From risk assessment to decisions in the EU and the US

From risk assessment to decisions in the EU and the US is a page where two timely policy processes related to risk assessment have been described. These are the REACH (registration, evaluation, and authorisation of chemicals) in the EU, and the Risk Assessment Bulletin by the Office of Management and Budget in the US. Both are about to reach the final decision stage in the near future (fall 2006), and both have raised controversial opinions and public interest.

This page has been prepared for the course Introduction to environmental risk analysis, in the University of Kuopio, 11-15 September, 2006

REACH

REACH in brief

Objectives in White Paper on the Strategy for a Future Chemicals Policy, published in February 2001 (COM (2001) 88):

• Protection of human health and the environment
• Maintenance and enhancement of the competitiveness of the EU chemical industry
• Prevention of fragmentation of the internal market
• Increased transparency
• Integration with international efforts
• Promotion of non-animal testing
• Conformity with EU international obligations under the WTO.

The estimated cost of compliance is 2.3 billion euros over 11 years. However, there have been different studies on the estimated cost which vary considerably in the outcome.

Timeline

It has already been significantly amended since the original version initiated by the en:European Commission in 2003. It passed the first reading in the en:European Parliament on 2005-11-17, and the en:Council of Ministers approved it on 2005-12-13 [1].

• The Proposal was communicated to the European Parliament and the Council in November 2003. During the first reading, 10 parliamentary committees tabled amendments.
• The European Parliament adopted its first reading opinion in its plenary session on 17 November 2005.
• The Council reached a political agreement on a Common Position in the Competitiveness Council of 13 December 2005 under the UK Presidency.
• The formal Common Position of the Council was approved under the Austrian Presidency on 27 June 2006.
• The Finnish Presidency formally submitted this position to the European Parliament in July which intends to formally accept it in the first plenary session of September, hereby formally starting the second reading of the proposal.
• The Commission adopted a Communication on the Common Position on 12 July, in which it expressed its full support for the Common Position.
• Final adoption of the proposal is thus expected by the end of 2006 under the Finnish Presidency.
• REACH would then come into force by spring 2007.
• The European Chemicals Agency becomes operational one year later.

Basic elements of REACH

Its basic elements are described below as they are set out in the Council’s Common Position:

1. All substances are covered by this regulation unless they are explicitly exempted from its scope.
2. Registration requires manufacturers and importers of chemicals to obtain relevant information on their substances and to use that data to manage them safely.
3. To reduce testing on vertebrate animals, data sharing is required for studies on such animals. For other tests, data sharing is required on request.
4. Better information on hazards and risks and how to manage them will be passed down and up the supply chain.
5. Downstream users are brought into the system.
6. Evaluation is undertaken by the Agency to evaluate testing proposals made by industry or to check compliance with the registration requirements. The Agency will also co-ordinate substance evaluation by the authorities to investigate chemicals with perceived risks. This assessment may be used later to prepare proposals for restrictions or authorisation.
7. Substances with properties of very high concern will be made subject to authorisation; the Agency will publish a list containing such candidate substances. Applicants will have to demonstrate that risks associated with uses of these substances are adequately controlled or that the socio-economic benefits of their use outweigh the risks and there are no suitable alternative substitute substances or technologies.
8. The Restrictions provide a procedure to regulate that the manufacture, placing on the market or use of certain dangerous substances shall be either subject to conditions or prohibited. Thus, restrictions act as a safety net to manage Community wide risks that are otherwise not adequately controlled.
9. The European Chemicals Agency (ECHA) will manage the technical, scientific and administrative aspects of the REACH system at Community level, aiming to ensure that REACH functions well and has credibility with all stakeholders.
10. A classification and labelling inventory of dangerous substances will help promote agreement within industry on classification of a substance. For some substances of high concern there may be a Community wide harmonisation of classification by the authorities.
11. Access to information rules combine a system of publicly available information over the internet, the current system of requests for access to information and REACH specific rules on the protection of confidential business information.

REACH will create a single system for both what are currently described as “existing” and “new” substances; substances are now described as

• non-phase-in substances (i.e. those not produced or marketed prior to the entry into force of REACH)
• phase-in substances (those substances listed in the EINECS, or those that have been manufactured in the Community, but not placed on the Community market, in the last 15 years or the so-called “no longer polymers” of Directive 67/548).

The key player: manufacturer or importer of a substance.

