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Science and Technology Task Group

Science and Technology Task Group. May 2013. Completed. Styrene and SO in KO mice – no toxicity in absence of CYP2F2 metabolism: published Styrene and SO in TG mice – no toxicity when human CYP2F1 substituted for normal mouse CYP2F2: published

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Science and Technology Task Group

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  1. Science and TechnologyTask Group May 2013

  2. Completed • Styrene and SO in KO mice – no toxicity in absence of CYP2F2 metabolism: published • Styrene and SO in TG mice – no toxicity when human CYP2F1 substituted for normal mouse CYP2F2: published • 4-Hydroxystyrene limited toxicity in KO and TG mice: published

  3. In Progress • Styrene metabolism in WT, KO and TG mice • Reduced production of 4-hydroxySO and 3,4-dihydroxystyrene in KO and TG mice • Currently comparing to previous studies using mouse, rat and human microsomes

  4. Future • Genomic analysis/pilot study • Inhalation for 4 weeks at 40 and 160 ppm to WT, KO, and TG mice • Mice terminated at 1 and 4 weeks for genomic analysis in lung • Demonstration of methods for BrdU and genomic analysis • Timing- as soon as possible to arrange • Need 100 gallons of commercial styrene

  5. Future • Chronic study in WT, KO, and TG mice • Breeding of mice underway; will be available in January 2014 • Received bids from 3 labs; eliminated one in England due to potential difficulty shipping mice to UK and high cost • Considering WIL and Hamner • EPA resisted idea of doing 12-month study instead of 24 month • EPA agreed to examining only lungs for tumors

  6. MOA Workshop • Air Force very interested in sponsoring (naphthalene in jet fuel) • Developing updated review on genotoxicty data • Hoping for first half of July

  7. EPA MOA Workshop • Cruzan to serve on Organizing committee • Target Date September 5,6 • Initial draft agenda from EPA needs better focus on chemicals of interest

  8. EDSP • Current Tier 1 tests cost about $1M • 2 EPA scientists propose reduced Tier 1; EDSP staff not interested • EPA indicated next list of chemicals for Tier 1 to be released in September; styrene likely to be on list. • SIRC submitted summary of existing data, but EPA has not exempted other chemicals based on existing data

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