in coolers, which were stored in 

the pharmacy room.

Figure 2. Chemotherapy drug bags 

were stored on a counter in the 

clinic pharmacy along with personal 

protective equipment.

Figure 3. One of two chemotherapy 

administration rooms used by patients.
Health Hazard Evaluation Report 2009-0148-3158 Page 3

Assessment

Surface and Hand Wipe Samples

In the September 2009 evaluation, we collected surface and 

hand wipe samples for platinum-containing chemotherapy drugs 

and analyzed the samples for total platinum (Figure 4). We used 

professional judgment to select sample locations where clinic 

employees handled or administered chemotherapy drugs. In the 

November 2010 evaluation, we collected surface wipe (but no 

hand wipe) samples for platinum-containing chemotherapy drugs 

in similar locations as in the 2009 evaluation. However, in the 

November 2010 evaluation we sampled for cyclophosphamide, 

ifosfamide, and doxorubicin at the beginning of the work day 

before these chemotherapy drugs were unpacked and again 

after the last chemotherapy treatment was completed but before 

the housekeeping staff arrived for the overnight cleaning. The 

intent of collecting these morning and evening surface wipe 

samples was to help evaluate the effectiveness of the overnight 

housekeeping procedures in removing residual chemotherapy 

drugs from surfaces in the clinic. Figure 5 illustrates collecting a 

surface wipe sample on the work surface of the Class 2 BSC using 

a sample template. Appendix A describes the surface and hand 

wipe sampling methods used in this evaluation for platinumcontaining chemotherapy drugs, cyclophosphamide, ifosfamide, 

and doxorubicin.

To assess environmental exposures to platinum-containing 

chemotherapy agents such as cisplatin, carboplatin, and oxaliplatin, 

we sampled for platinum, a metal not typically present in the 

environment. Because several platinum-containing chemotherapy 

agents were used at the clinic, this sampling approach did not 

allow us to specifically identify the chemotherapy agent that may 

have been the source of the platinum. However, it did allow 

us to indirectly measure platinum-containing chemotherapy 

agents on surfaces in the clinic and thus to evaluate the efficacy 

of engineering and administrative controls, work practices, and 

housekeeping in minimizing employee exposures. Appendix B 

discusses the OELs and health effects of chemotherapy drugs.

Health Interviews and Review of Injury/

illness Records

We selected a convenience sample of 10 clinical and 4 

administration staff among the 54 employees who were present 

Figure 4. NIOSH investigator collecting 

a hand wipe sample from a nurse after 

she administered a chemotherapy drug.

Figure 5. NIOSH investigator using a 

sampling template to collect a surface 

wipe sample inside the Class 2 BSC.
Page 4 Health Hazard Evaluation Report 2009-0148-3158

on September 21–22, 2009, for health interviews. We asked about 

procedures for handling and administering chemotherapy drugs, 

acute and chronic health symptoms potentially associated with 

chemotherapy drugs, personal cancer history, reproductive health, 

use of PPE, and workplace health and safety training. We reviewed 

OSHA Form 300 Log of Work-Related Injuries and Illnesses for 

years 2006 through 2008.

Biological Safety Cabinet Evaluation

We observed employees using the Class 2 BSC, reviewed the 

biannual certification records, and asked staff and managers about 

the performance and operating procedures for the BSC. The BSC 

had a HEPA filter and exhausted 100% of the captured air outside 

the clinic. We used a thermal anemometer to evaluate the face 

velocity of the BSC (Appendix A).

Review of Housekeeping Practices

A third-party contractor performed housekeeping duties after 

the clinic closed. Although we did not observe the housekeeping 

staff performing their duties, we reviewed their procedures and 

discussed the housekeeping practices with the clinic management 

and employees.

Assessment

 (continued)
Health Hazard Evaluation Report 2009-0148-3158 Page 5

Surface and Hand Wipe Samples

We detected platinum in 18 of the 26 surface wipe samples (69%) 

collected during our September 2009 evaluation (Appendix C, 

Table C1). Of the 18 wipe samples that contained platinum, 14 

had levels that ranged between the LOD and LOQ, meaning 

some uncertainty was associated with the quantitative results. 

The highest level we measured, 91 ng/100 cm2, was collected in 

the clinic pharmacy on the floor in front of the BSC. We did not 

detect platinum (<0.7 ng /sample) in either of two hand wipe 

samples collected from two nurses who had recently administered 

chemotherapy drugs.

We detected platinum in 16 of the 20 surface wipe samples (80%) 

collected during our November 2010 evaluation. Two of the 16 

wipe samples (12%) had levels that were between the LOD and 

the LOQ. The highest surface wipe levels were collected in the 

clinic pharmacy (12 ng/100 cm2, on the middle of the BSC work 

surface) and in the right treatment room (13 ng/100 cm2, on the 

countertop next to the sink in the bedroom).

Surface wipe samples detected cyclophosphamide and ifosfamide 

in the clinic pharmacy, left and right treatment rooms, and the 

checkout area. The highest level of cyclophosphamide (28,000 

ng/100 cm2) was measured in the left treatment room underneath 

the IV stand. Every sample collected for cyclophosphamide from 

underneath the IV stand in the left treatment room was detected 

above the LOQ of 17 ng/sample. All detectable ifosfamide levels 

(two samples from the floor in front of the BSC in the clinic 

pharmacy) were between the LOD and the LOQ. No other sample 

locations had detectable ifosfamide levels. Doxorubicin was not 

detected (LOD = 7 ng/sample) in any of the surface wipe samples 

collected in the clinic. However, the recovery of doxorubicin may 

have been poor because the wipe samples were frozen for 7 months 

prior to analysis (see Discussion). Appendix C, Table C2 contains 

detailed sample results for cyclophosphamide; Appendix C, Table 

C3 contains the detailed sample results for ifosfamide.

Health Interviews and Review of Injury/

illness Records

The average employment of the 14 employees we interviewed (10 

clinical and 4 administrative staff) at the clinic was 7 years. Nine 

clinical staff reported handling chemotherapy drugs; of these 

Results
Page 6 Health Hazard Evaluation Report 2009-0148-3158

Results

 (continued) employees, five reported preparing and administering IV drugs. 

Four employees reported health symptoms consisting of runny 

nose, sneezing, eye irritation, and headache that improved on their 

days off work. One of the four employees reported a recurring 

“burning” rash on his nose after handling chemotherapy drug 

waste. None of the employees interviewed reported a history of 

cancer or reproductive health problems. Employees reported 

adequate training about the safe preparation, administration, and 

disposal of chemotherapy drugs; however, a few employees reported 

inadequate training on the potential risk of short- and long-term 

health effects of chemotherapy drug exposure.

Of the entries for injuries or illnesses on the OSHA Logs from 

2006 through 2008, one entry was recorded for burn from 

intravenous tubing, one for skin rash, and five for needlestick 

injuries. As determined in discussions with managers and 

employees, no medical surveillance program existed at the clinic 

that was specific to chemotherapy drug exposure.

