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

Exposure assessment of 17α-ethinylestradiol in surface waters of the United States and Europe

An evaluation of measured and predicted concentrations of 17α ethinyl estradiol (EE2) in surface waters of the United States (U.S.) and Europe was conducted to develop expected long term exposure concentrations for this compound. Measured environmental concentrations (MECs) in surface waters were identified from the literature. Predicted environmental concentrations (PECs) were generated for European and U.S. watersheds using the GREAT-ER and PhATE™ models, respectively. The majority of MECs are non-detect and generally consistent with model PECs and conservative mass balance calculations. However, the highest MECs are not consistent with concentrations derived from conservative (worst case) mass balance estimates or model PECs. A review of analytical methods suggests that tandem or high resolution mass spectrometry (MS) methods with extract cleanup result in lower detection limits and lower reported concentrations consistent with model predictions and bounding estimates. Based on model results using PhATE and GREAT ER, the 90th percentile low flow PECs in surface water are approximately 0.2 and 0.3 ng/L for the U.S. and Europe, respectively. These levels represent conservative estimates of long-term exposure that can be used for risk assessment purposes. Our analysis also indicates that average concentrations are one to two orders of magnitude lower than these 90th percentile estimates. Higher reported concentrations (e.g., greater than the 99th percentile PEC of ~1 ng/l) could result from methodological problems or unusual environmental circumstances; however, such concentrations are not representative of levels generally found in the environment, warrant special scrutiny, and are not appropriate for use in risk assessments of long-term exposures

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

Disruption of a ciliary B9 protein complex causes Meckel syndrome

Nearly every ciliated organism possesses three B9 domain-containing proteins: MKS1, B9D1, and B9D2. Mutations in human MKS1 cause Meckel syndrome (MKS), a severe ciliopathy characterized by occipital encephalocele, liver ductal plate malformations, polydactyly, and kidney cysts. Mouse mutations in either Mks1 or B9d2 compromise ciliogenesis and result in phenotypes similar to those of MKS. Given the importance of these two B9 proteins to ciliogenesis, we examined the role of the third B9 protein, B9d1. Mice lacking B9d1 displayed polydactyly, kidney cysts, ductal plate malformations, and abnormal patterning of the neural tube, concomitant with compromised ciliogenesis, ciliary protein localization, and Hedgehog (Hh) signal transduction. These data prompted us to screen MKS patients for mutations in B9D1 and B9D2. We identified a homozygous c.301A>C (p.Ser101Arg) B9D2 mutation that segregates with MKS, affects an evolutionarily conserved residue, and is absent from controls. Unlike wild-type B9D2 mRNA, the p.Ser101Arg mutation failed to rescue zebrafish phenotypes induced by the suppression of b9d2. With coimmunoprecipitation and mass spectrometric analyses, we found that Mks1, B9d1, and B9d2 interact physically, but that the p.Ser101Arg mutation abrogates the ability of B9d2 to interact with Mks1, further suggesting that the mutation compromises B9d2 function. Our data indicate that B9d1 is required for normal Hh signaling, ciliogenesis, and ciliary protein localization and that B9d1 and B9d2 are essential components of a B9 protein complex, disruption of which causes MKS