Registration

Registration is required for each substance manufactured or imported in quantities of 1 tonne or above per year.

REACH requires all substances that are intended to be released from articles during normal and reasonably foreseeable conditions of use to be registered according to the normal rules, including tonnage deadlines and information requirements, if those substances are present in the articles above 1 tonne per year.

However, the Regulation exempts certain substances that are

• adequately regulated under other legislation, like medicinal products,
• generally present such low risks as not to require registration, like water, oxygen, certain noble gases, and cellulose pulp
• substances occurring in nature such as minerals, ores and ore concentrates, cement clinker etc are not required to be registered
  • as long as they are not chemically modified.
  • Polymers are exempted as well from the requirement to register, since they usually are not very hazardous,
  • but in certain circumstances monomers in polymers have to be registered.
• However, the registration of polymers may be reviewed later.

General rules are also set out for the use of existing information, techniques such as (Q)SARs ((Quantitative) Structure Activity Relationship) and read across, and for waiving of tests.

Definitions

• CMR = Carcinogenic, Mutagenic, Reproductive toxic
• PBT = Persistent, Bioaccumulative, Toxic
• vPvB = very persistent, very Bioaccumulative

Production 1-10 tonnes per year per producer

• All substances: a technical dossier
  • basic physicochemical information
  • any available (eco)toxiciological information
• Special substances: defined set of information (Annex VII)
  • PBT, vPvB
  • potentially dangerous to health or environment, and are used in a dispersive way

Production 10-100 tonnes per year per producer

• Same as above, and in addition
• a chemical safety report (CSR)
• information derived from the application of the relevant testing annexes (VII and VIII)
• relevant information the registrant has

Production 100-1000 tonnes per year per producer

• Same as above
• Annex IX

Production over 1000 tonnes per year per producer

• Same as above
• Annex X: proposals for testing for the purpose of registration
• The agency will check the necessity for and the quality

of the testing proposal to save animals’ lives and unnecessary costs.

The chemical safety report (CSR)

• documents the hazards and classification of a substance
• whether the substance is PBT or vPvB
• describes exposure scenarios for specific uses of substances that are classified as dangerous or are PBT or vPvB substances.
  • Exposure scenarios are sets of conditions that describe how substances are manufactured or used during their life-cycle
  • how the manufacturer or importer controls, or recommends to control, exposures of humans and the environment.
  • The exposure scenarios must include the appropriate risk management measures and operational conditions that, when properly implemented, ensure that the risks from the uses of the substance are adequately controlled.
  • Exposure scenarios need to be developed to cover all “identified uses” which are the manufacturers’ or importers’ own uses, and uses which are made known to the manufacturer or importer by his downstream users and which the manufacturer or importer includes in his assessment.
  • Relevant exposure scenarios will need to be annexed to the safety data sheets that will be supplied to downstream users and distributors.

Deadlines for REACH registration. CMRs and potential PBT/vPvBs are classified with N:R50-53. Source: European Commission, 2006.

Data sharing

• phase-in substances are required to pre-register them between 12 and 18 months after the entry into force of REACH.
• data gained by vertebrate animal testing are to be shared, in exchange for payment.
• Information not involving tests on vertebrate animals (e.g. in vitro studies and QSARs) must be shared on the request of a potential registrant.
• Registrants must agree on the generation of new test data in a Substance Information Exchange Forum.

Information in supply chain

• Information relating to health, safety and environmental properties, risks and risk management measures is required to be passed both down and up the supply chain.
• Commercially sensitive information is not required to be exchanged.
• Primary tool: safety data sheet (SDS) for all dangerous substances.
• Downstream users (DU) must check that their use(s) are "covered" by the SDS, i.e. that they use a substance within the conditions described in the exposure scenarios in the Annex to the SDS, and apply these conditions.
  • To get the relevant information, downstream users have the right to make their uses known to their suppliers.
  • A DU can also choose to keep his use confidential or decide to use a substance outside the conditions described in the exposure scenario(s) communicated to him. In these cases he will have to perform a chemical safety assessment (CSA) developing the exposure scenarios for his intended uses and, if necessary, a refinement of the supplier’s hazard assessment.

