Multiple Sclerosis 

Cluster Evaluation 

in an Inpatient 

Oncology Ward – 

Wisconsin 

Elena Page, MD, MPH

James Couch, CIH, MS, REHS/RS

Health Hazard Evaluation Report

HETA 2011-0047-3143

October 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 2011-0047-3143 Page i

Appendix A

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

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

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

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

Assessment.........................................................................1

Results.................................................................................2

Discussion ...........................................................................6

Conclusions.........................................................................9

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

References ........................................................................13

Contents

Risk Factors for Multiple Sclerosis.....................................21

Chemotherapy Methods ....................................................15

Occupational Exposure Limits and Health Effects.............16

Acknowledgment

Appendix B

Appendix C

Acknowledgments and Availability of Report.....................23
Page ii Health Hazard Evaluation Report 2011-0047-3143

ACGIH® American Conference of Governmental Industrial Hygienists

CFR Code of Federal Regulations

cm Centimeter

cm2 Centimeter squared

CO Carbon monoxide

HHE Health hazard evaluation

IARC International Agency for Research on Cancer 

LC/MS/MS Liquid chromatography/mass spectrometry/mass spectrometry

LOD Limit of detection

LOQ Limit of quantification

mL Milliliter

MS Multiple sclerosis

NAICS North American Industry Classification System

ND Not detected

ng Nanogram

ng/cm2 Nanograms per square centimeter

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

ppm Parts per million

REL Recommended exposure limit

STEL Short-term exposure limit

TLV® Threshold limit value

TWA Time-weighted average

WEELTM Workplace environmental exposure level

Abbreviat
Health Hazard Evaluation Report 2011-0047-3143 Page iii

What NIOSH Did

● We visited the unit in May 2011.

● We interviewed employees about their work practices and 

health concerns.

● We sampled work surfaces in the unit for two chemotherapy 

drugs. We tested the samples for cyclophosphamide and 

ifosfamide.

● We measured carbon monoxide in the air in the unit.

● We looked at the helicopter landing area. We wanted to see 

if helicopter exhaust could enter the hospital ventilation 

system.

What NIOSH Found

● We found no association between the cases of multiple 

sclerosis and the work environment. 

● Several employees reported symptoms when they smelled 

helicopter exhaust. Their symptoms included headache, 

dizziness, and nausea. 

● Housekeepers reported symptoms when they used diluted 

bleach. Symptoms included headache, sore throat, and 

exacerbation of asthma. 

● Most employees followed policies on the use of personal 

protective equipment (PPE). 

● We found very small amounts of cyclophosphamide and 

ifosfamide on some surfaces.

● Levels of carbon monoxide were well below occupational 

exposure limits.

● We found the potential for hazardous drugs to contaminate 

the family areas of the hospital.

● Helicopter exhaust could enter the hospital ventilation 

system. 

The National Institute for 

Occupational Safety and 

Health (NIOSH) received 

an employee request for a 

health hazard evaluation 

at the inpatient oncology 

unit of a university 

hospital in Wisconsin.

Employees submitted 

the request because of 

concerns about exposure 

to chemotherapy drugs, 

the metabolites of these 

drugs (specifically 

acrolein), and helicopter 

exhaust. Three nurses had 

been recently diagnosed 

with multiple sclerosis, 

and several other staff 

reported symptoms 

possibly from exposure to 

the exhaust. 

Highlights of 

NIOSH 

Hazard Eval
Page iv Health Hazard Evaluation Report 2011-0047-3143

Highlights of 

NIOSH 

Hazard Eval

(continued

What Managers Can Do

● Continue to review and revise employee training on 

hazardous drugs and health effects. Make sure the training 

complies with the Occupational Safety and Health 

Administration’s Hazard Communication Standard. 

● Enforce use of PPE when handling hazardous drugs. 

● Start a medical surveillance program for employees who 

handle hazardous drugs.

● Follow the NIOSH policy for handling hazardous drugs. 

● Double bag hazardous drugs that will be transported from 

the central pharmacy to the unit. 

● Relocate and expand the chemotherapy waste disposal 

system. 

● Start a health and safety committee to look at hazardous 

drugs. 

● Tell patient’s families that hazardous drugs are used on the 

unit and how to reduce their exposure to these drugs. 

What Employees Can Do

● Follow recommended work practices and PPE procedures.

● Continue to learn how to safely work with hazardous drugs.
Health Hazard Evaluation Report 2011-0047-3143 Page v

In January 2011 NIOSH received an employee HHE request 

concerning a potential cluster of MS cases among nurses 

employed in the inpatient oncology unit of a university hospital 

in Wisconsin. The request detailed concern about acrolein as a 

potential exposure from metabolized chemotherapy drugs used in 

the unit (cyclophosphamide and ifosfamide) and as a component 

of helicopter exhaust from the nearby hospital landing pad. 

We visited the hospital on May 23–24, 2011. We observed work 

processes, practices, and conditions in the oncology unit. We 

interviewed employees in the unit about their concerns related 

to chemotherapy drugs. We collected surface wipe samples for 

two chemotherapy drugs used in the unit, cyclophosphamide and 

ifosfamide. Additionally, we examined the helicopter landing pad 

and its proximity to the outdoor air intake for the ventilation 

system for the oncology unit and sampled for CO (a constituent of 

the helicopter exhaust).

We interviewed all 29 employees working first or second shift 

in the unit, and one employee by phone. Of the interviewed 

employees, 17 reported no work-related symptoms. The remaining 

employees reported symptoms, including headache, dizziness, 

nausea, and light sensitivity, when they smelled helicopter exhaust. 

