bluuebunny/crossref_metadata_2025 huggingface dataset:
Quantitative structure-activity relationships for human health effects: Commonalities with other endpoints
Authors: Cronin Mark T. D. , Dearden John C. , Walker John D. , Worth Andrew P.
Published: November 2004

This article describes the use of quantitative structure-activity relationships (QSARs) to predict toxicity endpoints for ecologically relevant and human-surrogate species. The interrelationships between the endpoints, and the possibilities of exploring the commonalities of chemical action from one species to another as well as from one endpoint to another, are evaluated. A number of toxic endpoints are discussed including mutagenicity and carcinogenicity; developmental toxicity (teratogenicity); acute toxicity; skin sensitization; skin, eye, and sensory irritation; and the modeling of membrane permeability. A number of electrophilic molecular substructures have been identified that are common to a number of toxicities. It is postulated that if such a substructure is observed in a molecule, it may exhibit a range of toxicities. Further, there appear to be relationships between the toxicity to ecologically relevant and human-surrogate species, which may allow for appreciation and possible extrapolation in both directions. Overall, however, QSARs are limited by the paucity of available toxicological data and information.
Recent developments in broadly applicable structure-biodegradability relationships
Authors: Jaworska Joanna S. , Boethling Robert S. , Howard Philip H.
Published: November 2004

Biodegradation is one of the most important processes influencing concentration of a chemical substance after its release to the environment. It is the main process for removal of many chemicals from the environment and therefore is an important factor in risk assessments. This article reviews available methods and models for predicting biodegradability of organic chemicals from structure. The first section of the article briefly discusses current needs for biodegradability estimation methods related to new and existing chemicals and in the context of multimedia exposure models. Following sections include biodegradation test methods and endpoints used in modeling, with special attention given to the Japanese Ministry of International Trade and Industry test; a primer on modeling, describing the various approaches that have been used in the structure/biodegradability relationship work, and contrasting statistical and mechanistic approaches; and recent developments in structure/biodegradability relationships, divided into group contribution, chemometric, and artificial intelligence approaches.
Quantitative structure-activity relationship models for prediction of estrogen receptor binding affinity of structurally diverse chemicals
Authors: Schmieder Patricia K. , Ankley Gerald , Mekenyan Ovanes , Walker John D. , Bradbury Steven
Published: November 2004

The demonstrated ability of a variety of structurally diverse chemicals to bind to the estrogen receptor has raised the concern that chemicals in the environment may be causing adverse effects through interference with nuclear receptor pathways. Many structure-activity relationship models have been developed to predict chemical binding to the estrogen receptor as an indication of potential estrogenicity. Models based on either two-dimensional or three-dimensional molecular descriptions that have been used to predict potential for binding to the estrogen receptor are the subject of the current review. The utility of such approaches to predict binding potential of diverse chemical structures in large chemical inventories, with potential application in a tiered risk assessment scheme, is discussed.
Quantitative structure-activity relationships for predicting percutaneous absorption rates
Authors: Walker John D. , Rodford Rosemary , Patlewicz Grace
Published: November 2004

Quantitative structure-activity relationships (QSARs) for predicting percutaneous absorption rates were reviewed. Overall progress has been hampered by the sparseness of good quality experimental data. A number of researchers have used the same data set to develop QSARs for predicting percutaneous absorption rates, a fact that makes it difficult, at this time, to recommend one or two QSARs for predicting percutaneous absorption rates. Identification of chemicals within domains of large chemical universes that should be tested to improve QSARs and the subsequent development of experimental percutaneous absorption rates for those chemicals will facilitate the development of more robust QSARs for predicting percutaneous absorption rates.
Quantitative structure-activity relationships for predicting metabolism and modeling cytochrome P450 enzyme activities
Authors: Long Anthony , Walker John D.
Published: November 2004

Quantitative structure-activity relationships (QSARs) for predicting phase I and phase II metabolism and for modeling cytochrome P450 enzyme activities are described and reviewed. Papers dealing with three-dimensional techniques such as comparative molecular field analysis and pharmacophore modeling are included. This review focuses on those cytochrome P450 isoenzymes that are expressed in human hepatocytes and that are commonly responsible for the majority of drug and xenobiotic metabolism. Substrate-type selectivity information for those isoenzymes is included. The importance of lipophilicity correlations in xenobiotic metabolism predictions are outlined. A brief inclusion of available material on the prediction phase II conjugation biotransformations such as glucuronidation, sulfation, glycination, and glutathionation are included. Historical information is briefly discussed, but more detailed reviews are provided for papers published since 1997.
Quantitative structure-property relationships for predicting henry's law constant from molecular structure
Authors: Dearden John C. , Schüürmann Gerrit
Published: November 2004

