Introduction to workplace characterization and

evaluation

Gunnar Damgård NielsenPhD, Dr Sc (Pharm)

Updated 24.03.2015

Bhopal (1984) ≥ 2000 death due to methylisocyanate exposure

Bhopal was asleep when the gas struck. Simple advice to move upwind or stay indoors and seal doors and windows with damp cloths could have saved thousands but Union Carbide had not told people what to do if there was a leak.

Crowds of terrified people fled.

Bhopal's hospital was overwhelmed, lacking information about the gas or antidote.

After this, redesign of the American chemical industry to just in time production

Overall - what went wrong?• Storage of a large quantity of a hazardous

compound in close proximity to a densely populated area

• Wrong design of the plant and processes

• Insufficient education of the workers

• No operating emergency plan

Large quantities of dangerous substances are regulated by the Seveso III directive (2012/18/EU)

Types of hazard

•Chemical exposure, e.g white spirit•Biological exposure, e.g. legionella•Ergonomic loads (e.g. heavy lifting)•Noise•Cold/warm/draught•Fall•Electricity (shock)•Psychological effects, e.g. stress•Explosions, e.g. Bhopal

General procedure for workplace characterization.Each process steep is evaluated separately

Raw material reception

Weighing/mixing/manipulation/dilution

Production of product

Filling/packing

Storing/transport

Degree of mechanization•Manual•Mechanical•Automatic

Operation•Start-up•Normal •Breakdown•Maintenance•Closing

Langaa Jensen, J & O. Broberg. Analyse af produktionsprocesser. Ed. T. Schneider. Teknink Arbejdshygiejne. Bd.I. København, Arbejdstilsynet, Arbejdsmiljøinstituttet, 1996, 22-34.

Composed ofunit operations

Evaluation of chemical exposures

• Qualitative exposure assessment used for hazard based prevention

• Quantitative exposure assessment used for risk based prevention

Control banding (CB): qualitative or semi quantitative risk assessment and risk management approaches

used World-Wide. Differ from place to place.

• Initiated within the pharmaceutical industry due to many compounds with limited toxicological data.

• Modern development by the UK Health and Safety Executive (HSE), but not intended for evaluation of pesticides, pharmaceuticals, process generated hazards, e.g. wood and silica dust, and welding fumes or otherwise regulated compounds as lead and asbestos.

• Hazards bands from EU risk R-phrases (replaced by new EU-CLP classification) (HSE)

• Exposure from amount of chemical handled (low, medium, high) and volatility or dustiness (low, medium, high).

• Integrates to control guidance (risk management).• Limitation: lack of quantitative exposure data; CB is a complement to

classically industrial hygienen approaches

Zalk and Nelson. History and evaluation of control banding: a review. J Occup Environ Hyg 2008, 5, 330-346

Hazard based risk management

Classification and labelling Toxicological data bases

Google: reach-it or http://echa.europa.eu

Information on Chemicals

E.g. toluene

C & L inventory

Select/find toluene

• GHS• Dangerous

substance directive (R/S sentences)

http://echemportal.org

Substance search

e.g. toluene

Different databases recommended by ECHA and OECD

Risikovurdering (Risk Assessment)

A. Farevurdering (Hazard Identification)(iboende egenskaber hos stof)

B. Dosis-effekt/respons sammenhæng (Dose-effect/response relationship)

(fx fastsættelse af NOAEL og LOAEL)

C. Eksponeringsvurdering (Exposure Assessment)

(koncentration/dosis)

Risikokarakterisering (Risk Characterisation)(incidens/alvorlighed/sandsynligheder)

Risk assessment of occupational exposures follows the general approaches for risk assessment

Quantitative exposure assessment

• Determined by measurement• Estimated from the scientific

literature• Estimated by model calculations

Aims of measurement•Control of production process, e.g. compliance

with OEL

•Health surveillance and epidemiological studies

•Source identification, e.g. from a leakage

If measurements are performed, it should be possible to interpret or use the results

Stationary sampling•Process emission•Room mean level

From Baron PA et al. 2003

Two different measurement strategiesPersonal sampling

Exposure assessment of gases and vapours

•Measurement methodsa) Collection on adsorbent tubes followed by

desorption and determination by GC or HPLC.

b) Direct reading instruments (indicator tubes, IR,photoionization detector, portable GC)

•Exposure assessment based on literature data

•Exposure assessments from the mass balance equation

•Exposure assessment from modelling, e.g. evaporation from solvents 1)

1.Lennert et al. Evaluation of evaporation and concentration distribution models – a test chamberStudy. Ann Occup Hyg 1997, 41, 625-641.

