The Occupational Exposure Limit (OEL) is defined as the airborne concentration of a substance (expressed as a weighted average in time for a working day of 8 hours/day and 40 hours/working week) under which it is believed that nearly all workers may be repeatedly exposed (day after day, over a working lifetime) without adverse health effects (ACGIH, 2006; DFG, 2005). Occupational exposure limits (OELs) are a useful tool to prevent adverse effects on health when managing chemical substances. On a European scale… • Employers are legally obliged to provide a work environment that does not threaten the health of the workers (Chemical Agent Directive 98/24/EC and Framework Directive 89/391/EEC). • Under Directive 89/391/EEC, OELs can be developed nationally, Indicative Occupational Exposure Limit Values (IOELVs).

1. QUANTITATIVE RISK ASSESSMENT
AND THE CATEGORISATION OF
OCCUPATIONAL EXPOSURE TO
CHEMICAL AGENTS/APIs

2. 1. INTRODUCTION
2. RISK ASSESSMENT
3. CATEGORIZATION
2

3. INTRODUCTION

4. INTRODUCTION
The Occupational Exposure Limit (OEL) is defined as the airborne concentration of a
substance (expressed as a weighted average in time for a working day of 8 hours/day
and 40 hours/working week) under which it is believed that nearly all workers may
be repeatedly exposed (day after day, over a working lifetime) without adverse
health effects (ACGIH, 2006; DFG, 2005).
Occupational exposure limits (OELs) are a useful tool to prevent adverse effects on
health when managing chemical substances.
On a European scale…
• Employers are legally obliged to provide a work environment that does not
threaten the health of the workers (Chemical Agent Directive 98/24/EC and
Framework Directive 89/391/EEC).
• Under Directive 89/391/EEC, OELs can be developed nationally, Indicative
Occupational Exposure Limit Values (IOELVs).
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5. INTRODUCTION
SOME LIMIT VALUES IN THE WORLD
• TLV ®(1950): Threshold Limit Value
American Conference of Governmental Industrial Hygienists (ACGIH)
• REL®: Recomended Exposure Limits
National Institute for Occupational Safety and Health (NIOSH)
• PEL®: Permissible Exposure Limits
Occupational Safety and Health Administration (OSHA)
• OEL®: Occupational Exposure Limits
Health and Safety Executive (HSE)
• VME®: Valeurs Moyennes d´Exposition
Institute National de la Recherche et la Securité (INRS)
• MAK®: Maximale Arbeitsplatzkoncentrationen
Deustche Forschungsgemeinschaft (DFG)
GESTIS - International limit values for chemical agents
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6. 6
RISK ASSESSMENT

7. RISK ASSESSMENT (ECETOC TR No. 101)
What should we do if
there is no regulatory OEL
value?
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8. RISK ASSESSMENT(ECETOC TR No. 101)
We calculate the OEL based on:
• Epidemiological studies or
• Toxicological data selecting the point of departure (POD) established by
repeated dosage studies in animals and applying appropriate correction
factors (ECETOC, 2003a) to take uncertainty and variability in the set of data
into account:
➢ NOAEL no-observed-adverse-effect level and
➢ LOAEL lowest-observed-adverse-effect level
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9. RISK ASSESSMENT
9
D. A. Dankovic, B. D. Naumann et al. The Scientific Basis of Uncertainty Factors Used in Setting
Occupational Exposure Limits. J Occup Environ Hyg. 2015 Nov 25; 12(sup1): S55–S68.

10. RISK ASSESSMENT (ECETOC TR No. 101)
Relevant points to establish an OEL:
• Repeated dosage studies must last for at least 28 days.
• Toxicokinetic studies can provide information on the extent to which the
manner of exposure, distribution, metabolism and excretion of the substance
in animals are adequate to establish an OEL in humans.
• The criteria to select a NOAEL include the selection of the most relevant
species for man. If several studies are conducted with different species, the
highest NOAEL must be used, but this NOAEL must not exceed the LOAEL in
any of the other studies
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11. RISK ASSESSMENT
Correction factors:
11
D. A. Dankovic, B. D. Naumann et al. The Scientific Basis of Uncertainty Factors Used in Setting Occupational
Exposure Limits. J Occup Environ Hyg. 2015 Nov 25; 12(sup1): S55–S68.

