Dose: Time-to-effect analyses can identify hazardous chemicals at an early stage of product development.

Abstract

Expenditure for discovery and development of a new crop protection product is now approaching the $ 300 million mark, while at the same time underpinning information gaps in environmental safety assessment. Large information gaps also exist for the safety of a vast number of existing chemicals in commerce. Addressing safety information gaps of new and existing chemicals with increased conventional toxicity testing would skyrocket costs and animal usage and contravene the 3Rs principles to refine, reduce, and replace animal testing. There is a great need to improve predictive safety assessment with minimum animal use. Recent progress in the understanding of the molecular biology of chemical dose response relationships, which has confirmed general applicability of the Druckrey-Kupfmuller theorem for receptor-mediated toxicity, can now be employed at an early stage of product development to identify (and eliminate) hazardous chemicals using short-term chronic dose response tests in invertebrates. Time-to-effect (TTE) approaches can identify hazardous chemicals with time-cumulative toxicity. This approach would shift research and development programs to chemicals with ascertained strictly dosedependent toxicity, for which no-observable-adverse-effect levels (NOAELs) can be reliably established with short-term tests, which could make a myriad of resource-intensive animal studies obsolete.