Biological Monitoring for Evaluating Occupational Exposure to Toxic Chemicals This slide...

Biological Monitoring for Evaluating Occupational Exposure

to Toxic Chemicals

Biological Monitoring for Evaluating Occupational Exposure

to Toxic Chemicals

This slide presentation was prepared by

The AIHA Biological Monitoring Committee

All rights reserved ©2004

An Introduction

Acknowledgements in alphabetical order

Acknowledgements in alphabetical order

Mark Boeniger, NIOSH, Cincinnati

Tim Buckley, Johns Hopkins Univ., Baltimore

Larry Lowry, Univ. of Texas Health Center, Tyler

Shane Que Hee, Univ. Calif., Los Angeles

Glenn Talaska, Univ. of Cincinnati

Paul Ullucci, ESA Labs, Inc., Chelmsford, MA

Mark Boeniger, NIOSH, Cincinnati

Tim Buckley, Johns Hopkins Univ., Baltimore

Larry Lowry, Univ. of Texas Health Center, Tyler

Shane Que Hee, Univ. Calif., Los Angeles

Glenn Talaska, Univ. of Cincinnati

Paul Ullucci, ESA Labs, Inc., Chelmsford, MA

AcknowledgementAcknowledgement

AcknowledgementsAcknowledgements

Contributions are appreciated from members of

The American Conference of Governmental Industrial Hygienists

Biological Exposure Indices Committee

Scope of Industrial Hygiene and the Context for Biological MonitoringScope of Industrial Hygiene and the Context for Biological Monitoring

Anticipation

Recognition

Evaluation

Control

GOAL: PROTECT THE HEALTH OF THE WORKER

Anticipation

Recognition

Evaluation

Control

GOAL: PROTECT THE HEALTH OF THE WORKER

BiologicalMonitoringBiologicalMonitoring

Means of Evaluating ExposureMeans of Evaluating Exposure

Air sampling

Skin sampling

Surface samplingBiological monitoring –

measures inside body

Air sampling

Skin sampling

Surface samplingBiological monitoring –

measures inside body

Measured outside the body

Strengths of Air SamplingStrengths of Air Sampling

Long-standing tradition

Good worker acceptance

Established standards & guidelines

Good equipment

Standard methods available

Long-standing tradition

Good worker acceptance

Established standards & guidelines

Good equipment

Standard methods available

Weaknesses of Air SamplingWeaknesses of Air Sampling

Does not account for:

All routes of exposure, esp. skin

Workload

Individual differences in absorption of inhaled dose

Misuse or malfunction of PPE

Concomitant exposures

Sensitive individuals

Does not account for:

All routes of exposure, esp. skin

Workload

Individual differences in absorption of inhaled dose

Misuse or malfunction of PPE

Concomitant exposures

Sensitive individuals

Strengths of Surface SamplingStrengths of Surface Sampling

Can identify potential for surface derived exposures

Easy to obtain

Minimally disruptive of operations

Favored by OSHA, EPA, HUD

Weakness of Surface SamplingWeakness of Surface Sampling

Highly variable results

Surface transfer to skin is variable and poorly understood

May overestimate absorbed dose

Strengths of Skin SamplingStrengths of Skin Sampling

Differences between techniques, some overestimate or underestimate exposure

Relevance to biologically available or absorbed dose uncertain

Weakness of Skin SamplingWeakness of Skin Sampling

• Indicates individual skin

contamination

• Indicates individual skin

contamination

BiomarkersBiomarkers

Measure of exposure, effect, or susceptibility by

analyzing biological sample media

Measure of exposure, effect, or susceptibility by

analyzing biological sample media

Exposure to Effect Continuum

Air

Water

Soil

Food

Dust

Inh

alat

ion

Ing

esti

on

Der

mal

So

urc

es

Exp

osu

reE

xpo

sure

Exp

osu

re

Po

ten

tia

l Do

se

Ab

so

rbe

d D

os

e

Bo

dy

Bu

rden

Bio

mar

ker

s

PATHWAYS ROUTES

Behavior / Activity Location

Urine

BloodBreath

Contact Rate / Physiology

PBPK Modeling: Partition, Coefficients, Blood Flow, Metabolism

EXTERNAL INTERNAL

Soil

Water

The Role of Biological Monitoring

Biological Monitoring

Industrial Hygiene

Medical Surveillance

•Air Monitoring

•Detects dermal, inhalation and ingestion exposures•Detects non-workplace exposures•Evaluates effectiveness of PPE•Captures worker hygiene, contact rate (e.g., respiration) and metabolism variability

•Health Monitoring

Lauwerys’ TriangleLauwerys’ Triangle

External ExposureExternal Exposure

Adverse EffectAdverse EffectInternal DoseInternal Dose

EnvironmentalMonitoring

Biological Monitoring Biological Monitoring (non-adverse effects)(non-adverse effects)

Health/Medical Monitoring

(adverse effects)

AA BB

CC

Biological MonitoringBiological Monitoring

ExposureExposure

Internal doseInternal dose Early biologicalEarly biologicaleffecteffect

IllnessIllness

Biomarkers of Biomarkers of SusceptibilitySusceptibility

Biomarkers of Biomarkers of ExposureExposure

Biomarkers of Biomarkers of EffectEffect

Types of biological monitoringTypes of biological monitoring

Biomarkers Of ExposureBiomarkers Of Exposure

Markers of internal dose

Markers of biologically effective dose

Markers of internal dose

Markers of biologically effective dose

A biomarker of exposure is an exogenous substance, its metabolite, or the product of an

interaction between a xenobiotic agent and some target molecule or cell that is measured

in a compartment within an organism.

