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Because associations between agents and environmental effects are not necessarily causal, it is necessary to assess causation before using such relationships in environmental management. The authors adapted epidemiological methods to assess general causal hypotheses. General causation establishes that an agent is capable of causing an effect. The method uses all relevant and good-quality evidence in a weight-of-evidence system. The system is credible due to its explicit a priori criteria. The evidence is organized in terms of six characteristics of causation: cooccurrence, preceding causation, interaction, alteration, sufficiency, and time order. The causal assessment proceeds through six steps that generate, organize, and score evidence to determine whether causation is adequately supported by the body of evidence. Environ. Toxicol. Chem. 2013;32:272276. (C) 2012 SETAC