Various models are available for the prediction of Henry's law constant (H) or the air-water partition coefficient (Kaw), its dimensionless counterpart. Incremental methods are based on structural features such as atom types, bond types, and local structural environments; other regression models employ physicochemical properties, structural descriptors such as connectivity indices, and descriptors reflecting the electronic structure. There are also methods to calculate H from the ratio of vapor pressure (pv) and water solubility (Sw) that in turn can be estimated from molecular structure, and quantum chemical continuum-solvation models to predict H via the solvation-free energy (ΔGs). This review is confined to methods that calculate H from molecular strúcture without experimental information and covers more than 40 methods published in the last 26 years. For a subset of eight incremental methods and four continuum-solvation models, a comparative analysis of their prediction performance is made using a test set of 700 compounds that includes a significant number of more complex and drug-like chemical structures. The results reveal substantial differences in the application range as well as in the prediction capability, a general decrease in prediction performance with decreasing H, and surprisingly large individual prediction errors, which are particularly striking for some quantum chemical schemes. The overall best-performing method appears to be the bond contribution method as implemented in the HEN-RYWIN software package, yielding a predictive squared correlation coefficient (q2) of 0.87 and a standard error of 1.03 log units for the test set.
Biotransformation of dissolved and sediment-bound fluoranthene in the polychaete, Capitella sp. I
Authors: Selck Henriette , Palmqvist Annemette , Forbes Valery E.
Published: November 2004

Polycyclic aromatic hydrocarbons (PAHs) are widely distributed in the marine environment and have physicochemical properties that make them likely to bioaccumulate. The main purpose of this study was to investigate fluoranthene (FLU) uptake, biotransformation and elimination in the deposit-feeding polychaete Capitella sp. I exposed via different routes. Individual worms were exposed to either dissolved FLU or to both dissolved and sediment-bound FLU. The 14C-FLU was used as a tracer to determine the amounts of unmetabolized FLU (parent), water-soluble (aqueous)- and water-insoluble (polar) FLU metabolites and FLU residues (unextractable fraction) in sediment, water, and worm tissue. Capitella was capable of accumulating and biotransforming FLU regardless of route of exposure, thus suggesting that biotransformation activity is not restricted to gut tissues. Although both feeding and nonfeeding worms were able to biotransform FLU extensively, feeding worms eliminated/transformed parent FLU faster than both aqueous and polar FLU metabolites after transfer to clean conditions, whereas nonfeeding worms barely excreted FLU in any form. The high biotransformation capability of Capitella sp. I, along with the dependency of elimination on exposure route, demonstrates the potential importance of these processes in controlling the fate and effects of PAH and possibly other organic toxicants in contaminated marine sediments.
A model to understand the confounding effects of natural sediments in toxicity tests with Chironomus riparius
Authors: Péry Alexandre R. R. , Sulmon Vanessa , Mons Raphaël , Flammarion Patrick , Lagadic Laurent , Garric Jeanne
Published: November 2004

Recently, we built a model to link feeding input with growth, emergence, and reproduction of the midge Chironomus riparius exposed to an artificial sandy sediment. This model is based on assumptions about both feeding behavior and use of energy. Here, we show how it can be used for toxicity tests with natural sediments to understand and model the influence of sediment characteristics. We measured growth, emergence, and reproduction of chironomids exposed in beakers to four unpolluted natural sediments and three feeding conditions (no feeding, 0.2 mg Tetramin®/larva/d, and 1.4 mg Tetramin/larva/d) and compared the results with data obtained on our artificial sandy sediment. Sediment characteristics had lower influence on growth than feeding level, but their influence could not be neglected. First, we could distinguish between sandy sediments and other sediments. This difference resulted in a significant delay of about 18 h in the growth curves. Second, in case of food limitation, chironomids could use the organic materials in the sediment, provided that the C:N ratio of the sediment was less than 14. Our model proved to be able to incorporate those two phenomena. As for reproduction, we observed a better reproduction (measured in number of eggs per mass) for natural sediments than for artificial sediments. We showed that this difference could be due to the lipid content of the natural sediments.
Determination of the estrogenic and antiestrogenic effects of environmental contaminants in chicken embryo hepatocyte cultures by quantitative-polymerase chain reaction
Authors: Lorenzen Angela , Williams Kim L. , Oon Thomas W. M
Published: November 2004

A method was developed to measure the estrogenic and antiestrogenic effects of various chemicals and organochlorine extracts in chicken embryo primary hepatocyte cultures. Messenger RNAs (mRNAs) for the estrogen-inducible egg yolk proteins, vitellogenin II (VTGII), and very low-density lipoprotein apoprotein II (apoII), were measured by multiplex quantitative reverse transcription-polymerase chain reaction (Q-PCR). After 48 h of exposure, both VTGII and apoII mRNA levels were induced by moxestrol (1–1,000 nM), 17pj-estradiol (10–1,000 nM), α, p'-DDT (apoII: 1,000 and 10,000 nM, VTGII: 10,000 nM), 4-tert-octylphenol ([OP]; apoII: 20 and 50 μM, VTGII: 10–50μM), and methoxychlor ([MXCL]; apoII: 5–50 μM, VTGII: 20 and 50 μM). Tamoxifen (100 and 1,000 nM) induced apoII mRNA only, and bisphenol A (BPA) was not estrogenic. Inhibition of moxestrol-mediated VTGII or apoII mRNA induction by MXCL, o,p'-DDT and tamoxifen indicated that these chemicals were also antiestrogenic at concentrations similar to those which caused estrogenic responses. Organochlorine extracts prepared from herring gull embryo yolk sacs obtained from three Great Lakes sites and one Atlantic coast site (reference site) did not show any estrogenic activities. However, the same extracts from all three Great Lakes sites had antiestrogenic activities. These results indicate that wild birds may be susceptible to the estrogenic or antiestrogenic effects of environmental contaminants.
Enhancing toxicity test performance by using a statistical criterion
Authors: Denton Debra L. , Fox John F. , Fulk Florence A.
Published: November 2004

