Trends and Developments in the Future Use of OELs

Slides:



Advertisements
Similar presentations
Eduardo J Salazar-Vega, MPH CPH Jan Koehn, MS CIH.
Advertisements

Session III: Assessing Cumulative Effects of Endocrine Active Substances 9:15 - 9:30 Introduction” Rick Becker (Session Chair and Panel Moderator) 9:30.
Regulatory Toxicology James Swenberg, D.V.M., Ph.D.
Carcinogen Classification Criteria Patricia Richter Ph.D., DABT Tobacco Products Scientific Advisory Committee June 8, 2010.
Guidelines for Carcinogen Risk Assessment and Supplemental Guidance for Assessing Cancer Risks from Early-Life Exposures March 29, 2005 Hugh A. Barton,
Fundamentals of Industrial Hygiene 6th Edition
CE 510 Hazardous Waste Engineering
1 Development & Evaluation of Ecotoxicity Predictive Tools EPA Development Team Regional Stakeholder Meetings January 11-22, 2010.
Elizabeth L. Pullen, CIH APOSHO 26 & Australasian
William H. Farland, Ph.D. Acting Deputy Assistant Administrator for Science Office of Research and Development U.S. ENVIRONMENTAL PROTECTION AGENCY Biomarkers:
It Takes a Village to Raise a Child Roberta L. Grant, Ph.D. Toxicology Section - Chief Engineer’s Office Texas Commission on Environmental Quality.
NSF/ANSI STANDARD 61 FRAMEWORK FOR RISK ASSESSMENTS For use by Toxicology Sub-committee only Please do not copy or distribute.
Introduction to the State-Level Mitigation 20/20 TM Software for Management of State-Level Hazard Mitigation Planning and Programming A software program.
Sources of Uncertainty and Current Practice for Addressing Them: Toxicological Perspective David A. Bussard U.S. Environmental Protection Agency The views.
What Do Toxicologists Do?
1 REACh Registration, Evaluation and Authorization of Chemicals and Restriction! Ohio Valley SOT Wednesday, August 26, 2009 REACh: The New Toxicology Frontier.
Risk Assessment: A Conceptual Introduction
FAO/WHO CODEX TRAINING PACKAGE
Codex Guidelines for the Application of HACCP
Toxicity Evaluation of Chemicals with Limited Toxicity Data Roberta L. Grant, Ph.D. Toxicology Division - Chief Engineer’s Office Texas Commission on Environmental.
TCEQ/NUATRC Air Toxics Workshop: Session V – Human Health Effects Nathan Pechacek, M.S. Toxicology Section Texas Commission on Environmental Quality
Environmental Risk Analysis
Lynn H. Pottenger, PhD, DABT The Dow Chemical Company
Committee on Carcinogenicity (COC) Approach to Risk Assessment of Genotoxic Carcinogens David H. Phillips* COC Chairman Descriptive vs. Quantitative.
Basics of OHSAS Occupational Health & Safety Management System
CE Introduction to Environmental Engineering and Science Readings for This Class: Chapter 4 O hio N orthern U niversity Introduction Chemistry,
Dr. Manfred Wentz Director, Hohenstein Institutes (USA) Head, Oeko-Tex Certification Body (USA) AAFA – Environmental Committee Meeting November 10, 2008.
SCHC, 9/27/2005 US Implementation of the Globally Harmonized System The GHS Journey Continues…
HERA at CED XXXI C.Lally 1 Human & Environmental Risk Assessment Human Health Risk Assessment under HERA: Challenges and Solutions Christeine Lally Co-Chair.
1 Issues in Assessment in Higher Education: Science Higher Education Forum on Scientific Competencies Medellin-Colombia Nov 2-4, 2005 Dr Hans Wagemaker.
Evidence-Based Public Health Nancy Allee, MLS, MPH University of Michigan November 6, 2004.
Forging Partnerships on Emerging Contaminants November 2, 2005 John Vandenberg Associate Director for Health National Center for Environmental Assessment.
OELs vs. DNELS – Why Are They (Not) the Same?
Beyond and Decisions: From Problem Formulation to Dose- Response.
Module 3 Risk Analysis and its Components. Risk Analysis ● WTO SPS agreement puts emphasis on sound science ● Risk analysis = integrated mechanism to.
Quantitative Assessment of Cumulative Impacts: Challenges and Progress Lauren Zeise Cal/EPA Office of Environmental Health Hazard Assessment CAPCOA Workshop:
Prof. Dr. Wolfgang Dekant Department of Toxicology University of Würzburg Germany Risk, Hazard, and Innovation.
Screen 1 of 20 Vulnerability Vulnerability Assessment LEARNING OBJECTIVES Define the purpose and scope of vulnerability assessment. Understand how vulnerability.
Chapter 2 Using Science to Address Environmental Problems.
McKim Conference on Predictive Toxicology
Air Toxics Risk Assessment: Traditional versus New Approaches Mark Saperstein BP Product Stewardship Group.
George M. Woodall, PhD NCEA Toxicologist Leland Urban Air Toxics Research Center October 18, 2005 EPA Reference Values: Regulatory Context.
An Overview of the Objectives, Approach, and Components of ComET™ Mr. Paul Price The LifeLine Group All slides and material Copyright protected.
International Atomic Energy Agency Regulatory Review of Safety Cases for Radioactive Waste Disposal Facilities David G Bennett 7 April 2014.
Prioritization Process and Development of the Hazard Characterization Documents Office of Pollution Prevention and Toxics U.S. Environmental Protection.
NUATRC/TCEQ Air Toxics Workshop October Air Toxics Air Toxics: What We Know, What we Don’t Know, and What We Need to Know Human Health Effects –
Berkeley Lab Exposure Assessment: thoughts after an ISM Audit Tim Roberts, Industrial Hygiene Jim Floyd, ALS LBNL.
RISK DUE TO AIR POLLUTANTS
Perspective on the current state-of-knowledge of mode of action as it relates to the dose response assessment of cancer and noncancer toxicity Jennifer.
Office of Research and Development National Center for Environmental Assessment Human Health Risk Assessment and Information for SRP July 28, 2009 Reeder.
Abstract A step-wise or ‘tiered’ approach has been used as a rational procedure to conduct environmental risk assessments in many disciplines. The Technical.
Volker J. Soballa Evonik Degussa GmbH Essen, Germany
Acute Toxicity Studies Single dose - rat, mouse (5/sex/dose), dog, monkey (1/sex/dose) 14 day observation In-life observations (body wt., food consumption,
Considerations for Developing Alternative Health Risk Assessment Approaches for Addressing Multiple Chemicals, Exposures and Effects External Review Draft.
Lowell Randel Global Cold Chain Alliance/ International Institute of Ammonia Refrigeration.
1 Risk Assessment for Air Toxics: The 4 Basic Steps NESCAUM Health Effects Workshop Bordentown, NJ July 30, 2008.
MEASUREMENT OF TOXICITY By, Dr. M. David Department of Zoology, Karnatak University Dharwad.
1 Beyond Science and Decisions: From Problem Formulation to Dose-Response - Framework.
DATA COLLECTION METHODS IN NURSING RESEARCH
FIFRA SAP Meeting February 2, 2010
Evaluating Cumulative Impacts: The Value of Epidemiology
Fundamentals of Industrial Hygiene 6th Edition
General Concepts in QSAR for Using the QSAR Application Toolbox
Decision Contexts in a Changing Toxicology Paradigm
European Commission, DG Environment Air & Industrial Emissions Unit
Evaluating Cumulative Impacts: The Value of Epidemiology
TOXICOLOGY.
EFSA’s Chemical Hazards Database
Introduction to Risk Assessment
VICH GL 54, Studies to evaluate the safety of residues of veterinary drugs in human food: General approach to establish an Acute Reference Dose (ARfD)
Presentation transcript:

