Chemotherapy 

Drug Evaluation at a 

Medical Laboratory – 

Pennsylvania 

James Couch, MS, CIH, REHS/RS

Marie A. de Perio, MD

Health Hazard Evaluation Report

HETA 2010-0118-3142

September 2011

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 2010-0118-3142 Page i

Appendix

Report Abbreviations.......................................................................i

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

Summary ............................................................................iv

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

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

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

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

Conclusions.........................................................................8

Recommendations...............................................................9

References ........................................................................11

Contents

Occupational Exposure Limits and Health Effects.............12

Acknowledgments Acknowledgments and Availability of Report.....................1
Page ii Health Hazard Evaluation Report 2010-0118-3142

ACGIH® American Conference of Governmental Industrial Hygienists

BSC Biological safety cabinet

CFR Code of Federal Regulations

cm Centimeter

cm2 Centimeter squared

HHE Health hazard evaluation

IARC International Agency for Research on Cancer

LOD Limit of detection

LOQ Limit of quantification

NAICS North American Industry Classification System

ng Nanogram

ng/100 cm2 Nanograms per one hundred centimeters squared

NIOSH National Institute for Occupational Safety and Health

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

Abbreviatio
Health Hazard Evaluation Report 2010-0118-3142 Page iii

What NIOSH Did

● We visited the medical laboratory in March 2011. 

● We watched employees work and interviewed them about 

their work practices and health concerns.

● We reviewed employee training on handling chemotherapy 

drugs and the health effects that could occur as a result.

● We tested work surfaces for cyclophosphamide, a 

chemotherapy drug. 

What NIOSH Found

● We did not find cyclophosphamide on any work surfaces.

● We found the work practices for handling chemotherapy 

drugs to be appropriate.

● The employee chemotherapy drug and health effects training 

should be more specific to the work being done at the 

laboratory. 

● None of the employees whom we interviewed reported 

chronic health problems that were related to their work. 

What Managers Can Do

● Include information in the chemotherapy drug and health 

effects training that is pertinent to the job tasks that 

employees will perform. 

● Provide employees with information about chemotherapy 

drugs and reproductive health.

What Employees Can Do

● Follow recommended work practices and personal protective 

equipment procedures.

● Continue to learn how to work with chemotherapy drugs 

safely.

The National Institute for 

Occupational Safety and 

Health (NIOSH) received 

an employee request for a 

health hazard evaluation 

at a medical laboratory in 

Pennsylvania. Employees 

were concerned with 

potential adverse health 

effects associated with 

working with a wide range 

of chemotherapy drugs.

Highlights of 

NIOSH 

Hazard Eval
Page iv Health Hazard Evaluation Report 2010-0118-3142

In June 2010, NIOSH received an HHE request from employees 

who were concerned about their potential exposure to 

chemotherapy drugs at a medical laboratory in Pennsylvania. The 

chemotherapy drugs were used to treat biological specimens to help 

determine which chemotherapy drug protocol would potentially 

benefit the patient the most. Employees were concerned with 

reproductive problems and adverse health effects associated with 

these drugs.

We visited the medical laboratory on March 22–23, 2011. We 

observed work processes, practices, and conditions. We interviewed 

51 employees about their health and their concerns related to 

chemotherapy drugs and collected surface wipe samples for 

cyclophosphamide, one of several chemotherapy drugs used at the 

medical laboratory. 

We detected no cyclophosphamide on work surfaces. While 

most of the 51 interviewed employees at the laboratory reported 

handling chemotherapy drugs during the course of their work, 

none reported chronic health effects associated with their work, 

and three reported experiencing acute symptoms during their 

work. Employees were aware of the potential risks from exposure to 

chemotherapy drugs and closely followed administrative procedures 

and PPE recommendations.

We recommended that the medical laboratory continue to control 

exposures to chemotherapy drugs to levels as low as are reasonably 

achievable because the facility uses drugs that are considered 

hazardous [NIOSH 2010]. Control of these exposures can be 

validated by routine surface sampling for chemotherapy drugs used 

at the facility. 

NIOSH evaluated 

potential exposures to 

chemotherapy drugs 

among employees of 

a medical laboratory. 

