Showing papers in "Environmental Toxicology and Chemistry in 2009"
TL;DR: In this paper, the authors investigated the environmental fate of active pharmaceutical ingredients in a major production area for the global bulk drug market, where water samples were taken from a common effluent treatment plant near Hyderabad, India, which receives process water from approximately 90 bulk drug manufacturers.
Abstract: Low levels of pharmaceuticals are detected in surface, ground, and drinking water worldwide. Usage and incorrect disposal have been considered the major environmental sources of these microcontaminants. Recent publications, however, suggest that wastewater from drug production can potentially be a source of much higher concentrations in certain locations. The present study investigated the environmental fate of active pharmaceutical ingredients in a major production area for the global bulk drug market. Water samples were taken from a common effluent treatment plant near Hyderabad, India, which receives process water from approximately 90 bulk drug manufacturers. Surface water was analyzed from the recipient stream and from two lakes that are not contaminated by the treatment plant. Water samples were also taken from wells in six nearby villages. The samples were analyzed for the presence of 12 pharmaceuticals with liquid chromatography-mass spectrometry. All wells were determined to be contaminated with drugs. Ciprofloxacin, enoxacin, cetirizine, terbinafine, and citalopram were detected at more than 1 microg/L in several wells. Very high concentrations of ciprofloxacin (14 mg/L) and cetirizine (2.1 mg/L) were found in the effluent of the treatment plant, together with high concentrations of seven additional pharmaceuticals. Very high concentrations of ciprofloxacin (up to 6.5 mg/L), cetirizine (up to 1.2 mg/L), norfloxacin (up to 0.52 mg/L), and enoxacin (up to 0.16 mg/L) were also detected in the two lakes, which clearly shows that the investigated area has additional environmental sources of insufficiently treated industrial waste. Thus, insufficient wastewater management in one of the world's largest centers for bulk drug production leads to unprecedented drug contamination of surface, ground, and drinking water. This raises serious concerns regarding the development of antibiotic resistance, and it creates a major challenge for producers and regulatory agencies to improve the situation.
741 citations
TL;DR: Results suggest that the detection of pharmaceuticals and personal care products was dependent on the degree of wastewater treatment employed, and more pharmaceuticals were detected at higher concentrations and with greater frequency in liver than in fillet tissues.
Abstract: Pharmaceuticals and personal care products are being increasingly reported in a variety of biological matrices, including fish tissue; however, screening studies have presently not encompassed broad geographical areas. A national pilot study was initiated in the United States to assess the accumulation of pharmaceuticals and personal care products in fish sampled from five effluent-dominated rivers that receive direct discharge from wastewater treatment facilities in Chicago, Illinois; Dallas, Texas; Orlando, Florida; Phoenix, Arizona; and West Chester, Pennsylvania, USA. Fish were also collected from the Gila River, New Mexico, USA, as a reference condition expected to be minimally impacted by anthropogenic influence. High performance liquid chromatography-tandem mass spectrometry analysis of pharmaceuticals revealed the presence of norfluoxetine, sertraline, diphenhydramine, diltiazem, and carbamazepine at nanogram-per-gram concentrations in fillet composites from effluent-dominated sampling locations; the additional presence of fluoxetine and gemfibrozil was confirmed in liver tissue. Sertraline was detected at concentrations as high as 19 and 545 ng/g in fillet and liver tissue, respectively. Gas chromatography-tandem mass spectrometry analysis of personal care products in fillet composites revealed the presence of galaxolide and tonalide at maximum concentrations of 2,100 and 290 ng/g, respectively, and trace levels of triclosan. In general, more pharmaceuticals were detected at higher concentrations and with greater frequency in liver than in fillet tissues. Higher lipid content in liver tissue could not account for this discrepancy as no significant positive correlations were found between accumulated pharmaceutical concentrations and lipid content for either tissue type from any sampling site. In contrast, accumulation of the personal care products galaxolide and tonalide was significantly related to lipid content. Results suggest that the detection of pharmaceuticals and personal care products was dependent on the degree of wastewater treatment employed.
459 citations
TL;DR: This review focuses on the potential Hg‐Se compounds that are responsible for the antagonism at the molecular level, with an emphasis on the bis[methylmercuric]selenide, methylmercury selenocysteinate, selenoprotein P‐bound HgSe clusters, and the biominerals HgSexS1−x.
Abstract: The interaction between mercury (Hg) and selenium (Se) is one of the best known examples of biological antagonism, yet the underlying mechanism remains unclear. This review focuses on the possible pathways leading to the Hg-Se antagonism, with an emphasis on the potential Hg-Se compounds that are responsible for the antagonism at the molecular level (i.e., bis[methylmercuric]selenide, methylmercury selenocysteinate, selenoprotein P-bound HgSe clusters, and the biominerals HgSexS1−x). The presence of these compounds in biological systems has been suggested by direct or indirect evidence, and their chemical properties support their potentially key roles in alleviating the toxicity of Hg and Se (at high Hg and Se exposures, respectively) and deficiency of Se (at low Se exposures). Direct analytical evidences are needed, however, to confirm their in vivo presence and metabolic pathways, as well as to identify the roles of other potential Hg-Se compounds. Further studies are also warranted for the determination of thermodynamic properties of these compounds under physiological conditions toward a better understanding of the Hg-Se antagonism in biota, particularly under real world exposure scenarios.
401 citations
TL;DR: The corrections for aging and for modifying effects of soil properties in metal-salt-amended soils are shown to be the main factors by which PNEC values rise above the natural background range.
