Health Hazard Evaluation Report 2010-0078-3177 Page 1

Evaluation of Pharmaceutical Dust Exposures 

at an Outpatient Pharmacy

Report No. 2010-0078-3177

April 2013

Kenneth W. Fent, PhD

Srinivas Durgam, MSPH, MSChE, CIH

Mark Methner, PhD, CIH

U.S. Department of Health and Human Services

Centers for Disease Control and Prevention

National Institute for Occupational Safety and Health
Page 2 Health Hazard Evaluation Report 2010-0078-3177

Contents

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

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

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

Methods ............................................... 2

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

Discussion .......................................... 13

Conclusions........................................ 15

Recommendations............................. 15

Appendix A ........................................ 18

Appendix B......................................... 20

Appendix C......................................... 26

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

Acknowledgements........................... 31

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

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

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

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

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

not be related to this Health Hazard Evaluation.
Health Hazard Evaluation Report 2010-0078-3177 Page i

Work activities in the outpatient 

pharmacy generated dusts 

that exposed employees to 

pharmaceutical ingredients. 

One employee had personal air 

concentrations of lisinopril near 

or above the manufacturer’s 

exposure limit. We recommend 

doing dust-generating tasks 

under a local exhaust hood 

and using a vacuum with 

high-efficiency particulate air 

filtration to clean canisters. 

Highlights of this Evaluation

The Health Hazard Evaluation Program received a request from an outpatient pharmacy. The 

employer was concerned about employee exposures to pharmaceutical dust.

What We Did

● We did exposure sampling at the pharmacy in April 2011. We returned in April 2012 to 

do more sampling.

● We measured particle levels 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. They were also analyzed for lactose 

(common inactive filler in tablets) and active 

pharmaceutical ingredients.

● We sampled surfaces for lactose to look 

for possible pharmaceutical contamination 

throughout the pharmacy.

What We Found

● One employee was exposed to lisinopril on 

two workdays at levels near or above the 

manufacturer’s exposure limit.

● Dust was released into the air when automatic 

dispensing machine canisters were cleaned with 

compressed air. Filling canisters with tablets 

produced lower levels of dust in the air. 

● After employees used compressed air to clean canisters, more than an hour passed 

before the small particles produced were no longer in the air.

● We found lactose and active pharmaceutical ingredients in the dust in the air. Lactose 

was found on surfaces throughout the pharmacy. This suggests that some dust in air and 

on surfaces was from pharmaceuticals.

● Some employees wore nitrile gloves when handling pharmaceuticals. Employees did 

not wear protective clothing or safety glasses.

 What the Employer Can Do

● Develop a list of pharmaceuticals that are dusty and gather exposure guidelines and 

toxicity data for those pharmaceuticals. Use this information to guide future exposure 

assessments and determine how these pharmaceuticals should be handled.

● Install a partially-enclosed local exhaust hood for cleaning and filling canisters with 

tablets or doing other tasks that could send pharmaceutical dust into the air.
Page ii Health Hazard Evaluation Report 2010-0078-3177

 What the Employer Can Do (continued)

● Continue to use the vacuum daily to clean the Optifill machine. Make sure the vacuum 

contains a high efficiency particulate air filter. Change the filter routinely according to the 

manufacturer’s guidelines.

● Use the vacuum with a long narrow nozzle to clean canisters. Stop using compressed air 

for this task. 

● Provide safety glasses and protective clothing to employees who do tasks outside the 

hood that could send pharmaceutical dust into the air. 

● Train employees on the need to wear nitrile gloves when handling pharmaceuticals.

● Clean work surfaces with alcohol wipes before breaks and at the end of the workday.

● 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 local exhaust hood.

● Wear nitrile gloves when handling pharmaceuticals.

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

● Tell your supervisor about workplace health or safety concerns you have.

● Become active in the health and safety committee.
Health Hazard Evaluation Report 2010-0078-3177 Page iii

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 of this report.
Page iv Health Hazard Evaluation Report 2010-0078-3177

Abbreviations

°C Degrees Celsius

μg/cm2 Micrograms per square centimeter

μg/m3 Micrograms per cubic meter

μm Micrometer

API Active pharmaceutical ingredient

BVNA Bureau Veritas North America, Inc.

CFR Code of Federal Regulations 

HCTZ Hydrochlorothiazide

HEPA High-efficiency particulate air

HHPC Handheld airborne particle counter

IOM Institute of Occupational Medicine

Lpm Liters per minute

MDC Minimum detectable concentration

mL Milliliter

mm Millimeter

mM Millimolar

MQC Minimum quantifiable concentration

n Number of samples

NA Not applicable

NAICS North American Industry Classification System

ND Not detected

NIOSH National Institute for Occupational Safety and Health

No. Number

OEL Occupational exposure limit

p/L Particles per liter

PTFE Polytetrafluoroethylene

TWA Time-weighted average 
Health Hazard Evaluation Report 2010-0078-3177 Page 1

Introduction 

The Health Hazard Evaluation Program received a request from managers at an outpatient 

pharmacy in Ohio. The request concerned potential employee exposures to pharmaceutical 

dust. We evaluated exposures at the pharmacy in April 2011 and April 2012.

Twenty or more employees 

worked at the pharmacy, which 

operated a single shift 6 days 

per week (Monday through 

Saturday). The pharmacy filled 

7,000 to 8,000 prescriptions 

per week primarily using 

automatic dispensing 

machines. An Optifill® IIPlus machine (Figure 1, 

AmerisourceBergen®, Valley 

Forge, Pennsylvania) was 

used for most refills and 

a PharmAssist® machine 

(Figure 2, Innovation, 

Johnson City, New York) was 

used for filling most initial 

prescriptions. On occasion, 

some technicians used a desktop counter 

(model no. KL15df, KirbyLester, Lake 

Forest, Illinois) to fill prescriptions. All 

these machines used gravity to dispense 

pharmaceutical tablets and capsules. 

One pharmacy technician hand filled 

prescriptions for controlled substances 

(schedule III–V) in a dedicated area. 

Some prescriptions did not require any 

counting as they came prepackaged from 

the manufacturer as a unit dose or the usual 

prescribed dose. All prescriptions were 

verified by pharmacists.

The Optifill machine was maintained by 

two pharmacy technicians. Maintenance 

activities included refilling canisters; using 

compressed air to clean canisters; and 

cleaning the inside of the Optifill machine 

with a 3M field service vacuum (3M, 

St. Paul, Minnesota), isopropyl alcohol 

Figure 1. Optifill machine. 