Other Workplace Observations

When preparing chemotherapy drugs, all clinic employees 

reported using gloves, goggles, and chemotherapy protective gowns. 

However, we observed some employees not consistently double 

gloving or using chemotherapy protective gowns when handling 

or administering chemotherapy drugs. Specifically, one employee 

was observed handling a chemotherapy drug and using her gloved 

hand to brush her hair away from her eyes. Another employee was 

carrying chemotherapy drugs in her arms and against her body, but 

was not wearing a chemotherapy protective gown or carrying a spill 

kit. These work practices increase the risk of getting chemotherapy 

drugs on clothing or skin.

Four employees reported voluntarily wearing and reusing 

disposable filtering facepiece respirators and/or surgical masks 

and changing them once per week. According to the employees, 

the respirators and surgical masks were worn to lessen the chance 

of contaminating the chemotherapy drugs and the patients. We 

observed what appeared to be dirt around the nose area of some 

of these respirators and surgical masks. Additionally, some of these 

employees improperly stored their respirators and surgical masks by 

hanging them on hooks directly over the chemotherapy drug bags 

and plastic containers used to transport the chemotherapy drugs to 

the patient (Figure 2).
Health Hazard Evaluation Report 2009-0148-3158 Page 7

Results

 (continued) We observed containers of bleach and alcohol stored in the 

clinic pharmacy that did not have hazard warning information as 

required by the OSHA hazard communication standard [29 CFR 

1910.1200]. We also observed food stored on a counter that was 

also used to prepare chemotherapy drug doses.

Biological Safety Cabinet Face Velocity 

The average face velocity (275 feet per minute) of the Class 2 BSC 

met the CDC recommendation of at least 100 feet per minute 

[CDC 2007]. The sash alarm that worked intermittently during our 

initial visit had been repaired. However, the BSC was not physically 

marked to indicate a hood sash location that would ensure at least 

100 feet per minute of air flow.

Housekeeping Practices

During our interviews, employees and the employer expressed 

concerns that housekeeping practices related to cleaning and 

disposal of chemotherapy drug waste were inadequate. One 

employee reported that during the day shift, chemotherapy drug 

waste containers were not regularly emptied; this employee was 

concerned about exposure to contaminated equipment.
Page 8 Health Hazard Evaluation Report 2009-0148-3158

Discussion

We found platinum in several of our surface wipe samples, 

demonstrating that employees may be exposed to platinumcontaining chemotherapy drugs, including cisplatin. Other 

researchers have found platinum contamination in pharmacies 

[Brouwers et al. 2007]. Currently no OELs exist for platinumcontaining chemotherapy drugs on surfaces or in the air. However, 

considering the carcinogenicity of these chemotherapy drugs 

[IARC 2004] it would be prudent to maintain exposures as low as 

reasonably achievable.

During the November 2010 site visit we detected 

cyclophosphamide in the clinic pharmacy (on the floor in front of 

the BSC and the prepared drugs), the left treatment room (under 

the IV stand next to the first chair), and the checkout (desk surface 

on the right). The highest level (28,000 ng/100 cm2) was found in 

the left treatment room beneath an IV stand. Although no spills 

or accidents were reported, it is possible that there may have been 

surface contamination or an undetected leak on the IV bag. The 

results from surface samples collected at this location over the 

following 2 days of the November 2010 evaluation were also among 

the highest we collected, suggesting that cyclophosphamide is 

stable in the environment and that housekeeping procedures were 

not effectively removing this chemotherapy drug in one cleaning. 

The NIOSH Alert on handling chemotherapy drugs provides 

detailed information on housekeeping and cleaning procedures 

to effectively and promptly remove these drugs from work surfaces 

[NIOSH 2004].

Cyclophosphamide was detected in every surface wipe sample 

collected in the checkout area. Although most of these results were 

between the LOD and the LOQ, the presence of cyclophosphamide 

is significant because no chemotherapy drugs were administered 

in the checkout area. As such, the clinic employees in this area did 

not wear PPE, and patients in the checkout area could unknowingly 

have been exposed to chemotherapy drugs that were not in their 

oncology drug treatment protocols. Additionally, family members 

and the general public in the checkout area could have been 

exposed to chemotherapy drugs. We did not identify the source of 

the chemotherapy drugs in the checkout area but contaminated 

paperwork, contaminated skin of employees, or the patients 

themselves, may have been possible sources.

Although we detected cyclophosphamide and ifosfamide, we did 

not detect doxorubicin. The surface wipe samples for these drugs 
Health Hazard Evaluation Report 2009-0148-3158 Page 9

were kept frozen for approximately 7 months while an analytical 

method was developed. NIOSH has conducted stability studies 

of cyclophosphamide and ifosfamide when collected on surface 

wipe samples, and no degradation of recovery was observed 

[Burr 2011a]. However, NIOSH chemists have observed in 

laboratory experiments that doxorubicin degraded after being 

frozen [Burr 2011b]. Therefore, we cannot exclude the possibility 

that doxorubicin may have been present when the surface wipe 

samples were collected.

Upper respiratory symptoms and rash that were worse at work 

were reported by four clinic employees. Given the inconsistent 

use of PPE reported and evidence of chemotherapy drug residue 

in the work environment, employees were at risk of acute and 

chronic health effects from exposure to chemotherapy drugs. 

Occupational exposures to chemotherapy drugs can lead to 

acute effects such as skin rash and upper respiratory irritation 

[McDiarmid and Egan 1988; Krstev et al. 2003; NIOSH 2004]. 

However, other factors that we did not account for, such as use 

of latex gloves and hospital cleaning solutions in the workplace, 

may cause upper respiratory symptoms and rash. Therefore, 

because of the small number of employees reporting symptoms 

and the nonspecific nature of these symptoms, we cannot 

determine if they are directly related to chemotherapy drug 

exposures from this evaluation. Chronic health effects known to 

be associated with exposure to chemotherapy drugs are cancer 

and adverse reproductive health outcomes, and they may not 

manifest until later in life [Skov et al. 1992; Valanis et al. 1999; 

Harrison 2001; Krstev et al. 2003; NIOSH 2004].

The typical routes of exposure to chemotherapy drugs in 

healthcare settings are inhalation, dermal, and oral. Inhalation 

exposure may occur from airborne droplets, vapors, or dust 

generated by crushing tablets. Dermal exposure may occur when 

employees touch contaminated surfaces during the preparation, 

administration, or disposal of chemotherapy drugs, and oral 

exposure may occur from hand-to mouth contact. Accidental 

injection with a chemotherapy drug, although rare, has been 

documented [Connor and McDiarmid 2008] and this may be 

a source of exposure for the employees given past incidents of 

needlestick injuries recorded on the OSHA Logs. We did not 

evaluate or observe any activities during our evaluation that 

should require the use of respiratory protection.
Page 10 Health Hazard Evaluation Report 2009-0148-3158

Conclusions

Recommendations

We found chemotherapy drugs in surface wipe samples collected 

throughout the clinic, and cyclophosphamide was found in 

checkout, an area that should not have any chemotherapy 

drug contamination. One sample location remained positive 

for cyclophosphamide throughout our 3 day November 2010 

evaluation, suggesting that housekeeping procedures were not 

effectively removing this chemotherapy drug in one cleaning. 