Aquatic toxicity tests are laboratory experiments that measure the biological effect (e.g., growth, survival, reproduction) of effluents, receiving waters, or storm water on aquatic organisms. These toxicity tests must be performed using the best laboratory practices, and every effort must be made to enhance repeatability of the test method. We evaluated the generated reference toxicant test data for insurance of a level of quality assurance for tests over time within a laboratory and among laboratories. We recommend the reporting and evaluation of the percent minimum significant difference (PMSD) value for all toxicity test results. The minimum significant difference (MSD) represents the smallest difference between the control mean and a treatment mean that leads to the statistical rejection of the null hypothesis (i.e., no toxicity) at each concentration of the toxicity test dilution series. The MSD provides an indication of within-test variability, and smaller values of MSD are associated with increased power to detect a toxic effect. We recommend upper and lower PMSD bounds for each test method in order to minimize within-test variability and increase statistical power. To ensure that PMSD does not exceed an upper bound, testing laboratories may need to increase replication, decrease variability among replicates, or increase the control mean performance.
Formation of benzo[a]pyrene and 7,12-dimethylbenz[a]anthracene adducts in vascular endothelia of cytochrome P4501A–induced chicken embryos
Authors: Granberg Lizette , Brunström Björn , Brandt Ingvar
Published: November 2004

Polycyclic aromatic hydrocarbons (PAHs) are widespread in the environment and birds may be exposed to PAHs via diet, from preening feathers contaminated with oil, or through contamination of the eggshell during embryo development. In the present study, tissue distribution and the cell-specific binding of two labeled PAHs, benzo[a]pyrene ([3H]BaP) and 7,12-dimethylbenz[a]anthracene ([3H]DMBA), were examined in chicken embryos exposed in ovo to CYP1A inducers. Tape-section auto-radiograms revealed high concentrations of radioactivity in the bile, liver, kidneys, heart, and leptomeninges. Light microscopy autoradiography of solvent-extracted tissue slices showed a high and selective binding in endothelial cells in certain blood vessels in brain, heart, lung, and chest muscle. Binding was also observed in blood vessel endothelial cells in the chorioallantoic membrane (CAM), an extraembryonal tissue lining the eggshell. Endothelial binding was confirmed in CAM exposed in vitro, implying that tissue-binding metabolites were formed in situ. The CYP1A inhibitor ellipticine abolished binding in the target endothelial cells in CAM. It is thus concluded that blood vessel endothelia in various tissues in birds can bioactivate environmental contaminants and be targets for their toxicity. In view of its critical position beneath the shell, the CAM could be an important target for toxicants following external exposure in oviparous species.
Ecotoxicologic impacts of agricultural drain water in the Salinas River, California, USA
Authors: Anderson Brian S. , Hunt John W. , Phillips Bryn M. , Nicely Patricia A. , Gilbert Kristine D. , de Vlaming Victor , Connor Valerie , Richard Nancy , Tjeerdema Ronald S.
Published: November 2004

The Salinas River is the largest of the three rivers that drain into the Monterey Bay National Marine Sanctuary in central California (USA). Large areas of this watershed are cultivated year-round in row crops, and previous laboratory studies have demonstrated that acute toxicity of agricultural drain water to Ceriodaphnia dubia is caused by the organophosphate (OP) pesticides chlorpyrifos and diazinon. We investigated chemical contamination and toxicity in waters and sediments in the river downstream of an agricultural drain water input. Ecological impacts of drain water were investigated by using bioassessments of macroinvertebrate community structure. Toxicity identification evaluations were used to characterize chemicals responsible for toxicity. Salinas River water downstream of the agricultural drain was acutely toxic to the cladoceran Ceriodaphnia dubia, and toxicity to C. dubia was highly correlated with combined toxic units (TUs) of chlorpyrifos and diazinon. Laboratory tests were used to demonstrate that sediments in this system were acutely toxic to the amphipod Hyalella azteca, a resident invertebrate. Toxicity identification evaluations (TIEs) conducted on sediment pore water suggested that toxicity to amphipods was due in part to OP pesticides; concentrations of chlorpyrifos in pore water sometimes exceeded the 10-d mean lethal concentration (LC50) for H. azteca. Potentiation of toxicity with addition of the metabolic inhibitor piperonyl butoxide suggested that sediment toxicity also was due to other non–metabolically activated compounds. Macroinvertebrate community structure was highly impacted downstream of the agricultural drain input, and a number of macroinvertebrate community metrics were negatively correlated with combined TUs of chlorpyrifos and diazinon, as well as turbidity associated with the drain water. Some macroinvertebrate metrics were also correlated with bank vegetation cover. This study suggests that pesticide pollution is the likely cause of ecological damage in the Salinas River, and this factor may interact with other stressors associated with agricultural drain water to impact the macroinvertebrate community in the system.
Sublethal effects of copper on coho salmon: Impacts on nonoverlapping receptor pathways in the peripheral olfactory nervous system
Authors: Baldwin David H. , Sandahl Jason F. , Labenia Jana S. , Scholz Nathaniel L.
Published: November 2004

