Table 2.

Strength of evidence definitions for non­human studies.^a

Strength rating	Definition
Sufficient evidence of toxicity	A positive relationship is observed between exposure and adverse outcome in multiple studies or a single appropriate study in a single species.b The available evidence includes results from one or more well-designed, well-conducted studies, and the conclusion is unlikely to be strongly affected by the results of future studies.c
Limited evidence of toxicity	The data suggest a positive relationship between exposure and adverse outcome, but there are important limitations in the quality of the body of evidence. Confidence in the relationship is constrained by factors such as the number, size, or quality of individual studies, or inconsistency of findings across individual studies.c As more information becomes available, the observed effect could change, and this change may be large enough to alter the conclusion.
Inadequate evidence of toxicity	The available evidence is insufficient to assess effects of the exposure. Evidence is insufficient because of the limited number or size of studies, low quality of individual studies, or inconsistency of findings across individual studies. More information may allow an assessment of effects.
Evidence of lack of toxicity	Data on an adequate array of end points from more than one study with at least two species showed no adverse effects at doses that were minimally toxic in terms of inducing an adverse effect. Information on pharmacokinetics, mechanisms, or known properties of the chemical class may also strengthen the evidence.d The conclusion is limited to the species, age at exposure, and/or other conditions and levels of exposure studied, and is unlikely to be strongly affected by the results of future studies.c
aThe Navigation Guide rates the quality and strength of evidence of human and non­human evidence streams separately as “sufficient,” “limited,” “inadequate,” or “evidence of lack of toxicity,” and then these two ratings are combined to produce one of five possible statements about the overall strength of the evidence of a chemical’s reproductive/developmental toxicity. The methodology is adapted from the criteria used by IARC to categorize the carcinogenicity of substances (IARC 2006) except as noted. bIARC’s criteria for sufficient evidence of carcinogenicity in animals requires multiple positive results (species, studies, sexes) (IARC 2006). The Navigation Guide integrates the U.S. EPA’s minimum criteria for animal data for a reproductive or developmental hazard (i.e., data demonstrating an adverse reproductive effect in a single appropriate, well-executed study in a single test species) (U.S. EPA 1996). The Navigation Guide also incorporates the U.S. EPA’s ”sufficient evidence category,” which includes data that “collectively provide enough information to judge whether or not a reproductive hazard exists within the context of effect as well as dose, duration, timing, and route of exposure. This category may include both human and experimental animal evidence” (U.S. EPA 1996). The U.S. EPA statement for developmental hazards is slightly different but includes the same relevant information regarding dose, duration, timing, and so on (U.S. EPA 1991). cLanguage for the definitions of the rating categories were adapted from descriptions of levels of certainty provided by the U.S. Preventive Services Task Force Levels of Certainty Regarding Net Benefit (Sawaya et al. 2007). dBased on minimum data requirements according to U.S. EPA guidelines for assessing reproductive toxicity (U.S. EPA 1996).