Transcript English - OIC-VET

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 TLVTWA, 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.
where OEL-TWA values were set
in situations
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. nonthreshold).
• 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 and DNELs: differences, cntd.
• 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
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 illhealth 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 nonthreshold 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.
29
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
Interspecies
Systemic
effects
Local
effects
-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 GLP
procedures and complete data, default
assessment factor is 1, in other cases expert
judgement.
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.
Animal data and laboratory studies
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.
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 Carcinogens, cntd.
• 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 .
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:
Cn
C1
C2

 ...
1
OEL1 OEL2
OELn
Calculation of OEL
The approach used to set OELs was based on the "noobserved-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.
Calculation of OEL
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.
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