TABLE 5-1 EPA’s Weight-of-Evidence Approach for Evaluating Degree of Concern for Prenatal and Postnatal Toxicity on the Basis of Human and Animal Data

Factor

Degree of Concern

Increasing Weight—Higher Degree of Concern

Decreasing Weight—Lower Degree of Concern

Pre- and postnatal toxicity

Effects found in humans related to exposure

Same types of effects seen in more then one species

Effects of a different type with greater potential consequences in young than in adults

Persistence or relatively longer recovery of effects in young than in adults

No adverse human or animal effects associated with exposure

Similar response in young with relatively shorter recovery than in adults

Dose-response relationship

Effects observed at a lower dose in young than in adults

NOAEL not identified

Poor data on dose-response relationship

Effects at higher dose in young than in adults or only at high dose in presence of severe generalized toxicity

Good data on dose-response relationship that allows confident identification of NOAEL or BMD

Pharmacokinetics

Metabolic profile indicates higher internal dose of active moiety in young than in adults or in humans than in animals

Metabolic profile indicates lower internal dose of active moiety in young than in adults or in humans than in animals

Mode of action

Mode of action supports relevance to humans and concern for animal findings

Mode of action may lead to several adverse consequences in offspring

Evidence indicates that mode of action is species-specific and thus not relevant to humans

Evidence indicates that humans are less sensitive than animal model

 

Source: Adapted from EPA 2002a.



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