Health Hazard Evaluation Report 2012-0044-3199 Page 1

Evaluation of Safety Climate, Health 

Concerns, and Pharmaceutical Dust 

Exposures at a Mail Order Pharmacy

Report No. 2012-0044-3199

December 2013

Kenneth W. Fent, PhD, CIH

Loren Tapp, MD, MS

Douglas Wiegand, PhD

U.S. Department of Health and Human Services

Centers for Disease Control and Prevention

National Institute for Occupational Safety and Health
Page 2 Health Hazard Evaluation Report 2012-0044-3199

Contents

Highlights...............................................i

Abbreviations ..................................... iv

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

Methods ............................................... 3

Results .................................................. 6

Discussion .......................................... 23

Conclusions........................................ 28

Recommendations............................. 29

Appendix A ........................................ 33

Appendix B......................................... 39

Appendix C......................................... 46

Appendix D ........................................ 47

References.......................................... 50

The employer is required to post a copy of this report for 30 days at or near the 

workplace(s) of affected employees. The employer must take steps to ensure 

that the posted report is not altered, defaced, or covered by other material.

The cover photo is a close-up image of sorbent tubes, which are used by the HHE 

Program to measure airborne exposures. This photo is an artistic representation that may 

not be related to this Health Hazard Evaluation. Photo by NIOSH.
Health Hazard Evaluation Report 2012-0044-3199 Page i

The safety climate at 

the pharmacy needs 

improvement. Employees 

were concerned about 

prolonged standing and 

repetitive tasks. Contractor 

employees reported more 

eye, nose, throat, and 

skin irritation and cough 

associated with work than 

did company employees. 

Employees were exposed 

to pharmaceutical 

dust. We recommend 

filling hazardous drug 

prescriptions and doing 

other dust-generating tasks 

under a local exhaust hood. 

Highlights of this Evaluation

The Health Hazard Evaluation Program received a request from a mail order pharmacy. 

Employees were concerned about possible health effects from exposures to hazardous drugs 

and pharmaceutical dust. The employees were also concerned about communication and other 

workplace safety climate issues.

What We Did

● We visited the pharmacy in August 2012.

● We asked employees about job stress, work-related health concerns, and perceptions of 

the job and social factors at work.

● We talked to employees privately about their dust 

exposures, health history, and possible work-related 

health problems. 

● We measured particle levels in the air over time at 

different processes. 

● We sampled air for dust, lactose, and active 

pharmaceutical ingredients. We sampled work 

surfaces for lactose and active pharmaceutical 

ingredients. Lactose is an inactive ingredient in 

pharmaceuticals.

What We Found

● Many contractor employees were not comfortable 

taking time off work when ill.

● Some employees were concerned about repetitive 

tasks and prolonged standing. 

● Contractor employees reported more eye, nose, 

throat, and skin irritation and cough associated with 

work than company employees. 

● No employees reported any changes in their health 

consistent with exposures to hazardous drugs. 

● Employees released particles into the air during certain job tasks.

● Employees who worked in the Baker machine area had among the highest exposures to 

inhalable dust and lactose. 

● An employee who cleaned and repaired Baker machine cells was exposed to airborne 

lisinopril above the exposure limit. A few employees were exposed to multiple active 

pharmaceutical ingredients.

● We found a hazardous drug, methotrexate, in air at levels below the manufacturer’s 

exposure limit. We also found it on a work surface. 
Page ii Health Hazard Evaluation Report 2012-0044-3199

What We Found (continued) 

● Employees were provided vinyl gloves but no other protective clothing. We measured 

lactose on work surfaces and saw pharmaceutical dust on personal clothing. Take-home 

exposure is possible.

What the Employer Can Do

● Create a health and safety committee.

● Create a list of pharmaceuticals that are dusty, along with any exposure guidelines. Use this 

information to determine how to handle these pharmaceuticals.

● Use local exhaust ventilation hoods that are ducted outdoors for filling hazardous drug 

prescriptions and other tasks that could create pharmaceutical dust. 

● Provide seats at workstations.

● Stop the punitive “point system” for discouraging absences.

● Require employees to wear nitrile gloves. Provide safety glasses and long-sleeve 

protective clothing to employees who hand fill hazardous drug prescriptions or create 

pharmaceutical dust.

What the Employees Can Do

● Tell your supervisor or occupational safety and health specialist if you have workplace 

concerns or suggestions for improving the health and safety at the workplace.

● Follow the procedures for using and maintaining the local exhaust hood.

● Wear all required personal protective equipment and clothing.
Health Hazard Evaluation Report 2012-0044-3199 Page iii

This page left intentionally blank.
Page iv Health Hazard Evaluation Report 2012-0044-3199

Abbreviations

μm Micrometer

μg/m3 Micrograms per cubic meter

API Active pharmaceutical ingredient

BVNA Bureau Veritas North America

HCTZ Hydrochlorothiazide

HEPA High efficiency particulate air

M Mean/average

MDC Minimum detectable concentration

mL Milliliter

mL/min Milliliter per minute

mm Millimeter

mM Millimolar

MQC Minimum quantifiable concentration

n Number of samples

N Number of employees

NA Not applicable

ND Not detectable

NIOSH National Institute for Occupational Safety and Health

OEL Occupational exposure limit

OSHA Occupational Safety and Health Administration

Particles/L Particles per liter
Health Hazard Evaluation Report 2012-0044-3199 Page 1

Introduction 

The Health Hazard Evaluation Program received a request from a mail order pharmacy. The 

pharmacy’s contractor employees who submitted the request were concerned about exposures 

to pharmaceutical dust, including hazardous drugs, and the potential health effects from those 

exposures. They also were concerned about communication and other workplace health and 

safety climate issues. We evaluated pharmaceutical exposures, health effects, job stress, workrelated health concerns, and psychosocial factors at the pharmacy in August 2012. In March 

2013, we sent an interim report summarizing the type and number of samples collected.

The mail order pharmacy filled prescriptions using automated and manual distribution systems 

for delivery to its customers throughout the country. Approximately 175 employees worked 

on either the first or second shift. The majority were non-unionized contractors who reported 

to their own managers. The remaining employees were unionized company employees. 

On average, the company filled 74,000 prescriptions per day during our evaluation. All 

prescriptions were verified by pharmacists. Most of these were unit-of-issue prescriptions that 

do not require counting. These were processed in the A-frame area of the pharmacy.

A Baker automatic dispensing 

machine (McKesson 

Corporation) was used for 

many of the commonly 

prescribed pharmaceuticals. 

This machine had an 

elevated work platform 

where canisters containing 

pharmaceuticals were located. 

Pharmacy technicians 

periodically refilled these 

canisters by emptying 

original manufacturer bottles 

containing the appropriate 

pharmaceuticals into cups 

that were then emptied into 

the labeled canisters (Figure 

1). The pharmaceuticals in 

the canisters were gravity 

fed into the cells below the platform. A conveyor belt on the outside of the machine carried 

empty prescription bottles to a nozzle below the appropriate cell, and a valve in the cell opened to 

dispense the pharmaceutical into the bottle (Figure 2). Pharmacy technicians maintained the Baker 

machine. This included freeing jams, identifying bottles that did not receive pharmaceuticals, and 

cleaning and repairing malfunctioning cells. To clean or repair the cells, the pharmacy technicians 

emptied the cell into a bin, vacuumed the inside of the cell using a 3M vacuum with highefficiency particulate air (HEPA) filtration, wiped the inside of the cells with isopropyl alcohol, 

made any necessary repairs, and returned the pharmaceuticals to the cells. According to the 

Figure 1. Pharmacy technician filling canisters on the platform above 

the Baker machine. Photo by NIOSH.
Page 2 Health Hazard Evaluation Report 2012-0044-3199

standard operating procedures, 

the pharmacy technicians 

were required to do this 

work inside a recirculating 

exhaust hood with HEPA 

filtration (Labconco XPert 

Filtered Balance System). 

The pharmacy had standard 

operating procedures for 

determining when to change 

the HEPA filter (using pressure 

drop) and how to change the 

HEPA filter (bag-in/bag-out) 

in the exhaust hood. These 

procedures were based on the 

manufacturer’s guidelines. 

Pharmacy technicians also 

filled prescriptions in the 

manual count, controlled drug (controls), and bulk/hazardous drug areas of the pharmacy. 

They used KirbyLester desktop automated counters to fill less common or special-handling 

prescriptions in the manual count area. They hand filled prescriptions for controlled substances 

(Schedule III–V), mostly with unit of issue pre-counted bottles, in the controls area. In addition, 

they prepared bulk prescriptions (e.g., insulin) and occasionally hand filled hazardous drug 

prescriptions in the bulk/hazardous drug area. Hazardous drugs are drugs known or suspected 

to cause adverse health effects from exposures in the workplace [NIOSH 2004]. The pharmacy 

stocked 54 hazardous drugs included on the National Institute for Occupational Safety and Health 

(NIOSH) list of hazardous drugs [NIOSH 2012], 32 of which were available as tablets. Tablets are 

more likely than capsules to produce airborne dust. 

The pharmacy had standard operating procedures for the safe handling of pharmaceuticals, 

including hazardous drugs. All hazardous drugs (as defined by the NIOSH list [NIOSH 2012]) 

were stored in a cabinet labeled “cytotoxics.” Employees were required to wear vinyl gloves 

when filling these prescriptions. They were also required to clean their workstations and counting 

trays with isopropyl alcohol wipes immediately after filling these prescriptions. Employees who 

unpacked boxes containing hazardous drug shipments were not required to wear gloves. In case of 

a hazardous drug spill, employees were required to notify personnel in the area and a supervisor. 

Employees trained on hazardous spill clean-up procedures were responsible for cleaning the spills. 

Spill kits were available and included cleaning supplies and neoprene gloves.

Employees performed other jobs including labeling, packaging, housekeeping, and administrative 

functions. Administrative functions were performed in offices that were separated from the rest 

of the pharmacy. Employees put labels on prescription bottles in the labeling area. Employees put 

filled prescriptions into mailing envelopes or boxes in the packaging area. The packaging area 

was located next to the Baker machine area. The housekeeping employees swept the floors with a 

Figure 2. Baker machine nozzle where pharmaceuticals were dispensed into prescription bottles. Photo by NIOSH.
Health Hazard Evaluation Report 2012-0044-3199 Page 3

broom and disposed of trash. They also used a Dayton® Model 3UP66 12-gallon wet/dry vacuum 

to clean the surfaces of the Baker machine during break periods. This vacuum contained a HEPA 

filter, and the vacuum bags used were rated high efficiency for fine dust collection. 

All employees were required to wear vinyl gloves (High Five 600 Series) when handling 

pharmaceuticals. No other personal protective equipment or clothing was required. However, 

NIOSH-approved filtering facepiece respirators (Honeywell/Wilson Saf-T-Fit Plus) and hearing 

protection (3M Tekk/AO Safety Product no. 90581) were available for voluntary use. All 

employees were provided with Appendix D of the Occupational Safety and Health Administration 

(OSHA) respiratory protection standard [29 CFR 1910.134].

In general, company employees performed most administrative functions, and contractor 

employees performed most production functions (e.g., filling, labeling, packaging, and 

housekeeping). Company and contractor pharmacists and pharmacy technicians often 

worked side-by-side. Company employee safety and health issues were reported to company 

management; contractor employee safety and health issues were reported to contractor 

management and the company safety committee that included contractor and company 

management representatives. 

Methods

We evaluated the pharmacy for 3 days in August 2012. Our objectives were to (1) assess safety 

climate, job stress, work-related health concerns, and psychosocial factors among employees; 

(2) evaluate potential work-related employee symptoms and health problems; (3) determine 

if and how pharmaceutical dust was released into the air; (4) measure the concentration of the 

airborne dust; (5) measure specific active pharmaceutical agents (APIs) and other pharmaceutical 

ingredients in the airborne dust; and (6) determine if surfaces were contaminated with 

pharmaceutical ingredients. 

Employee Surveys

We asked 71 full-time, non-supervisory employees who worked with pharmaceuticals on two 

shifts to complete a survey about safety climate, psychosocial factors in the workplace, job 

stress, work-related health concerns, and employer-employee relations. We selected 50 of the 

157 contractor employees from roster lists using a systematic pattern, choosing every third, 

then every fourth employee, and repeating this pattern down the list. Because so few company 

employees worked with pharmaceuticals, we asked all 18 of them to participate. We selected 3 

of 7 housekeeping employees based on their availability. One additional contractor employee 

voluntarily participated in the survey but not in the medical interview (N = 72).

The first section of the survey instructed employees to rate their level of agreement with 14 

statements exploring safety climate. Responses to these survey questions were measured with a 

five-point scale ranging from 1 (“strongly disagree”) to 5 (“strongly agree”). Safety climate refers 

to employees’ perceptions of the safety-related aspects of how their organization operates. One 

method of measuring safety climate [Neal et al. 2000] focuses on individual perceptions of how 
Page 4 Health Hazard Evaluation Report 2012-0044-3199

the organization values safety, comprised of the following dimensions: management values (the 

extent to which the employer places a high priority on safety), safety communication (the extent 

to which an open exchange of information regarding safety exists), safety training (the extent 

to which training is accessible, relevant, and comprehensive), and safety systems (the extent to 

which safety policies and procedures are perceived to be effective in preventing safety incidents) 

[Neal et al. 2000]. We also included the dimension of safety risk (the extent to which employees 

believe they are exposed to inherent dangers of the workplace). Internal consistency for the items 

measuring these five dimensions was analyzed using Cronbach’s coefficient (α) after adjusting for 

the directionality of items, where necessary. We created composite scores for survey items within 

the management values, safety communication, safety training, safety systems, and safety risk 

dimensions where α > 0.7 by calculating the mean of the individual scores for each respondent. 

