Toxicology and Epidemiology: Improving the Science with a Framework for Combining Toxicological and Epidemiological Evidence to Establish Causal Inference

Abstract

Historically, toxicology has played a significant role in verifying conclusions drawn on the basis of epidemiological findings. Agents that were suggested to have a role in human diseases have been tested in animals to firmly establish a causative link. Bacterial pathogens are perhaps the oldest examples, and tobacco smoke and lung cancer and asbestos and mesothelioma provide two more recent examples. With the advent of toxicity testing guidelines and protocols, toxicology took on a role that was intended to anticipate or predict potential adverse effects in humans, and epidemiology, in many cases, served a role in verifying or negating these toxicological predictions. The coupled role of epidemiology and toxicology in discerning human health effects by environmental agents is obvious, but there is currently no systematic and transparent way to bring the data and analysis of the two disciplines together in a way that provides a unified view on an adverse causal relationship between an agent and a disease. In working to advance the interaction between the fields of toxicology and epidemiology, we propose here a five-step “Epid-Tox” process that would focus on: (1) collection of all relevant studies, (2) assessment of their quality, (3) evaluation of the weight of evidence, (4) assignment of a scalable conclusion, and (5) placement on a causal relationship grid. The causal relationship grid provides a clear view of how epidemiological and toxicological data intersect, permits straightforward conclusions with regard to a causal relationship between agent and effect, and can show how additional data can influence conclusions of causality.

Systematic review of the literature on triclosan and health outcomes in humans

“…As the main and perhaps the only inarguable property of a causal link is the temporal relationship between exposure and outcome (Potischman and Weed 1999;Rothman and Greenland 2005), cross-sectional and other prevalence-based studies are usually inadequate for confirming or refuting causal associations (Adami et al 2011). Most of the studies in this review fall into this category.…”

Antídotos e medicamentos utilizados para tratar intoxicações no Brasil: necessidades, disponibilidade e oportunidades

“…Devido a limitações éticas e práticas de conduzir ensaios clínicos randomizados em situação de intoxicação aguda, a maior parte das informações científicas em toxicologia é proveniente de estudos não controlados, principalmente relatos e séries de casos 49 . Esse foi um confundimento que não pudemos controlar na análise.…”

Evidence-based toxicology for the 21st century: Opportunities and challenges

“…the launching of the eBtC is timely, as the toxicology literature increasingly invokes eB-related themes or practices such as transparency in decision-making (Schreider et al, 2010), systematic and transparent reviews of evidence , synthesis of types of evidence to establish causal inference (Adami et al, 2011), and assessment of bias/credibility (Conrad and Becker, 2010). We also see practical examples of the application of evidence-based methodology or terminology Abhyankar et al, 2011;Maull et al, 2012).…”