Figure 2. PharmAssist machine. 
Page 2 Health Hazard Evaluation Report 2010-0078-3177

wipes, and stainless steel cleaner. Several pharmacy technicians shared the maintenance of 

the PharmAssist machine. Maintenance included refilling canisters and using compressed 

air to clean canisters. Canisters required cleaning if they were extremely dusty or stopped 

functioning properly, usually due to dust accumulation. 

Methods

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) quantify specific 

active pharmaceutical agents (APIs) and other pharmaceutical ingredients in the airborne 

dust, and (4) determine the extent of surface contamination with pharmaceutical ingredients. 

Air Sampling

The air sampling methods used during visit 1 (April 2011) are summarized in Table 1. Seven 

total dust air samples were collected in the personal breathing zones of employees with 

(n = 4) and without (n = 3) an inline Personal DataRAM aerosol monitor (Thermo, Smyrna, 

Georgia), and six total dust air samples were collected at fixed locations in the pharmacy with 

(n = 2) and without (n = 4) an inline DustTrak aerosol monitor (TSI®, St. Paul, Minnesota). 

When sampling with the personal DataRAM, air was drawn through the inlet of Tygon® 

tubing positioned in the employee’s breathing zone. The primary purpose of visit 1 was to 

identify the processes that produced the most dust so we could follow up with more detailed 

sampling during visit 2 (April 2012).

The air and surface sampling methods used during visit 2 are summarized in Table 2. Over 

a period of three days, 27 inhalable dust air samples were collected. Nine personal air 

samples were collected, including two sets of side-by-side air samples worn on opposite 

shoulders on two separate days by the same employee. Side-by-side sampling was done to 

allow us to quantify more than one API in an employee’s breathing zone and to compare 

air concentrations measured on one side of the body to the other side of the body. Another 

18 area air samples were collected at fixed locations throughout the pharmacy. Total and 

inhalable dust air samples are intended to measure airborne dust that could be inhaled 

and deposited anywhere in the respiratory system (including the nose and mouth) [Kenny 

1997, ACGIH 2012]. However, compared to an inhalable dust sample, a total dust sample 

(in closed-face configuration) has been shown to undersample particles greater than 30 

micrometers (μm) in aerodynamic diameter because of its smaller inlet [Kenny 1997]. This 

issue prompted the sole use of inhalable dust samples for visit 2.
Health Hazard Evaluation Report 2010-0078-3177 Page 3

Table 1. Summary of the air sampling methods used during visit 1

Sampling media/

equipment

Flow rate 

(Lpm) Analytes Method

No. of 

personal 

samples

No. of 

area 

samples

Tared 37-mm PTFE 

filter, closed face 

cassette (n = 7)

4 Total dust

(by mass)

NIOSH Method 

0500*

3 4

Tared 37-mm PTFE 

filter, Personal 

DataRAM (n = 4) 

aerosol monitor

2.2 Total dust

(in real time)

NA 4 0

Total dust

(by mass)

NIOSH Method 

0500*

4 0

Tared 37-mm PTFE 

filter, DustTrakTM 

DRX aerosol 

monitor (n = 2)

3 Total dust

(in real time)

NA NA 2

Total dust

(by mass)

NIOSH Method 

0500*

NA 2

HHPC-6 optical 

particle counter

NA Particle count 

(in real time)

NA NA NA

HHPC = handheld airborne particle counter 

Lpm = liters per minute 

mm = millimeter 

NA = not applicable 

NIOSH = National Institute for Occupational Safety and Health 

PTFE = polytetrafluoroethylene

*NIOSH Manual of Analytical Methods [NIOSH 2010]
Page 4 Health Hazard Evaluation Report 2010-0078-3177

Table 2. Summary of the air and surface sampling methods used during visit 2

Sampling media/

equipment

Flow rate 

(Lpm) Analytes Method

No. of 

personal 

samples

No. of 

area 

samples

Air sampling

Tared 25-mm 

PTFE filter, IOM 

sampler (n = 27)

2 Inhalable dust

(by mass)

NIOSH Method 

0600*

9 18

Lactose BVNA internal 

method†

7 15

Lisinopril BVNA internal 

method†

3 3

HCTZ BVNA internal 

method†

3 0

Loratadine BVNA internal 

method†

1 0

Hydrocodone 

bitartrate

BVNA internal 

method†

0 2

Oxycodone BVNA internal 

method†

0 2

Codeine BVNA internal 

method†

0 2

Levothyroxine BVNA internal 

method†

1 0

Atenolol BVNA internal 

method†

0 1

HHPC-6 optical 

particle counter

NA Particle count

(in real time)

NA NA NA

Surface sampling

Alpha Texwipe 

pre-wetted with 

deionized water

NA Lactose BVNA internal 

method†

NA 18

BVNA = Bureau Veritas North America 

HCTZ = hydrochlorothiazide 

IOM = Institute of Medicine

*NIOSH Manual of Analytical Methods [NIOSH 2010]

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

During both visits, we followed some of the employees throughout their workday and held 

HHPC-6 real-time particle counters near their breathing zones to identify dusty tasks (i.e., 

peaks in particle concentration) (Figure 3). We also recorded the types of tablets handled 

so that we could later identify air samples collected during visit 2 (previously analyzed 

gravimetrically) to be further analyzed for lactose (a common inactive filler in tablets) 
Health Hazard Evaluation Report 2010-0078-3177 Page 5

and/or specific APIs (Table 2). Most of these air samples were analyzed for lactose, lisinopril, 

and HCTZ. Only a few of these air samples were analyzed for other APIs.

During visit 2, we sampled 

18 surfaces for lactose 

contamination (Table 2). 

This was done to estimate 

the extent of pharmaceutical 

dust contamination 

throughout the pharmacy. 

Templates (10 centimeters 

by 10 centimeters) were 

placed on top of a surface. 

While wearing nitrile 

gloves, we wiped the area 

inside the template with 

a prewetted towelette in 

three different directions. 

For irregularly shaped 

surfaces, the investigator 

estimated approximate 100 

square-centimeter areas 

and wiped the surface in a 

manner identical to that used for flat surfaces. Appendix A provides more information on the 

sampling and analytical methods.

Results 

Airborne Pharmaceutical Dust

Real-Time Particle Concentrations 

Results of the real-time particle measurements are in Figures B1–B6 of Appendix B. We 

used this information to decide which APIs to measure on the inhalable dust samples. The 

DustTrak data and some of the DataRAM and HHPC-6 data are not presented because they 

did not add to the information provided in Figures B1–B6. These figures show peaks in 

particle number and mass concentrations that were correlated with events involving specific 

APIs. Refilling canisters with uncoated tablets produced some airborne dust (Figures B4 and 

B6); however, the highest transient particle mass concentrations of total dust (up to 9,500 

micrograms per cubic meter [μg/m3

]) and total particle number concentrations (up to 350,000 

particles per liter [p/L]) were observed during the cleaning of canisters using compressed 

air (Figures B1 and B4). In most cases, these canisters housed uncoated tablets. After using 

compressed air, in some cases it took > 60 minutes for the number concentration of particles 

< 1 μm in aerodynamic diameter to return to the baseline concentration measured prior to the 

cleaning activity (Figures B2 and B5). 