We did not detect 

cyclophosphamide, a 

chemotherapy drug 

commonly used at the 

laboratory, on any work 

surfaces. Employees 

were observed using 

safe work practices and 

wearing appropriate 

protective equipment. We 

also found no adverse 

medical symptoms among 

employees that can be 

linked to occupational 

exposures at the 

laboratory.

Summ

Keywords: NAICS 621511(Medical Laboratories), chemotherapy 

drugs, oncology, antineoplastic drugs, cancer research
Health Hazard Evaluation Report 2010-0118-3142 Page 1

Introduct

In June 2010, NIOSH received an HHE request from employees 

at a medical laboratory in Pennsylvania. The employees were 

concerned about potential reproductive effects (miscarriages and 

irregular menstrual cycles), acute health effects (rash and cough), 

and chronic health effects (hair thinning, premature graying, 

and allergies) that they believed were related to their exposure to 

chemotherapy drugs. 

Because of an ongoing OSHA investigation, the NIOSH evaluation 

of the medical laboratory was delayed until March 22–23, 2011, 

when we observed work processes, practices, and conditions. We 

spoke with employees about health and workplace concerns related 

to chemotherapy drugs. We also collected surface wipe samples 

for cyclophosphamide, one of several chemotherapy drugs used 

at the medical laboratory. An interim letter containing the results 

from the surface wipe samples was sent to the medical laboratory 

management, an employee representative, and the HHE requestors 

in June 2011.

Process Description

The medical laboratory consisted of clinical laboratories, research 

laboratories, and administrative areas. The company employed 

more than 250 people, including approximately 50 clinical 

laboratory employees. 

The medical laboratory received biological specimens and treated 

them with chemotherapy drugs as directed by the ordering 

physician or on the basis of the type of cancer to identify the most 

effective chemotherapy drug(s) for treating the patient’s tumor 

or specimen. The biological specimen could consist of tissue 

biopsies or ascitic (pleural) fluid. The specimen was minimally 

processed by the ordering physician and shipped to the medical 

laboratory where it was manually plated onto growth media and 

placed into an incubator. After sufficient growth had occurred 

and the number of cells on the plate were counted and recorded, 

the specimen was ready for treatment with chemotherapy drugs. 

Chemotherapy drugs used at the medical laboratory included 

cyclophosphamide, doxorubicin, cisplatin, carboplatin, vincristine, 

paclitaxel, and many others. Cyclophosphamide is classified as a 

Group 1 Carcinogen by IARC, which means that the drug is a 

known human carcinogen [IARC 1998]. See the Appendix for 

more information on the health effects related to chemotherapy 

drugs. Figure 1 illustrates three employees applying chemotherapy 

drugs. 
Page 2 Health Hazard Evaluation Report 2010-0118-3142

Introducti

(continued

Figure 1. Clinical laboratory technicians working with chemotherapy 

drugs and patient biological specimens inside BSCs. 

A wide range of chemotherapy drugs as described by the ordering 

physician were prepared by clinical laboratory technicians in 

various dilutions and then administered to the specimen in 

assorted combinations. The amount of the chemotherapy drug 

applied to the biological specimen was approximately 100 – 1,000 

times lower than the amount of the drug used in patient treatment. 

Employees administered chemotherapy drugs to the specimens 

with automated pipettes or with a proprietary, fully automated 

computer-controlled system that distributed the chemotherapy 

drugs into wells containing a patient’s cells. After dispensing the 

drugs, the automated system discarded the tip into a chemotherapy 

waste receptacle. The chemotherapy waste receptacle was located 

below the automated system’s working surface and was emptied by 

employees at least daily.

Once treated, the specimen plates were incubated to allow the drug 

to stay in contact with the patient’s cells. After a predetermined 

amount of time the plates were retrieved and the chemotherapy 

drug treatment was evaluated for effectiveness (via cell count, 

morphology, etc.). The report from the laboratory to the ordering 

physician described the effectiveness of the chemotherapy drug as 

responsive, intermediate response, or nonresponsive. 
Health Hazard Evaluation Report 2010-0118-3142 Page 3

Exposure Assessment 

We collected cyclophosphamide surface wipe samples throughout 

the medical laboratory including the clinical laboratory areas, 

chemotherapy drug storage areas, research and development areas, 

and general office space. Although sampling methods exist for 

several drugs (e.g., cisplatin, doxorubicin, and ifosfamide), we 

sampled for cyclophosphamide because it was used extensively at 

the facility, a surface sampling method was available for this agent, 

and we believed that the results for this drug would be indicative of 

potential exposures to the other drugs. 