(NRC 1991)

A biomarker of exposure is an exogenous substance, its metabolite, or the product of an

interaction between a xenobiotic agent and some target molecule or cell that is measured

in a compartment within an organism.

(NRC 1991)

Includes:Includes:

Markers of Internal DoseMarkers of Internal Dose

Lead, cadmium, mercury, etc.; bloodTrichloroethylene; trichloroacetic acid; urinePhenol; urineToluene; o-cresol, urineXylene; methylhippuric acid, urine Methylenedianiline, urineToluene; expired air

Lead, cadmium, mercury, etc.; bloodTrichloroethylene; trichloroacetic acid; urinePhenol; urineToluene; o-cresol, urineXylene; methylhippuric acid, urine Methylenedianiline, urineToluene; expired air

Some ExamplesSome Examples

Markers of Biologically Effective DoseMarkers of Biologically Effective Dose

Carboxyhemoglobin (carbon monoxide reversibly binds to RBC); Blood

2,5-Hexanedione (metabolite of 2-hexanone and hexane); Urine

DNA Adducts (chemicals bind to

bases in DNA); Blood & Urine

Hemoglobin Adducts

N-(2-hydroxyethyl) valine in Hb; Blood

Carboxyhemoglobin (carbon monoxide reversibly binds to RBC); Blood

2,5-Hexanedione (metabolite of 2-hexanone and hexane); Urine

DNA Adducts (chemicals bind to

bases in DNA); Blood & Urine

Hemoglobin Adducts

N-(2-hydroxyethyl) valine in Hb; Blood

Biomarkers of SusceptibilityBiomarkers of Susceptibility

A biomarker of susceptibility indicates an organism’s inherent or acquired limited ability to

respond to the challenge of exposure to a specific xenobiotic substance.




• Genetic, inherited: — Alpha-1-antitrypsin phenotype — Acetylator phenotype— P-450 2D6 polymorphism

Acquired: — Antigens (hypersensitivity) in response to exposure

to toluene diisocyanate or cotton dust

• Co-existing conditions:

― Cirrhosis of the liver, renal deficiency

Biomarkers Of Effect Biomarkers Of Effect

A biomarker of effect or response is a measurable alteration - biochemical,

physiological, or other - within an organism that can be recognized, depending on its magnitude, as an established or potential

health impairment or disease.

A biomarker of effect or response is a measurable alteration - biochemical,

physiological, or other - within an organism that can be recognized, depending on its magnitude, as an established or potential

health impairment or disease.

Biomarkers of EffectBiomarkers of Effect Zinc protoporphyrin: lead

Delta-aminolevulinic acid: lead Carboxyhemoglobin: carbon monoxide; methylene

chloride Beta-2-microglobulin: cadmium Cholinesterase: organophosphorus pesticides Chromosome aberrations: antineoplastic drugs Sister chromatid exchanges: ethylene oxide Urine mutagenicity: antineoplastic drugs

Zinc protoporphyrin: leadDelta-aminolevulinic acid: lead

Carboxyhemoglobin: carbon monoxide; methylene chloride

Beta-2-microglobulin: cadmium Cholinesterase: organophosphorus pesticides Chromosome aberrations: antineoplastic drugs Sister chromatid exchanges: ethylene oxide Urine mutagenicity: antineoplastic drugs

Medical Monitoring Biomarkers — LiverMedical Monitoring Biomarkers — Liver

Albumin, bilirubin, globulin, total protein

Alkaline phosphatase (AP)

Gamma glutamyl transpeptidase (GGTP)

Alanine aminotransferase (ALT)

Aspartate aminotransferase (AST)

Lactate dehydrogenase (LDH)

Albumin, bilirubin, globulin, total protein

Alkaline phosphatase (AP)

Gamma glutamyl transpeptidase (GGTP)

Alanine aminotransferase (ALT)

Aspartate aminotransferase (AST)

Lactate dehydrogenase (LDH)

Common Biological Monitoring MediaCommon Biological Monitoring Media

Urine

Blood

Exhaled Breath

Urine

Blood

Exhaled Breath

24 hour urine

Spot urine

Timing preferences:

• End-of-shift

• end-of-shift, end-of-week

• prior to last shift of workweek

• not critical

24 hour urine

Spot urine

Timing preferences:

• End-of-shift

• end-of-shift, end-of-week

• prior to last shift of workweek

• not critical

Urine Collection Urine Collection

Name

Collection Time

Date

Processing Urine is SimpleProcessing Urine is Simple

Collection Bottles

Collection Bottles Optical

Refractometer

Optical Refractometer

Sample Aliquot Bottles

Sample Aliquot Bottles

Weigh or take

volume of samples

Weigh or take

volume of samples

BloodBlood

Evacuated tube with anticoagulant; need a blank tube also to check for contamination (hexane, toluene, xylene)

Transfer to vial with Teflon® lined cap, fill to top, no headspace in tube

Ship overnight, cold (not freezing)