None of the unusual patterns of reproductive health problems that 

can occur with exposure to many chemotherapeutics were seen. 

The three employees with MS were all women within the average 

age range for diagnosis of MS; none had a family history of MS. 

On the basis of what we currently know about the epidemiology, 

characteristics, and treatment of MS, it is unlikely that these cases 

are associated with workplace exposures, including acrolein. 

Most of the surface wipe samples we collected for 

cyclophosphamide and ifosfamide were below the LOQ; only one 

sample was above the LOQ. CO concentrations were well below 

OELs. We found that under certain meteorological conditions 

helicopter exhaust could enter the ventilation system of the unit. 

We recommended that the unit continue to control exposures to 

chemotherapy drugs to levels as low as are reasonably achievable 

because some of these drugs are considered hazardous [NIOSH 

2010a]. Control of exposures can be validated by routine surface 

sampling for chemotherapy drugs used in the unit. 

NIOSH investigators 

evaluated workplace 

exposures to acrolein, CO, 

and chemotherapy drugs 

in an inpatient oncology 

unit. We also investigated 

a potential cluster of MS. 

We found no association 

between the MS cases 

and the work environment. 

The CO levels were well 

below OELs, but some 

employees could smell 

helicopter exhaust, which 

they associated with 

headache, dizziness, 

and nausea. We found 

small amounts of 

cyclophosphamide and 

ifosfamide on some 

surfaces, including 

the family areas of the 

hospital wing, which 

could indicate breaches 

in the handling of 

chemotherapeutic agents 

in this unit. 

Summ

Keywords: NAICS 622110 (General Medical and Surgical Hospitals),

 acrolein, multiple sclerosis, hazardous drugs, chemotherapy drugs
: 

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Health Hazard Evaluation Report 2011-0047-3143 Page 1

Introduct

NIOSH received a request from three employees in the inpatient 

oncology unit (“unit”) of a university hospital in Wisconsin about 

exposures to chemotherapy drugs and helicopter exhaust. Three 

nurses in the unit were diagnosed with MS, and several other staff 

reported symptoms from exposure to the exhaust. The employees 

were also concerned that exposure to acrolein, a metabolite from 

exposure to some chemotherapy drugs that is also present in 

helicopter engine exhaust, may be associated with MS. 

The 39-bed unit housed hematology/oncology, bone marrow 

transplant, and palliative care patients. At the time of this 

evaluation, the average occupancy was 68%, and 17% of the 

patients received chemotherapy daily. A pharmacy in the unit 

was staffed by two pharmacists daily. Chemotherapy drugs were 

delivered to the unit by tube or by cart. These drugs left the 

pharmacy enclosed in resealable plastic bags that reportedly were 

cleaned before being delivered to the unit. Hazardous drugs were 

mixed, and lines were primed in the main pharmacy, but up until 

1 week before our visit pills were crushed on the unit. Registered 

nurses were the only hospital personnel allowed to clean up 

chemotherapy spills. They used commercially available spill kits. 

The unit had family lounges and no age restrictions on visitors; 

however, visitors were not supposed to use patient bathrooms. In 

the evenings patients and family members were allowed to use a 

washer and dryer behind the nurse’s station to do their personal 

laundry.

We visited the unit from May 24–26, 2011. During the visit 

we met with employer and employee representatives to discuss 

the HHE request. We observed work processes, practices, and 

workplace conditions and spoke with employees. We reviewed 

new chemotherapy PPE requirements, chemotherapy certification 

training, and the university policy for preventing occupational 

exposure to hazardous drugs. We held confidential interviews with 

all employees present on the day and evening shifts during our visit 

to discuss health and workplace concerns. 

Details of the sample collection and analysis for cyclophosphamide 

and ifosfamide, two chemotherapy drugs used in the unit, are 

provided in Appendix A. We collected surface wipe samples 

throughout the unit and in other locations in the hospital for 

Assessment
Page 2 Health Hazard Evaluation Report 2011-0047-3143

Assessment (continued) comparison. These samples were analyzed for cyclophosphamide

and ifosfamide by LC/MS/MS. 

We checked for CO by placing five GasAlert Extreme monitors 

(BW Technology America, Arlington, Texas) in the unit to measure 

CO concentrations from Tuesday afternoon until Wednesday 

evening. The CO concentrations were compared to the helicopter 

event log and the air quality log kept by the unit employees. Using 

a Q-TrakTM monitor (TSI, Shoreview, Minnesota), we also measured 

CO concentrations in the building housing the unit. 

We chose to measure CO instead of acrolein as an indicator for 

helicopter exhaust entering into the unit’s ventilation system for 

several reasons. One reason was that previous air sampling for 

acrolein by a consulting group hired by the hospital did not detect 

acrolein in the ventilation system that services the unit. Another 

reason was that we could continuously monitor CO levels in and 

around the unit over a 2-day period with direct-reading monitors. 

We checked the hospital’s helicopter landing area and its proximity 

to the outdoor air intake for the unit’s ventilation system and 

visually examined the plenum (the space above the suspended 

ceiling) in the unit.

During the opening conference, a problem with chemotherapy 

gloves breaking was raised. The gloves, Esteem® Stretchy Nitrile 

(Cardinal Health, Dublin, Ohio), were approved for use with 

chemotherapy drugs. The staff provided us with a box of gloves 

that was perceived to have a high breakage rate. We visually 

inspected the gloves and contacted the manufacturer. 

We interviewed 29 employees in person and one by phone. This 

included 13 registered nurses, 9 certified nurse assistants, 2 health 

unit clerks, 3 housekeepers, and 3 pharmacists. Three were men. 