The sublethal effects of copper on the sensory physiology of juvenile coho salmon (Oncorhynchus kisutch) were evaluated. In vivo field potential recordings from the olfactory epithelium (electro-olfactograms) were used to measure the impacts of copper on the responses of olfactory receptor neurons to natural odorants (L-serine and taurocholic acid) and an odorant mixture (L-arginine, L-aspartic acid, L-leucine, and L-serine) over a range of stimulus concentrations. Increases in copper impaired the neurophysiological response to all odorants within 10 min of exposure. The inhibitory effects of copper (1.0–20.0 μg/L) were dose-dependent and they were not influenced by water hardness. Toxicity thresholds for the different receptor pathways were determined by using the benchmark dose method and found to be similar (a 2.3–3.0 μg/L increase in total dissolved copper over background). Collectively, examination of these data indicates that copper is broadly toxic to the salmon olfactory nervous system. Consequently, short-term influxes of copper to surface waters may interfere with olfactory-mediated behaviors that are critical for the survival and migratory success of wild salmonids.
Sorption of phenanthrene and atrazine by plant cuticular fractions
Authors: Chefetz Benny
Published: November 2004

Several studies have shown selective preservation of plant cuticular materials in soils. However, very little is known about their function as sorbents for the hydrophobic organic contaminants (HOCs) in the soil. In this study, we investigated the sorption and desorption of phenanthrene and atrazine by cuticular fractions of pepper (bulk, dewaxed, nonsaponifiable, and nonhydrolyzable) to better understand the sorptive activity of cuticular matter in soils. The bulk and dewaxed cuticles exhibited carbon-normalized distribution coefficients (Koc) for phenanthrene and atrazine in the range of that reported for soil humic substances, although both samples were rich in aliphatic structures. No hysteresis was observed in the desorption isotherms of either solute. The nonhydrolyzable residue exhibited a very high Koc value for atrazine, whereas the nonsaponifiable sample exhibited the lowest Koc value for both sorbates. Based on solubility parameter data, it is suggested that the nonsaponifiable sample be considered an intermediate between the physical and chemical mixture of pectin and cutan/lignin-like fractions, whereas the dewaxed cuticle is a chemical blending of cutin and pectin. The n-hexane-normalized sorption data suggest that the pepper cuticle can interact specifically with atrazine. This study leads to the conclusion that the contribution of aliphatic-rich plant biopolymers to the sorption of HOCs can be significant because of their preservation and accumulation in soils.
Tenax extraction mimics benthic and terrestrial bioavailability of organic compounds
Authors: ten Hulscher Theodora E. M. , Postma Jaap , den Besten Pieter J. , Stroomberg Gerard J. , Belfroid Angelique , Wegener Jan Willem , Faber Jack H. , van der Pol Joost J. C. , Hendriks A. Jan , van Noort Paul C. M.
Published: November 2004

Biota to sediment accumulation factors (BSAFs) are widely used to describe the potential accumulation of organic contaminants in organisms. From field studies it is known that these BSAFs can vary dramatically between sediments of different origin, which is possibly explained by the variation in bioavailability of organic contaminants in sediments. In the present study it is shown that the variability in BSAF values for different sediment samples obtained at two Dutch freshwater sites could largely be explained by the variation in Tenax-extractable concentrations in these sediments. Variations of a factor of about 50 could be explained. The ratio between concentrations in biota and Tenax-extractable concentrations in sediment varied slightly between sediments and contaminant class, but was close to the theoretically expected value of 2. This is a strong indication that Tenax-extractable concentrations of contaminants in sediments are an excellent indicator of available concentrations.
Joint algal toxicity of phenylurea herbicides is equally predictable by concentration addition and independent action
Authors: Backhaus Thomas , Faust Michael , Scholze Martin , Gramatica Paola , Vighi Marco , Grimme L. Horst
Published: November 2004

Photosynthesis-inhibiting phenylurea derivatives, such as diuron, are widely used as herbicides. Diuron concentrations clearly exceeding the predicted-no-effect concentration have been regularly measured in European freshwater systems. The frequently observed exposure to mixtures of phenylureas additionally increases the hazard to aquatic primary producers. Fluctuating numbers and concentrations of individual toxicants make experimental testing of every potential mixture unfeasible. Thus, predictive approaches to the mixture hazard assessment are needed. For this purpose, two concepts are at hand, both of which make use of known toxicities of the individual components but are based on opposite mechanistic suppositions: Concentration addition is based on the idea of similar mechanisms of action, whereas independent action assumes dissimilarly acting mixture components. On the basis of pharmacological reasoning, it was therefore anticipated that the joint algal toxicity of phenylurea mixtures would be predictable by concentration addition. Indeed, we could demonstrate a high predictive power of concentration addition for these combinations. Surprisingly, however, the opposite concept of independent action proved to be equally valid, because both concepts predicted virtually identical mixture toxicities. This exceptional case has previously been derived from theoretical considerations. Now, the tested phenylurea mixtures serve as an example for the practical relevance of this situation for multicomponent mixtures.
Lethal and sublethal effects of atrazine, carbaryl, endosulfan, and octylphenol on the streamside salamander (Ambystoma barbouri)
Authors: Rohr Jason R. , Elskus Adria A. , Shepherd Brian S. , Crowley Philip H. , McCarthy Thomas M. , Niedzwiecki John H. , Sager Tyler , Sih Andrew , Palmer Brent D.
Published: November 2004