The samples were collected on Alpha® Texwipe swabs moistened 

with an extraction solvent comprised of 50% acetonitrile and 

50% deionized water. A 10 cm x 10 cm disposable square 

template was used to outline a 100 cm2 sampling area. Wipe 

samples were analyzed for cyclophosphamide by high performance 

liquid chromatography/mass spectrometry with an LOD of 

2.0 ng cyclophosphamide per sample and an LOQ of 6.7 ng of 

cyclophosphamide per sample. All media and field blanks were 

below the LOD. The sampling method is an internal procedure 

developed by Bureau Veritas North America, the NIOSH contract 

laboratory used for this HHE. Figure 2 illustrates two sample 

locations and the use of the sample templates. In areas where the 

template could not be used, a 100 cm2 sampling area was estimated. 

We observed employees handling chemotherapy drugs from the 

beginning of the process through drug disposal. We also reviewed 

written and video training materials for employees about handling 

chemotherapy drugs and the potential health effects related to 

these drugs. Clinical laboratory technicians are required to watch 

the training video on hire and annually. Upon completion of the 

training, they are required to pass a written exam to demonstrate 

competency. 

Assessment
Page 4 Health Hazard Evaluation Report 2010-0118-3142

Assessment (continued

Medical Assessment 

We held confidential interviews with clinical laboratory technicians 

and laboratory supervisors to discuss their work practices, 

medical (including pertinent reproductive) history, and symptoms 

experienced in the course of their employment. Symptoms asked 

about included constitutional, dermatologic, respiratory, and 

gastrointestinal symptoms. We interviewed employees in person 

and by telephone. After the visit we obtained additional employee 

information by telephone and pertinent medical records. All 51 

clinical laboratory technicians and laboratory supervisors on the 

first and second shifts participated in the interviews. 

Figure 2. A BSC containing a sample template on the airfoil of the BSC 

and a sample template on the floor directly in front of the BSC. 
Health Hazard Evaluation Report 2010-0118-3142 Page 5

We observed all employees wearing two pairs of chemotherapy 

protective gloves and removing their outer gloves properly when 

removing their hands from the BSC. Double gloving appeared 

consistent throughout the clinical laboratory areas. We also 

observed employees properly disposing chemotherapy drugs and 

chemotherapy drug contaminated equipment.

We noted that the doors to the automated dispensing machines 

could be lifted while the robotic head was still moving within the 

work envelope. Employees could enter into the work envelope to 

place or remove trays while the robotic head was still active. No 

electrical interlocks were installed on the automated dispensing 

machines. 

We noticed a small room that contained three doors leading to the 

Big Laboratory, the Small Laboratory, and the rest of the facility. 

Because all three doors opened inward into this small room, the 

area could quickly become congested with employees, some of 

whom were carrying chemotherapy drugs or chemotherapy drug 

treated wells. 

We observed that some employees changed their shoes when 

leaving the medical laboratory. While this was not a standard 

operating procedure at the laboratory, numerous employees 

reported wearing a dedicated pair of shoes within the laboratory 

and then changing into another pair of shoes before leaving the 

premises.

Employee training on handling chemotherapy drugs and their 

potential health effects was very comprehensive. The training video 

was detailed and discussed safe handling practices; the receipt, 

storage, labeling, and transport of drugs; the use of BSCs and 

PPE; and waste disposal and spill control procedures. However, 

individual training topics were not available for the specific job 

titles and job tasks at the medical laboratory, resulting in some 

employees receiving training in areas that were not pertinent to 

their work. 

Exposure Assessment 

The 40 surface wipe samples (Table 1) were analyzed for 

cyclophosphamide; all results were below the LOD of 2 ng 

per sample. These samples were collected in areas of high 

chemotherapy drug usage as well as office areas that would not be 

expected to have chemotherapy drug residue. 

