occupational exposure limits & other reference values

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Occupational Exposure Limits & Other Reference Values

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Occupational Exposure Limits&

Other Reference Values

Objective

To explain occupational exposure limits and other reference values.

Exposure

Exposure is the contact with chemical substances, high/low temperatures, noise, vibrations or other hazard by persons in the workplace.

The exposure to chemical substances occurs by inhalation, skin contact or swallowing, though inhalation is often the route in workplaces.

For a given hazard, the greater the exposure,the greater the risk of an adverse effect on health.

This is the because of the exposure-response relationship.

Occupational Exposure

Occupational exposure is a measure of the intensity and/or

extent to which the human body experiences a particular

hazard.

Chemical Exposure Limit

• Exposure limit is the maximum concentration that a large

number of workers can tolerate without adverse affects

on health, even if repeated for consecutive days.

(Tolerance Levels / Threshold Limit Values [TLV] by

American Conference of Governmental Industrial

Hygienists [ACGIH])

Chemical Exposure Limits

Recommend or mandotary occupational exposure limits (OELs) have been developed in many countries for airborne exposure to gases,vapours and particulates.

The most widely used limits,called threshold limit values (TLVs), are those issued in the USA by the American Conference of Governmental Industrial Hygenists (ACGIH).

Occupational Exposure Limits

ACGIH: American Conference of Governmental Industrial Hygienists NIOSH: National Institute of Occupational Safety and Health OSHA: Occupational Safety and Health Administration

Correction for Difference Between Experimental and Exposure Conditions

• Repeated animal inhalation experiment –usually 6 hr/d.

• Occupational exposure –usually 8 hr/d.

• General population exposure – 24 hr/d.

• Effects of exposure dependant on dose, concentration or

both

When The Exposure May Be Considered Acceptable

• Time weighted average (TWA) concentration is below or

equal to OEL.

• Short term concentration (15 min) is below or equal to STEL

• The sum of the ratios of concentrations of individual

compounds to their OELs must be less than or equal to one

• MAC Maximum Acceptable/ Admissible Concentration:

Maximum concentration of vapor in parts per million of

air in which a worker may work eight consecutive hours

without an air-fed mask; the lower the maximum

allowable concentration, the more toxic the substance

10

NOAEL (No Adverse Health Effects Level):

The highest tested dose of a substance that has been

reported to have no harmful (adverse) health effects on

people or animals.

11

TLV-STEL

• TLV-TWA (Threshold Limit Value - Time-Weighted Average) is defined as the time-weighted average concentration for a conventional 8-hour workday and a 40-hour workweek, to which it is believed that nearly all workers may be repeatedly exposed, day after day, without adverse health effect.

•TLV-STEL (Short-Term Exposure Limit); this is defined as a

15-minute TWA exposure which should not be exceeded at any time during a workday, even if the 8-hour TWA is within the TLV-TWA, Exposures above the TLV-TWA up to the TLV-STEL should not be longer than 15 minutes and should not occur more than four times per day. There should be at least 60 minutes between successive exposures in this range.

OEL - STEL

Short-term exposure limits - peak limitations, intended as

supplementary to TWA and protecting against short-time effects

like annoyance, irritation, CNS depression etc. in situations

where OEL-TWA values were set at levels only slightly lower

than the concentrations associated with the risk of short-term

exposure effects.

The definition stresses that STEL is not a ceiling value, the

essential difference being that no reference period is quoted for

the ceiling concentration. It should be noted, however, that

among the already published 90 indicative OEL values none

refers to the ceiling concentration.

STELs are needed where adverse health effects

(immediate or delayed) are not adequately controlled by

compliance with an 8 hour TWA.

The STEL is a limit value above which exposure should not

occur and usually relates to a 15 minute reference period. It

should be noted that the STEL is not a ‘ceiling’ value

(‘ceiling’ values are short term limits without a specific time

reference period, implying that the limit should not be

exceeded at any time during the work period or shift.

Occupational Exposure Limit Values: Protecting Workers Health Definitions

Occupational Exposure Limit Values: Definitions

Ceiling exposure limit (TLV-C) or maximum exposure concentration that should not be exceeded under any circumstance,while meeting the daily TLV-TWA.

Permissible Exposure Limits (PEL):The difference between TLVs and PELs is the agencies from which they come.

Biological exposure indices (BEIs)

Derived No Effect Level (DNEL)

The purpose of DNELs is to act as the reference value for

determining adequate control of exposure for specific

scenarios and required for 10 tonnes/yr chemicals.

DNELs (inhalation) for occupational exposure comparable

to MACs.

