Development and ApplicaCon of a Framework for the SelecCon of an Appropriate OccupaConal Exposure Limit 1,2 1 3 Michelle Deveau ; Dan Krewski ; Andrew Maier
1McLaughlin Centre for PopulaAon Health Risk Assessment, University of Olawa, Canada; 2Faculty of Graduate and Postdoctoral Studies, University of Olawa; 3Department of Environmental Health, College of Medicine, University of CincinnaA
• These divergent OELs can lead to difficulAes in selecAng the most appropriate value for health protecAon purposes. The objecAves of this work were to: • develop a tool to guide IHs in the selecAon of the most appropriate OEL for an occupaAonal risk scenario; and • apply the tool to demonstrate its versaAlity for both OEL-‐rich and OEL-‐poor scenarios.
NO RELIABLE VALUE AVAILABLE - Derive new value; - Make adjustments to existing OELs; - Use other OEL surrogates from the hierarchy of OELs; and/or - Use other risk management considerations, including communication or other administrative controls & hazard or control banding
Apply the regulatory standard
Reject OEL ?
Select OEL that most closely matches organizational policies from any remaining values
Figure 1. Framework for the selecAon of OELs. See the text box to the right for a more detailed descripAon of the applicaAon.
Acknowledgements We would like to thank our co-‐authors on an arAcle enAtled “The Global Landscape of OccupaAonal Exposure Limits—ImplementaAon of HarmonizaAon Principles to Guide Limit SelecAon,” which will be published in a forthcoming issue of JOEH. The co-‐authors are: C.-‐P. Chen, G. Johanson, K.J. Niven, S. Ripple, P.A. Schulte, J. Silk, J.H. Urbanus, D.M. Zalk, and R. Niemeier. Thanks also to G. Fazio for his graphic design experAse for Figure 1.
Assess availability and relevance of OELs Define use or scenario by idenAfying to whom and how the exposure of the compound will occur. Gather OELs, including documentaAon of the derivaAon of values, when available. Although the emphasis is on tradiAonal OELs (i.e. 8-‐hour TWAs), alternaAve exposure benchmarks that can be gathered in the absence of—or as a supplement to—tradiAonal OELs include: • Lower Aers of the hierarchy of OELs (Laszcz-‐Davis et al., 2014), such as values derived: - for internal use within a company, or by trade associaAons or vendors; - using a prescribed regulatory approach (e.g. DNELs under REACH); or - using semi-‐quanAtaAve approaches (e.g. Hazard Banding or Threshold of Toxicological Concern). • Exposure limits with different exposure scenarios from tradiAonal OELs, such as: - exposure limits intended for shorter duraAon (e.g. IDLH and AEGLs); or - environmental health exposure guidelines. Assess relevance by comparing the defined exposure scenario to OELs. Eliminate OELs that are not applicable to the defined scenario, or that cannot be adjusted to beler match the defined scenario. Compare mandatory standards to non-‐mandatory OELs to ensure regulatory compliance. Assess the reliability of OELs Risk science – Based on a recent literature review of the chemical’s health effects, evaluate the: • SelecAon of the Point of Departure (POD), the basis of the OEL calculaAon (e.g. no or lowest observed adverse effect levels or benchmark dose—NOAEL or LOAEL). Reject OELs based on studies or adverse effects that are no longer sufficiently protecAve, are not relevant to humans, or not based on current scienAfic principles. • ApplicaAon of uncertainty factors (UFs), which account for variability and uncertainAes in data used as the basis for the OEL. Reject OELs without sufficient margin of safety between the POD and OEL to account for variability in toxic responses among humans, and between animals and humans. • IntegraAon of weight of evidence; reject OELs that do not sufficiently consider all relevant human health aspects discussed in the literature. Risk policy – Based on the IH’s organizaAonal policies and pracAces, evaluate the: • Risk acceptance to verify whether the acceptable level of risk (typically in the range of 1/1,000 to 1/10,000 or 10-‐4 to 10-‐3 for occupaAonal scenarios) are in line with organizaAonal policies. • Feasibility to ensure that the organizaAon is capable of achieving the OEL with reasonable engineering and other controls, analyAcal approaches, and economic consideraAons. If more than one OEL is retained, select the most appropriate OEL. This selecAon can be based on the most conservaAve value, the most scienAfically robust value, or other factors—the primary recommendaAon is that the process is documented to ensure consistency. If no OELs are retained, consider developing a provisional OEL (de novo or by adjustment of rejected values), control banding or hazard banding, or other risk management approaches.