Results
Page 6 Health Hazard Evaluation Report 2010-0118-3142

Results (continued

Table 1. Cyclophosphamide surface wipe sample results, March 2011

Location Description Result

(ng/100 cm2)

Small Liquid handler grill* ND†

Laboratory Grill liquid handler BioProtect II on right* ND

Floor directly in front of BSC 2 ND

Floor seam* ND

Floor by liquid handler BioProtect II on right ND

BSC 2 airfoil* ND

BSC 14 airfoil* ND

Chemotherapy waste container lid ND

Incubator door ND

Floor directly in front of BSC 14 ND

Floor adjacent to waste container near BSC 4 ND

BSC 18 work surface ND

BSC 18 airfoil* ND

Liquid handler BioProtect II waste drop* ND

Liquid handler BioProtect II between trays 22-28* ND

Liquid handler tray 30* ND

Floor next to waste container near liquid handler ND

Big Floor directly in front of incubator ND

Laboratory BSC 3 work surface ND

BSC 3 airfoil* ND

Liquid handler BioProtect II waste drop* ND

Liquid handler BioProtect II tray 30* ND

Liquid handler grill* ND

Floor directly in front of liquid handler ND

Liquid handler grill* ND

ICC Countertop near microscope ND

Room Floor near balance ND

Balance table ND

Floor near freezer ND

Scanning Countertop ND

Room Floor near center bench ND

Counter ND

Research/ Liquid handler airfoil* ND

Development Floor directly in front of liquid handler ND

Liquid handler BioProtect II waste drop* ND

Shipping/ Table ND

Receiving Floor near refrigerator ND

Office Desk on second floor ND

Area Desk on first floor ND

Desk on first floor ND

*Estimated 100 cm2 surface area

†ND = Not detected; below the LOD of 2 ng/sample.
Health Hazard Evaluation Report 2010-0118-3142 Page 7

Results (continued) Medical Assessment

The median age of the 51 clinical laboratory technicians and 

supervisors interviewed was 25 years with a range of 22 to 49 years. 

Thirty-four (67%) were female. Twenty-five employees worked first 

shift, and 26 employees worked second shift. The median number 

of years worked at the laboratory was 1.5 with a range of 7 months 

to 4 years.

Most (96%) employees reported handling chemotherapy drugs 

during the course of their work. Their work activities included 

preparing chemotherapy drugs for treatment, treating tissue 

samples with chemotherapy drugs, disposing chemotherapy drug 

waste in the trash, and cleaning surfaces contaminated with 

chemotherapy drug waste. None reported handling chemotherapy 

drugs prior to their job at this laboratory.

Most employees denied health symptoms while handling 

chemotherapy drugs or while working near others handling 

chemotherapy drugs. Two employees reported experiencing 

headache, and one employee reported eye irritation either while 

handling chemotherapy drugs or while working near others who 

were working with chemotherapy drugs. 

None of the employees reported a history of cancer, leukemia, 

lymphoma, kidney disease, urinary tract disorder, liver disease, skin 

disorder, or multiple sclerosis. One employee reported a history of 

a blood disorder that, in most cases, is caused by an autoimmune 

response. This employee had worked at this laboratory for 

more than 2 years before receiving this diagnosis. However, the 

employee had evidence of this disorder before beginning work at 

this laboratory, making an occupational etiology less likely. This 

employee’s personal physician concurred with this assessment, 

and none of the other employees reported being diagnosed with 

any other autoimmune disorder or blood disorder during their 

employment at the laboratory.

All females interviewed reported having regular menstrual cycles, 

and none of the male or female employees reported any fertility 

issues. One employee reported having a miscarriage during the 

time of her employment. However, her conception occurred prior 

to the commencement of her employment, and the miscarriage 

occurred during her training period shortly after being hired. One 

employee reported having two successful pregnancies during her 

employment at the laboratory.
Page 8 Health Hazard Evaluation Report 2010-0118-3142

Results (continued) All employees reported being provided with written policies

regarding PPE use and receiving training on PPE use in the past 

12 months. Most (98%) employees reported receiving training on 

possible health effects related to exposure to chemotherapy drugs. 

