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Current Intelligence Bulletin XX

Reproductive Risks Associated with Hazardous Drug Exposures in Healthcare 

Workers and Recommendations for Reducing Exposures 

by 

Thomas H. Connor, PhD 

Christina C. Lawson, PhD 

Martha Polovich, PhD, RN, AOCN 

Melissa A. McDiarmid, MD, MPH, DABT 

DEPARTMENT OF HEALTH AND HUMAN SERVICES 

Centers for Disease Control and Prevention 

National Institute for Occupational Safety and Health 

Disclaimer: The findings and conclusions in this report are those of the author and do not necessarily 

represent the views of the National Institute for Occupational Safety and Health (NIOSH). Mention of any 

company or product does not constitute endorsement by NIOSH. In addition, citations to Web sites 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 Web sites. All Web addresses referenced in 

this document were accessible as of the publication date.
2 

This document is in the public domain and may be freely copied or reprinted. 

Disclaimer 

Ordering Information 

To receive documents or other information about occupational safety and health topics, contact NIOSH 

at 

 

DHHS (NIOSH) Publication No. 2012–XXX 
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Foreword 

The purpose of this Current Intelligence Bulletin is to increase awareness among healthcare 

workers and their employers about the potential adverse reproductive health effects from working with 

antineoplastic and other hazardous drugs. In addition, it will provide measures for protecting the reproductive health of workers and the health of their offspring. Healthcare workers who prepare or administer hazardous drugs or who work in areas where these drugs are used can be exposed when these agents 

are in the air or on work surfaces, drug vials and containers, contaminated clothing, medical equipment, 

and patient excreta. Workplace exposures to hazardous drugs have been associated with health effects 

such as skin disorders, adverse reproductive outcomes (including infertility, miscarriage, and congenital 

malformations), and possibly leukemia and other cancers. Of these, reproductive health is one of the 

most vulnerable endpoints, because many hazardous drugs used for cancer treatment target rapidly dividing cells in the same way teratogens target rapidly dividing embryonic cells. The risk can be influenced by the timing of the exposure and the potency and toxicity of the hazardous drug. 

The production, distribution, clinical preparation, administration, and disposal of pharmaceutical 

products are widespread and essential to the healthcare industry. New areas of pharmaceutical development are continually bringing new drugs and fundamental changes to methods for treating and preventing or minimizing diseases. At the same time, a large number of medications or mixed exposures 

can be hazardous to healthcare workers who handle them and to their fetuses or nursing offspring. This 

NIOSH Current Intelligence Bulletin will help make workers and employers more aware of these hazards and provide recommendations for preventing exposures. 

This Current Intelligence Bulletin applies to all healthcare workers who might handle hazardous 

drugs, such as pharmacists and pharmacy technicians, registered nurses, advanced practice registered 

nurses, licensed practical/vocational nurses, nurses’ aides, physicians, physicians’ assistants, operating 
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room personnel, shipping and receiving personnel, waste handlers, maintenance workers, laundry 

workers, laboratory personnel, and workers in veterinary practices. The current number of healthcare 

workers in the United States potentially exposed to hazardous drugs exceeds 8 million. However, not 

all of these workers will be exposed to hazardous drugs, and only a fraction of those who are exposed 

will be at reproductive risk. Workers in the drug manufacturing sector may also be exposed to hazardous drugs. However, the primary focus of this Current Intelligence Bulletin is workers in healthcare 

settings because of their unique potential to be in an environment of multiple exposures. 

 

 

John Howard, MD 

Director 

National Institute for Occupational 

Safety and Health 

Centers for Disease Control and 

Prevention 
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Abstract

Healthcare workers who handle, compound (prepare), administer, or dispose of hazardous drugs 

can incur risks to their health, including reproductive harm. This document describes the 

vulnerability of workers, fetuses, and nursing infants of exposed workers to reproductive and 

health hazards and reviews human and animal studies of exposure to hazardous drugs. On the basis of a review of published data, the National Institute for Occupational Safety and Health 

(NIOSH) recommends steps to reduce employee exposure to hazardous drugs for all healthcare 

workers and especially those at reproductive risk. Special consideration may be needed for those 

workers with underlying medical conditions that may put a worker at exceptional risk of harm. 

These steps involve adhering to established industrial hygiene procedures, education and training 

for employees and employers on the safe handling of hazardous drugs, and including the 

implementation of an alternative duty program when exposure cannot be eliminated. Employers 

and all workers in healthcare settings (including employees and nonemployees such as contractors 

and credentialed providers) can work together to establish a program to provide a safe working 

environment for all healthcare workers, especially those who are at reproductive risk if exposed to 

hazardous drugs. 
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Contents 

Foreword 

Abstract 

Acknowledgments 

Abbreviations 

Glossary 

Reproductive Risks Associated with Hazardous Drug Exposures in Healthcare Workers and 

Recommendations for Reducing Exposures 

Background 

Description of Exposure 

 When is a Worker Particularly Vulnerable to Reproductive Hazards? 

Vulnerability of the Developing Fetus and Newborns 

Experimental Studies 

 Animal Studies 

 Human Studies 

 Patients Treated with Antineoplastic Drugs 

 Patients Treated with Drugs Other Than Antineoplastic Drugs 

 Healthcare Workers Exposed to Hazardous Drugs 

 Exposure to Antineoplastic Drugs 

Recommendations 

 Use of Industrial Hygiene Practices to Reduce Exposure to Hazardous Drugs 

Implementation of an Alternative Duty or Temporary Reassignment Program 

Medical, Legal and Ethical Implications 

Summary 

References 

Tables 

Table 1. Review of Reproductive Epidemiology Studies of Occupational Exposure to 

Antineoplastic Drugs 

Figures 

 Figure 1. Initial Health and Safety Assessment for Couples Trying to Conceive and Women who 

are Pregnant or Breast Feeding 

Appendices 

 Appendix 1. Hazardous Drug Handling Activities in Healthcare Settings that can Result in 

 Exposure 

 Appendix 2. FDA Pregnancy Categories of Drugs that should be Handled as Hazardous 

 Appendix 3. FDA-Assigned Pregnancy Categories 

 Appendix 4. Databases Reviewed 

Appendix 5. Reproductive Health Recommendations for Alternative Duty Practices 

Acknowledgments 

The authors thank the following individuals for their assistance in reviewing this document: Kathleen 

Connick 
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Editorial review and production assistance were provided by Susan Afanuh and Vanessa B. Williams. 
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Abbreviations 

AHFS 

ANA 

American Hospital Formulary Service 

American Nurses Association 

ASHP American Society of Health System-Pharmacists 

(Formerly known as American Society of Hospital 

Pharmacy) 

BSC Biological safety cabinet 

CACI 

CAPhO 

CFR 

Compounding aseptic containment isolator 

Canadian Association of Pharmacy in Oncology 

Code of Federal Regulations 

CSTD 

HSE 

IARC 

Closed system drug-transfer device 

Health and Safety Executive 

International Agency for Research on Cancer 

NIOSH 

NRC 

NTP 

National Institute for Occupational Safety and 

Health 

Nuclear Regulatory Commission 

National Toxicology Program 

OSHA Occupational Safety and Health Administration 

ONS Oncology Nursing Society 

PPE 

SDS 

Personal protective equipment 

Safety Data Sheet (Formally Material Safety Data 

Sheet) 

USP United States Pharmacopeial Convention 
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Glossary 

Alternative duty: Temporary reassignment of duties, often within the same job, to avoid hazardous situations or agents (in this case, exposure to hazardous drugs). 

Antineoplastic drug: A chemotherapeutic agent that controls or kills cancer cells. Drugs used in the 

treatment of cancer are cytotoxic but are generally more damaging to dividing cells than to resting cells. 

Carcinogenicity: The ability or tendency to produce cancer. 

Chemotherapy drug: A chemical agent used to treat diseases. The term usually refers to a drug used to 

treat cancer. Similar drugs are also known as antineoplastic and cytotoxic. 

Closed system drug-transfer devices (CDTDs): A drug transfer device that mechanically prohibits the 

transfer of environmental contaminants into the system and the escape of hazardous drug or vapor concentrations outside the system. 

Cytotoxic: A pharmacologic compound that is detrimental or destructive to cells within the body. 

Engineering controls: Devices designed to eliminate or reduce worker exposures to chemical, biological, radiological, ergonomic, or physical hazards. Examples of those used in healthcare include laboratory fume hoods, glove bags, needleless systems, closed system transfer devices, biological safety cabinets, containment isolators, and robotic systems. 

Genotoxicity: The ability to damage or mutate DNA. Genotoxic substances are not necessarily carcinogenic. 

Hazardous drug: Any drug identified by at least one of the following criteria: carcinogenicity; teratogenicity or developmental toxicity; reproductive toxicity in humans; organ toxicity at low doses in humans or animals; genotoxicity; or new drugs that mimic existing hazardous drugs in structure or toxicity. 

Healthcare workers: All workers who are involved directly or indirectly in the care of patients. Examples of those at risk for exposure to hazardous drugs include pharmacists; pharmacy technicians; registered nurses, advanced practice registered nurses; licensed practical/vocational nurses; nurses’ aides; 

physicians; physicians’ assistants; home healthcare workers; and workers in environmental services 

(housekeeping, laundry, and waste disposal). 

Mutagenicity: The ability of increasing the spontaneous mutation rate by causing changes in the DNA. 

Personal protective equipment (PPE): Items such as gloves, gowns, respirators, goggles, face shields, 

and others that protect individual workers from hazardous physical or chemical exposures. 

Reproductive hazard: An agent that interferes with the ability of a couple to achieve a successful birth. 
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Reproductive hazards affect fertility, conception, pregnancy, and/or delivery. 