Abstract: Total concentrations of metals in soil are poor predictors of toxicity. In the last decade, considerable effort has been made to demonstrate how metal toxicity is affected by the abiotic properties of soil. Here this information is collated and shows how these data have been used in the European Union for defining predicted-no-effect concentrations (PNECs) of Cd, Cu, Co, Ni, Pb, and Zn in soil. Bioavailability models have been calibrated using data from more than 500 new chronic toxicity tests in soils amended with soluble metal salts, in experimentally aged soils, and in field-contaminated soils. In general, soil pH was a good predictor of metal solubility but a poor predictor of metal toxicity across soils. Toxicity thresholds based on the free metal ion activity were generally more variable than those expressed on total soil metal, which can be explained, but not predicted, using the concept of the biotic ligand model. The toxicity thresholds based on total soil metal concentrations rise almost proportionally to the effective cation exchange capacity of soil. Total soil metal concentrations yielding 10% inhibition in freshly amended soils were up to 100-fold smaller (median 3.4-fold, n = 110 comparative tests) than those in corresponding aged soils or field-contaminated soils. The change in isotopically exchangeable metal in soil proved to be a conservative estimate of the change in toxicity upon aging. The PNEC values for specific soil types were calculated using this information. The corrections for aging and for modifying effects of soil properties in metal-salt-amended soils are shown to be the main factors by which PNEC values rise above the natural background range.
370 citations
TL;DR: In addition to providing a framework for predicting contaminant fate and effects, food-web ecology can help to identify communities that are sensitive to contaminants, contaminants that are particularly insidious to communities, and species that are crucial for transmitting adverse effects across trophic levels.
Abstract: Community ecotoxicology is defined as the study of the effects of contaminants on patterns of species abundance, diversity, community composition, and species interactions. Recent discoveries that species diversity is positively associated with ecosystem stability, recovery, and services have made a community-level perspective on ecotoxicology more important than ever. Community ecotoxicology must explicitly consider both present and impending global change and shift from a purely descriptive to a more predictive science. Greater consideration of the ecological factors and threshold responses that determine community resistance and resilience should improve our ability to predict how and when communities will respond to, and recover from, xenobiotics. A better understanding of pollution-induced community tolerance, and of the costs of this tolerance, should facilitate identifying contaminant-impacted communities, thus forecasting the ecological consequences of contaminant exposure and determining the restoration effectiveness. Given the vast complexity of community ecotoxicology, simplifying assumptions, such as the possibility that the approximately 100,000 registered chemicals could be reduced to a more manageable number of contaminant classes with similar modes of action, must be identified and validated. In addition to providing a framework for predicting contaminant fate and effects, food-web ecology can help to identify communities that are sensitive to contaminants, contaminants that are particularly insidious to communities, and species that are crucial for transmitting adverse effects across trophic levels. Integration of basic ecological principles into the design and implementation of ecotoxicological research is essential for predicting contaminant effects within the context of rapidly changing, global environmental conditions.
292 citations
TL;DR: The neonicotinoids acetamiprid and thiamethoxam tested at the highest dose and fipronil at one‐five‐hundredth of LD50 have limited effects on the motor, sensory, and cognitive functions of the honeybee.
Abstract: Laboratory bioassays were conducted to evaluate on honeybee behavior the effects of sublethal doses of insecticides chronically administered orally or by contact. Emergent honeybees received a daily dose of insecticide ranging from one-fifth to one-five-hundredth of the median lethal dose (LD50) during 11 d. After exposure to fipronil (0.1 ng/bee and 0.01 ng/bee), acetamiprid (1 mug/bee and 0.1mug/bee) or thiamethoxam (1ng/bee and 0.1 ng/bee), behavioral functions of honeybees were tested on day 12. Fipronil, used at the dose of 0.1 ng/bee, induced mortality of all honeybees after one week of treatment. As a result of contact treatment at 0.01 ng/bee, honeybees spent significantly more time immobile in an open field apparatus and ingested significantly more water. In the olfactory conditioning paradigm, fipronil-treated honeybees failed to discriminate between a known and an unknown odorant. Thiamethoxam by contact induced either a significant decrease of olfactory memory 24 h after learning at 0.1 ng/bee or a significant impairment of learning performance with no effect on memory at 1 ng/bee. Responsiveness to antennal sucrose stimulation was significantly decreased for high sucrose concentrations in honeybees treated orally with thiamethoxam (1 ng/bee). The only significant effect of acetamiprid (administered orally, 0.1 mug/bee) was an increase in responsiveness to water. The neonicotinoids acetamiprid and thiamethoxam tested at the highest dose (one-tenth and one-fifth of their oral LD50 respectively) and fipronil at one-five-hundredth of LD50 have limited effects on the motor, sensory and cognitive functions of the honeybee. Our data on the intrinsic toxicity of the compounds after chronic exposure have to be taken into account for evaluation of risk to honeybees in field conditions.
287 citations
TL;DR: Mixtures of these four antidepressant pharmaceuticals slowed predator avoidance behaviors in larval fathead minnows regardless of the exposure window, providing an avenue to assess the ecological relevance of exposure in an assay of relatively short duration.
Abstract: The effects of embryonic and larval exposure to environmentally relevant (ng/L) concentrations of common antidepressants, fluoxetine, sertraline, venlafaxine, and bupropion (singularly and in mixture) on C-start escape behavior were evaluated in fathead minnows (Pimephales promelas). Embryos (postfertilization until hatching) were exposed for 5 d and, after hatching, were allowed to grow in control well water until 12 d old. Similarly, posthatch fathead minnows were exposed for 12 d to these compounds. High-speed (1,000 frames/s) video recordings of escape behavior were collected and transferred to National Institutes of Health Image for frame-by-frame analysis of latency periods, escape velocities, and total escape response (combination of latency period and escape velocity). When tested 12 d posthatch, fluoxetine and venlafaxine adversely affected C-start performance of larvae exposed as embryos. Conversely, larvae exposed for 12 d posthatch did not exhibit altered escape responses when exposed to fluoxetine but were affected by venlafaxine and bupropion exposure. Mixtures of these four antidepressant pharmaceuticals slowed predator avoidance behaviors in larval fathead minnows regardless of the exposure window. The direct impact of reduced C-start performance on survival and, ultimately, reproductive fitness provides an avenue to assess the ecological relevance of exposure in an assay of relatively short duration.
286 citations
TL;DR: Aluminum nanoparticles commonly are used in energetic formulations and may be released into the environment during their handling and use, but size, charge, and agglomeration rate of nanoparticles in the transport medium are predictive of nanoparticle mobility in soil.
