Exposures to 

Pharmaceutical Dust at 

a Mail Order Pharmacy 

– Illinois

Kenneth W. Fent, PhD

Srinivas Durgam, MSPH, MSChE, CIH

Carlos Aristeguieta, MD, MPH

Scott E. Brueck, MS, CIH

Health Hazard Evaluation Report

HETA 2010-0026-3150

December 2011 

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Centers for Disease Control and Prevention

Workplace

Safety and Health

 National Institute for Occupational 

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

for a period of 30 calendar days at or near 

the workplace(s) of affected employees. The 

employer shall take steps to insure that the 

posted determinations are not altered, defaced, 

or covered by other material during such 

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

amended at 45 FR 2653, January 14, 1980].
Health Hazard Evaluation Report 2010-0026-3150 Page i

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

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

Summary ........................................................................................................vi

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

Assessment.....................................................................................................5

Results..............................................................................................................8

Discussion.................................................................................................... 20

Conclusions................................................................................................. 24

Recommendations.................................................................................... 25

References.................................................................................................... 29

Contents

Acknowledgments Acknowledgments and Availability of Report................................ 45

Appendix B Occupational Exposure Limits and Health Effects................. 35

Appendix A Additional Information on Sampling and Analytical Methods. 32
Page ii Health Hazard Evaluation Report 2010-0026-3150

Abbreviations

μg/m3 Micrograms per cubic meter

μm Micrometer

ACGIH® American Conference of Governmental Industrial Hygienists

ADU Automatic dispensing unit

AL Action level

API Active pharmaceutical ingredient

BVNA Bureau Veritas North America, Inc.

CFR Code of Federal Regulations

dB Decibel

dBA Decibels, A-scale

DESI/MS Desorption electrospray ionization/mass spectrometry

HEPA High-efficiency particulate air

HHE Health hazard evaluation

HHPC Handheld airborne particle counter

Hz Hertz

IOM Institute of Occupational Medicine

Lpm Liters per minute

mL Milliliter

mm Millimeter

mg Milligram

MDC Minimum detectable concentration

MQC Minimum quantifiable concentration

NA Not applicable

NAICS North American Industry Classification System

NIOSH National Institute for Occupational Safety and Health

ND None detected

OEL Occupational exposure limit

OSHA Occupational Safety and Health Administration

Particles/L Particles per liter

PBZ Personal breathing zone

PEL Permissible exposure limit

PPE Personal protective equipment

PTFE Polytetrafluoroethylene

REL Recommended exposure limit

STEL Short-term exposure limit

TLV® Threshold limit value

TWA Time-weighted average

WEELTM Workplace environmental exposure level
Health Hazard Evaluation Report 2010-0026-3150 Page iii

The National Institute for 

Occupational Safety and 

Health (NIOSH) received 

an employer request for a 

health hazard evaluation 

at a mail order pharmacy 

in Illinois concerning 

employee exposures to 

pharmaceutical dust and 

the potential health effects 

from these exposures. 

This request was later 

changed to include an 

evaluation of noise.

Highlights of the

NIOSH Health

Hazard Evaluation

What NIOSH Did

● We visited the pharmacy in April 2010. We returned in 

December 2010 to do additional sampling.

● We measured particles over time at different processes. We 

did this to determine if pharmaceutical dust was released 

into the air.

● We sampled the air for dust. These air samples were weighed 

to determine the amount of dust in the air and analyzed 

for lactose (a common inactive ingredient) and active 

pharmaceutical ingredients (APIs).

● We measured noise levels in the pharmacy.

● We talked with employees privately about their symptoms 

and health concerns at work.

What NIOSH Found

● Dust was released into the air when cells were cleaned and 

canisters were filled with tablets.

● Lactose and APIs were found in the airborne dust. 

This suggests that some of the airborne dust was from 

pharmaceuticals.

● Levels of the two APIs we measured in air (warfarin and 

lisinopril) were below occupational exposure limits.

● Hazardous drugs were dispensed at the pharmacy. Some 

of these were tablets that could generate airborne dust. 

Hazardous drugs are drugs that are known or suspected to 

cause adverse health effects from exposures in the workplace.

● Surfaces in the pharmacy and employees’ clothing could have 

pharmaceutical dust on them. This could lead to secondary 

exposure to employees and their families.

● A pharmacy technician working at the Baker machine had 

a noise exposure above NIOSH and Occupational Safety 

and Health Administration (OSHA) exposure limits of 

85 A-weighted decibels. All other employees whom we 

monitored had noise exposures less than these exposure 

limits.

● Most of the noise came from the release of compressed air by 

pharmacy equipment.

● Some employees had eye and respiratory irritation.
Page iv Health Hazard Evaluation Report 2010-0026-3150

Highlights of the

NIOSH Health

Hazard Evaluation

 (continued)

What Managers Can Do

● Install tabletop ventilation booths for employees who hand 

fill hazardous drug prescriptions and for employees who 

clean, repair, and refill cells and canisters.

● Install movable capture hoods for employees who refill Baker 

machine canisters.

● Write procedures and establish a schedule for replacing 

the particulate filters in the ventilation booths and hoods. 

These procedures should list the required personal protective 

equipment.

● Identify and label all hazardous drugs.

● Modify the current procedure for hand filling hazardous drug 

prescriptions. These procedures should list all the personal 

protective equipment, control measures, and housekeeping 

practices needed to prevent exposures to employees.

● Require employees to wear NIOSH-approved half-mask N95-

filtering facepiece respirators when hand filling hazardous 

drug prescriptions and changing out particulate filters in the 

ventilation booths, hoods, and HEPA vacuums. The use of 

respirators can be discontinued for hand filling of hazardous 

drug prescriptions when a ventilation booth is available for 

this process.

● Start a comprehensive respiratory protection program 

for employees who are required to wear respirators. This 

program should follow the OSHA respiratory protection 

standard.

● Provide employees with lab coats or other protective clothing 

that remains at the worksite. These items should be thrown 

away after each use or laundered weekly by professionals.

● Emphasize to employees the need to wear nitrile gloves when 

handling pharmaceuticals.

● Provide employees with easy access to hand washing stations. 

Employees should be required to wash their hands before 

eating, drinking, or using tobacco products.

● Install mufflers on the exhaust ports of solenoid valves and 

actuators.

● Fix any leaks in compressed air lines.
Health Hazard Evaluation Report 2010-0026-3150 Page v

● Provide employees with hearing protection that has a noise 

reduction rating of 15–20 decibels. Pharmacy technicians 

working around the Baker machine should be required to 

wear this hearing protection.

● Do not allow employees to use personal music players 

because they can increase the risk of hearing loss.

● Create a health and safety committee. This committee 

should include employee and employer representatives who 

meet regularly to address health and safety concerns.

What Employees Can Do

● Follow the procedures for using and maintaining the 

ventilation booths and hoods.

● Follow all procedures when you fill a prescription for 

hazardous drugs.

● Wear gloves when handling pharmaceuticals.

● Wash your hands before you eat, drink, or use tobacco 

products.

● Tell your supervisor about any health or safety concerns 

you have.

● Wear hearing protection when you work near the Baker 

machine.

● Do not use personal music players.

● Become active in the health and safety committee.

Highlights of the

NIOSH Health

Hazard Evaluation

 (continued)
Page vi Health Hazard Evaluation Report 2010-0026-3150

NIOSH evaluated 

health symptoms, 

pharmaceutical dust, 

and noise exposures 

among employees at a 

mail order pharmacy. 

We found that dust was 

released, particularly 

during the cleaning, 

repairing, and refilling 

of cells and canisters. 

This dust contained 

APIs and lactose, a 

common ingredient 

in pharmaceuticals. 

Exposures to 

pharmaceutical dust 

could have contributed to 

eye and upper respiratory 

irritation reported by 

employees. High noise 

exposures were caused 

by release of compressed 

air, which could be 

reduced by installing 

noise controls.

Summary

NIOSH investigators conducted an HHE at a mail order pharmacy 

to determine whether employees were exposed to pharmaceutical 

dust and noise and were experiencing health effects related to these 

exposures. We observed work processes, practices, and workplace 

conditions. We collected air samples to characterize employees’ 

exposures. We measured employees’ noise exposures and sound 

levels in the production areas. We held confidential interviews with 

45 employees to learn about their health and workplace concerns.

Using real-time particle meters, we identified releases of dust 

during the cleaning, repairing, and refilling of cells and canisters. 

We sampled the air for different sizes of dust particles and 

analyzed the samples for APIs and lactose, a common ingredient 

of pharmaceuticals. Most of these air samples contained lactose 

and one or more APIs, suggesting that some of the airborne dust 

came from pharmaceuticals. We quantified two APIs on these air 

samples, warfarin and lisinopril; the air concentrations were well 

below applicable OELs.

Most employees wore protective gloves but did not wear protective 

clothing when handling pharmaceuticals. Consequently, personal 

clothing could become contaminated with APIs and become 

a source of secondary exposure to employees or their family 

members. Many employees washed hands before eating or smoking, 

which should minimize the ingestion of APIs. Some employees 

voluntarily wore N95 filtering facepiece respirators. However, these 

respirators were not always worn or maintained correctly. Shortly 

before our second visit, pharmacy managers developed standard 

operating procedures for the handling of hazardous drugs. These 

procedures required hazardous drug prescriptions to be filled and 

verified in a separate area by dedicated personnel. Gloves were the 

only control measure required for this process.

The most likely health effects from exposure to APIs are allergic 

reactions and upper respiratory irritation. Nearly half the 

employees reported eye and upper respiratory irritation, which 

could be related to their exposures to APIs. However, these 

symptoms could also be caused by general dust exposures or nonoccupational factors, such as weather conditions and seasonal 

allergies.

We were unable to quantify employees’ exposures to all APIs. 

Given the uncertainty of our exposure assessment, the potential 

for surface and personal clothing contamination, and the lack of 
Health Hazard Evaluation Report 2010-0026-3150 vii

Keywords: NAICS 446110 (Pharmacies and Drug Stores), drugs, 

pills, pill dust, active pharmaceutical ingredients, APIs, tablets, 

pharmaceuticals, mail order pharmacy, automatic pill dispensing 

machine, robotic pill dispenser, Hispanic, Spanish-speaking 

Summary

 (continued) knowledge regarding the toxicity of low-level exposures to multiple 

APIs, exposures to pharmaceutical dust should be reduced as 

much as feasible. We recommend installing ventilation booths 

and movable capture hoods that can be used when hand filling 

hazardous drug prescriptions and cleaning, repairing, and refilling 

cells and canisters. All hazardous drugs should be identified and 

labeled. All employees who handle drugs should wear lab coats 

or other protective clothing to minimize contamination of their 

personal clothing.