Steps of DNEL Derivation

• Collection of all available toxicity data; gathering typical dose descriptors.

• Decision on mode of action threshold vs. non-threshold).

• Selection of relevant dose descriptor(s) for the endpoint concerned.

• Modification of the dose descriptor to the correct starting point.

• Application of assessment factors, where necessary for the relevant exposure pattern.

• Selection of the critical effect .

OELs and DNELs: similarities

• the same objective, in general: concentration, that would not result in health impairment due to exposure.

• the same starting point, though assessment factors are different.

OELs and DNELs: differences

• OELs are developed strictly for OSH purposes and have direct application as a reference tool for the systematic monitoring of exposure

• DNELs primarily not intended for OSH purposes but as a tool for chemical safety assessment and selection of proper RMM

• DNELs have no direct impact on workplace regulations

• OELs are legally binding (responsibility of the Government) – legal instrument of enforcement of health policy, compliance supervised by governmental agencies or institutions

• DNELs introduced by companies only

• Representativeness and transparency of the OEL establishment process – lack of expert judgement in the DNEL derivation

• Different assessment factors; mostly default factors in DNELs vs expert judgement in OELs

OELs and DNELs: differences, cntd.

Objectives of OEL setting

• to prevent or limit the exposure of workers to dangerous substances at workplaces

• to protect the workers that are likely to be exposed to these substances

Criteria For The Selection of Priority Substances

When selecting candidate priority substances for setting OELs, the following criteria are taken into account: •Epidemiological evidence including reported cases of ill- health in the workplace •Availability of toxicological data •Severity of effects •Number of persons exposed •Availability of data on exposure•Availability of measurement methods

OELs at the EU level – legal aspects

• Council Directive 80/1107/EEC (amended by Directive 88/642/EEC) – setting out measures for the control of risks related to chemical, physical and biological agents

• Council Directive 90/394/EEC – provisions for setting up limit values for carcinogens

• Framework Directive 89/391/EEC – measures to encourage improvements in the safety and health of workers at work

• Council Directive 98/24/EC – legal basis for Community OELs

• Commission Directive 2000/39/EC establishing the first list of indicative OELs

Scientific Committee for Occupational Exposure Limits to Chemical Agents (SCOEL)

• Set up by the European Commission Decision 95/320/95 of 12 July 1995.

• to supply the Commission with opinions at the latter’s request on any matter relating to the toxicological examination of the chemicals for their effects on health of workers.

• to give in particular advice on the setting of OELs based on scientific data and where appropriate propose values which may include:

- the eight-hour time weighted average (TWA)- short-term limits/ excursion limits (STEL)- biological limit values

General Procedure for Setting OEL Proposals by SCOEL

• Assemble all available data on the hazards by the substance

• Determine whether the database is adequate for the setting of an OEL

• Identify the adverse effects due to exposure to the substance

• Establish which adverse effect(s) is (are) considered to be crucial in deriving OEL

• Identify the relevant studies which characterise these key effects (quality of these studies)

• Establish whether the substance acts via a non-threshold or threshold mechanism (crucial for health based OELs)

Steps Leading to the Establishment of EU OELs

For a 'case by case' approach to the setting of OELs,

considering each substance individually.

To establish an OEL, using the following general procedure

is recommended.

Information Relevant to the Establishment of OELs  

First of all, we should assemble all available data on the hazards of the substance. This will include human, animal and other experimental information, as well as background data (e.g. physical properties) relevant to the establishment of an OEL.

Information may derive from observations in humans, experiments in animals or laboratory investigations.

The key components of a relevant data set are likely to be:

•information on threshold effects,•information on non-threshold effects,•information on short term (acute) effects (effects of a single exposure),•information on long term effects and the effects of repeated exposure by an appropriate route (including dose-response relationships),•information on target organ(s) and the nature of the effect(s),•information on the methodology of measurement of airborne levels.

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Assessment Factors (AF)

• Assessment factors are numerical values used to address differences between experimental data and the human situation taking into account the uncertainties in the extrapolation procedure and the available data set.

• Substance-specific information should be used in the establishment of appropriate values for the various assessment factors.

• In the absence of substance-specific or analogous data use default assessment factors.

• It should be remembered that the default assessment factors are based on experience and not strictly on science and they may or not may be not suitable for a given substance.

Default Assessment Factors (AF)

Assessment factor Systemic effects

Local effects

Interspecies -differences in metabolic rate

per body weight

-remaining differences

AS

2,5

-

1 (2,5 metab.)