Evaluation

There are two types of evaluation with different aims:

• Dossier evaluation: the Agency will do a quality check of the registration dossiers:
  • Compliance check: the Agency may check the compliance of registration dossiers with the requirements laid down for registration in the Regulation. At least 5% of dossiers should be checked;
  • Checking of testing proposals: the aim here is to prevent unnecessary animal testing, i.e. the repetition of existing tests, and poor quality tests. Therefore, the Agency will check the testing proposals submitted as part of the registrations before such tests are performed;
• Substance evaluation: The Agency in co-ordination with the Competent Authorities of Member States may clarify suspicions of risks to human health or the environment by requesting further information from industry.

Authorisation

For substances of very high concern, an authorisation is required for their use and their placing on the market. The substances required to be authorised are substances which are:

• CMR category 1 and 2,
• PBT vPvBs, and
• identified from scientific evidence as causing probable serious effects to humans or the environment equivalent to those above on a case-by-case basis, such as endocrine disrupters. The European Commission will develop guidance to clarify the criteria for such a case-by case detection in close co-operation with in industry, Member States and other relevant stakeholders.

An authorisation will be granted if

• the applicant can demonstrate that the risk from the use of the substance is adequately controlled.
• It may also be granted if the socio-economic benefits outweigh the risks and there are no suitable alternative substances or processes.
• PBTs, vPvBs and those CMR substances for which a safe level cannot be defined, cannot be authorised based on adequate control of risk.

The European Chemical Agency (ECHA) in Helsinki will comprise the following elements:

• a Management Board,
• an Executive Director, reporting to the Management Board,
• a Committee on risk assessment and a Committee on socio-economic analysis
• a Member State Committee,
• a Forum for exchange of information on enforcement activities. This Forum integrates the

current informal network of Member States authorities into the Agency.

• a Secretariat that will provide technical, scientific and administrative support for the

Committees. It will also undertake a number of other tasks including under pre-registration, registration, evaluation and information provision.

• a Board of Appeal that will consider any appeals against the decisions of the Agency.

The ECHA will be located in Helsinki and is required to be operational 12 months after the entry into force of the REACH regulation.

Risk assessment bulletin

• Risk assessment bulletin of OMB As part of an ongoing effort to improve the quality, objectivity, utility, and integrity of information disseminated by the federal government to the public, the Office of Management and Budget (OMB), in consultation with the Office of Science and Technology Policy (OSTP), proposes to issue new technical guidance on risk assessments produced by the federal government.

Over twenty years after publication of the NAS report, there is general agreement that the risk assessment process can be improved. The process should be better understood, more transparent and more objective. Risk assessment can be most useful when those who rely on it to inform the risk management process understand its value, nature and limitations, and use it accordingly.

Uses of Risk Assessments

• Priority setting
  • Screening level
  • Full risk assessment
• Informing risk management decisions
• Informing the public and other audiences

Types of risk assessment

• Actuarial analysis of real-world human data. Often missing because
  • adequate data has not been collected
  • the adverse effects (e.g., certain types of leukemia) are too rare to analyze directly
• the exposures of concern are associated with a new technology or product, or
  • adverse effects may occur only after a long period (e.g., several decades) of exposure.
• Dose-response analysis using experimental data. Major problems:
  • Animal-to-human extrapolation
  • High-to-low dose extrapolation
• Infectious disease epidemic modeling. Scientific understanding of
  • biological mechanisms and
  • human behavior is needed.
• Failure analysis of physical structures
  • Fault-tree analysis and other probalistic methods

• The term “risk assessment” means a scientific and/or technical document that assembles and synthesizes scientific information to determine whether a potential hazard exists and/or the extent of possible risk to human health, safety, or the environment.
• The term “influential risk assessment” means a risk assessment the agency reasonably can determine will have or does have a clear and substantial impact on important public policies or private sector decisions. The term "influential" should be interpreted consistently with OMB's government-wide Information Quality Guidelines and the Information Quality Guidelines of the relevant agency.

Section I: Definitions:

This Bulletin applies to:

• Risk assessments
• Influential risk assessments
• documents that could be used for risk assessment purposes
  • such as an exposure or hazard assessment

• Documents that evaluate baseline risk as well as
• risk mitigation activities.

• Documents that can have a significant economic impact even if it is not part of a rulemaking.
  • For instance, the economic viability of a technology can be influenced by the government’s characterization of the risks associated with the use of the technology.
  • Alternatively, the federal government's assessment of risk can directly or indirectly influence the regulatory actions of state and local agencies or international bodies.