Upper respiratory symptoms were the most commonly reported 

among clinic employees but because these are nonspecific and 

common in the general population we do not know whether 

these symptoms are associated with chemotherapy drug exposures. 

Our findings suggest that employees are at risk from exposure 

to chemotherapy drugs, that employee work procedures can be 

improved, and that housekeeping practices were insufficient in 

removing some chemotherapy drugs from contaminated surfaces.

On the basis of our findings, we recommend the actions listed below 

to create a more healthful workplace. We encourage the clinic to use 

a labor-management health and safety committee or working group 

to discuss the recommendations in this report and develop an action 

plan. Those involved in the work can best set priorities and assess the 

feasibility of our recommendations for the specific situation at the 

clinic. Our recommendations are based on the hierarchy of controls 

approach (Appendix B: Occupational Exposure Limits and Health 

Effects). This approach groups actions by their likely effectiveness 

in reducing or removing hazards. In most cases, the preferred 

approach is to eliminate hazardous materials or processes and install 

engineering controls to reduce exposure or shield employees. Until 

such controls are in place, or if they are not effective or feasible, 

administrative measures and/or PPE may be needed.

Engineering Controls

Engineering controls reduce exposures to employees by removing the 

hazard from the process or placing a barrier between the hazard and 

the employee. Engineering controls are very effective at protecting 

employees without placing primary responsibility of implementation 

on the employee.

1. Transport chemotherapy drug bags and related equipment to 

the administration area in plastic bins to minimize contact 

with potentially contaminated surfaces. The plastic bin should 

be cleaned after each use.

2. Mark the BSC sash height that would ensure at least 100 feet 

per minute of air flow.
Health Hazard Evaluation Report 2009-0148-3158 Page 11

Recommendations

 (continued) Administrative Controls

Administrative controls are management-dictated work practices 

and policies to reduce or prevent exposures to workplace hazards. 

The effectiveness of administrative changes in work practices for 

controlling workplace hazards is dependent on both employer 

commitment and employee acceptance. Regular monitoring and 

reinforcement are necessary to ensure that control policies and 

procedures are not circumvented in the name of convenience or 

production.

1. Review policies and procedures, with participation from 

employee and employer representatives, of the clinic’s 

program for the safe handling and control of chemotherapy 

and other hazardous drugs. On the basis of this review, 

implement a hazard communication (worker and employer 

right-to know) program for any hazardous chemicals that 

are used in the clinic. The OSHA hazard communication 

standard (CFR 29, Part 1910.1200 [36]) provides 

information essential to establishing and maintaining a safe 

and healthful work environment, including:

a. creating a worksite health hazards inventory

b. informing employees about the hazardous 

compounds present and how to handle them

c. labeling all containers with the identity of the 

contents and with appropriate hazard warning 

information

2. Provide additional training to clinic employees on the 

proper procedures for handling chemotherapy drugs, 

wearing PPE, using BSCs, cleaning, housekeeping, 

disposing of chemotherapy drugs, and responding to spills. 

The training should also include a hands-on component 

to demonstrate proficiency. For example, test kits using 

fluorescein dye could help assess techniques of clinic 

employees who prepare, handle, or clean-up chemotherapy 

drugs. This training should be conducted upon hire before 

beginning duties and at least yearly (or more often if 

deficiencies are observed). Competency testing should be 

performed to evaluate training effectiveness [USP 2008].

3. Offer duty-specific training on the potential health and 

reproductive effects of chemotherapy drugs for exposed 

employees in receiving, transport, pharmacy preparation, 

administration, nursing, housekeeping, and disposal. The 
Page 12 Health Hazard Evaluation Report 2009-0148-3158

Recommendations 

(continued) level of detail and complexity of the training should be 

tailored to the specific job area.

4. Start a medical surveillance program for staff handling 

chemotherapy drugs. Establish and maintain a confidential 

database with information regarding each employee’s 

medical history, with linkage to exposure information. 

The database should include results of a general health 

questionnaire, complete blood count and urinalysis, physical 

examination at time of employment and annually, and 

follow-up for employees who have shown health changes 

[Connor and McDiarmid 2008]. Additional information on 

developing a medical surveillance program for employees 

exposed to chemotherapy drugs can be found in NIOSH 

guidelines at http://www.cdc.gov/niosh/docs/wpsolutions/2007-117 and OSHA guidelines at http://www.

osha.gov/dts/osta/otm/otm_vi/otm_vi_2.html#6 [OSHA 

1999; NIOSH 2007]. The medical surveillance program 

should include:

a. A general health and reproductive health 

questionnaire, completed upon hire, periodically 

(such as yearly), and at job termination or transfer. 

The health questionnaires and laboratory tests 

(recommended below) should be evaluated for 

trends that may indicate health changes due to 

chemotherapy drug exposure.

b. A complete blood count with differential and 

reticulocyte count should be performed as an 

indicator of bone marrow reserve upon hire, 

periodically (such as yearly), and at job termination 

or transfer. Additional tests such as liver function and 

transaminase should also be considered, particularly 

if employees are exposed to agents considered 

hepatotoxic. Urine should be monitored periodically 

by urine dipstick or microscopic examination for 

blood, as several chemotherapy drugs (such as 

cyclophosphamide) are known to cause bladder 

damage and blood in the urine of treated patients.

c. A physical exam should be completed upon hire 

or before assuming duties with chemotherapy drugs 

to establish a baseline for comparison and when 

indicated based on abnormal results from health 

questionnaire, urinalysis, or blood work.
Health Hazard Evaluation Report 2009-0148-3158 Page 13

Recommendations 

(continued) d. A follow-up medical exam should be provided if 

employees have health changes or have experienced a 

significant exposure to chemotherapy drugs, such as 

from a large spill, substantial skin exposure, etc.

e. Based on OSHA Technical Manual, TED 1-0.15A, 

Section VI, Chapter 2. Controlling Occupational 

Exposure to Hazardous Drugs, no biological 

monitoring tests (such as genotoxic markers) are 

currently recommended for routine use in employee 

medical surveillance programs [OSHA 1999].

5. Establish and clearly communicate with the cleaning 

contractor the janitorial policies and procedures for each 

clinic area where chemotherapy drugs are handled.

6. Observe patient and paperwork activities in the checkout 

area to identify potential sources of chemotherapy drug 

contamination.