We found that full-shift TWA noise exposures for employees 

working near the Baker machines could exceed the OSHA AL 

and NIOSH REL of 85 dBA. Employees’ noise exposures in 

other production areas were below these exposure limits. Some 

employees wore hearing protection, but the noise reduction rating 

was more than what was needed. We recommend providing 

hearing protectors with a noise reduction rating of 15–20 dB. We 

noted that many employees wore an earphone from a personal 

music player in one of their ears. Because this can increase the risk 

of hearing loss if the sound level from the earphone is higher than 

the background noise in the facility, we recommend that personal 

music players not be used in the workplace.

One-third octave band noise level measurements at several 

different work areas or around pharmacy equipment indicated 

that the highest noise levels occurred at high frequencies (greater 

than 8,000 Hz). To reduce noise levels and noise exposures, we 

recommend installing mufflers on the exhaust port of solenoid 

valves and actuators throughout the facility and constructing a 

better enclosure at the capper machine, located near the Baker 

machine.
viii Health Hazard Evaluation Report 2010-0026-3150

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Health Hazard Evaluation Report 2010-0026-3150 Page 1

Introduction

NIOSH received an HHE request from the management of a 

mail order pharmacy in Illinois concerning employee exposures 

to pharmaceutical dust and potential health effects from these 

exposures. In response to this HHE request, we conducted 

evaluations in April and December 2010. After our first visit, the 

pharmacy management asked us to evaluate noise exposures, which 

we did on the second visit.

The mail order pharmacy filled prescriptions using primarily 

automated distribution systems and delivered these prescriptions 

to its customers throughout the country. A total of 350 employees 

worked on the first or second shift. Spanish was the first language 

for a large percentage of the employees. The mail order pharmacy 

was divided into two areas: the pharmacy, where automatic 

dispensing machines were located and most prescriptions were 

filled, and the warehouse, where other activities were performed, 

such as manual counting and refilling of canisters. Two brands 

of automatic dispensing machines were used for high throughput 

prescriptions: Baker (one large customized machine, McKesson 

Corporation, San Francisco, California) and Optifill® (two 

smaller customized machines, AmerisourceBergen®, Valley 

Forge, Pennsylvania). Both machines used gravity to dispense 

pharmaceutical tablets and capsules.

The Baker machine had an elevated platform where the canisters 

containing pharmaceuticals were loaded into the machine 

(Figure 1). The pharmaceuticals were fed from a canister into a 

cell below the platform. A conveyor belt on the outside of the 

machine carried a prescription bottle to the nozzle below the 

appropriate cell (Figure 2), and a valve in the cell opened to 

dispense the pharmaceutical into the bottle. The Baker machine 

filled approximately 10,000 prescriptions per day during our 

evaluation. Two pharmacy technicians maintained the Baker 

machine. Their responsibilities included freeing jams, identifying 

bottles that did not receive pharmaceuticals, and cleaning and 

repairing malfunctioning cells. The Baker canisters were refilled 

in the offline replenishment area in the warehouse. In the offline 

replenishment area, two or three pharmacy technicians dumped 

bottles containing the appropriate pharmaceuticals into a funnel 

that fed into a labeled Baker canister (Figure 3).

Canisters were situated on the outside of each of the two Optifill 

machines (Figure 4). A conveyor belt carried prescription bottles 

through the middle of each machine. A bottle stopped below one 

Figure 1. Platform above the Baker 

machine where canisters containing 

pharmaceuticals were loaded into the 

machine.

Figure 2. Baker machine nozzle where 

pharmaceuticals were dispensed into 

prescription bottles.

Figure 3. Employee in the offline 

replenishment area dumping tablets 

into a funnel that feeds into a Baker 

canister.
Page 4 Health Hazard Evaluation Report 2010-0026-3150

Introduction

 (continued) of the eight shared chutes in each machine. A canister dispensed 

the appropriate pharmaceutical into the chute that funneled 

into the bottle. The Optifill machine filled approximately 2,000 

prescriptions per day during our evaluation. Two pharmacy 

technicians replenished and repaired the Optifill canisters. A 

pharmacist checked and verified all replenishments.

Some employees also worked in the repack, special handling, 

or manual count areas in the warehouse. Pharmacy technicians 

in the repack area filled multiple prescriptions of the same 

pharmaceutical using another automatic dispensing machine. One 

pharmacy technician transferred pharmaceuticals from bottles 

into larger totes. The contents of the totes were dumped into the 

hopper of the repack machine. The machine used vibration plates 

to feed the bottles. Use of the repack machine was permanently 

discontinued shortly after our first visit. A pharmacy technician in 

the special handling area primarily filled prescriptions of warfarin 

by hand. In the manual count area, two or three pharmacy 

technicians hand filled a variety of other prescriptions. On rare 

occasions, these pharmacy technicians filled prescriptions of 

hazardous drugs. Hazardous drugs are drugs known or suspected 

to cause adverse health effects from exposures in the workplace 

[NIOSH 2004, 2010a]. The hand filling of hazardous drugs was 

moved to a separate area with dedicated personnel shortly before 

our second visit.

During a night shift on our first visit, we observed the cleaning 

of the Optifill and Baker machines by four pharmacy technicians. 

The Optifill machine was cleaned by opening the cabinet doors, 

collecting pharmaceutical dust on the chutes with a HEPA vacuum, 

and then wiping the chutes with alcohol. The Baker machine 

was cleaned by emptying pharmaceuticals contained in a cell into 

a tote, disassembling and repairing any broken cell parts, and 

then cleaning the inside of the cell with alcohol and a dry wipe 

before reassembly. The pharmaceuticals held in the tote were then 

dumped back into the clean cell.

Figure 4. Employee replenishing an 

Optifill canister with the Optifill machine 

in the background.
Health Hazard Evaluation Report 2010-0026-3150 Page 5

Assessment

The purpose of this evaluation was to (1) determine if and during 

which activities dust was released into the air, (2) measure the 

concentration of the airborne dust, (3) determine if the airborne 

dust contained pharmaceuticals, (4) identify and quantify specific 

APIs in the airborne dust, (5) determine if employees were 

experiencing or at risk of adverse health effects related to their 

exposures, (6) measure production employees’ full-shift personal 

noise exposures to determine if hearing protection was needed, 

and (7) measure sound levels and noise frequency levels near 

equipment to help identify possible noise control approaches. 

Bilingual NIOSH investigators fluent in Spanish aided our 

communication with Hispanic employees during this evaluation.

Air Sampling

The methods we used to measure PBZ concentrations of total, 

respirable, and inhalable dust are summarized in Table 1. During 

the second visit, the total dust and inhalable dust samplers were 

positioned side by side in the employees’ PBZs. Each type of dust 

sampler collects particles in different size ranges. A respirable 

dust sampler has 50% collection efficiency for particles with an 

aerodynamic diameter of 4 μm. These respirable particles are able 

to penetrate deeply into the lower respiratory system [ACGIH 

2011]. An inhalable dust sampler collects larger particles than 

a total dust sampler (with closed-face configuration) because it 

has a larger inlet. An inhalable dust sampler has 50% collection 

efficiency for particles with an aerodynamic diameter of 100 

μm. These inhalable particles can be deposited anywhere in the 

respiratory system, including the nose [ACGIH 2011]. 

Real-time particle count measurements were collected near the 

PBZs of the employees during different tasks (Figure 5). These 

measurements along with the real-time PBZ concentrations of 

respirable dust were used to identify specific tasks that resulted in 

increased particle counts. The types of tablets that were handled 

during the releases of dust were recorded. Managers and employees 

at the pharmacy also provided us with a list of tablets that were 

especially dusty. Generally, capsules did not produce dust. Using 

this information, we generated lists of APIs that could potentially 

be present on each total dust air filter. More information about 

the dust sampling methods and particle count measurements is 

provided in Appendix A.

Figure 5. Using a real-time particle 

meter to measure particle counts near 

the PBZ of an employee cleaning a 

Baker cell.
Page 6 Health Hazard Evaluation Report 2010-0026-3150

Assessment 

(continued)

Table 1. Summary of the initial air sampling and analyses performed at the mail order pharmacy

Sampling media/equipment*

Flow 

rate 

(Lpm)

Analytes

NIOSH 

analytical 

method†

Personal air 

sampling

N‡ n§

First visit

37-mm PTFE filter, closed face cassette 4 Total dust (by mass) 0500 22 35

37-mm PTFE filter, cyclone, Personal DataRAM 2.2 Respirable dust (by 

mass and in real time) 0600 4 6

HHPC-6 optical particle counter NA Particle count (in real 

time) NA NA NA

Second visit

37-mm PTFE filter, closed face cassette 4 Total dust (by mass) 0500 11 25

25-mm PTFE filter, IOM sampler 2 Inhalable dust (by 

mass) 0600 11 25

HHPC-6 optical particle counter NA Particle count (in real 

time) NA NA NA

* Additional information provided in Appendix A.

†

 NIOSH Manual of Analytical Methods [NIOSH 2011]

‡

 Number of employees sampled

§

 Total number of air samples

Figure 6 illustrates the progression of other analyses done on 

the total and inhalable dust filters after they were analyzed 

gravimetrically. The NIOSH contract laboratory, BVNA (Novi, 

Michigan), quantified lactose, a common excipient (nonactive 

ingredient) in pharmaceuticals, on the inhalable dust filters using 

an internal analytical method. The total dust air filters were sent 

to Prosolia, Inc. (Indianapolis, Indiana) along with the lists of APIs 

likely to be present on each filter. Prosolia used a DESI/MS system 

[Takats et al. 2004] to identify specific APIs on the filters by cross 

referencing mass-to-charge ratios with the lists of APIs we provided.

We used the list of identified APIs and real-time air sampling results 

to select inhalable dust samples (collected side by side with the total 

dust air samples) for further analysis. We selected five inhalable 

dust samples for quantitation of lisinopril. Lisinopril was chosen for 

quantitation because the analytical method used by BVNA requires 
Health Hazard Evaluation Report 2010-0026-3150 Page 7

Assessment 

(continued) dissolution in water, and the inhalable dust samples were already 

dissolved in water for the lactose analysis. In addition, lisinopril 

has a relatively low manufacturer’s OEL of 10 μg/m3

 [BristolMyers Squibb Company 2008]. We also selected five total dust air 

samples for quantitation of warfarin using NIOSH Method 5002 

[NIOSH 2011]. We chose to analyze for warfarin because it was the 

predominant drug handled by the employees in the manual count 

(special handling) area. The analytical methods used to quantify 

lactose and lisinopril are summarized in Appendix A.