Intraspecies -worker

-general population

5

10

5

10

Exposure duration

-subacute to sub/semichronic

-sub/semichronic to chronic

- subacute to chronic

3

2

6

3

2

6

Dose/response -reliability of dose/response,

LOAEL/NOAEL, severity of effects

1 (NOAEL)

3-10 (LOAEL)

1 (NOAEL)

3-10 (LOAEL

Quality of database – completeness and consistency of available data: 1*

*deviations are possible

To Prepare Documentations; The Experts Utilize All The Available Information Which Usually Includes

Original bibliography collected through the data bases (TOXLINE, MEDLINE, CANCER-CD, OSH-ROM, NIOSHTIC, CHEM-BANK, RTECS, HSDB, ANALITICAL ABSTRACTS, CCINFOdisc, IRPTC, CHEMICAL ABSTRACTS)

Available documentations on exposure limits in other countries (USA, Germany, Sweden, EU)

WHO Environmental Health Criteria IARC evaluation of the carcinogenic risk due to chemicals Other reviews Unpublished documented data

Adequate Database For the Setting of an OEL

We should determine whether the database is adequate for the setting of an OEL. As an example, the following will determine the extent to which a chemical substance is absorbed through the skin: •the amount of the substance (per unit surface area) in direct contact with the skin (i.e. the dose) •the physicochemical properties of the substance (lipophilicity, molecular weight, volatility) •concomitant exposure to a vehicle or other chemicals which may enhance the rate of penetration  •the duration of exposure •the physical form of the substance.

Quality of The Database

• thorough analysis of available data• lacking data (long-term effects)• experimental conditions, quality of animals, control

groups, etc.• consistency of data

For experiments carried out according to GLPprocedures and complete data, defaultassessment factor is 1, in other cases expertjudgement.

Identification of the Adverse Effects

We should identify the adverse effects that may arise from exposure to the substance experimentally.

Human data •In general, good quality human data are to be preferred to animal data, but may frequently either not be available or be inadequate scientifically. Human data falls into one of four broad categories, as follows;  1.Individual case reports 2.Studies in human volunteers 3.Cross-sectional studies 4.Cohort and case-control studies.

With the exception of above, human studies generally suffer from poor characterisation of exposure and clear dose-response relationships are rarely demonstrated

Case reports can be useful in indicating relationships between exposure to given substances and specific adverse effects.

In many cases human data will either not be available or will be

inadequate.

In such instances it will be necessary to consider establishing an

OEL on the basis of data derived from experiments in animals.  

Animal studies clearly suffer from the disadvantage that the

species under investigation is not the human.

Animal data and laboratory studies

Nevertheless, animal studies possess some clear

advantages, particularly in respect of good characterisation

of exposure, adequate use of controls, extensive

pathological investigations and the potential to give clear

indications of dose/response.

Information available from animal studies falls into several

categories, which can be related to different aspects of the

OEL setting process.

•Single exposure data

•Repeated exposure data  

•Routes of exposure

•Toxicokinetic data

•Other information

Deriving the Level of the OEL

We should establish which adverse effect(s) is(are) considered

to be crucial in deriving the level of the OEL

In order to establish a 'health based' OEL it is necessary to have

sufficient information on both acute and chronic effects.

Information available from animal studies falls into several

categories, which can be related to different aspects of the OEL

setting process.

After completing this steps, you should assess the dose/response data for each

key effect. Establish 'no observed adverse effect levels' (NO(A)ELs) wherever

possible, otherwise establish 'lowest observed adverse effect levels'

(LO(A)ELs).

 

Next thing you should do is deciding whether a short term exposure limit

(STEL) is required in addition to an 8 h time weighted average (TWA) limit.

Following this decide whether a biological limit value might be established and,

if so, what kind of limit value it will be.

41

Biological Limit Value

Health protection of workers is based on two methodologies:

air monitoring & biological monitoring•Biological Limit Values are reference values for evaluation of potential health risks in the practice of occupational health.

•The interpretation of biological monitoring data reqires experties in the field of occupational medicine.

Biological methods used to assess exposure risks to health fall into two main categories:•Determination of the substance or its metabolite in a biological medium

•Measurement of biological effects

Biological Limit Values (BLVs) & Biological Exposure Indıces (BEIs)

Biological limit value or biological tolerance value for

occupational exposures is defined as the maximum permissible

deviation from the norm of biological parameters induced by these

substances in exposed humans.

The BLV is established on the basis of currently available scientific

data which indicate that these concentrations generally do not

affect the health of the employee adversely, even they are

attained regularly under workplace conditions.

Biological Limit Values (BLVs) & Biological Exposure Indıces (BEIs)

BLV can be defined as concentration or rates of formation or

excretion (quantity per unit time).BLVs are conceived as ceiling

values for healthy individuals.