Aricultural contaminants may be contributing to worldwide amphibian declines, but little is known about which agrichemicals pose the greatest threat to particular species. One reason for this is that tests of multiple contaminants under ecologically relevant conditions are rarely conducted concurrently. In this study, we examined the effects of 37-d exposure to the agrichemicals atrazine (4, 40, and 400 μg/L), carbaryl (0.5, 5, and 50 μg/L), endosulfan (0.1, 1, and 10 μg/L for 31 d and 0.1, 10, and 100 μg/L for the last 6 d), and octylphenol (5, 50, and 500 μg/L) and to a solvent control on streamside salamanders (Ambystoma barbouri) in the presence and absence of food. We found that none of the agrichemicals significantly affected embryo survival, but that hatching was delayed by the highest concentration of octylphenol. In contrast to embryos, larval survival was reduced by the highest concentrations of carbaryl, endosulfan, and octylphenol. Growth rates were lower in the highest concentrations of endosulfan and octylphenol than in all other treatments, and the highest concentration of endosulfan caused respiratory distress. Significantly more carbaryl, endosulfan, and octylphenol tanks had larvae with limb deformities than did control tanks. Refuge use was independent of chemical exposure, but 10 μg/L of endosulfan and 500 μg/L of octylphenol decreased larval activity. Systematically tapping tanks caused a greater activity increase in larvae exposed to 400 μg/L of atrazine and 10 μg/L of endosulfan relative to solvent controls, suggesting underlying nervous system malfunction. Hunger stimulated a decrease in refuge use and an increase in activity, but this response was least pronounced in larvae exposed to the highest concentration of any of the four agrichemicals, possibly because these larvae were the most lethargic. More studies are needed that concurrently examine the effect of multiple contaminants on amphibians so we can better identify effective mitigating measures.
Application of toxicity identification evaluation procedures for characterizing produced water using the tropical mysid, Metamysidopsis insularis
Authors: Elias-Samlalsingh Najila , Agard John B. R.
Published: November 2004

Toxicity identification evaluations (TIEs) were performed on seven produced water (PW) effluents from inland discharge facilities operated in Trinidad and Tobago, a Caribbean tropical country with one of the oldest commercial oil industries in the world. The research was performed to determine the presence and magnitude of toxicity and characterize which toxicants are responsible for observed effects. Marine effluent toxicity characterizations with Metamysidopsis insularis revealed high whole acute toxic-unit response for produced water ranged from 8.1 to >17.0 acute toxic-unit (initial toxicity test) and 5.7 to 1,111 acute toxic-unit (baseline toxicity test). Toxicity test results for all sites except one, which had the highest toxicity, are comparative with similar studies on produced water. The toxicological causality of this complex mixture differed for each PW with nonpolar organics being consistently toxic in all samples. Other potential toxicants contributing to overall toxicity to a much lesser extent were metals, ammonia, and volatile organic compounds. With the use of sodium thiosulfate and filtration manipulations for only PW6 sample, there was very slight reduction in toxicity; therefore, oxidants and filterable materials were not a great contributing factor. Whole effluent toxicity also can be attributed to ionic imbalance and the very stable oil-in-water emulsion that consists of fine oil droplets (less than 0.1–10 μm with an average diameter of 2.5 μm). This investigation is the first of its type in Trinidad and demonstrates clearly the applicability of this test method and local test species for evaluating complex effluents in tropical environments.
Biologically incorporated dietary silver has no ionoregulatory effects in American red crayfish (Procambarus clarkii)
Authors: Mann Reinier M. , Grosell Martin , Bianchini Adalto , Wood Chris M.
Published: November 2004

Two silver-contaminated diets were prepared by exposing juvenile rainbow trout for 8 d to waterborne silver thiosulfate as Ag at either 0.1 μg/L (low-Ag diet) or 80 mg/L (high-Ag diet). The level of total Ag accumulated in whole low-Ag fish was below the detection limit of analysis. Whole high-Ag fish accumulated Ag at 21.3 nmol/g. The livers of the low- and high-Ag fish accumulated Ag at 0.43 nmol/g and 1.01 μmol/g, respectively. The Ag-contaminated fish were then fed whole to adult crayfish in an 80-d dietary study to determine the effects of long-term trophic accumulation of Ag. In a second experiment, the livers of the high-Ag trout were fed to juvenile crayfish for either one or five weeks. Accumulation of Ag was demonstrated in both adult and juvenile crayfish. Silver accumulation in juvenile crayfish peaked at approximately 650 nmol/g at three weeks, after which Ag depuration occurred. In adult crayfish that consumed the high-Ag diet, the hepatopancreas accumulated more than 90% of assimilated Ag, rising 1,000-fold over control animals to approximately 740 nmol/g at 80 d. Crayfish that consumed the low-Ag diet had small, statistically insignificant elevations of Ag in some tissues. Dietary Ag had no effect on juvenile crayfish growth or adult mortality. Disturbances in osmoregulation, which are normally associated with acute waterborne Ag exposure, were not detected. Dietary Ag also had no effect on hemolymph concentrations of Na+, Cl−, Ca2+, Mg2+, or Cu; did not affect the concentration kinetics of Na+ or Cl− influx; and had no effect on the activity of gill Na+/K+-dependent adenosine triphosphatase. Hemolymph concentrations of glucose and lactate were similarly unaffected, indicating an absence of stress-related metabolic disturbance. However, a disproportionately low number of ecdysis events occurred among crayfish that consumed the high-Ag diet.
The effect of lead-contaminated soil from canadian prairie skeet ranges on the neutral red retention assay and fecundity in the earthworm Eisenia fetida
Authors: Booth Lynn , Palasz Fil , Darling Colin , Lanno Roman , Wickstrom Mark
Published: November 2004