7. Clean the BSCs with a deactivating agent and disinfectant 

at the beginning and end of the shift, before and after 

each activity, and after spills. The ASHP notes that strong 

oxidizing agents such as sodium hypochlorite solution 

may effectively deactivate many chemotherapy drugs 

[ASHP 2006]. Because of the corrosive nature of sodium 

hypochlorite on surfaces, using a thiosulfate-based solution 

after cleaning with sodium hypochlorite can help to 

neutralize its effect. The USP guidelines require a final 

cleaning with a residue-free disinfecting agent, such as sterile 

70% isopropyl alcohol [USP 2008].

8. Sample work surfaces in the clinic periodically for 

chemotherapy drugs. Although NIOSH and OSHA do 

not have OELs for surface levels of chemotherapy drugs, 

periodic sampling would allow comparisons over time to 

help evaluate the effectiveness of employee work practices, 

administrative controls, and housekeeping.

9. Encourage employees to report all health concerns to 

their supervisors. These employees should be evaluated 

by consulting healthcare providers knowledgeable about 

occupational diseases.

10. Prohibit the consumption of food or beverages in work areas 

where chemotherapy drugs are handled.
Page 14 Health Hazard Evaluation Report 2009-0148-3158

Recommendations 

(continued) Personal Protective Equipment

PPE is the least effective means for controlling employee exposures. 

Proper use of PPE requires a comprehensive program, and calls for a 

high level of employee involvement and commitment to be effective. 

The use of PPE requires the choice of the appropriate equipment 

to reduce the hazard and the development of supporting programs 

such as training, change-out schedules, and medical assessment 

if needed. PPE should not be relied upon as the sole method for 

limiting employee exposures. Rather, PPE should be used until 

engineering and administrative controls can be demonstrated to be 

effective in limiting exposures to acceptable levels.

1. Ensure that appropriate PPE (chemotherapy protective 

gloves, gowns, and protective eyewear) is readily available 

in work areas where exposure to chemotherapy drugs may 

occur. Gloves used should be tested and certified by the 

American Society for Testing and Materials for use against 

chemotherapy drugs [ASTM 2005] and should be labeled as 

chemotherapy gloves. Because of the risk for latex sensitivity, 

it is preferable to use nonlatex chemotherapy protective 

gloves. Gloves should be changed every 30 minutes or when 

torn, punctured, or contaminated. Employees should wash 

their hands immediately after gloves are removed. Protective 

gowns should be disposable and made of polyethylenecoated polypropylene (nonlinting and nonabsorbent) or 

other laminate materials. Gowns should have closed fronts, 

long sleeves, and elastic or knit closed cuffs. Dispose of 

gowns after each use. Eye and face protection should be 

worn whenever there is the potential for chemotherapy 

drugs to splash in the face or eyes.

2. Double glove with chemotherapy protective gloves when 

processing, preparing, administering, cleaning, or otherwise 

handling chemotherapy drugs.

3. Follow the OSHA respiratory protection standard [29 CFR 

1910.134] regarding voluntary use of respirators, including 

providing Appendix D of the OSHA respiratory protection 

standard [29 CFR 1910.134] to employees.

4. Require employees voluntarily wearing respirators to store 

them properly and to replace them when they become 

visibly clogged or difficult to breathe through.
Health Hazard Evaluation Report 2009-0148-3158 Page 15

References

 American Society of Health-System Pharmacists [2006]. ASHP 

Guidelines on Handling Hazardous Drugs. Am J Health Sys Pharm 

63(12): 1172-1193.

ASTM [2005]. ASTM D6978-05 Standard Practice for Assessment 

of Resistance of Medical Gloves to Permeation by Chemotherapy 

Drugs. West Conshohocken, PA: American Society for Testing and 

Materials International.

Brouwers, E, Huitema A, Bakker E, Douma J, Schimmel K, 

Weringh G, de Wolf P, Schellens J, Beijnen J [2007]. Monitoring 

of platinum surface contamination in seven Dutch hospital 

pharmacies using inductively coupled plasma mass spectrometry. 

Int Arch Occup Environ Health 80(8):689–699.

Burr G [2011a]. E-mail on October 7, 2011, between G. Burr, 

Division of Surveillance, Hazard Evaluations and Field Studies 

and J. Pretty, Division of Applied Research and Technology, 

National Institute for Occupational Safety and Health, Centers for 

Disease Control and Prevention, U.S. Department of Health and 

Human Services.

Burr G [2011b]. Personal communication on September 29, 2011, 

between G. Burr, Division of Surveillance, Hazard Evaluations 

and Field Studies and J. Pretty, Division of Applied Research and 

Technology, National Institute for Occupational Safety and Health, 

Centers for Disease Control and Prevention, U.S. Department of 

Health and Human Services.

CDC [2007]. Primary containment for biohazards: selection, 

installation and use of biological safety cabinets, 3rd edition. 

[http://www.cdc.gov/od/ohs/biosfty/primary_containment_for_

biohazards.pdf]. Date accessed: March 2012.

CFR. Code of Federal Regulations. Washington, DC: U.S. 

Government Printing Office, Office of the Federal Register.

Connor TH, McDiarmid MA [2008]. Preventing occupational 

exposures to antineoplastic drugs in health care settings. CA 

Cancer J Clin 56(6):354-365.

Harrison BR [2001]. Risks of handling cytotoxic drugs. In: Perry 

MC ed., The chemotherapy source book. 3rd ed. Philadelphia, PA: 

Lippincott, Williams and Wilkins, pp. 566–582.
Page 16 Health Hazard Evaluation Report 2009-0148-3158

References

 (continued) IARC [2004]. IARC monographs on the evaluation of the 

carcinogenic risk of chemicals to humans. Lyons, France: World 

Health Organization, International Agency for Research on 

Cancer. [http://monographs.iarc.fr/]. Date accessed: March 2012.

Krstev S, Perunicic B, Vidakovic A [2003]. Work practice and some 

adverse health effects in nurses handling antineoplastic drugs. Med 

Lav 94(5):432-439.

McDiarmid M, Egan T [1988]. Acute occupational exposure to 

antineoplastic agents J Occup Med 35(12):984-987.

NIOSH [2004]. NIOSH alert: preventing occupational exposures 

to antineoplastic and other hazardous drugs in health care settings. 

Cincinnati, OH: U.S. Department of Health and Human Services, 

Centers for Disease Control and Prevention, National Institute for 

Occupational Safety and Health, DHHS (NIOSH) Publication No. 

2004-165.

NIOSH [2007]. Workplace solutions: medical surveillance for 

healthcare workers exposed to hazardous drugs. Cincinnati, 

OH: U.S. Department of Health and Human Services, Centers 

for Disease Control and Prevention, National Institute for 

Occupational Safety and Health, DHHS (NIOSH) Publication No. 

2007-117.

OSHA [1999]. Technical Manual: controlling occupational 

exposure to hazardous drugs, Section V1 Chapter 2. Occupational 

Safety and Health Administration, Washington DC: TED 01-00-

015. U.S. Government Printing Office.

Skov T, Maarup B, Olsen J, Rørth M, Winthereik H, Lynge E 

[1992]. Leukaemia and reproductive outcome among nurses 

handling antineoplastic drugs. Br J Ind Med 49(12):855–861.