They are generally established for blood and urine and take into

account the effects of the substance and an appropriate safety

margin, being based on occupational medical and toxilogical

criteria for the prevention of adverse effects on health.

Derivation of Biological Limit Values (BLVs) & Biological Exposure Indıces

(BEIs)

The derivation of a BLV can be based on various

constellations of scientific data which reveal a quantitive

relation ship between exposure concentration and body

burden and therefore permit the linking of OEL and BLVs.

OELs and BLVs

In general, OELs and BLVs are based onsimilar quantities of internal

exposure

In the first instance BLVs represent the levels of determinants which

are likely to be observed in specimens collected from a worker

exposed to the chemical by inhalation,at the level of the OEL.

After all last steps will be establishing a numerical value for an 8 h TWA OEL at

or below the NO(A)EL or, if this is not possible, below the LO(A)EL),

incorporating an appropriate Uncertainty Factor (UF), establishing a numerical

value for a STEL (if required).

Establishing a numerical value for a BLV (if required), documenting the entire

process such that the rationale for the OEL is clear.

Finally you should assess the technical measurement feasibility of the air and

biological values recommended.

47

Uncertainty Factors & Their Application

An ‘Uncertainty Factor’ (UF) is a factor used in the process

of extrapolating from a necessarily restricted human and

animal data base to wider human populations, in order to

allow for uncertainties in the extrapolation process.

UFs must be established on a case-by-case basis and cannot be

forecast or established in advance.

Although specific factors could be grouped into similar circumstances,

(e.g. poor human data, differences in the human-animal metabolism,

etc), the interrelationship of many other characteristics inherent to

every dataset makes a rigidly standardized approach impractical.

Therefore, SCOEL will consider each substance individually, within the

context of the agreed general framework.

Reproductive Toxicity

The objective of OEL setting is to prevent adverse health effects

in occupationally exposed persons and/or their progeny.

Thus the potential of each substance to produce adverse effects

on various aspects of the reproductive process needs to be

considered, even though the availability of relevant data in this

field of toxicity is limited for quite a number of substances.

Reproductive toxicity includes the impairment of male and female

reproductive function or capacity and the induction of non-heritable

adverse effects in the progeny The potential of each chemical

substance to cause the following adverse effects should be

considered:

(1)Effects on male and female fertility

(2)Developmental toxicity

Reproductive effects arising from chemical exposure have, for a

few substances, been identified in humans, the relatively high

spontaneous background of such effects makes it difficult to

attribute a specific adverse effect to exposure at the workplace

or in the environment.

The Evaluation of Chemical Carcinogens & Mutagens

There is growing recognition that carcinogenic risk extrapolation to low doses (and standard setting) must consider the mode of action of a given chemical.

So far, there is agreement to distinguish between genotoxic and non-genotoxic chemicals, yet further differentiations seem appropriate.

For genotoxic carcinogens, case studies of chemicals point to a whole array of possibilities.

For a number of apparently genotoxic carcinogens, practical thresholds are a matter of discussion.

As summarised in the figure below, these and other mechanistic arguments, taken together, led SCOEL to the distinction of the following four main groups of carcinogens and mutagens in relation to setting OELs:

OELs for Carcinogens

Effective toxicity threshold does not exist or is impossible to be determined; each exposure to carinogenic genotoxic agent is assumed to be associated with the risk of cancer development. Not possible to determine the level of the substance concentration which does not produce adverse health effects in all the exposed individuals (a condition specified by most occupational exposure limit definitions)

For such substances the concentrations should be kept as low as possible (if their complete elimination from the production process is not feasible) legally binding exposure limits take into consideration the socio-economic factors and are based on the concept of acceptable cancer risk.

• OELs for carcinogenic substances are based on the data on the carcinogenicity of a specific substance in humans (epidemiological data) and/or experimental animals.

• Such limit may be derived from the data on unit risk or from the slope factor of the dose-response curve; in both cases the acceptable risk serves as the criterion.

• In general, in the occupational setting, the acceptable levels of cancer risk vary between 10-2 to 10-5 .

OELs for Carcinogens, cntd.

Classification of Carcinogens

• Classifications referring mainly to the strength of proof of their carcinogenic activity (IARC, ACGIH®, EU – Directive 2004/37/EC).

• In most cases the substances and technological processes are classified as:

carcinogenic to humans, suspected of being carcinogenic to humans, carcinogenic to experimental animals, not classifiable as a human carcinogen, not suspected as a human carcinogen.

• In some countries information on cancerogenity and/or mutagenicity included in the OEL list.