Medical Interviews

During our first visit, we conducted voluntary confidential medical 

interviews with a convenience sample of employees. The interviews 

focused on respiratory and skin symptoms as well as perceived 

exposure to dust and noise. We spoke to all 23 Baker and Optifill 

operators and to a comparable number of employees from other 

locations.

Figure 6. Flow chart showing the subanalyses performed on the total and inhalable dust samples.
Page 8 Health Hazard Evaluation Report 2010-0026-3150

Noise Measurements

During the second visit, we collected 36 full-shift TWA personal 

noise dosimetry measurements and 3 full-shift TWA area noise 

dosimetry measurements. We measured area noise levels and 

performed octave band noise frequency analysis (measurement of 

noise levels in different frequencies) at noisy equipment and work 

areas with a Larson Davis (Depew, New York) System 824 sound 

level meter and real-time frequency analyzer. Appendix A provides 

more information on the noise measurements.

Assessment 

(continued)

Results

Exposure to Pharmaceutical Dust

Figures 7 and 8 summarize the PBZ total dust (ranging from 

31–530 μg/m3

) and respirable dust (ranging from ND–33 μg/m3) 

concentrations from the first visit. Figure 9 summarizes the PBZ 

inhalable dust (ranging from 110–800 μg/m3

), total dust (ranging 

from 6–260 μg/m3

), and lactose concentrations (ranging from 

0.94–63 μg/m3

) from the second visit. Exposures to employees 

who maintained the Baker machine were stratified by the tasks 

they performed most (cleaning Baker cells versus maintaining the 

machine). This was done because exposure levels varied substantially 

between those two tasks. General area air concentrations (measured 

in the non-production areas of the pharmacy) are also included in 

Figure 9 to show the relatively low background levels of dust and 

lactose. Standard deviations are represented by error bars in all 

the figures. The MDCs and MQCs were calculated by dividing the 

analytical limits of detection and quantitation (mass units) by the 

average volume of air sampled. The MDCs and MQCs represent the 

smallest air concentrations that could have been detected (MDC) or 

quantified (MQC) on the basis of the volume of air sampled. Nondetectable levels of respirable dust were imputed values calculated by 

dividing their MDC of 20 μg/m3

 by the square root of 2 [Hornung 

and Reed 1990].

The total dust concentrations were similar between the two visits. 

However, the total dust concentration measured during the 

cleaning of Baker cells during the first visit was higher than that 

measured on the second visit. During the first visit, we collected 

total and respirable dust samples on employees doing similar 

processes, and the average total dust concentrations were 4 times 
Health Hazard Evaluation Report 2010-0026-3150 Page 9

Results

 (continued) higher than the respirable dust concentrations. During the second 

visit, the average inhalable dust concentrations were 1.3 to 3.7 times 

higher than the average total dust concentrations measured on the 

same employees. Lactose was a small fraction (0.08%–13%) of the 

inhalable dust, but was quantified in all inhalable dust air samples. 

Area air concentrations of lactose in the non-production areas of 

the pharmacy were significantly lower (P < 0.001) than the PBZ 

concentrations measured on employees in the production areas.

Other than the night shift, the total dust exposures overall were 

greater for employees in the warehouse than in the pharmacy during 

both visits. Inhalable dust exposures measured during the second 

visit were similar between the warehouse and pharmacy employees. 

During the second visit, the highest average total and inhalable dust 

exposures were measured in the PBZs of employees who did offline 

replenishment of Baker canisters, hand filling of prescriptions 

(manual count), online replenishment of Optifill canisters, and 

cleaning of Baker cells. Employees doing these processes, as well 

as the hand filling of prescriptions (special handling), also had the 

highest average PBZ concentrations of lactose.

Figure 7. Summary of average work-shift (approximately 8 hours) PBZ concentrations of total dust measured 

during the first visit by process and location at the facility. (Note: The night shift samples were task-based samples 

collected over 80 to 130 minutes.)
Page 10 Health Hazard Evaluation Report 2010-0026-3150

Results

 (continued)

Figure 8. Summary of average work-shift PBZ concentrations of respirable dust measured during the first visit by 

process and location at the facility.

Figure 9. Summary of average work-shift PBZ concentrations of inhalable dust, total dust, and lactose measured 

during the second visit by process and location at the facility.
Health Hazard Evaluation Report 2010-0026-3150 Page 11

Results

 (continued) Figures 10 and 11 show the real-time respirable particle 

concentrations, and Figures 12–15 show the real-time particle 

counts measured over time in the PBZs of employees doing 

different processes. The work-shift or task-based PBZ dust 

concentrations are also provided in these figures. Peaks in particle 

concentrations and counts were correlated with different tasks 

involving specific APIs. These APIs are noted in the figures 

above the corresponding peaks. Only tasks involving tablets 

were correlated with releases of dust. Because the respirable dust 

concentrations were so low (ND–33 μg/m3

), only the total dust 

samples were sent for further analysis for specific APIs. The names 

of the APIs in Figures 12–15 that were identified using DESI/

MS on the corresponding PBZ total dust samples are shown in red 

ovals. Although submicron (0.3–1 μm) particles dominated the 

particle counts (Figures 12–15), these small particles have negligible 

mass. Thus, the larger particles (>3 μm) contributed substantially 

more mass on the total and inhalable dust air samples than the 

small particles. 

Figure 10. Real-time respirable dust concentrations measured in the PBZ of Employee 7 who cleaned Baker cells 

as needed throughout the work day (April 6, 2010). The APIs contained in the cells that Employee 7 cleaned are 

noted above the peaks in respirable dust concentrations that occurred at the same time.
Page 12 Health Hazard Evaluation Report 2010-0026-3150

Results

 (continued)

Figure 11. Real-time respirable dust concentrations measured in the PBZ of Employee 6 who performed online 

replenishment of Optifill canisters throughout the work day (April 7, 2010). The APIs that Employee 6 handled 

during replenishment of the cells are noted above the peaks in respirable dust concentrations that occurred at the 

same time.

Figure 12. Real-time particle counts measured near the PBZ of Employee 7 who cleaned Baker cells as needed 

throughout the work day (April 8, 2010). The APIs contained in the cells that Employee 7 cleaned are noted 

above the peaks in particle counts that occurred at the same time. The names of the APIs identified on the 

corresponding total dust air sample are shown in the red ovals.
Health Hazard Evaluation Report 2010-0026-3150 Page 13

Results

 (continued)

Figure 13. Real-time particle counts measured near the PBZs of employees who cleaned the Optifill machine 

(Employees 4 and 25) and the Baker machine (Employee 10) during the night shift on April 7, 2010. The taskbased PBZ concentration of total dust is provided for Employee 10. The APIs contained in the cells that Employee 

10 cleaned with compressed air are noted above the peaks in particle counts that occurred at the same time. The 

names of the APIs identified on the corresponding total dust air sample are shown in the red ovals.

Figure 14. Real-time particle counts measured near the PBZs of Employees 9 and 20 (who worked near each 

other) during the offline replenishment of Baker canisters on December 7, 2010. The APIs that were handled 

during the filling of the canisters (and employees who handled them) are noted above the peaks in particle counts 

that occurred at the same time. The names of the APIs identified on the corresponding total dust air samples are 

shown in the red ovals.
Page 14 Health Hazard Evaluation Report 2010-0026-3150

Results

 (continued)

Figure 15. Real-time particle counts measured near the PBZs of Employees 9 and 18 during the offline 

replenishment of Baker canisters on December 8, 2010. The APIs that were handled during the filling of the 

canisters (and the employees who handled them) are noted above the peaks in particle counts that occurred at the 

same time. The names of the APIs identified on the corresponding total dust air samples are shown in the red ovals.

The 22 APIs identified on the total dust filters using DESI/MS 

are shown in Table 2. Appendix B provides more information on 

these APIs, their therapeutic uses, and manufacturers’ OELs (if 

available). Table 3 contains the PBZ air concentrations for warfarin 

and lisinopril. The PBZ concentrations of warfarin, measured 

during the hand filling of warfarin prescriptions (special handling), 

ranged from 0.19–3.8 μg/m3

 and were well below the NIOSH 

REL, OSHA PEL, and ACGIH TLV of 100 μg/m3

 [ACGIH 2001, 

NIOSH 2010b]. Likewise, the PBZ concentrations of lisinopril, 

measured during different processes, ranged from ND–0.44 μg/m3

and were well below the manufacturer’s OEL of 10 μg/m3

 [BristolMyers Squibb Company 2008].

Use of Surgical Masks, Respirators, and 

Protective Clothing

During our first visit, we observed several employees voluntarily 

wearing employer-provided surgical masks and dust masks 

(Medline Prohibit NON27381, Figure 4) that were not NIOSHapproved respirators. Employees believed that these masks 

protected them from exposure to the pharmaceutical dust. Surgical 
Health Hazard Evaluation Report 2010-0026-3150 Page 15

Results

 (continued)

Table 2. APIs identified on the total dust air samples using DESI/MS analysis (X denotes that the compound was identified in that 

sample)Process

Employee ID

Date

Allopurinol

Benazepril

Bethanechol

Buspirone

Carbidopa

Chlorpheniramine

Doxazosin

Glipizide

Hydralazine

Lamotrigine

Levodopa

Lisinopril

Meclizine

Metformin

Methocarbamol

Metoclopramide

Naproxen

Oxybutynin

Promethazine

Sotalol

Trazadone

Venlafaxine

Operating 

repack 

machine

3 4/8/2010 X X

Checking 

online 

replenishment 

of Optifill 

canisters

6

12/7/2010 X X

12/8/2010

12/9/2010 X X X

Cleaning 

Baker cells

7

4/8/2010 X X X X X

12/7/2010 X

12/8/2010 X X

12/9/2010 X X X

Offline 

replenishment 

of Baker 

canisters

9

12/7/2010 X

12/8/2010 X X X

Cleaning 

Baker 

machine 

(night shift)

10 4/7/2010 X X

Online 

replenishment 

of Optifill 

canisters

16

12/7/2010 X X X X

12/8/2010 X X X

12/9/2010 X

Hand filling of 

prescriptions 

(manual 

count)

