15 research outputs found
Pharmaceuticals and personal care products in the environment: What are the big questions?
Background: Over the past 10-15 years, a substantial amount of work has been done by the scientific, regulatory, and business communities to elucidate the effects and risks of pharmaceuticals and personal care products (PPCPs) in the environment. Objective: This review was undertaken to identify key outstanding issues regarding the effects of PPCPs on human and ecological health in order to ensure that future resources will be focused on the most important areas. Data sources: To better understand and manage the risks of PPCPs in the environment, we used the "key question" approach to identify the principle issues that need to be addressed. Initially, questions were solicited from academic, government, and business communities around the world. A list of 101 questions was then discussed at an international expert workshop, and a top-20 list was developed. Following the workshop, workshop attendees ranked the 20 questions by importance. Data synthesis: The top 20 priority questions fell into seven categories: a) prioritization of substances for assessment, b) pathways of exposure, c) bioavailability and uptake, d) effects characterization, e) risk and relative risk, f) antibiotic resistance, and g) risk management. Conclusions: A large body of information is now available on PPCPs in the environment. This exercise prioritized the most critical questions to aid in development of future research programs on the topic.Centro de Investigaciones del Medioambient
Leveraging available data for contaminants of emerging concern to develop an understanding of environmental hazard.
Contaminants 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.Ph.D
The ECOTOXicology Knowledgebase Literature Search and Review Processes for Identifying and Curating Toxicity Data for Ecological Risk Assessments
Presentation to the Society of Environmental Toxicology and Chemistry (SETAC) annual meeting November 2022
Search for CCTE records in EPA’s Science Inventory by typing in the title at this link.
https://cfpub.epa.gov/si/si_public_search_results.cfm?advSearch=true&showCriteria=2&keyword=CCTE&TIMSType=&TIMSSubTypeID=&epaNumber=&ombCat=Any&dateBeginPublishedPresented=07/01/2017&dateEndPublishedPresented=&dateBeginUpdated=&dateEndUpdated=&DEID=&personName=&personID=&role=Any&journalName=&journalID=&publisherName=&publisherID=&sortBy=pubDate&count=25</p
Using Transcriptomic Tools to Evaluate Biological Effects Across Effluent Gradients at a Diverse Set of Study Sites in Minnesota, USA
The aim of this study was to explore
the utility of “omics”
approaches in monitoring aquatic environments where complex, often
unknown stressors make chemical-specific risk assessment untenable.
We examined changes in the fathead minnow (<i>Pimephales promelas</i>) ovarian transcriptome following 4-day exposures conducted at three
sites in Minnesota (MN, USA). Within each site, fish were exposed
to water from three locations along a spatial gradient relative to
a wastewater treatment plant (WWTP) discharge. After exposure, site-specific
impacts on gene expression in ovaries were assessed. Using an intragradient
point of comparison, biological responses specifically associated
with the WWTP effluent were identified using functional enrichment
analyses. Fish exposed to water from locations downstream of the effluent
discharges exhibited many transcriptomic responses in common with
those exposed to the effluent, indicating that effects of the discharge
do not fully dissipate downstream. Functional analyses showed a range
of biological pathways impacted through effluent exposure at all three
sites. Several of those impacted pathways at each site could be linked
to potential adverse reproductive outcomes associated with the hypothalamic–pituitary–gonadal
(HPG) axis in female fathead minnows, specifically signaling pathways
associated with oocyte meiosis, TGF-beta signaling, gonadotropin-releasing
hormone (GnRH) and epidermal growth factor receptor family (ErbB),
and gene sets associated with cyclin B-1 and metalloproteinase. The
utility of this approach comes from the ability to identify biological
responses to pollutant exposure, particularly those that can be tied
to adverse outcomes at the population level and those that identify
molecular targets for future studies
Human Therapeutic Plasma Levels of the Selective Serotonin Reuptake Inhibitor (SSRI) Sertraline Decrease Serotonin Reuptake Transporter Binding and Shelter-Seeking Behavior in Adult Male Fathead Minnows
Selective serotonin reuptake inhibitors (SSRIs) represent
a class
of pharmaceuticals previously reported in aquatic ecosystems. SSRIs
are designed to treat depression and other disorders in humans, but
are recognized to elicit a variety of effects on aquatic organisms,
ranging from neuroendocrine disruption to behavioral perturbations.