They had worked on the unit from 3 months to 17 years. 

Of the interviewed employees, 17 reported no symptoms that 

they related to work. One employee reported coughing at work 

for several weeks when on the palliative wing near an area 

being renovated. Several reported symptoms when they smelled 

helicopter exhaust: four reported headache, two reported dizziness, 

two reported nausea, and one reported light sensitivity. In 

addition, one employee reported headaches and lightheadedness 

Results
Health Hazard Evaluation Report 2011-0047-3143 Page 3

Results (continued) at work unrelated to helicopter exhaust, and one reported having

a carboxyhemoglobin level of 1.9 (laboratory upper limit of 

normal 1.5) after fainting at work. A repeat measurement on 

another day was normal. All housekeepers reported that using 

household bleach diluted 1:10 caused symptoms, including 

asthma exacerbation in one. None of the unusual patterns of 

reproductive health problems that can occur with exposure to 

many chemotherapeutics were seen.

The three employees with MS were all women, and none had a 

family history of MS. One reported having mononucleosis as a 

child (a risk factor for MS). All were within the average age range 

for diagnosis of MS (usually between the ages of 20 and 50). One 

was born in May, one in November, and one in August (Cases of 

MS are more common in persons born in May, suggesting that 

seasonality and the gestational environment may influence the risk 

of MS.) Two reported menarche at age 11, one at 13 (There is some 

evidence that early menarche may increase risk of MS).

Hospital policy dictates that nurses are to don two pairs of 

chemotherapy protective gloves and a chemotherapy protective 

gown when handling chemotherapy drugs. Eleven nurses reported 

always wearing double gloves when handling chemotherapy drugs, 

one reported sometimes wearing double gloves, and one reported 

never wearing double gloves. The latter two reported wearing 

single gloves. Twelve nurses reported always wearing a gown when 

handling chemotherapy drugs, and one reported wearing a gown 

sometimes. Nursing assistants are supposed to wear double gloves, 

a gown, and a face shield when handling excreta from patients on 

cytotoxic precautions and single gloves for others. Seven nursing 

assistants reported always wearing double gloves when disposing 

of excreta from patients on cytotoxic precautions, one reported 

sometimes using double gloves, and one reported using single 

gloves for handling all excreta. Three reported wearing a gown 

always, four sometimes, and two reported never wearing a gown. 

Two reported always wearing a face shield, two reported sometimes 

wearing a face shield, and five reported never wearing a face shield. 

All registered nurses were required to take a 3-day chemotherapy 

certification course and a 1-day practicum and pass a test before 

administering these drugs. The course included a module on safe 

handling of cytotoxic agents but lacked hazard communication 

training for other personnel who handled or came into contact 

with these drugs. Nurses who handled chemotherapy drugs had a 
Page 4 Health Hazard Evaluation Report 2011-0047-3143

Results (continued) computer-based annual review, but that did not include the safe

handling module. Employees who handled hazardous drugs were 

not part of a medical surveillance program. 

The university policy for preventing occupational exposure 

to hazardous drugs was based upon the University Health 

Consortium Guidelines that categorizes hazardous drugs into high 

risk hazardous drugs, low risk hazardous drugs, and reproductive 

risk hazardous drugs. Employees who are trying to conceive or who 

are pregnant or nursing are considered at risk from reproductive 

risk hazardous drugs. 

The results of the surface samples for cyclophosphamide and 

ifosfamide are reported in Table 1. Most samples collected (29 of 

39) were below the LOD. Surface concentrations in nine samples 

were between the LOD and the LOQ for either cyclophosphamide 

or ifosfamide. The highest result, 6.7 ng/100cm2 for 

cyclophosphamide, was collected in Room B6-674 on the floor in 

front of the sink. 

All three samples collected in patient rooms on the floor in front 

of the sink were positive for cyclophosphamide, while one of the 

three was also positive for ifosfamide. The maximum concentration 

(6.7 ng/100 cm2) of cyclophosphamide was found in front of the 

sink in Room B6-674.

The maximum CO concentration measured by the direct reading 

monitors was 3 ppm. This occurred on May 24, 2011, around 

4:00 p.m. in the nurses’ charting area. According to a helicopter 

event log obtained from the university, no helicopter events were 

conducted around this time. All other CO monitors measured less 

than 1 ppm, the reporting limit for this device. 

The helicopter landing area was on the roof of a building next to 

the building housing the oncology unit. A large open green space 

separated the helicopter landing area from the unit’s outdoor 

air intakes. Additionally, the unit’s outdoor air intakes were on 

the side opposite from the helicopter pad, further decreasing the 

likelihood of helicopter exhaust entering the unit. These two 

factors suggest that helicopter exhaust would not routinely enter 

the unit’s outdoor air intakes. We spoke with the helicopter pilot 

who informed us that wind patterns normally would take the 

exhaust away from the unit’s outdoor air intakes but at times 

the wind would carry the exhaust towards the unit’s outdoor air 

intakes. 
Health Hazard Evaluation Report 2011-0047-3143 Page 5

Results (continued

Table 1. Surface wipe sample results: May 25, 2011

Room or Area Location Cyclophosphamide 

(ng/100 cm2)

Ifosfamide

(ng/100 cm2)