17

12/7/2010 X

12/9/2010

Offline 

replenishment 

of Baker 

canisters

18 12/8/2010 X X

Offline 

replenishment 

of Baker 

canisters

20

12/7/2010 X

12/9/2010 X

Cleaning 

Baker cells

21

12/7/2010 X X X

12/8/2010 X X X

Offline 

replenishment 

of Baker 

canisters

24 12/9/2010 X X
Page 16 Health Hazard Evaluation Report 2010-0026-3150

Results

 (continued)

Table 3. Personal breathing zone air concentrations of warfarin and lisinopril for employees who handled these 

tablets

Process Employee ID Date Warfarin (μg/m3

)

(total dust)

Lisinopril (μg/m3) 

(inhalable dust)

Hand filling prescriptions 

(special handling)

8 4/8/2010 3.8

11 4/6/2010 (0.19)

11 4/7/2010 3.1

23 12/8/2010 (0.64)

23 12/9/2010 (0.50)

Cleaning Baker cells

7 12/7/2010 (0.44)

7 12/8/2010 ND

7 12/9/2010 ND

21 12/7/2010 ND

Offline replenishment of Baker canisters 9 12/7/2010 ND

OEL 100* 10†

MDC 0.18–0.42 0.22

MQC 0.59–2.2 0.69

* NIOSH REL, OSHA PEL, and ACGIH TLV [NIOSH 2010b, ACGIH 2011]

†

 Manufacturer’s OEL [Bristol-Myers Squibb Company 2008]

masks are designed to protect nearby people, or as in this case, 

pharmaceuticals, from expectorated droplets released by the person 

wearing the mask. Some employees were wearing the dust masks 

incorrectly (upside down). We informed the employer about these 

observations and noted that the employer could allow voluntary 

use of respirators for employee protection but would need to 

follow the requirements in the OSHA respiratory protection 

standard [29 CFR 1910.134] pertaining to voluntary respirator 

use, such as providing employees with the standard’s Appendix 

D, “Information for Employees Using Respirators When Not 

Required Under the Standard.” We also recommended that they 

provide three sizes of at least two different models of NIOSH 

approved N95 filtering facepiece respirators and provide training 

on how to properly wear and maintain these respirators.

By our second visit, the pharmacy had implemented some of these 

recommendations. Employees were provided with Appendix D of 

the OSHA respiratory protection standard [29 CFR 1910.134]. Two 

different models of N95 filtering facepiece respirators (Moldex 
Health Hazard Evaluation Report 2010-0026-3150 Page 17

Results

 (continued) 220N95 and Moldex 2300N95) were available to employees. 

At least two different respirator sizes were available, but many 

employees did not know where to access them. Instead employees 

typically used the model and size respirator in their work area. 

Only sick employees were required to wear surgical masks to 

protect the pharmaceuticals from contamination. We still observed 

that some employees wore the respirators incorrectly. In particular, 

a few employees wore a respirator that was either too small or large 

for their facial structure and thus did not seal against their faces, 

limiting the protection afforded by the respirator. In addition, 

some employees were not properly storing their respirators. We 

recommend putting respirators in a bag or container between uses 

to prevent contamination of the interior of the respirator.

Most employees wore either vinyl examination gloves (0.14–0.17 

mm thickness) or nitrile gloves (0.12–0.18 mm thickness) when 

handling pharmaceuticals. The employees who did offline 

replenishment of the Baker cells also wore hair nets. In addition, a 

few employees who hand filled prescriptions wore cloth aprons.

Dispensing of Hazardous Drugs

The pharmacy stocked 61 hazardous drugs as per the NIOSH 

list of hazardous drugs [NIOSH 2010a], 35 of which were tablets 

and therefore potentially capable of producing dust. Of all the 

hazardous drugs, estrogen was probably distributed in the highest 

volumes with the Optifill machine. This estrogen medication 

was a low dose (< 0.625 mg) tablet; we did not identify it in any 

of the total dust air samples collected from the employees who 

replenished the Optifill canisters. The other hazardous drugs were 

distributed infrequently in the manual count area of the warehouse 

during our first visit. The manual count employees were instructed 

by the employer to wear nitrile gloves and N95 filtering facepiece 

respirators when filling hazardous drug prescriptions. This was 

the same policy for the special handling employees who primarily 

worked with warfarin. By our second visit, the N95 filtering 

facepiece respirators were no longer mandated in these areas, but 

were being used as part of a voluntary use program. The pharmacy 

did not have written standard operating procedures for work 

involving hazardous drugs until our second visit. These procedures 

required hazardous drug prescriptions to be filled and verified in 

a separate area by employees wearing gloves and gave directions on 

what to do in case a drug was spilled. No other control measures 

were required.
Page 18 Health Hazard Evaluation Report 2010-0026-3150

Results

 (continued)

Figure 16. White dust covering a 

computer keyboard at the workstation 

of an employee who did offline 

replenishment of Baker cells.

Other Observations

During the first visit, we observed the use of compressed air to 

clean Baker cells during the night shift, which resulted in the 

second highest PBZ total dust concentration. Pharmacy managers 

told us that this activity was prohibited, and we did not observe 

this activity during the day shift. We also observed white dust 

on surfaces at work stations (Figure 16) that may have been from 

pharmaceuticals. We noticed that many employees washed hands 

before eating; however, we did not carefully observe hand washing 

during our evaluation. Most, if not all, employees wore their work 

outfits when they left the worksite.

Health Symptoms

We interviewed 45 employees (31 first shift and 14 second shift 

employees). Seventeen worked on or near the Baker machine, 

and six worked on or near the Optifill machine. Twenty-four 

were female, with a mean age of 36 years. Eleven were pharmacy 

employees, and 34 were contractors. The job titles were as follows: 

9 shipping-packers, 28 pharmacy technicians, 4 pharmacists, and 1 

each housekeeper, material handler, cell maintenance technician, 

and labeler. Their mean employment duration was 5 years. Of 

the 23 Optifill and Baker machine employees, 19 said they were 

exposed to dust, 12 specifically to dust from drugs. Sixteen of the 

other employees said they were exposed to dust, seven specifically 

to dust from drugs. Twenty-one employees, seven of whom worked 

on or near the Baker or Optifill machines, reported eye and upper 

respiratory irritation. Noise was a concern in certain areas, such 

as near the Optifill bottle hoppers and at the end of the packing 

line. Heat in the summer was a common concern, especially in the 

warehouse area.

Exposures to Noise

One pharmacy technician working at the Baker machine had a 

TWA noise exposure that was above the OSHA AL and NIOSH 

REL of 85 dBA (Table 4). All other monitored employees’ TWA 

noise exposures were less than OSHA and NIOSH exposure 

limits. TWA noise exposures at the ADU labeling machine, offline 

replenishment, packing station and verification area were less than 

80 dBA.
Health Hazard Evaluation Report 2010-0026-3150 Page 19

Results

 (continued) One-third octave band noise level measurements from several 

work areas or pieces of equipment are shown Figure 17. The 

predominant noise frequencies for most were greater than 8,000 

Hz. In contrast, the highest noise levels at pharmacy station #5 

were at 630 Hz and 25 Hz. In addition to high noise levels above 

8,000 Hz, the capper also had a noise level peak at 125 Hz. The 

Optifill had a secondary peak at 630–800 Hz, and the other work 

areas had secondary peaks at frequencies below 500 Hz.

Table 4. Summary of TWA noise exposure measurements

Work area or equipment Job title N

NIOSH REL 

(dBA)

OSHA AL 

(dBA)

OSHA PEL 

(dBA)

ADU labeling machine Technician 2 75.5 – 77.8 67.9 – 72.1 56.2 – 59.0

Baker Technician 10 81.1 – 88.2 77.7 – 85.1 63.9 – 80.2

Pharmacist 4 77.4 – 80.6 73.2 – 75.8 49.3 – 60.9

Area sample 1 79.0 76.1 32.4

Labeling Team leader 2 79.9 – 81.6 76.1 – 78.1 60.5 – 65.3

Technician 5 69.9 – 81.2 58.0 – 77.7 46.9 – 65.1

Offline replenishment Technician 1 70.1 55.7 52.1

Area sample 2 65.5 – 65.9 50.3 – 51.1 41.6 – 41.8

Optifill Pharmacist 2 77.0 – 80.7 73.1 – 74.8 47.1 – 68.0

Packing station Packer 6 69.4 – 78.5 57.8 – 73.7 39.6 – 60.1

Verification Pharmacist 3 71.8 – 77.5 64.9 – 72.4 36.8 – 58.0

Noise Exposure Limits 85 85 90
Page 20 Health Hazard Evaluation Report 2010-0026-3150

Discussion

Results

 (continued)

Figure 17: Octave band noise frequency measurement results (unweighted sound levels shown in parentheses).

Several tasks involving the handling of tablets correlated with 

peaks in real-time respirable particle concentration (Figures 10 

and 11) and particle counts (Figures 12–15), suggesting that 

pharmaceutical dust was released into the air where it could be 

inhaled by employees. The low levels of respirable dust suggest that 

respirable particles did not contribute substantially to the dust 

concentrations. Total dust samplers (with closed-face configuration) 

have been shown to under sample particles larger than 30 μm in 

aerodynamic diameter [Kenny et al. 1997]. Thus, the higher levels 

of inhalable dust compared to total dust that we found suggest 

that some particles >30 μm were released. When inhaled, these 

larger particles are likely to be captured in the upper respiratory 

tract [Hinds 1999]. These larger particles also settle quickly to the 

ground. Thus, much of the pharmaceutical dust that was released 

probably did not stay suspended in the air for more than a few 

seconds.

Occupational exposure limits for general dust or particles not 

otherwise regulated are only applicable when the dust particles 

are biologically inert and are insoluble in water [ACGIH 2011]. 
Health Hazard Evaluation Report 2010-0026-3150 Page 21

Discussion

 (continued) Pharmaceutical dust does not meet these criteria because APIs are 

designed to elicit biological responses, and most tablets are water 

soluble. Our data suggest that at least some of the dust we collected 

on air samples came from pharmaceuticals. Lactose, a common 

excipient in pharmaceuticals, was present in all inhalable dust 

air samples, and specific APIs were identified in most of the total 

dust air samples. Moreover, we selected two APIs (warfarin and 

lisinopril) for quantitation in air and found them to be present 

in one or more air samples. The solubility of pharmaceuticals in 

water could cause inhaled particles to be systemically absorbed 

in the upper respiratory tract. If not absorbed, some of the 

particles would be cleared to the esophagus and ingested [Hinds 

1999]. Therefore, it is not appropriate to compare the PBZ 

dust concentrations we measured to the OELs for particles not 

otherwise specified or regulated.