Reproductive risk: Reproductive risk refers to risks to the reproductive systems of adult men and women, and outcomes of pregnancies, including: measurements of fertility in men and women, menstrual 

function, miscarriage (spontaneous abortion), preterm birth, abnormal birth weight, and developmental 

and reproductive outcomes in offspring. 

Reproductive toxicity: The ability to cause adverse effects on the male and/or female reproductive system. 

Risk assessment: Characterization of potentially adverse health effects from human exposure to environmental or occupational hazards. Risk assessment can be divided into five major steps: hazard identification, dose–response assessment, exposure assessment, risk characterization, and risk communication. 

Susceptible populations: Those individuals with medical history or personal fertility history (e.g., repeated miscarriages) or any other underlying medical conditions that may put them at exceptional risk of 

harm. 

Temporary reassignment: An assignment to another position, at the same pay scale, for a specified period. At the end of the temporary reassignment, the employee returns to the original position or to a position of comparable status, tenure, and pay. 

Teratogenicity: The capability of producing fetal malformations. 
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Reproductive	Risks	Associated	with	Hazardous	Drug	Exposures	in	

Healthcare	Workers	and	Recommendations	to	Reduce	Exposures	

Background

The acute and chronic toxicity of antineoplastic drugs is well recognized in treated patients including 

their reproductive and developmental toxicity. Healthcare workers who compound (prepare) or administer antineoplastic drugs, or who work in areas where these drugs are used can be exposed to these agents 

when they are present on contaminated work surfaces, drug vials and containers, contaminated clothing 

and medical equipment, and in patient excreta and secretions such as urine, feces, vomitus, and sweat 

(Appendix 1). The National Institute for Occupational Safety and Health (NIOSH) has developed an 

approach to minimizing exposure to antineoplastic and other hazardous drugs with the publication of the 

NIOSH Alert: Preventing Occupational Exposures to Antineoplastic and Other Hazardous Drugs in 

Health Care Settings [NIOSH 2004] that includes a combination of industrial hygiene practices, starting 

with engineering controls. Engineering controls place a barrier between the worker and the hazard to 

reduce exposure. These engineering controls include biological safety cabinets (BSCs) or compounding 

aseptic containment isolators (CACIs), closed system transfer devices (CSTDs), robotic systems, and 

needleless systems. Additional controls should include vigilant adherence to safe work practices and 

administrative controls. The use of personal protective equipment (such as gowns, gloves, and eye and 

respiratory protection) is also essential for worker protection [NIOSH 2009]. 

Measurement of surface contamination is currently the best indication of the level of environmental 

contamination in areas where hazardous drugs are prepared, administered to patients, or otherwise 

handled (such as receiving areas, transit routes throughout the facility, and waste storage areas) [Hon et 

al. 2011]. In a follow-up study, Hon and coworkers [2014] reported that 20% of the workers sampled 
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had detectable amounts of cyclophosphamide on their hands. Studies that have attempted to do so have 

shown an association between surface contamination and worker exposure [Pethran et al. 2003; Connor 

et al. 2010; Villarini 2011], and surface contamination is the most commonly used metric for evaluating 

the workplace for hazardous drugs. Workplace contamination with hazardous drugs in the United States 

has not changed considerably over the past decade or more [Connor et al. 1999; 2010, Wick et al. 2003; 

Sessink et al 2011; 2013]. This finding indicates that worker exposure probably has remained constant 

over that time, despite efforts to reduce or eliminate environmental contamination. 

The introduction of Class II BSCs for the preparation of hazardous drugs in the 1980s substantially 

reduced the potential for worker exposure [Anderson et al. 1982], but not as efficiently as first believed 

[Connor et al. 1999]. The more recent use of CACIs has not been widespread, and these have not been 

proven to offer more protection to workers than BSCs [Seger et al. 2012]. The use of robotic systems to 

prepare hazardous drugs may reduce environmental contamination and worker exposure to these drugs. 

However, their high cost makes them prohibitive for most facilities [Seger et al. 2012]. The addition of 

CSTDs for the preparation and administration of hazardous drugs has been shown to reduce surface 

contamination and possibly worker exposure, but they do not totally eliminate them [Connor et al. 2002; 

Wick et al. 2003; Harrison et al. 2006; Sessink et al. 2011, 2013]. Despite improvements in engineering 

controls and other attempts to reduce environmental contamination, hazardous drugs are still being 

released into the work environment and workers are being exposed to them. Therefore, for the 

foreseeable future, contamination of the workplace with hazardous drugs and/or worker exposure to 

them will be an issue with no suitable solution. 

Recent research has shown that even when all of these controls are used in healthcare settings, the 

potential for exposure to antineoplastic drugs cannot be completely eliminated [Schierl et al. 2009; 

Connor et al. 2010; Siderov et al. 2010; Yoshida et al. 2010; Davis et al. 2011; Sessink et al. 2011; Turci 
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et al. 2011; Chu et al. 2012; Polovich and Martin 2011; Kopp et al. 2013]. Therefore, an additional level 

of protection might be required for those healthcare workers who are most vulnerable to the 

reproductive and developmental effects of hazardous drugs in the form of voluntary temporary 

alternative duty.[ASHP 1990, 2006; OSHA 1999; HSE 2003; Lawson et al. 2006; ACOEM 2011; ONS 

2009; 2011].

Description of Exposure

In 2004, NIOSH published an alert on antineoplastic and other hazardous drugs that describes safe 

handling practices for all healthcare workers [NIOSH 2004]. The alert included a list of drugs that were 

considered hazardous to workers. That list of hazardous drugs was most recently updated in 2014 to 

include drugs newly approved by the U.S. Food and Drug Administration (FDA) and other drugs with 

new FDA safety warnings based on post-marketing information [NIOSH 2014]. This document also 

contains new guidance on the safe handling of hazardous drugs. Approximately half of the drugs listed 

as hazardous by NIOSH are classified as antineoplastic, and the remainder comprise hormonal agents, 

immunosuppressants, antiviral agents, and others. Although the current document pertains to published 

information on exposure to primarily antineoplastic drugs, the information and recommendations herein 

can be generalized to include other hazardous drugs. 

Appendix 2 lists all drugs that NIOSH considers potentially hazardous to healthcare workers as of 2014 

[NIOSH 2014]. Of the 184 drugs listed, 99 are FDA Pregnancy Category D and 43 are Pregnancy Category X; the remainder of the listed drugs is Category C or B. For Category D drugs, there is positive evidence of human fetal risk, based on adverse reaction data from investigational or marketing experience 

or studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks to the fetus (Appendix 3). Category X drugs are those for which the fetal risk clearly outweighs the benefits to patients [Timpe et al. 2004; Briggs et al. 2008; 21 CFR 201.57(c)(9)(i)]. Most of 
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the remaining 30 percent of the drugs are classified as Category C, in which animal reproduction studies 

have shown an adverse effect on the fetus; there have been no adequate, well-controlled studies in humans, but the potential benefits might warrant use of a Category C drug in pregnant patients despite the 

fetal risks. However, many drugs classified as Category C have reproductive warnings or properties similar to those of the drugs in Category D. Four of the drugs are classified as Category B, which differs 

from Category C in that animal reproduction studies have failed to demonstrate a risk to the fetus, but is 

similar in that there have not been adequate studies in humans and there is still potential for concern 

(Appendix 2). According to the FDA, the current pregnancy category labeling may be misleading [FDA, 

2008]. Using A, B, C, D and X to describe the risk of fetal harm implies that risk increases from one 

category to the next. In fact, C- and D-category drugs may have risks similar to those in category X, but 

risk is weighed against benefit. When considered in the context of occupational exposure, there are no 

benefits associated with drug exposure; therefore, occupational exposure of pregnant workers cannot be 

assumed to be harmless especially since the workers may be exposed to multiple hazardous drugs daily 

over many years. Because exposure to drugs that have adverse reproductive effects is possible in many 

healthcare settings, additional precautions and safeguards might be required to better protect vulnerable 

populations such as fetuses and breastfed infants. 

By definition, a reproductive hazard affects the reproductive function of women or men or the ability of 

couples to conceive or bear healthy children [HSE 2003]. Some chemicals, including many hazardous 

drugs, are considered reproductive hazards on the basis of laboratory studies in animals or 

epidemiological studies in humans that show they can affect fertility or pregnancy outcomes or cause 

birth defects. A substantial number of these drugs have been identified by NIOSH as hazardous and are 

also known or suspected human carcinogens [IARC 2014]. Many are teratogenic and/or have adverse 

reproductive effects. In addition, numerous highly hazardous but therapeutically useful drugs are known 

to be present in the breast milk of women who are being treated with them [Briggs et al. 2008]. Most 
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hazardous drugs are used to treat illnesses such as cancer, autoimmune disorders, or human immunodeficiency virus infection [NIOSH 2004; 2014]. However, healthcare workers who are unintentionally 

exposed to these drugs at work face several health risks, including reproductive risks (e.g., risks to the 

reproductive systems of adult men and women, and outcomes of pregnancies). 

In the United States, an estimated 8 million healthcare workers [BLS 2011] are potentially exposed to 

hazardous drugs at their worksites. It is not known how many are exposed to hazardous drugs but many 

of these workers are women of reproductive age and should be aware of the potential [Hood 2008; Alex 

2011]. Because the estimated number of U.S. workers potentially exposed to hazardous drugs is based 

on job classifications and work locations, not all of the workers in a particular job classification will be 

exposed. In addition, for males, the only reproductive risk is exposure during the period leading up to 

conception. Women who are not at risk for adverse reproductive outcomes are those who cannot 

conceive, are utilizing reliable means of contraception, or are post-menopausal. Therefore, the actual 

number of men and women who may be at reproductive risk while exposed to hazardous drugs is 

considerably less than 8 million. However, because of the nature of these drugs, workers may be at risk 

for other adverse health outcomes, such as acute and chronic effects of drug exposure. 

