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PubMed2005

An evaluation of logistic regression models for predicting amphipod toxicity from sediment chemistry.

An empirical screening level approach was developed to assess the probability of toxicity to benthic organisms associated with contaminated sediment exposure. The study was based on simple logistic regression models (LRMs) of matching sediment chemistry and toxicity data retrieved from a large database of field-collected sediment samples contaminated with multiple chemicals. Three decisions were made to simplify the application of LRMs to sediment samples contaminated with multiple chemicals. First, percent mortality information associated with each sediment sample was condensed into a dichotomous response (i.e., toxic or nontoxic). Second, each LRM assumed that toxicity was attributable to a single contaminant. Third, individual contaminants present at low concentrations were excluded from toxic sediment samples. Based on an analysis of the National Sediment Inventory database, the LRM approach classified 55% of nontoxic sediments as toxic (i.e., false-positives). Because this approach has been used to assess the probability of benthic toxicity as reported by the U.S. Environmental Protection Agency (U.S. EPA), the resultant estimates of potential toxicity convey a misleading impression of the increased hazard that sediments pose to the health of aquatic organisms at many sites in the United States. This could result in important resources needlessly being diverted from truly contaminated sites to evaluate and possibly remediate sediments at uncontaminated sites.

Amphipoda↗
PubMed1993

A comparison of combined amrinone and glucagon therapy to glucagon alone for cardiovascular depression associated with propranolol toxicity in a canine model.

Multiple inotropic agents may be required to improve hypotension associated with beta-blocker toxicity. This study compared combined amrinone and glucagon therapy to glucagon alone and saline control for the treatment of propranolol-induced cardiovascular depression in a canine model. Six animals were pretreated with 10 mg/kg of propranolol intravenously (i.v.), which resulted in significant depression in heart rate (HR), cardiac output (CO), mean arterial pressure (MAP), and maximal left ventricular change in pressure over time (dP/dt max) (P < .0001). Each canine received i.v. amrinone (4 mg/kg) plus glucagon (20 micrograms/kg) therapy during a 2-minute period after propranolol infusion was completed. Cardiovascular parameters were monitored at 1, 6, 11, 21, and 31 minutes after treatment was rendered. Results were compared with those of a previous study, consisting of six animals that received glucagon therapy alone (20 mg/kg) and six controls (normal saline only) in an identical protocol. The addition of i.v. amrinone to glucagon therapy did not increase significantly, HR, CO, stroke volume, or dP/dt max compared with glucagon alone. Total systemic peripheral resistance was reduced significantly during 31 minutes of observation after the administration of combined therapy compared with the control; glucagon alone also reduced systemic peripheral resistance at 1 and 6 minutes. At all time periods except 1 minute of observation there was a significant reduction in MAP when comparing combined therapy with that of glucagon therapy alone. In this model, the addition of amrinone to glucagon therapy seems to have a detrimental effect on the ability of glucagon to increase MAP resulting from propranolol toxicity.

Amrinone↗
PubMed2005

Biotic ligand model prediction of copper toxicity to daphnids in a range of natural waters in Chile.

The objective of this study was to assess the predictive capacity of the biotic ligand model (BLM) for acute copper toxicity to daphnids as applied to a number of freshwaters from Chile and to synthetic laboratory-prepared waters. Thirty-seven freshwater bodies were sampled, chemically characterized, and used to determine the copper concentration associated with the 50% of mortality (LC50) for Daphnia magna, Daphnia pulex, and Daphnia obtusa (native to Chile). The data were then used to run three versions of the acute copper BLM, and the predicted LC50s were compared to the observed ones. The same was done with synthetic assay media at various hardness and dissolved organic carbon (DOC) levels. The BLM versions differed in the affinity constants for some biotic ligand-ion pairs, stability constants for inorganic Cu complexes, and assumptions regarding Cu binding to DOC. All three versions showed a high degree of predictive performance, mostly within a twofold range of observed toxicity values. The D. obtusa data set was used to compare water quality criteria (WQC) derived from the observed toxicity values with those derived from either the BLM or the U.S. Environmental Protection Agency (U.S. EPA) procedure. For most low DOC waters, the three procedures generated similar WQCs. For the high-DOC waters, the EPA-derived criteria were significantly lower, that is, greatly overprotective. The results are also discussed in terms of the validation of the BLM for regulatory use.

Animals↗
PubMed2005

Essential role of extracellular matrix (ECM) overlay in establishing the functional integrity of primary neonatal rat Sertoli cell/gonocyte co-cultures: an improved in vitro model for assessment of male reproductive toxicity.