Measurement of gases and vapours

Solid sorbent tube/sampler: for longer measurement time

Snapshot: Indicator/detector tube. Read out as change of colour

Passive (diffusion) sampling of gases and vapoursQ=D (A/L) C T

Q=amount collectedD=diffusion coefficientA=sampling areaL=length of diffusionC=air concentrationT=sampling time

GC

HPLC

Estimation of gas/vapor concentrations

Maximum concentration (a worst case concentration(c)): saturated vapour concentration 1)

From the mass balance equation1), i.e. Emission (m)/mixing volume (V): C= m/V x p. Where inadequate mixing, the total ventilation rate may be multiplied by a mixing factor “p” in the range from 0.3 to 0.7 1)

Dispersion modelling (air velocity, diffusion and turbulence) 1)

Exposure models 2)

1) Jayjock MA. Assessment of inhalation exposure potential from vapours in the workplace. Am Ind Hyg Assoc J 1998; 49: 380-385.

2) WHO. Principles of characterizing and applying human exposure models. Geneva 2005.

Example 1. Use of the mass balance equation. Assumption: The offending agent evaporates immediately in a room andthe air exchange does not contribute to the mixing volume

100 ml of a cleaning product with 1% limonene (density: 0.84 g/ml) is diluted to 10 L wash water, e.g. 0.1 ml limonene/L or 84 mg/L wash water

The floor (8 m x 9 m) and the floor-to-ceiling height (4 m): Volume=288 m3

It is assumed that the wash water level after the cleaning is 1 mm=0.1 cm. The total amount left on the floor is 103 cm3/m2 x 8 m x 9 m x 1L/103 cm3 = 72 L (greatly overestimated)

C=mass/volume=72L x 84 mg/L / 288 m3 = 21 mg/m3

There is no expected toxicological effect from MOS/MOE = C/NOAEL of this the level

Limitations: The cleaner is close to the source, but the evaporation neednot be immediately. However as he/she is moving around in the room, the scenario is considered realistic

Example 2. Use of the mass balance equation to estimate body burden

Used amount of product (W mg) with the fraction (f) of the active compound.Emission during the production period: W•f mg

Volume (V m3) of working area with the air exchange rate (A hour-1) and working time (t hours): Mixing volume: V•A•t m3 when > V

Mean exposure concentration: W•f/ V•A•t mg/m3

Inhalation does during a t hour work period (1.25 m3/hour or 10 m3/8 h): (W • f • 1.25)/(V • A • b.w) mg/kg b.w. The body weight is b.w.

This value can be compared with a NOAEL from human or animal studies to estimate MOS/MOE.

For extended evaluation of exposure risks in relation to pregnancies, c.f. Mikkelsen et al.Kemikalietestning og risikovurdering. Dansk Kemi 2003; 84(1):17-20.

Evaluation strategies of particle exposuresZone of similar exposure/similar exposure groups (SEG)

Large (Visual cue; ~mg/m3)

Particles Nano (Background correction

induces uncertainty)

SEG

Hazard Based evaluation

Risk based evaluation

Personal sampling (6-10/SEG)

• Risk management• Epidemiology

Mass Number Surface area

Far field agglomeration?

SEG depending on exposure metrics with biological relevance

• Risk management• Epidemiology

Ramachandra et al. A strategy for assessing workplace exposures to nanomaterials. J Occup Environ Hyg 2011; 8: 673-685

Exposure assessment of particles

•Collection on filters and weighing 1,2)

•Direct reading instruments 1,2)

•Data from the literature

•Evaluation from models 3, 4)

1) McMurry PH. A review of atmospheric aerosol measurements. Atmospheric Environment 2000,34,1959-19992) Baron P. Personal aerosol sampler design: a review. Appl Occup Environ Hyg 1998, 13, 313-320.3) Tielemans et al. Conceptual model for assessment of inhalation exposure: defining modifying factors.