Abstract: Nanoparticles are being used in broad range of applications; therefore, these materials probably will enter the environment during their life cycle. The objective of the present study is to identify changes in properties of nanoparticles released into the environment with a case study on aluminum nanoparticles. Aluminum nanoparticles commonly are used in energetic formulations and may be released into the environment during their handling and use. To evaluate the transport of aluminum nanoparticles, it is necessary not only to understand the properties of the aluminum in its initial state but also to determine how the nanoparticle properties will change when exposed to relevant environmental conditions. Transport measurements were conducted with a soil-column system that delivers a constant upflow of a suspension of nanoparticles to a soil column and monitors the concentration, size, agglomeration state, and charge of the particles in the eluent. The type of solution and surface functionalization had a marked effect on the charge, stability, and agglomeration state of the nanoparticles, which in turn impacted transport through the receiving matrix. Transport also is dependent on the size of the nanoparticles, although it is the agglomerate size, not the primary size, that is correlated with transportability. Electrostatically induced binding events of positively charged aluminum nanoparticles to the soil matrix were greater than those for negatively charged aluminum nanoparticles. Many factors influence the transport of nanoparticles in the environment, but size, charge, and agglomeration rate of nanoparticles in the transport medium are predictive of nanoparticle mobility in soil.
286 citations
TL;DR: Assessment of the uptake and quantitative accumulation, as well as the depuration, of a model nanoparticle, a 20-nm fluorescent carboxylated polystyrene bead, in the aquatic invertebrate Daphnia magna and compared it to a larger, 1,000-nm particle found that both particle sizes have crossed the gut's epithelial barrier.
Abstract: The use of nanoparticles in various applications is steadily on the rise, with use in a range of applications, including printer toner, sunscreen, medical imaging, and enhanced drug delivery. While research on human effects via, for example, inhalation is relatively well developed, the environmental assessment of nanoparticles is in its infancy. In the present study, we assessed the uptake and quantitative accumulation, as well as the depuration, of a model nanoparticle, a 20-nm fluorescent carboxylated polystyrene bead, in the aquatic invertebrate Daphnia magna and compared it to a larger, 1,000-nm particle. Using confocal microscopy, rapid accumulation in the gastrointestinal tract was observed within an hour of exposure to both particle sizes in both adults and neonates. Fluorescence could also be observed in the oil storage droplets, suggesting that both particle sizes have crossed the gut's epithelial barrier. Quantification of fluorescence of both sizes of particles showed that although uptake of the 20-nm particles was lower in terms of mass it was equal to or greater than 1000-nm particle uptake when expressed as surface area or particle number. Depuration was relatively rapid for the 1000-nm beads, decreasing by more than 90% over 4 h. In contrast, depuration of the 20-nm beads was less extensive, reaching 40% over 4 h. Transmission electron microscopy confirmed uptake of 1,000-nm beads, but uptake of 20-nm beads was inconclusive since similar-sized inclusions could be observed in control treatments.
283 citations
TL;DR: A critical review of available literature on pharmaceutical metabolites is presented, primarily focusing on their analysis and toxicological significance, and is intended to provide an overview on the recent advances in analytical tools and strategies to facilitate metabolite identification in environmental samples.
Abstract: The occurrence of human and veterinary pharmaceuticals in the environment has been a subject of concern for the past decade because many of these emerging contaminants have been shown to persist in soil and water. Although recent studies indicate that pharmaceutical contaminants can pose long-term ecological risks, many of the investigations regarding risk assessment have only considered the ecotoxicity of the parent drug, with very little attention given to the potential contributions that metabolites may have. The scarcity of available environmental data on the human metabolites excreted into the environment or the microbial metabolites formed during environmental biodegradation of pharmaceutical residues can be attributed to the difficulty in analyzing trace amounts of previously unknown compounds in complex sample matrices. However, with the advent of highly sensitive and powerful analytical instrumentations that have become available commercially, it is likely that an increased number of pharmaceutical metabolites will be identified and included in environmental risk assessment. The present study will present a critical review of available literature on pharmaceutical metabolites, primarily focusing on their analysis and toxicological significance. It is also intended to provide an overview on the recent advances in analytical tools and strategies to facilitate metabolite identification in environmental samples. This review aims to provide insight on what future directions might be taken to help scientists in this challenging task of enhancing the available data on the fate, behavior, and ecotoxicity of pharmaceutical metabolites in the environment.
282 citations
TL;DR: The effects of two progestins currently marketed in contraceptive formulations, levonorgestrel (LNG) and drospirenone (DRSP), were investigated in adult fathead minnows following an Organization for Economic Cooperation and Development 21-d fish reproduction screening assay draft protocol with additional end points.
Abstract: Although it is well known that estrogenic steroidal hormones are able to affect the sexual development and reproduction of fish at low concentrations, no data on environmental effects of the class of progestogenic hormones are available yet. Synthetic gestagens (progestins) are a component in oral contraceptives. Upon their use, a fraction of the progestins will be excreted via urine into the aquatic environment. On the basis of their pharmacological action in mammals, it is supposed that fish reproduction is the most sensitive endpoint for the progestin treatment. In order to test this assumption, the effects of two progestins currently marketed in contraceptive formulations, levonorgestrel (LNG) and drospirenone (DRSP), were investigated in adult fathead minnows (Pimephales promelas) following an Organization for Economic Cooperation and Development 21-d fish reproduction screening assay draft protocol with additional end points. Levonorgestrel was tested at measured concentrations of 0.8, 3.3, and 29.6 ng/L, and DRSP at concentrations of 0.66, 6.5, and 70 mu g/L. Both tested progestins caused an inhibition of reproduction. For LNG, this occurred at concentrations of >= 0.8 ng/L, no no-observed-effect concentration (NOEC) could be defined. Higher concentrations resulted in masculinization of females with de novo synthesis of nuptial tubercles. Drospirenone treatment, however, affected the reproductive success of fathead minnow at concentrations of 6.5 mu g/L and higher with a clear dose-response relationship and a NOEC of 0.66 mu g/L, which is above environmentally relevant concentrations.
TL;DR: Data from both laboratory and field studies supporting the hypothesis that mercury in the aquatic environment impacts the reproductive health of fish are summarized, suggesting that the inhibitory effects of mercury on reproduction occur at multiple sites within the reproductive axis.