The sublethal effects of lead (Pb) on the earthworm Eisenia fetida were evaluated in the laboratory using freshly spiked soil and soil collected from Canadian prairie skeet ranges. After a four-week exposure to soil spiked with lead acetate, earthworm neutral red retention time (NRRT), soil Pb concentrations, and earthworm Pb body burdens were measured. Lysosomal NRRT was reduced in a concentration-dependent manner (p < 0.0001), and NRRT was negatively correlated with earthworm Pb body burdens (r = —0.80, p < 0.0001). To evaluate the effects of aged Pb, earthworms were exposed to soil from three skeet ranges, and responses were compared with three matched reference sites. After a four-week exposure, NRRT, growth, fecundity, soil total Pb levels, and earthworm Pb body burdens were measured. The potentially bioavailable fraction of Pb in these sites was measured using a Ca(NO3)2 extraction. Growth and fecundity did not differ significantly between any of the skeet ranges and their reference sites. However, NRRT was significantly reduced in all three ranges compared with their respective reference sites (p < 0.05), indicating that the neutral red retention assay (NRRA) may be useful for detecting toxicity and potential hazards at Pb-contaminated sites. Lysosomal NRRT was negatively correlated with soil Ca(NO3)2-extractable Pb (r = —0.80, p < 0.0001) and soil total Pb (r = —0.73, p = 0.001). Lysosomal NRRT was negatively correlated (r = —0.67, p < 0.002) with earthworm Pb tissue levels.
Effects of pharmaceutical mixtures in aquatic microcosms
Authors: Richards Sean M. , Wilson Christian J. , Johnson David J. , Castle Dawn M. , Lam Monica , Mabury Scott A. , Sibley Paul K. , Solomon Keith R.
Published: November 2004

Pharmaceuticals have a wide range of biological properties and are released into the environment in relatively large amounts, yet little information is available regarding their effects or potential ecological risks. We exposed outdoor aquatic microcosms to combinations of ibuprofen (a nonsteroidal anti-inflammatory drug), fluoxetine (a selective serotonin reuptake inhibitor), and ciprofloxacin (a DNA gyrase—inhibiting antibiotic) at concentrations of 6, 10, and 10 μg/L, respectively (low treatment [LT]); 60, 100, and 100 μg/L, respectively (medium treatment [MT]); and 600, 1,000, and 1,000 μg/L, respectively (high treatment [HT]). We maintained these concentrations for 35 d. Few responses were observed in the LT; however, effects were observed in the MT and HT. Fish mortality occurred in the MT (<35 d) and in the HT (<4 d). Phytoplankton increased in abundance and decreased in diversity (number of taxa) in the HT, with consistent trends being observed in the MT and LT. Zooplankton also showed increased abundance and decreases in diversity in the HT, with consistent trends being observed in the MT. Multivariate analyses for zooplankton and phytoplankton suggested interactions between these communities. Lemna gibba and Myriophyllum spp. showed mortality in the HT; growth of L. gibba was also reduced in the MT. Bacterial abundance did not change in the HT. All responses were observed at concentrations well below the equivalent pharmacologically active concentrations in mammals. Although the present data do not suggest that ibuprofen, fluoxetine, and ciprofloxacin are individually causing adverse effects in surface-water environments, questions remain about additive responses from mixtures.
The influence of pH and salinity on the toxicity of heavy metals in sediment to the estuarine clam Ruditapes philippinarum
Authors: Riba Inmaculada , Delvalls T. Ángel , Forja Jesús M. , Gómez-Parra Abelardo
Published: November 2004