These workers include pharmacists and pharmacy technicians, registered nurses, advanced practice registered nurses, licensed practical/vocational nurses, nurses’ aides, physicians, physicians’ assistants, 

operating room personnel, shipping and receiving personnel, waste handlers, maintenance workers, 

laundry workers, laboratory personnel, and workers in veterinary practices and potentially others working in healthcare settings who come into contact with drugs or drug waste [NIOSH 2004]. Healthcare 

workers are exposed to hazardous drugs when they compound, administer, or dispose of hazardous 

drugs, clean up spills or patient waste, or touch surfaces that are contaminated with these drugs. These 

activities can create aerosols or generate dust, thereby increasing exposure [OSHA 1999; NIOSH 2004; 

ASHP 2006; ONS 2011]. Skin absorption and inhalation are the most common ways a healthcare worker 
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may be exposed to hazardous drugs. However, ingestion (from hand-to-mouth contact), accidental 

injection through a needle stick, or other sharps injury is also possible [NIOSH 2014]. 

When	is	a	Worker	Particularly	Vulnerable	to	Reproductive	Hazards?	

Antineoplastic drugs can affect reproductive function in both males and females exposed to the drug. 

For reproductive health hazards, there is a “window of risk” when men and women are particularly 

vulnerable. In women treated with antineoplastic drugs, adverse effects have been reported including 

damage to ovarian follicles, decreased ovarian volume, and ovarian fibrosis resulting in amenorrhea and 

menopausal and other symptoms [Knobf 2006]. For pregnant women, the window of risk begins 

approximately one month before conception and lasts through the pregnancy. However, specific drugs 

may remain in the body for an extended period of time, especially if exposure is continuous. In 

addition, some drugs are known to enter the breast milk of treated patients [NIOSH 1996, 1999; HSE 

2003; Briggs et al. 2008]; therefore, the infants of healthcare workers could be exposed during 

breastfeeding. 

In men, reported adverse effects include primary or secondary hormonal changes. In addition, a man can 

expose his female partner and/or her developing fetus via contaminants on his skin or clothing, or during 

sexual intercourse [Pichini et al. 1994]. Men produce sperm over approximately a 2-month cycle; 

therefore, a man’s sperm is vulnerable to hazardous exposures from as early as 2 months before 

conception [Maltaris et al. 2006]. Consequently, both male and female workers who are handling 

hazardous drugs during any of these critical reproductive periods should be especially aware of risks to 

the health of their offspring. 

Vulnerability	of	the	Developing	Fetus	and	Newborns	
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Although adults can be adversely affected by prolonged exposures to certain chemicals, developing fetuses and newborns up to the age of 6 months are usually more sensitive to chemical toxicity because of 

the incomplete development of systems for biotransformation/detoxification and elimination of toxicants. Unlike older children and adults, such pathways are underdeveloped and cannot efficiently detoxify or excrete drugs. Therefore, toxicants remain in higher concentrations in the blood for longer periods 

[Scheuplein et al. 2002]. Examples of toxic substances and carcinogens that affect infants more than 

adults include some pesticides, tobacco smoke, radiation, and a variety of chemicals. With many chemical exposures, it is known that the fetus is more susceptible than the mother to the toxic chemical [NRC 

1993; Goldman 1995; Scheuplein et al. 2002; Brent et al. 2004; Perera 2011]. In addition, studies have 

shown that exposure to chemicals and radiation in utero and early in life can disproportionally increase 

the occurrence of childhood cancer compared with exposures that occur later in life [Perera 2011]. 

 

Reproductive effects might occur at lower exposure concentrations than exposure limits established by 

the Occupational Safety and Health Administration (OSHA) or recommended by NIOSH [2010] or the 

American Conference of Governmental Industrial Hygienists [ACGIH 2012]. This is because many of 

these limits are based on protecting adult workers from health effects other than reproductive endpoints 

(for example, neurotoxicity or cancer). In 1991, the General Accounting Office (GAO) reviewed 

regulations on environmental chemicals known to cause adverse reproductive and developmental 

outcomes. They reported that two-thirds of the major regulatory decisions for the 30 chemicals reviewed 

were based on cancer and acute toxicity, not reproductive or developmental effects [U.S. GAO 1991]. In 

addition, in most cases, exposure limits have not been established for hazardous drugs [NIOSH 2004]. 

Because the placenta is not an effective barrier to low-molecular-weight molecules, many of the 

antineoplastic and other hazardous drugs can reach the fetus in concentrations that could have 

deleterious effects [Arnon et al. 2001]. Drugs with a molecular weight of less than 600 Daltons usually 
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cross the placenta; those with molecular weights greater than 1000 Daltons typically do not. Since many 

antineoplastic drugs have a molecular weight within these parameters, they can readily cross the 

placenta [Pacifici and Nottoli 1995]. In addition, the placenta is also more permeable to lipophilic 

chemicals and drugs. Moreover, it has been hypothesized that many antineoplastic drugs actually target 

developing fetuses in the same way they target the rapidly proliferating cells and active DNA metabolism of cancer cells [Selig et al. 2012]. 

Experimental Studies

Animal	Studies	

Laboratory studies have demonstrated that many antineoplastic drugs are teratogenic, often in more than 

one animal species. Some classes of drugs are more hazardous than others [Shepard 1995; Schardein 

2000]. As a group, the antineoplastic drugs have been shown in animal studies to be some of the most 

potent teratogenic agents known at doses typically used in cancer treatment. Alkylating agents, 

anthracycline antineoplastic antibiotics, and antimetabolites all have potent teratogenic activity in multiple animal species. Antimetabolites are associated with birth defects more frequently than other 

antineoplastic agents. Alkylating agents are generally less teratogenic than the antimetabolites. Vinca 

alkaloids are potent teratogens in animals but do not appear to have similar effects in humans [Meirow 

and Schiff 2005]. Many antineoplastic drugs, in addition to the alkylating agents and antimetabolites, are 

also teratogenic in laboratory animals. In addition to the antineoplastic drugs, numerous other drugs 

have been demonstrated to be teratogenic in one or more species [Schardein 2000]. Preclinical laboratory testing of drugs in general demonstrates various adverse effects on reproduction and fertility, often in 

the absence of maternal toxicity [NIOSH 2004; 2014]. Additional information on teratogenic, reproductive, and fertility effects of specific drugs can be found in the drug package inserts and in the Safety Data Sheets (SDSs). 
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Human	Studies	

Patients Treated with Antineoplastic Drugs

Infertility following treatment with antineoplastic drugs has been reported for both men and 

women because of the gonadal toxicity of the drugs [McInnes and Schilsky 1996; Maltaris et al. 2007]. 

A number of individual antineoplastic drugs and some combinations of antineoplastic drugs have been 

identified as causing gonadal dysfunction in male cancer patients [Meistrich et al. 1997; Wallace et al. 

2005]. Individual drugs such as cyclophosphamide, melphalan, chlorambucil, procarbazine, and 

cisplatin and drug combinations such as MOPP (nitrogen mustard, oncovin, procarbazine, and 

prednisone) have produced prolonged azoospermia in males [Wallace et al. 2005]. The teratogenic 

effects on the fetuses of women treated with these drugs are well documented [Shepard 1995; Schardein 

2000; Meirow and Schiff 2005; Shahab and Doll 2008; Azim et al. 2010a,b; NTP 2013]. The observed 

teratogenic effects depend on the drug, the dose, and the developmental stage of the fetus at exposure. 

Schardein [2000] lists several common antineoplastic drugs as human teratogens. Although information 

is available from human studies about individual drug exposures, most malignancies are treated with 

multi-drug regimens [Azim et al. 2010a,b]. Therefore, many of the known teratogenic effects of 

individual drugs have been derived from animal studies. 

Three recent publications have reviewed the effects of cancer treatment on the developing fetus. The 

first reported the effects of antineoplastic drugs used to treat solid tumors, primarily breast and ovarian 

cancers [Azim et al. 2010a,b; Selig et al. 2012]. Although data are limited or not available for many 

drugs, the authors concluded that, in general, antineoplastic drugs have adverse effects on the fetus 

during the first trimester. Exposure during the first 2−3 weeks of pregnancy typically results in 

miscarriage, but not teratogenesis [Azim 2010a]. In patients treated with these drugs, brief exposures 

during early pregnancy to antineoplastic drugs (those for which there are data) had little effect on the 
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fetus. However, continued exposure resulted in congenital anomaly rates of approximately 20% which is 

in contrast to background rates that are normally 3-4 %. Most of the antineoplastic drugs they reviewed 

had little effect on the fetus in the second and third trimesters, with the exception of methotrexate. Since 

methotrexate causes malformations, the authors concluded this drug should be avoided altogether during 

pregnancy. 

The second article reviewed antineoplastic drugs used in the treatment of hematological tumors [Azim et 

al. 2010b]. In contrast to the drugs used to treat solid tumors, those used to treat hematological tumors 

were significantly associated with both miscarriages and fetal malformations when administered during 

the first trimester. Patients treated with imatinib during the first trimester but not the second were at high 

risk of fetal malformations. Daunorubicin and idarubicin have been associated with a high incidence of 

fetal malformations even when administered after the first trimester, and therefore they should be 

avoided throughout pregnancy. 