USP [2008]. Chapter 797, Pharmaceutical compoundings – sterile 

preparations. Rockville, MD: United States Pharmacopeia and 

National Formulary.

Valanis B, Vollmer WM, Steele P [1999]. Occupational 

exposure to antineoplastic agents: self-reported miscarriages and 

stillbirths among nurses and pharmacists. J Occup Environ Med 

41(8):632–638.
Health Hazard Evaluation Report 2009-0148-3158 Page 17

Appendix A: Methods

Surface and Hand Wipe Samples for Platinum-containing 

Chemotherapy Drugs

Surface and hand wipe samples were taken using Alpha Texwipe swabs moistened with deionized water. For 

surfaces we used a 10 cm × 10 cm disposable template to determine the sampling area. For hand wipes we held the 

moistened sample media with forceps while wiping the employee’s hands. For each wipe sample we wore a clean 

pair of chemotherapy–drug-resistant gloves. The wipe sample media were analyzed for platinum by inductively 

coupled plasma/mass spectrometry. For the samples collected during the September 2009 evaluation, the LOD 

was 0.7 ng platinum per sample, and the LOQ was 9.8 ng of platinum per sample. The LOD was 0.3 ng platinum 

per sample, and the LOQ was 0.84 ng platinum per sample for the samples collected during the November 2010 

evaluation. For both evaluations the sampling and analytical method for measuring platinum in surface and hand 

wipe samples was developed by Bureau Veritas North America.

Surface Samples for Cyclophosphamide, Ifosfamide, and Doxorubicin

Each surface wipe sample was collected using two Whatman filters (42 millimeter diameter) moistened with 

an extraction solvent comprised of 50% acetonitrile and 50% methanol. A 10 cm × 10 cm disposable template 

was used to outline a 100 cm2 sampling area. The sample area was wiped twice, once with the first Whatman 

filter, then again with the second Whatman filter. The two wipe samples were collectively analyzed by liquid 

chromatography mass spectrometry/mass spectrometry. All media and field blanks were below the LOD of 5 

ng/sample for cyclophosphamide, 2 ng/sample for ifosfamide, and 7 ng/sample for doxorubicin. The sampling 

and analytical method was developed by Bureau Veritas North America. Results of a NIOSH stability study 

with cyclophosphamide and ifosfamide showed no degradation of recovery after 7 to 8 months for wipe samples 

stored frozen [Burr 2011a]. On the basis of these results, we do not suspect significant degradation of our field 

samples with respect to these two drugs. However, NIOSH chemists have observed in laboratory experiments that 

doxorubicin degraded after being frozen [Burr 2011b].

Biological Safety Cabinet Face Velocity

We used a TSI VelociCalcTM Model 8386 thermal anemometer (TSI, Shoreview, Minnesota) to measure the face 

velocity of the BSC where chemotherapy drugs were mixed and prepared. We took 65 measurements in a grid 

pattern (every 4 inches along the horizontal, every 2 inches along the vertical), and an arithmetic average was taken 

to determine the average face velocity.

References

Burr G [2011a]. E-mail on October 7, 2011, between G. Burr, Division of Surveillance, Hazard Evaluations and 

Field Studies and J. Pretty, Division of Applied Research and Technology, National Institute for Occupational 

Safety and Health, Centers for Disease Control and Prevention, U.S. Department of Health and Human Services.

Burr G [2011b]. Personal communication on September 29, 2011, between G. Burr, Division of Surveillance, 

Hazard Evaluations and Field Studies and J. Pretty, Division of Applied Research and Technology, National 

Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, U.S. Department of 

Health and Human Services.
Page 18 Health Hazard Evaluation Report 2009-0148-3158

Appendix B: Occupational Exposure Limits and Health Effects

In evaluating the hazards posed by workplace exposures, NIOSH investigators use both mandatory (legally 

enforceable) and recommended OELs for chemical, physical, and biological agents as a guide for making 

recommendations. OELs have been developed by federal agencies and safety and health organizations to prevent 

the occurrence of adverse health effects from workplace exposures. Generally, OELs suggest levels of exposure 

that most employees may be exposed to for up to 10 hours per day, 40 hours per week, for a working lifetime, 

without experiencing adverse health effects. However, not all employees will be protected from adverse health 

effects even if their exposures are maintained below these levels. A small percentage may experience adverse health 

effects because of individual susceptibility, a pre-existing medical condition, and/or a hypersensitivity (allergy). 

In addition, some hazardous substances may act in combination with other workplace exposures, the general 

environment, or with medications or personal habits of the employee to produce adverse health effects even if the 

occupational exposures are controlled at the level set by the exposure limit. Also, some substances can be absorbed 

by direct contact with the skin and mucous membranes in addition to being inhaled, which contributes to the 

individual’s overall exposure.

Most OELs are expressed as a TWA exposure. A TWA refers to the average exposure during a normal 8- to 

10-hour workday. Some chemical substances and physical agents have recommended STEL or ceiling values 

where adverse health effects are caused by exposures over a short period. Unless otherwise noted, the STEL is a 

15-minute TWA exposure that should not be exceeded at any time during a workday, and the ceiling limit is an 

exposure that should not be exceeded at any time.

In the United States, OELs have been established by federal agencies, professional organizations, state and local 

governments, and other entities. Some OELs are legally enforceable limits, while others are recommendations. 

The U.S. Department of Labor OSHA PELs (29 CFR 1910 [general industry]; 29 CFR 1926 [construction 

industry]; and 29 CFR 1917 [maritime industry]) are legal limits enforceable in workplaces covered under the 

Occupational Safety and Health Act of 1970. NIOSH RELs are recommendations based on a critical review of 

the scientific and technical information available on a given hazard and the adequacy of methods to identify and 

control the hazard. NIOSH RELs can be found in the NIOSH Pocket Guide to Chemical Hazards [NIOSH 2010]. 

NIOSH also recommends different types of risk management practices (e.g., engineering controls, safe work 

practices, employee education/training, personal protective equipment, and exposure and medical monitoring) to 

minimize the risk of exposure and adverse health effects from these hazards. Other OELs that are commonly used 

and cited in the United States include the TLVs recommended by ACGIH, a professional organization, and the 

WEELs recommended by the American Industrial Hygiene Association, another professional organization. The 

TLVs and WEELs are developed by committee members of these associations from a review of the published, peerreviewed literature. They are not consensus standards. ACGIH TLVs are considered voluntary exposure guidelines 

for use by industrial hygienists and others trained in this discipline “to assist in the control of health hazards” 

[ACGIH 2011]. WEELs have been established for some chemicals “when no other legal or authoritative limits 

exist” [AIHA 2011].