All employees involved in preparing chemotherapy drugs reported 

always using a BSC. All employees reported always wearing double 

gloves and disposable gowns when handling chemotherapy drugs; 

these practices were confirmed by our observations. Most reported 

changing their outer gloves at least every 30 minutes (82%), their 

inner gloves at least every 60 minutes (78%), and their disposable 

gown every 3–6 hours (86%). None of the employees reported 

consuming food and drink in the work area.

Cyclophosphamide was not detected in the samples we collected 

during our visit. Because the facility uses a number of different 

chemotherapy drugs, it is possible that other drugs may have been 

present. We believe it is prudent and necessary to control potential 

exposures to all chemotherapy drugs to levels as low as reasonably 

achievable. It should be noted that we focused our evaluation 

on the clinical laboratory employees, so our findings may not 

be generalizable to other employees at the facility such as those 

working in the research laboratories or administration areas. 

While most clinical laboratory employees at the facility reported 

handling chemotherapy drugs during the course of their work, 

none reported chronic health effects associated with their work, 

and only three reported acute symptoms they associated with their 

work. We are unable to definitively determine the etiology of the 

headache and eye irritation reported by these three employees. 

However, our environmental sampling revealed low exposures, and 

employees adhered to strict handling of the chemotherapy drugs 

during our visit, so it is unlikely that these symptoms were related 

to chemotherapy drug exposure. 

Cyclophosphamide was not detected on any work surfaces. 

Employees were observed performing safe work practices and 

wearing appropriate PPE. No adverse health effects related to 

exposure to chemotherapy drugs were identified in employees at 

the medical laboratory.

Discussi

Conclusion
Health Hazard Evaluation Report 2010-0118-3142 Page 9

Although no cyclophosphamide was detected on any work surfaces, 

we nonetheless recommend the actions listed below to create a 

more healthful workplace. We encourage the laboratory 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 laboratory. Our recommendations are based on 

the hierarchy of controls approach. 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 personal protective equipment may be needed. Comprehensive 

exposure control strategies for chemotherapy drugs can be 

found in the OSHA Technical Manual, Section VI, Chapter 2: 

Controlling Occupational Exposure to Hazardous Drugs [OSHA 

1999] and the NIOSH Alert: Preventing Occupational Exposure 

to Antineoplastic and Other Hazardous Drugs in Health Care 

Settings [NIOSH 2004].

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. Install safeguards (i.e., interlocking system) on the liquid 

handlers to prevent entry into the robotic head work 

envelope during use.

2. Use a dedicated chemotherapy drug tray that is at least 2 

inches deep to contain any spilled drugs within the tray in 

case of an accident when transporting chemotherapy drugs 

or specimen plates containing treated cells. This may be of 

greatest concern in the congested small room connecting 

the Small Laboratory and the Big Laboratory.

Recommendatio
Page 10 Health Hazard Evaluation Report 2010-0118-3142

Recommendatio

(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 management 

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 and revise training materials to make the 

information more relevant to specific job titles and job 

requirements at the medical laboratory. For example, 

consider creating individual training modules addressing 

safe handling practices; potential health effects from 

working with chemotherapy drugs; the receipt, storage, 

labeling, and transport of drugs; the use of BSCs and PPE; 

and waste disposal and spill control procedures.

2. Ensure that employees know to whom they should report 

any possible work-related health problems. Encourage 

employees to notify appropriate management representatives 

in a timely manner.

3. Inform all employees of the risks, including reproductive 

risks, associated with exposure to chemotherapy drugs upon 

hire and annually. More information on the potential effects 

from occupational exposure to chemotherapy drugs can be 

found at http://www.cdc.gov/niosh/topics/antineoplastic/

effects.html#b.

4. Continue the medical surveillance program for employees 

and refer to the OSHA Technical Manual: Controlling 

Occupational Exposure to Hazardous Drugs, Section VI 

Chapter 2 [OSHA 1999]. The program should include 

a medical and exposure history, physical examination, a 

complete blood count with differential and reticulocyte 

count, and a urine dipstick or urinalysis on hire and 

annually.
Health Hazard Evaluation Report 2010-0118-3142 Page 11

Recommendatio

(continued

Referenc

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. Instruct employees to wear dedicated work shoes at the 

medical laboratory and change shoes when they leave 

to prevent contamination of their personal vehicles and 

homes.