The third review article [Selig et al. 2012] evaluated the adverse reproductive effects of single-agent and 

combination therapy and reported outcomes similar to those of Azim [2010 a,b]. They reported that the 

antimetabolites and alkylating agents had the highest rates of adverse pregnancy outcomes in 

comparison with mitotic inhibitors and antibiotics. Findings about single-agent exposures were mixed, 

perhaps due to small sample sizes, but Selig et al. noted that exposure of the fetus during the first 

trimester was most critical. A recent report by the National Toxicology Program [NTP 2013] provides a 

comprehensive summary of the effects of some antineoplastic drugs on reproductive outcomes in 

patients. This report also briefly addresses occupational exposure to these drugs and possible adverse 

reproductive outcomes in healthcare workers. A large number of antineoplastic drugs are available for 

treatment of cancer and other diseases, and data are not available for all drugs regarding adverse 

reproductive effects. However, most of these drugs have an adverse effect―especially resulting in 
21 

miscarriages―when given during the first trimester, particularly during the first 2−3 weeks of 

pregnancy. 

In summary, data from studies of patients being treated for cancer indicate that the first trimester is the 

most vulnerable time for exposure to result in adverse effects such as miscarriage and birth defects. This 

finding is supported by the recent study [Lawson et al. 2012] of occupational exposures among nursing 

personnel, which showed a stronger association of exposure to antineoplastic drugs with first-trimester 

miscarriages than with second-trimester miscarriages. However, as mentioned above, some drugs such 

as methotrexate, daunorubicin, and idarubicin might also have an effect on the fetus during the second 

and third trimesters. Post-marketing reports of adverse reproductive effects in patients and their 

offspring can often be found in the drug package inserts and the SDSs. 

Patients Treated with Hazardous Drugs Other Than Antineoplastic Drugs

Although the occupational studies listed in Table 1 dealt with antineoplastic drugs used to treat cancer, 

NIOSH has identified hazardous drugs that are used to treat noncancerous conditions [NIOSH 2004; 

2014]. Many of these drugs are reproductive hazards and are classified as FDA Pregnancy Category D 

or X (Appendix 2). Some examples of adverse reproductive effects in patients treated with hazardous 

drugs other than antineoplastic drugs include the following: 

 Thalidomide, though now used as a cancer treatment, has caused severe birth defects or fetal 

death following treatment of pregnant women for morning sickness. It is now available only 

under a restricted distribution program in order to prevent fetal exposure [Shahab and Doll 

2008]. 

 Diethylstilbestrol (DES), also commonly used in veterinary medicine, has been associated with 
22 

an increased risk of breast cancer in women who took this drug and is linked to breast, vaginal, 

and cervical cancers in the daughters of women who took it during their pregnancies [Hatch et al. 

1998; Palmer et al. 2002]. Adverse effects, including increased rates of testicular cancer in male 

offspring of treated mothers, have also been reported [Strohsnitter and Noller 2001]. 

 The anti-seizure medication valproic acid and products containing valproic acid are associated 

with increased risk of major malformations, including neural tube defects, when taken during 

pregnancy. In addition, children of mothers who took one of these drugs during pregnancy have 

an increased risk of low cognitive test scores [Garry and Truran 2011]. 

 When Paxil, an antidepressant, is taken during the first trimester, there is evidence of increased 

risk of birth defects, particularly heart defects [GlaxoSmithKline 2011]. 

 Ribavirin, an antiviral drug administered via nebulizer, can cause harm or death to the fetus in 

women taking it when they become pregnant. Fetal harm or death may also occur if the father 

was taking it when his partner became pregnant. Thus, for both men and women taking ribavirin, 

there are warnings against pregnancy. Two forms of birth control are required for both men and 

women, along with monthly pregnancy tests for women taking ribavirin and for female partners 

of men during treatment. The pregnancy tests must continue for 6 months after treatment [Merck 

Sharp & Dohme 2003]. 

 Finasteride, a drug used to treat benign prostatic hypertrophy, can be absorbed through the skin. 

If the film coating of the tablet has been broken or the tablet crushed, it should not be handled by 

a woman who is pregnant or may potentially be pregnant due to the potential risk to the male 

fetus [Merck Sharp & Dohme 2014]. 

Healthcare	Workers	Exposed	to	Hazardous	Drugs	

Exposure to Antineoplastic Drugs
23 

An extensive review of the literature linking occupational exposure to antineoplastic drugs and adverse 

reproductive effects was conducted through February 2014 using the databases as listed in Appendix 4. 

Tables 1-3 include studies of healthcare workers occupationally exposed to antineoplastic drugs and the 

occurrence of adverse reproductive outcomes, including infertility, miscarriages, stillbirths, pregnancy 

outcomes, and congenital malformations. All relevant published studies from the open literature were 

included in this summary. These data were summarized by Connor et al. [2014]. 

 

Table 1 summarizes 8 studies of occupational exposure to antineoplastic drugs and congenital anomalies 

observed in offspring of workers. The primary limitation of these studies is the small sample sizes; five 

of the eight studies had 10 or fewer exposed cases, and all studies had fewer than 20 exposed cases. The 

small sample sizes resulted in several other important limitations. These included a limited ability to 

adjust for confounding; the need to group anomalies that had different etiologies; and wide confidence 

intervals, which reflect poor statistical power. However, of the studies that had more than five exposed 

cases, three showed significantly increased risks associated with exposure [Hemminki et al. 1985; 

McDonald et al. 1988; Peelen et al. 1999], and two showed increased risks that were not statistically 

significant [Skov et al. 1992; Ratner et al. 2010]. The odds ratios of adjusted models ranged from 1.36 

(95% confidence interval, 0.59–3.14) [Skov et al. 1992] to 5.1 (95% confidence interval, 1.1–23.6) 

[Peelen et al. 1999]. A meta-analysis [Dranitsaris et al. 2005] of four studies with exposure periods 

ranging from 1966 to 1985 [Skov et al. 1992; Hemminki et al. 1985; Peelen et al. 1999; McAbee et al. 

1993] reported a crude odds ratio of 1.64 (95% confidence interval, 0.91–2.94) for all congenital 

anomalies combined. Although the preceeding studies suggest an increased risk for congenital 

anomalies with maternal occupational exposure, the limitations and wide confidence intervals make the 

size of the adverse effect uncertain. In addition, studies that reflect current exposure levels are needed, 

because the studies published to date include data that were collected before the year 2000, the majority 
24 

of which were conducted prior to 1985. 

Studies of maternal occupational exposure to antineoplastic drugs and miscarriage are shown in Table 2. 

We identified eight studies of miscarriage, an additional three studies that analyzed combined outcomes 

of miscarriage and stillbirth, four studies of stillbirths, and two studies of tubal pregnancies. The studies 

of miscarriage had mixed results, and three of these studies were limited by small sample sizes (fewer 

than 20 exposed cases). The three largest studies [Stücker et al. 1990; Valanis et al. 1999; Lawson et al. 

2012] showed increased occurrence of miscarriages among women who reported handling antineoplastic 

drugs during the first trimester. Most exposures were among oncology nurses or pharmacists. Other 

studies that did not find statistically significant associations had odds ratios ranging from 0.7 to 2.8. A 

meta-analysis that pooled the results of five studies [Selevan et al. 1985; Stücker et al. 1990; Valanis et 

al. 1999; Skov et al. 1992; Peelen et al. 1999] found an overall adjusted increased risk of 46% among 

exposed workers (95% confidence interval, 11% to 92%) [Dranitsaris et al. 2005]. All studies published 

to date contain data collected before 2002. 

More research is needed to examine the effects of occupational exposure to antineoplastic drugs and 

stillbirth because this is an uncommon outcome and therefore difficult to study. All of the studies of 

stillbirths (or of fetal loss, which combines miscarriage and stillbirth) had insufficient numbers of 

exposed cases (n = 1 to 13), resulting in wide confidence intervals [McDonald 1988; McAbee et al. 

1993; Rogers and Emmet 1987; Dranitsaris et al. 2005; Fransman et al. 2007; Peelen et al. 1999; Valanis 

et al. 1999; Ratner et al. 2010]. We found only two studies of tubal pregnancies, both with 10 or fewer 

exposed cases, and the results varied widely from OR=0.95 (95% CI 0.39-2.31) [Bouyer et al. 1998] to 

OR 11.4 (95% CI 2.7-17.6) [Saurel-Cubizolles et al. 1993]. 
25 

We found only two studies of occupational exposure to antineoplastic drugs and fertility or time to 

pregnancy (Table 3), though the results suggest that exposure to antineoplastic drugs is associated with 

an increased risk of subfertility [Valanis et al. 1997; Fransman et al. 2007]. Only one study evaluated 

menstrual cycle; it showed a statistically significant three-fold increased risk of menstrual cycle 

irregularities from occupational exposure to antineoplastic drugs [Shortridge et al. 1995]. A study of 

Danish oncology nurses showed no statistically significant differences in birth weight, gestational age, 

or sex ratio among exposed mothers [Skov et al 1992], while a study of French oncology nurses found 

the mean birth weight of offspring to be lower than those of unexposed pregnancies [Stücker et al 1993]. 

In summary, although the results of occupational studies vary, they are generally indicative of an 

increased risk of adverse reproductive outcomes with occupational exposure [Connor et al. 2014]. The 

risks seem to be higher with first trimester exposure, though there may still be risks with exposure 

during the second and third trimesters, depending on the specific drug or drugs to which a worker may 

be exposed. While none of these studies were conducted after the release of the NIOSH Alert in 2004, 

more recent studies have documented that workplaces are still contaminated with these drugs [Schierl et 

al. 2009; Connor et al. 2010; Siderov et al. 2010; Yoshida et al. 2010; Davis et al. 2011; Sessink et al. 

2011; Turci et al. 2011; Chu et al. 2012; Polovich and Martin 2011; Kopp et al. 2013] and exposures are 

most likely still occurring. When these data are considered in combination with the results of animal and 

patient studies, strong evidence shows a need for specific guidance for healthcare workers exposed to 

antineoplastic and other hazardous drugs in order to adequately protect the reproductive health of 

workers and their offspring. 