Figure 3. Using a real-time particle counter to measure particle 

concentration near the personal breathing zone of an employee 

cleaning a PharmAssist canister. 
Page 6 Health Hazard Evaluation Report 2010-0078-3177

Particles < 1 μm in aerodynamic diameter were elevated (up to 45,000 p/L) during the 

cleaning of the Optifill machine using a vacuum (Figure B4). The vacuum was capable of 

delivering high-efficiency particulate air (HEPA) filtration; however, the vacuum contained a 

non-HEPA designated 3M type II filter designed for copier/printer toner ink and dust (product 

no. 78-8005-5350-1). The task-based personal air concentration of inhalable dust collected 

(over 33 minutes) from employee 23 performing this task was 2,000 μg/m3

. The dust that was 

collected in this employee’s breathing zone also contained lactose (5.2 μg/m3

), but the other 

APIs (e.g., HCTZ and lisinopril) were not-detected (ND).

Air Concentrations of Total Dust during Visit 1

Tables 3 and 4 provide the personal and area air concentrations of total dust for visit 1. Figure 

4 shows the locations of the area air samples for visit 1. The air concentrations in these and 

subsequent tables are presented as 8-hour time-weighted averages (TWAs) or longer duration 

TWAs if the sample time was > 480 minutes. We stopped sampling only after employees 

finished working with pharmaceuticals. Therefore, we assumed zero exposure for any 

unsampled time periods during an 8-hour work shift. The minimum detectable concentrations 

(MDCs) and minimum quantifiable concentrations (MQCs) provided in these and subsequent 

tables were calculated by dividing the analytical limits of detection and quantitation (mass 

units) for each analyte by the average volume of air that would have been sampled over an 

8-hour period (unless otherwise noted). The MDCs and MQCs represent the smallest air 

concentrations that could have been detected (MDC) or quantified (MQC). 

Four of the personal total dust air samples (Table 3) were collected using sample media in 

line with a personal DataRAM. Tygon tubing was connected to the DataRAM, and the inlet 

of the tubing was positioned in the personal breathing zone. According to guidelines from 

the DataRAM manufacturer, use of the Tygon tubing can result in > 50% loss of particles > 

10 μm in aerodynamic diameter [Thermo 1995]. This could explain why most of the levels 

collected by these samples were ND. One of these samples (no. 133), however, collected 140 

μg/m3

 of total dust. The cleaning of a canister with compressed air was likely the main source 

of this dust. According to the real-time particle number concentrations measured during this 

task (Figure B3 in Appendix B), a large portion of this dust was < 3 μm in aerodynamic 

diameter. At this particle size, any losses from the Tygon tubing would be < 10% [Thermo 

1995]. Nevertheless, the total dust concentrations obtained using sample media in line with a 

DataRAM likely underestimated the actual concentrations.
Health Hazard Evaluation Report 2010-0078-3177 Page 7

Table 3. Work-shift personal air concentrations of total dust for visit 1

Day Employee ID Process description Sample 

no.*

Sample time

(minutes)

TWA personal air 

concentration of 

total dust (μg/m3)†

1 11 PharmAssist and Optifill 

canister cleaning

14 280 410

12 Manual counting, middle 

station

134 352 ND‡

13 Optifill canister refill 135 289 ND‡

14 Manual counting, station #1 15 400 ND

2 11 PharmAssist and Optifill 

canister refill and cleaning

133 444 (140)‡

12 Packaging, end of line 12 487 (42)

13 Optifill canister refill 131 457 ND‡

MDC 60

MQC 180

*Sample numbers are provided for referring to the figures in Appendix B.

†TWA over 8 hours. Assumed zero exposure during any unsampled periods. If sample time was > 

480 minutes, then the TWA over that time period is provided. Values between the MDC and MQC 

are shown in parentheses to point out that there is more uncertainty associated with these values 

than with concentrations above the MQC. 

‡Air in an employee’s personal breathing zone was drawn through tubing into a personal DataRAM 

and then collected on sample media. The mass concentration measured by the sample media may 

underestimate the actual concentration because of particle losses in the tubing.
Page 8 Health Hazard Evaluation Report 2010-0078-3177

Table 4. Work-shift area air concentrations of total dust for visit 1

Sample 

duration Day Location description Sample no.*

Sample time

(minutes)

TWA area air 

concentration of 

total dust (μg/m3

)†

Work shift 

(~8 hours)

1 Top of PharmAssist Pod B 19 395 (52)

2 Top of PharmAssist Pod B 110 490 ND

Workstation next to 

PharmAssist Pod A

13 385 ND

Manual fill station #1 18 384 ND

MDC 40

MQC 140

> 30 

hours

1 and 2 Shelf #1, next to Optifill 

machine

115 1864 (23)‡

Shelf #2, west end, close 

to manual fill station #2

112 1860 (14)‡

MDC 10§

MQC 47§

*Sample numbers are provided for referring to the sample locations in Figure 4.

†TWA over 8 hours. Assumed zero exposure during any unsampled periods. If sample time was > 

480 minutes, then the TWA over that time period is provided. Values between the MDC and MQC 

are shown in parentheses to point out that there is more uncertainty associated with these values 

than with concentrations above the MQC. 

‡Collected using sample media in line with a DustTrak aerosol monitor.

§Calculated using average volume of air that was sampled over 1,860 minutes.

Figure 4. Area air sample locations during visit 1. 
Health Hazard Evaluation Report 2010-0078-3177 Page 9

Air Concentrations of Inhalable Dust, Lactose, and Active Pharmaceutical 

Ingredients during Visit 2 

Tables 5 and 6 provide the personal and area air concentrations of inhalable dust, lactose, 

lisinopril, and HCTZ (personal only) for visit 2. Figure 5 shows the locations of the area air 

samples for visit 2. The manufacturer’s occupational exposure limits (OELs) for lisinopril 

and HCTZ [Bristol-Myers Squibb Company 2012a,b] are provided in Tables 5 and 6. The 

lower bound of the manufacturer’s hazard control band for lisinopril [Bristol-Myers Squibb 

Company 2012b] was used for comparing employee exposures and is the most conservative 

way of establishing an OEL on the basis of a hazard control band. More information on 

control banding and OELs is provided in Appendix C.