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.

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 list of antineoplastic and other hazardous 

drugs in healthcare settings 2010. 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. 2010-167.

OSHA [1999]. OSHA technical manual, TED 1–0.15A, Sec VI, 

Chapter II: Categorization of drugs as hazardous. [http://www.

osha.gov/dts/osta/otm/otm_toc.html]. Date accessed: August 

2011. 
Page 12 Health Hazard Evaluation Report 2010-0118-3142

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 preexisting 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, peer-reviewed 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 

Appendix: Occupational Exposure Limits and H
Health Hazard Evaluation Report 2010-0118-3142 Page 13

Appendix: Occupational Exposure Limits and He          

Insurance) maintains a database of international OELs from European Union member states, Canada 

(Québec), Japan, Switzerland, and 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.

Cyclophosphamide 

Cyclophosphamide has been categorized as a Group 1 Carcinogen (carcinogenic to humans) [IARC 

1998]. This designation means that there is sufficient evidence that cyclophosphamide can cause cancer in 

humans. Cyclophosphamide metabolizes in the body to acrolein, which can cause adverse health effects in 

the bladder.

Cyclophosphamide is a cytotoxic drug that is used for a wide range of neoplastic diseases including breast 

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

agent or in combination with other chemotherapy drugs and can be administered via oral tablets or 

intravenously. 

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

brought into liquid solution by the addition of water and infused with sodium chloride, glucose, or 
Page 14 Health Hazard Evaluation Report 2010-0118-3142

Appendix: Occupational Exposure Limits and He          

glucose/saline solutions. Once in solution, it is recommended that cyclophosphamide be administered to 

the patient within 8 hours to prevent degradation or be stored at cold temperatures (but never frozen).

There are currently no OELs for cyclophosphamide. However, because of the carcinogenic nature of the 

drug, exposures to cyclophosphamide should be kept as low as reasonably achievable.

Hazardous Drugs in Healthcare Settings

Employee exposures to hazardous drugs including 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 hazardous 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 absorption, use of ventilated cabinets, PPE, and work practices. The likelihood that an employee will 

experience adverse effects from hazardous drugs increases with the amount and frequency of exposure and the 

lack of proper work practices [NIOSH 2004].

Surveys have associated workplace exposures to antineoplastic 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].

A recent review of 14 studies described an association between exposure to antineoplastic drugs and adverse 

reproductive effects, and 9 studies showed some positive association [Harrison 2001]. 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 healthcare employee 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.

Currently, no NIOSH RELs, OSHA PELs, or ACGIH TLVs have been established for hazardous drugs in 

general.
Health Hazard Evaluation Report 2010-0118-3142 Page 15

Appendix: Occupational Exposure Limits and He          

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, 

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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.

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: August 2011.

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

hospital personnel (in Dutch). Netherlands: Elsevier.
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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 occupational 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]. The 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 

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Health Hazard Evaluation Report 2010-0118-3142 Page 17

Acknowledgments a

Availability of Rep

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 

endorsement by NIOSH. In addition, citations to websites 

external to NIOSH do not constitute NIOSH endorsement of 

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 Marie de Perio of 

HETAB, Division of Surveillance, Hazard Evaluations and Field 

Studies. Subject matter consultation and industrial hygiene field 

assistance was provided by Thomas Connor of the Division of 

Applied Research and Technology. Industrial hygiene equipment 

and logistical support was provided by Donnie Booher and 

Karl Feldmann. Health communication assistance was provided 

by Stefanie Evans. Editorial assistance was provided by Ellen 

Galloway. Desktop publishing was performed by Robin Smith.

Copies of this report have been sent to employee and 

management representatives at the medical laboratory, the state 

health department, and the Occupational Safety and Health 

Administration Regional Office. This report is not copyrighted and 

may be freely reproduced. The report may be viewed and printed at 

http://www.cdc.gov/niosh/hhe/. 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 [2011]. Health hazard evaluation report: hazardous drug evaluation at a 

medical laboratory – Pennsylvania. By Couch J, de Perio MA. 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. 2010-0118-3142.

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