The second section of the survey included questions targeting specific psychosocial factors of 

interest to the HHE requestors, including perceptions of job security, attending work while ill, and 

perceived hostility from management. These items were rated with a five-point scale ranging from 

1 (“strongly disagree”) to 5 (“strongly agree”).

The third section of the survey included questions with 11-point response scales and open-ended 

questions regarding job stress, work-related health concerns, and perceptions of the relationship 

between employees and their employer.

Employee Medical Interviews

The 71 employees who participated in the survey also met with us individually for confidential 

medical interviews. We asked employees about demographic information, work exposure history, 

medical history (including reproductive health and hormone disorders), and whether they had any 

work-related health problems. We asked if the employee had experienced specific symptoms such 

as eye, nose, throat, or skin irritation, respiratory symptoms, dizziness, and heart palpitations, in 

the past month and if symptom(s) were better, worse, or unchanged when away from work. If the 

symptom(s) experienced were better when away from work, we defined those symptoms to be 

“work-related.” We also asked if the employees had any comments or concerns about their work.

Air Sampling

We used the air sampling methods summarized in Table 1. We selected employees for personal air 

sampling among the various job tasks at the pharmacy, focusing primarily on employees who did 

tasks or were near tasks that we thought could generate pharmaceutical dust. In 3 days, we collected 

37 personal air samples, including three sets of side-by-side samples, by attaching the air samplers 

to the employees’ shirt collars. We collected 21 area air samples at fixed locations throughout 

the pharmacy. These 58 air samples measured inhalable dust, which is dust that could be inhaled 

and deposited anywhere in the respiratory system including the nose and mouth [ACGIH 2013]. 

Sampling for inhalable dust is the preferred method for assessing this type of exposure, because 

most pharmaceuticals are water soluble and can be absorbed anywhere in the respiratory system. Of 

the 58 samples, 54 were full-shift samples collected during first shift. Three samples were collected 

for part of second shift (day 2), and one sample was collected during a specific task.
Health Hazard Evaluation Report 2012-0044-3199 Page 5

Table 1. Summary of the air sampling methods

Analytes Method No. of 

personal 

samples

No. of 

area 

samples

Comments

Inhalable dust NIOSH Method 0600* 37 21 •	 Total no. of inhalable

dust samples = 58.

•	 Collected on tared, 

25-mm diameter

polytetrafluoroethylene

sample filters.

•	 Used Institute of

Medicine samplers

operating at a flow rate

of 2 Lpm.

•	 Subsequently analyzed

as noted.

Lactose BVNA internal method† 22 15

HCTZ‡ BVNA internal method† 2 7

Lisinopril BVNA internal method† 2 7

Hydrocodone BVNA internal method† 4 1

Warfarin BVNA internal method† 3 0

Methotrexate BVNA internal method† 1 2

Methocarbamol BVNA internal method† 1 1

Levothyroxine BVNA internal method† 1 1

Buspirone BVNA internal method† 1 0

Gabapentin BVNA internal method† 1 0

Captopril BVNA internal method† 1 0

Naproxen BVNA internal method† 1 0

Furosemide BVNA internal method† 1 0

Triamterene BVNA internal method† 0 1

Particle count NA NA NA •	 6-channel optical

particle counter,

real-time

BVNA = Bureau Veritas North America

HCTZ = hydrochlorothiazide

mm = millimeter

NA = not applicable

*NIOSH Manual of Analytical Methods [NIOSH 2013b]

†More information on the BVNA analytical methods is provided in Appendix A.

We followed some of the employees who wore air samplers throughout their workday 

and held real-time optical particle counters (MetOne HHPC-6) near their breathing zones 

to identify dusty tasks that appeared as peaks in particle number concentrations on the 

optical particle counters. We also noted the types of tablets handled so that we could later 

identify which personal air samples (previously analyzed gravimetrically) could be further 

analyzed for lactose (common inactive filler in tablets) and/or specific active pharmaceutical 

ingredients (APIs) (Table 1). Although lactose is inactive, its presence in air at levels above 

background (i.e., levels in nonproduction areas) suggests that pharmaceuticals were the 

source of some of the airborne dust.
Page 6 Health Hazard Evaluation Report 2012-0044-3199

The side-by-side personal air samples that we collected allowed us to quantify more 

than one API in an employee’s breathing zone. We used information on the dustiness of 

pharmaceuticals to identify area air samples for analysis of lactose and/or APIs. We generally 

focused on APIs that had occupational exposure limits (OELs) or hazard control bands 

established by pharmaceutical manufacturers. We also made sure that our contract lab, 

BVNA, had methods for the APIs we selected. More information on the analytical methods 

is provided in Appendix A. Methotrexate was the only API we selected for analysis from the 

NIOSH list of hazardous drugs [NIOSH 2012]. 

Surface Sampling

Table 2 summarizes the surface sampling methods used during the evaluation. We sampled 

22 surfaces for pharmaceutical ingredients to estimate the extent of pharmaceutical 

dust contamination throughout the pharmacy. The surfaces we sampled were primarily 

work surfaces in offices, near the Baker machine, or in the controls area. We placed a 10 

centimeters by 10 centimeters template on top of a surface. While wearing nitrile gloves, 

we wiped the work surface area inside the template with a prewetted AlphaWipe® towelette 

(Texwipe® TX1004) in three different directions. For irregularly-shaped surfaces, we 

estimated 100 square centimeters and wiped the surface in a manner identical to that used for 

flat surfaces. 

Table 2. Summary of the surface sampling methods

Analytes Method No. of samples Comments

Lactose BVNA internal method* 9 •	 Total no. of wipe 

samples = 22.

•	 Used towelettes 

prewetted with deionized water.

Methotrexate BVNA internal method* 8

Hydrocodone BVNA internal method* 3

Methocarbamol BVNA internal method* 1

Glipizide BVNA internal method* 1

*More information on the BVNA analytical methods is provided in Appendix A.

Results 

Employee Surveys and Medical Interviews

We selected 71 employees to interview, as described previously, and all consented to 

participate. One additional contractor employee voluntarily participated in the survey but not 

in the medical interview (N = 72). Job titles of the employees (excluding the housekeepers) 

included pharmacy technicians, pharmacists, shipper/packers, material handlers, supply 

technicians, and industrial equipment mechanics. Table 3 shows the number of employees in 

each job title among company and contractor employees. 
Health Hazard Evaluation Report 2012-0044-3199 Page 7

Table 3. Job titles among participating company (N = 18) and contractor employees (N = 50)

Job title Company employees

N (%)

Contractor employees

N (%)

Pharmacists 2 (11) 4 (8)

Pharmacy technicians 11 (61) 33 (66)

Shipping/packing 0 13 (26)

Material handler 3 (17) 0

Supply and equipment mechanics 2 (11) 0

Because the housekeeping employees were few and employed by a different contractor, we 

briefly summarize their responses to the surveys and interviews in the text rather than the 

tables or figures. Overall, the housekeeping employees’ responses did not indicate problems 

regarding safety climate or job stress. 

Table 4 compares demographic information between company and contractor employees. 

Company and contractor employees were similar in age, sex, and the number of years 

working at their current job.

Table 4. Demographic information reported by company (N =18) and contractor employees (N = 50)

Demographic Company employees Contractor employees

Number female (%) 12 (67) 38 (76)

Average age in years (range) 42 (26–55) 41 (21–74)

Average years in this job (range) 4 (0.33–16) 5 (0.08–15)

Employee Survey

The first section of the survey explored employees’ perceptions of safety climate. Mean 

scores (N = 69) of the composite safety climate dimensions were calculated based on a fivepoint scale, with higher numbers indicating a more positive response. The most highly rated 

safety climate dimension was management value for safety (M = 3.9), followed by safety 

training (M = 3.8), safety systems (M = 3.5), safety communication (M = 3.5), and safety 

risk (M = 3.4). Overall, employees reported positive perceptions of safety climate. Among 

pharmacists and pharmacy technicians (the most prevalent job title), however, the perceptions 

about safety climate were more positive among those employed by the company than those 

employed by the contractor (Table 5). This was especially true for the safety training and 

safety risk dimensions.
Page 8 Health Hazard Evaluation Report 2012-0044-3199

Table 5. Safety climate dimension mean scores for pharmacists/pharmacy technicians by employer

Safety climate dimension Company pharmacists/pharmacy 

technicians (N = 14)

Mean 

Contractor pharmacists/pharmacy 

technicians (N = 37)

Mean 

Management value for 

safety

4.3 3.8 

Safety training 4.4 3.6 

Safety communication 3.9 3.4 

Safety systems 3.8 3.5 

Safety risk* 4.3 3.3 

*Survey items reversed scored

We asked employees to rate their level of agreement with several statements regarding job 

security, comfort with taking a sick day if not feeling well, and perceived hostility from 

management. These were issues of specific interest to the HHE requestors. We analyzed 

these variables by employer, since company and contractor employees could have different 

experiences with each. Table 6 shows the proportions of contractor and company employees 

who indicated agreement with the statements by scoring the question as either a 4 or 5 on the 

five-point scale (where 5 is “strongly agree”). 

Table 6. Number of employees agreeing with survey items by employer (company employees N = 

18; contractor employees N = 51) 

Survey item Number of 

company 

employees (%) 

in agreement

Number of 

contractor 

employees (%) 

in agreement

I am satisfied with my level of job security 16 (89) 21 (41)

I am comfortable taking a sick day if I am not feeling well 15 (83) 5 (10)

I am exposed to hostility or conflict from my supervisor 1 (6) 16 (31)

Most company employees were satisfied with their level of job security and felt comfortable 

taking a sick day if they were not feeling well. Very few company employees reported facing 

hostility from their supervisors.

Most contractor employees reported that they were not satisfied with job security and few 

(10%) reported that they were comfortable taking a sick day when ill. Approximately one 

third of contractor employees reported facing hostility from their supervisor.

Job Stress

We asked participants to rate their level of job stress over the past week on a scale from 0 (as 

low as it can be) to 10 (as high as it can be). The average job stress score for all employees 

was 4.3 (N = 69). When separated by employer, the average job stress score was 3.8 (N = 

18) for company employees and 4.5 (N = 51) for contractor employees. When grouped by 

job titles, shipper/packers had the highest average job stress score of 4.8 (N = 14), followed 

by pharmacists/pharmacy technicians (M = 4.2; N = 51), and material handlers/suppliers/

equipment mechanics (grouped due to a small number of employees with these job titles; M 

= 4.0; N = 4).
Health Hazard Evaluation Report 2012-0044-3199 Page 9

Company Employees’ Reported Job Stressors

We asked participants to identify one or more major source(s) of job stress, if any, in an openended question. Twelve (66%) company employees reported one or more job stressor(s). 

Three company employees reported interpersonal problems with their supervisor as being a 

job stressor. Other job stressors were reported, but each of these were reported by less than 

three individuals and are therefore not listed here. 

Contractor Employees’ Reported Job Stressors

Thirty-eight (75%) contractor employees reported one or more job stressor(s). Job stressors 

reported by three or more participating contractor employees are listed in Table 7.

Table 7. Frequency of reported job stressors for contractor 

employees (N = 51)

Job stressor Number (%) of 

contractor employees 

reporting 

Lack of sick leave 15 (29)

No stressors reported 13 (25)

Interpersonal problems with 

supervisor

11 (22)

High workload 10 (20)

Poor communication at work 6 (12)

Interpersonal problems with 

coworkers

4 (8)

Concern about making errors 4 (8)

Concern about losing one’s job 4 (8)

Contractor employees were not allowed sick leave and received “points” for absences and 

tardiness. Employees received 3–6 points for an absence, depending on the day of the week. 

Employees received 1 point for up to 15 minutes tardiness initially and then 2 points for each 

subsequent 15-minute period. The points were cumulative and led to disciplinary actions 

ranging from a verbal warning (9 points) to 3 months of probation (21 points). Each quarter, 

employees with perfect attendance were rewarded with a 3-point deduction. Employees 

reported that the point system created job stress related to fear of punishment, lack of control, 

and interference with work-life balance (e.g., needing to stay home to care for an ill child). 

Some employees also reported concerns that they were being exposed to germs from ill 

coworkers. The other most frequently reported job stressors included having interpersonal 

problems with one’s supervisor and a heavy workload. 

Work-related Health Concerns 

We asked participants to rate their level of work-related health concern on a scale from 0 (as 

low as it can be) to 10 (as high as it can be). The average work-related health concern score 

for all employees was 4.1 (N = 68). Contractor employees had a higher average work-related 
Page 10 Health Hazard Evaluation Report 2012-0044-3199

health concern score (M = 4.8; N = 51) than company employees (M = 2.1; N = 17). This 

remained true when comparing the pharmacists/pharmacy technicians between contractor 

(M = 4.2; N = 14) and company employees (M = 1.3; N = 37). When grouped by job titles, 

shipper/packers had the highest average work-related health concern score of 6.4 (N = 

14), followed by material handlers/suppliers/equipment mechanics (M = 4.5; N = 4) and 

pharmacists/pharmacy technicians (M = 3.4; N = 50).

Company Employees’ Reported Work-Related Health Concerns 

We asked participants to explain their work-related health concern score in an openended question. Four (22%) company employees responded to this item. Two company 

employees reported a concern about developing a musculoskeletal disorder. Several other 

concerns were reported, but each concern was only reported by a single individual and is 

therefore not listed here. 

Contractor Employees’ Reported Work-Related Health Concerns 

Thirty-two (63%) contractor employees responded to the open-ended question. Work-related 

health concerns reported by three or more contractor employees are listed in Table 8.