The PBZ air concentrations of warfarin and lisinopril did not 

exceed their respective OELs. The NIOSH REL, OSHA PEL, 

and ACGIH TLV for warfarin are intended to minimize the 

potential for hemorrhage of biological tissues, such as mucous 

membranes [ACGIH 2001, NIOSH 2010b]. The manufacturer’s 

OEL for lisinopril [Bristol-Myers Squibb Company 2008] was 

established using a control banding process that considers a variety 

of toxicological data. See Appendix B for more information about 

control banding in the pharmaceutical industry.

Allergic reactions and upper respiratory irritation are probably the 

most likely health effects from inhalation exposure to low levels 

of APIs (well below therapeutic doses). Most of the employees 

interviewed did not report having work-related health effects. 

When symptoms were reported, they were compatible with 

general exposure to dust (i.e., eye and upper-respiratory irritation). 

Exposure to APIs could also contribute to these symptoms.

We believe it is prudent to reduce exposures to pharmaceutical 

dust for the following reasons:

1. Employees are being exposed to low levels of APIs that they 

were not prescribed. Moreover, they are inhaling these APIs 

rather than ingesting them, which could change how the 

chemical affects the body.

2. Some individuals may be allergic to specific APIs or may be 

taking medications that could interact with APIs that they 

inhale at work.
Page 22 Health Hazard Evaluation Report 2010-0026-3150

3. We cannot be certain that exposures to all the APIs did not 

exceed OELs or acceptable levels. We quantified only two 

of the 22 APIs that we identified in air. In addition, not all 

APIs have published OELs. The absence of an OEL does 

not mean the chemical is safe.

4. The potential health effects from exposures to multiple 

APIs are unknown. We identified as many as five APIs 

on one total dust air sample. It is possible that one API 

could enhance the effect of another API, although allergic 

reactions and upper respiratory irritation are the most likely 

health effects.

5. Pharmaceutical dust is likely to contaminate surfaces (Figure 

16) and clothing. If employees do not wear gloves or wash 

hands before eating or using tobacco products as mandated, 

they could ingest APIs. Dermal absorption is also possible 

depending on the chemical makeup of APIs. Secondary 

exposure to family members could occur if personal clothing 

becomes contaminated with pharmaceutical dust and is 

worn at home. Children may be especially susceptible to 

adverse health effects from API exposures [Brent et al. 2004].

At this mail order pharmacy, exposure to hazardous drugs (per 

the NIOSH list of hazardous drugs [NIOSH 2010a]) presents the 

greatest potential health risk to pharmacy employees. Most of these 

drugs were dispensed manually, although at least one hormone 

medication (estrogen) was dispensed in the Optifill machine. 

Without proper precautions, exposures can occur when hazardous 

drugs are handled, particularly if these drugs are in tablet form and 

capable of producing dust. Exposures to hazardous drugs, even at 

low levels, can lead to serious health effects including skin rashes, 

reproductive problems, and possibly cancer [NIOSH 2004]. To 

provide employees with the greatest protection, employers should 

implement necessary engineering and administrative controls 

and ensure that employees use sound procedures for handling 

hazardous drugs and proper protective equipment [NIOSH 2004].

While most of the hazardous drugs were handled in a designated 

area, the other pharmaceuticals of varying toxicity were handled 

throughout the mail order pharmacy. Therefore, prioritization of 

control measures for work involving these pharmaceuticals should 

be based on the dust levels observed during different processes. In 

general, employees who cleaned cells, replenished canisters, and 

hand filled prescriptions had the highest PBZ concentrations of 

Discussion

 (continued)
Page 23

total dust, inhalable dust, and lactose. The potential for exposure 

to pharmaceutical dust also existed during the operation of the 

repack machine, particularly when tablets were dumped into totes 

and when the totes were emptied into the machine, but the use of 

the repack machine was discontinued shortly after our first visit.

For some work areas, such as the offline replenishment, exception 

station, and Baker machine, high frequency noise was generated by 

compressed air exhausting from solenoid valves and actuators. For 

most of the solenoid valves, compressed air was exhausted directly 

out of the exhaust port (Figure 18), generating substantial high 

frequency noise from air turbulence as the compressed air exited 

the exhaust port. However, a few of the exhaust ports had mufflers 

(Figure 19) to reduce noise. Additionally, reducing the pressure in 

the compressed air system may help reduce noise levels. In a few 

work areas, such as the offline replenishment, leaking compressed 

air also generated noise. Identification and repair of leaks in the 

compressed air system will eliminate this noise.

The capper, located near the west side of the Baker machine, 

generated a high frequency noise when caps were screwed onto 

prescription bottles and was a major source of noise in that area. 

The capper had an enclosure around most of the unit (Figure 20). 

Equipment enclosures are a common and often useful approach 

for controlling and reducing high frequency noise exposures. 

However, the capper was not enclosed on the bottom and had 

thin gaps along the corners and a small opening in the side panel 

(Figure 21) for prescription bottles to pass through. Adding a 

bottom panel, sealing the gaps along the corners, and reducing the 

size of any opening may reduce noise levels near the capper.

Noise at the Optifill bottler was generated by a short burst of 

compressed air released when a bottle was not properly aligned. 

In addition, the burst of air propelled the bottle and caused it to 

strike the hard plastic cover of the Optifill machine. Reduction of 

air pressure may reduce noise from the compressed air burst and 

prevent prescription bottles from striking the cover. Additionally, 

using a thicker plastic cover on the Optifill machine will dampen 

the sound if a bottle does hit the cover.

Some work areas, particularly the capper, offline replenishment, 

and pharmacy station, had high noise levels in low frequencies (< 

500 Hz). Low frequency noise is commonly caused by equipment 

vibration. Unlike high frequency noise, machine enclosures are 

Health Hazard Evaluation Report 2010-0026-3150

Discussion

 (continued)

Figure 18. Exhaust ports of a solenoid 

valve without silencing mufflers.

Figure 19. Mufflers on an exhaust port 

of a solenoid valve.

Figure 20. The capper unit enclosure.
Page 24 Health Hazard Evaluation Report 2010-0026-3150

not effective in reducing low frequency noise. Noise reduction 

strategies for low frequency noise should focus on reducing 

equipment vibration. For example, installing appropriately 

designed vibration isolation pads or springs can reduce vibration 

transmitted from operating equipment to surrounding surfaces.

A few employees wore foam insert hearing protection, but most 

of those wearing hearing protection did not insert the hearing 

protectors deeply enough into their ear canal. The hearing 

protectors provided by the employer had a noise reduction rating 

of 29 dB, which is more noise reduction than is actually needed 

for the noise levels in the facility. When hearing protectors reduce 

noise more than necessary, employees commonly feel that the 

hearing protection impairs communication and therefore do not 

wear the hearing protection, or wear it incorrectly to increase their 

hearing capacity. On the basis of noise level measurements, hearing 

protection with a noise reduction rating of 15–20 dB would 

provide adequate protection even after adjusting for workplace 

conditions (i.e., subtracting 7 dB from the manufacturer’s noise 

reduction rating and multiplying the result by 50%). Until TWA 

noise exposures for pharmacy technicians at the Baker machine are 

reduced below the OSHA AL and NIOSH REL, these employees 

should wear hearing protection, and a hearing conservation 

program should be implemented.

Many employees wore an earphone from a personal music player in 

one of their ears for much of the workday. Although the measured 

TWA noise exposures, with the exception of noise exposures near 

the Baker machine, should not present hearing loss risk, if the 

sound level from the earphone is greater than the background 

noise in the facility, employees could be at risk for hearing loss.

Discussion

 (continued)

Figure 21. Opening in the side panel of 

the capper enclosure.

Conclusions

The airborne dust levels measured in the PBZs of employees at 

the mail order pharmacy contained APIs. We did not quantify 

exposures to all the APIs that were identified in air, but for 

those two that we did, exposures were below their applicable 

OELs. Using real-time particle meters, we identified releases 

of pharmaceutical dust during specific tasks, in particular the 

cleaning of cells and replenishment of canisters with tablets. 

Employees were exposed to APIs that they were not prescribed, 

which could be particularly harmful for individuals who are allergic 

to a particular API or taking medications that could interact 
Health Hazard Evaluation Report 2010-0026-3150 Page 25

Recommendations

with low concentrations of APIs. However, allergic reactions 

and upper respiratory irritation are the most likely health effects 

from exposure to low levels of APIs. Most TWA noise exposures 

were below OSHA and NIOSH exposure limits. However, TWA 

noise exposures at the Baker machine can exceed the OSHA AL 

and NIOSH REL. The recommendations listed below will help 

minimize exposures to pharmaceutical dust and reduce noise levels.

Conclusions

 (continued)

Our recommendations are based on the hierarchy of controls 

approach (see Appendix B for more information). This approach 

groups actions by their likely effectiveness in reducing or removing 

hazards. In most cases, the preferred approach is to eliminate 

hazardous materials or processes and install engineering controls to 

reduce exposure or shield employees. Until such control measures 

are in place and shown to be effective, administrative controls or 

personal protective equipment may be needed. We encourage the 

pharmacy to use a labor-management health and safety committee 

or working group to discuss the recommendations in this report 

and develop an action plan.

Elimination and Substitution

Elimination or substitution of a hazardous process material is 

a highly effective means for reducing exposures. This strategy is 

most effective because it reduces the need for additional control 

measures in the future. However, we recognize that the elimination 

or substitution of materials is not always feasible.

1. Substitute uncoated tablets with coated tablets that are less 

likely to generate dust when choosing between uncoated and 

coated tablets that are pharmacologically the same.

Engineering Controls

Engineering controls reduce exposures to employees by removing 

the hazard from the process or placing a barrier between the 

hazard and the employee. Engineering controls are very effective 

at protecting employees without placing primary responsibility of 

implementation on the employee.
Page 26 Health Hazard Evaluation Report 2010-0026-3150

Recommendations

 (continued) 1. Install tabletop ventilation booths near the Baker and 

Optifill machines for use during the cleaning, repairing, 

and replenishment of Baker cells and Optifill canisters 

and in the hazardous drug area for use during the filling 

of hazardous drug prescriptions. Booths similar in design 

to a small tabletop paint booth would work well for this 

application. Figure VS-75-02 in “Industrial Ventilation: a 

Manual of Recommended Practice for Design” [ACGIH 

2007], provides a design plan for this type of booth. 