Recommendations
26 

Use	of	Industrial	Hygiene	Practices	to	Reduce	Exposure	to	Hazardous	

Drugs	

NIOSH recommends that a workplace be safe for all workers, regardless of their reproductive status, 

including workplaces where hazardous drugs are present. Recommendations to protect workers from 

occupational exposure to hazardous drugs have been developed by several organizations [OSHA 1999; 

NIOSH 2004; ASHP 2006; USP 2008; ONS 2011]. In general, they all adhere to the hierarchy of controls for standard industrial hygiene practices [Soule 1978]. These recommendations include the proper 

use of engineering controls, administrative controls, and personal protective equipment [NIOSH 2009]. 

In addition, training of personnel and other critical work practices are instrumental in protecting workers 

from exposure [NIOSH 2004, 2013]. However, NIOSH recognizes that current work practices do not 

completely eliminate hazardous drug contamination from the workplace, and therefore worker exposure 

to these drugs can occur. As noted above, several recent studies have added to the wealth of earlier information on workplace contamination with antineoplastic drugs. Therefore, employers should use and 

maintain the most up-to-date engineering controls and follow current recommendations in order to reduce as much as possible or eliminate worker exposure to hazardous drugs. These include recommendations from NIOSH, OSHA, ASHP, ONS, USP and other professional organizations. Additional information on adverse reproductive effects of these drugs can be found in the drug package inserts and in the 

SDS for the drugs. However, on the basis of recent studies of workplace contamination, current engineering controls and other precautions do not completely eliminate the potential for worker exposure 

and thus may not be enough to protect vulnerable offspring of male and female workers who handle 

these drugs. 

Implementation	of	an	Alternative	Duty	or	Temporary	Reassignment
27 

Program	

Given that a developing fetus and a newborn infant are uniquely vulnerable to certain hazardous drugs, 

especially antineoplastic drugs, because they are rapidly developing and their metabolic, detoxification 

and excretion processes are immature, and given the potentially devastating impact of such exposures, it 

is reasonable to take extra precautions to protect them [Gonzalez 2011]. One such additional precaution 

is to offer employees who are pregnant, breast-feeding, or actively trying to conceive the option of alternative duty. Alternative duty does not mean the worker is excused from work. It does suggest some reassignment of duties, often within the same job, to avoid handling hazardous drugs. For example, various nursing or pharmacy duties can be redistributed among a team of workers, or the organization of 

work can be altered to allow those needing reassignment to still work in many aspects of their jobs. In 

some instances, however, a true temporary position re-assignment might be necessary to avoid exposure 

to hazardous drugs. 

It is estimated that 68% of working women will become pregnant at least once during their working life 

[Cleveland et al. 2000]. Two-thirds of women work during their first pregnancy, and more than half 

(55%) of all births are to working women [U.S. Census Bureau 2010]. Beyond the benefits to the health 

of workers and their offspring, providing accommodations to expectant and nursing workers may reduce 

turnover and increases morale and productivity. 

NIOSH reviewed existing policies from several professional and government organizations that have 

recommendations for alternative duty or temporary reassignment for healthcare workers who may be at 

risk of exposure to hazardous drugs during critical times in reproduction (Appendix 5). Typically, these 

include times when couples (males and females) are actively trying to conceive and when women are 

pregnant and/or breastfeeding. However, conception can be a difficult issue to deal with because approximately 50% of all pregnancies are not planned [Finer and Zolna 2006]. Temporary reassignment 
28 

should also be considered when an individual’s medical history or risk factors suggest a need for requesting reassignment from working with hazardous drugs based on personal fertility history and any 

other underlying medical conditions that may put a worker at exceptional risk of harm [ACOEM 2011]. 

The majority of these policies indicate that the employer should offer alternative duty and that the worker’s decision to accept it should be voluntary. Since 1995, OSHA has recommended that healthcare facilities have a policy in place regarding reproductive risks associated with occupational exposure of 

workers to hazardous drugs and that such a policy should be followed [OSHA 1999]. Some recommendations state that an initial risk assessment should be performed in order to determine if there is potential 

reproductive harm to the fetus or offspring [HSE 2003; ACOEM 2011]. However, because there are no 

established permissible exposure limits (PELs) or other guidance values for these drugs [NIOSH 2004], 

a complete risk assessment is usually not possible. Nonetheless, workers potentially at risk may be identified by an exposure assessment. In some cases, workers (such as pharmacy personnel, nursing personnel, and housekeeping and waste disposal personnel) may be identified as at-risk on the basis of their job 

classification, indicating their duties may potentially expose them to hazardous drugs. An exposure assessment may also identify other workers with potential exposure, since studies have shown that wherever hazardous drugs are present in a healthcare facility, environmental contamination is common. 

After carefully reviewing animal studies, human studies of patients and workers, and the properties of 

hazardous drugs that provide clues about the mechanistic plausibility of reproductive risk from exposure, NIOSH recommends that healthcare workplaces where antineoplastic and other hazardous drugs 

are present have a policy for alternative duty for exposed workers who are a reproductive risk [Figure 1]. 

An alternative-duty or temporary-reassignment program typically includes the following elements: 

 Identifying drugs in the workplace with potential adverse reproductive effects. 

 Identifying job functions or tasks that present a potential for exposure to reproductive hazards. 
29 

 Conduct an initial risk assessment for the drugs being used. 

 Identifying job functions or tasks that can be safely performed by workers requesting alternative 

duty for reproductive issues. 

 Developing new-employee and annual refresher training as part of the management’s hazard 

communication program. Training should help healthcare workers identify their potential for exposure during their windows of risk. During training, workers should be informed that windows 

of vulnerability to developmental health typically begin before fertilization or before a pregnancy 

is recognized, thus necessitating the provision of alternative duty during or before actively trying 

to conceive. 

 Developing mechanisms by which workers who are actively trying to conceive, who are pregnant, or who are breast-feeding can request alternative duty or reassignment. 

 Workers should be encouraged to notify their employer of their request for reassignment before their 

window of risk, or as soon as possible once risk is recognized, with the understanding that such information is confidential. The notification should be done through the employee health unit. If this is not 

feasible, then notification should be made through their immediate supervisor. 

Medical, Legal and Ethical Issues

The development and implementation of policies for protection of reproductive health involve complex 

issues related to both science and law. Safety from reproductive hazards and freedom from discrimination on the basis of gender or pregnancy can appear to present conflict or appear intrusive into personal 

areas of an employee’s reproductive and health status. When a worker requests alternative duty, confidential information and matters of the employee’s privacy might become known in the workplace [Saiki 

et al. 1994]. Because of the legal implications of requests for special accommodations during pregnancy, 
30 

several states have adopted laws that require employers to provide at least some accommodations if requested. 

The 1978 Pregnancy Discrimination Act amended Title VII of the Civil Rights Act to include the wording “because of or on the basis of pregnancy, childbirth, or related medical conditions” in reference to 

unlawful employment practices that “...in any way...would deprive or tend to deprive any individual of 

employment opportunities or otherwise adversely affect his [sic] status as an employee...” A woman or 

man cannot be denied employment or be removed from employment because of her or his reproductive 

status. If an employer provides alternative duty on the basis of reproductive status in order to limit 

workers’ exposure to hazardous drugs, then the policy will not violate Title VII as long as employees 

retain the right to remain in their positions if they choose. 

It is important that alternative duty or other workplace policies intended to protect workers and their offspring do so in a manner that does not discriminate against workers on the basis of gender or other protected characteristics. Forcing an employee to accept alternative duty on the basis of gender or pregnancy is unlawful; alternative duty policies should therefore be voluntary. Employers may offer voluntary 

alternative duty on the basis of reproductive status, even if alternative duty is not offered to other employees with temporary disabilities. Offering this type of accommodation should not be seen as an admission on the part of an employer of dangerous conditions in the workplace. Rather, offering the option 

for alternative duty should be seen as evidence of the employer’s commitment to doing everything possible to assure the well-being of workers and their families. Reassigned workers should retain wages, 

seniority, and other benefits that might otherwise be lost by a job transfer and should not be discriminated against on the basis of their job status. 

In preparing an alternative duty policy, it is important to consider both male and female reproduction 

issues equally. Alternative duty policies should protect the reproductive capacity and offspring of both 
31 

male and female workers, although the appropriate type and timing of accommodations may vary. 

	Summary	

The primary limitation of the studies we evaluated is the era of the data collection; all studies published 

to date evaluate data collected prior to 2002, and most data were collected in the 1980’s. Though there 

has been a lot of attention recently to raise awareness of controlling occupational exposure to antineoplastic and other hazardous drugs, studies continue to show that exposures are still occurring. Another 

important limitation of the literature is the small sample sizes, particularly the small numbers of exposed 

cases. Because of this limitation, studies were often unable to adjust for confounding factors and reported wide confidence intervals. However, most of the studies we reviewed that had larger relative sample 

sizes indicated an increased risk of adverse reproductive health outcomes. Though there are few studies 

of fertility, there appears to be an indication of a risk with exposure. Finally, most studies lacked enough 

statistical power or proper exposure assessment to evaluate dose. 

Considering the biologic plausibility of the mechanisms of action of many hazardous antineoplastic 

drugs, and observations of adverse reproductive and developmental health outcomes observed in treated 

cancer patients, this review suggests, fairly consistently, that there are also elevated risks to reproductive 

health for exposed workers. Workplace contamination studies indicate that hazardous drug exposure is 

widespread, commonly occurring during any handling activity, despite use of current safety guidance. 

