Toxicology of simple and complex mixtures

Peer Reviewed: Internal Exposure: Linking Bioavailability to Effects

“…PBPK modeling is a strong tool for extrapolating among different exposure routes and different species (11,31). It also allows analysis of multiple uptake routes and combined effects in organisms after they are exposured to mixtures of compounds (32). These models are time-resolved and therefore can be used with sequential and pulsed exposure, which are challenges in ecotoxicology (33).…”

International issues on human health effects of exposure to chemical mixtures.

“…The present survey deals with a variety of mixture studies ranging from the development of a new computer program (35) and a new mathematical model as the foundation for rules predicting the toxicity of mixtures (40) to the application of gene expression technologies for detecting joint or interactive effects (34,69). Moreover, risk assessment of real-life mixtures such as the simultaneous intake of food additives (92), combined exposure to fine particles and gases in ambient air (46)(47)(48)(49)(50)(51)(52)(53)(54)(55)(56)(57), and DBPs in drinking water (77,79,80) were addressed.…”

“…Toxicology will benefit enormously from the application of genomics (transcriptomics, proteomics, metabolomics) to analyze chemically induced alterations in gene expression. Because of the integrated and holistic nature of genomics, in all likelihood such changes in gene expression can be identified at exposure levels lower than those affecting more conventional parameters (34,69). Once validated, the use of combined transcriptomics, proteomics, and metabolomics will make it possible to map early toxicity-related alterations in cells, tissues, or animals exposed to chemicals, and thus will lead to insight in numerous toxicologically relevant cellular processes simultaneously.…”

The Antioxidant Response System in Wheat Exposed to Pesticides and its Combined-induced Oxidative Damage

“…22 Testing mixture in this way, it would be possible to identify the compound(s) responsible for possible interactions. As mixture models improve, more precise data throughout the toxicity range could be required.…”