Table 5. Work-shift personal air concentrations of inhalable dust, lactose, and select APIs during visit 2

Day Employee 

ID

Process 

description

Sample 

no.†

Sample 

time 

(minutes)

TWA personal air concentration (μg/m3

)‡

Inhalable 

dust Lactose Lisinopril HCTZ

1 21 Optifill canister 

refill and cleaning 

and manual 

counting*

223/25 350 Error§ 5.3 0.96 (0.24)

225/25 351 (130) 3.7 0.55 (0.17)

22 Vault hand filling 

and canister 

cleaning

213 366 (400) NA NA NA

216 405 (350) NA NA NA

2 21 Optifill canister 

refill and cleaning

230 341 ND 3.3 NA NA

231 285 ND 5.6 1.1 (0.20)

24 Manual counting 23 162 (150) 1.7 NA NA

MDC 100 0.003 0.1 0.1

MQC 320 0.0089 0.35 0.35

Manufacturer’s OEL 1¶ 100¶

*Optifill canister cleaning was done in the morning (~130 minutes), and manual counting was done in the 

afternoon (~220 minutes).

†Sample numbers are provided for referring to the figures in Appendix B. If more than one set of sample 

numbers is listed per process description, then side-by-side air sampling was performed.

‡TWA over 8 hours. Assumed zero exposure during any unsampled periods. If sample time was 

> 480 minutes, then the TWA over that time period is provided.

§A large piece of debris (not pharmaceutical) was collected by the sample media. This made gravimetric 

analysis unreliable.

¶According to safety data sheets [Bristol-Myers Squibb Company 2012a,b]. The OEL for lisinopril is the 

lower bound of the hazard control band (1–10 μg/m3

).
Page 10 Health Hazard Evaluation Report 2010-0078-3177

Table 6. Work-shift area air concentrations of inhalable dust, lactose and lisinopril during visit 2

Day Location description Sample 

no.*

Sample 

time 

(minutes)

TWA area air concentration (μg/

m3

)†

Inhalable 

dust Lactose Lisinopril

1 Captain’s office to the left inside the door

(6 feet high)

215 566 ND 0.98 ND

Shelf #4 to the south of the Optifill machine 217 543 (118) 2.8 (0.27)

Pharmacist checking station

(6 feet high)

218 565 (120) 2.3 NA

Just north of supervisor’s desk behind

the belt

221 553 (140) 5.4 NA

Break room on top of fridge (5.5 feet) 229 552 ND 1.7 ND

Optifill workstation top shelf

(7 feet above fan)

236 550 (140) 46 NA

North side of PharmAssist machine

(5.5 feet high)

237 544 ND 3.3 (0.18)

Below 40-59 cabinet to the east of the 

Optifill (3.5 feet high)

239 558 ND 2.3 NA

Shelf to the south of vault work station

(4 feet high)

240 569 ND 0.34 ND

2 South wall of the Pod A room (6 feet high) 21 521 ND 0.02 NA

On fridge in break room (5.5 feet high) 27 507 ND 0.16 NA

North end of the manual fill table, near the 

compressed air line

29 521 (110) 1.2 (0.24)

Below the 40-59 cabinet to the east of the 

optifill machine (3.5 feet high)

210 495 (140) 0.33 ND

Corner just east of the janitor’s closet

(5.5 feet high)

211 500 (230) 0.37 NA

Above the pharmacist checking station, 

north end (5 feet high)

212 500 (160) 0.25 NA

Vault corner shelf (6 feet high) 214 484 (160) ND NA

Checking station 226 482 ND ND NA

Manual fill station #2 232 517 ND ND NA

MDC 100 0.003 0.1

MQC 290 0.008 0.32

*Sample numbers are provided for referring to sample locations in Figure 5.

†TWA over the sampled time period.
Health Hazard Evaluation Report 2010-0078-3177 Page 11

Figure 5. Area air sample locations during visit 2. 

We compared the work-shift TWA personal air concentrations to published manufacturers’ 

OELs (Table C1 in Appendix C). All HCTZ personal air concentrations were below the 

manufacturer’s OEL. Employee 21 had personal air concentrations of lisinopril during 

two workdays that were near (0.96 μg/m3

) or above (1.1 μg/m3) the manufacturer’s OEL 

of 1 μg/m3

. This employee refilled and cleaned Optifill canisters during both workdays. 

Employee 22, who cleaned canisters containing loratadine and levothyroxine (Figure B5 in 

Appendix B), had a personal air concentration of loratadine of 6.5 μg/m3

 and a personal air 

concentration of levothyroxine of 0.0068 μg/m3

. The levothyroxine concentration was below 

the manufacturer’s OEL of < 1 μg/m3

 [Pfizer 2011]. We were not able to find a published 

manufacturer’s OEL for loratadine. 

Area air concentrations of hydrocodone, oxycodone, codeine, and atenolol were ND (below 

their MDCs). The MDCs of hydrocodone, codeine, and atenolol were 0.10 μg/m3

, and the 

MDC of oxycodone was 0.01 μg/m3

. The MDCs of hydrocodone, codeine, and oxycodone 

were well below the manufacturers’ OELs [GlaxoSmithKline 2006; Purdue Pharma 2008; 

Abbott Labs 2011]. We were not able to find a manufacturer’s OEL for atenolol. 

Surface Contamination with Lactose

The surface levels of lactose are presented in Table 7; they ranged from ND (below the limit 

of detection of 0.0001 micrograms per square centimeter [μg/cm2

]) to 19 μg/cm2. Figure 6 

shows the locations where the surface samples were collected. The highest contamination 

level was measured from a surface used in refilling canisters before it was cleaned; therefore, 
Page 12 Health Hazard Evaluation Report 2010-0078-3177

it should be considered a positive control. Lactose contamination varied throughout the 

pharmacy, but in general, higher amounts of lactose were found on work surfaces than on 

undisturbed areas (e.g., elevated shelving).