Contact Michelle Deveau University of Olawa Olawa, Ontario, Canada email:
[email protected]
Define exposure scenario
Auto mechanics in the U.S. exposed for several hours daily to n-‐hexane in aerosol degreasers
Gather OELs
GESTIS InternaAonal Limit Values database (2014) listed >25 8-‐hour OELs 6 values retained — see Table 1
Most values were eliminated from further review due to absence of documentaAon describing derivaAon
Assess relevance
All OELs were relevant to the populaAon, duraAon & route of exposure
Compare Mandatory vs. Non-‐mandatory OELs
OSHA PEL is ≥10-‐fold higher than all other values — applying other values will ensure regulatory compliance
Evaluate risk science basis
• OELs all based on neurotoxicity / electrophysiology • Non-‐OSHA L/NOAELs in similar range • Applied UFs for non-‐OSHA OELs appear to be sufficient
OSHA PEL ELIMINATED: Date of assessment would prevent the inclusion of some more protecAve LOAELs & NOAELs
Evaluate risk policy basis
• Threshold (non-‐cancer), therefore risk acceptance is inherent in UF selecAon, which was considered appropriate • Remaining OELs measurable (NIOSH Manual of AnalyAcal Methods) • OELs achievable with exisAng engineering & administraAve controls
Select most appropriate OEL
Example of applicaCon #2: OEL-‐poor situaCon*
Assess availability & relevance of OELs
• As a result of the proliferaAon of OEL-‐se}ng bodies, industrial hygienists (IHs) can be confronted with mulAple relevant—but oJen conflicAng—OELs for a chemical.
Guidance for IHs on the assessment of OELs for availability, relevance, and reliability was translated into a tool (Figure 1) that builds upon concepts presented previously, including a hierarchy of OELs (Laszcz-‐Davis et al., 2014) and framework for OEL evaluaAon and interpretaAon (Maier et al., 2012). The stages of the assessment are briefly outlined below.
Assess availability & relevance of OELs
• OccupaAonal exposure limits (OELs) serve as benchmarks for the interpretaAon of workplace exposures within a health risk context.
Example of applicaCon #1: OEL-‐rich situaCon*
Assess reliability of OELs
Framework for the SelecCon of OELs
Assess reliability of OELs
Background and ObjecCves
(ppm)
50
Germany MAK
50
Neurotoxic effects in workers (NOAEL of 58 ppm) and electrophysiological effects in animals (NOAEL of 100 ppm). UF not specified, but 1 for humans and 2 for animal studies.
NIOSH REL
50
OSHA PEL
500
(ACGIH, 2001)
(DFG, 2000)
(NIOSH, 2011) (OSHA, 2012)
Poland NDS (Jakubowski, 2006)
SCOEL IOELV
20
20
(EC, 1995)
Peripheral neuropathy at 210 ppm (LOAEL) & delay in onset of neurological symptoms. UF was not stated, but ~4-‐fold. Based on CNS depression, nausea, headache, narcosis, and eye and throat irritaAon. Details of OEL derivaAon could not be obtained (based on 1968 ACGIH TLV documentaAon). Value of 100 mg/m3 (28 ppm) was proposed based on a NOAEL of 204 mg/m3 (58 ppm) for neurotoxic effect in workers and UF of 2 for individual sensiAvity; therefore, the SCOEL of 20 ppm was deemed appropriate. Electromyographic abnormaliAes in workers at 70 ppm (LOAEL), supported by various workplace observaAons of these changes at 50–100 ppm. UF of 2, which was sufficient for mild effects.
Table 1. OELs examined for risk science and risk policy evaluaAon for n-‐hexane
No tradiAonal OELs for meth; only guideline is California EPA Reference Dose of 0.3 μg/kg-‐d
Assess relevance
Target populaAon (toddlers), duraAon of exposure (24 h/d, 7 d/wk) & route of exposure (ingesAon / total exposure) of RfD not relevant to scenario
Compare Mandatory vs. Non-‐mandatory OELs Evaluate risk science basis Evaluate risk policy basis
*Please note that the scenarios described in this poster are purely hypotheAcal and are intended to demonstrate the types of decisions that could be made during the process of selecAon of an OEL. All exposure guidelines described in the examples, however, are factual. The OELs selected and proposed are considered to be relevant to the scenarios presented herein, and might not be applicable to all exposure scenarios. Industrial hygienists should apply the framework for each specific scenario of interest to idenAfy the appropriate OELs for their situaAon.
10 LOAEL ÷ UF
8h 5d 8 m 3 DuraAon Route Interim value
of a djustment provided below) (Further details
Select most appropriate OEL
2) Exposure duraAon adjustment – to extrapolate from a conAnuous exposure value to 5 weekly 8-‐hour shiJs, the LOAEL was mulAplied by 24h/8h and 7d/5d. 3) Exposure route adjustment – default assumpAons of 8 m3 inhalaAon/shiJ and 55 kg bodyweight were used to adjust the value from mg/kg-‐d to mg/m3. The resulAng interim OEL for meth was 0.23 mg/m3 (230 μg/m3).
Discussion & Conclusions • The need to idenAfy the most appropriate OEL for a compound when a range of values exists presents a challenge for the IH pracAAoner; however, applicaAon of a systemaAc framework is helpful in guiding the selecAon process. • The proposed framework is sufficiently flexible to support risk management decisions by an IH in both OEL-‐rich and -‐poor situaAons. • Most OEL-‐deriving organizaAons did not publish details on the risk science and risk policy decisions behind the calculaAon of values, complicaAng the selecAon process. • To help IHs in their applicaAon of OELs, increased transparency by most OEL-‐deriving organizaAons is highly recommended. • Future work related to this project will involve the development and publicaAon of: • more detailed guidance for IHs on adjusAng exisAng OELs; and • guides on available OELs and alternaAve exposure benchmarks.