Crossdraft ventilation is used for this type of booth to draw 

particles away from the product (and employees) and into 

particulate filters at the back of the booth. Position the 

booths at heights that minimize bending over or excessive 

reaching. Install a bracket in the ventilation booth for the 

Baker machine for holding the cells in an upright position 

during refilling.

2. Install movable capture hoods in the offline replenishment 

area for use during the replenishment of Baker canisters. 

Hoods similar in design to a capturing hood for low toxicity 

welding may work well for this application. Figure VS-90-

02 in “Industrial Ventilation: a Manual of Recommended 

Practice for Design” [ACGIH 2007], provides a design plan 

for this type of hood. Instruct employees to place the inlet of 

the hoods near where dust is generated without interfering 

with the process. Install particulate filters on the negative 

pressure side of the exhaust fan.

3. Consult a ventilation specialist to design and install the 

booths and hoods and certify the booths annually.

4. Train employees annually on how to properly use and 

maintain the booths and hoods.

5. Reduce noise levels through the following noise controls:

a. Install mufflers on the exhaust ports of solenoid valves 

and actuators, and investigate whether the air pressure in 

the compressed air system can be reduced.

b. Maintain the compressed air system properly, and 

promptly repair leaks.

c. At the capper, add a bottom panel, seal the gaps along 

the corners, and reduce the size of any openings.

d. Reduce air pressure at the Optifill machine, and install a 

thicker plastic cover.
Health Hazard Evaluation Report 2010-0026-3150 Page 27

Recommendations

 (continued) e. Install vibration isolation pads on equipment that 

generates low frequency noise near the capper, offline 

replenishment, and pharmacy station.

Administrative Controls

Administrative controls are management-dictated work practices 

and policies to reduce or prevent exposures to workplace hazards. 

The effectiveness of these control measures is dependent on 

management commitment and employee acceptance. Regular 

monitoring and reinforcement are necessary to ensure that 

following policies and procedures are not circumvented in the 

name of convenience or production.

1. Identify and label all hazardous drugs so that any employee 

can easily identify them [NIOSH 2010a].

2. Evaluate the potential for employee exposures from the 

dispensing of hazardous drugs in the automatic dispensing 

machines (estrogen). If these drugs can produce dust 

containing APIs during dispensing, then they should be 

transferred to the hazardous drug area where employee 

exposures can be more tightly controlled (see the next 

recommendation).

3. Modify standard operating procedures for the filling 

of hazardous drug prescriptions. The NIOSH Alert, 

“Preventing Occupational Exposure to Antineoplastic 

and Other Hazardous Drugs in Health Care Settings,” 

provides guidelines on the control measures that should 

be used when handling hazardous drugs. These guidelines 

are intended primarily for oncology clinics and hospital 

pharmacies, but can be adapted for this mail order 

pharmacy. These procedures should include using a tabletop 

ventilation booth when filling hazardous drug prescriptions, 

wearing at least one pair of nitrile gloves, wearing a lab coat, 

and training employees on how to remove and discard gloves 

and clean the workstation so their skin is not contaminated. 

NIOSH-approved particulate respirators should be worn 

until the ventilation booth or other local exhaust ventilation 

system is available to use (see personal protective equipment 

recommendations).

4. Develop written standard operating procedures and a 

schedule for the change out of particulate filters used in the 

ventilation booths, hoods, and HEPA vacuums. These filters 
Page 28 Health Hazard Evaluation Report 2010-0026-3150

Recommendations

 (continued) could expose employees to pharmaceutical dust (including 

hazardous drugs) if proper safeguards are not in place. These 

procedures should involve a team of two employees who 

wear disposable gloves, disposable gowns, safety glasses, 

and NIOSH-approved particulate respirators (see personal 

protective equipment recommendations). One employee 

should hold a plastic bag, while the other employee removes 

the filter and places it in the bag. The bag should then 

be sealed. A HEPA vacuum should be used to collect any 

residual dust on surfaces. After replacing the filters, all PPE 

should be sealed in a plastic bag for disposal.

5. Use the HEPA vacuum daily to collect pharmaceutical 

dust that accumulates under the Baker cell nozzles, Optifill 

canisters, and other areas where pharmaceutical dust may 

collect.

6. Provide easier access to hand washing stations, and continue 

to require employees to wash their hands before eating 

or using tobacco products to prevent the hand-to-mouth 

ingestion of pharmaceutical particles.

7. Ensure that employees are not using compressed air for 

cleaning cells. Remove the compressed airline and nozzle if 

it is no longer needed.

8. Have employees report any workplace symptoms to their 

supervisors, who may in turn refer them for medical 

evaluation as appropriate.

9. Organize a health and safety committee consisting of 

employee and management representatives who meet 

regularly to address health and safety concerns.

10. Eliminate the use of personal music players in work areas.

11. Implement a hearing conservation program if noise 

exposures at the Baker machine cannot be reduced below 

the OSHA AL.

Personal Protective Equipment

PPE is the least effective means for controlling employee exposures. 

Proper use of PPE requires a comprehensive program, and calls 

for a high level of employee involvement and commitment to be 

effective. The use of PPE requires the selection of the appropriate 

equipment to reduce the hazard and the development of 

supporting programs such as training, change-out schedules, and 
Health Hazard Evaluation Report 2010-0026-3150 Page 29

Recommendations

 (continued) medical assessment if needed. PPE should not be relied upon as 

the sole method for limiting employee exposures. Rather, PPE 

should be used until engineering and administrative controls 

reduce exposures to acceptable levels.

1. Require employees to wear NIOSH-approved half-mask 

N95 filtering facepiece respirators or other NIOSHapproved particulate respirators with comparable or higher 

protection factors during the hand filling of hazardous 

drug prescriptions and change-out of particulate filters 

in the ventilation booths, hoods, and HEPA vacuums. 

Discontinue the use of respirators for hand filling hazardous 

drug prescriptions once a ventilation booth or other local 

exhaust ventilation system is available for this process and 

demonstrated to be effective in limiting dust exposures. 

Include employees required to wear respirators in a 

comprehensive respiratory protection program that adheres 

to the OSHA standard [29 CFR 1910.134].

2. Provide employees with lab coats or other personal 

protective clothing that can be discarded after use or 

laundered weekly by professionals. This will help prevent the 

contamination of personal clothing with APIs and minimize 

secondary exposures.

3. Emphasize to employees the importance of wearing nitrile 

gloves when handling pharmaceuticals.

4. Provide hearing protection with a noise reduction rating of 

15–20 dB, and require that pharmacy technicians working 

around the Baker machine use the hearing protection.

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limit values and biological exposure indices. Cincinnati, OH: 

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ACGIH [2007]. Industrial ventilation: a manual of recommended 

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Conference of Governmental Industrial Hygienists.

ACGIH [2011]. Threshold limit values for chemical substances and 

physical agents and biological exposure indices. Cincinnati, OH: 

American Conference of Governmental Industrial Hygienists.
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Hornung RW, Reed LD [1990]. Estimation of average 

concentration in the presence of non-detectable values. Appl 

Occup Environ Hyg 5(1):46–51.

Kenny LC, Aitken R, Chalmers C, Fabries JF, Gonzalez-Fernandez 

E, Kromhout H, Liden G, Mark D, Riediger G, Prodi V [1997]. A 

collaborative European study of personal inhalable aerosol sampler 

performance. Ann Occup Hyg 41(2):135–153.

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, National Institute for Occupational 

Safety and Health, DHHS (NIOSH) Publication No. 2004-165.

NIOSH [2010a]. NIOSH list of antineoplastic and other hazardous 

drugs in health care settings 2010. Cincinnati, OH: U.S. 

Department of Health and Human Services, Centers for Disease 

Control, National Institute for Occupational Safety and Health, 

DHHS (NIOSH) Publication No. 2010-167.

NIOSH [2010b]. NIOSH pocket guide to chemical hazards. 

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

Centers for Disease Control and Prevention, National Institute for 

Occupational Safety and Health (NIOSH) Publication No. 2010-

168c. [http://www.cdc.gov/niosh/npg/]. Date accessed: October 

2011.

References

 (continued)
Health Hazard Evaluation Report 2010-0026-3150 Page 31

NIOSH [2011]. 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/].

Takats Z, Wiseman JM, Gologan B, Cooks RG [2004]. Mass 

spectrometry sampling under ambient conditions with desorption 

electrospray ionization. Science 306(5695):471–473.

References

 (continued)
Page 32 Health Hazard Evaluation Report 2010-0026-3150

Appendix A: Additional Information on Sampling and

Analytical Methods

Air Sampling Methods

AirChek XR5000 pumps (SKC, Inc., Eighty Four, Pennsylvania) were calibrated for an airflow rate of 4 

Lpm, and SKC AirChek 2000 pumps were calibrated for all other airflow rates listed in Table 1 (on page 

6). All pumps were precalibrated and postcalibrated with the sample media connected. The respirable 

dust sampling train consisted of a metal cyclone (model GK 2.05, BGI, Inc., Waltham, Massachusetts) 

connected to a Personal DataRAM aerosol monitor (Thermo, Smyrna, Georgia). Air was drawn through 

the inlet of Tygon® tubing positioned in the employee’s PBZ. According to guidelines from Thermo, 

use of the Tygon tubing should result in less than a 10% loss in particles smaller than 4 μm in diameter 

[Thermo 1995].

During both visits, we used a Met One HHPC-6 handheld airborne particle counter (Hach® Ultra 

Analytics, Inc., Loveland, Colorado) to identify releases of pharmaceutical dust into the air. During the 

first visit, we sampled approximately 0.5–1 liters of air with the particle counter before, during, and after 

specific tasks. During the second visit, we sampled 1 liter of air continuously (about every 30 seconds) 

throughout the workday. Spikes in particle counts suggested releases of pharmaceutical dust, which we 

were able to correlate with tasks involving specific APIs.

Analytical Methods

We used NIOSH analytical methods to measure total dust (NIOSH Method 0500), respirable dust 

(NIOSH Method 0600), and warfarin (NIOSH Method 5002) [NIOSH 2011]. The analytical method used 

by Prosolia to identify APIs on the surface of filters is described in the scientific literature [Takats et al. 

2004].

The analytical methods used for the quantitation of lactose and lisinopril were internal methods developed 

by BVNA. These methods are briefly described below.

Lactose

Filters were removed from the IOM samplers and extracted in glass vials using 1 mL of deionized water. 