SolventsSolvents

Metals

Special collection requirements

Contamination from tube stopper

Contamination from needle

•Chromium, nickel

•Cobalt, manganese

•Aluminum

Metals


Contamination from tube stopper


•Chromium, nickel

•Cobalt, manganese

•Aluminum

BloodBlood

Inert compounds with low blood solubility

Good correlation with ambient levels

— n-hexane/2-hexanone

Compounds of high blood solubility

Poor correlation with ambient levels

— acetone, MEK, toluene

Inert compounds with low blood solubility

Good correlation with ambient levels

— n-hexane/2-hexanone

Compounds of high blood solubility

Poor correlation with ambient levels

— acetone, MEK, toluene

Exhaled Air Exhaled Air

Principal Advantages Of Biological Monitoring Principal Advantages Of Biological Monitoring

Individual variation in the absorption of contaminants can be assessed

Measures total exposure including all routes of exposure

Individual variation in the absorption of contaminants can be assessed

Measures total exposure including all routes of exposure

Principal Advantages Of Biological Monitoring - (continued)Principal Advantages Of Biological Monitoring - (continued)

Effectiveness of PPE/work practices assessed

Exposure outside of the workplace identified

Individual absorption differences among workers identified

Can confirm compound absorption when skin and/or oral exposure occur

Provide powerful individual and group feedback and is an incentive for personal involvement in their own protection

Effectiveness of PPE/work practices assessed

Exposure outside of the workplace identified

Individual absorption differences among workers identified

Can confirm compound absorption when skin and/or oral exposure occur

Provide powerful individual and group feedback and is an incentive for personal involvement in their own protection

Biological Monitoring WeaknessesBiological Monitoring Weaknesses

Not as simple as air sampling

Reflects total exposure, not just occupational

May be invasive

Workers may perceive themselves as guinea pigs

Marker may not be agent specific, or only for workplace exposures

Few standards or guidelines are available

Analytical methods may not be available or costly

Management/workers may fear this type of information

Not as simple as air sampling

Reflects total exposure, not just occupational

May be invasive

Workers may perceive themselves as guinea pigs

Marker may not be agent specific, or only for workplace exposures

Few standards or guidelines are available

Analytical methods may not be available or costly

Management/workers may fear this type of information

Biological monitoring is often best for estimating absorbed dose

and risk

Biological monitoring is often best for estimating absorbed dose

and risk

Inhalation

IngestionPercutaneous

Individual Variation in Absorption of Individual Variation in Absorption of Airborne Contaminants Can Be AssessedAirborne Contaminants Can Be AssessedIndividual Variation in Absorption of Individual Variation in Absorption of Airborne Contaminants Can Be AssessedAirborne Contaminants Can Be Assessed

Pulmonary Absorption Rate Varies with the Ventilation Rate

Pulmonary Absorption Rate Varies with the Ventilation Rate

Physical Workload (W)Physical Workload (W)

AlveolarVentilation(L Air/Min)

AlveolarVentilation(L Air/Min)

HeartRate

(L/Min)

HeartRate

(L/Min)

IncreaseVentilation(vs. Light)

IncreaseVentilation(vs. Light)

0 (Rest) 5.0 6.0 1.0

50 (Light Work) 16.0 9.0 1.0

100 (Moderate) 27.0 13.0 1.7

150 (Heavy) 38.0 19.0 2.4

0 (Rest) 5.0 6.0 1.0

50 (Light Work) 16.0 9.0 1.0

100 (Moderate) 27.0 13.0 1.7

150 (Heavy) 38.0 19.0 2.4

4 8 12 16 20 24

40

32

24

16

8

Rest Exercise Clean AirExposure

100 ppm

Hip

pu

ric

Aci

d (

uM

ol/

min

)Effect of Exercise on Excretion of Hippuric Acid

Following Toluene Exposure

Hours

Example of Oral Ingestion via Contaminated Skin

Assumed Size of 1 drop

Relative Size of 1/1000 drop

by volume

The smaller drop, if composed of Pb, would be equivalent to the PEL for an 8-hour exposure and could easily be present on the skin and

available for hand-to-mouth transfer

Involving Hand-to-Mouth Transfer of Lead

Before lunch After lunch

Pb (ug) per hand wipe

0

500

1000

1500

2000

2500

3000

SBS

SBS

SBS

Hea

t Se

al

Line

Op

Acid R

m

Cell

Repai

r

Burne

r

Mat

er. H

and.

Lead

Man

OSHA Max. Daily Dose

Lead on Hands Remaining After Washing and After

Eating in Workplace Cafeteria

Lead on Hands Remaining After Washing and After

Eating in Workplace Cafeteria

Skin can be an Important Route of AbsorptionSkin can be an Important Route of AbsorptionRelative Absorption of Chemicals from Exposureto the Hands or by Inhalation to TLV® for 8 Hrs.