Outside the United States, OELs have been established by various agencies and organizations and include both 

legal and recommended limits. The Institut für Arbeitsschutz der Deutschen Gesetzlichen Unfallversicherung 

(IFA, Institute for Occupational Safety and Health of the German Social Accident Insurance) maintains a 

database of international OELs from European Union member states, Canada (Québec), Japan, Switzerland, and 
Health Hazard Evaluation Report 2009-0148-3158 Page 19

Appendix B: Occupational Exposure Limits and Health Effects

 (continued)

the United States. The database, available at http://www.dguv.de/ifa/en/gestis/limit_values/index.jsp, contains 

international limits for over 1,500 hazardous substances and is updated periodically.

Employers should understand that not all hazardous chemicals have specific OSHA PELs, and for some agents 

the legally enforceable and recommended limits may not reflect current health-based information. However, an 

employer is still required by OSHA to protect its employees from hazards even in the absence of a specific OSHA 

PEL. OSHA requires an employer to furnish employees a place of employment free from recognized hazards that 

cause or are likely to cause death or serious physical harm [Occupational Safety and Health Act of 1970 (Public 

Law 91–596, sec. 5(a)(1))]. Thus, NIOSH investigators encourage employers to make use of other OELs when 

making risk assessments and risk management decisions to best protect the health of their employees. NIOSH 

investigators also encourage the use of the traditional hierarchy of controls approach to eliminate or minimize 

identified workplace hazards. This includes, in order of preference, the use of (1) substitution or elimination of the 

hazardous agent, (2) engineering controls (e.g., local exhaust ventilation, process enclosure, dilution ventilation), 

(3) administrative controls (e.g., limiting time of exposure, employee training, work practice changes, medical 

surveillance), and (4) personal protective equipment (e.g., respiratory protection, gloves, eye protection, hearing 

protection). Control banding, a qualitative risk assessment and risk management tool, is a complementary 

approach to protecting employee health that focuses resources on exposure controls by describing how a risk needs 

to be managed. Information on control banding is available at http://www.cdc.gov/niosh/topics/ctrlbanding/. 

This approach can be applied in situations where OELs have not been established or can be used to supplement 

the OELs, when available.

Below we provide the OELs and surface contamination limits for the compounds we measured, as well as a 

discussion of the potential health effects from exposure to these compounds.

Platinum-containing Chemotherapy Drugs

Platinum-containing chemotherapy drugs include cisplatin, oxiplatin, and carboplatin, among others. OSHA and 

NIOSH have not established OELs for platinum-containing chemotherapy drugs either as a group or as individual 

agents. However, these drugs can be considered individually based on their adverse health effects, carcinogenicity, 

teratogenicity, and other factors. For example, cisplatin is categorized at a Group 2A Carcinogen, meaning that 

there is inadequate evidence to designate it as a human carcinogen [IARC 2004].

Cyclophosphamide

Although OSHA and NIOSH have not established OELs for cyclophosphamide, it has been categorized as a 

Group 1 Carcinogen (carcinogenic to humans) by IARC [IARC 1998]. It metabolizes in the body to acrolein, 

which can cause adverse effects in the bladder.

Cyclophosphamide is a chemotherapy drug that is used for a wide range of neoplastic diseases such as breast 

and lung cancer, pediatric malignancies, leukemia, and lymphomas. It can be prescribed as a single drug or in 

combination with other chemotherapy drugs and can be administered via oral tablets or intravenously.
Page 20 Health Hazard Evaluation Report 2009-0148-3158

Appendix B: Occupational Exposure Limits and Health Effects

 (continued)

Cyclophosphamide is normally found in a white powder form for chemical stability and is typically brought into 

liquid solution by the addition of water and infused with sodium chloride, glucose, or glucose/saline solutions. 

Once in solution, it is recommended that cyclophosphamide be administered to the patient within 8 hours or 

stored cold (but not frozen) to prevent degradation. The surface wipe samples collected during this evaluation for 

cyclophosphamide, (as well as for ifosfamide and doxorubicin) were shipped cold from the field to the NIOSH 

laboratory. These wipe samples were then kept frozen for approximately 7 months pending development of an 

analytical method. There are currently no OELs for cyclophosphamide. However, because of its carcinogenic 

nature, exposures to cyclophosphamide should be controlled to the lowest achievable levels.

Ifosfamide

Ifosfamide is a chemotherapy drug that is used for a wide range of neoplastic diseases including ovary, testes, lung, 

breast, and soft-tissue sarcomas. It can be prescribed as a single drug or in combination with other chemotherapy 

drugs and can be administered via either oral tablets or intravenously. Ifosfamide is normally found in a white 

powder form for chemical stability and is normally brought into solution by the addition of water and infused with 

sodium chloride, glucose, or glucose/saline solutions.

Ifosfamide is a not designated as carcinogenic to humans by IARC, OSHA, or NIOSH. It has been reported to be 

mutagenic in bacterial cells through the Ames test. Ifosfamide metabolizes in the body to acrolein, which can cause 

adverse effects in the bladder. There are currently no OELs for ifosfamide.

Doxorubicin

Doxorubicin is a chemotherapy drug that is used for neoplastic diseases including leukemia, soft-tissue sarcomas, 

and solid tumors such as breast and lung cancer. It can be prescribed singly or in combination with other 

chemotherapy drugs and can be administered via oral tablets or intravenously. It is categorized as a Group 2A 

Carcinogen [IARC 1987], meaning that there is inadequate evidence to designate it as a human carcinogen.

Chemotherapy Drugs in Health Care Settings

Occupational exposures to chemotherapy drugs may occur through inhalation, skin contact, skin absorption, 

ingestion, or injection. Inhalation and skin contact/absorption are the most likely routes of exposure, but 

unintentional ingestion from hand to mouth contact and unintentional injection through a needlestick or sharps 

injury are also possible [Duvall and Baumann 1980; Black and Presson 1997; Schreiber et al. 2003].

Protection from chemotherapy drug exposures depends on safety programs established by employers and 

followed by employees. Factors that affect employee exposures include drug handling circumstances (preparation, 

administration, or disposal), amount of drug prepared, frequency and duration of drug handling, potential for 
Health Hazard Evaluation Report 2009-0148-3158 Page 21

Appendix B: Occupational Exposure Limits and Health Effects

 (continued)

absorption, use of ventilated cabinets, PPE, and work practices. The chance that an employee will experience 

adverse effects from chemotherapy drugs increases with the amount and frequency of exposure and the lack of 

proper work practices [NIOSH 2004].

Studies have associated workplace exposures to chemotherapy drugs with acute health effects, primarily in nurses. 

These included hair loss, headaches, acute irritation, and/or hypersensitivity [Valanis et al. 1993a; Valanis et al. 

1993b]. The major reproductive effects found in these studies were increased fetal loss [Selevan et al. 1985; Stücker 

et al. 1990], congenital malformations depending on the length of exposure [Hemminki et al. 1985], low birth 

weight and congenital abnormalities [Peelen et al. 1999], and infertility [Valanis et al. 1999].