Trends and Developments in the Future Use of OELs Dr. Andrew Maier

Learning Objectives Harmonization concept as a tool for putting the confusing landscape of occupational risk assessment guidance into perspective. The concept of problem formation and use of tiered risk assessment: clarifying how OELs and DNELs, and other metrics, serve their own purposes. Other opportunities on the horizon for OEL Setting.

Harmonization of Occupational Exposure Guidelines

Exposure Guideline Disharmony? n-Hexane Exposure Guidelines Type of Limit Value (ppm) Agency DNEL – Derived No Effect Level 4.7 REACH – European Union IOELV - Indicative Occupational Exposure Limit Values 20 SCOEL – European Union TLV® – Threshold Limit Value 50 ACGIH – American Conference of Governmental Industrial Hygienists AEGL2 – Acute Exposure Guideline Level (2) 4800 (10-min) 3300 (30-min to 8-hr) NRC – National Research Council IDLH – Immediately Dangerous to Life and Health 1,100 NIOSH – National Institute for Occupational Health and Safety RFC – Inhalation Reference Concentration 0.2 U.S. EPA – Environmental Protection Agency

What is Harmonization? Harmonization is not standardization. Understanding the methods and practices used by various organizations. Developing confidence in and acceptance of assessments using different approaches. Willingness to work toward a convergence of methodologies as long-term goal. Harmonization does not imply moving away from weight of evidence or diminish role of expert judgment by a group of peer experts. It does, however, provide a framework to guide the evaluation of data.