Methylene Chloride

Methyl Chloroform

Lindane

Styrene

2-Ethoxyethanol

DMF

Dieldrin

o-Cresol

Biphenyl

Aniline

0 0.1 1 10 100

Skin/Pulmonary Absorption Ratio

Total Immersion2 hands / 8 hrs2 hands / 2 hrs1 hand / 0.25 hr

Data from Droz-PO, et al., 1990

Skin Absorption Versus InhalationSkin Absorption Versus Inhalation

PCBs1 mg/m3 airborne exposure for 8

hours— 8 mg

One drop of 70% PCB on one hand— 54 mg

PCBs1 mg/m3 airborne exposure for 8

hours— 8 mg

One drop of 70% PCB on one hand— 54 mg

The Importance of Skin Exposure is OftenOverlooked or Under-appreciatedThe Importance of Skin Exposure is OftenOverlooked or Under-appreciated

Dermal Exposure Can Be Hiddenand WidespreadDermal Exposure Can Be Hiddenand Widespread

The case of the toxic paperwork

Thou shall not steal

The door knob did it

The almost protected worker

The case of the toxic paperwork

Thou shall not steal

The door knob did it

The almost protected worker

VanRooij JGM; Van Lieshout EMA; Bodelier-Bade MM; Jongeneelen FJ (1993): Effect of reduction of skin contamination on the internal dose of creosote workers exposed to polycyclic aromatic hydrocarbons. Scandinavian J. Work Environ. Health 19:200-207.

Estimates of Pyrene Uptake During 5 Days

Dose (nmol)Dermal

78%

IDose (nmol)nhalation

22%

Why Worry About Dermal Exposure?

0

200

400

600

800

1000

1200

1400

1 2 3 4 5 6 7 8 9 10 11 12 median

Worker

Py

ren

e U

pta

ke

(n

mo

l)

The Skin & Percutaneous PermeationThe Skin & Percutaneous Permeation

Chemicals that are somewhat soluble in organic oils and lipids as well as water are absorbed

most readily through skin.

Those that are highly insoluble in either oils or water are poorly absorbed.

Chemicals that are somewhat soluble in organic oils and lipids as well as water are absorbed

most readily through skin.

Those that are highly insoluble in either oils or water are poorly absorbed.

Factors Affecting Skin AbsorptionFactors Affecting Skin Absorption

Location of skin on the bodyHydration or wetnessTemperatureSkin condition

Location of skin on the bodyHydration or wetnessTemperatureSkin condition

Aniline and Skin TemperatureAniline and Skin Temperature

0.1

0.2

0.3

0.4

0.5

0.6

0.7

Ab

so

rpti

on

(g

/hr)

0.8

30 31 33 34 35 36

Temperature (°C)

32

How Biological Monitoring is Used to Assess Potential for Dermal Exposure

Compare Air Hazard Index (Ka)

Ka = Ci / TLVi

To Kb, the Biological Hazard Index

(ECi - BCi) / BEIi-BCi BEI)

When Kb is > Ka, suspect dermal exposure

Effectiveness of PPE and work practices can be assessed

Effectiveness of PPE and work practices can be assessed

Influence of Personal Protection and Work Practices On the Average Pre-shift and Post-shift Urine

N-Dimethylformamide Concentration

Int. Arch. Occup. Environ. Health 45:189 (1980)

Morning & Evening Samples

0

50

100

150

Uri

ne C

on

cen

trati

on

Gloves Barrier Cream

Gloves+ Caution

MaskOnly

Exposure outside of the workplace can be identified

Exposure outside of the workplace can be identified

Biological Monitoring Standards & GuidelinesBiological Monitoring Standards & Guidelines

OSHA Mandated Biological Monitoring

• Lead

• Cadmium

ACGIH BEIs

• Advisory only

German BATs

OSHA Mandated Biological Monitoring

• Lead

• Cadmium

ACGIH BEIs

• Advisory only

German BATs

BEIs - Biological Exposure IndicesBEIs - Biological Exposure Indices

Definition

Reference Values of Biological determinants; the levels most likely observed when healthy persons are exposed to air concentrations at the TLV®.

Definition

Reference Values of Biological determinants; the levels most likely observed when healthy persons are exposed to air concentrations at the TLV®.

The Dermal Exposure Gap

ACGIH TLVsn=861

with Skin Notationn=196

ACGIH TLV® Skin Notation:“potential significant contribution to the overall exposure by the cutaneous route . . . by direct skin contact with the substance.”

with BEIn=40

BEIsBEIs

Major Intended Uses

— Compare exposure from all routes of exposure

— Give absorbed dose relationship to individual’s integrated air sampling

— Determine the effectiveness of PPE

Major Intended Uses

— Compare exposure from all routes of exposure

— Give absorbed dose relationship to individual’s integrated air sampling

— Determine the effectiveness of PPE

BEIsBEIs

Based on Human Data

— Experimental and Field Studies

— Relationship between external and internal doses at TLV® levels

— Relationship between internal dose and reversible health effects

Based on Human Data

— Experimental and Field Studies

— Relationship between external and internal doses at TLV® levels

— Relationship between internal dose and reversible health effects

BEI TableBEI Table

Includes the following:

• Chemical

• Determinant

• Specimen to collect

• Time of collection

• BEI

• Notation

Includes the following:

• Chemical

• Determinant

• Specimen to collect

• Time of collection

• BEI

• Notation

BEI - Time of CollectionBEI - Time of Collection

Biological Half - Life of Determinant

— Short half-life indicates recent exposure

— Long half-life indicates integrated exposure over time

— Very long half-life, collection is not critical, cadmium half-life is 20 years!

Biological Half - Life of Determinant

— Short half-life indicates recent exposure

— Long half-life indicates integrated exposure over time

— Very long half-life, collection is not critical, cadmium half-life is 20 years!

BEI NotationsBEI Notations

“B” – Background: found in non-exposed population.