The development of in vitro models for testicular toxicity may provide important tools for investigating specific mechanisms of toxicity in the testis. Although various systems have been reported, their application in toxicological studies has been limited by the poor ability to replicate the complex biochemical, molecular, and functional interactions observed in the testis. In the present study, we evaluated a significantly improved Sertoli cell/gonocyte co-culture (SGC) system that employs a 3-dimensional extracellular matrix Matrigel (ECM) applied as an overlay instead of a substratum. We explored the dose- and time-dependent effects of the addition of such an ECM overlay on cytoskeletal and morphological changes in the SGC system, and the resulting effects on cellular integrity. Furthermore, we correlated the latter effects with the ECM-dependent modulation of stress and survival signaling pathways and, most critically, the expression levels of the spermatogonia-specific protein, c-Kit. Finally, we applied this co-culture system to investigate the dose- and time-dependent effects on the morphology and induction of apoptosis of cadmium. We observed that the dose-dependent addition of an ECM overlay led to an enhanced attachment of Sertoli cells and facilitated the establishment of SGC communication and cytoskeletal structure, with a dramatic improvement in cell viability. The latter was consistent with the observed dose- and time-dependent modulation of both stress signaling pathways (SAPK/JNK) and survival signaling pathways (ERK and AKT) in the presence of the ECM overlay. Furthermore, the dose-dependent stabilization of c-Kit protein expression confirmed the functional integrity of this co-culture system. We conclude that this modified SGC system will provide investigators with a simple, efficient, and highly reproducible alternative in the screen for testicular cell-specific cytotoxicity and the assessment of molecular mechanisms associated with both normal development and reproductive toxicity induced by environmental toxicants.

Actins↗
PubMed1998

Approaches to developing alternative and predictive toxicology based on PBPK/PD and QSAR modeling.

Systematic toxicity testing, using conventional toxicology methodologies, of single chemicals and chemical mixtures is highly impractical because of the immense numbers of chemicals and chemical mixtures involved and the limited scientific resources. Therefore, the development of unconventional, efficient, and predictive toxicology methods is imperative. Using carcinogenicity as an end point, we present approaches for developing predictive tools for toxicologic evaluation of chemicals and chemical mixtures relevant to environmental contamination. Central to the approaches presented is the integration of physiologically based pharmacokinetic/pharmacodynamic (PBPK/PD) and quantitative structure--activity relationship (QSAR) modeling with focused mechanistically based experimental toxicology. In this development, molecular and cellular biomarkers critical to the carcinogenesis process are evaluated quantitatively between different chemicals and/or chemical mixtures. Examples presented include the integration of PBPK/PD and QSAR modeling with a time-course medium-term liver foci assay, molecular biology and cell proliferation studies. Fourier transform infrared spectroscopic analyses of DNA changes, and cancer modeling to assess and attempt to predict the carcinogenicity of the series of 12 chlorobenzene isomers. Also presented is an ongoing effort to develop and apply a similar approach to chemical mixtures using in vitro cell culture (Syrian hamster embryo cell transformation assay and human keratinocytes) methodologies and in vivo studies. The promise and pitfalls of these developments are elaborated. When successfully applied, these approaches may greatly reduce animal usage, personnel, resources, and time required to evaluate the carcinogenicity of chemicals and chemical mixtures.

Algorithms↗
PubMed1995

Biological modeling of 5-fluorouracil developmental toxicity.

A biologically-based dose-response (BBDR) model is a mathematical description of the biological events leading to expression of a toxic response. As an alternative to current approaches in non-cancer risk assessment, such models will reduce uncertainty in that they will provide a more comprehensive description of toxicity. We are involved in construction of a BBDR model for the developmental toxicity of 5-fluorouracil (5-FU) in the rat using multiple approaches. First, to identify critical events in the pathogenesis of 5-FU developmental toxicity, thymidylate synthetase (TS) inhibition and alterations in cell kinetics and growth were examined in embryos following maternal administration of 5-FU on day 14 of gestation. A dose-related decline in TS activity was observed within 1 h; however, maximal inhibition and recovery were similar at 10, 20 and 40 mg/kg. Dose-dependent cell cycle alterations were observed within 4 h after exposure and were maximal at 8 h. Hindlimb growth reduction was observed 24 h after exposure to 40 mg/kg, but not at lower doses. At term hindlimb defects were observed at doses above 30 mg/kg. An integrated dose-response model for hindlimb defects was derived from empirical relationships among these events. The resultant dose-response somewhat over-predicted the developmental toxicity of 5-FU, although results of a Monte Carlo simulation indicated that these data were not incompatible with model predictions. Overall, the results suggest that TS inhibition is a key component of the mechanism of 5-FU developmental toxicology, but the model does not capture all of the critical events in the induction of hindlimb defects. A preliminary mechanistic model for the inhibition of embryonic TS, DNA synthesis and cell cycle following maternal exposure to 5-FU, independently derived from literature data to further examine the potential role of this pathway in its developmental toxicity, predicted a dose-response for TS inhibition and DNA synthesis that closely reflected the observed patterns. These results further suggest that TS inhibition, resultant deficits in DNA synthesis and cell cycle perturbations represent a critical mechanistic pathway in the developmental toxicity of 5-FU.