Table 8. Frequency of contractor employees’ reported workrelated health concerns (N = 51)

Work-related health concern Number of contractor 

employees reporting

N (%)

No work-related health concern(s) 

reported

19 (37)

Prolonged standing 14 (27)

Exposure to pill dust 14 (27)

Repetitive motion leading to potential 

musculoskeletal disorder

10 (20)

Noise 3 (6)

Indoor environmental quality affecting 

health

3 (6)

Perceptions of the Relationship between Employees and Employers

Company Employees

We asked survey participants to describe their perceptions of the relationship between 

employees and employers in an open-ended question. Comments made by three or more 

individuals are listed in Table 9. 
Health Hazard Evaluation Report 2012-0044-3199 Page 11

Table 9. Descriptions of the employer-employee relationship 

among company employees (N = 18)

Description of supervisor-employee 

relationship

Number of 

participants 

reporting

N (%)

The relationship is positive 9 (50)

There is open communication 3 (17)

Supervisors address employees’ concerns 3 (17)

My supervisor is “distant” 3 (17)

No response 2 (11)

Contractor Employees

Comments made by at least three contractors regarding the employer-employee relationship 

are listed in Table 10.

Table 10. Descriptions of the employer-employee relationship among contractor employees (N = 51)

Description of employer-employee relationship Number of contractor 

employees reporting

N (%) 

There is a poor relationship 22 (43)

There is poor communication between my supervisor and employees 14 (27)

The relationship is positive 10 (20)

My supervisor is disrespectful to employees 10 (20)

My supervisor shows favoritism towards certain employees 9 (18)

My supervisor is “distant” 8 (16)

My supervisor is unapproachable 6 (12)

My supervisor is intimidating 5 (10)

My supervisor offers no praise for good work 5 (10)

Employees are treated “like machines” 5 (10)

Employees are limited in who they can voice concerns to 3 (6)

Medical Interviews 

Most contractor employees (32 of 50) reported handling what they considered to be 

hazardous drugs; however, 10 reported only handling warfarin, which is not on the NIOSH 

list of hazardous drugs. Of the remaining 22 employees, four said they only handled 

hazardous drugs if a bottle spilled. Five of the 18 company employees reported handling 

hazardous drugs. When we looked only at employees whose job titles were pharmacist or 

pharmacy technician, we found about the same percentages of company (31%) and contractor 

(30%) pharmacists/pharmacy technicians reported handling hazardous drugs. However, over 

twice the percentage of contractor pharmacists/pharmacy technicians (70%) reported working 

on the Baker machine as company pharmacists/pharmacy technicians (31%). 

When asked about their medical history, six contractor employees (five pharmacists/

pharmacy technicians and one shipper/packer) reported having asthma or asthma-like 
Page 12 Health Hazard Evaluation Report 2012-0044-3199

symptoms; four of the six reported having asthma prior to being hired, and two reported 

developing asthma-like symptoms since being hired (one pharmacist/pharmacy technician 

and one shipper/packer). Some employees with pre-existing asthma reported having more 

asthma symptoms at work. No company employees reported having asthma.

When we asked about hormone problems, five company and seven contractor employees 

reported thyroid disorders including hypothyroidism (6), hyperthyroidism (1), noncancerous 

thyroid tumor (1), and unknown type (4). All of these employees were female pharmacists/

pharmacy technicians, at least eight had been diagnosed with the disorder prior to working 

at this facility, and more than half had worked with pharmaceuticals prior to this job. 

No employees reported being diagnosed with cancer, reproductive or immunodeficiency 

disorders, miscarriages, or giving birth to a child with a birth defect since being hired.

When asked “do you think you have any health problems related to working at [this 

company]?” 17 employees responded “yes,” 2 company and 15 contractor employees. Of 

the two company employees, one reported breaking out in hives twice when working in 

the Baker machine area, and one reported recurrent headaches. Both employees had sought 

medical care. Of the 15 contractor employees reporting a possible work-related health 

problem, ten reported musculoskeletal problems, four reported respiratory problems, three 

reported headaches, and one reported an infection. The musculoskeletal illnesses included 

back, foot, knee, leg, shoulder, hand/wrist, arm, and neck pain, with no one type reported 

by more than three employees. Ten of the 15 employees had seen a medical provider. When 

asked what they thought caused their health problem, six reported repetitive tasks, four 

reported prolonged standing, three reported pill dust, two reported stress, one reported noise, 

and two did not know. 

Most of the interviewed employees reported wearing gloves when handling hazardous drugs 

and when cleaning the Baker machine. Some employees reported wearing an N95 filtering 

facepiece respirator during certain activities, such as cleaning up spills or cleaning the Baker 

machine. Some shipping/packing employees were concerned that they were being exposed to 

dust from the adjacent Baker machine and/or pill dust on the outside of prescription bottles 

that they handled when preparing them for shipping. 

The three housekeeping employees had worked at the facility 3 years or less. None reported a 

work-related health problem, although one reported eye irritation that was worse at work, and 

one reported throat irritation that was worse at work.

Symptom Survey

Table 11 describes the responses to a symptom survey among company and contractor 

employees. Employees were asked if they had any of these symptoms in the past month 

and whether the symptom was better, worse, or the same when off of work. If the symptom 

was better when off of work, we defined the symptom as being associated with work. 

Although several symptoms had low numbers of employees reporting them, the percentage 

of contractor employees reporting eye, nasal, throat, and skin irritation and cough that were 

associated with work was more than twice that of company employees. 
Health Hazard Evaluation Report 2012-0044-3199 Page 13

Table 11. Health symptoms in the month before our visit among company employees (N = 18) and 

contractor employees (N = 50) 

Symptom Company employees Contractor employees

Yes

N (%)

Work-related

N (%)

Yes

N (%)

Work-related

N (%)

Eye irritation 6 (33) 2 (11) 20 (40) 14 (28)

Nasal irritation 4 (22) 1 (6) 17 (34) 10 (20)

Throat irritation 4 (22) 1 (6) 13 (26) 7 (14)

Headache 6 (33) 4 (22) 19 (38) 7 (14)

Shortness of breath 3 (17) 1 (6) 8 (16) 1 (2)

Cough 2 (11) 0 (0) 13 (26) 7 (14)

Wheeze 1 (6) 0 (0) 7 (14) 2 (4)

Nausea 1 (6) 1 (6) 5 (10) 1 (2)

Dizziness 2 (11) 1 (6) 6 (12) 3 (6)

Confusion 2 (11) 1 (6) 1 (2) 1 (2)

Feeling faint 0 (0) 0 (0) 2 (4) 2 (4)

Heart racing 1 (6) 1 (6) 5 (10) 1 (2)

Skin irritation 0 (0) 0 (0) 9 (18) 7 (14)

Irregular heart rhythm 1 (6) 0 (0) 1 (2) 0 (0)

We grouped pharmacists and pharmacy technicians by employer and compared their 

responses to the symptom survey questions (Table 12). A greater percentage of contractor 

pharmacists/pharmacy technicians reported skin, eye, nose, and throat irritation and 

respiratory symptoms than company pharmacists/pharmacy technicians.
Page 14 Health Hazard Evaluation Report 2012-0044-3199

Table 12. Health symptoms in the month before our visit among company (N = 13) and 

contractor (N = 37) pharmacists/pharmacy technicians

Symptom Company pharmacists and 

pharmacy technicians

Contractor pharmacists and 

pharmacy technicians

Yes

N (%)

Work-related

N (%)

Yes

N (%)

Work-related

N (%)

Eye irritation 3 (23) 1 (8) 15 (41) 9 (24)

Nasal irritation 2 (15) 0 (0) 13 (35) 7 (19)

Throat irritation 2 (15) 0 (0) 10 (27) 5 (14)

Headache 4 (31) 3 (23) 13 (35) 5 (14)

Shortness of breath 2 (15) 0 (0) 4 (11) 1 (3)

Cough 2 (15) 0 (0) 8 (22) 5 (14)

Wheeze 1 (8) 0 (0) 5 (14) 2 (5)

Skin irritation 0 (0) 0 (0) 4 (11) 2 (5)

We looked at the symptoms of nausea, dizziness, confusion, feeling faint, heart racing, and 

irregular heart rhythm reported by more than one employee in each job title. Contractor 

shippers/packers (N = 13) were the only employee group to have more than one employee 

report dizziness (3) and feeling faint (2) that was better when away from work. No company 

or contractor pharmacist/pharmacy technicians reported these as work-related symptoms.

Medical Record Review

We reviewed medical records of four employees. Two employees’ records documented 

symptoms of shortness of breath, but no diagnosis was given regarding these symptoms. One 

employee’s record documented frequent severe headaches, but did not indicate an association 

with work exposures. The fourth employee’s medical record documented an episode of 

headache and vomiting that began at work, but did not assess whether the symptoms 

were associated with work exposures. Overall, we saw no clear association between work 

exposures and the employees’ symptoms or medical conditions. We focused our record 

review on symptoms that could be related to pharmaceutical dust exposure; we did not 

request records regarding musculoskeletal injuries or disorders.

Occupational Safety and Health Administration Form 300 Log of Work-Related 

Injuries and Illnesses Review

We reviewed company and contractor OSHA Logs from 2009 through 2012. The most 

common entries in both company and contractor logs for all years were musculoskeletal 

injuries and disorders followed by lacerations, contusions, and abrasions. There was one 

entry for respiratory illness in 2009 and one entry for dermatitis in 2012.
Health Hazard Evaluation Report 2012-0044-3199 Page 15

Sampling Pharmaceutical Dust in Air and on Surfaces 

Real-time Particle Concentrations 

Results of the real-time particle measurements are in Appendix B, Figures B1–B7. We used 

this information, along with comments provided by employees on the dustiness of different 

pharmaceutical tablets, to decide which APIs to measure in the air samples. These figures 

show peaks in particle number concentrations that correlated with events involving specific 

APIs. Refilling Baker machine canisters with uncoated tablets (Appendix B, Figures B1–B3) 

and cleaning automated counters with canned air in the manual count area (Appendix B, 

Figure B6) produced elevated airborne dust concentrations. However, the highest transient 

particle number concentrations (up to 39,000 particles per liter) were measured during the 

cleaning and repairing of Baker machine cells by an employee on second shift (Appendix 

B, Figure B4). An employee who did this task on first shift (Appendix B, Figure B5) also 

generated airborne dust (up to 8,000 particles per liter). These employees wore vinyl gloves 

but no other personal protective equipment or clothing. Emptying uncoated tablets from cells 

into bins and returning those tablets back to the cells (after cleaning or repairing the cells) 

produced the most airborne dust. Most of the particles released during cleaning and repairing 

of cells were > 10 micrometers (μm) in aerodynamic diameter. Conversely, most of the 

particles produced when an employee cleaned the automated counter with canned air were 

< 1 μm in aerodynamic diameter. Particles 0.3 to > 10 μm in aerodynamic diameter were 

produced when refilling canisters.

Air Concentrations of Inhalable Dust, Lactose, and Active Pharmaceutical 

Ingredients

The full-shift (~8 hours) personal and area air sample concentrations of inhalable dust 

are summarized in Figure 3. The full-shift personal and area air concentrations of lactose 

(inactive filler in tablets) are summarized in Figure 4. Values that were not detectable 

(ND) in the bar graphs were assigned values created by dividing the minimum detectable 

concentrations (MDCs) by the square root of two. The MDCs and minimum quantifiable 

concentrations (MQCs) were calculated by dividing the analytical limits of detection and 

quantitation (mass units) for each analyte by the average volume of air sampled. The MDCs 

and MQCs represent the lowest air concentrations that could have been detected (MDC) or 

quantified (MQC) and are provided in Appendix C, Figure C1 for each analyte. 
Page 16 Health Hazard Evaluation Report 2012-0044-3199

The personal air concentrations are more informative than the area air concentrations because 

they represent what employees could inhale. The highest average personal inhalable dust 

concentrations were measured on employees in the bulk/hazardous drug area and Baker refill 

area, as well as on the housekeeping employees. The highest maximum personal inhalable 

dust concentrations were measured on employees in the Baker maintenance and refill areas. 

The highest average and maximum personal lactose concentrations were measured on 

employees who worked in the Baker maintenance and refill areas. The background area air 

concentrations of lactose measured in the offices were significantly less than the area air 

concentrations of lactose measured in the production areas (two-sample t-test; P = 0.035) 

and the personal air concentrations of lactose measured on employees who worked in the 

production areas (two-sample t-test; P = 0.029). This finding suggests that pharmaceuticals 

were the main source of airborne lactose (minimal outside sources).

Figure 3. Average full-shift personal and area air concentrations of inhalable dust by process or work 

area. The number of samples and error bars representing the minimum and maximum concentrations 

are provided if more than one sample was collected.
Health Hazard Evaluation Report 2012-0044-3199 Page 17

Figure 4. Average full-shift personal and area air concentrations of lactose by process or work area. 

The number of samples and error bars representing the minimum and maximum concentrations are 

provided if more than one sample was collected.

In addition to the full-shift air samples, we collected a task-based (20-minute) personal 

air sample on a housekeeping employee emptying a wet/dry vacuum (day 3). This sample 

measured no inhalable dust (< MDC of 2,400 micrograms per cubic meter [μg/m3]) and 

40 μg/m3 of lactose. This level of lactose suggests that some pharmaceutical dust was 

released into the air where it could be inhaled during this task. The slightly elevated realtime particle measurements during this task (Appendix B, Figure B5) provide additional 

support for this conclusion. The housekeeping employee wore nitrile gloves and a NIOSHapproved N95 filtering facepiece respirator (Honeywell/Wilson Saf-T-Fit Plus) during this 

task; however, we observed that the respirator did not seal properly around the employee’s 

face. We also collected a personal air sample on an employee who hand-filled prescriptions 

in the manual count area during second shift (day 2). This sample was collected for only 

part of the shift (260 minutes) and measured 810 μg/m3 of inhalable dust and 5.2 μg/m3 of 

lactose during that time period. 
Page 18 Health Hazard Evaluation Report 2012-0044-3199

Figure 5. Average full-shift personal and area air concentrations of specific APIs measured in the Baker 

refill area. Background area air concentrations of lisinopril and HCTZ (measured in the offices) are also 

provided. The number of samples and error bars representing the minimum and maximum concentrations are provided if more than one sample was collected.