12. RISK ASSESSMENT
Correction factors
UFA
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13. RISK ASSESSMENT
Correction factors:
• UFH : A value of 10 is normally used for the general population, in the absence of
specific chemical data.
• UFL : 1 (POD=NOAEL), 10 (POD=LOAEL)
• UFS : The purpose of OELs is to protect workers that are exposed throughout
their working life, in animals this is usually compared with a chronic study (e.g.
two (2) years for rats and mice).
13
D. A. Dankovic, B. D. Naumann et al. The Scientific Basis of Uncertainty Factors Used in Setting Occupational Exposure Limits.
J Occup Environ Hyg. 2015 Nov 25; 12(sup1): S55–S68.

14. RISK ASSESSMENT
UFD: 1-10. Incomplete toxicological data (studies of a single species, there are no
reproduction or development data, etc.)
Toxicokinetic (TK) adjustment:
Example: If an OEL is established from a critical effect in an oral study with a
bioavailability of 10%, bearing in mind that bioavailability for inhalation is 100%:
1.0/0.1 or a factor of 10.
Modification factor (MF): This factor is adjusted for uncertainties not tackled by
the UFs described above (<1 to 10).
14
D. A. Dankovic, B. D. Naumann et al. The Scientific Basis of Uncertainty Factors Used in Setting Occupational
Exposure Limits. J Occup Environ Hyg. 2015 Nov 25; 12(sup1): S55–S68.

15. RISK ASSESSMENT (ECETOC TR No. 101)
If there is no NOAEL/LOAEL:
• The maximum tolerated dose in long term studies can be used to establish an
OEL. If this is not known, the maximum tolerated dose can be predicted based
on acute oral toxicity (lethal dose in rats) and the octanol-water distribution
coefficient.
Molecules with a molecular mass of <500 and a Kow log of 0–4 are absorbed well
orally or by inhalation.
• Lethal concentrations of four hours of inhalation studies in rats can be
directly used to calculate the OEL.
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16. RISK ASSESSMENT (ECETOC TR No. 101)
If there is no NOAEL/LOAEL:
• The use of QSARs to predict the toxicity is not reliable enough, therefore, they
are of limited value when it comes to establishing the OEL. It is better to look
for substances with similar structures and known toxicity (Read-across).
ChemIDplus (http://chem.sis.nlm.nih.gov/chemidplus/) (NLM, 2004).
• You can resort to the Threshold of Toxicological Concern (TTC), which is
normally used for food contaminants to determine the OEL by the most
conservative method. The first step in applying the TTC concept for a
particular substance is to identify the possible genotoxic effects and/or highly
potent carcinogens. If estimated intake does not exceed 1.5 μg / person / day,
you would not expect the substance to be a safety problem.
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17. RISK ASSESSMENT (ECETOC TR No. 101)
At present, there are no procedures to establish the OELs for data-poor
substances.
Data poor substances: Substances that fall under Annex V of REACH (volume of
up to 10 t/year) form part of this category.
One possibility could be to use the derived-no-effect level (DNEL), taking this as
an OEL equivalent.
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Considerations to be taken into account:
• The absorption of a chemical substance is conditioned by:
➢ Physical state: Gas (inhalation), liquid (vapour inhalation, aerosol
droplets, directly through the skin), solid (aerosol inhalation)
➢ Temperature: When handling, during shipment, storage, etc.
➢ Dust of any type can become a hazardous substance when it is
present in airborne concentrations equal to or over 10 mg / m3 of
inhalable dust or 4 mg / m3 of respirable dust.
RISK ASSESSMENT (ECETOC TR No. 101)

