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Assessing Cumulative Effects of Endocrine Active Substances…

or What happens when I’m exposed to a whole bunch of endocrine active substances??. Assessing Cumulative Effects of Endocrine Active Substances…. Tim Pastoor, PhD, DABT September 10, 2009. Coumestrol. Ethinylestradiol (EE). Toxaphene. Dioxin. Genistein. Endrin.

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Assessing Cumulative Effects of Endocrine Active Substances…

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  1. orWhat happens when I’m exposed to a whole bunch of endocrine active substances?? Assessing Cumulative Effects of Endocrine Active Substances… Tim Pastoor, PhD, DABT September 10, 2009

  2. Coumestrol Ethinylestradiol (EE) Toxaphene Dioxin Genistein Endrin Methoxychlor Isobutylparaben Chlordane Estrone Heptaclor Daidzein Butylparaben Lindane Tim Pastoor, PhD, DABT

  3. (From R. Golden)Comparative Potency of Xenoestrogens in Rodent Uterotropic Assay Tim Pastoor, PhD, DABT

  4. Hypothetical Illustration of TEF/TEQ Approach for WEEDs in Drinking Water Tim Pastoor, PhD, DABT

  5. Receptor Terminology: Law of Mass Action Drug-Receptor Complex Drug + Receptor Response(s) • Affinity: the “tenacity” by which a drug binds to its receptor. • Intrinsic activity: the relative maximal response caused by a drug in a tissue preparation. • Intrinsic efficacy: a drug’s ability to affect a receptor and cause a biological response. • Potency: the relative ability of a drug to cause a measured biological or functional change. Tim Pastoor, PhD, DABT

  6. The chain of events required for estrogen-induced uterine thickening Jonathan G. Moggs, et al. Phenotypic Anchoring of Gene Expression Changes during Estrogen-Induced Uterine Growth. Environ Health Perspect 112:1589–1606 (2004). doi:10.1289/txg.7345 Tim Pastoor, PhD, DABT

  7. Time Course of Estrogen-Induced Uterine Growth Jonathan G. Moggs, et al. Phenotypic Anchoring of Gene Expression Changes during Estrogen-Induced Uterine Growth. Environ Health Perspect 112:1589–1606 (2004). doi:10.1289/txg.7345 Tim Pastoor, PhD, DABT

  8. Receptor Terminology: Law of Mass Action Drug-Receptor Complex Drug + Receptor Response(s) • Affinity: the “tenacity” by which a drug binds to its receptor. • Intrinsic activity: the relative maximal response caused by a drug in a tissue preparation. • Intrinsic efficacy: a drug’s ability to affect a receptor and cause a biological response. • Potency: the relative ability of a drug to cause a measured biological or functional change. Tim Pastoor, PhD, DABT

  9. Working Hypothesis: Can we state with reasonable certainty that a cumulative risk assessment of multiple week endocrine active substances is an exercise in adding zeroes?? Tim Pastoor, PhD, DABT

  10. Coumestrol Ethinylestradiol (EE) Toxaphene Dioxin Genistein Endrin Methoxychlor Isobutylparaben Estrone Chlordane Heptaclor Daidzein Butylparaben Lindane Tim Pastoor, PhD, DABT

  11. Sneezing in a Hurricane Tim Pastoor, PhD, DABT September 10, 2009

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