The samples were capped and swirled. After extraction, the samples were transferred to autosampler vials 

and analyzed by high performance liquid chromatography using the parameters below.

Instrument: Dionex 3000

Column: Dionex CarboPac PA1, 4 × 250 mm

Column flow rate: 1 mL per minute

Column temperature: Ambient

Injection volume: 200 microliter

Detector: Electrochemical detector

Mobile phase: Isocratic, 200 millimolar sodium hydroxide in deionized water
Health Hazard Evaluation Report 2010-0026-3150 Page 33

Appendix A: Additional Information on Sampling and

Analytical Methods (continued)

Lisinopril

Filters were previously processed for quantitation of lactose and were already desorbed in 1 mL of 

deionized water. Samples were transferred to autosampler vials and analyzed by high performance liquid 

chromatography using the parameters below.

Instrument: Waters 2690 separations module

Column: Agilent Zorbax Bonus-RP, 5 μm column 250 × 4.6 mm

Column flow rate: 1 mL per minute

Column temperature: Ambient

Injection volume: 25 microliter

Detector: Waters 2487 dual wavelength ultraviolet detector

Wavelength: 210 nanometers

Run time: 12 minutes

Mobile phase: 85% buffer/15% acetonitrile (buffer=1000 mL deionized water/8.25mL 

triethanolamine/11.75 mL phosphoric acid)

Noise Sampling Methods

We used Larson-Davis (Provo, Utah) Spark® model 705P or model 706-RC noise dosimeters. Both models 

of dosimeters functioned identically. For employee monitoring, we attached the noise dosimeters to the 

employees’ belts and fastened the small dosimeter microphones to the employees’ shirts at a point midway 

between the ear and the outside of the shoulder. We placed one area monitor on top of a pharmacist desk 

near the Baker machine and two area monitors in the offline replenishment area. The area monitors were 

intended to represent exposures of an employee working in those areas for an entire work shift. We placed 

windscreens over the microphones during measurements to reduce or eliminate artifact noise that can 

occur if objects bump against an unprotected microphone.

The dosimeters collected noise data using three different settings so that we could directly compare the 

noise measurement results with the three different noise exposure limits referenced in this HHE report: 

the OSHA PEL, OSHA AL, and the NIOSH REL. OSHA uses a 90-dBA criterion and a 5-dB exchange 

rate for both the PEL and AL. However, the PEL has a 90-dBA threshold, and the AL has an 80-dBA 

threshold. NIOSH has an 85-dBA criterion and uses an 80-dBA threshold. During noise dosimetry 

measurements, noise levels below the threshold level are not integrated by the dosimeter for accumulation 

of dose and calculation of TWA noise level. The dosimeters averaged noise levels every second during 

monitoring. At the end of the work shift, the dosimeters were removed, and the noise measurement 

information stored in the dosimeters was downloaded to a computer for interpretation with Larson Davis 

Blaze® computer software. The dosimeters were calibrated before and after the measurement periods 

according to the manufacturer’s instructions.

The sound level meters were equipped with 0.5-inch random incidence Type 1 electret microphones. The 

sound level meters were calibrated according to the manufacturer’s instructions. Sound level meters were 

either handheld or mounted on a tripod at a height of approximately 5 feet.
Page 34 Health Hazard Evaluation Report 2010-0026-3150

References

NIOSH [2011]. 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/].

Takats Z, Wiseman JM, Gologan B, Cooks RG [2004]. Mass spectrometry sampling under ambient 

conditions with desorption electrospray ionization. Science 306(5695):471–473.

Thermo [1995]. Thermo technical guidelines: Inlet tubing guidelines for MIE dust monitors. Franklin, 

MA: Thermo Electron Corporation Publication No. 19-A.

Appendix A: Additional Information on Sampling and

Analytical Methods (continued)
Health Hazard Evaluation Report 2010-0026-3150 Page 35

Appendix B: Occupational Exposure Limits and Health Effects

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

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

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

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

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

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

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

may experience adverse health effects because of individual susceptibility, a preexisting medical condition, 

and/or a hypersensitivity (allergy). In addition, some hazardous substances may act in combination with 

other workplace exposures, the general environment, or with medications or personal habits of the 

employee to produce adverse health effects even if the occupational exposures are controlled at the level set 

by the exposure limit. Also, some substances can be absorbed by direct contact with the skin and mucous 

membranes in addition to being inhaled, which contributes to the individual’s overall exposure.

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

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

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

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

the ceiling limit is an exposure that should not be exceeded at any time.

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

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

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

CFR 1926 [construction industry]; and 29 CFR 1917 [maritime industry]) are legal limits enforceable 

in workplaces covered under the Occupational Safety and Health Act of 1970. NIOSH RELs are 

recommendations based on a critical review of the scientific and technical information available on a 

given hazard and the adequacy of methods to identify and control the hazard. NIOSH RELs can be 

found in the NIOSH Pocket Guide to Chemical Hazards [NIOSH 2010]. NIOSH also recommends different 

types of risk management practices (e.g., engineering controls, safe work practices, employee education/

training, personal protective equipment, and exposure and medical monitoring) to minimize the risk of 

exposure and adverse health effects from these hazards. Other OELs that are commonly used and cited 

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

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

The TLVs and WEELs are developed by committee members of these associations from a review of the 

published, peer-reviewed literature. They are not consensus standards. ACGIH TLVs are considered 

voluntary exposure guidelines for use by industrial hygienists and others trained in this discipline “to assist 

in the control of health hazards” [ACGIH 2011]. WEELs have been established for some chemicals “when 

no other legal or authoritative limits exist” [AIHA 2011].

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

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

Unfallversicherung (IFA, Institute for Occupational Safety and Health of the German Social Accident 
Page 38 Health Hazard Evaluation Report 2010-0026-3150

Appendix B: Occupational Exposure Limits and Health Effects

 (continued)

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

(Québec), Japan, Switzerland, and the United States. The database, available at http://www.dguv.de/ifa/

en/gestis/limit_values/index.jsp, contains international limits for over 1,500 hazardous substances and is 

updated periodically.

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

agents the legally enforceable and recommended limits may not reflect current health-based information. 

However, an employer is still required by OSHA to protect its employees from hazards even in the absence 

of a specific OSHA PEL. OSHA requires an employer to furnish employees a place of employment free 

from recognized hazards that cause or are likely to cause death or serious physical harm [Occupational 

Safety and Health Act of 1970 (Public Law 91–596, sec. 5(a)(1))]. Thus, NIOSH investigators encourage 

employers to make use of other OELs when making risk assessments and risk management decisions to 

best protect the health of their employees. NIOSH investigators also encourage the use of the traditional 

hierarchy of controls approach to eliminate or minimize identified workplace hazards. This includes, in 

order of preference, the use of (1) substitution or elimination of the hazardous agent, (2) engineering 

controls (e.g., local exhaust ventilation, process enclosure, dilution ventilation), (3) administrative controls 

(e.g., limiting time of exposure, employee training, work practice changes, medical surveillance), and (4) 

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

Control banding, a qualitative risk assessment and risk management tool, is a complementary approach 

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

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

ctrlbanding/. This approach can be applied in situations where OELs have not been established or can be 

used to supplement the OELs, when available.

Active Pharmaceutical Ingredients

Of the compounds we identified in air, only warfarin has an OEL established by a U.S. national agency or 

organization. Warfarin is an anticoagulant prescribed for people with certain types of irregular heartbeat, 

people with prosthetic (replacement or mechanical) heart valves, and people who have suffered a heart 

attack. Warfarin is also used to treat or prevent venous thrombosis (swelling and blood clot in a vein) 

and pulmonary embolism (a blood clot in the lung) [PubMed Health 2011]. The NIOSH REL, OSHA 

PEL, and ACGIH TLV for warfarin (100 μg/m3

) are based on the potential for hemorrhage of biological 

tissues [ACGIH 2001, NIOSH 2010]. ACGIH specifically states that its TLV is intended to minimize the 

potential for hemorrhage of the mucous membranes and gastrointestinal and genitourinary tracts [ACGIH 

2001]. For the other APIs that we identified in air, Table B1 provides a summary of their therapeutic uses 

and manufacturers’ OELs (if available). The manufacturers’ OELs were established by pharmaceutical 

companies using a control banding process, which places APIs 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]. Hazard categories have acceptable levels of exposure or OELs.
Health Hazard Evaluation Report 2010-0026-3150 Page 39

Appendix B: Occupational Exposure Limits and Health Effects

 (continued)

Table B1. Prescribed uses and manufacturers’ OELs for the APIs identified in air

API Prescribed for*

Manufacturer OEL 

(μg/m3)†

Allopurinol Gout 5,000

Benazepril High blood pressure None published

Bethanechol chloride Urination problems None published

Buspirone HCl Anxiety None published

Carbidopa / levodopa Parkinson disease and Parkinson-like symptoms 100

Chlorpheniramine maleate Allergies 10

Doxazosin mesylate Enlarged prostate or high blood pressure 30

Glipizide Type 2 diabetes None published

Hydralazine HCl High blood pressure None published

Lamotrigine Epileptic seizures, depression, mania and other 

abnormal moods in patients with bipolar disorder

200

Lisinopril High blood pressure, heart failure 10

Meclizine HCl Motion sickness 70

Metformin Type 2 diabetes 800

Methocarbamol Muscle pain None published

Metoclopramide HCl Heart burn, ulcers, acid reflux 40

Naproxen sodium Pain, reducing fever 1,000

Oxybutynin Overactive bladder None published

Promethazine HCl Allergies, conjunctivitis, skin reactions, motion 

sickness

None published

Sotalol HCl Irregular heartbeat None published

Trazadone HCl Depression None published

Venlafaxine HCl Depression, anxiety, panic disorder 250

* [PubMed Health 2011]

†

 Allopurinol [GlaxoSmithKline 2006], carbidopa [Bristol-Myers Squibb Company 2010], chlorpheniramine maleate 

[GlaxoSmithKline 2005], doxazosin mesylate [Pfizer 2009], lamotrigine [GlaxoSmithKline 2007], lisinopril [BristolMyers Squibb Company 2008a], meclizine HCl [Pfizer 2003], metformin [Bristol-Myers Squibb Company 2008b], 

metoclopramide HCl [Hospira 2008], naproxen sodium [Roche 2006], venlafaxine [Pfizer 2007]
Page 40 Health Hazard Evaluation Report 2010-0026-3150

Appendix B: Occupational Exposure Limits and Health Effects

 (continued)

Noise

Noise-induced hearing loss is an irreversible, sensorineural condition that progresses with exposure. 