Table 7. Levels of lactose on surfaces during visit 2

Day Location description Sample 

no.*

Lactose 

(μg/cm2

)

1 Top shelf of Optifill workstation (7 feet high) S1 0.0026

Optifill workstation, in front of computer keyboard, next to fan S2 0.040

On top of Optifill machine, southwest corner (7 feet high) S3 ND

On top of Optifill machine, northeast corner (7 feet high) S4 0.0005

Shelf north of the Optifill machine S5 ND

Shelf in the Captain’s office just to the left of the door (7 feet high) S6 ND

Top of shelf in vault area (7 feet high) S7 0.0008

Work surface in vault area S8 0.32

Aisle #4 top shelf (7 feet high) S9 ND

Corner of manual filling area (7 feet high) S10 0.0008

Shelf north of the Optifill machine where employee 21 was filling 

canisters

S11 19

Computer mouse at Optifill workstation, next to fan S12 0.056

2 On top of lockers in the break room S13 0.065

Prescription check workstation S14 0.036

Packaging workstation S15 0.096

PharmAssist computer #2 workstation S16 0.30

Manual fill station #2 computer mouse S17 0.30

Shelf above manual fill station #2 (8 feet high) S18 0.056

Limit of detection 0.0001

Limit of quantitation 0.0003

*Sample numbers are provided for referring to sample locations in Figure 6.
Health Hazard Evaluation Report 2010-0078-3177 Page 13

Figure 6. Surface sample locations during visit 2. 

Use of Personal Protective Equipment and Other Observations 

We observed sporadic use of nitrile gloves for all processes, and none of the employees wore 

protective clothing, eye protection, or respiratory protection during our visits. The vacuum was 

the only engineering control that was used, primarily for cleaning the Optifill machine. The 

Optifill machine was routinely cleaned once per day, and the vacuum filter was routinely changed 

every 3 to 4 months. We did not carefully monitor hand-washing activities before breaks.

Discussion

Several tasks involving uncoated tablets correlated with peaks in real-time particle number 

concentration and particle mass concentration. The largest increase in total particle number 

concentration occurred when canisters were cleaned using compressed air. Most of the 

particles released during cleaning with compressed air were < 3 μm in aerodynamic 

diameter. In comparison, during a previous evaluation at a large mail order pharmacy, 

particles > 10 μm in aerodynamic diameter contributed more to the total particle number 

concentrations measured during the cleaning of canisters without the use of compressed air. 

The maximum total particle number concentration measured during the cleaning of canisters 

in that evaluation was five times lower than in this evaluation [NIOSH 2011]. Therefore, 

the use of compressed air to clean canisters appears to generate higher particle number 

concentrations that are dominated by smaller particles (i.e., < 3 μm). These small particles 

have relatively slow settling velocities, meaning they can remain buoyant in air for hours, 

and they are capable of penetrating deep into the lungs. The slow settling velocities probably 

explains why we found elevated concentrations of particles with aerodynamic diameters < 1 

μm more than 60 minutes after canisters had been cleaned with compressed air.
Page 14 Health Hazard Evaluation Report 2010-0078-3177

The use of the vacuum to clean the Optifill machine also produced elevated airborne particle 

number concentrations and personal inhalable dust concentrations (2,000 μg/m3) during that 

task. However, the particle number concentrations were dominated by submicron (< 1 μm) 

particles. Particles with an aerodynamic diameter around 0.3 μm are the most difficult to 

capture with filters [EPA 2008]. HEPA filters are required to have at least 99.97% collection 

efficiency for these particles [EPA 2008]. Therefore, using a HEPA-certified filter in the 

vacuum would likely reduce airborne levels of these small particles. 

We measured personal air concentrations of total dust during visit 1 and inhalable dust during 

visit 2. Both of these sample types estimate what could be inhaled and deposited anywhere 

in the respiratory system [Kenny 1997; ACGIH 2012]. However, compared to inhalable dust 

samplers, total dust samplers can undersample particles > 30 μm in aerodynamic diameter 

[Kenny 1997]. These large particles are most likely to be deposited in the nose or mouth [Hinds 

1999]. Because many APIs are water soluble, they can be absorbed in the upper respiratory 

system including nasal passages. Thus, inhalable dust is the most appropriate sample type 

for measuring exposure to pharmaceuticals. Lactose and specific APIs were analyzed on the 

inhalable dust samples (after the sample was weighed) but not the total dust samples. 

The highest personal air concentrations of lactose, lisinopril, and HCTZ (inhalable dust) on 

visit 2 were measured on the employee who used compressed air to clean canisters. Two 

personal air concentrations of lisinopril measured on this employee were near or above the 

manufacturer’s OEL of 1 μg/m3

. This employee’s side-by-side air sampling results varied 

by less than a factor of two. Although the DataRAM and Tygon tubing caused some of the 

total dust samples to underestimate the actual concentrations, the highest air concentrations 

of total dust on visit 1 were also measured on the employee who used compressed air to 

clean canisters. The total dust, inhalable dust, and lactose concentrations we measured are 

comparable to what we measured in a previous evaluation at a large mail order pharmacy. 

However, the personal air concentrations of lisinopril are higher than what we measured in 

that evaluation [NIOSH 2011]. 

In general, the highest area air concentrations of lisinopril and lactose were found near the 

Optifill machine where much of the compressed-air cleaning took place. Hard-to-reach 

surfaces had the lowest levels of lactose, and work surfaces used when directly handing APIs 

had the highest levels. This suggests that pharmaceutical dust was spread to many areas in 

the pharmacy, but was most concentrated near the areas where APIs were directly handled or 

canisters were cleaned using compressed air.

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

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

dusts or “particles not otherwise specified” do not apply [ACGIH 2012]. Thus, we used 

manufacturers’ OELs for comparing our results. Other than lisinopril, none of the measured 

APIs that had manufacturers’ OELs were present in air at concentrations above their OELs. 

Possible acute health effects from high exposures to lisinopril listed on the safety data sheet 

included dizziness, headache, and allergic reactions [Bristol-Myers Squibb Company 2012b]. 

Maintaining airborne lisinopril exposures below the manufacturer’s OEL should prevent 
Health Hazard Evaluation Report 2010-0078-3177 Page 15

these health effects in most employees. Although exposures to levothyroxine were below 

the manufacturer’s OEL, the safety data sheet specifically recommends that, “All operations 

should be fully enclosed. No air recirculation permitted [Pfizer 2011].”

OELs typically do not consider possible synergistic effects from multiple API exposures. 

Although we could not measure all APIs in air, the nature of the work activities and the data 

we collected indicate that some employees were exposed to multiple APIs. The potential 

health effects from exposures to multiple APIs are largely unknown. Therefore, exposures 

to multiple APIs could present an unacceptable health risk to an employee, even if each 

individual API air concentration was below its manufacturer’s OEL. 

In addition to the inhalation route, pharmaceuticals that deposit onto unprotected skin and 

are not washed off could be inadvertently ingested. Some pharmaceuticals, depending on 

their chemical makeup, could also be absorbed through the skin. Unprotected eyes could also 

be a route of absorption for pharmaceuticals. Finally, pharmaceuticals on personal clothing 

could be brought home and potentially be a source of exposure for family members. Children 

may be especially susceptible to adverse health effects from API exposures [Brent et al. 