Figure 5 summarizes the full-shift personal and area air concentrations of specific APIs 

measured in the Baker refill area. The background air concentrations of lisinopril and HCTZ 

measured in the office areas are also provided for comparison. We compared the personal 

air concentrations to published manufacturers’ OELs or the lower bound of published 

manufacturer’s hazard control bands (Appendix D, Table D1). All air concentrations were 

below these limits except for one area air concentration of lisinopril (1.1 μg/m3). This area 

air sample was collected above the canister of HCTZ/lisinopril tablets. Although this sample 

does not represent personal exposure, it does indicate that lisinopril dust was released into the 

work environment. Personal air concentrations of lisinopril, however, were all ND (same as 

background levels).
Health Hazard Evaluation Report 2012-0044-3199 Page 19

Figure 6 presents the full-shift personal and area air concentrations of specific APIs measured 

in the Baker maintenance area. Dust containing these APIs was released when cells were 

cleaned. The personal air concentration of naproxen was below the manufacturer’s OEL 

[Roche 2006]. The manufacturer’s hazard control band for levothyroxine is < 1 μg/m3

[Pfizer 2011]; hence, the arrows in the figure indicate a lower bound of the hazard control 

band somewhere below 1 μg/m3. Because most hazard control bands established by 

pharmaceutical manufacturers span one order of magnitude, a lower bound of 0.1 μg/m3 may 

be reasonable for evaluating exposure. All air concentrations of levothyroxine were below 

0.1 μg/m3. 

Figure 6. Full-shift personal and area air concentrations of levothyroxine and naproxen measured in the 

Baker maintenance area.
Page 20 Health Hazard Evaluation Report 2012-0044-3199

Figure 7. Average full-shift personal and area air concentrations of hydrocodone measured in the controls 

area. The number of samples and error bars representing the minimum and maximum concentrations are 

provided if more than one sample was collected.

Employees’ exposures to multiple APIs (during a single work shift) cannot be seen in the 

bar graphs. The results from sampling multiple APIs in three employees’ personal breathing 

zones are therefore provided in Table 13. The Baker maintenance employee on second 

shift was only sampled for part of the shift. This employee’s personal air concentration 

of lisinopril during the sampled period was above the lower bound of the manufacturer’s 

hazard control band [Bristol-Myers Squibb Company 2012b]. Assuming zero exposure for 

the unsampled time period is not appropriate because this employee continued to do tasks 

that could release pharmaceutical dust (e.g., clean cells). However, even if no other lisinopril 

exposure occurred for the rest of the shift, this employee’s 8-hour time-weighted average 

(1.5 μg/m3) would still exceed the manufacturer’s OEL. All other personal air concentrations 

were below applicable manufacturer’s OELs.

The full-shift personal and area air concentrations of hydrocodone measured in the controls 

area are summarized in Figure 7. All air concentrations were below the manufacturer’s OEL 

of 5 μg/m3 [Abbott Labs 2011]. 
Health Hazard Evaluation Report 2012-0044-3199 Page 21

Table 13. Results from sampling multiple APIs in an employee’s personal breathing zone

Process 

description

Sample 

no.*

Sample 

time 

(min)

Personal air concentration (μg/m3)

Inhalable 

dust

Lactose

HCTZ

Lisinopril

Furosemide

Gabapentin

Buspirone

Baker refill, 

day 1,

first shift

13/17† 481 ND–370 NA NA NA NA ND ND

Baker refill,

day 2,

first shift

25/40† 481 (330)§–490 9.2 0.21 ND (0.10)§ NA NA

Baker 

maintenance, 

day 2,

second shift

21 279 1,600 67 36 2.5 NA NA NA

MDC‡ 100 0.003 0.02 0.1 0.05 0.05 5

MQC‡ 470 0.01 0.065 0.36 0.18 0.18 18

Manufacturer 

OEL or hazard 

control band¶

NA NA 100 1–10 NA 1,200 10

*Sample numbers are provided for cross-referencing with the figures in Appendix B.

†Side-by-side personal air samples were collected.

‡MDC and MQC provided were based on 8 hours of sampling.

§Values between the MDC and MQC are shown in parentheses to point out that there is more 

uncertainty associated with these values than with concentrations above the MQC.

¶HCTZ [Bristol-Myers Squibb Company 2012a], Lisinopril [Bristol-Myers Squibb Company 

2012b], Gabapentin [Pfizer 2010], Buspirone [U.S. Pharmacopeia 2006]. More information on the 

manufacturer’s OELs is provided in Appendix D.

Air Concentrations of Hazardous Drugs

Of the 32 hazardous drugs dispensed as tablets at the pharmacy, we only observed the 

filling of methotrexate prescriptions. Appendix B, Figure B7 shows the real-time particle 

measurements near the breathing zone of the employee who filled methotrexate prescriptions 

(day 1). These measurements do not show particle levels above background while 

methotrexate tablets were being handled. However, methotrexate dust was measured in two 

full-shift area air samples collected during this workday. The area air sample positioned 

near the employee who hand-filled the methotrexate prescriptions measured 0.008 μg/m3 of 

methotrexate. A fan on the wall behind this employee produced a current of air through the 

hazardous drug area that could transport pharmaceutical dust to other workstations. The area 

air sample that was positioned downwind at a pharmacy technician’s workstation measured 

0.0003 μg/m3 of methotrexate. A personal air sample was collected on an employee who 

hand-filled methotrexate prescriptions during second shift (day 2) and methotrexate was 

ND (< 0.0006 μg/m3). However, this sample only ran for 94 minutes because this employee 
Page 22 Health Hazard Evaluation Report 2012-0044-3199

was moved to a different area shortly after starting the shift. All of these air concentrations 

were more than an order of magnitude below the manufacturer’s OEL of 0.3 μg/m3 [U.S. 

Pharmacopeia 2013b].

Surface Contamination Levels of Lactose and Active Pharmaceutical Ingredients

Table 14 gives the levels of lactose and hydrocodone measured on surfaces in the pharmacy. 

We sampled in the offices to estimate background contamination. Levels of lactose measured 

on surfaces in the offices were below the levels measured on surfaces in the Baker machine 

area. Hydrocodone was detected at each sampled workstation in the controls area. In 

addition, eight surface samples were collected in the hazardous drug area for methotrexate. 

All were ND (< 0.001 μg/m3) except for a sample collected from the workstation of the 

employee who filled methotrexate prescriptions (day 1). This sample was collected before 

the employee cleaned the surface with isopropyl alcohol wipes. Two other surface samples 

were collected in the Baker refill area on surfaces where dust had accumulated. One of these 

samples measured 2.8 μg/100 cm2 of glipizide on the shelf below a canister of glipizide; the 

other sample measured 6,900 μg/100 cm2 of methocarbamol above the canister containing 

this drug.

Table 14. Surface contamination levels (μg/100 cm2) of lactose and hydrocodone

General location Specific location Lactose Hydrocodone

Background Administrative office desk (0.04)* NA

Fiscal office desk (0.03)* NA

Procurement office desk (0.02)* NA

Sign-in podium in entrance (0.02)* NA

Baker machine Workstation surface between monitors 0.79 NA

Electrical box near pharmacist verification station 1.2 NA

Electrical box near exhaust hood 8.5 NA

A-frame near the machine 18 NA

Above primidone canister 3.7 NA

Controls CT1 workstation NA 3.2

CT3 workstation NA 1.9

CT4 workstation/cart lower shelf NA (1.3)*

Detection limit 0.02 0.5

Quantitation limit 0.06 1.7

*Values between the detection limit and quantitation limit are shown in parentheses to point out that 

there is more uncertainty associated with these values than with levels above the quantitation limit.

Other Observations and Findings

Employees demonstrated good housekeeping and hand-washing practices. Employees 

cleaned their workstations periodically throughout the day, typically using isopropyl alcohol 

wipes. The housekeeping employees cleaned surfaces (e.g., sweeping and vacuuming) and 

emptied trash throughout the day. During the first shift, the employees we observed washed 

their hands before eating during their lunch break.
Health Hazard Evaluation Report 2012-0044-3199 Page 23

Protective clothing and eyewear were not required or provided to employees in any areas of 

the pharmacy. Most employees wore vinyl gloves when handling pharmaceuticals as required 

by the employer and when cleaning surfaces with isopropyl alcohol wipes. We observed 

no employees voluntarily wearing hearing protection, but we did observe a housekeeping 

employee voluntarily wearing an N95 filtering facepiece respirator when emptying 

the bag in the wet/dry vacuum. We saw white dust on a black shirt of a Baker machine 

maintenance employee after this employee cleaned several cells. This dust likely was from 

the pharmaceuticals. This employee did not use the exhaust hood even though the standard 

operating procedures required its use. 

We observed one Baker maintenance employee using the exhaust hood when cleaning a cell. 

The exhaust hood effectively captured airborne dust released when this employee HEPA 

vacuumed the cell inside the hood. However, the employee emptied and refilled the cell 

outside the hood. The hood did not appear large enough to accommodate these tasks, which 

our data suggest have potential to produce airborne pharmaceutical dust. 

Discussion

Overall, employees had a positive perception of safety climate. However, contractor 

pharmacists and pharmacy technicians had less favorable views of safety training and the 

amount of risk employees are exposed to when compared to company employees with the same 

job titles. These differences should be explored further to determine what causes the difference 

in perception between contractor and company employees, and whether the issues are related 

(e.g., is the perception of risk greater for contractor employees due to gaps in training?).

A common theme reported by contractor employees was that the work attendance policy is 

associated with job stress and a strain on employer-employee relations. Contractor employees 

reported being penalized for staying home if they were ill, even if their illness was serious, 

and they had a doctor’s note. Only five (10%) contractor employees reported that they 

were comfortable staying home if they were ill. The punitive attendance system encourages 

presenteeism, which is defined as “attending work while ill” [Johns 2010]. Presenteeism 

is associated with productivity loss [Schultz and Edington 2007] and the spreading of 

contagious illnesses throughout the workplace [Widera et al. 2010]. Some studies have 

shown that presenteeism results in as much if not more costs than absenteeism [Stewart et al. 

2003; Cooper and Dewe 2008]. 

Of the 22 employees who described a poor employer-employee relationship, 14 (64%) 

specifically mentioned the point system for punishing illness absences when describing the 

relationship. While the attendance policy appears to play a role in contractor employees’ 

reports of a strained relationship with their supervisor, other factors should also be further 

explored to determine the nature of the interpersonal conflict. Interpersonal conflict at work 

is associated with greater levels of stress, psychosomatic complaints, and burnout among 

employees [De Dreu et al. 2003]. 
Page 24 Health Hazard Evaluation Report 2012-0044-3199

Contractor employees with the job title of shipper/packer reported the greatest amount of 

concern about exposures at work impacting their health. These employees also reported 

the greatest amount of job stress compared to employees with other titles. These findings 

warrant further investigation to determine what factors are associated with shippers/packers’ 

perceptions of job stress and work-related health concerns. 

Pharmaceutical dust can irritate the eyes, nose, throat, and skin. Our medical assessment 

found higher percentages of contractor employees reporting respiratory symptoms and eye, 

nasal, throat, and skin irritation that were associated with work than company employees. 

This is likely due to contractors performing job tasks with higher potential pill dust 

exposures. Two contractor employees reported developing asthma-like symptoms since 

being hired. Although medical records did not document asthma as a diagnosis, patients with 

asthma may have intermittent bronchial hyperreactivity and not exhibit symptoms at the 

time of medical evaluation. Other employees with pre-existing asthma reported increased 

symptoms at work, and one employee reported developing hives when working near the 

Baker machine. These employees may have developed sensitization to certain pharmaceutical 

dusts. Pharmaceutical dust exposures may elicit allergic respiratory and skin symptoms in 

sensitive individuals, potentially resulting in allergic medical conditions such as allergic 

asthma, rhinitis, urticaria (hives), and contact dermatitis [Teichman et al. 1988; Bernstein et 

al. 1999; Heron and Pickering 2003; Zuskin et al. 2004]. 

About one fourth of employees reported concerns about prolonged standing and repetitive, 

forceful motions using extreme postures. Musculoskeletal disorders are conditions that involve 

the soft tissues, including the nerves, tendons, and muscles. They can be characterized by 

intermittent pain which can restrict mobility and interfere with normal activity. Work-related 

musculoskeletal disorders refer to musculoskeletal disorders to which the work environment 

and the performance of work contribute significantly or are made worse by work conditions. A 

substantial body of data provides strong evidence of an association between musculoskeletal 

disorders and certain work-related factors (physical, work organizational, psychosocial, 

individual, and sociocultural). Personal factors can also influence the response to risk factors 

for musculoskeletal disorders; these personal factors include age, sex, smoking, physical 

activity, strength, and body measurements such as height and weight. Although personal factors 

may affect an individual's susceptibility to overexertion injuries/disorders, studies in highrisk industries show that the risk associated with personal factors is small compared to that 

associated with occupational exposures [NIOSH 1997a]. In all cases, the preferred method 

for preventing and controlling musculoskeletal disorders is to design jobs, workstations, tools, 

and other equipment to match the physiological, anatomical, and capabilities of the employee. 

Under these conditions, exposures to risk factors considered potentially hazardous are reduced 

or eliminated.