Countertop near pill crusher ND ND

B6-666 Countertop beneath suspended IV bags ND ND

Pharmacy Floor in front of medicine station ND ND

Top of chemotherapy waste receptacle ND ND

Countertop near first computer ND ND

B6-663 Countertop between two computers ND ND

Nurse Floor between two computers ND ND

Station Hallway directly outside nurse station ND ND

Computer keyboard near printer ND ND

B6-622 Hallway floor outside patient room ND ND

B6-670 Hallway floor outside patient room near keyboard (1.4)* ND

B6-616 Hallway floor outside patient room near keyboard ND ND

Coffee table surface ND ND

B6-604 Family Cyclophosphamide sampled on the right arm of chair

Ifosfamide sampled on the left arm of chair

 (2.1)† (3.7)†

Lounge Exercise bike. Cyclophosphamide sampled on right 

handle bar and ifosfamide sampled on left handlebar

 (3.0)† ND†

Table surface ND ND

Cyclophosphamide sampled on inside door handle 

and ifosfamide sampled on exterior handle

 ND† ND†

B6-652 Floor in front of sink (3.0) (2.9)

Top of bedside table ND ND

B6-BMT Top of coffee table ND ND

Family Room Top of table (1.7) ND

Food rollaway table ND ND

B6-672 Bathroom door handle ND† ND†

Floor in front of sink (2.1) ND

Bathroom door handle ND† ND†

B6-674 Floor in front of sink 6.7 ND

Food rollaway table ND ND

B6-687 Floor near coffee table ND ND

Family Entrance door ND ND

Room Top of coffee table ND ND

B6-665 Floor near computer (1.9) ND

Break Room Floor near doorway (2.6) ND

Chart Area Table top ND ND

B6-699 Staff bathroom door handle ND† ND†

Staff bathroom floor (1.7) ND

Door handle ND† ND†

Floor near doors ND ND

HSLC Floor near stairs ND ND

Atrium Table top in lounge ND ND

Stair hand rail near middle of stairs ND† ND†

ND = Not detected. The LOD was 1 ng/sample for cyclophosphamide and 2 ng/sample for ifosfamide.

*Parentheses indicate that more uncertainty is associated with these sample concentrations because they were 

between the LOD and the LOQ. The LOQ was 3.5 ng/sample for cyclophosphamide and 6.7 ng/sample for 

ifosfamide.

†Estimated 100 cm2
Page 6 Health Hazard Evaluation Report 2011-0047-3143

Results (continued) The outdoor air dampers on the ventilation intake system for the

building containing the helicopter pad could be electronically 

opened or closed depending on helicopter arrivals and departures. 

However, the outdoor air damper for the unit’s ventilation system 

was not connected to this electronic control system. During 

departures, the dispatcher remotely closed the outdoor air dampers 

prior to the helicopter engine starting. The outdoor air dampers 

were reopened approximately 15 minutes after a departure. 

For arrivals, the dampers were closed and not reopened until 

approximately 15 minutes after the helicopter engines had been 

shut down. 

The maximum CO concentration we measured in spot checks 

with the Q-Trak handheld instrument was 1.0 ppm, well below the 

NIOSH REL of 35 ppm for a full-shift TWA and a ceiling limit of 

200 ppm [NIOSH 2010b]. The ventilation system in the plenum of 

the unit appeared clean and well maintained. 

Our visual inspection of the gloves from the high breakage box 

revealed no abnormalities. We also asked several volunteers to put 

on two pairs of the gloves (simulating double-gloving) and observed 

no breakage problems. The manufacturer had received no reports 

of problems with the gloves or the specific lot number of the gloves 

that was provided to us.

Multiple Sclerosis

MS is the most common inflammatory disease of the central 

nervous system. The incidence of MS varies depending on the 

population and geographic area, but ranges from less than 5 to 

200 per 100,000 persons [Milo and Kahana 2010]. MS is more 

common in women and usually is diagnosed between the ages of 

20 and 50, with a peak at about 30 years of age [Milo and Kahana 

2010]. MS is significantly more common in persons born in May 

and significantly less common in persons born in November, 

suggesting that the gestational environment and seasonality may 

influence the risk of MS later in life [Pugliatti et al. 2008]. This 

disease is uncommon in Asia and in tropical and subtropical 

parts of all continents. In temperate climates, MS incidence 

and prevalence are generally higher with increasing latitude (for 

example, in colder climates); however, this latitude gradient is 

Discussi
Health Hazard Evaluation Report 2011-0047-3143 Page 7

Discussio  (continued) disappearing [Ascherio and Munger 2007]. The incidence of 

in migrants usually lies between the incidence of their birthplace 

and the incidence of their final residence. MS risk declines for 

persons migrating from high to low risk areas, but does not always 

increase if migration is in the opposite direction [Ascherio and 

Munger 2007]. Thus, migration data imply that exposures early in 

life determine if a person gets MS, although Australian migration 

studies indicate that the risk may extend into early adulthood 

[Hammond et al. 2000].

Although we know some of the risk factors associated with MS,

we do not know what causes this disease. Some studies suggest an 

interaction between genes and the environment [Giovannoni and 

Ebers 2007; Asherio and Munger 2008; Pugliatti et al. 2008]. The 

incidence of MS is about 30 times higher in siblings of MS patients 

than in the general population [Asherio and Munger 2008]. In 

addition, this appears to be related to the mother, with maternal 

half-siblings having much higher risk than paternal half-siblings 

[Ebers et al. 2004; Handel et al. 2010; Ramagopalan et al. 2010]. 

HLA-DRB1 and HLA-DBQ1 are genetic loci currently linked to 

MS [Giovannoni and Ebers 2007; Asherio and Munger 2008].

The three main theories about environmental risk factors 

for MS, sunlight and vitamin D, infection (especially with 

Epstein-Barr virus), and smoking are discussed in Appendix 

C. Employees in this evaluation were concerned that exposure 

to acrolein (an aldehyde) caused an increased risk of MS. 

