02485nas a2200289   4500000000100000000000100001008004100002260000900043653003200052653001200084653001100096653002000107653001600127653002900143653003100172653003000203653002200233653001600255100002300271700001600294700001800310245010600328300001200434490000700446520172800453022001402181       2022                            d  c202210aAnimal Testing Alternatives10aAnimals10aHumans10aRisk Assessment10aUncertainty10achemical risk assessment10aevidence-based methodology10aevidence-based toxicology10aSystematic review10aUncertainty1 aSebastian Hoffmann1 aPaul Whaley1 aKatya Tsaioun00aHow evidence-based methodologies can help identify and reduce uncertainty in chemical risk assessment  a175-1820 v393 aEvidence-based methodology, in particular systematic review, is increasingly being applied in environmental, public, and occupational health to increase the transparency, comprehensiveness, and objectivity of the processes by which existing evidence is gathered, assessed, and synthesized in answering research questions. This development is also changing risk assessment practices and will impact the assessment of uncertainties in the evidence for risks to human health that are posed by exposure to chemicals. The potential of evidence-based methodology for characterizing uncertainties in risk assessment has been widely recognized, while its contribution to uncertainty reduction is yet to be fully elucidated. We therefore present some key aspects of the evidence-based approach to risk assessment, showing how they can contribute to the identification and the assessment of uncertainties. We focus on the pre-specification of an assessment method­ology in a protocol, comprehensive search strategies, study selection using predefined eligibility criteria, critical appraisal of individual studies, and an evidence integration and uncertainty characterization process based on certainty of evi­dence frameworks that are well-established in health care research. We also provide examples of uncertainty in risk assessment and discuss how evidence-based methodology could address those. This perspective, which neither claims to be comprehensive nor complete, is intended to stimulate discussion of the topic and to motivate detailed exploration of how evidence-based methodology contributes to characterization of uncertainties, and how it will lead to uncertainty reduction in the conduct of health risk assessment.  a1868-8551