“Ns” – Non-specific: the determinant detected in other chemical exposures.

“Sq” – relationship is semiquantitative.

“Nq” – monitoring is recommended, but no BEI available.

“Sc” – increased susceptibility in some populations.

“B” – Background: found in non-exposed population.

“Ns” – Non-specific: the determinant detected in other chemical exposures.

“Sq” – relationship is semiquantitative.

“Nq” – monitoring is recommended, but no BEI available.

“Sc” – increased susceptibility in some populations.

BATs – Biologischer Arbeitsstoff-Toleranz-WertBATs – Biologischer Arbeitsstoff-Toleranz-Wert

Definition

The BAT value “biological tolerance value for occupational exposures,” is the maximum permissible quantity of a chemical substance or its metabolites, or the maximum permissible deviation from the norm of biological parameters induced by these substances in exposed humans.

Definition

The BAT value “biological tolerance value for occupational exposures,” is the maximum permissible quantity of a chemical substance or its metabolites, or the maximum permissible deviation from the norm of biological parameters induced by these substances in exposed humans.

BATsBATsBased on:

— Currently available scientific data

— Reflect concentrations that generally do not adversely affect health of the worker

— For exposures of 8 hours per day, 40 hours per week

— 48 established

Based on:

— Currently available scientific data

— Reflect concentrations that generally do not adversely affect health of the worker

— For exposures of 8 hours per day, 40 hours per week

— 48 established

BATsBATs

For Carcinogenic Substances:

— Not possible to specify safe level

— Provide correlations between concentration of substance in air and biological media

— 10 have been established

For Carcinogenic Substances:

— Not possible to specify safe level

— Provide correlations between concentration of substance in air and biological media

— 10 have been established

Issues in Biological MonitoringIssues in Biological Monitoring

Why are you doing this sampling? Who are you going to sample? What are you going to measure? When and Where are you going to sample? How are you going to transport and store the sample? How will the samples be analyzed? How will the results be reported? What criteria will be used to determine what actions

will be taken?

Biological Monitoring-- A Collaborative Effort

Biological Monitoring-- A Collaborative Effort

Industrial Hygienists

• exposure assessment

Occupational Health Physician

• interpretation of results

Occupational Health Nurse

• sample collection, coordination

Industrial Hygienists

• exposure assessment

Occupational Health Physician

• interpretation of results

Occupational Health Nurse

• sample collection, coordination

End of Core ModuleEnd of Core Module

Individual Differences Among WorkersIndividual Differences Among Workers

Absorption

Distribution

Storage

Metabolism

Excretion

Absorption

Distribution

Storage

Metabolism

Excretion

Factors Influencing AbsorptionFactors Influencing Absorption

RoutePhysical formSolubilityPhysical workloadExposure concentrationExposure durationSkin characteristics

RoutePhysical formSolubilityPhysical workloadExposure concentrationExposure durationSkin characteristics

Factors Affecting DistributionFactors Affecting Distribution

Body sizeBody compositionProtein bindingPhysical workloadExposure concentrationExposure durationVolume of distribution

Body sizeBody compositionProtein bindingPhysical workloadExposure concentrationExposure durationVolume of distribution

Internal Distribution & StorageInternal Distribution & Storage

Fat

Bone and teeth

Target organs

Plasma protein binding

Free and bound

Fat

Bone and teeth

Target organs

Plasma protein binding

Free and bound

MetabolismMetabolism

Genetic factors

Age and sex

Environment

Chemical intake

Physical activity

Protein binding

Lifestyle

Exposure level

Genetic factors

Age and sex

Environment

Chemical intake

Physical activity

Protein binding

Lifestyle

Exposure level

Inorganic compounds

Metals

Critical organ

Inorganic compounds

Metals

Critical organ


Cadmium Kidney

Mercury Brain

Lead Blood/

Bone

Arsenic Lung

Cadmium Kidney

Mercury Brain

Lead Blood/

Bone

Arsenic Lung

MetabolismMetabolismForeign Compound

Phase I Processes

Primary Products

Phase II Processes

Secondary Products

Excretion

Foreign Compound

Phase I Processes

Primary Products

Phase II Processes

Secondary Products

Excretion


Phase I Processes

Hydrolysis— Esters alcohols or

acids

Oxidation— Benzene phenol

Reduction— Nitrobenzene aniline

Phase I Processes

Hydrolysis— Esters alcohols or

acids

Oxidation— Benzene phenol

Reduction— Nitrobenzene aniline

Organic CompoundsOrganic Compounds


Phase II Reactions

Conjugation

— Amino acid

— Activated acetic acid

— Glucuronic acid

Phase II Reactions

Conjugation

— Amino acid

— Activated acetic acid

— Glucuronic acid

Organic CompoundsOrganic Compounds

Toluene Benzoic acid Hippuric acid Aniline N-acetyl-aniline

Benzene phenol phenol glucuronide

Toluene Benzoic acid Hippuric acid Aniline N-acetyl-aniline

Benzene phenol phenol glucuronide

Medical Markers — KidneyMedical Markers — Kidney

BUN (Blood Urea Nitrogen)

Creatinine

Uric acid

BUN (Blood Urea Nitrogen)