Increased levels of reactive aldehydes, including acrolein, in the 

brain and cerebrospinal fluid have been noted in a number of 

neurodegenerative diseases [Wood et al. 2007]. A recent study 

induced experimental autoimmune encephalomyelitis (the animal 

model of MS) in mice and determined acrolein levels in these and 

mice without the disease [Leung et al. 2011]. This particular study 

led the nurses on the unit to suspect acrolein as the cause of their 

MS because cyclophosphamide and ifosfamide, two commonly 

used chemotherapeutic agents, are metabolized to acrolein. In 

addition, acrolein exposure from the helicopter exhaust was a 

concern because exhaust can contain acrolein.

Acrolein is difficult to study because it is ubiquitous in food and 

the environment and can be produced within the body [Stevens 

and Maier 2008]. While the role of acrolein in MS is unclear, 

refractory MS (MS that resists treatment) can be successfully 

treated with high doses of cyclophosphamide [Krishnan et al. 
Page 8 Health Hazard Evaluation Report 2011-0047-3143

Discussio  (continued) 2008]. No published studies demonstrating a higher risk of MS 

persons treated with cyclophosphamide or ifosfamide for cancer or 

other medical conditions could be found.

Disease Clusters 

It may be helpful to discuss disease clusters because of the three 

cases of MS in this small work group. Diseases often appear 

to occur in clusters, which scientists define as an unusual 

concentration of cases in a defined area or time [CDC 1990]. 

The cases may have a common cause or may be the coincidental 

occurrence of unrelated causes. The number of cases may seem 

high, particularly among the small group of people who have 

something in common with the cases, such as working in the same 

building. Although the occurrence of a disease may be random, 

diseases often are not distributed randomly in the population, 

and clusters of disease may arise by chance alone [Metz and 

McGuinness 1997]. 

In many workplaces the number of cases is small. This makes 

detecting whether the cases have a common cause difficult, 

especially when there are no apparent causative exposures. It is 

common for the borders of the perceived cluster to be drawn 

around where the cases are located (in this case, the unit), instead 

of defining the population and geographic area first. This often 

leads to the inaccurate belief that the rate of disease is high. This 

is referred to as the “Texas sharpshooter effect” because the Texas 

sharpshooter shoots at the barn and then draws his bull’s eye 

around the bullet hole. This may well be the case on this unit. 

It is possible, even likely, that the population is a much larger 

population, possibly the entire hospital, including past and present 

employees, and even visitors and patients. It may be larger than the 

hospital. In addition, no clusters of MS among employees handling 

chemotherapy drugs were identified in our search of the medical 

literature. One cluster of MS was reported among nurses in Key 

West, Florida, in the 1980s, with 7 of 307 nurses diagnosed with 

MS [Dean and Gray 1990]. This led to a study of MS death rates 

among nurses and qualified medical practitioners in the United 

Kingdom, which found no increase compared to the general 

population [Dean and Gray 1990]. 
Health Hazard Evaluation Report 2011-0047-3143 Page 9

Discussio  (continued) Environmental Exposur

We found small amounts of cyclophosphamide and ifosfamide 

on surfaces in the unit, including the family areas. This suggests 

breaches in hospital controls when handling these drugs. This is 

important because even small amounts of these drugs can cause 

serious adverse effects, including cancer and adverse reproductive 

outcomes. We believe that when dealing with hazardous drugs, 

programmatic efforts towards continuous improvement are 

paramount in controlling potential exposures to as low as 

reasonably achievable. Control of these exposures should be 

confirmed by routine sampling for chemotherapy drugs that are 

used on the unit. 

Although CO exposures were low, employees occasionally reported 

odors and symptoms when the helicopter took off or landed. 

Activated charcoal filters were recently installed on the unit 

ventilation system to address the odor and potential helicopter 

exhaust issues. While the activated charcoal filters will not 

effectively remove CO, they would be effective in removing acrolein 

and helping reduce nuisance odors from the air. 

On the basis of what we currently know about MS, its 

epidemiology, characteristics, and treatment, it is unlikely that the 

MS cases are associated with workplace exposures. Small amounts 

of cyclophosphamide or ifosfamide were detected on some surface 

wipe samples, including samples collected from family areas. 

The measured CO levels were well below OELs, suggesting that 

helicopter exhaust was not routinely entering the ventilation 

system servicing the unit.

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

below to create a more healthful workplace. We encourage the 

hospital 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 hospital. Our recommendations are 

based on the hierarchy of controls approach (refer to Appendix B: 

Occupational Exposure Limits and Health Effects). This approach 

Conclusion

Recommendatio
Page 10 Health Hazard Evaluation Report 2011-0047-3143

Recommendatio

(continued) 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. 

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. Investigate the feasibility of incorporating the ventilation 

system for the unit into the existing electronic system for 

opening and closing outdoor air ventilation intakes during 

takeoff and landing helicopter events. Ensure that closing 

the intakes will not negatively affect any special ventilation 

requirements in the unit, i.e., positive and negative air 

pressure rooms.

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. Ensure compliance with the OSHA Hazard 

Communications Standard, 29 CFR 1910.1200. The Safe 

Handling and Disposal of Chemotherapy training module 

that is part of the initial chemotherapy certification course 

may be modified to fulfill the initial training requirement. 

All employees who may be exposed to chemotherapy 

drugs, not only registered nurses who will be administering 

chemotherapy, should participate in this training before 

beginning work. 
Health Hazard Evaluation Report 2011-0047-3143 Page 11

Recommendatio

(continued) 2. Follow the NIOSH policy for handling hazardous drugs

instead of the University Health Consortium guidelines. 