• Examples of “influential risk assessments” include, but are not limited to,
  • assessments that determine the level of risk regarding health, safety and environment.
    • reference doses
    • reference concentrations
    • minimal risk levels

• Documents that address some but not all aspects of risk assessment are covered by this Bulletin.
  • margin of exposure estimates
  • hazard determinations
  • EPA Integrated Risk Information System (IRIS) values
  • risk assessments which support EPA National Ambient Air Quality Standards
  • FDA tolerance values
  • ATSDR toxicological profiles
  • HHS/NTP substance profiles
  • NIOSH current intelligence bulletins and criteria documents
  • risk assessments performed as part of economically significant rulemakings.

Section II: Applicability

Section II states that, to the extent appropriate, all publicly available agency risk assessments shall comply with the standards of this Bulletin.

This Bulletin does not apply to

• risk assessments that arise in the course of individual agency adjudications or permit proceedings
• any risk assessment performed with respect to an individual product label, or any risk characterization appearing on any such label, if the individual product label is required by law to be approved by a Federal agency prior to use.
  • E.g. risk assessments performed for labeling of individual pharmaceutical products.

Section III: Goals

For each covered risk assessment, this Bulletin lays out five aspirational goals.

1. Goals Related to Problem Formulation:

• risk assessors should engage in an iterative dialogue with the agency decision makers

2. Goals Related to Completeness

• Balance between the desire for scientific completeness and the need to provide relevant information to decision makers.
  • Consider the benefits and cost of acquiring further information.

3. Goals Related to Effort Expended

• The level of effort should be commensurate with the importance of the risk assessment, taking into consideration the nature of the potential hazard, the available data, and the decision needs.

4. Goals Related to Resources Expended

• Agencies should take into account the importance of the risk assessment in gauging the resources.

5. Goals Related to Peer Review and Public Participation

• Agencies should consider appropriate procedures for peer review and public participation.
• A draft assessment: the agency is required to clarify that the report does not represent the official views of the federal government.

Section IV: General Risk Assessment and Reporting Standards

• OMB’s Information Quality Guidelines and the agency’s Information Quality Guidelines.
• Key attributes
  • utility
  • objectivity
  • integrity

1. Standards Relating to Informational Needs and Objectives

A risk assessment should clearly state the informational needs driving the assessment as well as the objectives of the assessment.

2. Standards Relating to Scope

Every risk assessment should clearly summarize the scope of the assessment.

1. Framing the scope:
   • the agent
   • technology and/or activity
   • the hazard of concern.
2. Address all of the factors within the intended scope of the assessment.
3. Identify the affected entities. If a risk assessment is to address only specific subpopulations, the scope should be very clear about this limitation.
   • populations
   • subpopulations
   • individuals
   • natural resources
   • animals
   • plants
   • other entities.
4. Define
   • the exposure or event scenarios
   • the type of event-consequence or dose-response relationship for the exposure
5. Search for completeness:
   • Analysis of different health effects and multiple target populations
   • Errors in human behavior in fault tree analyses
   • Causative role of other factors
   • Confounding and/or synergistic factors
   • However, will vary depending upon the nature of the assessment.

3. Standards Related to Characterization of Risk

Every risk assessment should provide a characterization of risk, qualitatively and, whenever possible, quantitatively.

• Expressing multiple estimates of risk
• Comprehensive, informative, and understandable presentation of information.
• Specify, to the extent practicable—
  1. each population addressed by any estimate [of applicable risk effects]
  2. the expected risk or central estimate of risk for the specific populations [affected]
  3. each appropriate upper-bound or lower-bound estimate of risk
  4. each significant uncertainty identified in the process of the assessment of [risk] effects and the studies that would assist in resolving the uncertainty
  5. peer-reviewed studies known to the [agency] that support, are directly relevant to, or fail to support any estimate of [risk] effects and the methodology used to reconcile inconsistencies in the scientific data.

4. Standards Related to Objectivity

• Risk assessments must be scientifically objective, neither minimizing nor exaggerating the nature and magnitude of the risks.
• Objectivity criteria:
  1. accurate,
  2. clear,
  3. complete,
  4. reliable,
  5. unbiased information.
• Weight should be given to both positive and negative studies.
• Sound statistical and research methods.
• The best available, peer-reviewed science and supporting studies conducted in accordance with sound and objective scientific practices
• Data collected by accepted methods or best available methods

5. Standards Related to Critical Assumptions

• Explain the basis of each critical assumption
• Discuss empirical data supporting or conflicting the assumption.
• Discuss the range of scientific opinions regarding the likelihood of plausible alternate assumptions.
• Whenever possible, a quantitative evaluation of reasonable alternative assumptions should be provided.
• If an assessment combines multiple assumptions, the basis and rationale for combining the assumptions should be clearly explained.

