OECD workshop on approaches for establishing Occupational Exposure Limits Stefan Vink Health Council of the Netherlands.pdf

The OECD workshop on approaches for establishing Occupational Exposure Limits (OELs) presented the outcomes of the OECD survey report on the OELs setting and explored the possible opportunities for harmonisation approaches for setting OELs amongst countries. In addition, the workshop introduced Japan’s new legal framework on OELs, which aims to establish approximately 500 new OELs in the next three years.

This workshop was jointly hosted by Japan and the OECD. Japan provided English-Japanese interpretation to facilitate the discussion at the workshop.

Watch the replay at: https://www.oecd.org/en/events/2022/10/oecd-workshop-on-approaches-for-establishing-occupational-exposure-limits.html

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EstablishingOELsfor
carcinogensin the
Netherlands
Stefan Vink
Scientificstaffmember
Toxicologistandoccupationalhygienist
Health Councilof the Netherlands
OECD OEL Workshop 2022

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Health Council andDutch OEL-system
2
“The Health Council of the Netherlands: an independentscientific advisory body whose legal task it
is to advise ministers and Parliament in the field of public health and health/healthcare research.”
Request
Health-based
recommendedOEL
RecommendedOEL
‘science’ ‘feasibility’

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DECOS: Permanent committee
| Gezondheidsraad3
•Dutch Expert Committeeon OccupationalSafety
•Independent committeeof experts
•Toxicologists
•Epidemiologists
•Toxicological-pathologist
•Occupationalphysician
•Occupationalhygienist
•Tasks: performhazard assessments forsubstancesand deriveOELs

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2 types of OELsforcarcinogens
| Gezondheidsraad4
•Threshold-basedOELsandrisk-basedOELs
Carcinogens
Indirect or non-genotoxic
mechanism
Threshold-basedOEL
Direct genotoxic
mechanism
Cancer risk values
The Nordic Expert Group for Criteria Documentation of Health Risks from Chemicals
154. Approaches for the setting of occupational exposure limits (OELs) for carcinogens

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Risk levelsappliedin the Netherlands
5
•CRVsare exposure levels thatcorrespondto risksset bytheMinistry
•Target risk level: risk of cancerof 4:100.000 duetooccupationalexposure (acceptable)
•Prohibitiverisk level: 4:1.000 (is nottobeexceeded)
•Target risk level often not achievable in practice
•OELsare set at exposure levels betweenthese risk levels
•Risk levels are lifetimerisks; dueto40y occupationalexposure
•Risk levels are risksin additionto the background risk:
SubstanceX Lungcancer 100,000 11,200 11,204
SubstanceY Angiosarcoma 100,000 0 4
Non-exposedPopulationsize Exposed
Implicationof a risk-basedOEL at
a risk level of 4:100,000:

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Considerationsselectingstartingpoint
•Useof epidemiologicaldata are preferred
•Assessqualityand reliabilityof the availabledata
•Animalstudies
•Studyproperlyexecutedand reported(design, numberoranimals,
histopathologicalanalysis, exposureduration)? International guidelines
followed?
•Epidemiologicalstudies
•Proper design, accountedforconfounding, reliableexposureassessment?
•Determinecriticalcarcinogeniceffect andhuman relevance

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Step 1: Select startingpoint (animaldata)
*
•Startingpoint: Increasedincidenceof
malignant(relevant) tumors in rats or mice
•BMD analysis or single exposure group
Guideline for the calculation of risk values for carcinogenic
compounds. The Hague: Health Council of the Netherlands,
2012; publication no. 2012/16E

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BMD-guideline:
https://efsa.onlinelibrary.wiley.com/doi/10.2903/j.efsa.2017.4658
AverageBMD using
model averaging

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Step 2: Determinecarcinogenicpotency
9
•Carcinogenicpotencyis calculatedbasedon exposure for24 h/d, 7 d/w, life time
Tumourincidence,
correctedforbackground
incidence(e.g. BMR)
Exposure
concentrationof
startingpoint (e.g.
BMD)
Correctionsforexposure duration
duringstudycomparedtolife time
exposure

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Step 3: conversiontooccupationalsituation
21 november 2016| Gezondheidsraad10
mg/m3
incidence
0.004
0.00004
Cancer Risk Value
I
concentration, forinstance
Defaultvaluesforoccupationalexposure
Defaultvaluesfornon-occupationalexposure
Cancer risk value:
Target risk level >
Prohibitiverisk level >

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CRVsbasedonhumandata
•No uncertaintyrelatedto interspeciesdifferences
•Useof humandata: exposureand effect are bothquantified
•Differencewithanimaldata: risksexpressedas relativerisks(RR)
•Simple, direct estimationof extra cancerrisk basedon RR:
(RR x background cases) –background cases
(2.5 x 16.3) –16.3 = 24.5 (per 1000)
RR = 2.5
Backgr. cases = 16.3 (per 1000)
e.g.: Exposureto
substanceleadsto 2.5
foldincreasedrisk
Takes notintoaccount:
•Datasets thatcanbemodeled
•Age-dependencyof cancer

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Exposure-response modeling
•Multiple exposure categories> datapoints
•Deriveexposure-response model

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Age dependency: Life tableanalysis
Life table: A table which shows, for each age, what the probability is that a person of that
age will develop cancer or die from cancer:
Age
0
100

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AgeCancer Other At riskTotalCancer
1 0.000010.00139100000 140.51.1
2 0.000010.0008599859.585.4 1.0
…
20 0.000020.0002499515.525.3 1.5
…
60 0.000230.0069292277.4658.021.5
…
1000.001410.57958631.7 278.30.7
AgeRR Cancer Other At riskTotalCancer
1 1.00.000010.00139100000140.51.1
2 1.00.000010.0008599859.585.4 1.0
…
20 1.10.000030.0002499515.525.4 1.6
…
60 1.20.000280.0069292245.2662.526.1
…
1001.20.001720.57958625.2 275.60.8
Examplelife tableforsubstancecausingleukemia:
Fraction
dyingof
cancer
Fraction
dyingof
other
causes
+
1941
Non-exposedcohort Exposedcohort
Increased
risk dueto
exposure
Increased
leukemia
mortality
+
2341
400 extra/100000

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Mainpoint summary
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•Health Council onlyrecommends; Minister sets limit
•Cancer risk values(CRVs) are exposure levels thatcorrespondto life time
cancerrisks
•CRVsare derivedfordirect-actinggenotoxiccarcinogens
•Human data are usedmore and more often
•Exposure-response modellingand life tableanalysis have refinedthecalculation

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