Therefore, additional precautions to prevent exposure during uniquely vulnerable windows of fetal and 

newborn development should be considered. 
32 

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Table 1. Studies of Congenital Anomalies Associated with Parental Occupational Exposure to Antineoplastic DReference Exposure

Period

StudyLocation

Population Study

Design

OverallSampleSize

Number of

exposedcases

Results Comments

Fransman etal. 2007

1990–1997 Netherlands Oncology

& other

types of nurses

Survey 1,519 5 in highest expo‐

sure category

No significant

associations; CIs

were wide

Retrospective exposu

on frequency of task

sure. No evidence of 

Hemminki etal. 1985

<1985 Finland Finnish hospital

nurses

Case–control;

survey

38 cases; 99

controls

19 Adj OR, 4.7 (1.2–

18.1)

11 exposed cases ha

expo cases handled o

McAbee et al.

1993

1985 US Nurses and uni‐

versity employ‐

ees

Cross‐sectionalsurvey

633 women

(1,133 preg‐nancies)

10 Oncology nurses

reported more

birth defectsthan the control

group (p = 0.02

for crude analy‐

sis).

Response rate was 3

cies separately from 

McDonald et

al. 1988

1982–1984 Montreal Population

based; doctorsand nurses

Survey 152 exposed

pregnancies

8 8/4 = observed /

expected

Used medical record

Peelen et al.

1999

<1985 Netherlands Oncology nurses Survey 229 exposed +

956 unexposed

7 OR, 5.1 (1.1–

23.6) amongnurses whoprepared haz‐ardous drugs

Had to work in oncol

during pregnancy

Ratner et al.2010

1974–2000 Canada Registered nurses Survey; regis‐

try

12,741 17 Adj OR, 1.42

(0.86–2.36)

Based on RNs who w

in oncology

Skov et al.

1992

1985 Denmark Oncology nurses Retrospective

cohort

266 exposed

+770 unex‐posed

16 Adj OR, 1.36

(0.59–3.14) in

highest exposure

category

Prepared or administ

ing pregnancy

Lorente et al.

2000

1989–1992 Europe Population‐based Case–control 64 cleft lip /

palate + 36cleft palate +

751 controls

3 Cleft lip: OR,

3.35 (0.37–3.12);Cleft palate: OR,

11.25 (1.98–

63.7)

CIs were wide.

*Previously published. Connor et al. 2014
Table 2. Studies of Miscarriage, Stillbirth, Tubal Pregnancy Associated with Occupational Exposure to AntinReference Exposure

Period

StudyLocation

Population Study De‐

sign

OverallSampleSize

Number of

exposed cas‐es

Results Comments

Fransman etal. 2007

1990–1997 Netherlands Oncology and

other types of

nurses

Survey 1,519 34, but divided

into 3 categories

No significant

associations; CIs

were wide for

miscarriage

Small numbers in cat

not clearly reported. 

assessment among n

Hemminki etal. 1985

<1985 Finland Finnish hospital

nurses

Case‐control 169 cases + 469

controls

12 Adj OR, 0.8 (0.3–

1.7) for miscar‐

riage

50% Response rate

Lawson et al.

2012

1993–2001 U.S. U.S. registered

nurses

Survey 775 cases +

6,707 live births

48 Adj OR, 1.94

(1.32–2.86) for

miscarriage

Peelen et al.

1999

<1985 Netherlands Oncology nurs‐

es

Survey 249 exposed +

1,010 unex‐

posed

Unclear OR, 1.4 (0.8–2.6)

for miscarriage

Small numbers, limit

Fransman study that 

Selevan et al.

1985

<1985 Finland Nurses Case–control 124 cases +321

controls

18 OR, 2.3 (1.21–

4.39) for miscar‐

riage

First‐trimester expos

more than once per w

Skov et al.

1992

1985 Denmark Oncology nurs‐

es

Retrospective

cohort

281 exposed +809 unexposed

18 Adj OR, 0.74

(0.40–1.38) for

miscarriage

Prepared or administ

time during pregnan

Stücker et al.

1990

1985 France Hospital per‐

sonnel

Survey 139 exposed

+357 unex‐posed

36 Adj OR, 1.7

(1.03–2.80) formiscarriage

Prepared hazardous 

Valanis et al.

1999

1985 U.S. Nurses and

pharmacists

Survey 1,448 exposed

+ 5,297 unex‐

posed

223 Adj OR, 1.50

(1.25–1.80) for

miscarriage

Exposure to hazardo

McDonald et

al. 1988

1982–1984 Montreal Population

based

In‐person sur‐

vey

22,613 13 13 observed

/13.4 expected

miscarriages andstillbirths

Administered hazard

mester

McAbee et al.

1993

1985 U.S. Nurses and

universityemployees

Cross‐sectional

survey

663 women

(1,133 preg‐

nancies)

3 Adj OR of 0.67

for miscarriage

and stillbirth

Low response rates (

Rogers andEmmett 1987 <1985 U.S.

Oncology andcommunityhealth nurses

Survey 233 13 OR, 2.5 (p < 0.04)

for miscarriage

and stillbirth

OR didn’t change wit
Fransman etal. 2007

1990–1997 Netherlands Oncology &

other types of

nurses

Survey 1,519 1 in the highest

category

No significantassociations; CIs

were wide for

stillbirth

Retrospective exposu

of tasks, dermal expo

Peelen et al.

1999

1990–1997 Netherlands Oncology nurs‐

es

Survey 249 exposed +

1,010 unex‐

posed

2 OR, 1.2 (0.65–

2.20) for still‐

birth

Small numbers

Valanis et al.

1999

1985 U.S. Nurses and

pharmacists

Survey 7,094 12 Adj OR, 1.10

(0.55–2.20) forstillbirth

Ratner et al.2010

1974–2000 Canada Registered

nurses

Cohort 147/23,222 3 Adj OR, 0.67

(0.21–2.13) forstillbirth

Bouyer et al.1998

1993–1994 France Hospital per‐

sonnel

Case‐–control 104 cases/

279 controls

10 Adj OR, 0.95

(0.39–2.31) fortubal pregnancy

Studied only preconc

of Saurel‐Cubizolles 1

adjusted; included pr

were wide question.

Saurel‐Cubizolles etal. 1993

1985 Paris Hospital nurses Self‐

administered

survey

85 exposed and

599 unexposed

6 Adj OR, 11.4

(2.7–17.6) for

tubal pregnancy

Exposure to hazardo

mester. See Bouyer u

*Previously published. Connor et al. 2014
Table 3. Studies of Fertility, Time to Pregnancy, Menstrual Function, Birthweight, Gestational Age, and Sex Rwith Occupational Exposure to Antineoplastic Drugs*Reference Exposure

Period

StudyLocation

Population Study De‐

sign

OverallSampleSize

Number of

exposed cas‐es

Results Comments

Valanis et al.

1997

<1985 U.S. Nurses and

pharmacypersonnel

Case‐ control 405 cases+ 1,215

controls

78 OR, 1.5 (1.1–2.0)

for infertility

Fransman etal. 2007

1990–1997 Netherlands Oncology and

other types of

nurses

Survey 126 26 in highest

category

Hazard ratio, 0.8

(0.6–‐0.9) for

time to pregnan‐

cy

Retrospective exposu

nurses

Shortridge et

al. 1995

1986 U.S. ONS and ANA

members

Survey 1,458 172 Adj OR, 3.4 (1.6–

7.3) for men‐

strual dysfunc‐

tion among

nurses whoadministeredchemotherapy

Menstrual dysfunctio

following: a) 3+ mon

length of <25 or >31 

<2 or >7 days

Skov et al.

1992

1985 Denmark Oncology nurs‐

es

Retrospective

cohort

266 exposed /

770 unexposed

266 No statistically

significant differ‐

ences in adjustedanalyses be‐

tween exposedand unexposedfor birthweight,

gestational age,or sex ratio

Stücker et al.

1993

1985–1986 France Oncology nurs‐

es

Survey 420 Singleton live

births

107 exposed

pregnancies

In adjusted

models, meanbirthweight of

exposed preg‐nancies was 56 g

lower than un‐

exposed (95% CI,

minus 155.1 to

43.1)

No difference in gest

posed and unexpose

*Previously published. Connor et al. 2014 Abbreviations used: OR-odds ratio; AdOR-adjusted odds ratio; CI-confidence interval 

Appendix 1. Hazardous Drug (HD) Handling Activities in Healthcare Workers that can Result in Exposure Workers Potentially Exposed Activity Pharmacists, pharmacy technicians  Handling drug-contaminated vials 

 Reconstituting powdered or lyophilized drugs and fu

reconstituted powder or concentrated liquid forms of haz

 Expelling air from syringes filled with hazardous drugs  Compounding HD powders into custom-dosage forms  Transferring drug solution to IV bag or bottle. 