The NIOSH policy is to use standard precautions or a 

universal precautions approach to hazardous drugs. This 

means that all hazardous drugs should be handled in 

the same manner as outlined in the NIOSH Alert titled 

“NIOSH List of Antineoplastic and Other Hazardous Drugs 

in Healthcare Settings 2010,” which is available at http://

www.cdc.gov/niosh/docs/2010-167/. 

3. Clarify the central pharmacy procedures to determine if 

the pharmacy is cleaning the outside of bags containing 

hazardous drugs before they are transported outside the 

pharmacy. 

4. Use double bags to transport hazardous drugs from the 

central pharmacy to the unit to reduce the potential for bag 

contamination and to contain accidental spills.

5. Relocate and expand the chemotherapy waste disposal 

system. The central disposal unit currently in the pharmacy 

is relatively small and may require removal during the day 

when the pharmacy has high occupancy and foot traffic. 

6. Implement a medical surveillance program for employees 

potentially exposed to hazardous drugs as recommended 

in the NIOSH document titled “Medical Surveillance 

for Health Care Workers Exposed to Hazardous Drugs,” 

which is available at http://www.cdc.gov/niosh/docs/wpsolutions/2007-117/pdfs/2007-117.pdf. 

7. Form a hazardous drug health and safety committee to 

discuss topics specific to the use and disposal of hazardous 

drugs. This committee should include at least one employee 

representative who can voice the concerns of his or her 

peers. The committee should also include a safety and 

health professional to provide insight into controlling 

occupational exposures to these drugs. 

8. Inform family members of patients who visit the unit that 

hazardous drugs are used on the unit and how to minimize 

exposure to them, i.e., washing hands upon leaving the 

unit. This includes family members of patients not receiving 

hazardous drugs themselves because the family lounge areas 

and bathrooms are shared by all visitors. This information 

could be conveyed to the patient and family at the time 

of admission, and reinforced by placement of posters or 

placards throughout the unit. 
Page 12 Health Hazard Evaluation Report 2011-0047-3143

Recommendatio

(continued) 9. Review the cleaning procedures for the family areas to

determine how chemotherapy drug contamination occurs 

and revise to ensure the surfaces are cleaned appropriately.

10.Alert housekeeping staff of the potential for chemotherapy 

drug contamination in the family areas and remind them 

to wear chemotherapy protective gloves when cleaning these 

areas.

11. Continue to log air quality events in the unit including 

time, location, duration, and associated health effects. 

The logs should be reported to or reviewed weekly by the 

nurse manager. Report concerns about air quality to plant 

engineering for investigation and potential corrective action.

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.

Educate employees on the proper techniques for donning and 

doffing chemotherapy protective gloves. This education should 

include the potential for tears of the gloves by fingernails, rings, etc.

1. Consider changing to a different chemotherapy protective 

glove or offer an alternative glove for employees who are 

experiencing breakage if the perceived high breakage rates 

continue.
Health Hazard Evaluation Report 2011-0047-3143 Page 13

Referenc

Ascherio A, Munger K [2007]. Environmental risk factors for 

multiple sclerosis. Part 1: The role of infection. Ann Neurol 

61(4):288–299.

Ascherio A, Munger K [2008]. Epidemiology of multiple sclerosis: 

from risk factors to prevention. Semin Neurol 28(1):17–28. 

CDC (Centers for Disease Control and Prevention) [1990]. 

Guidelines for investigating clusters of health events. MMWR 

39(11).

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

Government Printing Office, Office of the Federal Register.

Dean G, Gray R [1990]. Do nurses or doctors have an increased 

risk of developing multiple sclerosis? J Neurol Neurosurg Psychiatry

53(10):899–902.

Ebers GC, Sadovnick AD, Dyment DA, Yee IM, Willer CJ, Risch 

N [2004]. Parent-of-origin effect in multiple sclerosis: observations 

in half-siblings. Lancet 363(9423):1733–1734. 

Giovannoni G, Ebers G [2007]. Multiple sclerosis: the 

environment and causation. Curr Opin Neurol 20(3):261–268.

Hammond SR, English DR, McLeod JG [2000]. The age-range 

of risk of developing multiple sclerosis: evidence from a migrant 

population in Australia. Brain 123(Part 5):968–974. 

Handel AE, Giovannoni G, Ebers GC, Ramagopalan SV [2010]. 

Environmental factors and their timing in adult-onset multiple 

sclerosis. Nat Rev Neurol 6(3):156–166.

Krishnan C, Kaplin AI, Brodsky RA, Drachman DB, Jones RJ, 

Pham DL, Richert ND, Pardo CA, Yousem DM, Hammond E, 

Quigg M, Trecker C, McArthur JC, Nath A, Greenberg BM, 

Calabresi PA, Kerr DA [2008]. Reduction of disease activity and 

disability with high-dose cyclophosphamide in patients with 

aggressive multiple sclerosis. Arch Neurol 65(8):1044–1051.

Leung G, Sun W, Zheng L, Brookes S, Tully M, Shi R [2011]. Antiacrolein treatment improves behavioral outcome and alleviates 

myelin damage in experimental autoimmune encephalomyelitis 

mouse. Neuroscience 173:150–155. 
Page 14 Health Hazard Evaluation Report 2011-0047-3143

Reference  (continued) Metz LM, McGuinness S [1997]. Responding to reported cluste

of common diseases: the case of multiple sclerosis. Can J Public 

Health 88(4):277-279.

Milo R, Kahana E [2010]. Multiple sclerosis: geoepidemiology, 

genetics, and the environment. Autoimmun Rev 9(5):A387–A394.