Creatinine

Uric acid

Medical Monitoring — Blood FormingMedical Monitoring — Blood Forming

CBC

• Differential

• WBC, RBC

• Hemoglobin & hematocrit

• Reticulocyte count

CBC

• Differential

• WBC, RBC

• Hemoglobin & hematocrit

• Reticulocyte count

Medical Monitoring — GeneralMedical Monitoring — General

Urinalysis

• Appearance, color, ketones

• Bile, occult blood, pH

• Glucose, protein

• Microscopic evaluation of sediment

Urinalysis

• Appearance, color, ketones

• Bile, occult blood, pH

• Glucose, protein

• Microscopic evaluation of sediment


Genetic Polymorphism in Enzyme activity

• N-acetyltransferase

• Cytochrome P-450

• Glutathione-S-transferase

Genetic Polymorphism in Enzyme activity

• N-acetyltransferase

• Cytochrome P-450

• Glutathione-S-transferase

AcetoneAcetone

Determinant: Acetone in urine

Sampling Time: End of Shift

BEI: 50 mg/L

BAT: 40 mg/L

Notation: Nonspecific (NS)

Route: Pulmonary, Dermal

Determinant: Acetone in urine


BEI: 50 mg/L

BAT: 40 mg/L


Route: Pulmonary, Dermal

Aniline BEIAniline BEI

Determinant:Total p-aminophenol, urine


BEI: 50 mg/g creatinine


Determinant:Total p-aminophenol, urine


BEI: 50 mg/g creatinine


Creatinine CorrectionCreatinine Correction

Normalization factor, dilution correction

Calculation: (mg marker/L urine) / (g creatinine/L urine) = mg marker/g creatinine

Acceptable range: 0.5 – 3.0 g/L

Limitations: excretion mechanisms

kidney damage


Calculation: (mg marker/L urine) / (g creatinine/L urine) = mg marker/g creatinine

Acceptable range: 0.5 – 3.0 g/L

Limitations: excretion mechanisms

kidney damage

Aniline — BEIAniline — BEI

Determinant: aniline, urine or Methemoglobin, blood

Sampling: During or end of shift

BEI: 1.5% Hemoglobin

Notations: Background (B), non-specific (Ns), semi-quantitative (Sq)

Determinant: aniline, urine or Methemoglobin, blood

Sampling: During or end of shift

BEI: 1.5% Hemoglobin

Notations: Background (B), non-specific (Ns), semi-quantitative (Sq)

Aniline — BATAniline — BAT

Determinant: Aniline; total, urine

Sampling: End of shift

BAT: 1 mg/L

Determinant: Aniline; released from aniline-hemoglobin adduct in blood


BAT: 100 μg/L

Determinant: Aniline; total, urine


BAT: 1 mg/L

Determinant: Aniline; released from aniline-hemoglobin adduct in blood


BAT: 100 μg/L

Arsenic, Soluble Compounds, ArsineBEIArsenic, Soluble Compounds, ArsineBEI

Determinant: Inorganic arsenic and methylated metabolites, urine

Sampling: End of shift at end of work week BEI: 35 μg/L Notation: Background (B) No BAT, air / urine values Air Urine

0.10 mg/m3 50 μg/L

0.05 mg/m3 90 μg/L

Determinant: Inorganic arsenic and methylated metabolites, urine

Sampling: End of shift at end of work week BEI: 35 μg/L Notation: Background (B) No BAT, air / urine values Air Urine

0.10 mg/m3 50 μg/L

0.05 mg/m3 90 μg/L

OSHA Inorganic Arsenic Subjects Monitored

OSHA Inorganic Arsenic Subjects Monitored

Employees over Action Level for at least 30 days per year

Symptoms or signs of exposure

Breathing difficulty during respirator fit-test

Employees over Action Level for at least 30 days per year

Symptoms or signs of exposure

Breathing difficulty during respirator fit-test

OSHA Inorganic Arsenic Monitoring Frequency

OSHA Inorganic Arsenic Monitoring Frequency

At placement

Yearly for those <45 years age <10 exposure

Every six months for all others

If symptoms appear

At termination

At placement

Yearly for those <45 years age <10 exposure

Every six months for all others

If symptoms appear

At termination

OSHA Inorganic Arsenic Items Monitored

OSHA Inorganic Arsenic Items Monitored

Medical and work history

Medical exam

• Chest X-ray

• Sputum cytology

• Nasal

• Skin

• Other tests deemed appropriate


Medical exam

• Chest X-ray

• Sputum cytology

• Nasal

• Skin

• Other tests deemed appropriate

Cadmium — OSHACadmium — OSHA

Determinant: Cadmium in blood, urine

Sampling: Not critical

Value: Urine: <3 μg/g creatinineBlood: <5 μg/L

Effect Marker: Beta-2-microglobulin

Value: <300 μg/g creatinine



Value: Urine: <3 μg/g creatinineBlood: <5 μg/L

Effect Marker: Beta-2-microglobulin

Value: <300 μg/g creatinine

Cadmium — BEICadmium — BEI

Determinant: Cadmium blood, urine


BEI: Urine: 5 μg/g creatinineBlood: 5 μg/L

Notation: Background (B)

Determinant: Cadmium blood, urine


BEI: Urine: 5 μg/g creatinineBlood: 5 μg/L

Notation: Background (B)