Several reports have addressed the relationship of cancer occurrence to health care employees’ exposures to 

chemotherapy drugs [NIOSH 2004]. A significantly increased risk of leukemia has been reported among oncology 

nurses identified in the Danish cancer registry for the period 1943–1987 [Skov et al. 1992]. The same group [Skov 

et al. 1990] found an increased, but not significant, risk of leukemia in physicians employed for at least 6 months 

in a department where patients were treated with chemotherapy drugs.

References

ACGIH [2011]. 2011 TLVs® and BEIs®: threshold limit values for chemical substances and physical agents and 

biological exposure indices. Cincinnati, OH: American Conference of Governmental Industrial Hygienists.

AIHA [2011]. AIHA 2011 Emergency response planning guidelines (ERPG) & workplace environmental exposure 

levels (WEEL) handbook. Fairfax, VA: American Industrial Hygiene Association.

Black LA, Presson AC [1997]. Hazardous drugs. Occup Med: State of the Art Rev 12(4):669–685.

CFR. Code of Federal Regulations. Washington, DC: U.S. Government Printing Office, Office of the Federal 

Register.

Duvall E, Baumann B [1980]. An unusual accident during the administration of chemotherapy. Cancer Nurs 

3(4):305–306.

Harrison BR [2001]. Risks of handling cytotoxic drugs. In: Perry MC, ed. The chemotherapy source book. 3rd ed. 

Philadelphia, PA: Lippincott, Williams and Wilkins, pp. 566–582.

Hemminki K, Kyyrönen P, Lindbohm M-L [1985]. Spontaneous abortions and malformations in the offspring of 

nurses exposed to anesthetic gases, cytostatic drugs, and other potential hazards in hospitals, based on registered 

information of outcome. J Epidemiol Commun Health 39:141–147. 

IARC [1987]. Overall Evaluations of Carcinogenicity: an updating of IARC Monographs Volumes 1 to 42. Lyon: 

IARC monographs on the evaluation of carcinogenic risks to humans; Supplement 7. International Agency for 

Research on Cancer.
Page 22 Health Hazard Evaluation Report 2009-0148-3158

IARC [1998]. Some antineoplastic and immunosuppressive agents. Lyon: IARC monographs on the evaluation of 

carcinogenic risks to humans, vol 26. International Agency for Research on Cancer.

IARC [2004]. IARC monographs on the evaluation of the carcinogenic risk of chemicals to humans. Lyons, 

France: World Health Organization, International Agency for Research on Cancer. [http://monographs.iarc.fr/]. 

Date accessed: March 2012.

NIOSH [2004]. NIOSH alert: preventing occupational exposure to antineoplastic and other hazardous drugs 

in health care settings. Cincinnati, OH: U.S. Department of Health and Human Services, Centers for Disease 

Control and Prevention, National Institute for Occupational Safety and Health, DHHS (NIOSH) Publication No. 

2004-165.

NIOSH [2010]. NIOSH pocket guide to chemical hazards. Cincinnati, OH: U.S. Department of Health and 

Human Services, Centers for Disease Control and Prevention, National Institute for Occupational Safety and 

Health, DHHS (NIOSH) Publication No. 2010-168c. [http://www.cdc.gov/niosh/npg/]. Date accessed: March 

2012.

Peelen S, Roeleveld N, Heederik D, Krombout H, de Kort W [1999]. Toxic effects on reproduction in hospital 

personnel (in Dutch). Netherlands: Elsevier.

Schreiber C, Radon K, Pethran A, Schierl R, Hauff K, Grimm C-H, Boos K-S, Nowak D. [2003]. Uptake of 

antineoplastic agents in pharmacy personnel. Part 2: study of work-related risk factors. Int Arch Occup Environ 

Health 76(1):11–16.

Selevan SG, Lindbohm M-L, Hornung RW, Hemminki K [1985]. A study of occupa¬tional exposure to 

antineoplastic drugs and fetal loss in nurses. N Engl J Med 313(19):1173–1178.

Skov T, Lynge E, Maarup B, Olsen J, Rørth M, Winthereik H [1990]. Risk for physicians handling antineoplastic 

drugs [letter to the editor]. Lancet 336(8728):1446.

Skov T, Maarup B, Olsen J, Rørth M, Winthereik H, Lynge E [1992]. Leukaemia and reproductive outcome 

among nurses handling antineoplastic drugs. Br J Ind Med 49(12):855–861.

Stücker I, Caillard J-F, Collin R, Gout M, Poyen D, Hémon D [1990]. Risk of spontaneous abortion among nurses 

handling antineoplastic drugs. Scand J Work Environ Health 16(2):102–107.

Valanis BG, Vollmer WM, Labuhn KT, Glass AG [1993a]. Acute symptoms associated with antineoplastic drug 

handling among nurses. Cancer Nurs 16(4):288–295.

Valanis BG, Vollmer WM, Labuhn KT, Glass AG [1993b]. Association of antineoplastic drug handling with acute 

adverse effects in pharmacy personnel. Am J Hosp Pharm 50(3):455–462.

Appendix B: Occupational Exposure Limits and Health Effects

 (continued)
Health Hazard Evaluation Report 2009-0148-3158 Page 23

Valanis B, Vollmer WM, Steele P [1999]. Occupational exposure to antineoplastic agents: self-reported 

miscarriages and stillbirths among nurses and pharmacists. J Occup Environ Med 41(8):632–638.

Appendix B: Occupational Exposure Limits and Health Effects

 (continued)
Page 24 Health Hazard Evaluation Report 2009-0148-3158

Appendix C: Tables

Table C1. Platinum-containing chemotherapy drugs in surface wipe samples collected in September 2009 and 

November 2010

Location Description

Results

ng/100 cm2

September 

2009†

November 

2010‡

Clinic

pharmacy

Countertop in front of prepared drugs 48 3.4

On top of chemo-waste container (gowns/jackets) (3.4) NS

Middle of chemotherapy preparation hood 14 12

On floor in front of prepared drugs 91 3.3

Inside empty pharmacy cooler (2.0) (0.48)

Outside of oxaliplatin bag ND NS

On floor in front of pharmacy hood (8.5) 5.7

Inside the door handle exiting pharmacy* (1.6) NS

Countertop underneath oxaliplatin bag (7.2) NS

Next to sink 11 5.0

Left treatment

room

Arm of first chair (2.1) 2.9

Under IV stand next to first chair (1.3) 2.1

Keypad of IV pump next to first chair (1.5) (0.77)

Table to left of first chair (0.85) NS

Supply area sink (left side) behind nurse station (2.3) NS

“Quiet Room” area on the arm of chair (1.5) NS

Handle of faucet* ND NS

Nurse station Desk on the right side of keyboard ND (0.38)

Exam room #4 Countertop to the right of sink ND ND

Dictation room Desk on the right side of keyboard ND ND

Waiting room Table next to first chair ND ND

Checkout First desk on right ND ND

Right treatment

room

Under IV stand on floor (1.4) 5.9

Arm of first chair (1.0) 0.97

Food rollaway table ND (0.77)

Countertop next to sink in bedroom (1.6) 13

Injection room Side table next to recliner NS (0.57)

Room behind nurse station On edge of countertop near wastebasket NS 1.4

*Estimated 100 cm2 sampling area

†September 2009: LOD = 0.7 ng platinum/sample and LOQ = 9.8 ng platinum/sample

‡November 2010: LOD = 0.3 ng platinum/sample and LOQ = 0.84 ng platinum/sample

( ) Sample results in parentheses were between the LOD and the LOQ, meaning that they have more uncertainty 

associated with them.

