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    Pharmaceutical biomarkers to inform public and environmental health law and policy
    (Montana State University - Bozeman, College of Agriculture, 2020) Margetts, Miranda Lee; Chairperson, Graduate Committee: Robert K. D. Peterson and Deborah Keil (co-chair); Aparna Keshaviah, Cindy Hu, Victoria Troeger, Jordan Sykes, Nicholas Bishop, Tammy Jones-Lepp, Marisa Henry and Deborah E. Keil were co-authors of the article, 'Using wastewater-based epidemiology with local indicators of opioid and illicit drug use to overcome data gaps' submitted to the journal 'Journal of the American Medical Association' which is contained within this dissertation.; Terri Mavencamp, Jordan Sykes, Tammy Jones-Lepp, Nicholas Bishop, Victoria Troeger, Robert K. D. Peterson and Deborah E. Keil were co-authors of the article, 'The environmental impact of substance use in Montana's waterways: investigation of prescription, illicit, and recreational drug metabolite concentrations into receiving waters' which is contained within this dissertation.; Trent McCallson and Deborah E. Keil were co-authors of the article, 'Wastewater testing to support new environmental health compliance obligations in the healthcare industry' which is contained within this dissertation.
    The increasing awareness of the prevalence of prescription and illicit drug metabolites in wastewater is affecting changes to public and environmental health laws and policies. Drug takeback laws have been enacted to limit environmental pollution from drugs flushed into sewers; however, these laws only apply to legally prescribed drugs. Wastewater-based epidemiology, which relies on the measurement of drug concentrations in untreated wastewater, is also emerging as a complementary drug-use data tool to estimate drug consumption patterns by a community in near real-time. We sampled both the untreated influent and treated effluent at two locations in Montana over three months from April to June, 2019, to ascertain the concentrations of certain prescription and illicit drugs of abuse. The concentrations of drugs obtained from the untreated influent were used to inform a wastewater-based epidemiology study that compared drug-dose estimates from our wastewater samples against existing local drug-use sources (emergency medical services calls, drug seizures, and prescription dispense data). We also measured the treated effluent to determine the concentration at which drugs of abuse are persisting through the wastewater-treatment process and potentially affecting aquatic life exposed to those concentrations in receiving waters. We undertook a risk assessment whereby measured drug concentrations were assessed against corresponding ecotoxicology thresholds. Our results indicate that both codeine and morphine concentrations were above predicted no-effect concentrations. The overall results indicate that (1) wastewater-based epidemiology may be an effective tool to better describe substance abuse in communities and (2) drugs are persisting at levels above ecotoxicological thresholds from wastewater treatment plants into receiving waters. To our knowledge, these investigations are the first of their kind to have been conducted in Montana.
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    Environmental concentrations, fate, and risk assessment of insecticides used for adult mosquito management
    (Montana State University - Bozeman, College of Agriculture, 2008) Schleier, Jerome Joseph, III; Chairperson, Graduate Committee: Robert K. D. Peterson.
    One of the most effective ways of managing adult mosquitoes that vector human and animal pathogens is the use of ultra-low-volume (ULV) insecticides. Due to a lack of studies examining the environmental fate of ULV insecticides and because previous risk assessments have shown that environmental concentrations of insecticides contributed the largest amount of variance to the estimated total exposure, I measured deposition onto surfaces and air concentrations of permethrin and naled. I also conducted risk assessments for human and other non-target organisms using the values I measured. Deposition concentrations of permethrin and naled generally decreased as distance from the spray source increased. Overall, approximately 3.2% of the permethrin and 15% of the naled applied deposited on the ground within 75 m from the spray source 1 h after application. Concentrations of permethrin and naled 12 h after application were not significantly different than concentrations 1 h after application. The results of my probabilistic human-health risk assessment using actual environmental concentrations showed that previous risk assessments overestimated risks. Thus they were conservative in protecting human health. The non-target risk assessment and field bioassay using the house cricket, Acheta domesticus (L.), as a surrogate for medium- to large-bodied ground dwelling insects showed that ULV applications most likely would not result in impacts on populations. I also measured actual environmental concentrations of pyrethrins and piperonyl butoxide (PBO) after aerial ULV applications. Pyrethrins were not detected in the water or on deposition pads. However PBO was detected in the water and on deposition samples, but concentrations rapidly decreased to background levels by 36 h after application. The estimated risks of pyrethrins and PBO to aquatic surrogates were lower than those estimated by previous ecological risk assessments. My study is the first to relate actual environmental concentrations of ULV insecticides to estimates of human-health risks. Results of my environmental fate studies, human-health and non-target risk assessments, and the current weight of scientific evidence, demonstrate that the risks to humans and the environment after ULV applications of insecticides most likely are below regulatory levels of concern.