Pharmacists, pharmacy technicians, nursing personnel 

 Counting out individual, uncoated oral doses from multi Unit-dosing uncoated tablets in a unit-dose machine  Crushing tablets or opening capsules to make oral liquid  Opening ampoules  Preparing topical drugs 

Nursing personnel  Administering antineoplastic drugs by injection (intram

intravenous (IV)), by inhalation or by nasogastric tube 

 Spiking the IV set into an HD-containing IV bag (witho
 Priming the IV set with a drug-containing solution at the  Connecting and disconnecting the IV set to an IV pump 

Nursing personnel, support staff, housekeeping personnel, laundry personnel 

 Handling body fluids or body-fluid-contaminated clo

bedpans, urinals and other materials 

 Handling contaminated wastes generated at any ste

administration process 

Pharmacists, pharmacy technicians, nursing personnel, housekeeping personnel, environmental services personnel 

 Contacting hazardous drugs present on drug vial exterio

and final drug products (bottles, bags, cassettes, and syri

 Handling unused antineoplastic drugs or antineoplastic d Decontaminating and cleaning drug preparation or clinic

 Cleaning hazardous drug spills 

Physicians, nursing personnel, operating room personnel 

 Performing certain specialized HD administratio

intraperitoneal chemotherapy (in the operating room or instillation, isolated limb perfusion 

Support staff  Transporting hazardous throughout the facility Nursing personnel, housekeeping personnel, waste disposal personnel 

 Transporting hazardous waste containers 

Pharmacists, pharmacy technicians, nursing  Removing and disposing of personal protective e
personnel, housekeeping personnel hazardous drugs or waste 
Appendix 2. FDA Pregnancy Categories of Drugs Listed by NIOSH as Hazardous1Drugs that Should be Handled as Hazardous FDA Pregnancy 

Category2

AHFS Pharmacologic-Therapeutic Classification2

Abacavir C 8:18.08.20 Nucleoside and reverse transcriptase inhibitors Abiraterone X 10:00 Antineoplastic agents Acitretin X 88:04 Vitamin A Ado-trastuzumab emtansine D 10:00 Antineoplastic agents Ambrisentan X 24:12.92 Vasodilating agents, miscellaneous Alefacept B 84:92 Skin and mucous membrane agents, miscellaneous Alitretinoin D 84:92 Skin and mucous membrane agents, miscellaneous Altretamine D 10:00 Antineoplastic agents Anastrozole X 10:00 Antineoplastic agents Apomorphine C 28:36.20.08 Nonergot-derivative dopamine receptor 

agonists 

Arsenic trioxide D 10:00 Antineoplastic agents Azacitidine D 10:00 Antineoplastic agents Azathioprine D 92:44 Immunosuppressant agents Bacillus Calmette-Guerin (BCG) 

C 80:12 Vaccines 

Bendamustine D 10:00 Antineoplastic agents Bexarotene X 10:00 Antineoplastic agents Bicalutamide X 10:00 Antineoplastic agents Bleomycin D 10:00 Antineoplastic agents Bortezomib D 10:00 Antineoplastic agents Bosentan X 24:12.92 Vasodilating agents, miscellaneous Brentuximab vedotin D 10:00 Antineoplastic agents Busulfan D 10:00 Antineoplastic agents Cabazitaxel D 10:00 antineoplastic agents 
Cabergoline B 28:36. 20.04 Ergot-derivative dopamine receptor agonistsCapecitabine D 10:00 Antineoplastic agents Carbamazepine D 28:12.92 Anticonvulsants, miscellaneous Carboplatin D 10:00 Antineoplastic agents Carmustine D 10:00 Antineoplastic agents Cetrorelix X 92:40 Gonadotropin-releasing hormone antagonists Chlorambucil D 10:00 Antineoplastic agents Chloramphenicol C 8:12.08 Chloramphenicols Choriogonadotropin alfa X 68:18 Gonadotropins Cidofovir C 8:18.32 Nucleosides and nucleotides Cisplatin D 10:00 Antineoplastic agents Cladribine D 10:00 Antineoplastic agents Drugs that Should be Handled as Hazardous (Continued)

FDA Pregnancy Category

AHFS Pharmacologic-Therapeutic Classification

Clofarabine D 10:00 Antineoplastic agents Clonazepam D 28:12.08 Benzodiazepines Colchicine C 92:16 Antigout agents Crizotinib D 10:00 Antineoplastic agents Cyclophosphamide D 10:00 Antineoplastic agents Cyclosporin C 92:44 Immunosuppressive agents Cytarabine D 10:00 Antineoplastic agents Dacarbazine C 10:00 Antineoplastic agents Dactinomycin D 10:00 Antineoplastic agents Dasatinib D 10:00 Antineoplastic agents Daunorubicin D 10:00 Antineoplastic agents Decitabine D 10:00 Antineoplastic agents Deferiprone D 64:00 Heavy metal antagonists Degarelix X 10:00 Antineoplastic agents Dexrazoxane C 92:56 Protective agents Diethylstilbestrol X Not in AHFS (nonsteroidal synthetic estrogen) 
Dinoprostone C 76:00 Oxytocics Docetaxel D 10:00 Antineoplastic agents Doxorubicin D 10:00 Antineoplastic agents Dronedarone X 20:04.04 Antiarrythmics Dutasteride X 92:08 5-alpha reductase inhibitors Entecavir C 8:18.32 Nucleosides and nucleotides Epirubicin D 10:00 Antineoplastic agents Eribulin D 10:00 Antineoplastic agents Erlotinib D 10:00 Antineoplastic agents Ergonovine/ methylergonovine 

C 76:00 Oxytocics 

Estradiol X 68:16.04 Estrogens Estramustine X 10:00 Antineoplastic agents Estrogen-progestin combinations X 68:12 Contraceptives Estrogens, conjugated X 68:16.04 Estrogens Estrogens, esterified X 68:16.04 Estrogens Estropipate X 68:16.04 Estrogens Etoposide D 10:00 Antineoplastic agents Everolimus X 10:00 Antineoplastic agents Exemestane D 10:00 Antineoplastic agents Finasteride X 92:08 5-alpha reductase inhibitors Fingolimod C 92:20 Biologic response modifiers 
Drugs that Should be Handled as Hazardous (Continued)

FDA Pregnancy Category

AHFS Pharmacologic-Therapeutic Classification

Floxuridine D 10:00 Antineoplastic agents Fluconazole C 8:18.08 Azoles Fludarabine D 10:00 Antineoplastic agents Fluorouracil D/X3 10:00 Antineoplastic agents Fluoxymesterone X 68:08 Androgens Flutamide D 10:00 Antineoplastic agents Fosphenytoin D 28:12.12 Hydantoins Fulvestrant D 10:00 Antineoplastic agents Ganciclovir C 8:18.32 Nucleosides and nucleotides Ganirelix X 92:40 Gonadotropin-releasing hormone antagonists Gemcitabine D 10:00 Antineoplastic agents Gemtuzumab ozogamicin D 10:00 Antineoplastic agents Gonadotropin, chorionic X 68:18 Gonadotropins Goserelin X 10:00 Antineoplastic agents Hydroxyurea D 10:00 Antineoplastic agents Icatibant C 92:32 Complement inhibitors Idarubicin D 10:00 Antineoplastic agents Ifosfamide D 10:00 Antineoplastic agents Imatinib D 10:00 Antineoplastic agents Irinotecan D 10:00 Antineoplastic agents Ixabepilone D 10:00 Antineoplastic agents Leflunomide X 92:36 Disease-modifying antirheumatic agents Lenalidomide X 92:20 Biologic response modifiers Letrozole X 10:00 Antineoplastic agents Leuprolide X 10:00 Antineoplastic agents Liraglutide recombinant C 68:20.06 Incretin mimetics Lomustine D 10:00 Antineoplastic agents Mechlorethamine D 10:00 Antineoplastic agents Medroxyprogesterone X 68:32 Progestins 
acetate Megestrol X 10:00 Antineoplastic agents Melphalan D 10:00 Antineoplastic agents Menotropins X 68:18 Gonadotropins Mercaptopurine D 10:00 Antineoplastic agents Methotrexate X 10:00 Antineoplastic agents Methyltestosterone X 68:08 Androgens Mifepristone X 76:00 Oxytocics 
Drugs that Should be Handled as Hazardous (Continued)

FDA Pregnancy Category

AHFS Pharmacologic-Therapeutic Classification

Misoprostol X 56:28.28 Prostaglandins Mitomycin D 10:00 Antineoplastic agents Mitotane D 10:00 Antineoplastic agents Mitoxantrone D 10:00 Antineoplastic agents Mycophenolate mofetil D 92:44 Immunosuppressive agents Mycolphenolic acid D 92.44 Immunosuppressive agents Nafarelin X 68:18 Gonadotropins Nelarabine D 10:00 Antineoplastic agents Nevirapine B 8:18.08.16 Nonnucleoside reverse transcriptase inhibitors Nilotinib D 10:00 Antineoplastic agents Omacetaxin D 10:00 Antineoplastic agents Oxaliplatin D 10:00 Antineoplastic agents Oxcarbazepine C 28:12.92 Anticonvulsants. Miscellaneous Oxytocin C 76:00 Oxytocics Paclitaxel D 10:00 Antineoplastic agents Palifermin C 84:16 Cell stimulants and proliferants Paroxetine D 28:16.04.20 Selective seretonin uptake inhibitors Pazopanib D 10:00 Antineoplastic agents Pemetrexed D 10:00 Antineoplastic agents Pentetate calcium trisodium C Not in AHFS Pentostatin D 10:00 Antineoplastic agents Phenoxybenzamine C 12:16.04.04 Non-selective alpha-adrenergic blocking 

agents 

Phenytoin D 28:12.12 Hydantoins Plerixafor D 20:16 Hematopoietic agents Pralatrexate D 10:00 Antineoplastic agents Procarbazine D 10:00 Antineoplastic agents Progesterone B 68:32 Progestins 
Progestins X 68:12 Contraceptives Propylthiouracil D 68:36.08 Antithyroid agents Raloxifene X 68:16.12 Estrogen agonists-antagonists Rasagiline C 28:36 Antiparkinsonian agents Ribavirin X 8:18.32 Nucleosides and nucleotides Risperidone C 28:16.08.04 Atypical antipsychotics Romidepsin D 10:00 Antineoplastic agents Sirolimus C 92:44 Immunosuppressive agents Sorafenib D 10:00 Antineoplastic agents 
Drugs that Should be Handled as Hazardous (Continued) FDA Pregnancy Category AHFS Pharmacologic-Therapeutic ClassificationSpironolactone C 24:32.20 Mineralocorticoid receptor antagonists Streptozocin D 10:00 Antineoplastic agents Sunitinib D 10:00 Antineoplastic agents Tacrolimus C 92:44 Immunosuppressive agents Tamoxifen D 10:00 Antineoplastic agents Televancin C 8:12.28.16 Glycopeptides Temozolomide D 10:00 Antineoplastic agents Temsirolimus D 10:00 Antineoplastic agents Teniposide D 10:00 Antineoplastic agents Testosterone X 68:08 Androgens Thalidomide X 92:20 Biologic response modifiers Thioguanine D 10:00 Antineoplastic agents Thiotepa D 10:00 Antineoplastic agents Topiramate D 28:12.92 Anticonvulsants, miscellaneous Topotecan D 10:00 Antineoplastic agents Toremifene D 10:00 Antineoplastic agents Tretinoin C/D3 84:16 Cell stimulants and proliferants Triptorelin X 10:00 Antineoplastic agents Ulipristal X 68:12 Contraceptives Uracil mustard D N/A Valganciclovir C 8:18.32 Nucleosides and nucleotides Valproic acid/divalproex Na D 28:12.92 Anticonvulsants. Miscellaneous Valrubicin C 10:00 Antineoplastic agents Vandetanib D 10:00 Antineoplastic agents Vemurafenib D 10:00 Antineoplastic agents Vigabatrin C 28:12.92 Antinconvulsants, miscellaneous Vinblastine sulfate D 10:00 Antineoplastic agents Vincristine sulfate D 10:00 Antineoplastic agents Vinorelbine tartrate D 10:00 Antineoplastic agents 
Voriconazole D 8:14.08 Azoles 

