GlobalChem 2013: A robust approach to risk assessment

22 February 2013 10:28  [Source: ICB]

Chemical risk assessment is undergoing tremendous change at present. The availability of chemical hazard data is growing exponentially as various regulatory regimes - such as those in Canada and the EU, as well as the US - publish more information; meanwhile, the science of exposure assessment is also evolving rapidly.

test tubes Rex Features

 Rex Features

Coupled with these developments in traditional risk assessment, new thinking is emerging on several fronts. Alternative approaches are being developed to investigate the properties of substances at the cellular level, with the goal of using knowledge of biological pathways to reduce, or at some point avoid altogether, the use of laboratory animals. Scientists are seeking to understand the mechanisms through which substances produce effects on human health and the environment - their "mode of action".

Both the American Chemistry Council (ACC) and Society of Chemical Manufacturers & Affiliates (SOCMA) help members understand the current challenges and coordinate industry responses to specific initiatives.

Looking at traditional approaches to risk assessment, ACC's senior director for health and products, Dr Rick Becker, notes that the US Environmental Protection Agency (EPA) is currently taking "a hard look" at the Integrated Risk Information System (IRIS) programme, which provides human health assessments to support decision-making at the agency. It is looking for ways to improve how risk assessments are done following a peer review by the National Academy of Sciences (NAS) of the agency's draft IRIS report for formaldehyde, which was released in April 2011. This provided a detailed set of recommendations for improving the assessments and the IRIS programme overall.

Becker says: "We and others have made the point for years that the scientific approaches and methods of IRIS clearly were lagging behind the current understanding of chemical hazard modes of action and risks at environmentally relevant levels of exposure. When the NAS peer review came out on the draft formaldehyde IRIS risk assessment it made some strong recommendations, with a whole chapter devoted to a roadmap to improve IRIS."

ACC's Dr Nancy Beck says: "While the IRIS programme was initially slow to act, we have recently seen an improvement in process which coincides with Dr Ken Olden taking the helm of NCEA, the organisation in EPA that contains the IRIS programme." In the past, stakeholder involvement has been minimal. Now, she says, the agency has released its first draft planning and scoping document, and has held a stakeholder workshop to discuss issues that might inform an assessment before it starts.

"It is much more open and participatory than we have previously seen from the IRIS programme," she says. The first assessment seeing these changes is that for inorganic arsenic. However, Becker says there are still improvements to be made. ACC has provided EPA, at public comment sessions and professional society meetings, with its recommendations for improvements in project design and scoping and data acquisition. These include more open discussion on the key issues, the data that needs to be assessed, the key questions and methods.


Particularly important are the methods of evaluation used to answer the key questions of concern, he says. "By spending more time upfront designing the assessment correctly, it will be more efficient and effective and will better inform the risk management decision that needs to be made. That investment upfront will cut down on the time at the back-end to fix something that started out the wrong way," he adds.

Looking forward, ACC wants more standard and consistent data evaluation procedures - and this is echoed in the NAS recommendations. In addition, Becker asserts, "There is a real need for the EPA to improve the way it does study integration or weight-of-evidence evaluation. At its core, weight of evidence is about integrating across lines of evidence - human epidemiological data, lab animal toxicological studies and mechanistic information - to reach causal conclusions."

Tucker Helmes

"We are encouraged by efforts to make the IRIS proces more robust and transparent"

Dr.Tucker Helmes
Managing director, Association Management Services, SOCMA

For its contribution to the debate, ACC's Center for Advancing Risk Assessment Science and Policy commissioned a White Paper that evaluated 50 different frameworks on weight of evidence published in the scientific literature and then hosted a workshop on its work early in December where the paper was discussed with scientists from academia, industry, the EPA and NGOs. The best practice recommendations for conducting weight-of-evidence evaluations flowing from the White Paper and workshop will be submitted for publication in a scientific journal in the coming weeks.

"With chemical risk assessment, we now know more than ever before about specific chemical modes of action and how they produce different effects in cells and organisms. Mode of action has to be central in the weight of evidence risk assessment determination: that is an important recommendation," says Becker. He notes that the science is still evolving, and methods to evaluate modes of action and the relationship between dose responses and certain threshold values needs further work. Nevertheless, Becker states, "It's clear that there's a pressing need to adopt best practices and placing mode of action as a focal point in weight of evidence evaluations to ensure the best available science is used in risk assessments."

While SOCMA is not engaged in the review of the IRIS process, one of its affiliate groups has submitted data to the IRIS review of biphenyl to clarify its view on the substances' mechanism of action. Dr Tucker Helmes, managing director of Association Management Services at SOCMA, says: "We are encouraged by efforts to make the IRIS process more robust and transparent."

The current focus is on improving IRIS, but the same principles apply elsewhere, says Becker; for example, for the National Toxicology Program Report on Carcinogens (ROC) and other chemical hazard and risk evaluations, such as the workplan risk assessments - which cover substances identified by EPA as posing potential risks to consumers. "Our approach is to be constructively engaged, not to just criticise but also to bring forward suggestions and practical approaches," he adds.


Beck says ACC is currently looking at the first five EPA TSCA workplan chemical assessments, which were released early in January. Unlike IRIS, the assessments examine hazards and exposure to determine whether a chemical is safe for an intended use. "These assessments could be viewed as precedent setting. The process is something we really support," she says.

"But we are now looking at how the agency selects information and the use scenario. For example, they have looked at dermal exposure and assumed the consumer does not wear gloves - but why choose that scenario if the material safety data sheet and the current standard practice is to wear gloves?

"If this was a screening level assessment to eliminate things that are not of concern, it might be appropriate, but it is not clear from what EPA put out what kind of refinement, if any, it is planning to do before moving towards decision-making," she says.

SOCMA's senior manager for government relations, Dan Newton, adds: "We are interested in how the EPA targets chemicals for risk assessment; we are interested in the process and we are going to track what EPA does. It is important for our members as it is precedent-setting and could impact the way chemicals are treated in the future."

Another interesting development with the workplan assessments is the use by the EPA of data produced in the EU as well as other organisations, particularly in planning and scoping its work. "This really makes sense," says Beck. "There was a time when the EPA did not acknowledge such information was available."

On the relationship between risk assessment science and policy, Becker says: "If you improve the quality, transparency and objectivity of assessments, and do a better job of fully characterising risks - not just the upper boundaries or the worst case, but by providing a better understanding of overall distribution of risk across the general population - then you are providing better information for risk managers."

SOCMA's Helmes says: "In general, all companies embrace the concept of introducing better science into the whole process, and they support using risk assessment as opposed to hazard evaluation for regulatory decisions and setting priorities. I think a lot of the good science is available from industry."

Looking to the future, ACC's Becker says a lot of progress has been made in the area of 21st-century toxicology - including the use of in vitro tests, high-throughput assays and in silico computer-driven screening methods. "We are not at the stage where we can use those methods to replace the current approaches we use to evaluate chemicals safety," he says.

"We need confidence the approaches are scientifically valid." A binding assay may suggest some activity, but the relationship between that assay and the potency and exposure and effects in an organism need to be understood. He also says it is important to consider how toxicology questions are framed so that evaluation strategies - integrated testing and assessment - can be designed and implanted so that the outputs are more useful.

SOCMA's Helmes adds that predictive toxicology tools will be useful for priority setting or hazard evaluation, but says this will vary from chemical class to chemical class. "Some classes - because of their structure - lend themselves to this sort of predictive toxicology, whereas others would not at all," he adds.

By: Emma Chynoweth
+44 20 8652 3214

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