Abstract: Mercury is a potent neurotoxin, and increasing levels have led to concern for human and wildlife health in many regions of the world. During the past three decades, studies in fish have examined the effects of sublethal mercury exposure on a range of endpoints within the reproductive axis. Mercury studies have varied from highly concentrated aqueous exposures to ecologically relevant dietary exposures using levels comparable to those currently found in the environment. This review summarizes data from both laboratory and field studies supporting the hypothesis that mercury in the aquatic environment impacts the reproductive health of fish. The evidence presented suggests that the inhibitory effects of mercury on reproduction occur at multiple sites within the reproductive axis, including the hypothalamus, pituitary, and gonads. Accumulation of mercury in the fish brain has resulted in reduced neurosecretory material, hypothalamic neuron degeneration, and alterations in parameters of monoaminergic neurotransmission. At the level of the pituitary, mercury exposure has reduced and/or inactivated gonadotropin-secreting cells. Finally, studies have examined the effects of mercury on the reproductive organs and demonstrated a range of effects, including reductions in gonad size, circulating reproductive steroids, gamete production, and spawning success. Despite some variation between studies, there appears to be sufficient evidence from laboratory studies to link exposure to mercury with reproductive impairment in many fish species. Currently, the mechanisms underlying these effects are unknown; however, several physiological and cellular mechanisms are proposed within this review.
TL;DR: In this paper, the authors present a comprehensive examination of secondary routes of active pharmaceutical ingredients (APIs) release to the environment and for direct but unintentional human exposure, and discuss the health hazards associated with: partially used devices, medication disposal practices of consumers, and interpersonal dermal transfer of API residues.
Abstract: The combined excretion of active pharmaceutical ingredients (APIs) via urine and feces is considered the primary route by which APIs from human pharmaceuticals enter the environment. Disposal of unwanted, leftover medications by flushing into sewers has been considered a secondary route—one that does not contribute substantially to overall environmental loadings. The present study presents the first comprehensive examination of secondary routes of API release to the environment and for direct but unintentional human exposure. These include bathing, washing, and laundering, all of which release APIs remaining on the skin from the use of high-content dermal applications or from excretion to the skin via sweating, and disposal of unused and partially used high-content devices. Also discussed are the health hazards associated with: partially used devices, medication disposal practices of consumers, and interpersonal dermal transfer of API residues. Understanding these secondary routes is important from the perspective of pollution prevention, because actions can be designed more easily for reducing the environmental impact of APIs compared with the route of direct excretion (via urine and feces), for reducing the incidence of unintentional and purposeful poisonings of humans and pets, and for improving the quality and cost-effectiveness of health care. Overall, unintentional exposure to APIs for humans via these routes is possibly more important than exposure to trace residues recycled from the environment in drinking water or foods.
TL;DR: Tests of lethal concentrations estimated to kill 50% of a population after 96 h (LC5096‐h) on a wider diversity of species from both eastern and western North America are conducted, substantially increases the available data on amphibian sensitivity to glyphosate formulations that include either POEA surfactant or the equally moderately to highly toxic surfactants of Roundup Original Max.
Abstract: With the increased use of glyphosate-based herbicides (marketed under several names, including Roundup and Vision), there has been a concomitant increased concern about the unintended impacts that particular formulations containing the popular surfactant polyethoxylated tallowamine (POEA) might have on amphibians. Published studies have examined a relatively small number of anuran species (primarily from Australia and eastern North America) and, surprisingly, no species of salamanders. Using a popular formulation of glyphosate (Roundup Original Max), the goal of the present study was to conduct tests of lethal concentrations estimated to kill 50% of a population after 96 h (LC50(96-h)) on a wider diversity of species from both eastern and western North America. Tests were conducted on nine species of stage 25, larval anurans from three families (Ranidae: Rana pipiens, R. clamitans, R. sylvatica, R. catesbeiana, R. cascadae; Bufonidae: Bufo americanus, B. boreas; and Hylidae: Hyla versicolor, Pseudacris crucifer) and four species of larval salamanders from two families (Ambystomatidae: Ambystoma gracile, A. maculatum, A. laterale; and Salamandridae: Notophthalmus viridescens). For the nine species of larval anurans, LC50(96-h) values ranged from 0.8- to 2.0-mg acid equivalents per liter with relatively little pattern in differential sensitivity among the species or families. The four species of larval salamanders were less sensitive than the anurans, with LC50(96-h) values ranging from 2.7- to 3.2-mg acid equivalents per liter and no substantial differences among the species of salamanders. This work substantially increases the available data on amphibian sensitivity to glyphosate formulations that include either POEA surfactants or the equally moderately to highly toxic surfactants of Roundup Original Max and should be useful for improving future risk assessments.
TL;DR: It is demonstrated that manufactured ZnO‐NPs have toxicity to the nematode C. elegans similar to that of aqueous ZnCl2.
Abstract: Information describing the possible impacts of manufactured nanoparticles on human health and ecological receptors is limited. The objective of the present study was to evaluate the potential toxicological effects of manufactured zinc oxide nanoparticles (ZnO-NPs; 1.5 nm) compared to aqueous zinc chloride (ZnCl2) in the free-living nematode Caenorhabditis elegans. Toxicity of both types of Zn was investigated using the ecologically relevant endpoints of lethality, behavior, reproduction, and transgene expression in a mtl-2::GFP (gene encoding green fluorescence protein fused onto the metallothionein-2 gene promoter) transgenic strain of C. elegans. Zinc oxide nanoparticles showed no significant difference from ZnCl2 regarding either lethality or reproduction in C. elegans, as indicated by their median lethal concentrations (LC50s; p = 0.29, n=3) and median effective concentrations (EC50s; Z = 0.835, p = 0.797). Also, no significant difference was found in EC50s for behavioral change between ZnO-NPs (635 mg Zn/L; 95% confidence interval [CI], 477-844 mg Zn/L) and ZnCl2 (546 mg Zn/L; 95% CI, 447-666 mg Zn/L) (Z = 0.907, p = 0.834). Zinc oxide nanoparticles induced transgene expression in the mtl-2::GFP transgenic C. elegans in a manner similar to that of ZnCl2, suggesting that intracellular biotransformation of the nanoparticles might have occurred or the nanoparticles have dissolved to Zn2+ to enact toxicity. These findings demonstrate that manufactured ZnO-NPs have toxicity to the nematode C. elegans similar to that of aqueous ZnCl2.