Cleaning automated counters with canned air in the manual count area, refilling canisters, 

and cleaning and repairing cells in the Baker machine area correlated with peaks in realtime particle number concentrations. The emptying and refilling of cells during the cleaning 

and repairing process (second shift, day 2) produced the largest increase in particle number 

concentrations. Particles of various sizes were measured (0.3 to > 10 μm in aerodynamic 
Health Hazard Evaluation Report 2012-0044-3199 Page 25

diameter); the predominant particle size produced depended on the task. For example, most 

particles produced during the cleaning and repairing of cells were > 10 μm in aerodynamic 

diameter; while most particles produced when an employee cleaned the automated counter 

with canned air were < 1 μm in aerodynamic diameter. In an evaluation at an outpatient 

pharmacy, we found that mostly small particles (< 3 μm) were generated when compressed 

air was used to clean canisters [NIOSH 2013a]. Thus, it appears that using canned or 

compressed air to clean pharmaceutical equipment can produce a greater portion of small 

particles than what other common tasks (e.g., refilling cells or canisters) produce. Particles 

< 3 μm in diameter remain airborne longer than particles > 10 μm in diameter (hours versus 

minutes) and are capable of penetrating deeper into the lungs.

Our inhalable dust air samples collected particles that can be deposited anywhere in the 

respiratory system, including the nose and mouth. These particles range from < 1 μm to 

> 100 μm in aerodynamic diameter. Measuring inhalable dust is appropriate for 

pharmaceutical exposure assessments because many APIs are water soluble and can be 

absorbed anywhere in the respiratory system, including nasal passages. The inhalable dust 

concentrations provide a relative indication of the areas that are the dustiest. However, 

inhalable dust is not specific to pharmaceuticals because it can include dust from other 

sources. That we found lactose (an inactive filler in tablets) in significantly higher air 

concentrations in the production areas compared to the nonproduction areas suggests that 

pharmaceuticals were the main source of lactose. Average concentrations of lactose were 

highest in the personal breathing zones of employees in the Baker maintenance and refill 

areas. Employees in these areas also had the highest maximum personal air concentrations of 

inhalable dust. 

Most APIs do not have OELs set by federal agencies or national organizations. Because 

pharmaceuticals are biologically active and typically water soluble, OELs for nuisance dusts 

or “particles not otherwise specified” do not apply [ACGIH 2013]. Thus, when available, we 

used manufacturers’ OELs for comparing our results. Pharmaceutical manufacturers establish 

OELs or hazard control bands primarily using a control banding process. Appendix D 

provides more information on control banding. All personal air concentrations of APIs were 

below manufacturer’s OELs, except for the personal air concentration of lisinopril measured 

on the Baker maintenance employee during second shift (day 2). Possible acute health effects 

from high exposures to lisinopril listed on the safety data sheet included dizziness, headache, 

and allergic reactions [Bristol-Myers Squibb Company 2012b]. Maintaining airborne 

lisinopril exposures below the manufacturer’s OEL should prevent these health effects in 

most employees. Although a Baker maintenance employee’s exposures to levothyroxine were 

below the manufacturer’s hazard control band upper bound (no lower bound was provided), 

the safety data sheet specifically recommends that “All operations should be fully enclosed 

[with] no air recirculation permitted” [Pfizer 2011]. This employee cleaned the cell that 

housed levothyroxine outside of the exhaust hood. The exhaust hood recirculated air through 

a HEPA filter.

Methotrexate was the only hazardous drug we observed being dispensed, and hence, the 

only hazardous drug we sampled in air. The health risk from hazardous drugs depends 
Page 26 Health Hazard Evaluation Report 2012-0044-3199

on how much exposure an employee has to these drugs and how toxic they are [NIOSH 

2004]. Methotrexate has been shown to cause birth defects in infants of women who took 

therapeutic doses of the drug while pregnant [Lloyd et al. 1999; Pfizer 2012]. However, the 

therapeutic dose of methotrexate (milligram levels) is substantially higher than the dose 

that would typically be obtained from working with the drug in a pharmacy (microgram 

levels) especially if workplace exposures are kept below the manufacturer’s OEL. We found 

quantifiable levels of methotrexate in air near two employees who worked in the hazardous 

drug area. Although these were not personal air samples, they indicate a potential for 

inhalation exposure. However, both of these air concentrations were more than an order of 

magnitude below the manufacturer’s OEL [U.S. Pharmacopeia 2013b]. Even lower exposures 

are expected if employees use engineering controls. The safety data sheet for methotrexate 

recommends that employees “Use a laboratory fume hood, vented enclosure, glove box, or 

other effective containment” [U.S. Pharmacopeia 2013b]. 

NIOSH considers pharmaceuticals to be hazardous drugs when they exhibit one or more of 

the following characteristics in humans or animals: (1) carcinogenicity, (2) teratogenicity 

(toxic effects to the fetus in utero), (3) reproductive effects (infertility), (4) organ toxicity at 

low doses, (5) genotoxicity (chromosomal mutations), and (6) have structures and toxicity 

profiles that mimic existing hazardous drugs [NIOSH 2012]. Exposure to APIs not classified 

as hazardous are still capable of producing a biological effect in the body that may result in 

adverse health effects [Teichman et al. 1988; Heron and Pickering 2003]. For example, it 

is possible that substantial exposure to high blood pressure medication dust can lead to low 

blood pressure in some employees and could result in symptoms of dizziness and headaches 

[Bristol-Myers Squibb Company 2012b]. Headaches were reported in about one third of 

company and contractor employees; however, headaches are very common in the general 

population, and their cause is often difficult to determine. There was no evidence gathered 

during our evaluation that headaches reported by employees were related to exposure 

to high blood pressure medication dust. No employees reported miscarriages, infertility 

problems, giving birth to a child with birth defects, or being diagnosed with cancer or 

immunodeficiency disorders since being hired to work at this facility. 

The thyroid gland produces hormones that help regulate the body’s metabolism, that is, the 

rate of many activities in the body. A thyroid working correctly will produce the right amount 

of hormones needed to keep the body’s metabolism working at a rate that is not too fast or 

too slow. When it is not working correctly, the thyroid can produce more hormones than 

it needs (hyperthyroidism) or much less than it needs (hypothyroidism). Hyperthyroidism 

and hypothyroidism can be caused by hereditary factors, autoimmune disorders, an excess 

or deficiency of iodine, and prior radiation treatment, but some causes remain unknown. 

Hypothyroidism is fairly common in the United States, occurring in close to 5% of the 

population. Hypothyroidism is more common among women, whites, and Latinos [Ladenson 

and Kim 2008]. Hyperthyroidism is less common, with a lifetime prevalence of 1%. The rates 

of reported thyroid disorders among interviewed employees appear high when compared to 

the general population; however, comparing a working group with very small numbers to 

the general population in the U.S. is neither reliable nor accurate. Rates are highly variable 

in small populations (such as a workplace) and rarely match the overall rate for a larger 
Health Hazard Evaluation Report 2012-0044-3199 Page 27

area, such as a state, so that for any given time period some populations have rates above the 

overall rate and others have rates below the overall rate. So, even when a higher rate occurs, 

this may be completely consistent with the expected random variability. Although exposure 

to some APIs (e.g., levothyroxine) could affect normal thyroid function, six of the eight cases 

of known thyroid conditions reported by the employees were hypothyroidism, which would 

not have been related to levothyroxine exposures. 

Our sampling results demonstrate that employees can be exposed to dust that contains 

hazardous drugs. If hazardous drugs continue to be filled the same way, the potential 

for overexposures will depend on the dustiness of the tablets, formulation of the tablets 

(percentage of tablets that is the hazardous drug), and how many prescriptions are filled. 

Even if no overexposures to hazardous drugs occur, reducing exposures as much as feasible 

is prudent and encouraged in the NIOSH Alert, “Preventing Occupational Exposure to 

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

Our finding of air concentrations of APIs below manufacturer’s OELs for most of the 

processes does not necessarily mean that employees are adequately protected all the time. 

We were not able to quantify all possible API exposures primarily because of laboratory 

analytical limitations, and not all the quantified APIs had published manufacturer’s OELs for 

comparison. Also, the air samples we collected over a 3-day period may not be representative 

of exposures throughout the year because exposures can vary over time. In addition, our 

sampling results demonstrated that some employees (i.e., one who refilled Baker machine 

canisters and one who maintained the Baker machine) were exposed to multiple APIs during 

their workday. Additive or synergistic effects from multiple API exposures are possible but 

not well understood. 

The surface sampling results indicate that pharmaceutical dust deposits onto surfaces in 

the four areas where we focused our sampling: Baker maintenance, Baker refill, controls, 

and hazardous drugs. Specific APIs were detected on work surfaces used when filling 

prescriptions (e.g., hydrocodone and methotrexate) and on surfaces near where canisters were 

refilled (e.g., methocarbamol and glipizide). The presence of lactose, although not specific 

to any particular API, suggests the presence of APIs; no other sources of lactose existed in 

this environment. These results also indicate a potential for skin or clothing contamination. 

We observed suspected pharmaceutical dust on one employee’s shirt after this employee 

cleaned several canisters. Such contamination of skin or clothing could lead to hand-tomouth ingestion of pharmaceuticals during eating or smoking and to take-home exposure. 

Children at home may be especially susceptible to adverse health effects from API exposures 

[Brent et al. 2004]. These results, therefore, underscore the importance of having adequate 

housekeeping and hand-washing practices, and wearing protective clothing and eyewear in 

these areas at least until engineering controls are implemented and shown to be effective at 

reducing employee exposures and work surface contamination to the lowest feasible levels. 

The pharmacy employees demonstrated good housekeeping and hand-washing practices, but 

none of the employees were provided or otherwise wore protective clothing or eyewear.
Page 28 Health Hazard Evaluation Report 2012-0044-3199

We identified a few deficiencies related to the personal protective equipment and engineering 

controls used at the pharmacy. Our observation of one employee’s use of the N95 filtering 

facepiece respirator suggests a need for retraining on how to select the appropriate size of 

respirator and how to adjust the respirator to seal properly around the face. Vinyl gloves 

were worn by most employees when handling pharmaceuticals or when cleaning surfaces 

or equipment with isopropyl alcohol wipes. However, nitrile gloves are more resistant than 

vinyl gloves to isopropyl alcohol [Forsberg and Mansdorf 2007]. If isopropyl alcohol were 

to permeate through vinyl gloves, it could deliver APIs on the gloves to the skin underneath. 

This route of exposure is of special concern for employees who handle cytotoxic or other 

hazardous drugs because these drugs can damage the skin or, in some cases, absorb through 

the skin and become systemically available. Compared to vinyl gloves, the neoprene gloves 

provided in the hazardous drug spill kits are resistant to far more chemicals [Forsberg and 

Mansdorf 2007]. However, neoprene gloves have not been tested against liquid hazardous 

drugs. Employees who unpacked drug shipments, including hazardous drugs, did not always 

wear gloves. Investigators in other studies have found contamination on the outside of vials 

containing antineoplastic drugs [Connor et al. 2005; Schierl et al. 2010]. Although not part 

of our evaluation, some pharmaceutical bottles could be contaminated with APIs. Therefore, 

employees should wear nitrile gloves when unpacking pharmaceutical shipments, especially 

hazardous drug shipments. Likewise, employees should wear nitrile gloves when handling 

prescription bottles filled with hazardous drugs. Although cleaning and repairing Baker 

machine cells produced among the highest levels of particle number concentrations, inhalable 

dust, lactose, and certain APIs (e.g., lisinopril), we observed only one Baker maintenance 

employee using the recirculating exhaust hood for cleaning and repairing cells. More Baker 

maintenance employees may have used the recirculating exhaust hood had it been large 

enough to accommodate all the cleaning tasks.

Conclusions 

The system of penalizing contractor employees for not reporting to work when ill could 

have negative effects on productivity and morale. Compared to company employees, the 

higher numbers of reported eye, skin, and upper and lower respiratory irritation by contractor 

employees could be related to pharmaceutical dust exposures. Some health conditions 

reported by contractor employees, such as hives and asthma, are consistent with an allergic 

response to certain present APIs. Prompt medical attention is needed to sort out workrelatedness when these conditions occur, and a good medical surveillance program can ensure 

early identification and needed action. Our air sampling results indicate that employees 

cleaning or repairing Baker machine cells, refilling Baker machine canisters, cleaning 

automated counters with canned air, and hand-filling hazardous drug prescriptions may be 

exposed to airborne dust from uncoated tablets. Inhalation exposures to APIs were mostly 

below manufacturers’ OELs (if an OEL was available). However, some employees were 

exposed to multiple APIs, the effects of which are not well understood. The surface sampling 

results and our observations also indicate the potential for personal clothing contamination 

with APIs and take home exposure. 
Health Hazard Evaluation Report 2012-0044-3199 Page 29

Recommendations

We encourage the pharmacy to use an employer-employee health and safety committee or 

working group to discuss the recommendations in this report and develop an action plan. 

These recommendations are based on the hierarchy of controls approach that groups actions 

by their likely effectiveness in reducing or removing hazards. 

An important first step in the management of occupational exposures to pharmaceuticals 

is obtaining information on the potential for workplace exposures to APIs and risk of 

those exposures. We gathered some of this information during our evaluation. However, 

additional information should be gathered now and in the future, especially as new 

pharmaceuticals and formulations enter the market and are brought into the pharmacy. We 

recommend determining which pharmaceuticals are more friable and capable of producing 

dust. Employees who work with the pharmaceuticals may be able to help identify these 

dusty pharmaceuticals. We also recommend obtaining safety data sheets and reviewing 

manufacturer exposure guidelines and toxicity data for all tablets. Safety data sheets from 

the original manufacturer of the name-brand pharmaceutical or from U.S. Pharmacopeia 

may contain the most detailed information. This information can then be used to develop a 

priority list of dusty pharmaceuticals that are potentially hazardous at low concentrations 

(e.g., manufacturers’ OELs < 10 μg/m3 or on the NIOSH list of hazardous drugs). Employees 

who handle these pharmaceuticals in ways that could cause the dust to become airborne may 

require a higher level of protection than other employees. 