Ann Occup Hyg 2008, 52, 577-5864) Cherrie and Schneider. Validation of a new method for structured subjective assessment of past concentrations.

Ann Occup Hyg 1999, 43, 235-245.

Mass aerodynamic diameter

1 g/cm3

The aerodynamic diameter is the diameter of a unit densitysphere that has the same settling velocity as the particle

The particle size distribution can be obtained by means of a cascade impactor

The size of the dust determines where the dust is deposited and wherean offending effect occurs. Different samplers are used for the

different depositions

0.1 1 10 1000

20

40

60

80

100

Diameter, mikrometer

%

Particle characterizationOccupational exposure characterization

Inhalable fraction is the part of the aerosol particles that can pass the naresThe thoracic fraction can pass to the thoraxThe respirable fraction can pass to the alveoli

Outdoor air exposure characterization

PM10 (”Particulate matter); corresponds to the thoracic fractionPM2.5

Sampling of dust on filters

Inhalable dust Respirable dust

Pump

Pump

Examples of samplers

Inhalable dustMedian diameter: 100μm

Thoracic dust fractionMedian diameter: 10μm

Respirable dustMedian diameter: 4μm

IOM sampler (standard) - IOM with foam

Button sampler - -

Grimm optical aerosolmonitor (real time)

Grimm optical aerosolmonitor (real time)

Grimm optical aerosolmonitor (real time)

- - Cyclone

Dekati two-stage cascade impator

Dekati two-stage cascade impator

Dekati two-stage cascade impator

Linnainmaa et al. Laboratory and field testing of sampling methods for inhalable and respirable dust. J Occup Environ Hyg 2008, 5, 28-35.

Direct reading instruments for dust characterization

Most use light scattering

Thorpe A. Assessment of personal direct-reading dust monitors for the measurementof airborne inhalable dust. Ann Occup Hyg 2007, 51, 97-112.

Personal (portable) direct-reading dust monitors

• Most often based on light scattering (laser or diodes).• Responses depend on particle size, shape and density,

and on the refractive index.• Needs calibration with appropriate particle distributions.• Underestimate often inhalable dust level.• More appropriate for respirable dust concentrations (due

to calibration)

Thorpe A. Assessment of personal direct-reading dust monitors for the Measurement of airborne inhalable dust. Ann Occup Hyg 2007,51, 97-112.

Examples of nanoparticle sizing instruments• TSI fast Mobility Particle Sizer (FMPS)• Engine Exhaust Particle Sizer (EEPS)• Scanning Mobility Particle Sizer ((SMPS)

Airborne particles measured with EEPs or FMPS: 6-560 nm

Impactor collects particles> 1 µm

Charging of particles

Electrometer: Size distributionSmall particles

Large particles

Zimmerman et al. Comparison of three nanoparticle sizing instruments: the influence of particle morphology. Atmos Environ 2014; 86: 140-147.

Dust emission increases with:

• Amount of substance (not proportional a)

• Energy input a)

• Handling time (the dust emission is often maximal in the beginning of a process) a)

• Proportional with the drop height b)

a) Hjemsted K., Schneider T. Documentation of a dustiness drum test. Ann. Occup. Hyg. 1996; 40: 627-643.

b) Cowherd et al. Dust inhalation exposures from the handling of small volumes of powders. Am. Ind. Hyg. Assoc. J. 1989; 50: 131-138.

Dust emission by transferring 3.8 L of a powder at 1-min intervals to a 23 L bucket over a 30 min interval. Lab size 36.8 m3 and an air exchange rate 4.5 •hour-1 a)

Compound Number of transfers

Transferedkg

Drop Heightcm

Respirabledust (mg/m3)

SP b)

(mg/m3)Emission factor (mg/kg)

Talc 43 88 14 3.7 34

Talc 42 88 22 12 56 107

NaCl 28 100 14 16 85 118

NaCl 29 100 22 39 124 181

Cement 29 126 14 3.5 14 15.4

Cement 29 126 22 6.8 39 36.8

DY4 dye 36 54 14 - 5.6 19.3

DY4 dye 36 54 22 - 12 29.7

a) Cowherd et al. Dust inhalation exposures from the handling of small volumes of powders. Am. Ind. Hyg. Assoc. J. 1989; 50: 131-138.