Cadmium — BATCadmium — BAT


Sampling: not critical

BAT: Urine: 15 μg/LBlood: 15 μg/L


Sampling: not critical

BAT: Urine: 15 μg/LBlood: 15 μg/L

OSHA Cadmium Monitoring Subjects

OSHA Cadmium Monitoring Subjects

Employees exposed at or above action level for 30 or more days per year

Employees who wear respirators

Employees acutely exposed due to emergency

Employees exposed at or above action level for 30 or more days per year

Employees who wear respirators

Employees acutely exposed due to emergency

OSHA Cadmium Monitoring Frequency

OSHA Cadmium Monitoring Frequency


• At placement and annually

• Quarterly if levels raised, or on medical removal

Medical Exam

• Bi-annual

• Semi-annual if levels raised, or on medical removal


• At placement and annually

• Quarterly if levels raised, or on medical removal

Medical Exam

• Bi-annual

• Semi-annual if levels raised, or on medical removal

OSHA Cadmium Items Monitored

OSHA Cadmium Items Monitored

Blood Cd

Urine Cd and β-2-microglobulin

Medical exam

BP, Chest x-ray, pulmonary function

Males >40 prostate test(s)

Respirator test

Blood Cd

Urine Cd and β-2-microglobulin

Medical exam

BP, Chest x-ray, pulmonary function

Males >40 prostate test(s)

Respirator test

Lead — OSHALead — OSHA

Determinant: Lead in blood


Value: <50 μg/dL

Effect Biomarker: Zinc Protoporphyrin(ZPP) in blood

Value: <60 μg/L



Value: <50 μg/dL

Effect Biomarker: Zinc Protoporphyrin(ZPP) in blood

Value: <60 μg/L

Lead — BEILead — BEI



Value: 30 μg/dL

Notation: Women of childbearing potential, >10 μg/dL, risk to child



Value: 30 μg/dL

Notation: Women of childbearing potential, >10 μg/dL, risk to child

Lead — BATLead — BAT



Value: 70 μg/dL30 μg/dL (women <45 years)

Effect Marker: delta-aminolevulinic acid

Value: 15 mg/L6 mg/L (women <45 years)



Value: 70 μg/dL30 μg/dL (women <45 years)

Effect Marker: delta-aminolevulinic acid

Value: 15 mg/L6 mg/L (women <45 years)

OSHA Lead, General Industry Monitoring Frequency

OSHA Lead, General Industry Monitoring Frequency

At placement

Annually

Every two months if Pb >40 μg/dL

Monthly if on medical removal

At placement

Annually

Every two months if Pb >40 μg/dL


OSHA Lead, General Industry Medical Monitoring Subjects

OSHA Lead, General Industry Medical Monitoring Subjects

Exposure at Action Level for >30 days per year

If symptoms of exposure appear

If concerns about past exposure or procreation

Breathing difficulties

Exposure at Action Level for >30 days per year

If symptoms of exposure appear

If concerns about past exposure or procreation

Breathing difficulties

OSHA Lead, General Industry Item Monitored

OSHA Lead, General Industry Item Monitored

Blood lead and ZPP

Medical Exam

BP, Hematology

Blood urea nitrogen, creatinine, urinalysis

Respirator wearing ability

Blood lead and ZPP

Medical Exam

BP, Hematology

Blood urea nitrogen, creatinine, urinalysis

Respirator wearing ability

OSHA Lead, Construction Monitoring Frequency

OSHA Lead, Construction Monitoring Frequency

Initial, every 2 months for first 6 months

Every 6 months thereafter

Every 2 months if Pb > 40 μg/L


Two weeks if Pb > removal level

Med exam annually if Pb > 40 μg/L or symptoms

Initial, every 2 months for first 6 months

Every 6 months thereafter

Every 2 months if Pb > 40 μg/L


Two weeks if Pb > removal level

Med exam annually if Pb > 40 μg/L or symptoms

OSHA Lead, Construction Monitoring Subjects

OSHA Lead, Construction Monitoring Subjects

Employee’s performing lead related tasks

Exposed at or above Action Level on any day

Exposed at or above Action Level for more than 30 days in 12 consecutive months

Employee’s performing lead related tasks

Exposed at or above Action Level on any day

Exposed at or above Action Level for more than 30 days in 12 consecutive months

OSHA Lead, Construction Item Monitored

OSHA Lead, Construction Item Monitored

Blood, Pb, and ZPPMedical ExamBP, hematologyBUN, creatinine, and urinalysisPregnancy or fertility testsRespirator fit-testAny other test MD deems necessary

Blood, Pb, and ZPPMedical ExamBP, hematologyBUN, creatinine, and urinalysisPregnancy or fertility testsRespirator fit-testAny other test MD deems necessary

Benzene — BEIBenzene — BEI

Determinant: S-phenylmercapturic acid

Sampling: End of Shift

Value: 25 μg/g creatinine

Notation: Background

1996 Determinant: Total phenol in urine


Determinant: S-phenylmercapturic acid



Notation: Background

1996 Determinant: Total phenol in urine


OSHA Benzene Subjects Monitored

OSHA Benzene Subjects Monitored

Employees at or above action level

At or above PEL for 10 or more days per year

At 10 ppm or above for 30 days per year

Tire industry using solvents containing >0.1% benzene

Employees at or above action level

At or above PEL for 10 or more days per year

At 10 ppm or above for 30 days per year

Tire industry using solvents containing >0.1% benzene

OSHA Benzene Monitoring Frequency

OSHA Benzene Monitoring Frequency

Prior to assignment

Annually

When symptoms occur

In respirators for 30 or more days per year

Exposed during emergency

Prior to assignment

Annually

When symptoms occur

In respirators for 30 or more days per year

Exposed during emergency

OSHA Benzene Items Monitored

OSHA Benzene Items Monitored


Physical exam

Hematology: CBC

Urine Phenol (exposed in emergency)