NIOSH [2010a]. 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 Number 2010–167. 

[http://www.cdc.gov/niosh/docs/2010-167/pdfs/2010-167.pdf]. 

Date accessed: August 2011. 

NIOSH [2010b]. 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.

Pugliatti M, Harbo HF, Holmoy T, Kampman MT, Myhr KM, 

Riise T, Wolfson C [2008]. Environmental risk factors in multiple 

sclerosis. Acta Neurol Scand 117(Suppl. 188):34–40. 

Ramagopalan SV, Dobson R, Meier UC, Giovannoni G [2010]. 

Multiple sclerosis: risk factors, prodromes, and potential causal 

pathways. Lancet Neurol 9(7):727–739. 

Stevens JF, Maier CS [2008]. Acrolein: sources, metabolism, and 

biomolecular interactions relevant to human health and disease. 

Mol Nut Food Res 52(1):7–25. 

Wood PL, Khan MA, Moskal JR [2007]. The concept of “aldehyde 

load” in neurodegenerative mechanisms: cytotoxicity of the 

polyamine degradation products hydrogen peroxide, acrolein, 

3-aminopropanal, 3-acetamidopropanal and 4-aminobutanal in a 

retinal ganglion cell line. Brain Res Epub 1145:150–156. 
Health Hazard Evaluation Report 2011-0047-3143 Page 15

The cyclophosphamide 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 LC/MS/MS with an LOD of 1 ng of cyclophosphamide/sample and an LOQ of 3.5 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.

The ifosfamide samples were collected on 70-mL glass fiber filters moistened with 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 ifosfamide by LC/MS/MS with an LOD of 2 ng of ifosfamide/sample and an LOQ of 6.7 ng 

of ifosfamide/sample. All media and field blank results were below the LOD. The sampling method is an 

internal procedure developed by Bureau Veritas North America.

Appendix A: Chemotherapy M
Page 16 Health Hazard Evaluation Report 2011-0047-3143

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 recommended 

exposure limits 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 B: Occupational Exposure Limits and H
Health Hazard Evaluation Report 2011-0047-3143 Page 17

Appendix B: Occupational Exposure Limits and Heh Effects 

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 is 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 effects in the bladder.

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

lung cancer, pediatric malignancies, leukemia, lymphomas, etc. 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 usually brought 

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

solutions. Once in solution, it is recommended that cyclophosphamide be administered to the patient 

within 8 hours to prevent degradation or stored at cold temperatures but never frozen.
Page 18 Health Hazard Evaluation Report 2011-0047-3143

Appendix B: Occupational Exposure Limits and He Effects  

No OELs for cyclophosphamide exist. However, because of the carcinogenic nature of the drug, NIOSH 

investigators believe that exposures to cyclophosphamide should be kept as low as reasonably achievable.

Ifosfamide 

Ifosfamide is a cytotoxic drug used for a wide range of neoplastic diseases including ovary, testis, lung, 

and breast cancers, and soft-tissue sarcomas. It can be prescribed as a single agent or in combination with 

other chemotherapy drugs and can be administered via oral tablets or intravenously. Ifosfamide is normally 

found in a white powder form for chemical stability and is usually brought into solution by the addition of 

water and infused with sodium chloride, glucose, or glucose/saline solutions.

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

to be mutagenic in bacterial cells through the Ames test. Ifosfamide metabolizes in the body to acrolein, 

which can cause adverse effects in the bladder. No OELs for ifosfamide exist. However, because of its 

highly reactive nature within the human body, NIOSH investigators believe that exposures to ifosfamide 

should be kept as low as reasonably achievable. 

Hazardous Drugs in Healthcare Settings 

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 workers. Factors that affect worker 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. More information 

on this topic is available in the NIOSH Alert titled “Preventing Occupational Exposure to Antineoplastic 

and Other Hazardous Drugs in Health Care Settings” [NIOSH 2004]. 

Carbon Monoxide 

CO is a colorless, odorless, tasteless gas produced by incomplete burning of carbon-containing materials. 

The initial symptoms of CO poisoning may include headache, dizziness, drowsiness, or nausea. Symptoms 

may advance to vomiting, loss of consciousness, and collapse if exposures to much higher concentrations 

than those measured in this evaluation are encountered. The NIOSH REL for CO is 35 ppm for full-shift 

TWA exposure [NIOSH 1972]. NIOSH has established a CO ceiling limit of 200 ppm that should never 

be exceeded and an immediately dangerous to life or health value of 1200 ppm [NIOSH 1992, 2000]. The 
Health Hazard Evaluation Report 2011-0047-3143 Page 19

Appendix B: Occupational Exposure Limits and Heh Effects 

ACGIH recommends an 8-hour TWA TLV of 25 ppm [ACGIH 2011], and the OSHA PEL for CO is 50 

ppm for an 8-hour TWA exposure [29 CFR 1910.1000]. 

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 [2010]. AIHA 2010 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.

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 [1972]. Criteria for a recommended standard: occupational exposure to carbon monoxide. 

Cincinnati, OH: U.S. Department of Health, Education, and Welfare, Health Services and Mental Health 

Administration, National Institute for Occupational Safety and Health, DHEW (NIOSH) Publication No. 

73-11000.

NIOSH [1992]. Recommendations for occupational safety and health: compendium of policy documents 

and statements. 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. 92-100.

NIOSH [2000]. Documentation for immediately dangerous to life or health concentrations. In: NIOSH 

Pocket guide to chemical hazards and other databases. 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. 2000-130.

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.
Page 20 Health Hazard Evaluation Report 2011-0047-3143

Appendix B: Occupational Exposure Limits and He Effects  

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.

