This paper studies alternative toxicological approaches, with new (Skin sensitization, Toxcast) and previous (Carcinogenicity) analyses. Quantitative modeling of rate-limiting steps in Skin sensitization and Carcinogenicity predicts the majority of toxicants. Similarly, successful QSAR models exploit the quantification of only one, or few rate-limiting steps. High-throughput assays within Toxcast point to promising associations with endocrine disruption, whereas markers for pathways intermediate events have limited correlation with most endpoints. Since the types of pathways may be very different (often not simple linear chains of events), quantitative analysis is necessary to identify the type of mechanism, and build the appropriate model.