2004]. These routes of exposure are pertinent at this workplace as nitrile gloves were used 

sporadically, and protective clothing and safety glasses were not used at all during our visits.

Conclusions 

Use of compressed air to clean automatic dispensing machine canisters caused the largest 

releases of dust. Uncoated tablets were the main source of this dust. Although we did 

not quantify all possible APIs in air, multiple APIs were detected in employees’ personal 

breathing zones. For the APIs with exposure criteria, most air concentrations (except for 

one personal air concentration of lisinopril) were below the manufacturers’ OELs. However, 

OELs do not consider possible synergistic effects from multiple API exposures. Lactose, an 

inactive filler in tablets, was present on work surfaces, suggesting that surface contamination 

with APIs was also possible. Recommendations are listed below to reduce pharmaceutical 

dust exposures. Eliminating the use of compressed air, in particular, should substantially 

reduce airborne exposures and surface contamination levels of pharmaceuticals. 

Recommendations 

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. 

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

by their likely effectiveness in reducing or removing hazards. 

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

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

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

information should be gathered now and in the future, especially as new pharmaceuticals 
Page 16 Health Hazard Evaluation Report 2010-0078-3177

and formulations enter the market. We recommend determining which pharmaceuticals are 

dusty. Although uncoated tablets are generally dusty, employees may be able to identify 

those that produce more dust. We also recommend obtaining safety data sheets and reviewing 

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

from the original manufacturer of the name-brand pharmaceutical may contain the most 

detailed information. This information can then be used to develop a priority list of dusty 

pharmaceuticals that are potentially hazardous at low concentrations (e.g., manufacturers’ 

OELs < 10 μg/m3

). Employees who handle these pharmaceuticals in ways that could cause 

the dust to become airborne may require a higher level of protection. 

Engineering Controls

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

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

employees effectively without placing primary responsibility of implementation on the 

employee. 

1. Install a partially enclosed local exhaust hood that is ducted outdoors. Use this hood 

when filling prescriptions or refilling canisters with pharmaceuticals on your priority 

list. Ducting the hood outdoors will prevent the re-entrainment of APIs into the work 

environment. For some APIs (e.g., levothyroxine), the manufacturer specifically states 

that no air recirculation is permitted. The American Conference of Governmental 

Industrial Hygienists Industrial Ventilation Manual provides guidelines on the optimal 

duct and face velocity for the control of very fine light dusts [ACGIH 2010]. 

2. Use a HEPA vacuum with a long narrow tip to clean hard to reach areas of the 

automatic dispensing machine canisters rather than using compressed air to clean the 

canisters. Make sure the filter in the vacuum is HEPA certified and properly seated 

in the vacuum. Doing this process inside the local exhaust hood would help further 

control small particles that penetrate the HEPA filter or are otherwise generated by the 

cleaning process. Disconnect the compressed air line if it has no other purpose.

Administrative Controls 

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

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

commitment and employee acceptance. Regular monitoring and reinforcement are necessary 

to ensure that policies and procedures are followed consistently.

1. Consult a ventilation specialist to install and commission the local exhaust hood. Hood 

performance should be validated at least annually.

2. Train employees annually on how to properly use and maintain the local exhaust hood.

3. Replace the HEPA vacuum filter cartridge according to the manufacturer’s guidelines. 

Wear nitrile gloves and work under the hood when performing this task. 
Health Hazard Evaluation Report 2010-0078-3177 Page 17

4. Use the HEPA vacuum daily to clean the Optifill machine and collect pharmaceutical 

dust that accumulates under the canisters. Wear nitrile gloves, long-sleeve protective 

clothing, and safety glasses when performing this task.

5. Clean any residual dust on work surfaces with isopropyl alcohol wipes before breaks 

and at the end of the day. Wear nitrile gloves when cleaning surfaces.

6. Remind employees of the importance of washing their hands before eating or using 

tobacco products to prevent the hand-to-mouth ingestion of pharmaceutical particles.

Personal Protective Equipment

Personal protective equipment is the least effective means for controlling hazardous 

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

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

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

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

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

1. Train employees on the importance of wearing nitrile gloves when handling 

pharmaceuticals, working with objects containing pharmaceutical dust, or cleaning 

surfaces with pharmaceutical dust.

2. Provide safety glasses and long-sleeve protective clothing to employees who perform 

tasks outside the hood that could generate airborne pharmaceutical dust. The protective 

clothing should either be disposable or kept at work and laundered weekly by a 

laundry service. Wearing protective clothing should minimize the potential for take 

home exposure. 
Page 18 Health Hazard Evaluation Report 2010-0078-3177

Appendix A: Additional Information on 

Pharmaceutical Analytical Methods

Gravimetric analysis of the personal and area air samples was performed using NIOSH 

Methods 0500 and 0600 [NIOSH 2012]. After gravimetric analysis, the air samples were 

further analyzed for lactose and/or specific APIs using BVNA methods. The surface wipe 

samples were also analyzed for lactose using a BVNA method. These methods are briefly 

summarized below for each analyte.

Lactose

Filters were removed from the IOM samplers and extracted in glass vials using 2 milliliters 

(mL) of deionized water and sonicated for 15 minutes. 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 x 250 mm

Column flow rate: 1 mL per minute

Column temperature: Ambient

Injection volume: 200 microliter

Detector: Electrochemical detector

Mobile phase: Isocratic, 200 millimolar (mM) sodium hydroxide in deionized water

Lisinopril and Hydrochlorothiazide

Filters were processed as described for lactose analysis and analyzed by high performance 

liquid chromatography using the parameters below.

Instrument: Agilent 1100 

Column: Waters Spherisorb C8, 150 mm x 4.6 mm 5 μm particle size

Column flow rate: 1 mL per minute

Column temperature: 40°C

Injection volume: 30 microliter

Detector: Ultraviolet/visible 

Wavelength: 215 nanometer

Mobile phase: Isocratic 85% (Dipotassium phosphate, 0.1% phosphoric acid)/15% methanol

Loratadine 

Filters were desorbed in 2 mL of a 40% (1% triethylamine, 0.75% phosphoric acid)/60% 

acetonitrile solution and sonicated for 15 minutes. Samples were transferred to autosampler 

vials for analysis by high performance liquid chromatography using the parameters below.

Instrument: Dionex ICS 3000

Column: Dionex CarboPac PA1, 250 mm by 4 mm

Column flow rate: 1 mL per minute

Column temperature: Ambient

Injection volume: 200 microliter

Detector: Ultraviolet/visible 

Wavelength: 215 nanometer

Mobile phase: Isocratic 40% (1% triethylamine, 0.75% phosphoric acid)/60% acetonitrile
Health Hazard Evaluation Report 2010-0078-3177 Page 19

Hydrocodone, Oxycodone, and Codeine 

Filters were desorbed in 2 mL of a 50% (15 mM sodium lauryl sulfate, 15 mM dipotassium 

phosphate, 0.1% phosphoric acid)/5% acetonitrile/45% methanol solution and sonicated for 

15 minutes. Samples were transferred to autosampler vials for analysis by high performance 

liquid chromatography using the parameters below.

