1. An Overview of Methods to Develop
XX Word Congress on Safety and Health at Work 2014
Symposium on Threshold Limit Values
for Chemical Substances and Nanomaterials
An Overview of Methods to Develop
Occupational Exposure Limits in Europe
Hermann M. Bolt
Leibniz Research Centre for Working Environment and Human Factors, TU Dortmund (IfADo)
Chair, Scientific Committee for Occupational Exposure Limits (SCOEL), Luxemburg
WHO Collaborating Centre for Occupational Health
Aug. 25, 2014

2. The Position of Scientific Advisory Bodies
The general discourse and interplay leading to OEL/BLV
regulations is similar at national and EU levels:
Political
authorities
Legislation on
occupational standards
Scientific experts
Social partners:
employers/industry,
trade unions

3. OELs and BLVs: Development of the SCOEL Mandate
1990: SEG established
SCOEL strategy
for carcinogens
1980
1988
1989
1990
1995
1997
2004
2007
Revision/extension of
„Biological Monitoring“
EUR 19253“Methodology of derivation of OELs“
Commission Decision 95/320/EC  setting up SCOEL
Council Directive 90/394/EEC  protection of workers to carcinogens
Council Directive 89/391/EEC  introduction of measures/safety and health
of workers
Council Directive 88/642/EEC  amending the Directive of 1980
Council Directive 80/1107/EEC  protection of workers from the risk related to exposure
to chemical, physical and biological agents at work

4. Commission Decision (95/320/EC) of 12 July 1995,
setting up a Scientific Committee for Occupational
Exposure Limits to Chemical Agents (SCOEL)
Article 2 (1)
... „The Committee shall in particular give advice on the setting of Occupational
Exposure Limits (OELs) based on scientific data and, where appropriate, shall
propose values which may include:
the eight-hour time-weighted average (TWA),
short-term limits/excursion limits (STEL),
biological limit values.
The OELs may be supplemented, as appropriate, by further notations.
The Committee shall advise on any absorption of the substance in question
via other routes (such as skin and/or mucous membranes) which is likely
to occur.“
Review: European aspects of standard setting in
occupational hygiene and medicine. Rev.Environ.Health 16:81-86

5. „Indicative Values“ vs. „Binding Values“
Two ways for the legal implementation of values
D 98/24/CE on chemical agents (indicative and binding values)
D 2004/37/CE on carcinogens and mutagens (only binding)
- IOELVs : Based on health criteria, derived from the assessment of updated and validated scientific data
Below this exposure no adverse effects are expected.
- BOELVs : Take also into account practical and socio-economical factors and the risk accepted by society
They are considered “political-type” values*.
* Political decision: to define “acceptable” versus “non-acceptable” risk
Aug. 25, 2014

6. Formal Procedures Development of limit values
Prioritisation of chemicals
Collection of existing data (by SCOEL members, contractor or JRC)
Evaluation of scientific data
Recommendation of limit value(s)
Scientific discussion (including 6 months consultation) and final recommendation (including analytical methods)
Consultation of social partners
Adoption (Commission/EP + Council)
Transposition (national) and use
Aug. 25, 2014

7. SCOEL’s Mandate
Scientific assessment to the EC ( D 95/320/CE) , especifically in relation to the legislation ( 98/24/CE /37/CE) foreseen to set occupational exposure limits (OELs)
Identification of available scientific data
Evaluation of the relationship exposure/effects
Recommendation of "OELs" : 8-h TWA, 15-min STEL, BLVs and “notations” (eg. skin absorption, sensitisation, carcinogen category) based on own methodology
Published recommendations (Aug. 2014) : 172
Aug. 24, 2014

8. Procedures Methodology Evaluations on a “case by case“ basis
Recommendations with clear justifications (published on the
EU website)
Critical effects and mechanisms of action, described as detailed as necessary
NOAEL and/or LOAEL, extrapolation model used, quantitative considerations in detail
Systematic update of key scientific factors and of criteria (e.g. carcinogenicity)
Aug. 25, 2014

9. Procedures Methodology
Developed by the Committee parallel to its work (started 1990 as SEG)
Published in 1999 and continuously updated since then
Includes criteria on:
General principles
Uncertainty factors
Time-weighted (8-hours) average values (TWA)
Short term exposure (generally 15min) levels (STEL)
Absorption through the skin
Toxicity to reproduction
Respiratory sensitisers
BLVs (Biological Limit Values) / BGVs (Biological Guidance Values)
Carcinogenic and mutagenic substances / risk assessment
Aug. 25, 2014

10. Dose-Effect Relations in the Low Dose Range and Risk Evaluation
(Concept adopted by SCOEL – published in Archives of Toxicology 82: 61-64, 2008)
Chemical carcinogen,
causing tumours in humans and/or experimental animals
Genotoxic
Non-genotoxic
DNA reactive,
causing mutations
Genotoxicity only on chromosome
level (e.g. spindle, topoisomerase)
Clearly
DNA-reactive
& initiating
Weak genotoxin,
secondary mecha-
nisms important
Borderline
cases
A: No threshold,
LNT model to apply
B: Situation not clear
 LNT as default
C: Practical/apparent
threshold likely
D: Perfect/statistical
threshold likely
Numerical risk assessment,
 risk management procedures
NOAEL
 health-based exposure limits

11. Groups of Carcinogens and Examples
No threshold, LNT (Linear Non-Threshold) model to apply: A 12
vinyl chloride / vinyl bromide (risk assessment) MDA
dimethyl / diethyl sulfate 1,3-butadiene (risk assessment)
LNT as „default assumption“: B 11
acrylonitrile benzene (provisional assignment) arsenic
naphthalene hexavalent chromium o-anisidine
2,6-dimethylaniline (insuff. data) naphthalene
Practical/apparent threshold: C 10
formaldehyde vinyl acetate nitrobenzene pyridine
silica lead (provisional OEL); lead chromate TRI DCM
Ni glyceryl trinitrate
Perfect/statistical threshold: D 4
 carbon tetrachloride chloroform 1,4-dichlorobenzene
Important distinction between B and C!