TL;DR: Whether pharmaceuticals in river water affect the local benthic community structure (diatoms and invertebrates) of this system is studied and a potential causal association between the concentrations of some anti-inflammatories and beta-blockers and the abundance and biomass of several bentho-biota is revealed.
Abstract: A wide range of human pharmaceuticals are present at low concentrations in freshwater systems, particularly in sections of polluted river. These compounds show high biological activity, often associated with a high stability. These characteristics imply a potential impact of these substances on aquatic biota even when present at low environmental concentrations. Low flow conditions in Mediterranean rivers, most of which flow through densely populated areas and are subjected to intensive water use, increase the environmental risk of these emergent compounds. Here, we studied whether pharmaceuticals in river water affect the local benthic community structure (diatoms and invertebrates). For this purpose, we analyzed the occurrence of pharmaceuticals along the Llobregat River and examined the benthic community structure (diatoms and invertebrates) of this system. Some pharmaceutical products in the Llobregat River registered concentrations greater than those cited in the literature. Multivariate analyses revealed a potential causal association between the concentrations of some anti-inflammatories and β-blockers and the abundance and biomass of several benthic invertebrates (Chironomus spp. and Tubifex tubifex). Further interpretation in terms of cause-and-effect relationships is discussed; however, it must be always taken with caution because other pollutants also may have significant contributions. Combined with further community experiments in the laboratory, our approach could be a desirable way to proceed in future risk management decisions.
TL;DR: The present study presents, to the authors' knowledge, the first national, catchment-based risk assessment for steroid estrogens in the world, which predicted the concentrations of estradiol (E2), estrone, and ethinylestradiol, which were combined and compared with known biological effect levels to predict the risk of endocrine disruption for 10,313 individual river reaches in England and Wales.
Abstract: The occurrence of intersex fish is widespread in the rivers of England and Wales. The extent of intersex in fish populations is believed to be strongly linked to their exposure to steroid oestrogens. This paper presents the first national, catchment-based, risk assessment for steroid oestrogens in the world. A Graphical Information System-based model predicted the concentrations of estradiol (E2), estrone (E1) and ethinylestradiol (EE2) which were combined and compared with known biological effect levels to predict endocrine disruption risk for 10,313 individual river reaches (21,452 km) receiving effluent from more than 2,000 sewage treatment plants (STPs) serving over 29 million people. The large scale of this assessment underlines the usefulness of computer based risk assessment methods. Overall, 39% of the modelled reaches (all percentages are expressed as % of the total river length modelled) in England and Wales were predicted to be not at risk from endocrine disruption (mean concentrations 10 ng/L E2 equivalents). However, many of these high risk reaches were ditches which were composed almost entirely of sewage effluent. The model could equally well be applied to any other chemical of concern emanating from the human population and which would be impracticable to assess by measurement.
TL;DR: The results suggest that arsenic adsorption to the nanoparticles was not significantly affected by the pH, ionic strength and temperature in the ranges tested, which are typical of most potable water sources.
Abstract: Little work has been conducted on the adsorption of arsenic to the mixed iron [Fe(II)/(III)] oxide magnetite and the effect that environmental parameters, such as pH, ionic strength, and temperature, have on adsorption. Magnetite nanoparticles are unique because of their affinity for both arsenate and arsenite and increased adsorption capacity from their bulk counterparts. This article shows the effect of various magnetite nanoparticle concentrations on arsenic adsorption kinetics. The adsorption data show the ability of the magnetite nanoparticles to remove arsenate and arsenite from solution in both synthetic and natural waters, and the data fit a first-order rate equation. Because of the increased surface area of these particles, less than 1 g/L of magnetite nanoparticles was needed. The results suggest that arsenic adsorption to the nanoparticles was not significantly affected by the pH, ionic strength and temperature in the ranges tested, which are typical of most potable water sources.
TL;DR: Data show that East Greenland polar bears do not accumulate high levels of mercury in their brain stems, and decreased levels of NMDA receptors could be one of the most sensitive indicators of mercury's subclinical and early effects.
Abstract: Polar bears (Ursus maritimus) are exposed to high concentrations of mercury because they are apex predators in the Arctic ecosystem. Although mercury is a potent neurotoxic heavy metal, it is not known whether current exposures are of neurotoxicological concern to polar bears. We tested the hypotheses that polar bears accumulate levels of mercury in their brains that exceed the estimated lowest observable adverse effect level (20 microg/g dry wt) for mammalian wildlife and that such exposures are associated with subtle neurological damage, as determined by measuring neurochemical biomarkers previously shown to be disrupted by mercury in other high-trophic wildlife. Brain stem (medulla oblongata) tissues from 82 polar bears subsistence hunted in East Greenland were studied. Despite surprisingly low levels of mercury in the brain stem region (total mercury = 0.36 +/- 0.12 microg/g dry wt), a significant negative correlation was measured between N-methyl-D-aspartate (NMDA) receptor levels and both total mercury (r = -0.34, p < 0.01) and methylmercury (r = -0.89, p < 0.05). No relationships were observed among mercury, selenium, and several other neurochemical biomarkers (dopamine-2, gamma-aminobutyric acid type A, muscarinic cholinergic, and nicotinic cholinergic receptors; cholinesterase and monoamine oxidase enzymes). These data show that East Greenland polar bears do not accumulate high levels of mercury in their brain stems. However, decreased levels of NMDA receptors could be one of the most sensitive indicators of mercury's subclinical and early effects.
TL;DR: Changes in the blood isomer profiles over time and their inverse correlation to isomer elimination patterns in urine, feces, or both provided unequivocal evidence of significant isomer-specific biological handling.