19. 19
Considerations to be taken into account:
✓ The substance can also cause harm when:
• being absorbed through the skin;
• being ingested; or
• acting directly on the body at the point
of contact, e.g. the skin.
RISK ASSESSMENT (ECETOC TR No. 101)

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RESPIRATORY/SKIN/EYE IRRITANT AGENT
Because of its limited solubility in water, the substance may reach:
• The alveoli or
• Be inhaled as critically-sized particles ("respirable dust"),
The OEL must be based on the prevention of:
➢ Damage to the lung epithelium in the short term
➢ COPD, emphysema or pulmonary fibrosis after long-term exposure.
Contact with the skin can cause irritation and contact dermatitis. If a substance has
a high octanol-water partition coefficient and a low skin DL50, e.g. 1000 mg / kg,
the possibility of skin irritation must be considered.
RISK ASSESSMENT

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RESPIRATORY SENSITISER AGENT
A substance is considered to cause occupational asthma if, on account of exposure in
the workplace:
➢ It provokes a biological change known as a “hypersensitive state” in the
respiratory tracts; and
➢ It provokes a subsequent reaction in those respiratory tracts.
• Substances may not be hazardous in solid form but may indeed by so in fine
powder or dust form which can be inhaled into the lungs.
• Nanoparticles (<100 nanometres) can be more toxic than bigger ones of the same
substance.
• Impurities in a substance can make it more dangerous.
RISK ASSESSMENT

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SKIN SENSITISER AGENT
Allergic skin contact: Repeated exposure to a relatively low concentration.
There is a class of chemical substances that can cause allergic reactions in the skin
after exposure to sunlight or ultraviolet (UV) light. These chemical products are
known as photosensitisers.
Penetration of the skin can increase in highly humid settings. When temperatures
are high, perspiration can contribute to greater skin absorption.
RISK ASSESSMENT

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An adjusted OEL (AOEL) can be calculated when worker exposure time is not 8 hours a
day
RISK ASSESSMENT- AOELs

24. How is the OEL calculated in compounds?
Three possible compound cases are considered:
Synergistic substances: Quite uncommon. These are the most serious cases.
Additive substances: when there are reasons to believe that the effect of the
components are additive and are based on the same effects on health.
Independent substances: when the synergistic or additive effects are not known or
considered unlikely, the constituents can be considered as working independently and
the requisite measures are analysed to attain adequate control separately.
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RISK ASSESSMENT- COMPOUNDS (ECETOC TR
No. 101)

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➢ If the total is < 1, exposure to the compound is below the OEL value
➢ If the total is > 1, exposure to the compound is above the OEL value
RISK ASSESSMENT- COMPOUNDS (ECETOC TR
No. 101)
Additive:

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RISK ASSESSMENT- COMPOUNDS (ECETOC TR
No. 101)

27. 27
✓ Toxicology databases for the work environment
✓ Buscatox
✓ QSAR/READ-ACROSS
✓ Danish QSAR
✓ Toxtree
✓ Vega
RISK ASSESSMENT- DATA BASE

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CATEGORIZATION

29. CATEGORIZATION SYSTEMS
Naumann et al., 1996:
• system based on five (5) categories
• range of permissible occupational exposure limits (PEL) that range from 1000 - 5000
μg/m3 in category 1 to those values under 100 ng/m3 in category 5.
Safebridge (SB) proposes, as does the ISPE
• a system based on four (4) categories
• a broader band range than in the previous case.
INSHT (NTP 798)
System based on five (5) categories
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30. CATEGORIZATION SYSTEMS - AZIERTA
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See the table in www.azierta.eu
Once the OEL value has been calculated and the toxicological analysis of the
substance carried out, a categorization of the substance shall be carried out taking
into account the toxicological and pharmacological characteristics as well as the
physicochemical properties of the substance.

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