ND = not detected (below the LOD)

NS = location was not sampled
Health Hazard Evaluation Report 2009-0148-3158 Page 25

Appendix C: Tables

 (continued)

Table C2. Cyclophosphamide in surface wipe samples collected in November 2010 

Room Location

Results reported in ng/100 cm2

Day 1 Day 2 Day 3 Day 4

PM AM PM AM PM AM

Clinic 

pharmacy

Prepared drugs countertop ND ND ND ND ND ND

BSC work surface ND NS NS NS NS NS

Floor in front of prepared 

drugs

36 (13) 20 (13) (16) 18

Inside empty cooler ND NS NS NS NS NS

On floor in front of BSC 41 59 56 63 69 50

Countertop next to sink ND ND ND ND ND ND

Left treatment 

room

Arm of first chair ND ND ND ND (7.8) ND

Under IV stand next to first 

chair

33 43 28,000 470 120 54

Keypad of IV pump next to 

chair*

ND ND ND ND ND ND

Nurse station Desk near keyboard ND ND ND ND ND ND

Exam room 4 Countertop next to sink ND ND ND ND ND ND

Dictation room Desk near computer 

keyboard

ND ND ND ND ND ND

Waiting room Coffee table ND NS NS NS NS NS

Checkout Desk surface on right (15) 22 (5.7) (12) (17) (8.0)

Right 

treatment 

room

Under IV stand 21 NS NS NS NS NS

Arm of first chair ND NS NS NS NS NS

Food rollaway table ND NS NS NS NS NS

Countertop next to sink ND ND ND ND ND ND

Room behind 

nurse station

Desk on countertop ND ND ND ND ND ND

Injection room Side table next to recliner ND ND ND ND ND ND

*Estimated 100 cm2 sampling area

AM = Sample collected in the morning prior to any chemotherapy drug administration

PM = Sample collected at the end of the day prior to housecleaning activities

LOD = 5 ng/sample

LOQ = 17 ng/sample

ND = not detected (below the LOD)

NS = location was not sampled

( ) Sample results in parentheses were between the LOD and the LOQ, meaning that they have more uncertainty 

associated with them.
Page 26 Health Hazard Evaluation Report 2009-0148-3158

Appendix C: Tables

 (continued)

Table C3. Ifosfamide in surface wipe samples collected in November 2010 

Room Location Results reported in ng/100 cm2

Day 1 Day 2 Day 3 Day 4

PM AM PM AM PM AM

Clinic 

pharmacy

Prepared drugs countertop ND ND ND ND ND ND

BSC work surface ND NS NS NS NS NS

Floor in front of prepared drugs ND ND ND ND ND ND

Inside empty cooler ND NS NS NS NS NS

On floor in front of BSC ND ND ND (2.0) (2.7) ND

Countertop next to sink ND ND ND ND ND ND

Left treatment 

room

Arm of first chair ND ND ND ND ND ND

Under IV stand next to first chair ND ND ND ND ND ND

Keypad of IV pump next to chair* ND ND ND ND ND ND

Nurse station Desk near keyboard ND ND ND ND ND ND

Exam room 4 Countertop next to sink ND ND ND ND ND ND

Dictation room Desk near computer keyboard ND ND ND ND ND ND

Waiting room Coffee table ND NS NS NS NS NS

Checkout Desk surface on right ND ND ND ND ND ND

Right treatment 

room

Under IV stand ND NS NS NS NS NS

Arm of first chair ND NS NS NS NS NS

Food rollaway table ND NS NS NS NS NS

Countertop next to sink ND ND ND ND ND ND

Room behind 

nurse station Desk on countertop ND ND ND ND ND ND

Injection room Side table next to recliner ND ND ND ND ND ND

*Estimated 100 cm2 sampling area

AM = Sample collected in the morning prior to any chemotherapy drug administration

PM = Sample collected at the end of the day prior to housecleaning activities

LOD = 2 ng/sample

LOQ = 7.3 ng/sample

ND = not detected (below the LOD)

NS = location was not sampled

( ) Sample results in parentheses were between the LOD and the LOQ, meaning that they have more uncertainty 

associated with them.
Health Hazard Evaluation Report 2009-0148-3158 Page 27

Acknowledgments and

Availability of Report

The Hazard Evaluations and Technical Assistance Branch 

(HETAB) of the National Institute for Occupational Safety and 

Health (NIOSH) conducts field investigations of possible health 

hazards in the workplace. These investigations are conducted 

under the authority of Section 20(a)(6) of the Occupational Safety 

and Health Act of 1970, 29 U.S.C. 669(a)(6) which authorizes 

the Secretary of Health and Human Services, following a written 

request from any employer or authorized representative of 

employees, to determine whether any substance normally found 

in the place of employment has potentially toxic effects in such 

concentrations as used or found. HETAB also provides, upon 

request, technical and consultative assistance to federal, state, and 

local agencies; labor; industry; and other groups or individuals to 

control occupational health hazards and to prevent related trauma 

and disease.

Mention of any company or product does not constitute 

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the sponsoring organizations or their programs or products. 

Furthermore, NIOSH is not responsible for the content of these 

websites. All Web addresses referenced in this document were 

accessible as of the publication date.

This report was prepared by James Couch and Christine West 

of HETAB, Division of Surveillance, Hazard Evaluations and 

Field Studies. Industrial hygiene field assistance was provided by 

Scott Brueck and Bradley King. Industrial hygiene equipment 

and logistical support was provided by Donald Booher and Karl 

Feldmann. Health communication assistance was provided 

by Stefanie Evans. Editorial assistance was provided by Ellen 

Galloway. Desktop publishing was performed by Greg Hartle and 

Mary Winfree.

Copies of this report have been sent to employee and management 

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Copies may be purchased from the National Technical Information 

Service at 5825 Port Royal Road, Springfield, Virginia 22161.
Below is a recommended citation for this report:

NIOSH [2012]. Health hazard evaluation report: chemotherapy drug exposures at 

an oncology clinic – Florida. By Couch J, West C. Cincinnati, OH: U.S. Department 

of Health and Human Services, Centers for Disease Control and Prevention, 

National Institute for Occupational Safety and Health, NIOSH HETA No. 2009-

0148-3158.

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