Instrument: Agilent 1100

Column: MacMod Halo C18, 4.6 mm by 75 mm, 2.7 μm particle size

Column flow rate: 1.5 mL per minute

Column temperature: 40°C

Injection volume: 50 microliter

Detector: Ultraviolet/visible 

Wavelength: 210 nanometer

Mobile phase: Isocratic 50% 15 mM sodium lauryl sulfate, 15 mM dipotassium 

phosphate, 0.1% phosphoric acid, 5% acetonitrile

Atenolol

Filters were desorbed in 2 mL of a 92.5% 100 mM dipotassium phosphate/7.5% acetonitrile 

solution and sonicated for 15 minutes. Samples were transferred to autosampler vials for 

analysis by high performance liquid chromatography using the parameters below.

Instrument: Agilent 1100

Column: Xterrra C18, 150 mm by 4.6 mm, 3.5 μm particle size

Column flow rate: 1 mL per minute

Column temperature: Ambient

Injection volume: 50 microliter

Detector: Ultraviolet/visible 

Wavelength: 226 nanometer

Mobile phase: Isocratic 92.5% 100 mM dipotassium phosphate/7.5% acetonitrile

Levothyroxine

Filters were desorbed in 20 nanogram/mL thyroxine in 30% deionized water (0.1% formic 

acid)/70% acetonitrile solution and sonicated for 15 minutes. Samples were transferred to 

autosampler vials for analysis by liquid chromatography/tandem mass spectrometry using the 

parameters below.

Instrument: Agilent 1100

Column: Atlantis Hilic Silica, 50 mm by 2.1 mm, 3 μm pore size

Column flow rate: 0.3 mL per minute

Column temperature: 35°C

Injection volume: 20 microliter

Detector: AB Sciex API 3000 MS/MS with turbo ion spry source

Source temperature: 350°C

MS function: Multiple reaction monitoring 

Levothyroxine quantitation transition: 777.8–731.8 atomic mass units

Thyroxine (internal standard) transition: 783.78–737.65 atomic mass units

Mobile phase: Isocratic 30% deionized water (0.1% formic acid)/70% acetonitrile 

(0.1% formic acid)
Page 20 Health Hazard Evaluation Report 2010-0078-3177

Appendix B: Real-Time Particle Measurement 

Results

Figure B1. Real-time mass concentration of total dust measured in the personal breathing zone of 

employee 13 who refilled Optifill canisters during day 1 of visit 1. Tasks associated with increases in 

mass concentrations are noted in the figure. 
Health Hazard Evaluation Report 2010-0078-3177 Page 21

Figure B2. Real-time particle number concentrations measured near the personal breathing zone of 

employee 11 who cleaned canisters using compressed air during day 1 of visit 1. The APIs contained in 

the canisters that were cleaned are noted above the peaks in particle concentrations that occurred at 

the same time. 
Page 22 Health Hazard Evaluation Report 2010-0078-3177

Figure B3. Real-time particle number concentrations measured near the personal breathing zone of 

employee 11 who refilled and cleaned canisters using compressed air during day 2 of visit 1. The APIs 

contained in the canisters that were cleaned are noted above the peaks in particle concentrations that 

occurred at the same time.
Health Hazard Evaluation Report 2010-0078-3177 Page 23

Figure B4. Real-time particle number concentrations measured near the personal breathing zones 

of employee 21 (who performed Optifill refill during the first part of the day and manual fill during 

the second part of the day) and employee 26 (who cleaned the Optifill machine towards the end 

of the day) during day 1 of visit 2. The APIs that were handled during these tasks are noted above 

the peaks in particle concentrations that occurred at the same time. The largest increases in particle 

concentrations were due to tasks performed by nearby employees, which are also noted above the 

corresponding peaks.
Page 24 Health Hazard Evaluation Report 2010-0078-3177

Figure B5. Real-time particle concentrations measured near the personal breathing zone of employee 22, 

who used compressed air to clean PharmAssist canisters during day 1 of visit 2. The APIs contained in the 

canisters that were cleaned are noted above the peaks in particle concentrations that occurred at the same 

time. Other tasks performed by nearby employees that also resulted in increased particle concentrations are 

noted above the corresponding peaks.
Health Hazard Evaluation Report 2010-0078-3177 Page 25

Figure B6. Real-time particle number concentrations measured near the personal breathing zone 

of employee 21, who mostly performed Optifill refill during day 2 of visit 2. The APIs that were 

handled during refill are noted above the peaks in particle concentrations that occurred at the same 

time. Cleaning of the manual pill counter machine, which resulted in the largest increase in particle 

concentration, is also noted above the corresponding peak. 
Page 26 Health Hazard Evaluation Report 2010-0078-3177

Appendix C: Occupational Exposure Limits and 

Health Effects

NIOSH investigators refer to mandatory (legally enforceable) and recommended OELs for 

chemical, physical, and biological agents when evaluating workplace hazards. OELs have 

been developed by federal agencies and safety and health organizations to prevent adverse 

health effects from workplace exposures. Generally, OELs suggest levels of exposure that 

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

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

will be protected if their exposures are maintained below these levels. Some may have 

adverse health effects because of individual susceptibility, a pre-existing medical condition, 

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

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

the employee to produce adverse health effects. Most OELs address airborne exposures, but 

some substances can be absorbed directly through the skin and mucous membranes.

Most OELs are expressed as a 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 short-term exposure limits or ceiling values. Unless otherwise noted, the shortterm exposure limit is a 15-minute TWA exposure. It should not be exceeded at any time 

during a workday. The ceiling limit should not be exceeded at any time.

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

organizations, state and local governments, and other entities. Some OELs are legally 

enforceable limits; others are recommendations. 

● The U.S. Department of Labor Occupational Safety and Health Administration 

permissible exposure limits (29 CFR 1910 [general industry]; 29 CFR 1926 

[construction industry]; and 29 CFR 1917 [maritime industry]) are legal limits. These 

limits are enforceable in workplaces covered under the Occupational Safety and Health 

Act of 1970. 