Elimination and Substitution

Eliminating or substituting hazardous processes or materials reduces hazards and protects 

employees more effectively than other approaches. Prevention through design, considering 

elimination or substitution when designing or developing a project, reduces the need for 

additional controls in the future.

1. Substitute uncoated tablets with coated tablets when that option is available. Coated 

tablets are less likely to produce dust.

Engineering Controls 

Engineering controls reduce employees’ exposures by removing the hazard from the process 

or by placing a barrier between the hazard and the employee. Engineering controls protect 

employees effectively without placing primary responsibility of implementation on the 

employee. 

1. Install one or two partially enclosed local exhaust hoods that are ducted outdoors. The 

American Conference of Governmental Industrial Hygienists Industrial Ventilation 

Manual provides guidelines on the optimal duct and face velocity for the control of 

very fine light dusts [ACGIH 2010]. If two hoods are installed, one could be used for 

hand filling hazardous drug prescriptions in a dedicated area, and the other could be 

used for filling prescriptions or refilling canisters with pharmaceuticals on the priority 
Page 30 Health Hazard Evaluation Report 2012-0044-3199

list or when cleaning cells that housed pharmaceuticals on the priority list. Make 

sure the hoods are large enough to accommodate the tasks that will be done inside 

the hoods. Ducting the hoods outdoors, ideally 30 feet or more from the building’s 

air intakes, should prevent the re-entrainment of APIs into the work environment 

[ASHRAE 2010]. Alternatively, a local exhaust hood with recirculated HEPA 

filtration could be used for work involving nonvolatile pharmaceuticals provided the 

manufacturers of the pharmaceuticals permit this. 

2. Install seats at workstations that currently require prolonged periods of standing. 

Doing so will give employees an opportunity to take pressure off their feet periodically 

throughout the day.

3. Install adjustable workstations that can accommodate up to 90% of employees. You 

may want to consult with an ergonomist. Ergonomics programs have been shown to be 

cost effective, and ergonomic improvements may result in increased productivity and 

higher product quality. Promoting employee involvement in these efforts can enhance 

job satisfaction and increases problem-solving capabilities [NIOSH 1997b].

Administrative Controls

The term “administrative controls” refers to employer-dictated work practices and policies 

to reduce or prevent hazardous exposures. Their effectiveness depends on employer 

commitment and employee acceptance. Regular monitoring and reinforcement are necessary 

to ensure that policies and procedures are followed consistently.

1. Create a formal procedure for employees to report and receive feedback regarding 

health and safety concerns, perhaps through formation of a health and safety 

committee. This would involve documenting the concerns, explaining what will 

be done to address the concerns, or explaining why no action is necessary. The 

documentation of this process can then be shared with all employees. Increasing 

employee involvement in identifying and mitigating safety policies and procedures 

may benefit the company if employees feel that their concerns and suggestions are 

heard and appreciated.

2. Create a mechanism whereby all employees have the opportunity to make anonymous 

reports of health and safety concerns. 

3. Discontinue the point system for contractor employees’ illness absences. Point systems 

can discourage reporting of illness and encourage workers to report to work when 

they are ill. When workers report to work with a contagious illness, they put their 

coworkers at increased risk of becoming ill. 

4. Explore further why some contractor employees reported a strained interpersonal 

relationship with their supervisor. An anonymous survey focusing on this topic may be 

helpful. A survey can be done by an external consultant, who can also hold confidential 

interviews or focus groups with employees about employer-employee relations. The 

Society for Industrial and Organizational Psychology maintains a consultant locator 

at http://www.siop.org/consultantlocator/search.aspx. The American Society of Safety 
Health Hazard Evaluation Report 2012-0044-3199 Page 31

Engineers also maintains directories of qualified consultants at http://www.asse.org/

practicespecialties/consultants/.

5. Encourage all employees to report possible work-related health conditions early. 

Employees with persistent symptoms should be evaluated by an occupational medicine 

physician or a medical provider specializing in workplace diseases and illnesses.

6. Under the guidance of an occupational medicine physician, employees who experience 

signs and symptoms of allergy to specific pharmaceuticals should be moved to a new 

work area. Wages and benefits should be maintained as per the original position.

7. Update the standard operating procedures and training on the safe handling of 

pharmaceuticals (including hazardous drugs) to include the control measures that you 

implement from our recommendations. For example, procedures and annual training 

on how to properly use and maintain engineering controls (e.g., local exhaust hood) 

and personal protective equipment may need updating.

8. Consult a ventilation specialist to install and commission the local exhaust hood(s). 

Validate hood performance at least annually.

9. Ask the company industrial hygienist to evaluate potential exposures to 

pharmaceutical dust when employees replace the HEPA filter in the local exhaust 

hood if the decision is made to continue using a recirculating hood. The purpose of 

this evaluation would be to verify whether the current standard operating procedure 

protects employees from being exposed to a mixture of pharmaceuticals. 

10.Follow the manufacturer’s guidelines when replacing the HEPA filter in the vacuum. 

Wear nitrile gloves and work under a hood when doing this task.

Personal Protective Equipment

Personal protective equipment is the least effective means for controlling hazardous 

exposures. Proper use of personal protective equipment requires a comprehensive program 

and a high level of employee involvement and commitment. The right personal protective 

equipment must be chosen for each hazard. Supporting programs such as training, changeout schedules, and medical assessment may be needed. Personal protective equipment should 

not be the sole method for controlling hazardous exposures. Rather, personal protective 

equipment should be used until effective engineering and administrative controls are in place.

1. Require employees to wear nitrile gloves instead of vinyl gloves when dermal exposure 

to pharmaceutical dust is possible, including when unpacking shipments of hazardous 

drugs or handling prescription bottles filled with hazardous drugs. Nitrile gloves are 

more resistant to isopropyl alcohol and many other chemicals than vinyl gloves.

2. Replace neoprene gloves in the existing hazardous drug spill kits with chemotherapy 

gloves approved by the U.S. Food and Drug Administration. These gloves provide 

protection against liquid chemotherapy drugs.
Page 32 Health Hazard Evaluation Report 2012-0044-3199

3. Provide a sufficient number of respirator models and sizes from which employees can 

choose a respirator for voluntary use. Train employees on how to select the appropriate 

size N95 filtering facepiece respirator and how to adjust these respirators to seal around 

their face. Notify all employees of the location(s) where these respirators are located.

4. Provide safety glasses and long-sleeve protective clothing to employees who perform 

tasks outside the hood that could generate airborne pharmaceutical dust or hand fill 

hazardous drug prescriptions even when filling them inside the local exhaust hood. 

The protective clothing should either be disposable or kept at work and laundered 

weekly by a laundry service. Wearing protective clothing should minimize the 

potential for take-home exposure. 
Health Hazard Evaluation Report 2012-0044-3199 Page 33

Appendix A: Analytical Methods

Gravimetric analysis of the personal and area inhalable dust air samples was performed using 

NIOSH Method 0600 [NIOSH 2012]. After gravimetric analysis, the air samples were further 

analyzed for lactose and/or specific APIs. The surface wipe samples were also analyzed for 

lactose or specific APIs. Of these APIs, warfarin was analyzed using NIOSH Method 5002 

[NIOSH 2012]. All other APIs and lactose were analyzed using BVNA methods. These 

methods are briefly summarized below for each analyte.

Lactose 

Air samples were extracted in 2 milliliters (mL) of deionized water. The wipe samples were 

extracted in 10 mL of deionized water. After sonicating for 15 minutes, the samples were 

allowed to stand for 15 minutes before being transferred to autosampler vials. The extracted 

samples (air and wipe) were analyzed by high performance liquid chromatography using the 

parameters below.

Instrument: Dionex 3000

Column: Dionex CarboPac PA1, 4 mm × 250 mm

Column flow rate: 1 mL per minute

Column temperature: Ambient

Injection volume: 200 microliters

Detector: Electrochemical detector

Mobile phase: Isocratic, 200 millimolar (mM) sodium hydroxide in deionized water

Lisinopril and Hydrochlorothiazide

Air samples were processed as described for lactose analysis and analyzed by high 

performance liquid chromatography using the parameters below.

Instrument: Agilent 1100 

Column: Waters Spherisorb C8, 150 mm × 4.6 mm, 5 μm particle size

Column flow rate: 1 mL per minute

Column temperature: 40°C

Injection volume: 30 microliters

Detector: Ultraviolet/visible 

Wavelength: 215 nanometer

Mobile phase: Isocratic 85% (Dipotassium phosphate, 0.1% phosphoric 

acid)/15% methanol

Hydrochlorothiazide and Triamterene

Air samples were transferred into an extraction vessel. Then, 2 mL of 90% 5 mM 

monopotassium phosphate in deionized water (pH = 4 with monopotassium phosphate)/10% 

acetonitrile solution was rinsed through the cowl and added to each sample. After sonicating 

for 15 minutes, the samples were allowed to stand for 15 minutes before being transferred 

to autosampler vials for analysis by high performance liquid chromatography using the 

parameters below.
Page 34 Health Hazard Evaluation Report 2012-0044-3199

Instrument: Agilent 1100 

Column: Waters Spherisorb C8, 150 mm × 4.6 mm, 5 μm particle size 

Column flow rate: 1.0 milliliters per minute (mL/min) 

Column temperature: 40°C 

Injection volume: 50 microliters 

Detector: Ultraviolet/visible 

Wavelength: 271 nanometer

Mobile phase: Isocratic 90% 5 mM monopotassium phosphate in deionized water 

(pH = 4 with H3PO4), 10% acetonitrile

Hydrocodone 

Air samples were extracted in 2 mL of a 50% (15 mM sodium lauryl sulfate, 15 mM 

dipotassium phosphate, 0.1% phosphoric acid)/5% acetonitrile/45% methanol solution. Wipe 

samples were extracted in 10 mL of the same extraction solvent. After sonicating for 15 

minutes, the samples were transferred to autosampler vials. The extracted samples (air and 

wipe) were analyzed by liquid chromatography/mass spectrometry using the parameters below. 

Instrument: Agilent 1100

Column: MacMod Halo C18, 4.6 mm × 75 mm, 2.7 μm particle size

Column flow rate: 1.5 mL per minute

Column temperature: 40°C

Injection volume: 50 microliters

Detector: Ultraviolet/visible 

Wavelength: 210 nanometer

Mobile phase: Isocratic 50% 15 mM sodium lauryl sulfate, 15 mM dipotassium 

phosphate, 0.1% phosphoric acid, 5% acetonitrile

Methotrexate 

Air samples were extracted in 1 mL of a 25% 10 mM ammonium acetate (0.1% formic 

acid)/75% acetonitrile (0.1% formic acid) solution. After shaking the samples for 30 

minutes, the samples were transferred to autosampler vials. All calibration points, quality 

control spikes, and samples were then spiked with 10 microliter concentrated internal 

standard (200 nanograms per mL methotrexate-D3). Wipe samples were extracted in 10 

mL of a 2 nanograms per mL methotrexate-D3 in 25% 10 mM ammonium acetate (0.1% 

formic acid)/75% acetonitrile (0.1% formic acid) solution. After sonicating for 15 minutes, 

the samples were allowed to stand for 15 minutes before being transferred to autosampler 

vials. The extracted samples (air and wipe) were analyzed by liquid chromatography/mass 

spectrometry using the parameters below. 

Instrument: Agilent 1200 

Column: Atlantis Hilic Silica, 4.6 mm × 100 mm, 3 um particle size 

Column flow rate: 1.0 mL per minute 

Column temperature: 30°C 

Injection volume: 10 microliters

Detector: API 4000 Turbo V source with electro-spray ionization probe 
Health Hazard Evaluation Report 2012-0044-3199 Page 35

Ions used: 455.2/308.2; Internal Standard 458.3/311.2

Mobile phase: Isocratic 25% 10 mM ammonium acetate (0.1% formic acid), 75% 

acetonitrile (0.1% formic acid)

Methocarbamol

Air samples were extracted in 2 mL of a 60% 20 mM monopotassium phosphate (pH = 3 

with phosphoric acid) in deionized water/40% methanol solution was added to each sample. 

Wipe samples were extracted in 10 mL of a 90% (15 mM heptane sulfonic acid/10 mM 

dipotassium phosphate/0.1% phosphoric acid)/10% acetonitrile solution. After sonicating 

for 15 minutes, the samples were allowed to stand for 15 minutes before being transferred to 

autosampler vials. The extracted samples (air and wipe) were analyzed by high performance 

liquid chromatography using the parameters below.

Instrument: Agilent 1100 

Column: Waters Symmetry C18, 4.6 mm × 150 mm, 5 um particle size 

Column flow rate: 1.0 mL/min 

Column temperature: 25°C 

Injection volume: 50 microliters 

Detector: Ultraviolet/visible 

Detection wavelength: 275 nanometer

Mobile phase: Isocratic 60% 20 mM monopotassium phosphate (pH = 3 with 

phosphoric acid) in deionized water, 40% methanol

Buspirone 

Air samples were transferred into an extraction vessel. Then, 2 mL of a 70% 10 mM 

monopotassium phosphate in deionized water/30% acetonitrile solution was rinsed through 

the cowl and added to each sample. After sonicating for 15 minutes, the samples were 

allowed to stand for 15 minutes before being transferred to autosampler vials for analysis by 

high performance liquid chromatography using the parameters below. 