b) Suspenden particulate matter: open-face 37-mm cassett at 1,8 L/min

Dust exposures from the scientific literature. Example, ”default values” for pharmaceutical processes

Process mg/m3 Process mg/m3

Dumping from drums 0.9 Film coating 0.1

Dumping from bags 1.2 Sieving 0.8

Scooping out of drums 0.8 Granulating 0.9

Filling drums from a blender 0.6 Compressing 0.08

Bin transfers 0.2 Packing 0.01

Digging centrifuge 0.3 Sampling 0.01

Milling 2.3 Encapsulating 0.05

Tray dumping 2.7

Neumann & Sargent. Setting occupational exposure limits for pharmaceuticals.Occupational Medicine: State of the Art Reviews. 1997; 12: 67-80.

Reporting of exposure assessment

• Summary: Main points/conclusions• Introduction: Problem formulation, study design and

sampling approaches• Methods: Data gathering (analytical- and modeling),

formulae used, assumptions and default values• Results and exposure characterization: • Conclusion: Main outputs from the exposure assessment

and interpretation in the context of compliance checking and risk assessment

The Interdepartmental Group on Health Risks from Chemicals. Guidelines for good exposureAssessment practice for human health effects of chemicals. Institute of Environmental Health,University of Leicester 2004. ISBN 1 899110 39 9

Process Com-pound

Amount handlee(Wi,X) a)

Concen-tration b)

(Ci,X)

Rele-vantOEL orSTEL

C/standard(OEL or STEL)

Time (t)

C x t Other hazardsc)

Trans-port(i)Pro-cess(i)

ABC

Wi,A

Wi,B

Wi,C

Ci,A

Ci,B

Ci,C

OELA

OELB

OELC

Ci,A/OELA ti,A Ci,A x ti,A

Transport (i+1)

a) Ergonomic risk is considered if ……b) Dust, gases and vapoursc) For example, noise (N), mechanical accident (A), burn (B)….

Example of a content of an exposure assessment and risk characterization report

TWA for compound A: ΣC,i,A x ti,A/Σti,A = Mean A; Hazard index: Mean A/OELATWA for compound B: ΣC,i,B x ti,B/Σti,B = Mean B; Hazard index: Mean B/OELBIf additive: Sum = Mean A/OELA + Mean B/OELB + etc.Accepted if 1≥Sum and not accepted if 1<Sum

Risk management

Prioritized risk management strategiesControl strategy ExampleElimination/source control Substitution (enzymes, white spirit,

vegetable oil-based press wash, electric forklifts)

Engineering control Ventilation, operations and maintenance (e.g. prevents leaks)

Administrative controls Education (isocyanates)

Work practices Housekeeping, personal hygiene(Pb)

Personal protective equipment Respirators

Roelofs CR, Barbeau EM, Ellenbecker MJ, Moure-Eraso R. Prevention strategies in industrial hygiene: a critical literature review. AIHA Journal 2003; 64: 62-67.

Substitution

• Granulation and encapsulation of enzymes• Elimination of white spirit from paints• Vegetable oil-based press wash• Electric forklifts versus diesel driven

engine• Pigments in a paste versus dry pigments

All ventilation systems have to be controlled and cleaned periodically, and

maintained properly 3)

1) Breum and Valbjørn. Arbejdstilsynet informener. Ventilation I kontorer,industri m.m. Oktober 81.

2) Tseng et al. Correlation between airflow patterns and performance of a laboratory fume hood. J Occup Environ Hyg 2006, 3, 694-706.

3) Estill et al. The impact of maintenance and design for ventilation systems.Appl Occup Environ Hyg 2002, 17, 344-351.

Types of ventilation systems1,2)

General ventilation

Clean air should be supplied so the worker is in the clean air zone, whereas the polluted air is captured by the ventilation system

Shunt with polluted air? Should supply clean air

Purpose: Control of the manyminor sources

Local exhaust ventilation for a specific source control

The capture air velocity has to be sufficient

D

In a distance of one diameter(D) from the exhaust outlet the air velocity is 10% of the outlet air velocity at the opening

In a distance of 2D from the opening, the air velocity is < 5% of the velocity at the opening

Closed system (encapsulation)