Due to the rapid development in industries such as agriculture and transportation, the variety and quantity of environmental chemicals have been increasing dramatically, posing potential exposure threats to human health. To minimize the adverse effects of exposure to environmental chemicals, some countries and institutions have established relevant risk assessment guidelines as the foundation for environmental health risk management (Klimish et al. 1997, Tlucziewicz et al. 2013). Health risk assessment of environmental chemicals requires comprehensive collection, thorough analysis, and scientific evaluation of extensive research data. It is imperative to establish a systematic, transparent, and relatively consistent scientific research process to evaluate these diverse pieces of evidence and derive a comprehensive, scientific, and effective conclusion at the current stage.
The TRAEC strategy provides standardized procedures as guidelines for targeted risk assessment. Within the TRAEC framework, we first need to formulate scientific questions based on the research objectives. Secondly, researchers must conduct targeted evidence searches and gather new experimental evidence to find a wide range of available evidence sources, including in vitro, in vivo, and epidemiological studies. Additionally, as the most critical part of this strategy, we have developed a scoring scale and relevant calculation methods. This scale offers a quantitative assessment of study quality and reporting information, covering key quality aspects of different experimental methods. Ultimately, the health risks of target chemicals are classified into low, medium, or high levels, with quantifiable scores available as reference values for comparison.
The TRAEC strategy, through detailed and scientific operational guidelines, standardizes the main steps of risk assessment, thereby enhancing the controllability of execution. The literature retrieval and scoring processes are carried out by two independently trained researchers. Any conflicting content should be adjudicated by an expert panel to improve reproducibility and reliability. Researchers accurately assess specific outcomes of target chemicals through the workflow, needing only supplementary or targeted studies rather than researching all aspects of health risk, thereby effectively improving work efficiency, reducing research costs, decreasing animal sacrifice, and ultimately enhancing the scientific and comprehensive nature of the results. Overall, the TRAEC strategy provides an open framework for sustainable updates and optimizations, making full use of newly conducted and published evidence, comprehensively integrating various types of research data, and ultimately achieving quantitative descriptions and assessments of the health risks of target chemicals.
Step 1: Problem Formulation
Researchers can select target environmental chemical referring to their interest and experience, and determine a general range of health effects according to their respective research fields. If the assessment is conducted for application, this process can be skipped. A systematic literature search was conducted to find evidence of the health effects of the target chemical in the target range. Researchers are recommended to prepare a simple protocol first, incorporating a list of retrieval platforms (searching engines and public databases), key words, and inclusion/exclusion criteria. Both primary research and secondary research are acceptable.
A scientific question is formulated at the beginning of the risk assessment to guide the entire research process. For assessments with a specific research purpose, the target chemicals and health outcomes have already been determined. For those without a specific research purpose, a research question should be posed in which the target health outcome is the only undetermined component. Of all possible health effects, the mechanism of most interest to the investigator is selected as the target mechanism based on the study results.
Step 2: Evidence Collection
Risk assessment of environmental chemicals requires a comprehensive evaluation of available research evidence, including targeted evidence searches and the investigator's own experiments. Specific information on three aspects of epidemiological, in vivo and in vitro studies, is obtained by integrating data from different sources, such as databases, authorities, and researchers' laboratories.
① Epidemiological studies
Risk management is conducted for human health, and risk assessment is incomplete without data from human health studies. For epidemiological studies, the target population must first be identified. The investigator then needs to assess the exposure to the target chemical, such as information route of exposure, dose, etc.
In addition to this, baseline information on the study population such as personally identifiable information, lifestyle, disease history, treatment and fertility is included. This process of assessing exposure is optional and in some cases may also utilize retrospective survey methods such as completing standardized questionnaires online or by telephone. In addition, to identify and quantify adverse health effects in populations associated with the target chemical, researchers can investigate the incidence under the corresponding exposure through the literature, public databases. If not found, researchers conduct their studies to collect epidemiological data to assess dose-response/effect relationships in the population.
② In vitro studies
Researchers need to consult the literature to review the relevant results of published in vitro studies. In addition, for unarticulated mechanisms, researchers can conduct their own in vitro studies to validate and supplement the literature evidence, including molecular initiation events, cellular responses, or cellular phenotypes of target chemicals, etc
③ In vivo studies
Similar to the design of in vitro studies, for mechanisms that have not been elucidated by existing in vivo studies. Researchers can conduct experiments to validate and complement organ responses and the organism's response to exposure to target chemicals.
Step 3: Evidence scoring & conclusion
Risk assessment of environmental chemicals requires an integrated evaluation of existing research evidence, which ranges from epidemiological studies to in vivo and in vitro studies. For individual researchers, it remains elusive how to evaluate comprehensive evidence in a systematic, transparent, and consistent manner to conclude with high reliability. Therefore, the Comprehensive Evidence Scoring Rules were developed to meet such challenges.
With data from diverse sources, such as databases, authoritative institutions, and researchers’ labs. The numerical framework can be used to assess health risk by integrating three key items, including reliability scores, weight of concentration and correlation scores. The scores of diverse evidence are combined and the final result is calculated according to the formula to represent the overall validity of the evidence, the direction, and the strength of the association.
All evidence is recommended to be scored independently by two researchers, with their average as the final score of each item. If a score differs by 2 or more points, it needs to be arbitrated by another advanced researcher. In particular, if a study is mixed by any two or more evidence types, i.e., epidemiological/in vivo/in vitro evidence, researchers need to sum up the scores of both/all types.