12. Example for „C“: Vinyl acetate (SCOEL 2005/2006):
Local metabolism:
Local tumours at the point of entry into the organsim
No systemic bioavailability upon inhalation

13. Reasoning: Vinyl acetate, B or C ?
Local tumours in animals upon inhalation and oral dosing
Local hydrolysis to acetaldehyde and acetic acid
Local genotoxicity of acetaldehyde plus cytotoxicity by cell acidification (M. Bogdanffy, EUROTOX Budapest 2002)
Argumentation by von SCOEL (2005)
Cell proliferation / irritation necessary for tumour developmpent
No evidence of systemic effects
Group C: OEL = 5 ppm

14. Example for „B“: Acrylonitrile
Carcinogenic in rats (oral and inhalation dosing)
Weak mutagen, but mutagenic epoxide metabolite
Argumentation concerning brain tumours:
No DNA adducts in brain
Oxidative DNA damage in astrocytes in vitro
Reversible „gap junctions“ damage in exposed astrocytes
Dose-effect-curve sublinear
Genotoxicity in vivo not clear
But: multi-organ carcinogen!
Acute toxicity through cyanide metabolite !
Gruppe B; no health-based OEL

15. Summary of the SCOEL Strategy for Carcinogens
The scientific development allows to identify carcinogens
with a threshold-type mode of action. For these compounds
health based OELs (and BLVs, where appropriate) can be
derived.
Such a mechanism-based assignment is independent of the
formal classification of carcinogens (i.e., former EU cate-
gories 1, 2 or 3, equivalent to GHS categories 1A, 1B, 2)!
When derivation of a health-based OEL/BLV is not possible,
SCOEL assesses the quantitative cancer risk, whenever
data are sufficient.
When data are not sufficient for a risk assessment, SCOEL
gives recommendations on possible strategies for risk
minimisation, if possible.

16. Special SCOEL Topics (with support of JRC, Ispra)
Further development of biological monitoring
Sensitising compounds (diisocyanates and others)
PSLT = Poorly Soluble Low Toxicity („inert“) dusts
Nanomaterials and carbon nanotubes
Asbestos
Bitumen
Rubber industry and related compounds
Diesel exhaust
Aviation-related questions: aviation fuels, exhaust,
oils and hydraulic fluids

17. Biological Monitoring: 13 Compounds with BLVs / BGVs (Feb. 2014)
Acrylamide (BGV), aniline, benzene, Be, Cd,
carbon disulphide, N,N-dimethylformamide,
4,6-dinitro-o-cresol, 2-ethoxyethanol (and acetate),
hexachlorobenzene, hydrogen fluoride / fluorides,
lead compounds, including lead chromate

18. Debate on Nanomaterials
EU definition: particles sized nm
(Off J Eur Union L 275: 38-40)
Scientific discussion: increasing numbers of publications, conferences,
congresses (see Foth et al. Arch Toxicol 86: , 2012)
Present SCOEL discussion points:
Toxicokinetics different from those of larger materials.
Accumulation in cells / organs?
Cardiovascular effects?
Effect thresholds?
Aug. 25, 2014

19. Nanomaterials Recent MAK Commission Report (DFG 2013)
Open questions concerning measurement:
aggregation, agglomeration,
- relation to mass (mg/m3) not optimal!
In principle similar effects of nanoparticles and microparticles, but quantitative differences
(e.g. inflammation, oxidative stress, genotoxicity).
Special problems in case of metal-based nanoparticles!
Local / systemic effects?
Definition of research needs
Aug. 25, 2014

20. Nanoparticles may have local and systemic effects
Systemic effects not well investigated
In discussion (SCOEL):
Transport via olfactoric nerve
into CNS
Cardiovascular effects
Persistence in organs

21. Experimental Rodent Studies with Carbon Nanotubes
Local inflammation
effects in the lung
N(L)OAEL:
0.1 mg/m3
Agglomerates!
Aug. 24, 2014

22. Carbon Nanotubes: Summary for SCOEL
State of discussion:
Low local skin and eye toxicity
CNT not sensitising themselves, but
amplifying effect possible
Low experimental toxicity, but chronic
effects not well investigated
Effects on foetus only after i.v. dosing
Carcinogenicity and genotoxicity ?
Aug. 25, 2014

23. Summary: Exposure Limits in Europe
Since 1990 SCOEL has developed a methodology to derive OELs.
SCOEL closely cooperates with national scientific OEL panels
(especially MAK, DECOS, ANSES, Nordic Exports).
Continuous review of chemicals of key interest
Further development of biological monitoring
Establishment of a new procedure for carcinogens
Development of broader topics of key interest, partly on request by
European official bodies (Commission, Parliament)
Current discourse with ECHA on coherence with REACH
procedures, especially the derivation of „DNELs“ vs. OELs