Animals↗
PubMed1998

Analysis of the influence of environmental parameters on Clostridium botulinum time-to-toxicity by using three modeling approaches.

This study used the technique of waiting time modeling to analyze the combined effects of temperature, pH, carbohydrate, protein, and lipid on the time-to-toxicity of Clostridium botulinum 56A. Waiting time models can be used whenever the time to the occurrence of some event is the variable of interest. In the case of the time-to-toxicity data, the variable is the time from the beginning of an experiment until a tube is identified as positive. The statistical analysis used the SAS procedure LIFEREG and included determination of the form of the response surface, identification of the error distribution, and simplification of the response surface. We found that increasing the macromolecule concentration decreased the probability of toxin formation. The probability of toxin formation also decreased at lower temperatures and at pHs further from the optimum. The waiting time modeling approach to developing models for botulinal toxin formation compared favorably with other approaches but had one specific advantage. Waiting time models have the inherent advantage that safety concerns regarding predictions are automatically quantified in the analysis by formally identifying a distribution of times-to-toxicity. The use of this time-to-toxicity distribution permits a customizable margin of safety (e.g., one in a million) not possible with other approaches.

Botulinum Toxins↗
PubMed1991

Dapsone in low doses prevents Pneumocystis carinii pneumonia in the rat model.

Less toxic drugs are needed for the prophylaxis and treatment of Pneumocystis carinii pneumonia (PCP) in patients with AIDS. Rats immunosuppressed with cortisone were given dapsone, chlorproguanil (CPG) and chlorcycloguanil (CCG), alone or in combination, in the diet and the P. carinii attack rate was compared with that of untreated controls. Dapsone alone at doses of 25 and 5 mg/kg/day was 100% effective in preventing PCP. The efficacy of CPG and CCG, however, could not be properly assessed because of the lack of acceptance of the diet by the animals. Even so, as a result of the findings with dapsone in this study, and because of its pharmacokinetics and minimum inhibitory concentration for P. carinii in vitro, a clinical trial of reduced dosage of dapsone given prophylactically to human beings is suggested. Such a trial may show a decrease in the toxicity of the drug that usually accompanies its long-term administration but retention of its efficacy.

Administration, Oral↗
PubMed2002

Clusterin promotes amyloid plaque formation and is critical for neuritic toxicity in a mouse model of Alzheimer's disease.

Studies have shown that clusterin (also called apolipoprotein J) can influence the structure and toxicity of amyloid-beta (Abeta) in vitro. To determine whether endogenous clusterin plays a role in influencing Abeta deposition, structure, and toxicity in vivo, we bred PDAPP mice, a transgenic mouse model of Alzheimer's disease, to clusterin(-/-) mice. By 12 months of age, PDAPP, clusterin(-/-) mice had similar levels of brain Abeta deposition as did PDAPP, clusterin(+/+) mice. Although Abeta deposition was similar, PDAPP, clusterin(-/-) mice had significantly fewer fibrillar Abeta (amyloid) deposits than PDAPP mice expressing clusterin. In the absence of clusterin, neuritic dystrophy associated with the deposited amyloid was markedly reduced, resulting in a dissociation between fibrillar amyloid formation and neuritic dystrophy. These findings demonstrate that clusterin markedly influences Abeta structure and neuritic toxicity in vivo and is likely to play an important role in Alzheimer's disease pathogenesis.

Alzheimer Disease↗
PubMed1988

In vitro toxicology: a commercial proposition?