Abstract: Perfluorinated acids (PFAs) and their precursors (PFA-precursors) exist in the environment as linear and multiple branched isomers. These isomers are hypothesized to have different biological properties, but no isomer-specific data are currently available. The present study is the first in a two-part project examining PFA isomer-specific uptake, tissue distribution, and elimination in a rodent model. Seven male Sprague-Dawley rats were administered a single gavage dose of approximately 500 microg/kg body weight perfluorooctane sulfonate (C(8)F(17)SO(3)(-), PFOS), perfluorooctanoic acid (C(7)F(15)CO(2)H, PFOA), and perfluorononanoic acid (C(8)F(17)CO(2)H, PFNA) and 30 microg/kg body weight perfluorohexane sulfonate (C(6)F(13)SO(3)(-), PFHxS). Over the subsequent 38 d, urine, feces, and tail-vein blood samples were collected intermittently, while larger blood volumes and tissues were collected on days 3 and 38 for isomer analysis by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). For all PFAs, branched isomers generally had lower blood depuration half-lives than the corresponding linear isomer. The most remarkable exception was for the PFOS isomer containing an alpha-perfluoromethyl branch (1m-PFOS), which was threefold more persistent than linear PFOS, possibly due to steric shielding of the hydrophilic sulfonate moiety. For perfluoromonomethyl-branched isomers of PFOS, a structure-property relationship was observed whereby branching toward the sulfonate end of the perfluoroalkyl chain resulted in increased half-lives. For PFHxS, PFOA, and PFOS, preferential elimination of branched isomers occurred primarily via urine, whereas for PFNA preferential elimination of the isopropyl isomer occurred via both urine and feces. Changes in the blood isomer profiles over time and their inverse correlation to isomer elimination patterns in urine, feces, or both provided unequivocal evidence of significant isomer-specific biological handling. Source assignment based on PFA isomer profiles in biota must therefore be conducted with caution, because isomer profiles are unlikely to be conserved in biological samples.
TL;DR: A temperature TIE model was confirmed and trends also held true in sediment exposures with chlorpyrifos and permethrin, indicating that water‐only exposures were adequate substitutes for examining this mechanism.
Abstract: Toxicity identification evaluation (TIE) methods can be used to identify toxic compounds in environmental samples using a variety of laboratory techniques. Whereas TIEs exist for nonpolar organics, relatively few methods are established for individual contaminant classes. Toxicity identification evaluations have shown pesticides to be the cause of toxicity in agricultural waters and effluents, and more recent studies have shown that the insecticide class of concern is pyrethroids. The primary objectives of the present study were to confirm a temperature TIE model and mechanistically explain these trends. This was achieved by comparing the relative toxicity and influence of temperature (13 vs 23°C) on Chironomus dilutus exposed to four insecticides, including two pyrethroids, an organophosphate, and an organochlorine, and then explaining these changes using toxicokinetics. A 10°C temperature decrease increased the toxicity of pyrethroids and DDT but decreased the toxicity of chlorpyrifos. The decrease in chlorpyrifos toxicity was driven primarily by the reduction of the formation of more toxic products via decreased biotransformation. The increase in DDT toxicity, in contrast, can be attributed to increased nerve sensitivity at 13 versus 23°C. The pyrethroid toxicity change, however, resulted from a combination of increased accumulation of parent compound and increased nerve sensitivity, exacerbating the toxicity of pyrethroids at 13°C. These trends also held true in sediment exposures with chlorpyrifos and permethrin, indicating that water-only exposures were adequate substitutes for examining this mechanism.
TL;DR: Results indicate that increased hepatic T4 glucuronidation via UGT1A1 and increased thyroidal conversion of T4 to T3 via DIO1 were responsible in part for PFOS‐induced hypothyroxinemia in rats.
Abstract: The potential toxicity of perfluorooctane sulfonate (PFOS), an environmentally persistent organic pollutant, is of great concern. The present study examines the ability of PFOS to disturb thyroid function and the possible mechanisms involved in PFOS-induced thyroid hormone alteration. Male Sprague-Dawley rats were exposed to 1.7, 5.0, and 15.0 mg/L of PFOS in drinking water for 91 consecutive days. Serum was collected for analysis of total and free thyroxine (T4), total triiodothyronine (T3), and thyrotrophin (TSH). Thyroid and liver were removed for the measurement of endpoints closely related to thyroid hormone biosynthesis and metabolism following PFOS exposure. Determined endpoints were the messenger RNA (mRNA) levels for two isoforms of uridine diphosphoglucuronosyl transferases (UGT1A6 and UGT1A1) and type 1 deiodinase (DIO1) in liver, sodium iodide symporter (NIS), TSH receptor (TSHR), and DIO1 in thyroid as well as the activity of thyroid peroxidase (TPO). Serum total T4 level decreased significantly at all applied dosages, whereas total T3 level increased markedly only at 1.7 mg/L of PFOS. No statistically significant toxic effects of PFOS on serum TSH were observed. Hepatic UGT1A1, but not UGT1A6, mRNA was up-regulated at 5.0 and 15.0 mg/L of PFOS. Treatment with PFOS lowered hepatic DIO1 mRNA at 15.0 mg/L but increased thyroidal DIO1 mRNA dose dependently. The activity of TPO, NIS, and TSHR mRNA in thyroid were unaffected by PFOS treatment. These results indicate that increased hepatic T4 glucuronidation via UGT1A1 and increased thyroidal conversion of T4 to T3 via DIO1 were responsible in part for PFOS-induced hypothyroxinemia in rats.
TL;DR: Relating site-specific pH variability of surface waters to ionization state may allow researchers to reduce uncertainty during ecological risk assessment of pharmaceuticals by improving estimates of biological effects associated with exposure.