No Threshold Substances

• Cancerogenic and mutagenic substances cat. I and II

• DMEL (derived minimal effect level)• DAEL (derived accepted effect level)• Accepted risk of occupational cancer: 10-5 to 10-3.

Processing Mixtures

In practice, exposure is frequently to mixtures, rather than to one

substance in isolation.

It is not practicable to make an evaluation of the effects of all

possible combinations of exposure.

However, when this is of particular significance at the workplace,

it will be noted in the documentation summarising the

recommendation.

Types of Mixture

• Natural mixtures

• Petroleum based mixtures

• Formulated mixtures

• Processing mixtures

• Combined mixtures

Natural Mixtures

• Source – extraction and/or processing naturally occurring

substances (mineral ores, vegetable oils, tea etc.)

• Composition may be not known and vary depending on source and

season

• Defined by mostly by their physical properties or technological

processes

• In most cases no OELs assigned

• Specific ill-efects usually well documented

Petroleum Based Mixtures

• Sub-group of „natural mixtures”

• Relates to distillation fractions of oil (white spirit, fuels, naphtas

etc.)

• Defined by by physical properties (e.g. boiling range)

• Composition may vary depending on origin and processing

• The mixture and/or its components may have been assignrd

OELs

Formulated Mixtures

• Produced by mixing components to a pre-defined formula to give

products for specific applications (paints, adhesives, cleaning

preparations)

• The composition is usually known; some components may be

already natural mixtures

• Composition is controlled

• No OEL for the mixture, individual components may have been

assigned OELs

Processing Mixtures

• Arise from the technological processes (plastic fumes, welding

fumes, rubber fumes etc)

• Composition changes with process parameters (temperature,

pressure, oxygen supply etc)

• Contain both identified and unidentified compounds

• Some compounds may have or may have not OELs assigned

• Some of the process mixtures may have been assigned OELs

What To Measure?

All, or many of the individual components (require

knowledge of the mixture components and availability of

the appropriate analytical method)

The „total mixture” (if OEL is for the mixture or if the total

mixture exposure serves as a measure of control)

A single substance, as a guide to exposure and control

A Single Substance As a Measure Of Exposure

• Measurement methods not available for all the pollutants

many components without OELs and there are unidentified

components.

• Quantification of all components would be excessively

expensive.

Selection Of the Key Components To Be Measured

• The existence of OELs

• Concentration in the mixture

• The toxicity of the individual substances

Categories Of Possible Joint Toxic Effects

• Independent action – each component acts in an individual way in the human body which is different from, and unaffected by, the effects of other components

• Additive action - the combined toxic effects are the simple sum of toxic effects of each component acting alone

• Synergistic action – the combined toxic effects are greater than the simple sum of the toxic effects of the single components acting alone

• Antagonistic effect – the combined toxic effects are less than the simple sum of the toxic effects of each component acting alone

Calculation Of The Additive Exposure

If the workers are exposed simultaneously or consecutively to

more than one agent during the same work-shift, the sum of the

ratios of measured exposures for individual exposures (C) to their

OELs must be less than, or equal to, one, according to the formula:

1...2

2

1

1 n

n

OEL

C

OEL

C

OEL

C

Calculation of OEL

The approach used to set OELs was based on the "no-observed-effect-level/safety factor (NOEL/SF) approach.

1. In this approach, all of the pertinent animal studies are reviewed and the highest dose that did not cause an effect in the most sensitive health endpoint (the NOEL) is identified.

2. Once a NOEL has been identified, a set of uncertainty (or safety) factors are applied to this value to accommodate for limitations in the data and to try to assure that workers are protected.

(The number and magnitude of these safety factors depend on the quality of the data.)

***If a NOEL is not available, then a LOEL can be used. The LOEL, or lowest-observed effect-level, is the lowest dose that causes an effect in the most sensitive health endpoint.

Calculation of OEL

OEL = [(NOEL) x (human body weight)]/[(safety factor)n

x (human breathing rate)]

NOEL is typically in units of milligram of chemical administered/kilogram of animal body weight/day;

Human body weight typically is assumed to be 70 kilograms for an adult male;

Safety factors for accomodating limitations in the data,

Breathing rate in workers typically is assumed to be 10 m 3/8-hour workday.

Calculation of OEL

Example of OEL Calculation

Example of using this approach for the synthetic estrogen,

ethinyl estradiol:

The NOEL in humans has been estimated to be around

3.5 μ g/day. (Because it is reported in these units, there is

no need to multiply by the human body weight).

If one assumes a safety factor of 10 for the human

variability in response and a breathing rate 10

m3/8-hour workday, then the OEL is estimated to be

0.035 μ g/m3.

Thank you for your attention