1. The commercial value of any test system must be equated with its scientific value. In vitro toxicity tests only have scientific value when they are accurate models of toxicity in vivo. 2. Toxicity is a complex event so that the simple tests of cell viability are unlikely to be useful models as these tests often use cell lines which are functionally remote from cells in tissues of the whole animal. 3. Primary cultures retain their differentiated function for hours (hepatocytes) or days (nerve cells) and may acquire differentiated functions in vitro (embryo cells) and are the models of choice for predicting toxic hazard. 4. When the in vitro test is a satisfactory predictive model of toxicity there are sound commercial reasons for its use. It saves time and effort and can be used at an early stage in compound development to sort out the toxic from the non-toxic candidate compounds. Large numbers of structurally similar compounds can be tested (QSAR studies) and a greater understanding of the mechanism of toxic action can often be achieved than in vivo because of the numbers of animals required and the interplay of different organ systems in the toxic events that make interpretation difficult. Thus the in vitro test can not only save animals but can also save compounds.

Animals↗
PubMed1998

Using metal-ligand binding characteristics to predict metal toxicity: quantitative ion character-activity relationships (QICARs).

Ecological risk assessment can be enhanced with predictive models for metal toxicity. Modelings of published data were done under the simplifying assumption that intermetal trends in toxicity reflect relative metal-ligand complex stabilities. This idea has been invoked successfully since 1904 but has yet to be applied widely in quantitative ecotoxicology. Intermetal trends in toxicity were successfully modeled with ion characteristics reflecting metal binding to ligands for a wide range of effects. Most models were useful for predictive purposes based on an F-ratio criterion and cross-validation, but anomalous predictions did occur if speciation was ignored. In general, models for metals with the same valence (i.e., divalent metals) were better than those combining mono-, di-, and trivalent metals. The softness parameter (sigma p) and the absolute value of the log of the first hydrolysis constant ([symbol: see text] log KOH [symbol: see text]) were especially useful in model construction. Also, delta E0 contributed substantially to several of the two-variable models. In contrast, quantitative attempts to predict metal interactions in binary mixtures based on metal-ligand complex stabilities were not successful.

Algorithms↗
PubMed1992

A novel model to assess developmental toxicity of dihaloalkanes in humans: bioactivation of 1,2-dibromoethane by the isozymes of human fetal liver glutathione S-transferase.

Glutathione S-transferase (GST) isozymes from human fetal liver (16-18 weeks gestation) were purified by affinity chromatography followed by ion-exchange high performance liquid chromatography (HPLC). The purified isozymes were used to investigate toxicity of 1,2-dibromoethane(EDB) in an in vitro model of rat embryos in culture as passive targets. At least five isozymes of GST were found in the human fetal liver. Two anionic forms [pI values 5.5 (P-2) and 4.5 (P-3)] and one basic form [pI value 8.7 (P-6)] were clearly separated. The presence of two near-neutral forms was also identified. All the isozymes of the human fetal liver GSTs tested metabolized EDB (specific activities were 2.1, 7.0, and 2.0 mumol of GSH consumed/min/mg protein for P-2, P-3, and P-6 isozymes, respectively). Covalent binding of EDB to DNA and protein was 144% and 212% higher, respectively, with the P-3 anionic isozyme when compared to the P-6 basic isozyme of GST. No covalent binding to either protein or DNA was observed with the P-2 isozyme. EDB bioactivation by the GST isozyme P-3 (15 units; 1 unit = 1 nmol of GSH consumed/min) resulted in toxicity to cultured rat embryos. Significant reductions of crown rump length, yolk sac diameter, and the composite score of morphological parameters (Brown and Fabro method) were observed. The central nervous system, optic and olfactory systems, and the hind limb were most significantly affected. The results of this investigation suggest that EDB may be classified as a suspected developmental toxicant in humans.

Animals↗
PubMed2004

Evaluation of the developmental and reproductive toxicity of methoxychlor using an anuran (Xenopus tropicalis) chronic exposure model.