6. Standards Related to the Executive Summary

Every risk assessment should contain an executive summary which discloses the objectives and scope, the key findings of the assessment, and the key scientific limitations and uncertainties in the risk assessment.

7. Standards Related to Regulatory Analysis

For major rules involving annual economic effects of $1 billion or more, a formal quantitative analysis of the relevant uncertainties about benefits and costs is required.

1. Alternative options should be evaluated.
2. Comparison to baseline risk should be included.
3. Timing of exposure, effects, control measures, and reduction of risk should be explained.
4. When individual risks are presented, always population-level risks should also be developed.
5. Quantitative estimates should include a range of plausible estimates, including central estimate.

Section V: Special Standards for Influential Risk Assessments

• 1. Standard for Reproducibility
  • The assessment should be capable of being substantitally reproduced. Public access to original data is necessary.
• 2. Standard for Comparison to Other Results
  • An agency should find and examine previously conducted risk assessments on the same topic.
• 3. Standard for Presentation of Numerical Estimates
  • Range of plausible risk estimates, along with a central (i.e., expected) estimate should be given.
• 4. Standard for Characterizing Uncertainty
  • Uncertainty should be characterised with likelihood distribution.
  • Sensitivity analysis should be performed. Professional judgement is required to determine what range of assumptions is plausible enough.
  • Model uncertainty (nature and degree) needs to be documented. Expert weighting of models may be informative.
• 5. Standard for Characterizing Results
  • Describe how the selection of an effect or a study influences the assessment.
  • Evaluate and discuss alternative theories.
• 6. Standard for Characterizing Variability
• Reflect the different affected populations. Sufficiently describe the variability.
• 7. Standard for Characterizing Human Health Effects (applies to non-human effects as well)
  • Distinguish adverse and non-adverse effects. Concentration is not equal to harm.
  • Provide a graphical portrayal of different “safe levels” based on different effects observed in various experiments.
• 8. Standard for Discussing Scientific Limitations
  • Provide a discussion regarding the nature, difficulty, feasibility, cost and time associated with undertaking research to resolve a report’s key scientific limitations and uncertainties.
• 9. Standard for Addressing Significant Comments
  • Consider all of the significant comments received on a draft influential risk assessment report. Scientific comments shall be presumed to be significant.
  • Provide an explicit rationale if the agency has not adopted the position suggested.

Section VI: Updates

It is useful for assessments to disclose how fast the relevant database and assumptions are evolving and how likely it is that the database and assumptions will be significantly different within several months or years.

Section VII: Certification

For each risk assessment subject to this Bulletin, the agency shall include a certification, as part of the risk assessment document, explaining that the agency has complied with the requirements of this Bulletin and the applicable Information Quality Guidelines, except as provided in Section VIII.

Section VIII: Deferral and Waiver

The agency head may waive or defer some or all of the requirements of this Bulletin where warranted by compelling rationale (rare situation, e.g. assessment is time-sensitive or need to be released due to an emergency situation).

Interesting links

• Technical Guidance Document] in support of Commission Directive 93/67/EEC on Risk Assessment for new notified substances, Commission Regulation (EC) No 1488/94 on Risk Assessment for existing substances and Directive 98/8/EC of the European Parliament and of the Council concerning the placing of biocidal products on the market.
• Risk assessment bulletin of OMB As part of an ongoing effort to improve the quality, objectivity, utility, and integrity of information disseminated by the federal government to the public, the Office of Management and Budget (OMB), in consultation with the Office of Science and Technology Policy (OSTP), proposes to issue new technical guidance on risk assessments produced by the federal government.
• REACH A proposal on a new EU regulatory framework for Registration, Evaluation and Authorisation of CHemicals (REACH) was adopted 29 October 2003. REACH aims to improve the protection of human health and the environment while maintaining the competitiveness and enhancing the innovative capability of the EU chemicals industry. ECB has the responsibility of developing methodologies, tools and technical guidance needed for REACH through a number of REACH Implementation Projects (RIPs).

This is managed under Action no 1313 - Support to future chemicals legislation (REACH) or in short REACH Support. REACH in brief