Although hearing ability declines with age (presbycusis), noise exposure produces more hearing loss than 

that resulting from aging alone. This noise-induced hearing loss is caused by damage to nerve cells of the 

inner ear (cochlea) and, unlike some conductive hearing disorders, cannot be treated medically [Berger et 

al. 2003]. In most cases, noise-induced hearing loss develops slowly and usually occurs before it is noticed. 

Hearing loss is often severe enough to permanently affect a person’s ability to hear and understand speech. 

For example, people with hearing loss may not be able to distinguish words such as “fish” from “fist” 

[Suter 1978].

The dBA is the preferred unit for measuring sound levels to assess employee noise exposures. The dBA 

noise scale is weighted to approximate the sensory response of human ears to sound frequencies near 

the hearing threshold. Because the dBA scale is logarithmic, increases of 3 dBA, 10 dBA, and 20 dBA 

represent a doubling, tenfold increase, and hundredfold increase of sound energy, respectively. Noise 

exposures expressed in dBA cannot be averaged by taking the arithmetic mean.

The OSHA noise standard [29 CFR 1910.95] specifies a PEL of 90 dBA, as an 8-hour TWA. The OSHA 

PEL is calculated using a 5-dB exchange rate. This means that a person may be exposed to noise levels of 

95 dBA for no more than 4 hours, 100 dBA for 2 hours, 105 dBA for 1 hour, etc. An employee’s daily 

noise dose, based on the duration and intensity of noise exposure, can be calculated according to the 

formula

 Dose = 100 X (C1/T1 + C2/T2 + ... + Cn/Tn ),

where Cn indicates the total time of exposure at a specific noise level and Tn indicates the reference 

duration for that level as given in Table G-16a of the OSHA noise regulation. Doses greater than 100% are 

in excess of the OSHA PEL.

When noise exposures exceed the PEL of 90 dBA, OSHA requires that employees wear hearing protection, 

and that an employer implement feasible engineering or administrative controls to reduce noise exposures. 

The OSHA noise standard also requires an employer to implement a hearing conservation program 

when 8-hour TWA noise exposures exceed the AL 85 dBA. The program must include noise monitoring, 

employee notification, observation, audiometric testing, hearing protectors, training, and record keeping.

NIOSH [NIOSH 1998] and ACGIH [ACGIH 2011] recommend an exposure limit of 85 dBA, as an 

8-hour TWA. A more conservative 3 dB exchange rate is used in calculating exposure these limits. Using 

NIOSH criteria, an employee can be exposed to 85 dBA for 8 hours, but to no more than 88 dBA for 4 

hours, 91 dBA for 2 hours, 94 dBA for 1 hour, etc. Twelve-hour exposures have to be 83.2 dBA or less 

according to the NIOSH REL.
Health Hazard Evaluation Report 2010-0026-3150 Page 41

Audiometric evaluations of employees hearing thresholds must be conducted in quiet locations, preferably 

in a sound-attenuating booth, by presenting pure tones of varying frequencies at threshold levels (i.e., the 

level of a sound that the person can just barely hear). Zero dB hearing level represents the hearing level of 

an average, young individual with good hearing. OSHA requires hearing thresholds to be measured at test 

frequencies of 500, 1,000, 2,000, 3,000, 4,000, and 6,000 Hz. Individual employee’s annual audiograms 

are compared to their baseline audiogram to determine if a standard threshold shift has occurred. OSHA 

states that a standard threshold shift has occurred if the average threshold values at 2,000, 3,000, and 

4,000 Hz have increased by 10 dB or more in either ear when comparing the annual audiogram to the 

baseline audiogram [29 CFR 1910.95]. The NIOSH-recommended hearing threshold shift criterion is a 

15-dB shift at any frequency in either ear from 500–6,000 Hz measured twice in succession [NIOSH 1998]. 

Both of these hearing threshold shift criteria require at least two audiometric tests.

The audiogram profile is a plot of the hearing test frequencies (x-axis) versus the hearing threshold levels 

(y-axis). For many employees, the audiogram profile tends to slope downward toward the high frequencies 

with an improvement at the audiogram’s highest frequencies, forming a “notch” [Suter 2002]. A notch in 

the audiogram of an employee with otherwise normal hearing may indicate the early onset of hearing loss. 

The notch from occupational noise can occur between 3,000 and 6,000 Hz [ACOM 1989; Osguthorpe 

and Klein 2001]. However, it is generally accepted that a notch at 4,000 Hz indicates occupational hearing 

loss [Prince et al. 1997]. An individual may have notches at different frequencies in one or both ears [Suter 

2002]. For this evaluation, a notch is defined as the frequency where the hearing level is preceded by an 

improvement of at least 10 dB and followed by an improvement of at least 5 dB.

References

ACGIH [2001]. Warfarin. In: Documentation of the threshold limit values and biological exposure 

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

ACGIH [2011]. Threshold limit values for chemical substances and physical agents and biological exposure 

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

ACOM [1989]. Occupational noise-induced hearing loss. ACOM Noise and Hearing Conservation 

Committee. J Occup Med 31(12):996.

AIHA [2011]. AIHA 2009 Emergency response planning guidelines (ERPG) & workplace environmental 

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

Berger EH, Royster LH, Royster JD, Driscoll DP, Layne M, eds. [2003]. The noise manual. 5th rev. ed. 

Fairfax, VA: American Industrial Hygiene Association.

Bristol-Myers Squibb Company [2008a]. Safety data sheet: Lisinopril. [http://www.bmsmsds.com/

msdsweb/filebrowse?objectid=0900dfd480336149]. Date accessed: September 2011.

Appendix B: Occupational Exposure Limits and Health Effects

 (continued)
Page 42 Health Hazard Evaluation Report 2010-0026-3150

Bristol-Myers Squibb Company [2008b]. Safety data sheet: Metformin hydrochloride. [http://www.

bmsmsds.com/msdsweb/filebrowse?objectid=0900dfd480335b4f]. Date accessed: September 2011.

Bristol-Myers Squibb Company [2010]. Safety data sheet: Sinemet tablets - bulk and drug product. [http://

www.bmsmsds.com/msdsweb/filebrowse?objectid=0900dfd48038c302]. Date accessed: September 2011.

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Federal Register.

GlaxoSmithKline [2005]. Safety data sheet: Piriton syrup. [http://www.msds-gsk.com/uk_cons/12732103.

pdf]. Date accessed: September 2011.

GlaxoSmithKline [2006]. Safety data sheet: Zyloric tablets. [http://www.msds-gsk.com/uk_

presc/12703205.pdf]. Date accessed: September 2011.

GlaxoSmithKline [2007]. Safety data sheet: Lamictal dispersible tablets. [http://www.msds-gsk.

com/12701905.pdf]. Date accessed: September 2011.

Hospira [2008]. Safety data sheet: Metoclopramide. [http://www.bdipharma.com/MSDS/Hospira/

Metoclopramide.pdf]. Date accessed: September 2011.

Naumann BD [2005]. Control banding in the pharmaceutical industry. [http://www.aioh.org.au/

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Cincinnati, OH: U.S. Department of Health and Human Services, Centers for Disease Control, National 

Institute for Occupational Safety and Health, DHHS (NIOSH) Publication No. 2010-167.

Appendix B: Occupational Exposure Limits and Health Effects

 (continued)
Health Hazard Evaluation Report 2010-0026-3150 Page 43

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Appendix B: Occupational Exposure Limits and Health Effects

 (continued)
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Health Hazard Evaluation Report 2010-0026-3150 Page 45

Acknowledgments and

Availability of Report

The Hazard Evaluations and Technical Assistance Branch (HETAB) of 

the National Institute for Occupational Safety and Health (NIOSH) 

conducts field investigations of possible health hazards in the 

workplace. These investigations are conducted under the authority 

of Section 20(a)(6) of the Occupational Safety and Health Act of 

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

and Human Services, following a written request from any employer 

or authorized representative of employees, to determine whether any 

substance normally found in the place of employment has potentially 

toxic effects in such concentrations as used or found. HETAB also 

provides, upon request, technical and consultative assistance to 

federal, state, and local agencies; labor; industry; and other groups 

or individuals to control occupational health hazards and to prevent 

related trauma and disease.

Mention of any company or product does not constitute endorsement 

by NIOSH. In addition, citations to websites external to NIOSH do 

not constitute NIOSH endorsement of the sponsoring organizations 

or their programs or products. Furthermore, NIOSH is not 

responsible for the content of these websites. All Web addresses 

referenced in this document were accessible as of the publication date.

This report was prepared by Kenneth Fent, Srinivas Durgam, Carlos 

Aristeguieta, and Scott Brueck of HETAB, Division of Surveillance, 

Hazard Evaluations and Field Studies. Elena Page of HETAB assisted 

with the interpretation of the medical interview data and Donna 

Heidel of NIOSH Education and Information Division assisted 

with the interpretation of the active pharmaceutical ingredient 

exposure data. Industrial hygiene field assistance was provided by 

Chad Dowell and Diana Ceballos of HETAB. Industrial hygiene 

equipment and logistical support was provided by Donnie Booher 

and Karl Feldmann. Analytical support was provided by BVNA 

and Justin Wiseman and Joseph Kennedy at Prosolia, Indianapolis, 

Indiana. Health communication assistance was provided by Stefanie 

Evans. Editorial assistance was provided by Ellen Galloway. Desktop 

publishing was performed by Greg Hartle.

Copies of this report have been sent to employee and management 

representatives at the mail order pharmacy, the state health 

department, and the Occupational Safety and Health Administration 

Regional Office. This report is not copyrighted and may be freely 

reproduced. The report may be viewed and printed at http://www.

cdc.gov/niosh/hhe/. Copies may be purchased from the National 

Technical Information Service at 5825 Port Royal Road, Springfield, 

Virginia 22161.
Below is a recommended citation for this report:

NIOSH [2011]. Health hazard evaluation report: exposures to pharmaceutical dust 

at a mail order pharmacy – Illinois. By Fent KW, Durgam S, Aristeguieta C, Brueck 

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

Disease Control and Prevention, National Institute for Occupational Safety and 

Health, NIOSH HETA No. 2010-0026-3150.

To receive NIOSH documents or information about 

occupational safety and health topics, contact NIOSH at:

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

TTY: 1-888-232-6348

E-mail: cdcinfo@cdc.gov

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Delivering on the Nation’s promise:

Safety and health at work for all people

through research and prevention.

 National Institute for Occupational 

Safety and Health