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Highly-Complex Environmentally-Realistic Mixtures: Challenges and Advances
Citation:
SIMMONS, J. E. Highly-Complex Environmentally-Realistic Mixtures: Challenges and Advances. Presented at International Toxicology of Mixtures Conference, Arlington, VA, October 21 - 23, 2011.
Impact/Purpose:
This presentation will provide a perspective on similarities and differences between defined and complex mixtures research and risk assessment, focusing on the particular problems associated with complex mixtures and recent advances that enhance the ability to conduct, interpret and use the data from complex mixture experiments.
Description:
The difficulties involved in design, conduct, analysis and interpretation of defmed mixtures experiments and use of the resulting data in risk assessment are now wellknown to the toxicology, risk assessment and risk management communities. The arena of highly-complex environmentally-realistic mixtures is even more daunting as the generators and the users of the data must address not only the same or similar issues associated with defined mixtures but many more. This presentation will provide a perspective on similarities and differences between defined and complex mixtures research and risk assessment, focusing on the particular problems associated with complex mixtures and recent advances that enhance the ability to conduct, interpret and use the data from complex mixture experiments. Examples will be drawn from the body of knowledge on complex mixtures, including theU.S. EPA's Office of Research and Development (ORD) Four Lab study (a multi-disciplinary research effort conducted by four ORD laboratories and centers with a large number of extramural partners) on integrated chemical and toxicological assessment of the complex mixtures of disinfection byproducts formed during disinfection of water with oxidants. Challenges for complex mixtures that typically include a substantial amount of unknown mass include: determining when a complex mixtures approach is justified or needed; understanding complex exposure scenarios; preparing realistic, appropriate samples for chemical and toxicological analysis; assessing the stability of mixture components; maximizing the effective use of limited and expensive samples; designing and conducting meaningful experiments in the low-response region where traditional study designs may not provide adequate statistical power; apportioning observed mixture toxicity to chemicals in the mixture or between the known chemicals (or subsets ofthe known chemicals) and the unidentified fraction; and, extrapolating results across similar mixtures. (This abstract does not necessarily reflect EPA policy).