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    Development of an environmental fate model for risk assessment of ultra-low-volume insecticides
    (Montana State University - Bozeman, College of Agriculture, 2012) Schleier, Jerome Joseph, III; Chairperson, Graduate Committee: Robert K. D. Peterson.
    One of the most effective ways of managing adult mosquitoes that vector human and animal pathogens is the use of ultra-low-volume (ULV) insecticides. The U.S. Environmental Protection Agency uses models that are not validated for ULV insecticide applications and exposure assumptions to perform their human and ecological risk assessments. Currently, there is no validated model that can accurately predict deposition of insecticides applied using ULV technology for adult mosquito management. In addition, little is known about the deposition and drift of small droplets like those used under conditions encountered during ULV applications. The objectives of my dissertation were to perform field studies to measure environmental concentrations of insecticides and to develop a validated model to predict the deposition of ULV insecticides, and use the data generated from the field study to perform refined human and aquatic ecological risk assessments. To model the field data collected during the summers of 2009-2011 a regression model selected by the Bayesian Information Criterion and k-fold cross validation was used to validate the selected model. k-fold cross validation demonstrated that the mean square error and mean square prediction error were similar indicating good predictive ability. The human-health risk assessment demonstrated that previous risk assessments used conservative exposure scenarios that overestimated risks, thus being conservative in protecting human health. Our results demonstrated a 10-fold reduction in the RQ estimates when comparing risk assessments using estimated environmental concentrations and actual environmental concentrations from the environmental fate model. Because I used a large data set to model concentrations deposited on surfaces, this variance in exposure is due to the inherent variability in deposition concentrations after ULV applications and, therefore, would not warrant further refinement to improve risk assessments. The aquatic risk assessment using actual environmental concentrations showed that the 95th percentile estimated concentration would result in less than 0.0001% of the potentially affected fraction of species reaching their respective LC50. Our results are supported by the weight of evidence that pyrethroids applied by ground-based ULV applications will not result in deleterious effects on aquatic organisms.
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    The invasion potential and competitive ability of Camelina sativa (L.) Crantz (camelina) in rangeland ecosystems
    (Montana State University - Bozeman, College of Agriculture, 2010) Davis, Philip Browning; Chairperson, Graduate Committee: Fabian D. Menalled.
    Camelina sativa (L.) Crantz (large-seeded false-flax) is a recently introduced oilseed crop in Montana and has potential for large scale production for the biofuel market. However, due to weedy characteristics, the invasive potential of this species is of concern. A need exists to create a pre-entry protocol to accurately assess risk to minimize uncertainty inherent in qualitative weed risk assessment approaches. We assessed the probability of C. sativa to invade rangeland ecosystems of southwest Montana to address this concern. The objectives of this study were to 1) quantitatively assess the invasion potential of C. sativa by collecting demographic data over two years and developing a population dynamics model, 2) compare experimental results and modeling outcomes to predictions suggested by a qualitative weed risk assessment system, and 3) assess the impact of growing conditions on the relative competitiveness of C. sativa and Brassica napus (L.) (canola). Objective 1 was carried out in two contrasting rangeland ecosystems to assess the effects of disturbance and seeding season on emergence, survival, and fecundity rates of C. sativa. Population growth (lambda) was forecasted by developing a population dynamics model. Resulting lambda values from simulations using observed data never exceeded 0.03 and the maximum time to extinction was six years. The low lambda values indicate that the threat of invasion by this species in the studied ecosystems is low. Objective 2 compared quantitative results to predictions from the Australian weed risk assessment (WRA) model. In contrast to experimental results, outcomes from the WRA suggested that this species should not be allowed entry into the region. These opposing results highlight the need for a more comprehensive approach to weed risk assessment. Objective 3 was conducted over three trials in two greenhouses. A replacement series design was used to estimate the effects of soil conditions and the presence of an invasive weed, Bromus tectorum (L.) (cheatgrass, downy brome), on the competitive outcomes between C. sativa and canola. Replacement series diagrams determined that competition occurred and that canola was the superior competitor in all treatments, thus providing further evidence that the invasion potential of C. sativa is low.
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