The chronic toxicity of methoxychlor to the South African clawed frog, Xenopus (Silurana) tropicalis, was evaluated using a life cycle approach. The chronic exposure period ranged from mid-cell blastula stage [NF (Nieuwkoop and Faber, 1994) stage 8] to 90 days of exposure, during which time the organisms generally completed metamorphosis and emerged as juvenile frogs. Methoxychlor concentrations ranged from 1 to 100 micrograms/l. Methoxychlor concentrations >10 micrograms/l caused delayed development. Organisms exposed to 10 micrograms/l methoxychlor for 30 days showed enlarged thyroid glands with follicular hyperplasia. No increase in mortality or external malformation was observed at any of the test concentrations during early embryo-larval development (NF stage 8 to NF stage 46; ca. 2 days exposure). A concentration-dependent increase in external malformations and internal abnormalities of the liver and gonads were noted after 90 days of exposure, however. Skewing of the sex ratio toward the female gender decreased ovary weight and number of oocytes, and increased oocyte immaturity and necrosis were noted at methoxychlor concentrations of 100 micrograms/l. Reductions in testis weight and sperm cell count were also detected at 100 micrograms/l methoxychlor. Results from these studies suggested that methoxychlor was capable of altering the rate of larval development, but did not adversely affect early embryo-larval development (2 days of exposure) as manifested in external malformations. Internal malformations, increases in the ratio of phenotypic females, were induced by chronic methoxychlor exposure. In addition, reproductive endpoints, most notably in the female specimens, were adversely affected by methoxychlor exposure. These studies add to the standardization and validation of a useful amphibian test methods capable of evaluating both reproductive and developmental effects of potential endocrine disrupting chemicals over a life cycle exposure.

Animals↗
PubMed1997

Bacillus stearothermophilus as a model to evaluate membrane toxicity of a lipophilic environmental pollutant (DDT).

The thermophilic eubacterium Bacillus stearothermophilus has been used as a model system to identify DDT-promoted events in biological membranes putatively related with the insecticide toxicity. Two strategies have been approached: a) bacterial growth and viability were followed and the effects of DDT (2,2-bis(p-chlorophenyl)-1,1,1-trichloroethane) determined; b) biophysical studies with fluorescent probes were performed to elucidate the effects of DDT on the organization of the membrane lipid bilayer. The effects of DDT on growth and physical properties of the membrane were also determined in the presence of Ca2+ to further identify the interference of the insecticide at the membrane level and its putative contribution to cell toxicity. Growth inhibition by DDT is concentration-dependent, being attenuated or removed by the addition of 2.5-mM Ca2+ to bacterial cultures. Consistently, fluorescence polarization of 1,6-diphenyl-1,3,5-hexatriene (DPH) and its propionic acid derivative (DPH-PA) exhibited opposite effects of Ca2+ and DDT on the physical state of bacterial polar lipid dispersions. Growth and viability of bacterial cells are affected by DDT concentrations lower than those able to induce detectable bulk fluidity alterations, indicating high sensitivity of the intact bacterial system to alterations in limited membrane domains not directly probed by fluorescent probes that only report the average behavior of membrane lipid population.

DDT↗
PubMed1993

Ozone- and endotoxin-induced mucous cell metaplasias in rat airway epithelium: novel animal models to study toxicant-induced epithelial transformation in airways.

Mucous (goblet) cell proliferation and hypersecretion of airway mucus are important characteristics of human respiratory disorders, especially chronic bronchitis and cystic fibrosis. These changes in secretory patterns also occur in animals experimentally exposed to chemical irritants such as ozone (O3), sulfur dioxide (SO2), and cigarette smoke. The cellular and molecular mechanisms involved in irritant-induced mucous cell metaplasia (MCM; transformation of airway epithelium, normally devoid of mucous cells, to a secretory epithelium containing numerous mucous cells) are still unclear. We used two experimental models of toxicant-induced MCM in rat airways to study the cellular and molecular changes that occur during the development of this respiratory tract lesion. MCM can be induced in the nasal transitional epithelium of rats by repeated exposure to ambient levels of ozone. In addition, MCM can be induced in the tracheobronchial airways of rats repeatedly exposed to endotoxin, a lipopolysaccharide-protein molecule found in the outer walls of Gram-negative bacteria. The pathogenesis of ozone- or endotoxin-induced MCM has been partially characterized using a variety of morphometric and histochemical techniques. Toxicant-induced changes in the numbers and types of airway epithelial cells have been estimated using morphometric methods designed for estimating the abundance of cell populations. Nasal pulmonary airway tissues are also processed for light microscopy and stained with Alcian Blue (pH 2.5)/Periodic Acid Schiff (AB/PAS) for detection of acidic and neutral mucosubstances (the specific glycoprotein product of mucous cells), respectively, within the tissue. Computerized image analysis is used to quantitate the amount of the stained mucous product within the airway epithelium. To better characterize the molecular and cellular events in the pathogenesis of ozone- or endotoxin-induced MCM in the rat airway epithelium, we are conducting studies to determine when, and in which epithelial cells, the mucin gene is expressed after exposure to the toxicant. In these studies, rats undergo single or repeated exposures to ozone or endotoxin and are then sacrificed immediately or a few days after the end of the exposures. Airway tissues are microdissected from specific regions of the exposed respiratory tract, and changes in mucin core polypeptide mRNA are evaluated by Northern analysis using human and rat mucin cDNA. In future studies using in situ hybridization, we will establish when, and in which epithelial cells, the expression of high molecular weight airway mucin is initiated in response to ozone or endotoxin.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1995

Caffeine enhances doxorubicin cardiac toxicity in an animal model.