Abstract: Researchers recognize that ionization state may influence the biological activity of weak acids and bases. Dissociation in aqueous solutions is controlled by the pKa of a compound and the pH of the matrix. Because many pharmaceuticals are implicitly designed as ionizable compounds, site-specific variability in pH of receiving waters may introduce uncertainty to ecological risk assessments. The present study employed 48-h and 7-d toxicity tests with Pimephales promelas exposed to the model weak base pharmaceutical sertraline over a gradient of environmentally relevant surface water pHs. The 48-h experiments were completed in triplicate, and the average lethal concentration values were 647, 205, and 72 μL sertraline at pH 6.5, 7.5, and 8.5, respectively. Survivorship, growth, and feeding rate (a nontraditional endpoint linked by other researchers to sertraline's specific mode of action) were monitored during the 7-d experiment. Adverse effects were more pronounced when individuals were exposed to sertraline at pH 8.5 compared to pH 7.5 and 6.5. The pH-dependent toxicological relationships from these studies were related to in-stream pH data for two streams in the Brazos River basin of central Texas, USA. This predictive approach was taken because of the scarcity of environmental analytical data for sertraline. The results of this study emphasized temporal variability associated with in-stream pH linked to seasonal differences within and between these spatially related systems. Relating site-specific pH variability of surface waters to ionization state may allow researchers to reduce uncertainty during ecological risk assessment of pharmaceuticals by improving estimates of biological effects associated with exposure.
TL;DR: The effects of soil type, the presence of biosolids, and the impact of chemical mixture interactions on the degradation of three pharmaceuticals: naproxen, carbamazepine, and fluoxetine were assessed.
Abstract: Pharmaceuticals may be released to the soil environment through the application of biosolids to land. To understand those factors affecting the persistence of pharmaceuticals in the soil environment, the present study was performed to assess the effects of soil type, the presence of biosolids, and the impact of chemical mixture interactions on the degradation of three pharmaceuticals: naproxen, carbamazepine, and fluoxetine. Single-compound studies showed that naproxen degraded in a range of soils with half-lives ranging from 3.1 to 6.9 d and in biosolids with a half-life of 10.2 d. No relationships were observed between degradation rate and soil physicochemical properties and soil bioactivity. For naproxen, addition of biosolids to soils reduced the degradation rate observed in the soil-only studies, with half-lives in the soil-biosolid systems ranging from 3.9 to 15.1 d. Carbamazepine and fluoxetine were found to be persistent in soils, biosolids, and soil-biosolid mixtures. When degradation was assessed using a mixture of the three study compounds and the sulfonamide antibiotic sulfamethazine, the degradation behavior of fluoxetine and carbamazepine was similar to that observed in the single compound studies (i.e., no degradation). However, the degradation rate of naproxen in soils, biosolids, and soil-biosolid systems spiked with the mixture was significantly slower than in the single-compound studies. As degradation studies for risk assessment purposes are performed using single substances in soil-only studies, it is possible that current risk assessment procedures will underestimate environmental impacts. Further work is therefore warranted on a larger range of substances, soils, biosolid types, and chemical mixtures to better understand the fate of pharmaceuticals in terrestrial systems.
TL;DR: This model can predict biotransformation rate constants from chemical structure for screening level bioaccumulation hazard assessments, exposure and risk assessments, comparisons with other in vivo and in vitro estimates, and as a contribution to testing strategies that reduce animal usage.
Abstract: An evaluated database of whole body in vivo biotransformation rate estimates in fish was used to develop a model for predicting the primary biotransformation half-lives of organic chemicals. The estimated biotransformation rates were converted to half-lives and divided into a model development set (n=421) and an external validation set (n=211) to test the model. The model uses molecular substructures similar to those of other biodegradation models. The biotransformation half-life predictions were calculated based on multiple linear regressions of development set data against counts of 57 molecular substructures, the octanol-water partition coefficient, and molar mass. The coefficient of determination (r2) for the development set was 0.82, the cross-validation (leave-one-out coefficient of determination, q2) was 0.75, and the mean absolute error (MAE) was 0.38 log units (factor of 2.4). Results for the external validation of the model using an independent test set were r2 = 0.73 and MAE = 0.45 log units (factor of 2.8). For the development set, 68 and 95% of the predicted values were within a factor of 3 and a factor of 10 of the expected values, respectively. For the test (or validation) set, 63 and 90% of the predicted values were within a factor of 3 and a factor of 10 of the expected values, respectively. Reasons for discrepancies between model predictions and expected values are discussed and recommendations are made for improving the model. This model can predict biotransformation rate constants from chemical structure for screening level bioaccumulation hazard assessments, exposure and risk assessments, comparisons with other in vivo and in vitro estimates, and as a contribution to testing strategies that reduce animal usage.
TL;DR: In this article, a database with BCF of 73 acids and 65 bases was collected from the literature, and a dynamic cell model based on the Fick- Nernst-Planck equation was tested.
Abstract: The bioaccumulation potential is an important criterion in risk assessment of chemicals. Several regressions between bioconcentration factor (BCF) in fish and octanol-water partition coefficient (K(OW)) have been developed for neutral organic compounds, but very few approaches address the BCF of ionizable compounds. A database with BCFs of 73 acids and 65 bases was collected from the literature. The BCF estimation method recommended by the Technical Guidance Document (TGD) for chemical risk assessment in the European Union was tested for ionizing substances using log K(OW) (corrected for the neutral species, log[ f(n) x K(OW)]) and log D (sum of log K(OW) of neutral and ionic molecule, apparent log K(OW)) as predictors. In addition, the method of Meylan et al. (Environ Toxicol Chem 1999; 18:664-672) for ionizable compounds and a dynamic cell model based on the Fick- Nernst-Planck equation were tested. Moreover, our own regressions for the BCF were established from log K(OW) and pK(a). The bioaccumulation of lipophilic compounds depends mainly on their lipophilicity, and the best predictor is log D. Dissociation, the pH-dependent ion trap, and electrical attraction of cations impact the BCF. Several methods showed acceptable results. The TGD regressions gave good predictions when log( f(n) x K(OW)) or log D were used as a predictor instead of log K(OW). The new regressions to log K(OW) and pK(a) performed similarly, with mean errors of approximately 0.4. The method of Meylan et al. did not perform as well. The cell model showed weak results for acids but was among the best methods for bases.
TL;DR: The distributions demonstrated that at environmentally relevant concentrations in developed countries there is limited acute or subchronic aquatic hazard of parabens to the organisms and responses examined.