References 1. 2. 3. 4. 5. 6. 7. 8. 9. 10.
NO RELEVANT VALUE AVAILABLE However, because no other exposure guidelines were available for meth, the CalEPA RfD was adjusted to derive an interim OEL that beler fits the exposure palern and populaAon of the defined scenario 0.08 mg/kg-d 24h 7d 55 kg = 0.23 mg/m 3 × × ×
• UF of 3 for absence of data in toddlers was removed because this populaAon was not relevant. • UF of 10 for interindividual variability was reduced to √10 (i.e. 3) to reflect less variability among healthy workers • UF of 10 for use of a LOAEL was reduced to √10 (i.e. 3) due to dose–response palerns
Basis Neurotoxic effects and narcosis, as well eye & mucous membrane irritaAon. LOAELs of 500 ppm in humans and 250 ppm in animals. UFs were not explicitly stated, but value of 50 if based on human data.
ACGIH TLV
Gather OELs
CalEPA RfD: 0.3 μg/kg-‐d, based on a LOAEL of 0.08 mg/kg-‐d for decrease in bodyweight gain (as a proxy for neurological effects) in a controlled dosing study of pregnant women, and divided by a UF of 300. In the absence of more appropriate OELs, this RfD was adjusted for the scenario by: 1) Uncertainty factor adjustment – CalEPA UF of 300 was reduced to 10 because:
Figure 2. ApplicaAon of the OEL selecAon framework for hypotheAcal n-‐hexane exposures. TWA
Workers regularly remediaAng recently condemned methamphetamine (meth) labs
Figure 3. ApplicaAon of the OEL selecAon framework for hypotheAcal methamphetamine exposures.
Of the retained values, the SCOEL IOELV (20 ppm) was selected because: • The auto mechanic shop wanted to rely on most protecAve approach • The IOELV documentaAon idenAfied electrophysiological changes as low as 50 ppm; therefore, to allow for sufficient applicaAon of UFs, the value of 20 ppm was selected.
OEL
Define exposure scenario
ACGIH. (2001) DocumentaAon of the Threshold Limit Values and Biological Exposure Indices, 7th EdiAon: Hexane (n-‐Hexane). American Conference of Governmental Industrial Hygienists, CincinnaA. California Environmental ProtecAon Agency Office of Environmental Health Hazard Assessment. (2009) Development of a Reference Dose (RfD) for Methamphetamine. hlp://www.oehha.ca.gov/public_info/public/kids/pdf/MethRfDFinal022609.pdf DFG. (2000) MAK Value DocumentaAon for Hexane (n-‐Hexane).. In: The MAK CollecAon for OccupaAonal Health and Safety. hlp://onlinelibrary.wiley.com/book/10.1002/3527600418/topics?filter=MAKSmbe11054#MAKSmbe11054 EC. (1995) RecommendaAon from the ScienAfic Expert Group on OccupaAonal Exposure Limits for n-‐Hexane. hlp://ec.europa.eu/social/BlobServlet?docId=6795&langId=en GESTIS. (2014) InternaAonal Limit Values for Chemical Agents: OccupaAonal Exposure Limits: OccupaAonal Exposure Limits. hlp://www.dguv.de/ifa/Gefahrstoffdatenbanken/GESTIS-‐InternaAonale-‐Grenzwerte-‐f%C3%BCr-‐chemische-‐Substanzen-‐limit-‐values-‐for-‐chemical-‐agents/index-‐2.jsp Jakubowski M. (2006) Heksan: Dokumentacja dopuszczalnych wielkości narażenia zawodowego [Polish]. Podstawy i Metody Oceny Środowiska Pracy 21(1(47): 109–129. hlp://archiwum.ciop.pl/zasoby/Heksan.pdf Translated by Google Translate. Laszcz-‐Davis C., Maier A., and Perkins J. (2014) The Hierarchy of OELs: A New Organizing Principle for OccupaAonal Risk Assessment. The Synergist, March 2014, p. 26–30. hlp://www.aihasynergist-‐digital.org/aihasynergist/201403#pg31 Maier A., Sussman R., Naumann B., and Roy R. (2012) Characterizing the Impacts of Uncertainty and ScienAfic Judgment in Exposure Limit Development. Poster presented at AIHce 2012. hlp://www.tera.org/OARS/posters/OEL%20Uncertainty%20Poster%20-‐%2011%20x17%20Final.pdf NIOSH. (2011) CDC–NIOSH 1988 OSHA PEL Project DocumentaAon: List by Chemical Name: n-‐HEXANE. hlp://www.cdc.gov/niosh/pel88/110-‐54.html OSHA. (2012) Chemical Sampling InformaAon: Hexane (n-‐Hexane). hlps://www.osha.gov/dts/chemicalsampling/data/CH_245400.html