Need for Harmonization OELs and other guidance may exist for the same chemical often vary considerably among organizations. Few organizations have written methodology documents. Most of these do not provide detailed guidance on OEL- setting that addresses key science in a definitive way. Continued efforts are needed to provide such guidance, building on basic biology and risk science – this will allow for harmonization of OEL approaches.

http://www.who.int/ipcs/methods/harmonization/en/

Key Points on Harmonization OELs play a critical role in occupational health. Methods and resulting OELs and other Occupational Exposure Guidelines differ among agencies. There is growing emphasis on harmonization of methods. Shared information facilitates harmonization. Numerous sources of information are available, but no unified source of aggregated OEL information has been compiled. Decision guides assist to sort through the confusing landscape of guidance.

Types of Exposure Guidance There are many sources and types of exposure limit information that can be applied to different scenarios: Purpose of assessment Priority setting, Registration, Worker exposure assessment? Exposure duration Acute versus chronic? Exposure population Responders, workers, general population? Exposure frequency Routine or infrequent? How do you find these and select one for your scenario? .

Why Does the IH Need to Know? Increased duties outside of routine operation: Growing role in product stewardship support, Increased role in evaluating off-site community exposures or releases for emergency response, Greater roles in assessing releases that affect the general population. Understanding basis of other values – allows for better judgments in: Interpreting results for an existing value, Current value seems reasonable compared to array of existing values? Filling gaps when an existing value is not available or may be out-dated. IH professionals will apply a wide range of exposure guides for diverse scenarios

Selecting Among Resources How to decide which value among many? Mandated regulatory hierarchy in-place? Other considerations to weigh in decision: Relevance of the guide value to the scenario or use of interest, The degree to which the exposure guidance includes current literature and methods, Confidence in the value, Screening vs. full assessment Robustness of limit setting process (e.g., authoritative agency, peer review, etc.).

Availability of relevant exposure guidelines Are exposure guidelines reliable? No Define Use or Scenario Are exposure guidelines available for the use of the assessment? Are exposure guidelines available for the population, time pattern , and exposure route of Interest? NOT VERIFIED Risk management considerations Communication basis considerations Yes Is the value reliable? Apply Selection/ Ranking Criteria Does the value reflect current science? Is there confidence in the value (peer reviewed)? Provisional exposure guideline verified? Use selected value No Reliable Value Available Derive value Adopt value modified from alternative scenario Evaluate Relevance of New Value

The Continuum of Occupational Exposure Guidelines

Progressions in Occupational Risk Assessment Normal progression in risk assessment is from reliance on qualitative hazard-based approaches to quantitative risk-based assessments as data increases. Hazard approach, Advantage: rapid assessment allows for action to be taken quickly to address most likely health concerns, Disadvantage: absence of an objective measure of likelihood for health concern can lead to: 1) inadequate protection, 2) less confidence in the assessment, 3) difficulty in communicating risks. The preferred IH practice is to use hazard-based approaches as an interim procedure until an OEL can be developed.

Fig. 1. A conceptual representation of the framework M.E. (Bette) Meek, Boobis AR, Crofton KM, Heinemeyer G, Van Raaij M, Vickers C. 2011. Risk assessment of combined exposure to multiple chemicals: A WHO/IPCS framework. Regul Toxicol Pharmacol. In press.

AGF “Hoppering Process”

Guidance for Data-Poor Chemicals Threshold of Toxicological Concern, Statistical correlations with acute or longer-term effects, In Silico and Quantitative Structure Activity Relationships (QSAR) – read across, Hazard Banding Algorithms, Default calculation schemes – e.g., DNEL approach.

Correlation Approaches No toxicology data, some physicochemical property (P) or relative potency data OELa = (Pa/Pb) x OELb Irritancy Acidity (pKa) for organic acids RD50 values Lethality Acute Lethality (LD50 and LC50) Systemic Toxicity Subchronic NOAELs or LOAELs

Hazard Banding Array existing data for a series of key end points. Establish criteria for categorizing each end point. Typically assign hazard band based on worst of the identified hazard categories. Preliminary OEL ranges often associated with each hazard band. Many systems exist, but there are moves toward harmonizing criteria, including validation exercises.

Other Approaches Toxicity Prediction Default algorithms Use chemical and physical property to predict potency with software. Read across - use data for a related chemical as a surrogate. Default algorithms e.g., DNEL approach

Future Developments in OEL Setting

Drivers for Change Science Drivers Regulatory Drivers Improved understanding of molecular toxicology. Incorporation of biomathematics with improved computing resources. Regulatory Drivers Focus on MOA Frameworks. EU Driven initiatives (e.g., REACH: DNEL, AAT). Assessment focus on aggregate and cumulative exposure – nontraditional exposures.

Risk Assessment Directives Better integration of dose-response methods across endpoints – use growing biology knowledge. Increased use of problem formulation – Use the right risk tool for the job. Consider cumulative exposure and risk – think exposome. NRC (National Research Council). 2009. Science AND Decisions: Advancing Risk Assessment. Board on Environmental Studies and Toxicology. National Academy Press, Washington, DC.