However, an understanding of the relationships among mechanistic responses
associated with SSRI targets and ecologically important behavioral
responses of fish remains elusive. Herein, linking Adverse Outcomes
Pathways (AOP) models with internal dosimetry represent potential
approaches for developing an understanding of pharmaceutical risks
to aquatic life. We selected sertraline as a model SSRI for a 28-d
study with adult male fathead minnows. Binding activity of the serotonin
reuptake transporter (SERT), previously demonstrated in mammals and
fish models to respond to sertraline exposure, was selected as an
endpoint associated with therapeutic activity. Shelter-seeking behavior
was monitored using digital tracking software to diagnose behavioral
abnormalities. Fish plasma levels of sertraline exceeding human therapeutic
doses were accurately modeled from external exposure concentrations
when pH influences on ionization and log D were considered. We observed
statistically significant decreases in binding at the therapeutic
target (SERT) and shelter-seeking behavior when fish plasma levels
exceeded human therapeutic thresholds. Such observations highlights
the strengths of coupling physiologically based pharmacokinetic modeling
and AOP approaches and suggest that internal dosimetry should be monitored
to advance an understanding of the ecological consequences of SSRI
exposure to aquatic vertebrates
Leveraging existing data for prioritization of the ecological risks of human and veterinary pharmaceuticals to aquatic organisms
One uncertainty factor does not fit all: Identifying mode of action and species specific acute to chronic ratios for aquatic life
Pharmaceuticals and personal care products in the environment: What are the big questions?
Background: Over the past 10-15 years, a substantial amount of work has been done by the scientific, regulatory, and business communities to elucidate the effects and risks of pharmaceuticals and personal care products (PPCPs) in the environment. Objective: This review was undertaken to identify key outstanding issues regarding the effects of PPCPs on human and ecological health in order to ensure that future resources will be focused on the most important areas. Data sources: To better understand and manage the risks of PPCPs in the environment, we used the "key question" approach to identify the principle issues that need to be addressed. Initially, questions were solicited from academic, government, and business communities around the world. A list of 101 questions was then discussed at an international expert workshop, and a top-20 list was developed. Following the workshop, workshop attendees ranked the 20 questions by importance. Data synthesis: The top 20 priority questions fell into seven categories: a) prioritization of substances for assessment, b) pathways of exposure, c) bioavailability and uptake, d) effects characterization, e) risk and relative risk, f) antibiotic resistance, and g) risk management. Conclusions: A large body of information is now available on PPCPs in the environment. This exercise prioritized the most critical questions to aid in development of future research programs on the topic.Fil: Boxall, Alistair B. A.. University of York; Reino UnidoFil: Rudd, Murray A.. University of York; Reino UnidoFil: Brooks, Bryan W.. Baylor University; Estados UnidosFil: Caldwell, Daniel J.. Johnson & Johnson; Estados UnidosFil: Choi, Kyungho. Seoul National University; Corea del SurFil: Hickmann, Silke. Umweltbundesamt; AlemaniaFil: Innes, Elizabeth. Health Canada; CanadáFil: Ostapyk, Kim. Health Canada; CanadáFil: Staveley, Jane P.. Exponent; Estados UnidosFil: Verslycke, Tim. Gradient; Estados UnidosFil: Ankley, Gerald T.. United States Environmental Protection Agency; Estados UnidosFil: Beazley, Karen F.. Dalhousie University Halifax; CanadáFil: Belanger, Scott E.. Procter And Gamble; Estados UnidosFil: Berninger, Jason P.. Baylor University; Estados UnidosFil: Carriquiriborde, Pedro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Química. Centro de Investigaciones del Medio Ambiente; ArgentinaFil: Coors, Anja. Ect Oekotoxikologie Gmbh; AlemaniaFil: DeLeo, Paul C.. American Cleaning Institute; Estados UnidosFil: Dyer, Scott D.. Procter And Gamble; Estados UnidosFil: Ericson, Jon F.. Pfizer Inc.; Estados UnidosFil: Gagné, François. Environment Canada; CanadáFil: Giesy, John P.. University of Saskatchewan; CanadáFil: Gouin, Todd. Unilever; Reino UnidoFil: Hallstrom, Lars. University of Alberta; CanadáFil: Karlsson, Maja V.. University of York; Reino UnidoFil: Joakim Larsson, D.G.. University of Göteborg; AlemaniaFil: Lazorchak, James M.. United States Environmental Protection Agency; Estados UnidosFil: Mastrocco, Frank. Pfizer Inc.; Estados UnidosFil: McLaughlin, Alison. Health Canada; CanadáFil: McMaster, Mark E.. Environment Canada; CanadáFil: Meyerhoff, Roger D.. Eli Lilly And Company; Estados UnidosFil: Moore, Roberta. Health Canada; CanadáFil: Parrott, Joanne L.. Environment Canada; CanadáFil: Snape, Jason R.. AstraZeneca UK Ltd.; Reino UnidoFil: Murray-Smith, Richard. AstraZeneca UK Ltd.; Reino UnidoFil: Servos, Mark R.. University of Waterloo; CanadáFil: Sibley, Paul K.. University of Guelph; CanadáFil: Straub, Jürg Oliver. F. Hoffmann-La Roche Ltd.; SuizaFil: Szabo, Nora D.. University of Ottawa; CanadáFil: Topp, Edward. Agriculture Et Agroalimentaire Canada; CanadáFil: Tetreault, Gerald R.. University of Waterloo; CanadáFil: Trudeau, Vance L.. University of Ottawa; CanadáFil: Van Der Kraak, Glen. University of Guelph; Canad