Evidence-based toxicology

Part of a series on
Evidence-based practices

The discipline of evidence-based toxicology (EBT) strives to transparently, consistently, and objectively assess available scientific evidence in order to answer questions in toxicology,[1] the study of the adverse effects of chemical, physical, or biological agents on living organisms and the environment, including the prevention and amelioration of such effects.[2] EBT has the potential to address concerns in the toxicological community about the limitations of current approaches to assessing the state of the science.[3][4] These include concerns related to transparency in decision making, synthesis of different types of evidence, and the assessment of bias and credibility.[5][6][7] Evidence-based toxicology has its roots in the larger movement towards evidence-based practices.

By analogy to evidence-based medicine (EBM),[8] the umbrella term evidence-based toxicology (EBT) has been coined to group all approaches intended to better implement the above-mentioned evidence-based principles in toxicology in general and in toxicological decision-making in particular. Besides systematic reviews, the core evidence-based tool, such approaches include inter alia the establishment and universal use of a common ontology, justified design and rigorous conduct of studies, consistently structured and detailed reporting of experimental evidence, probabilistic uncertainty and risk assessment, and the development of synthesis methodology to integrate evidence from diverse evidence streams, e.g. from human observational studies, animal studies, in vitro studies and in silico modeling. A main initial impetus for translating evidence-based approaches to toxicology was the need to improve the performance assessment of toxicological test methods.[9] The U.S. National Research Council (NRC) concurs that new means of assessment are needed to keep pace with recent advances in the development of toxicological test methods, capitalizing on enhanced scientific understanding through modern biochemistry and molecular biology.[10]

A key tool in evidence-based medicine that holds promise for EBT is the systematic review. Historically, authors of reviews assessing the results of toxicological studies on a particular topic have searched, selected, and weighed the scientific evidence in a non-systematic and non-transparent way. Due to their narrative nature, these reviews tend to be subjective, potentially biased, and not readily reproducible.[1] Two examples highlighting these deficiencies are the risk assessments of trichloroethylene and bisphenol A (BPA). Twenty-seven different risk assessments of the evidence that trichloroethylene causes cancer have come to substantially different conclusions.[11] Assessments of BPA range from low risk of harm to the public to potential risks (for some populations), leading to different political decisions.[12] Systematic reviews can help reducing such divergent views.[3] In contrast with narrative reviews, they reflect a highly structured approach to reviewing and synthesizing the scientific literature while limiting bias.[3] The steps to carrying out a systematic review include framing the question to be addressed; identifying and retrieving relevant studies; determining if any retrieved studies should be excluded from the analysis; and appraising the included studies in terms of their methodological quality and risk of bias. Ultimately the data should be synthesized across studies, if possible by a meta-analysis. A protocol of how the review will be conducted is prepared ahead of time and ideally should be registered and/or published.

Scientists have made progress in their efforts to apply the systematic review framework to evaluating the evidence for associations between environmental toxicants and human health risks. To date, researchers have shown that important elements of the framework established in evidence-based medicine can be adapted to toxicology with little change, and some studies have been attempted.[13][14][15] Researchers using the systematic review methodology to address toxicological concerns include a group of scientists from government, industry, and academia in North America and the European Union (EU) who have joined together to promote evidence-based approaches to toxicology through the nonprofit Evidence-based Toxicology Collaboration (EBTC). The EBTC brings together the international toxicology community to develop EBT methodology and facilitate the use of EBT to inform regulatory, environmental and public health.[3][16][17]