Based on in vitro data suggesting an interaction between methylxanthines and doxorubicin in regulating Ca2+ across muscle sarcoplasmic reticulum, this study was designed to test the hypothesis that a commonly used methylxanthine, caffeine, might influence the cardiac toxicity of doxorubicin. Three days following doxorubicin treatment, in vivo intracardiac pressures, cardiac outputs, in vitro cardiac weights, and cardiac electron microscopy were performed. Guinea pigs were treated with doxorubicin alone, doxorubicin plus caffeine, caffeine alone, and sterile saline as a control measure. Animals treated with doxorubicin had no significant differences in in vivo hemodynamics compared to the control animals. The average histology score was slightly but not statistically greater than the control animals, score (1.19 +/- 0.36 vs 1.60 +/- 0.34, respectively, P = NS). Animals receiving both doxorubicin and caffeine compared to the control animals had important differences in left ventricular systolic pressure (67 +/- 10 vs 92 +/- 7 mmHg; P = .003), cardiac output (154 +/- 35 vs 217 +/- 41 mL/min; P = .0174), stroke volume (.59 +/- 12 vs .79 +/- .07 mL; P = .0045), and histology score (2.36 +/- 0.21 vs 1.19 +/- 0.36; P = .028). There were no differences in left or right heart filling pressures between treatment groups. As an independent confirmation, there was a weak but statistically significant negative correlation between the biopsy score and cardiac output or stroke volume for all four groups of animals (r = .44, P = .031 and r = -.42, P = .040, respectively). These data are consistent with caffeine and doxorubicin having additive or potentiating effects on cardiac toxicity in this animal model.

Animals↗
PubMed1997

A proposed approach to study the toxicology of complex mixtures of petroleum products: the integrated use of QSAR, lumping analysis and PBPK/PD modeling.

Mixture toxicity is a topic that has become a matter of concern during the last two decades. One of the major problems with assessing the toxicity of mixtures and the associated human and environmental risk is the large number of possible mixtures, as well as the fact that the actual mixture effect for a given set of constituents might strongly depend on the actual composition of the mixture, i.e., the ratios of the constituent, as well as their nature. This paper presents a possible approach to describe and thereby better understand the pharmacokinetics and dynamics of complex mixtures by combining quantitative structure-activity relationships to predict needed parameters, lumping to reduce the complexity of the problem, and physiologically based pharmacokinetic/pharmacodynamic modeling to integrate all this information into a complete toxicological description of the mixture. It is our hope that by presenting this conceptual approach we might be able to stimulate some criticisms and discussions in the toxicology community regarding this complex and yet very important area of research.

Animals↗
PubMed2006

Validation and update of a model used to predict copper toxicity to the marine bivalve Mytilus sp.

A model was recently published that relates the toxicity of copper to the most sensitive taxa in the U.S. Environmental Protection Agency's criteria database (Mytilus sp.) with dissolved organic carbon concentrations in saltwater. This model was developed for potential use in risk assessment and in the development of site-specific criteria (SSC) for copper in saltwater environments where Mytilus sp. is considered an appropriate indicator species. This manuscript presents the results of a field validation study of that model. Effective concentration 50% (EC(50)) values (n = 21) for seven sites were all predicted by the model within the previously established range of acceptability. Slopes and intercepts of the two data sets were not significantly different. Consequently, the data were pooled, and new equations were developed. Dissolved copper EC(50) values were highly correlated (r(2) = 0.76, n = 75, P < 0.0001) across a wide range of sample dissolved organic carbon (DOC) concentrations (0.3-12 mg C/L) and were explained by the equation EC(50) = 11.22 DOC(0.60). Two updated equations are proposed for consideration as a means of estimating site-specific final chronic criteria (FCC) and final acute criteria (FAC) for copper in marine and estuarine environments (copper FCC(DOC) = 3.59 DOC(0.60); copper FAC(DOC) = 5.61 DOC(0.60)).

Animals↗