An approach is presented for determining the influence of two key variables, pH and salinity(S), on the toxicity of four common heavy metals bound to sediments in estuaries. Two samples of environmental sediment taken from two estuaries in southern Spain (the Huelva estuary and the Guadalquivir River estuary), together with a dilution of toxic mud from the Aznalcóllar (Spain) mining spill (April 1998) were used to determine their toxicity at different values of pH (6.5, 7.5, and 8.5) and salinity (10, 20, and 30) on the estuarine clam Ruditapes philippinarum. Two different endpoints, sublethal, indicated by clam reburial (median effective burial time [ET50]), and relative mortality (median lethal concentration [LC50]), were used to quantify the toxicity associated with the heavy metals. Neither salinity nor pH was found to influence the toxic responses measured by the behavioral endpoint (ET50). However, a strong effect on the LC50 related to pH and salinity was detected, with the toxicity of the heavy metals being increased at low values of both variables (pH = 6.5 and S = 10). The mechanism of heavy metals uptake through water may explain this influence of pH and salinity on the lethal toxicity detected. The results show differences in the toxicity of these heavy metals bound to sediments depending on whether the origin of metal contamination is chronic or acute.
Isoform-specific quantification of metallothionein in the terrestrial gastropod Helix pomatia I. molecular, biochemical, and methodical background
Authors: Dallinger Reinhard , Chabicovsky Monika , Berger Burkhard
Published: November 2004

The biomarker concept is an important approach of modern ecotoxicology based on the detection and quantification of molecular, biochemical, cellular, or physiological alterations in organisms as the result of exposure to toxic compounds. In the present study, the biomarker potential of two metallothionein (MT) isoforms from hepatopancreas and mantle tissue of the Roman snail, Helix pomatia L., is evaluated. This species possesses two MT isoforms with specific functions: The Cd-specific isoform (Cd-MT) is predominantly induced and expressed in the hepatopancreas upon Cd exposure. It binds and inactivates this potentially toxic trace element. The second isoform is Cu-specific (Cu-MT), primarily expressed in the mantle tissue and responsible for the homeostatic regulation of Cu. The differential expression and metal-specificity of the two isoforms make them potential candidates for a dual MT biomarker system based on an isoform-specific approach. This study shows that Cd-MT and Cu-MT of H. pomatia can reliably be quantified by a differential metal saturation approach that could be used for environmental biomarker studies. The approach works by virtue of the following preconditions: The two isoforms differ from each other with respect to their molecular and biochemical features, they show metal-specific binding preferences, they are organ-specific, they exhibit distinct induction patterns in response to the metals to which they bind, and their biological and functional background is thoroughly known.
Isoform-specific quantification of metallothionein in the terrestrial gastropod Helix pomatia. II. A differential biomarker approach under laboratory and field conditions
Authors: Dallinger Reinhard , Chabicovsky Monika , Lagg Bernhard , Schipflinger Rouven , Weirich Harald G. , Berger Burkhard
Published: November 2004

The two function-specific metallothionein (MT) isoforms characterized from the midgut gland and mantle tissue of Helix pomatia differ substantially in their metal-binding preferences, as well as molecular and biochemical features. These differences make them potential candidates for biomarker studies based on a differential, isoform-specific approach. To prove this hypothesis, induction experiments with two metals (Cd and Cu) that are normally bound by the two isoforms were compared with a range of organic chemicals and physical stressors under laboratory conditions to test the responsiveness of the two isoforms to the stressors applied. In addition, field studies were conducted with Roman snails and substrate samples collected from different metal-contaminated sites in Austria to test the suitability of the two isoforms as biomarkers under field conditions. The results of these combined laboratory and field studies confirmed the validity of the biomarker approach with the two metal- and tissue-specific isoforms. It is demonstrated that the Cd-binding MT specifically and exclusively responds to Cd exposure by increasing concentrations, whereas the Cu-binding MT isoform decreases in its concentration upon exposure to physical stress (X-ray irradiation and cold). This suggests researchers should adopt, under certain preconditions, a dual biomarker approach by combining the simultaneous quantification of Cd-MT concentrations in the midgut gland as a biomarker for Cd pollution and of Cu-MT concentration in the mantle as a biomarker for the impairment of snails by additional physical stressors.
Cytological changes in association with ethoxyresorufin O-deethylase induction in fish upon dietary exposure to benzo[a]pyrene
Authors: Au Doris W. T. , Chen Ping , Pollino Carmel A.
Published: November 2004

Juvenile areolated grouper (Epinephelus areolatus) were exposed to two levels of dietary benzo[a]pyrene (BaP; 0.25–12.5 μg/g body wt/d) for four weeks, followed by four weeks of depuration. Significant increase in hepatic ethoxyresorufin O-deethylase (EROD) activities was found after one week, preceding an increase in lipopigments (as measured by quantitative transmission electron microscopy) in week 2 of exposure. The EROD activities in the BaP-treated fish subsided at week 4 of exposure and throughout the depuration period. Lipopigments in the high-dose group appeared to be more persistent than that of the EROD activity during the exposure period and remained significantly higher than that of the controls at week 4. Levels of lipopigments, however, rapidly subsided on withdrawal of BaP exposure. These results appear to suggest that changes in EROD activities would precede cytological changes and that both the observed cytological and biochemical changes are reversible. Results of the present study also lend further support to our earlier findings on Solea ovata, that a significant relationship exists between EROD activity and lipopigment accumulation (as measured by volume density, absolute volume, numerical density, and absolute density; r = 0.483–0.358, p < 0.05), regardless offish species (S. ovata and aerolated grouper) as well as the routes of exposure to BaP (intraperitoneal injection or dietary exposure). This provides strong supporting evidence that elevated EROD activities in fish liver do not merely indicate exposure to polyaromatic hydrocarbons (PAHs) but are also associated with significant biological effects. Our results showed that hepatic EROD activity and lipopigments could be used to indicate recent exposure of the fish to BaP/PAHs.
Effects of methoprene, its metabolites, and breakdown products on retinoid-activated pathways in transfected cell lines
Authors: Schoff Patrick K. , Ankley Gerald T.
Published: November 2004