Abstract: Parabens are common antimicrobial agents found in thousands of pharmaceuticals and personal care products. Parabens are introduced into aquatic ecosystems from wastewater treatment plant effluents and have been detected in surface waters in the low microgram per liter range. Although these compounds display low toxicity in mammals, paraben toxicity to aquatic organisms has not been investigated. Standardized acute and subchronic endpoints in larval fish (Pimephales promelas) and cladoceran (Daphnia magna) models were examined for seven different parabens (methyl-, ethyl-, isopropyl-, propyl-, isobutyl-, butyl-, benzylparaben), which encompassed a range of log P values. Paraben 48 h median lethal concentration values (LC50) ranged from 4.0 to 24.6 mg/L in D. magna and 3.3 to >160.0 mg/L in fathead minnow. Growth and reproduction in D. magna had lowest-observed-effect concentrations (LOECs) ranging from 0.12 to 9.0 mg/L and 1.5 to 6.0 mg/L, respectively. Fathead minnow growth was adversely affected at levels ranging from 1.0 to 25.0 mg/L. Aquatic toxicity of the parabens was inversely related to lipophilicity, suggesting that responses using standardized endpoints resulted from narcosis. Utilizing toxicity benchmark concentrations (e.g., LC50s, LOECs) for each compound, chemical toxicity distributions, a probabilistic hazard assessment technique, were developed to assess the probabilities of detecting parabens that elicit a response at or below a given concentration. For the responses assessed in the present study, the 5th centile values (the concentration at which 5% of parabens elicit a response) ranged from 15 microg/L to 2.43 mg/L, with D. magna growth eliciting the lowest 5th centile value and acute D. magna mortality eliciting the highest. The distributions demonstrated that at environmentally relevant concentrations in developed countries there is limited acute or subchronic aquatic hazard of parabens to the organisms and responses examined.
TL;DR: This special issue of Environmental Toxicology and Chemistry includes a timely collection of manuscripts examining the environmental chemistry, toxicology, risk assessment, and management of PPCPs.
Abstract: Pharmaceuticals and personal care products (PPCPs) include numerous classes of chemicals with unique physiochemical properties and biological activities. Over the past decade research on the occurrence, fate, effects, risk assessment, and management of PPCPs in the environment has peaked. It is important to appreciate the utility of traditional approaches for examining contaminant hazard and risk while understanding relevant limitations and important research needs to advance environmental risk assessment (ERA) and management efforts for PPCPs. Spurred initially by the critical reviews of Halling-Sorensen et al. [1] (755 citations as of 6 July 2009) and Daughton and Ternes [2] (778 citations as of 6 July 2009), this special issue of Environmental Toxicology and Chemistry includes a timely collection of manuscripts examining the environmental chemistry, toxicology, risk assessment, and management of PPCPs.
TL;DR: The findings indicate that waterbirds demethylate mercury in their livers if exposure exceeds a threshold value and suggest that taxonomic differences in demethylation ability may be an important factor in evaluating species-specific risk to MeHg exposure.
Abstract: We assessed methylmercury (MeHg) demethylation in the livers of adults and chicks of four waterbird species that commonly breed in San Francisco Bay: American avocets, black-necked stilts, Caspian terns, and Forster's terns. In adults (all species combined), we found strong evidence for a threshold model where MeHg demethylation occurred above a hepatic total mercury concentration threshold of 8.51 +/- 0.93 microg/g dry weight, and there was a strong decline in %MeHg values as total mercury (THg) concentrations increased above 8.51 microg/g dry weight. Conversely, there was no evidence for a demethylation threshold in chicks, and we found that %MeHg values declined linearly with increasing THg concentrations. For adults, we also found taxonomic differences in the demethylation responses, with avocets and stilts showing a higher demethylation rate than that of terns when concentrations exceeded the threshold, whereas terns had a lower demethylation threshold (7.48 +/- 1.48 microg/g dry wt) than that of avocets and stilts (9.91 +/- 1.29 microg/g dry wt). Finally, we assessed the role of selenium (Se) in the demethylation process. Selenium concentrations were positively correlated with inorganic Hg in livers of birds above the demethylation threshold but not below. This suggests that Se may act as a binding site for demethylated Hg and may reduce the potential for secondary toxicity. Our findings indicate that waterbirds demethylate mercury in their livers if exposure exceeds a threshold value and suggest that taxonomic differences in demethylation ability may be an important factor in evaluating species-specific risk to MeHg exposure. Further, we provide strong evidence for a threshold of approximately 8.5 microg/g dry weight of THg in the liver where demethylation is initiated.
TL;DR: The chronic toxicity of two of the insecticides most commonly used in the Central Valley and found in the mountains, chlorpyrifos and endosulfan, to larval Pacific treefrogs and foothill yellow‐legged frogs is examined and the implications of this toxicity to declining amphibian populations are discussed.
Abstract: Contaminants have been associated with population declines of several amphibian species in California (USA). Pesticides from the Central Valley of California are transported by winds into the Sierra Nevada Mountains and precipitate into wet meadows where amphibians breed. The present study examined the chronic toxicity of two of the insecticides most commonly used in the Central Valley and found in the mountains, chlorpyrifos and endosulfan, to larval Pacific treefrogs (Pseudacris regilla) and foothill yellow-legged frogs (Rana boylii) and discusses the implications of this toxicity to declining amphibian populations. Larvae were exposed to the pesticides from Gosner stages 25 to 26 through metamorphosis. The estimated median lethal concentration (LC50) for chlorpyrifos was 365 microg/L in P. regilla and 66.5 microg/L for R. boylii. Time to metamorphosis increased with concentration of chlorpyrifos in both species, and cholinesterase activity declined with exposure concentration in metamorphs of both species at Gosner stages 42 to 46. For endosulfan, the estimated LC50 was 15.6 microg/L for P. regilla and 0.55 microg/L for R. boylii. All R. boylii exposed to concentrations of greater than 0.8 microg/L died before they entered metamorphosis. Pseudacris regilla remains relatively abundant and is broadly distributed throughout California. In contrast, R. boylii is among the species experiencing severe population declines. The present study adds to the increasing evidence that pesticides are very harmful to amphibians living in areas that are miles from sources of pesticide application.