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 76:11–16.
Health Hazard Evaluation Report 2011-0047-3143 Page 21

MS is the most common inflammatory disease of the central nervous system and is characterized by 

demyelination, loss of axons, gliosis, and perivascular infiltration of monocytes primarily in the white 

matter [Milo and Kahana 2010]. MS patients usually present with a clinically isolated syndrome, which 

is a first neurological event with documented demyelination in the optic nerve or central nervous 

system [Ramagopalan et al. 2010]. More than half of individuals with a clinically isolated syndrome go 

on to develop MS. Radiological abnormalities consistent with MS can be identified in persons without 

symptoms; this is called a radiologically isolated syndrome, and these individuals also have a high risk of 

developing MS [Ramagopalan et al. 2010]. MS manifests in a variety of ways, including numbness and or 

tingling in the extremities, tremors, visual disturbances, and muscle weakness. 

The three main theories about environmental risk factors for MS involve sunlight and vitamin D, 

infection (especially with Epstein-Barr virus), and smoking. Latitude is related to numerous physical, 

chemical, biological, and social factors, but one of its strongest correlates is the intensity and the duration 

of sunlight, the primary source of vitamin D. Numerous studies support a role of sunlight exposure and 

vitamin D in development of MS. For example, outdoor workers are significantly less likely to die from 

MS than indoor workers, and actinic damage to the skin is inversely related to MS incidence [Asherio and 

Munger 2007]. Other studies have shown an inverse relationship between vitamin D intake and MS risk, 

and between serum 25(OH)D levels prior to diagnosis of MS and the risk of MS [Asherio and Munger 

2007]. Having higher serum levels of 25(OH)D exerts a much stronger protective effect before age 20 than 

after [Asherio and Munger 2007]. In addition, exposure to ultraviolet radiation has an immunosuppressive 

effect. 

Numerous studies support a role of infection in risk for MS. Evidence for Epstein-Barr virus infection 

as a risk factor is the strongest [Giovannoni and Ebers 2007; Pugliatti et al. 2008]. Epstein-Barr virus is a 

lifelong dormant infection in B cells. More than 99% of MS patients are infected with Epstein-Barr virus 

compared to about 90% of controls [Ebers et al. 2004; Giovannoni and Ebers 2007]. Individuals negative 

for Epstein-Barr virus have a 10-fold lower risk of developing MS than those with evidence of asymptomatic 

childhood infection [Pugliatti et al. 2008]. In addition, infectious mononucleosis, which is symptomatic 

Epstein-Barr virus infection, places people who have had this condition at more than twice the risk of 

developing MS than those who have not [Ebers et al. 2004; Giovannoni and Ebers 2007; Pugliatti et al. 

2008; Ramagopalan et al. 2010]. Higher titers of anti-Epstein-Barr virus are associated with increased risk 

of developing MS than lower titers [Ramagopalan et al. 2010].

Several studies documented a positive association between cigarette smoking and MS [Ebers et al. 2004; 

Asherio and Munger 2007; Giovannoni and Ebers 2007; Pugliatti et al. 2008]. Smoking has also been 

linked to aggravation of MS [Asherio and Munger 2007].

Appendix C: Risk Factors for Multiple 
Page 22 Health Hazard Evaluation Report 2011-0047-3143

Appendix C: Risk Factors for Multiple S         (

References 

Ascherio A, Munger K [2007]. Environmental risk factors for multiple sclerosis. Part 2: noninfectious 

factors. Ann Neurol 61(6):504–513.

Ebers GC, Sadovnick AD, Dyment DA, Yee IM, Willer CJ, Risch N [2004]. Parent-of-origin effect in 

multiple sclerosis: observations in half-siblings. Lancet 363(9423):1733–1734. 

Giovannoni G, Ebers G [2007]. Multiple sclerosis: the environment and causation. Curr Opin Neurol 

20(3):261–268.

Milo R, Kahana E [2010]. Multiple sclerosis: geoepidemiology, genetics, and the environment. Autoimmun 

Rev 9(5):A397–A394.

Pugliatti M, Harbo HF, Holmoy T, Kampman MT, Myhr KM, Riise T, Wolfson C [2008]. Environmental 

risk factors in multiple sclerosis. Acta Neurol Scand 117(Suppl. 188):34–40. 

Ramagopalan SV, Dobson R, Meier UC, Giovannoni G [2010]. Multiple sclerosis: risk factors, prodromes, 

and potential causal pathways. Lancet Neurol 9(7):727–739. 
Health Hazard Evaluation Report 2011-0047-3143 Page 23

Acknowledgments a

Availability of Re

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 Elena Page and James Couch of 

HETAB, Division of Surveillance, Hazard Evaluations and Field 

Studies. Industrial hygiene field assistance was provided by Kemka 

Hekerem. Industrial hygiene equipment and logistical support 

was provided by Donnie Booher and Karl Feldmann. Analytical 

support was provided by Bureau Veritas North America. 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 hospital, 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: multiple sclerosis cluster evaluation 

in an inpatient oncology ward – Wisconsin. By Page E, Couch J. 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. 2011-0047-3143.

To receive NIOSH documents or information about 

occupational safety and health topics, contact NIOSH at:

1-800-CDC-INFO (1-800-232-4636)

TTY: 1-888-232-6348

E-mail: cdcinfo@cdc.gov

or visit the NIOSH web site at: www.cdc.gov/niosh.

For a monthly update on news at NIOSH, subscribe to 

NIOSH eNews by visiting www.cdc.gov/niosh/eNews.

Delivering on the Nation’s promise:

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Safety and Health