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dc.contributor.advisorBrooks, Bryan W.
dc.contributor.authorBerninger, Jason P.
dc.date.accessioned2011-09-14T12:31:54Z
dc.date.available2011-09-14T12:31:54Z
dc.date.copyright2011-08
dc.date.issued2011-09-14
dc.identifier.citationBerninger, J. P. and Brooks, B. W. "Leveraging mammalian pharmaceutical toxicology and pharmacology data to predict chronic fish responses to pharmaceuticals." Toxicology Letters 193 (2010): 69–78.en_US
dc.identifier.citationBerninger, J. P., Du, B., Connors, K. A., Eytcheson, S. A., Prosser, K. N., Valenti, T. W., Chambliss, C. K., and Brooks, B. W. "Effects of the antihistamine diphenhydramine to selected aquatic organisms." Environmental Toxicology and Chemistry Accepted manuscript online (6 June 2011).en_US
dc.identifier.citationBerninger, J. P., Williams, E. S., and Brooks, B. W. "An initial probabilistic hazard assessment of oil dispersants approved by the United States National Contingency Plan." Environmental Toxicology and Chemistry 30 (2011): 1704–1708.en_US
dc.identifier.urihttp://hdl.handle.net/2104/8201
dc.description.abstractContaminants of emerging concern (CEC) are classes of compounds with relatively limited information available on environmental exposure, fate, and effects. The purpose of this research was to develop and test approaches that leverage available data using probabilistic models to advance an understanding of aquatic hazards of CECs. Pharmaceuticals are one such group of CECs. Though extrapolation approaches with fish models can provide important bridges between the biomedical and environmental sciences, little data is available addressing the sublethal effects of therapeutics in aquatic organisms. Seldom is the drug’s Mode of Action (MOA) considered in selection of chronic endpoints for an assessment, though mammalian pharmacological information is available for most drugs. A statistically significant relationship (r²=0.846, p<0.001) between mammalian pharmacology and toxicology data (margin of safety) and available fish acute to chronic data was identified, when therapeutic MOA was considered in selecting a chronic response variable. Based on this relationship, metrics to assess potency and internal effective dose were developed. These metrics were then evaluated using probabilistic distributions in an effort to prioritize drugs based on potential hazard. These probabilistic assessments identified specific drugs and drug classes as potentially presenting greater hazard to fish. To test these models, toxicity experiments with diphenhydramine, an antihistamine drug, were conducted to characterize standardized endpoints and novel, MOA-related ecotoxicological endpoints. The results confirmed that sublethal endpoints (e.g., behavior) related to therapeutic may be more appropriate for fish and that leveraging mammalian pharmacology and toxicology data may be predictive for MOA related responses when evolutionary conservation of targets are considered. It further highlighted the importance of carefully selecting model organisms for study of pharmaceuticals with multiple MOAs, because reproduction of the invertebrate Daphnia magna was sensitive to diphenydramine, potentially resulting from its histaminergic and cholinergic activities. A similar probabilistic approach was applied to oil dispersants, another CEC class, to assess potential impacts to aquatic systems. Leveraging the limited acute toxicity data available for an invertebrate and a fish model, probabilistic distributions were employed to predict the likelihood of oil dispersants exerting acute toxicity in the presence or absence of oil. This approach can be utilized in prospective and retrospective assessments to support emergency response decisions to oil spills and prioritize substances for further study. Lastly, probabilistic methods were used to develop uncertainty factors for acute to chronic rations for select biological active chemicals. For many chemical classes chronic effects data is lacking. Typically, default uncertainty factors are utilized to bridge this data gap. By leveraging the available chronic data using probabilistic methods, novel data-driven uncertainty factors were developed, potentially providing more protective extrapolation models.en_US
dc.language.isoen_USen_US
dc.publisheren
dc.rightsBaylor University theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. Contact librarywebmaster@baylor.edu for inquiries about permission.en_US
dc.subjectContaminants of emerging concern.en_US
dc.subjectOil dispersants.en_US
dc.subjectPharmaceuticals in the environment.en_US
dc.subjectPrioritization.en_US
dc.subjectUncertainty factors.en_US
dc.titleLeveraging available data for contaminants of emerging concern to develop an understanding of environmental hazard.en_US
dc.typeThesisen_US
dc.description.degreePh.D.en_US
dc.rights.accessrightsWorldwide access.en_US
dc.rights.accessrightsAccess changed 6/27/13.
dc.contributor.departmentBiomedical Studies.en_US
dc.contributor.schoolsBaylor University. Institute of Biomedical Studies.en_US


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