  1. ^ a b Hoffmann, S.; Hartung, T (2006). "Toward an evidence-based toxicology". Hum Exp Toxicol. 25 (9): 497–513. doi:10.1191/0960327106het648oa. PMID 17017003. S2CID 42202416.
  2. ^ "How do you define toxicology?". Society of Toxicology. Archived from the original on 2013-06-05. Retrieved 2017-06-17.
  3. ^ a b c d Stephens, M.; Andersen, M.; Becker, R.A.; Betts, K.; et al. (2013). "Evidence-based toxicology for the 21st century: Opportunities and challenges". ALTEX. 30 (1): 74–104. doi:10.14573/altex.2013.1.074. PMID 23338808.
  4. ^ Mandrioli, D.; Silbergeld, E. (2016). "Evidence from toxicology: the most essential science for the prevention". Environ Health Perspect. 124 (1): 6–11. doi:10.1289/ehp.1509880. PMC 4710610. PMID 26091173.
  5. ^ Schreider, J.; Barrow, C.; Birchfield, N.; et al. (2010). "Enhancing the credibility of decisions based on scientific conclusions: transparency is imperative". Toxicol Sci. 116 (1): 5–7. doi:10.1093/toxsci/kfq102. PMID 20363830.
  6. ^ Adami, H.O.; Berry, S.C.; Breckenridge, C.B.; Smith, L.L.; et al. (2011). "Toxicology and epidemiology: improving the science with a framework for combining toxicological and epidemiological evidence to establish causal inference". Toxicol Sci. 122 (2): 223–234. doi:10.1093/toxsci/kfr113. PMC 3155086. PMID 21561883.
  7. ^ Conrad, J.W.; Becker, R.A. (2011). "Enhancing credibility of chemical safety studies: an emerging consensus on key assessment criteria". Environ Health Perspect. 119 (6): 757–764. doi:10.1289/ehp.1002737. PMC 3114808. PMID 21163723.
  8. ^ Eddy, D.M. (2005). "Evidence-Based Medicine: A Unified Approach". Health Aff. 24 (1): 9–17. doi:10.1377/hlthaff.24.1.9. PMID 15647211.
  9. ^ Hoffmann, S.; Hartung, T (2005). "Diagnosis: toxic! Trying to apply approaches of clinical diagnostics and prevalence in toxicology considerations". Toxicol Sci. 85 (1): 422–428. CiteSeerX 10.1.1.546.8341. doi:10.1093/toxsci/kfi099. PMID 15689419.
  10. ^ National Research Council (2007). Toxicity Testing in the 21st Century: A Vision and a Strategy. Washington, DC: The National Academies Press.
  11. ^ Rudén, C. (2001). "The use and evaluation of primary data in 29 trichloroethylene carcinogen risk assessments". Regul Toxicol Pharmacol. 34 (1): 3–16. doi:10.1006/rtph.2001.1482. PMID 11502152.
  12. ^ Whaley, P.; Halsall, C.; Ågerstrand, R.A.; Aiassa, E.; et al. (2016). "Implementing systematic review techniques in chemical risk assessment: Challenges, opportunities and recommendations". Environ Int. 92–93: 556–564. doi:10.1016/j.envint.2015.11.002. PMC 4881816. PMID 26687863.
  13. ^ Navas-Acien, A.; Sharrett, A.R.; Silbergeld, E.K.; et al. (2005). "Arsenic exposure and cardiovascular disease: a systematic review of the epidemiologic evidence". Am J Epidemiol. 162 (11): 1037–1049. doi:10.1093/aje/kwi330. PMID 16269585.
  14. ^ Krauth, D.; Woodruff, T.J.; Bero, L.; et al. (2013). "Instruments for assessing risk of bias and other methodological criteria of published animal studies: a systematic review". Environ Health Perspect. 121 (9): 985–992. doi:10.1289/ehp.1206389. PMC 3764080. PMID 23771496.
  15. ^ Silbergeld, E.; Scherer, R.W. (2013). "Evidence-based toxicology: Strait is the gate, but the road is worth taking". ALTEX. 30 (1): 67–73. doi:10.14573/altex.2013.1.067. PMID 23338807.
  16. ^ Stephens, M.; Betts, K.; Beck, N.B.; Cogliano, V.; et al. (2016). "The emergence of systematic review in toxicology". Toxicol Sci. 152 (1): 10–16. doi:10.1093/toxsci/kfw059. PMC 4922539. PMID 27208075.
  17. ^ Samuel, G.O.; Hoffmann, S.; Wright, R.A.; Lalu, M.M.; et al. (2016). "Guidance on assessing the methodological and reporting quality of toxicologically relevant studies". Environ Int. 92–93: 630–46. doi:10.1016/j.envint.2016.03.010. PMID 27039952.