Instrument: Agilent 1100 

Column: Waters Xterra RP18, 4.6 mm × 150 mm, 3.5 μm particle size 

Column flow rate: 1.5 mL/min 

Column temperature: 30°C 

Injection volume: 25 microliters 

Detector: Ultraviolet/visible 

Detection wavelength: 238 nanometer

Mobile phase: Isocratic 70% 10 mM monopotassium phosphate in deionized water, 

30% acetonitrile 

Gabapentin

Air samples were transferred into an extraction vessel. Then, 2 mL of a 10 mM sodium 

borate decahydrate solution was rinsed through the cowl and added to each sample. After 

sonicating for 15 minutes, the samples were allowed to stand for 15 minutes. Finally, 100 

microliters of each sample, quality control spike, and calibration standard was transferred to 
Page 36 Health Hazard Evaluation Report 2012-0044-3199

autosampler vials and spiked with 15 microliters of derivatizing agent (Vial 2B added to Vial 

2A of Accq-flour Reagent Kit from Waters Lot #689882215), mixed, and analyzed by high 

performance liquid chromatography using the parameters below. 

Instrument: Agilent 1100 

Column: Zorbax SB C18, 4.6 mm × 250 mm, 5 μm particle size 

Column flow rate: 1.0 mL/min 

Column temperature: 35°C 

Injection volume: 10 microliters

Detector: Waters 474 fluorescence detector 

Excitation: 245 

Emission: 480

Mobile phase: Isocratic 70% (1% triethylamine, 0.75% H3PO4 in deionized water), 

30% acetonitrile

Captopril

Air samples were extracted in 2 mL of a 55% methanol/45% deionized water/0.05% 

phosphoric acid solution. After sonicating for 10 minutes, the samples were allowed to stand 

for 20 minutes before being transferred to autosampler vials for analysis by high performance 

liquid chromatography using the parameters below. 

Instrument: Agilent 1100 

Column: Zorbax XDB C18, 4.6 mm × 250 mm, 5 μm particle size 

Column flow rate: 1.0 mL/min 

Column temperature: 40°C 

Injection volume: 50 microliters 

Detector: Ultraviolet/visible

Detection wavelength: 220 nanometer 

Mobile Phase: Isocratic 55% methanol/45% deionized water/0.05% phosphoric 

acid solution

Naproxen

Air samples were transferred into an extraction vessel. Then, 2 mL of a 54% deionized 

water/5% acetonitrile/1% glacial acetic acid solution was rinsed through the cowl and added 

to each sample. After sonicating for 15 minutes, the samples were allowed to stand for 15 

minutes before being transferred to autosampler vials for analysis by high performance liquid 

chromatography using the parameters below. 

Instrument: Agilent 1100 

Column: MacMod Halo C18, 4.6 mm × 75 mm, 2.7 μm particle size 

Column flow rate: 1.0 mL/min 

Column temperature: 40°C 

Injection volume: 40 microliters 

Detector: Ultraviolet/visible

Detection wavelength: 238 nanometer

Mobile phase: Isocratic 54% deionized water/45% acetonitrile/1% glacial acetic acid
Health Hazard Evaluation Report 2012-0044-3199 Page 37

Furosemide

Air samples were transferred into an extraction vessel. Then, 1 mL of a 60% (2% acetic 

acid in deionized water)/40% acetonitrile solution was rinsed through the cowl and added 

to each sample. After sonicating for 15 minutes, the samples were allowed to stand for 15 

minutes before being transferred to autosampler vials for analysis by high performance liquid 

chromatography using the parameters below. 

Instrument: Agilent 1100 

Column: Waters Xterra RP18, 4.6 mm × 150 mm, 3.5 μm particle size 

Column flow rate: 1.0 mL/min 

Column temperature: 40°C 

Injection volume: 25 microliters 

Detector: Ultraviolet/visible 

Detection wavelength: 340 nanometer

Mobile phase: Isocratic 60% (2% acetic acid in deionized water), 40% acetonitrile

Levothyroxine

Air samples were desorbed in 20 nanograms per mL thyroxine in 30% deionized water 

(0.1% formic acid)/70% acetonitrile solution. After sonicating for 15 minutes, the samples 

were transferred to autosampler vials for analysis by liquid chromatography/tandem mass 

spectrometry using the parameters below.

Instrument: Agilent 1100

Column: Atlantis Hilic Silica, 50 mm × 2.1 mm, 3 μm pore size

Column flow rate: 0.3 mL per minute

Column temperature: 35°C

Injection volume: 20 microliters

Detector: AB Sciex API 3000 MS/MS with turbo ion spry source

Source temperature: 350°C

MS function: Multiple reaction monitoring 

Levothyroxine quantitation transition: 777.8–731.8 atomic mass units

Thyroxine (internal standard) transition: 783.78–737.65 atomic mass units

Mobile phase: Isocratic 30% deionized water (0.1% formic acid)/70% acetonitrile 

(0.1% formic acid)

Glipizide

Wipe samples were extracted in 10 mL of a 50% 20 mM dipotassium phosphate/50% 

methanol solution. After sonicating for 15 minutes, the samples were allowed to stand for 

15 minutes before being transferred to auto-sampler vials for analysis by high performance 

liquid chromatography using the parameters below. 

Instrument: Agilent 1100 

Column: Waters Xterra RP-18, 4.6 mm × 150 mm, 3.5 μm particle size 

Column flow rate: 0.75 mL/min 

Column temperature: 40°C 

Injection volume: 75 microliters 
Page 38 Health Hazard Evaluation Report 2012-0044-3199

Detector: Ultraviolet/visible 

Detection wavelength: 275 nanometer

Mobile phase: Gradient (linear) 

Mobile phase A: 10 mM dipotassium phosphate (pH 3 using phosphoric acid) 

Mobile phase B: Methanol 
Health Hazard Evaluation Report 2012-0044-3199 Page 39

Appendix B: Real-Time Particle Measurements

Real-time particle sampling was mostly done near the breathing zones of employees who also 

wore personal air samplers. Personal air sample numbers are provided in some of the figures 

below for cross-referencing with sample results in Table 13. 

Baker Refill

Figure B1. Real-time particle number concentrations measured near the breathing zone of an employee who 

refilled the Baker machine during first shift of day 1 (side-by-side sample nos. 13 and 17). The APIs that were 

handled during refill are noted above the peaks in particle concentrations that occurred at the same time. 

Number concentrations for particles 0.3–0.5 μm in diameter (20,000–40,000 particles per liter [particles/L]) 

exceeded the upper range of this graph.
Page 40 Health Hazard Evaluation Report 2012-0044-3199

Figure B2. Real-time particle number concentrations measured near the breathing zone of an employee who 

refilled the Baker machine during first shift of day 2 (side-by-side sample nos. 25 and 40). The APIs that were 

handled during refill are noted above the peaks in particle concentrations that occurred at the same time. 

Number concentrations for particles 0.3–0.5 μm in diameter (30,000–40,000 particles/L) exceeded the upper 

range of this graph.
Health Hazard Evaluation Report 2012-0044-3199 Page 41

Figure B3. Real-time particle number concentrations measured near the breathing zone of an employee who 

refilled the Baker machine during first shift of day 3. The APIs that were handled during refill are noted above 

the peaks in particle concentrations that occurred at the same time. Number concentrations for particles 

0.3–0.5 μm in diameter (15,000–35,000 particles/L) exceeded the upper range of this graph.
Page 42 Health Hazard Evaluation Report 2012-0044-3199

Baker Maintenance

Figure B4. Real-time particle number concentrations measured near the breathing zone of an employee who 

maintained the Baker machine during second shift of day 2 (sample no. 21). The APIs that were housed in 

cells that were cleaned or repaired are noted above the peaks in particle concentrations that occurred at the 

same time. 
Health Hazard Evaluation Report 2012-0044-3199 Page 43

Figure B5. Real-time particle number concentrations measured near the breathing zone of an employee 

who maintained the Baker machine during first shift of day 3. The APIs that were housed in cells that were 

cleaned or repaired are noted above the peaks in particle concentrations that occurred at the same time. 

For a brief period (~20 minutes), we also did real-time air sampling near the personal breathing zone of the 

housekeeping employee who emptied the wet/dry vacuum. 
Page 44 Health Hazard Evaluation Report 2012-0044-3199

Manual Count 

Figure B6. Real-time particle number concentrations measured near the breathing zone of an employee who 

manually filled prescriptions during first shift of day 2. Specific tasks are noted above the particle concentrations that occurred at the same time. 
Health Hazard Evaluation Report 2012-0044-3199 Page 45

Hazardous Drugs

Figure B7. Real-time particle number concentrations measured near the breathing zone of an employee who 

hand-filled bulk and hazardous drug prescriptions (i.e., methotrexate) during first shift of day 1. For a brief 

period (~20 minutes), we also did real-time air sampling near the personal breathing zone of the housekeeping employee who vacuumed around the Baker machine. Number concentrations for particles 0.3–0.5 μm in 

diameter (20,000–45,000 particles/L) exceeded the upper range of this graph.
Page 46 Health Hazard Evaluation Report 2012-0044-3199

Appendix C: Minimum Detectable and 

Quantifiable Concentrations

Table C1. MDCs and MQCs for inhalable dust, lactose, and APIs sampled in air*

Analyte MDC (μg/m3) MQC (μg/m3)

Inhalable dust 100 470

Lactose 0.003 0.0091

Warfarin 0.7 2.1

Methotrexate 0.0001 0.00035

HCTZ 0.02 0.065

Triamterene 0.02 0.065

Lisinopril 0.1 0.36

Buspirone 5 18

Captopril 0.09 0.28

Furosemide 0.05 0.18

Gabapentin 0.05 0.18

Hydrocodone 0.01 0.043

Methocarbamol 0.05 0.18

Naproxen 0.0001 0.00036

Levothyroxine 0.0003 0.00092

*Based on the average volume of air (0.92 cubic meters) collected during full-shift sampling 

(approximately 8 hours).
Health Hazard Evaluation Report 2012-0044-3199 Page 47

Appendix D: Occupational Exposure Limits and 

Health Effects

NIOSH investigators refer to mandatory (legally enforceable) and recommended OELs for 

chemical, physical, and biological agents when evaluating workplace hazards. OELs have 

been developed by federal agencies and safety and health organizations to prevent 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 if their exposures are maintained below these levels. Some may have 

adverse health effects because of individual susceptibility, a pre-existing medical condition, 

or a hypersensitivity (allergy). In addition, some hazardous substances act in combination 

with other exposures, with the general environment, or with medications or personal habits of 

the employee to produce adverse health effects. Most OELs address airborne exposures, but 

some substances can be absorbed directly through the skin and mucous membranes.

Most OELs are expressed as a time-weighted average exposure. A time-weighted average 

refers to the average exposure during a normal 8- to 10-hour workday. Some chemical 

substances and physical agents have recommended short-term exposure limit or ceiling 

values. Unless otherwise noted, the short-term exposure limit is a 15-minute time-weighted 

average exposure. It should not be exceeded at any time during a workday. The ceiling limit 

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; others are recommendations. 

● The U.S. Department of Labor OSHA permissible exposure limits (29 CFR 1910 

[general industry]; 29 CFR 1926 [construction industry]; and 29 CFR 1917 [maritime 

industry]) are legal limits. These limits are 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 and the adequacy of methods to identify 

and control the hazard. NIOSH recommended exposure limits are published in the 

NIOSH Pocket Guide to Chemical Hazards [NIOSH 2010]. NIOSH also recommends 

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.

● Other OELs commonly used and cited in the United States include the threshold 

limit values, which are recommended by the American Conference of Governmental 

Industrial Hygienists, a professional organization, and the workplace environmental 

exposure levels, which are recommended by the American Industrial Hygiene 

Association, another professional organization. The threshold limit values and 
Page 48 Health Hazard Evaluation Report 2012-0044-3199

workplace environmental exposure levels are developed by committee members of 

these associations from a review of the published, peer-reviewed literature. These OELs 

are not consensus standards. Threshold limit values 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 2013]. Workplace environmental exposure 

levels have been established for some chemicals “when no other legal or authoritative 

limits exist” [AIHA 2013].

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

and include legal and recommended limits. The Institut für Arbeitsschutz der Deutschen 

Gesetzlichen Unfallversicherung (Institute for Occupational Safety and Health of the German 

Social Accident Insurance) maintains a database of international OELs from European 

Union member states, Canada (Québec), Japan, Switzerland, and the United States. The 

database, available at http://www.dguv.de/ifa/Gefahrstoffdatenbanken/GESTIS-InternationaleGrenzwerte-für-chemische-Substanzen-limit-values-for-chemical-agents/index-2.jsp, contains 

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

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))]. This is 

true in the absence of a specific OEL. It also is important to keep in mind that OELs may not 

reflect current health-based information.

When multiple OELs exist for a substance or agent, NIOSH investigators generally 

encourage employers to use the lowest OEL when making risk assessment and risk 

management decisions. NIOSH investigators also encourage use of the hierarchy of controls 

approach to eliminate or minimize 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). 

Active Pharmaceutical Ingredients

Other than warfarin, none of the APIs measured in air have OELs established by federal 

agencies or national organizations. However, many of them do have OELs established by 

pharmaceutical companies using a control banding process. 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. This approach can be applied in situations where authoritative OELs have not 

been established or can be used to supplement such OELs. In the pharmaceutical industry, 

APIs are placed into hazard categories using data such as potency, severity of acute effects, 

lethal dose, irritation, and sensitization [Naumann et al. 1996; Naumann 2005; Zalk and 

Nelson 2008]. Once placed into hazard categories, pharmaceuticals are often assigned OELs 
Health Hazard Evaluation Report 2012-0044-3199 Page 49

or hazard control bands. Pharmaceutical companies may provide these OELs or hazard 

control bands on their safety data sheets, along with potential acute and chronic health 

effects from workplace exposures. Table C1 provides the manufacturers’ OELs or hazard 

control bands for the APIs measured in this evaluation. Other manufacturers may have OELs 

in addition to those listed in Table D1. Maintaining exposures below these manufacturers’ 

OELs should minimize any potential health effects. However, OELs typically do not consider 

possible synergistic effects from multiple API exposures. More information on control 

banding is available at http://www.cdc.gov/niosh/topics/ctrlbanding/.