● NIOSH recommended exposure limits are recommendations based on a critical review 

of the scientific and technical information and the adequacy of methods to identify 

and control the hazard. NIOSH recommended exposure limits are published in the 

NIOSH Pocket Guide to Chemical Hazards [NIOSH 2010]. NIOSH also recommends 

risk management practices (e.g., engineering controls, safe work practices, employee 

education/training, personal protective equipment, and exposure and medical 

monitoring) to minimize the risk of exposure and adverse health effects.

● Other OELs commonly used and cited in the United States include the Threshold 

Limit Values, which are recommended by the American Conference of Governmental 

Industrial Hygienists, a professional organization, and the workplace environmental 

exposure levels, which are recommended by the American Industrial Hygiene 

Association, another professional organization. The Threshold Limit Values and 
Health Hazard Evaluation Report 2010-0078-3177 Page 27

workplace environmental exposure levels are developed by committee members 

of these associations from a review of the published, peer-reviewed literature. 

These OELs are not consensus standards. Threshold Limit Values are considered 

voluntary exposure guidelines for use by industrial hygienists and others trained in 

this discipline “to assist in the control of health hazards” [ACGIH 2012]. Workplace 

environmental exposure levels 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 legal and recommended limits. The Institut für Arbeitsschutz 

der Deutschen Gesetzlichen Unfallversicherung (Institute for Occupational Safety and 

Health of the German Social Accident Insurance) maintains a database of international 

OELs from European Union member states, Canada (Québec), Japan, Switzerland, and the 

United States. The database, available at http://www.dguv.de/ifa/en/gestis/limit_values/

index.jsp, contains international limits for more than 1,500 hazardous substances and is 

updated periodically. 

The Occupational Safety and Health Administration requires an employer to furnish 

employees a place of employment free from recognized hazards that cause or are likely 

to cause death or serious physical harm [Occupational Safety and Health Act of 1970 

(Public Law 91–596, sec. 5(a)(1))]. This is true in the absence of a specific OEL. It also is 

important to keep in mind that OELs may not reflect current health-based information.

When multiple OELs exist for a substance or agent, NIOSH investigators generally 

encourage employers to use the lowest OEL when making risk assessment and risk 

management decisions. NIOSH investigators also encourage use of the hierarchy 

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

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

(2) engineering controls (e.g., local exhaust ventilation, process enclosure, dilution 

ventilation), (3) administrative controls (e.g., limiting time of exposure, employee training, 

work practice changes, medical surveillance), and (4) personal protective equipment (e.g., 

respiratory protection, gloves, eye protection, hearing protection). 

Active Pharmaceutical Ingredients 

None of the APIs measured in air have OELs established by federal agencies or national 

organizations. However, many of them do have OELs established by pharmaceutical 

companies using a control banding process. Control banding, a qualitative risk assessment 

and risk management tool, is a complementary approach to protecting employee health 

that focuses resources on exposure controls by describing how a risk needs to be managed. 

This approach can be applied in situations where authoritative OELs have not been 

established or can be used to supplement such OELs. In the pharmaceutical industry, APIs 

are placed into hazard categories using data such as potency, severity of acute effects, 

lethal dose, irritation, and sensitization [Naumann et al. 1996; Naumann 2005; Zalk and 

Nelson 2008]. Once placed into hazard categories, pharmaceuticals are often assigned 

OELs or hazard control bands. Pharmaceutical companies may provide these OELs or 
Page 28 Health Hazard Evaluation Report 2010-0078-3177

hazard control bands on their safety data sheets, along with potential acute and chronic 

health effects from workplace exposures. Table C1 provides the manufacturers’ OELs or 

hazard control bands for the APIs measured in this evaluation. Other manufacturers may 

have OELs in addition to those listed in Table C1. Maintaining exposures below these 

manufacturers’ OELs should minimize any potential health effects. However, OELs typically 

do not consider possible synergistic effects from multiple API exposures. More information 

on control banding is available at http://www.cdc.gov/niosh/topics/ctrlbanding/.

Table C1. Prescribed uses and manufacturers’ TWA-OELs for the APIs measured in air

API Prescribed for*

Manufacturer’s OEL 

or hazard control band 

(μg/m3)†

Atenolol High blood pressure None published

Codeine Pain relief or cough suppression 100

HCTZ High blood pressure and fluid retention 100

Hydrocodone Pain relief or cough suppression 5

Lisinopril High blood pressure, heart failure 1–10

Loratadine Allergies None published

Oxycodone Pain relief 40

Levothyroxine Hypothyroidism < 1

*[PubMed Health 2012]

†Codeine [GlaxoSmithKline 2006], HCTZ [Bristol-Myers Squibb Company 2012a], 

Hydrocodone [Abbott Labs 2011], Lisinopril [Bristol-Myers Squibb Company 2012b], 

Oxycodone [Purdue Pharma LP 2008], Levothyroxine [Pfizer 2011].
Health Hazard Evaluation Report 2010-0078-3177 Page 29

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Health Hazard Evaluation Report 2010-0078-3177 Page 31

The Health Hazard Evaluation Program investigates possible health hazards in the 

workplace under the authority of Section 20(a)(6) of the Occupational Safety and 

Health Act of 1970, 29 U.S.C. 669(a)(6). The Health Hazard Evaluation Program also 

provides, upon request, technical assistance to federal, state, and local agencies to control 

occupational health hazards and to prevent occupational illness and disease. Regulations 

guiding the Program can be found in Title 42, Code of Federal Regulations, Part 85; 

Requests for Health Hazard Evaluations (42 CFR 85).

Acknowledgments 

Analytical Support: Bureau Veritas North America

Desktop Publishers: Greg Hartle and Mary Winfree 

Editor: Ellen Galloway 

Health Communicator: Stefanie Brown 

Logistics: Donnie Booher and Karl Feldmann

Availability of Report

Copies of this report have been sent to the employer, employees, and union at the 

facility. The state and local health department and the Occupational Safety and Health 

Administration Regional Office have also received a copy. This report is not copyrighted 

and may be freely reproduced. 

This report is available at http://www.cdc.gov/niosh/hhe/reports/pdfs/2010-0078-3177.pdf

Recommended citation for this report:

NIOSH [2013]. Health hazard evaluation report: evaluation of 

pharmaceutical dust exposures at an outpatient pharmacy. By Fent KW, 

Durgam S*, Methner M. Cincinnati, OH: U.S. Department of Health and 

Human Services, Centers for Disease Control and Prevention, National 

Institute for Occupational Safety and Health, NIOSH HETA No. 2010-

0078-3177.

*Currently with General Electric, Niskayuna, New York.
Delivering on the Nation’s promise:

Safety and health at work for all people through research and prevention

To receive NIOSH documents or more information about 

occupational safety and health topics, please contact NIOSH:

Telephone: 1–800–CDC–INFO (1–800–232–4636)

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