Vorinostat D 10:00 Antineoplastic agents Warfarin D 20:12.04.08 Coumarin derivatives Zidovudine C 8:18:08 Antiretroviral agents Ziprasidone HCl C 28:16.08.04 Atypical antipsychotics Zoledronic acid D 92:24 Bone resorption inhibitors Zonisamide C 28:12.92 Anticonvulsant, miscellaneous 

1NIOSH 2014 2ASHP/AHFS 2012 3Varies with formulation 
Appendix 3. FDA-Assigned Pregnancy Categories1FDA Pregnancy Category Description A Adequate and well-controlled studies have failed to demonstrate a risk to the fetus in 

trimester of pregnancy (and there is no evidence of risk in later trimesters). 

B Animal reproduction studies have failed to demonstrate a risk to the fetus and there a

adequate and well-controlled studies in pregnant women. 

C Animal reproduction studies have shown an adverse effect on the fetus and there are 

quate and well-controlled studies in humans, but potential benefits may warrant use 

drug in pregnant women despite potential risks. 

D There is positive evidence of human fetal risk based on adverse reaction data from in

tional or marketing experience or studies in humans, but potential benefits may warrof the drug in pregnant women despite potential risks. 

X Studies in animals or humans have demonstrated fetal abnormalities and/or there is p

evidence of human fetal risk based on adverse reaction data from investigational or ming experience, and the risks involved in use of the drug in pregnant women clearly opotential benefits. 

1Briggs et al. 2008; 21 CFR 201.57(c)(9)(i) 
Appendix 4. Databases reviewed: Canadiana, CINAHL, CISILO, DTIC, Embase, Health & Safety Science NIOSHTIC-2, NTIS, OSHLine, PubMed, Risk Abstracts, Toxicology Abstracts, Toxline, Web of S

PubMed search terms: Antineoplastic agents/adverse effects, antineoplastic agents/prevention an

Hazardous Substances/adverse effects, Hazardous Substances/toxicity, Pharmaceutical Preparaantineoplastic, cytotoxic, cytostatic, chemotherap*, and Personnel, Hospital, Health Personnel, an

sure, Occupational Diseases, Environmental Exposure, occupational, and Reproduction, Infertility

Complications, pregnan*, infertility, reproducti*. In addition, the following terms were includantineoplastic , chemotherapeutic, cytotoxic, cytostatic, pregnan*, infertility, reproducti*, and occup
Appendix 5. Reproductive Health Recommendations for Alternative Duty PracticesOrganization and Topic Reproductive Health RecommendationsNational Study Commission on Cytotoxic Exposure. Recommendations for Handling Cytotoxic Agents [1987]. 

There are substantial data regarding the mutagenic, teratogenic, and abortifacient pro

certain cytotoxic agents, both in animals and in humans who have received therapeut

these agents. Additionally, the scientific literature suggests a possible association of otional exposure to certain cytotoxic agents during the first trimester of pregnancy witor malformation. These data suggest the need for caution when women who are pregattempting to conceive, handle cytotoxic agents. . . . it is prudent that women who are feeding should exercise caution in handling cytotoxic agents. . . . Personnel should be 

with information to make an individual decision. This information should be provideten form and it is advisable that a statement of understanding be signed. . . . It is esse

refer to individual state right-to-know laws to ensure compliance. 

European Agency for Safety and Health at Work [1992]. Directive 92/85/EEC: pregnant workers. 

Pregnant and breastfeeding workers may under no circumstances be obliged to perforfor which the assessment has revealed a risk of exposure to agents, which would jeoptheir safety or health. Those agents and working conditions are defined in Annex II orective. Women must not be dismissed from work because of their pregnancy and maternity friod from the beginning of their pregnancy to the end of the period of leave from wor

Occupational Safety and Health Administration (OSHA). OSHA Technical Manual, TED 1−0.15A, Sec 

VI Chapter 2: Categorization of drugs as hazardous. 

The examining physician should consider the reproductive status of employees and inthem regarding relevant reproductive issues. The reproductive toxicity of hazardous d

should be carefully explained to all workers who will be exposed to these chemicals, action] is required for those chemicals covered by the HCS [hazard communication sUnfortunately, no information is available regarding the reproductive risks of HD [hadrug] handling with the current use of BSCs [biological safety cabinets] and PPE [pe

protective equipment]. However, as discussed earlier, both spontaneous abortion and 

tal malformation excesses have been documented among workers handling some of twithout currently recommended engineering controls and precautions. The facility sha policy regarding reproductive toxicity of HDs and worker exposure in male and femployees and should follow that policy. 
Health and Safety Executive, United Kingdom (HSE) [2003]. New and expectant mothers at work; a guide to health professionals. 

The law requires every employer to assess workplace risks for all their employees, anpractical action to control those risks. In addition, employers must take particular accrisks to new and expectant mothers. The definition of a new or expectant mother is sowho is pregnant, has given birth within the previous six months, or is breastfeeding. Employers must identify hazards in their workplace that could pose a health or safety new and expectant mother and take appropriate action to remove or reduce the risk. Talso make this information known to all their female employees of childbearing age, those who have informed them they are pregnant. This is particularly important for emothers, as it is possible for the first 4−6 weeks of pregnancy to go undetected. 

If risks are identified go beyond the level of risk found outside the workplace, but canremoved, employers should adjust the woman’s working conditions or hours. If there risk, she must be offered suitable alternative work or, if that is not possible, suspendepay for as long as is necessary to protect her and her child’s health. 

American Society of HealthSystem Pharmacists (ASHP) [1990]. ASHP guidelines on handling hazardous drugs. 

Because reproductive risks have been associated with exposure to hazardous drugs, a

duty should be offered to individuals who are pregnant, breast-feeding, or attempting 

ceive or father a child. Employees’ physicians should be involved in making these detions. 

BC Cancer Agency [2008]. Safe handling of hazardous drugs. In: BC cancer agency pharmacy practice standards for hazardous drugs. 

It is the responsibility of the employee handling HDs [hazardous drugs] to discuss wiimmediate supervisor any desired change in work assignment as a result of their preg

breast-feeding, or attempt to reproduce. All attempts should be made by management assign personnel who are pregnant, , or planning imminent parenthood to work in ano

of the pharmacy in order to avoid working directly with hazardous drugs, if so reques

Canadian Association of Pharmacy in Oncology (CAPhO) [2009]. Standards of Practice for Oncology Pharmacy in Canada. November (Version 2). 

Employees who are pregnant, attempting to conceive or father a child, or are breast fmay request to be transferred to alternate duties which do not involve handling hazardrugs. A policy should exist to provide direction for personnel in these situations. 

American College of Occupational and Environmental Medicine (ACOEM) [2011]. Reproductive and Developmental Hazard Management 

...temporary reassignment should be recommended if the conclusion of the risk assesthat there is exposure to a reproductive or developmental toxicant that cannot be adeq

controlled through engineering or work practice controls alone. Assignment of women who are breast feeding to positions where there are exposures would result in an infant receiving a chemical intake in excess of the acceptable daily 
Guidance. that agent should be closely assessed. Oncology Nursing Society (ONS) [2009]. Chemotherapy and Biotherapy Guidelines and Recommendations for Practice. 

Employers should allow employees who are actively trying to conceive or are pregna

breast feeding to refrain from activities that may expose them and their infant to repr

health hazards such as chemical, physical, or biologic agents. Alternative duty that doinclude HD [hazardous drug] preparation or administration must be made available uquest to both men and women in the aforementioned situations or who have other mesons for not being exposed to HDs. 

American Nurses Association (ANA) [2012]. American Nurses Association’s House of Delegates, Reproductive Rights of Registered Nurses Handling Hazardous Drugs. 

Advocate that it is essential for all health care facilities to educate nurses who handle 

drugs about the risk of reproductive and developmental effects that have been associathese drugs; and Actively advocate for the right of nurses to engage in alternative duty that does not re

hazardous drug handling when trying to conceive, when pregnant, and when breastfe

U.S. Department of the Army [2013]. Occupational Health and Industrial Hygiene Guidance for the Management, Use and Disposal of Hazardous Drugs. 

...HCWs [healthcare workers] who are pregnant, breast-feeding, or are trying to conc

child should be given the option of being transferred to other comparable duties that 

volve handling HDs. 
63 

NIOSH has published an alert describing measures to control worker exposure to hazardous drugs: 

www.cdc.gov/niosh/docs/2004-165.

Additional information about hazardous drugs is available on the NIOSH Web site at 

www.cdc.gov/niosh/topics/hazdrug/default.html. 

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