Table D1. Prescribed uses and manufacturers’ OELs (full-shift time-weighted average) for the APIs 

measured in air

API Prescribed for* Manufacturer’s OEL or

hazard control band

(μg/m3)†

Buspirone Anxiety 10

Captopril High blood pressure and congestive heart failure 100

Furosemide High blood pressure and fluid retention None published

Gabapentin Seizures, restless legs syndrome, and

pain from shingles

1,200

HCTZ High blood pressure and fluid retention 100

Hydrocodone Pain relief or cough suppression 5

Lisinopril High blood pressure and heart failure 1–10

Levothyroxine Hypothyroidism < 1

Methocarbamol Muscle pain None published

Methotrexate Cancer of the blood, bone, lung, breast, head or neck, 

rheumatoid arthritis, or psoriasis

0.3

Naproxen Pain and fever 1,000

Triamterene High blood pressure and fluid retention 1,000

*[PubMed Health 2013]

†Buspirone [U.S. Pharmacopeia 2006], Captopril [U.S. Pharmacopeia 2013a], Gabapentin 

[Pfizer 2010], HCTZ [Bristol-Myers Squibb Company 2012a], Hydrocodone [Abbott Labs 2011], 

Lisinopril [Bristol-Myers Squibb Company 2012b], Levothyroxine [Pfizer 2011], Methotrexate [U.S. 

Pharmacopeia 2013b], Naproxen [Roche 2006], Triamterene [GlaxoSmithKline 2008].
Page 50 Health Hazard Evaluation Report 2012-0044-3199

References

Abbott Labs [2011]. Safety data sheet: Vicodin ES tablets. [http://www.abbott.com/global/

url/content/en_US/20.40:40/general_content/General_Content_00183.htm]. Date accessed: 

December 2013.

ACGIH [2010]. Industrial ventilation: a manual of recommended practice for design, 27th edition. 

Cincinnati, OH: American Conference of Governmental Industrial Hygienists (ACGIH).

ACGIH [2013]. 2013 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 [2013]. AIHA 2013 Emergency response planning guidelines (ERPG) & workplace 

environmental exposure levels (WEEL) handbook. Fairfax, VA: American Industrial 

Hygiene Association.

ASHRAE [2010]. ANSI/ASHRAE Standard 62.1-2010: Ventilation for acceptable indoor 

air quality. Atlanta, GA: American Society of Heating, Refrigerating, and Air-Conditioning 

Engineers, Inc.

Bernstein JA, Bernstein DI, Stauder T, Zana L, Bernstein LI [1999]. A cross-sectional survey 

of sensitization of Aspergillus oryzae-derived lactase in pharmaceutical workers. J Allergy 

Clin Immunol 103(6):1153–1157.

Brent RL, Tanski S, Weitzman M [2004]. A pediatric perspective on the unique vulnerability 

and resilience of the embryo and the child to environmental toxicants: the importance of 

rigorous research concerning age and agent. Pediatrics 113(4 Suppl):935–944.

Bristol-Myers Squibb Company [2012a]. Safety data sheet: Hydrochlorothiazide. [http://

www.bmsmsds.com/msdsweb/]. Date accessed: December 2013.

Bristol-Myers Squibb Company [2012b]. Safety data sheet: Lisinopril. [http://www.

bmsmsds.com/msdsweb/]. Date accessed: December 2013.

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

Office of the Federal Register.

Connor TH, Sessink PJ, Harrison BR, Pretty JR, Peters BG, Alfaro RM, Bilos A, Beckmann 

G, Bing MR, Anderson LM, Dechristoforo R [2005]. Surface contamination of chemotherapy 

drug vials and evaluation of new vial-cleaning techniques: results of three studies. Am J 

Health Syst Pharm 62(5):475–484.

Cooper C, Dewe P [2008]. Well-being – absenteeism, presenteeism, costs, and challenges. 

Occup Med (Lond.) 58(8):522–524.
Health Hazard Evaluation Report 2012-0044-3199 Page 51

De Dreu CKW, van Dierendonck D, De Best-Waldhober M [2003]. Conflict at work and 

individual well-being. In: Schabracq MJ, Winnubst JAM, Cooper CL, eds. Handbook of work 

and health psychology. 2nd ed. West Sussex, England: John Wiley and Sons, pp. 495–515. 

Forsberg K, Mansdorf SZ [2007]. Quick selection guide to chemical protective clothing. 5th 

ed. Hoboken, New Jersey: Wiley-Interscience.

GlaxoSmithKline [2008]. Safety data sheet: Dyazide capsules. [http://www.msds-gsk.

com/0029250e.pdf]. Date accessed: December 2013.

Heron RJL, Pickering FC [2003]. Health effects of exposure to active pharmaceutical 

ingredients (APIs). Occup Med (Lond.) 53(6):357–362.

Johns G [2010]. Presenteeism in the workplace: a review and research agenda. J Organiz 

Behav 31(4):519–542. 

Ladenson P, Kim M [2008]. Thyroid. In: Goldman L, Ausiello D, eds. Cecil textbook of 

medicine. 23rd rev. ed. Philadelphia, PA: Saunders Elsevier, pp. 1698–1712.

Lloyd ME, Carr M, McElhatton P, Hall GM, Hughes RA [1999]. The effects of methotrexate 

on pregnancy, fertility and lactation. QJM 92(10)(Review):551–563.

Neal A, Griffin MA, Hart PM [2000]. The impact of organizational climate on safety climate 

and individual behavior. Safety Sci 34(1–3):99–109.

Naumann BD, Sargent EV, Starkman BS, Fraser WJ, Becker GT, Kirk GD [1996]. 

Performance-based exposure control limits for pharmaceutical active ingredients. Am Ind 

Hyg Assoc J 57(1):33–42.

Naumann BD [2005]. In: Control banding in the pharmaceutical industry. [http://www.aioh.

org.au/downloads/documents/ControlBandingBNaumann.pdf]. Date accessed: December 

2013.

NIOSH [1997a]. Musculoskeletal disorders and workplace factors: a critical review of 

epidemiologic evidence for work-related musculoskeletal disorders of the neck, upper 

extremity, and low back. 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. 97–141. [http://www.cdc.gov/niosh/docs/97-141/]. 

Date accessed: December 2013.

NIOSH [1997b]. Elements of ergonomics programs: a primer based on workplace 

evaluations of musculoskeletal disorders. 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. 97–117.
Page 52 Health Hazard Evaluation Report 2012-0044-3199

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

other hazardous drugs in health care settings. Cincinnati, OH: U.S. Department of Health 

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

Occupational Safety and Health, DHHS (NIOSH) Publication No. 2004-165.

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

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

Institute for Occupational Safety and Health, DHHS (NIOSH) Publication No. 2010-168c. 

[http://www.cdc.gov/niosh/npg/]. Date accessed: December 2013.

NIOSH [2012]. NIOSH list of antineoplastic and other hazardous drugs in health care 

settings 2012. 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. 2012-150.

NIOSH [2013a]. Health hazard evaluation report: exposures to pharmaceutical dust at an 

outpatient pharmacy. By Fent KW, Durgam S, Methner M. Cincinnati, OH: U.S. Department 

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

Institute for Occupational Safety and Health, NIOSH Report No. 2010-0078-3177.

NIOSH [2013b]. NIOSH manual of analytical methods. 4th ed. Schlecht PC, O'Connor PF, 

eds. 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. 94-113 (August 1994); 1st Supplement Publication 96-135, 2nd 

Supplement Publication 98-119, 3rd Supplement Publication 2003-154. [http://www.cdc.gov/

niosh/docs/2003-154/].

Pfizer [2010]. Safety data sheet: Gabapentin tablets. [http://www.pfizer.com/files/products/

material_safety_data/PZ01158.pdf]. Date accessed: December 2013.

Pfizer [2011]. Safety data sheet: Levothyroxine sodium tablets. [http://www.pfizer.com/files/

products/material_safety_data/PZ01680.pdf]. Date accessed: December 2013.

Pfizer [2012]. Safety data sheet: Methotrexate tablets. [http://www.pfizer.com/files/products/

material_safety_data/PZ00130.pdf]. Date accessed: December 2013.

PubMed Health [2013]. Drugs and supplements. [http://www.ncbi.nlm.nih.gov/

pubmedhealth/s/drugs_and_supplements/a/]. Date accessed: December 2013.

Roche [2006]. Safety data sheet: Naproxen sodium. [http://www.roche.com/pages/csds/

english/out/0490628.20110225.8049.pdf]. Date accessed: December 2013.

Schierl R, Herwig A, Pfaller A, Groebmair S, Fischer E [2010]. Surface contamination of 

antineoplastic drug vials: comparison of unprotected and protected vials. Am J Health Syst 

Pharm 67(6):428–429.
Health Hazard Evaluation Report 2012-0044-3199 Page 53

Schultz AB, Edington DW [2007]. Employee health and presenteeism: a systematic review. J 

Occup Rehabil 17(3):547–579.

Stewart WF, Ricci JA, Chee E, Hahn SR, Morganstein D [2003]. Cost of lost productive 

work time among US workers with depression. JAMA 289(23):3135–3144.

Teichman RF, Fallon LF, Brandt-Rauf PW [1988]. Health effects on workers in the 

pharmaceutical industry: a review. J Soc Occup Med 38(3):55–57.

U.S. Pharmacopeia [2006]. USP reference standards, safety data sheet: Buspirone 

hydrochloride. [http://www.usp.org/pdf/EN/referenceStandards/msds/1078802.pdf]. Date 

accessed: December 2013. 

U.S. Pharmacopeia [2013a]. USP reference standards, safety data sheet: Captopril. [http://

www.usp.org/pdf/EN/referenceStandards/msds/1091200.pdf]. Date accessed: December 

2013.

U.S. Pharmacopeia [2013b]. USP reference standards, safety data sheet: Methotrexate. 

[http://www.usp.org/pdf/EN/referenceStandards/msds/1414003.pdf]. Date accessed: 

December 2013.

Widera E, Chang A, Chen HL [2010]. Presenteeism: a public health hazard. J Gen Intern Med 

25(11):1244–1247.

Zalk DM, Nelson DI [2008]. History and evolution of control banding: a review. J Occup 

Environ Hyg 5(5):330–346.

Zuskin E, Mustajbegovic J, Schachter EN, Kern J, Deckovic-Vukres V, Pucarin-Cvetkovic 

J, Nola-Premec IA [2004]. Respiratory findings in pharmaceutical workers. Am J Ind Med 

46(5):472–479.
Page 54 Health Hazard Evaluation Report 2012-0044-3199

Keywords: North American Industry Classification System 446110 (Pharmacies and Drug 

Stores), pharmaceutical dust, pill dust, lisinopril, methotrexate, hazardous drugs, automatic dispensing machines, mail order pharmacy, dust exposures, local exhaust ventilation, eye irritation, respiratory irritation, skin irritation, safety climate, job stress
Health Hazard Evaluation Report 2012-0044-3199 Page 55

The Health Hazard Evaluation Program investigates possible health hazards in the workplace under the 

authority of the Occupational Safety and Health Act of 1970 (29 U.S.C. § 669(a)(6)). The Health Hazard 

Evaluation Program also provides, upon request, technical assistance to federal, state, and local agencies 

to investigate occupational health hazards and to prevent occupational disease or injury. Regulations 

guiding the Program can be found in Title 42, Code of Federal Regulations, Part 85; Requests for Health 

Hazard Evaluations (42 CFR Part 85).

Disclaimer

The recommendations in this report are made on the basis of the findings at the workplace 

evaluated and may not be applicable to other workplaces.

Mention of any company or product in this report does not constitute endorsement by the National 

Institute for Occupational Safety and Health (NIOSH).

Citations to Web sites external to NIOSH do not constitute NIOSH endorsement of the sponsoring 

organizations or their programs or products. 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.

Acknowledgments 

Analytical Support: Bureau Veritas North America

Desktop Publishers: Mary Winfree 

Editor: Ellen Galloway 

Industrial Hygiene Field Assistance: Catherine Beaucham and Karl Feldmann

Logistics: Donnie Booher and Karl Feldmann

Medical Field Assistance: Kenneth Bennett

Availability of Report

Copies of this report have been sent to the employer, employees, and union at the facility. The state and 

local health department and the Occupational Safety and Health Administration Regional Office have also 

received a copy. This report is not copyrighted and may be freely reproduced. 

This report is available at http://www.cdc.gov/niosh/hhe/reports/pdfs/2012-0044-3199.pdf.

Recommended citation for this report:

NIOSH [2013]. Health hazard evaluation report: evaluation of safety climate, health concerns, 

and pharmaceutical dust exposures at a mail order pharmacy. By Fent KW, Tapp L, Wiegand 

D. Cincinnati, OH: U.S. Department of Health and Human Services, Centers for Disease 

Control and Prevention, National Institute for Occupational Safety and Health, NIOSH Report 

No. 2012-0044-3199.
Delivering on the Nation’s promise:

Safety and health at work for all people through research and prevention

To receive NIOSH documents or more information about 

occupational safety and health topics, please contact NIOSH:

Telephone: 1–800–CDC–INFO (1–800–232–4636)

TTY: 1–888–232–6348

CDC INFO: www.cdc.gov/info

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.