Area of Change – Mode of Action (MOA) Frameworks Overview of Risk Assessment Area of Change – Mode of Action (MOA) Frameworks MOA is not a detailed Molecular Description Identification of the sequence of key events and processes resulting in an adverse effect Use of our biology understanding via MOA is becoming more formalized as part of risk assessment IPCS (International Programme on Chemical Safety). 2008. IPCS Mode of Action Framework. IPCS Harmonization Project Document, No. 4. World Health Organization Press. TERA’s Dose-Response Assessment Boot Camp

Hypothesized Mode of Action for Tumor Response Metabolite Cell Damage & Proliferation T U M O R S DOSE Threshold Key events dose-response framework Key Event Kidney Tumors Nonlinearity / Threshold

Example of Calculation of a Benchmark Concentration Overview of Risk Assessment Example of Calculation of a Benchmark Concentration 0.2 0.4 0.6 0.8 1 50 100 % animals responding NOAEL BMDL BMD 150 200 Exposure Concentration ppm TERA’s Dose-Response Assessment Boot Camp

Area of Change – Cumulative Risk We are clearly moving to more systematic evaluation of “real-life” exposures. Multiple routes of exposure Mixtures of chemicals Total exposure (occupational plus non- occupational) Combined effects of chemicals plus non-chemical stresses We need “OELs” to address these new perspectives.

Definitions Aggregate exposure = one chemical, multiple routes Risk Characterization Definitions Aggregate exposure = one chemical, multiple routes Mixture = exposure to more than one chemical Cumulative risk = exposure to single or multiple chemicals and nonchemical stressors by all routes TERA’s Dose-Response Assessment Boot Camp

Exposome As a complementary approach to the genome, the exposome can be defined as: The totality of exposures over a lifetime, which predispose and predict health effects in an individual. Begins in utero, Encompasses environmental (including occupational) sources of injuries, irritations, and other stressors including lifestyle and diet, Dependent upon characteristics of the person.

Risk Characterisaton Step ECETOC (European Centre for Ecotoxicology and Toxicology of Chemicals). 2010. Guidance on Assessment Factors to Derive a DNEL. ECETOC TR No. 110.

EPA’s Pesticide Approach Identify Common Mechanism Group (CMG); Identify Potential Exposures; Characterize and Select Common Mechanism Endpoint(s); Determine The Need For a Dosimetry-Based Cumulative Risk Assessment; Determine Candidate Cumulative Assessment Group Conduct Dose- Response Analyses and Determine Relative Potency and Points of Departure; Develop Detailed Exposure Scenarios All Routes and Durations; Establish Exposure Input Parameters; Conduct Final Cumulative Risk Assessment; Conduct Characterization of Cumulative Risk. 2nd 5 steps can be dosimetry-based Common Mechanisms Group: The group of chemicals under evaluation that induce a common effect via the same mechanism of toxicity. The Initial Analysis begins with the identification of this group of chemicals For example – all OPs fall into the same CMG. But – not all OPs contribute meaningfully to the total OP risk. e.g. – some are being phased out or have negligible exposure. Cumulative Assessment Group: The group of chemicals surviving the Initial Analysis, for which a dosimetry-based cumulative Risk Assessment will be conducted. From the dosimetry-based guidance: If Chemical Q is omitted from the CMG due to lack of Effect X, the CRA will not properly characterize the cumulative risk for Chemicals A, B, C when Chemical Q is also present. For this reason, all chemicals that share common types of PK or PD interactions with biological targets should be considered as members of the CMG. This represents a specific extension of the process, as recommended by the available (OPP) guidance to address commonalities beyond those related to toxic manifestation: those pertaining to tissue doses of toxicologically active chemical species (metabolites). While OPP’s guidance defines the CMG based only on toxicodynamic events in the mechanism of action itself, The CMG is here defined differently. U.S. EPA. 2002. Guidance on Cumulative Risk Assessment of Pesticide Chemicals That Have a Common Mechanism of Toxicity. Office of Pesticide Programs. Washington, DC.

Conclusion This is a time of active change in occupational risk methods. OELs remain the most robust tool available and are here to stay – but IHs need to understand role other tools and metrics too. There are a variety of science, policy, and regulatory drivers for these changes: More robust OEL methods, Increased availability of OEL alternatives, More formal evaluation of multi-route and mixed exposures.

Final Thoughts The current landscape of approaches is confusing – e.g., OELs vs. DNELs. IHs will be seeing more DNELs as well other types of OEL guidance. Need to know how they are calculated and there intended purposes. OELs, DNELS and other types of guidance will need to coexist – but health-based remain a critical tool for worker protection.