Mthoprene (isopropyl (2E, 4E)-11-methoxy-3,7,11-trimethyl-2,4-dodecadienoate) is an insect juvenile hormone agonist that blocks metamorphosis in some insects. Recent evidence suggests that a metabolite, methoprene acid, activates vertebrate retinoid X receptors (RXRs), and may interfere with retinoic acid-regulated developmental processes. Methoprene, methoxy-methoprene acid, and two major breakdown products were tested for their ability to interfere with retinoid-regulated pathways when using transfected cells. The CV-1 cells were transiently transfected with genes encoding RXRs and response elements attached to luciferase reporters, and retinoic acid-sensitive F9 cells were stably transfected with retinoic acid receptor (RAR)/RXR response elements attached a lacZ reporter (Sil-REM/β-gal-NEO). Experiments confirmed that methoxy-methoprene acid acted as a ligand for RXRs and was capable of activating transcription through RAR/RXR response elements. However, neither methoprene nor the breakdown products, 7-methoxycitronellal and 7-methoxycitronellic acid, activated transcription in transfected CV-1 or F9 cells. Methoprene and methoxy-methoprene acid may interfere with the conversion of all-trans-retinol and all-trans-retinaldehyde to all-trans-retinoic acid in the F9-derived cell line. Methoprene was as effective as the retinol dehydrogenase inhibitor citral in blocking the retinol-induced transcription of RAR/RXR-regulated reporter genes, whereas methoxy-methoprene acid blocked transcription stimulated by retinaldehyde.
Effects of data manipulation and statistical methods on species sensitivity distributions
Authors: Duboudin Cédric , Ciffroy Philippe , Magaud Hélène
Published: November 2004

Species sensitivity distribution (SSD) methodology currently is used in environmental risk assessment to determine the predicted no-effect concentration (PNEC) of a substance in cases where a sufficient number of chronic ecotoxicological tests have been carried out on the substance, covering, for the aquatic environment with which we are concerned, three taxonomic groups: algae, invertebrates, and vertebrates. In particular, SSD methodology enables calculation of a hazardous concentration that is assumed to protect 95% of species (HC5). This approach is based on the hypothesis that the species for which results of ecotoxicological tests are known are representative, in terms of sensitivity, of the totality of the species in the environment, which raises a number of questions, both theoretical and practical. In this study, we compared various methods of constructing a species sensitivity- weighted distribution (SSWD). Each method is characterized by a different way of taking into account intraspecies variation and proportions of taxonomic groups (vertebrates, invertebrates, and algae), as well as by the statistical method of calculation of the HC5 and its confidence interval. Those methods are tested on 15 substances by using chronic no-observed-effect concentration data available in the literature. The choice of data (intraspecies variation and proportions between taxonomic groups) was found to have more effect on the value of the HC5 than the statistical method used to construct the distribution. The weight of each taxonomic group is the most important parameter for the result of the SSWD and letting literature references decide which proportions of data are used to construct it is not satisfactory.
Model-aided characterization of Tenax®-ta for aromatic compound uptake from water
Authors: Zhao Dongye , Pignatello Joseph J.
Published: November 2004

The polymer adsorbent Tenax® has been widely employed for studying desorption of organic contaminants in soils and sediments and for correlating physical availability with bioavailability. Although Tenax has been invoked to act as an infinite sink that completely and instantaneously removes solutes from the aqueous phase, to our knowledge no systematic characterization of Tenax resins has been carried out. The present study provides equilibrium and kinetic parameters for the uptake of benzene, nitrobenzene, naphthalene, phenanthrene, and pyrene by Tenax in selected water-solute-Tenax systems, and it offers guidelines for the use of Tenax resins. Sorption isotherms of the test compounds on Tenax-TA are nonlinear, and most show an inflection at high concentration, marking a change in physical state from glassy to rubbery. A simple dual-mode model was applied to the isotherms below the apparent inflection point. Sorption parameters for dissolution and hole-filling domains each correlate with the octanol-water partition coefficient. The effects of dissolved organic matter and salinity on Tenax-TA uptake are minor. Regeneration of Tenax-TA by hot-methanol extraction increased its affinity for naphthalene. Inclusion of 23% graphitized carbon in the polymer reduced affinity for phenanthrene. Uptake rate data were fit by the dual-mode diffusion model, which assumes diffusion in the polymer matrix. The obtained diffusion rate parameter correlates with molecular size. Equilibrium and kinetic parameters for benzene and nitrobenzene were comparable despite a three-orders-of-magnitude difference in their Henry's law coefficients, indicating that a pathway to the Tenax surface through the vapor phase is not required. Extrapolating to typical conditions in soil-desorption studies reveals that single-solute uptake is 95% or more complete within 4 min for the test compounds and within 7 min for benzo[a]pyrene. Thus, Tenax is suitable for compounds with desorption from soil or sediment that occurs over comparably longer timescales.