Physical exam

Hematology: CBC

Urine Phenol (exposed in emergency)

Acetylcholinesterase Inhibiting PesticidesAcetylcholinesterase Inhibiting Pesticides

Determinant: Cholinesterase activity in red blood cells

Sampling: Discretionary

Value: 70% of individual’s baseline

Notation: Non specific

Determinant: Cholinesterase activity in red blood cells

Sampling: Discretionary

Value: 70% of individual’s baseline

Notation: Non specific

4,4’-Methylene bis(2-chloroaniline) MBOCA4,4’-Methylene bis(2-chloroaniline) MBOCA

Determinant: Total MBOCA in urine


Value: No value

Notation: Nq, Biological Monitoring should be considered, but no specific BEI is provided due to lack of data

Determinant: Total MBOCA in urine


Value: No value

Notation: Nq, Biological Monitoring should be considered, but no specific BEI is provided due to lack of data

OSHA MDA (methylenedianiline) Monitoring Subjects

OSHA MDA (methylenedianiline) Monitoring Subjects

Employees at or above action level for 30 days per year

Employees subject to dermal exposure for 15 days per year

Employees exposed in emergency

Employees dermally exposed

Employees with signs and symptoms

Employees at or above action level for 30 days per year

Employees subject to dermal exposure for 15 days per year

Employees exposed in emergency

Employees dermally exposed

Employees with signs and symptoms

OSHA MDA Monitoring Frequency

OSHA MDA Monitoring Frequency

At placement then annually

At emergency, two and three weeks later

If signs or symptoms, and 2-3 weeks later

At placement then annually

At emergency, two and three weeks later

If signs or symptoms, and 2-3 weeks later

OSHA MDA Items Monitored

OSHA MDA Items Monitored


Physical exam

Skin exam

Liver function tests

Urinalysis

Other tests deemed necessary

Biological Monitoring??


Physical exam

Skin exam

Liver function tests

Urinalysis

Other tests deemed necessary

Biological Monitoring??

When Should Biological Monitoringbe Considered?When Should Biological Monitoringbe Considered?

When mandated

— Lead and cadmium

When BEIs recommended

Routes other than inhalationare important

— Contribute >30% of dose

— Skin notation

When PPE are being used

When mandated

— Lead and cadmium

When BEIs recommended

Routes other than inhalationare important

— Contribute >30% of dose

— Skin notation

When PPE are being used22952295

Biological Sample CollectionBiological Sample Collection

Urine

Whole Blood

Serum / Plasma

Exhaled Air

Urine

Whole Blood

Serum / Plasma

Exhaled Air

Creatinine CorrectionCreatinine Correction


Calculation: mg/L / g/L = mg/g creatinine

Typical Range: 0.5 – 3.0 g/L

Specific Gravity in Field: >1.015 is OK

Limitations: excretion mechanisms are complex and not absolutes


Calculation: mg/L / g/L = mg/g creatinine

Typical Range: 0.5 – 3.0 g/L

Specific Gravity in Field: >1.015 is OK

Limitations: excretion mechanisms are complex and not absolutes

Sample Preservation of Metabolites in UrineSample Preservation of Metabolites in Urine

Aromatic amines; aniline, MDA

• citric acid added

Glycol ether metabolites, mandelic acid, trichloroacetic acid, trichloroethanol

• hydrochloric acid inhibits bacterial formation

Aromatic amines; aniline, MDA

• citric acid added

Glycol ether metabolites, mandelic acid, trichloroacetic acid, trichloroethanol

• hydrochloric acid inhibits bacterial formation

Solvents in BloodSolvents in Blood

Vacutainer tube, checked for contamination (hexane, toluene, xylene)


Keep cold

Ship overnight, cold

Solvents in Urine : same as above

Vacutainer tube, checked for contamination (hexane, toluene, xylene)


Keep cold

Ship overnight, cold

Solvents in Urine : same as above

Trace Metals in BloodTrace Metals in Blood


Contamination from tube


• Chromium, nickel

• Cobalt, manganese

• Aluminum


Contamination from tube


• Chromium, nickel

• Cobalt, manganese

• Aluminum

Transportation of Sample to LabTransportation of Sample to Lab

Place labeled sample in sealed bag

Place in insulated shipping container

Add frozen refrigerant

Include proper requisition form

Place insulated container in an appropriate labeled shipping box

Ship next day or second day

Place labeled sample in sealed bag

Place in insulated shipping container

Add frozen refrigerant

Include proper requisition form

Place insulated container in an appropriate labeled shipping box

Ship next day or second day

And Now A Word From Our Sponsor

And Now A Word From Our Sponsor

American Industrial Hygiene Association

Biological Monitoring Committee

American Industrial Hygiene Association

Biological Monitoring Committee

PDCs Offered:

Biological MonitoringDermal Exposure Assessment

Developing and Managing a Medical Surveillance Program

PDCs Offered:

Biological MonitoringDermal Exposure Assessment

Developing and Managing a Medical Surveillance Program

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