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At least 163 records · Page 9Linked to original sources

Integral toxicity test of sea waters by an algal biosensor.

An integral toxicity test, based on an algal biosensor and suitable to be used in sea water, is presented. The biosensor was designed and built by coupling a Clark oxygen electrode as transducer and the marine alga Spirulina subsalsa as biological mediator; it constitutes the "core" in a lab-scale prototype of a flow apparatus suitable to continuously monitor, in sea water, the photosynthetic activity of the alga and, from its variation, the marine pollution from the toxicological point of view. Inorganic pollutants (heavy metals) were tested in previous researches while organic ones (chlorophenols, pesticides and surfactants) are the object of the present paper.

Bacterial Proteins↗

[Subacute toxicity test of cefoperazone in beagle dogs with the intravenous administration for 3 months (author's transl)].

The subacute toxicity test of cefoperazone (CPZ) in Beagle dogs with the intravenous administration for 35 days has been reported from our laboratory. In the present experiments, the subacute toxicity test of CPZ in Beagle dogs was carried out for longer administration period than before. CPZ was given intravenously to each group (2 or 4 dogs) at dose level of 100 mg/kg/day, 200 mg/kg/day and 400 mg/kg/day respectively for 3 months. Cefazolin (CEZ) was used intravenously for positive control using 4 dogs at dose level of 200 mg/kg/day and physiological saline was given intravenously to 2 dogs for 3 months. 1) In Beagle dogs received high dose of CPZ, transient vomiting, salivation and diarrhea were observed immediately after the administration. 2) Signs of anemia, such as decrease of erythrocyte and value of hemoglobin and hematocrit, and increase of reticulocytes of the peripheral blood and in fragility of red cell associated with decrease of food intake, were observed in 2 female dogs given CPZ of 400 mg/kg/day. In only one of these dogs, a positive reaction of COOMBS' test was shown. The anemia recognized in these 2 dogs seems to be of hemolytic nature. 3) The weight of thymus was decreased in all of 4 dogs given CPZ at 400 mg/kg/day and in 2 out of 4 dogs given CPZ at 200 mg/kg/day, respectively. 4) Based on the fact that no abnormalities were found in dogs given CPZ at 200 mg/kg/day except a slight decrease of weight of thymus in some of them, the maximum safety dose of CPZ was thought to be 200 mg/kg/day.

Animals↗

Comparison of several toxicity tests applied to complex wastewaters and mussel biomarkers in receiving waters.

In this study, the complex wastewaters/effluents discharged to coastal regions of Turkey and Greece were sampled, and various toxicity tests were applied. The bioassays used included the assessment of the luminescence inhibition of the bacterium Vibrio fisheri, the photosynthesis inhibition (14C uptake rate) and growth inhibition of the algal species Phaeodactylum tricornutum, and the mortality of the crustacean Artemia franciscana and rotifer Brachionus plicatilis. Additionally, "neutral red retention" and "filtration rate" sublethal biomarker techniques were performed by utilizing the mussel species Mytilus galloproviancialis, inhabiting the points of discharges in Turkey. All discharges tested were found to be acutely toxic to P. tricornutum and slightly toxic to V. fisheri, A. franciscana, and B. plicatilis. Test results showed that the 14C uptake rate toxicity test was the most sensitive one among the other bioassays. The biomarker results showed that the health status of mussels in the coastal areas decreased significantly, indicating the pollution of the receiving waters in Turkey. The conclusions drawn highlight the necessity for an intesive ecotoxicological monitoring scheme that will incorporate the most suitable bioassays and biomarkers to adequately contribute to the upgrading and maintenance of the ecological quality of the coastal waters in Greece and in Turkey.

Aliivibrio fischeri↗

Algal toxicity tests for environmental risk assessments of metals.

Current regulatory methods for assessing the effects of contaminants, and metals in particular, rely mainly on a limited number of standardized test methods and test species (OECD, ISO, ASTM, USEPA). However, these test protocols allow a certain degree of freedom in relation to physicochemical parameters or biological aspects, which may lead to large variability in test results. The current review, based on effects data and theoretical considerations reported in the literature, tried to determine and quantify the effect of variation of these factors on the outcome of metal toxicity tests with algae. Major physicochemical parameters that affect metal toxicity to algae are hardness, pH, preculture conditions, type of test medium, and presence of chelating agents: Literature data also clearly demonstrate the importance of test species or strain selection (inter- and intraspecies sensitivity variability) on the outcome of algal toxicity tests. For Zn, a factor of 8.3 is observed between the NOEC for Selenastrum capricornutum (currently renamed Pseudokirchneriella subcapitata) and Croococcus paris. An intraspecies difference for S. capricornutum of a factor of 60 is observed between various reported EC50S for Cd. Next to differences in physicochemical test conditions, possible adaptation or acclimation to deficient/elevated metal concentrations add to the reported differences: S. capricornutum became three times less sensitive to Zn when acclimated to 65 microg Zn/L compared to cultures in ISO medium. This review has revealed that currently accepted standard protocols used in regulatory frameworks contain a number of major shortcomings on the physicochemical and biological aspects of algal toxicity testing with metals. These shortcomings are summarized in Table 5, together with a number of suggestions that could help to modify and improve standard test protocols for evaluating metal toxicity to algae. Until now, important factors such as pH control during test performance, selection of test medium, test species, and the effects of possible adaptation/acclimation to natural metal concentrations have not been considered, which could have serious implications when the resulting unsuitable or irrelevant toxicity data are subsequently used for setting environmental management policies. These findings also have their consequences when extrapolating laboratory data to the field as the complexity of natural waters currently is not reflected in laboratory standard media. These media contain no dissolved organic matter, have a relatively high pH, and contain large amounts of essential nutrients. In addition, the limited number of laboratory test species do not reflect natural phytoplankton communities. Test procedures for assessing the environmental impact of metal contamination in a specified ecoregion should therefore be based on performing a battery of algal tests with species adapted to and tested under the specific natural conditions of the region.

Biological Availability↗

Biostatistical methods for the validation of alternative methods for in vitro toxicity testing.

Statistical methods for the validation of toxicological in vitro test assays are developed and applied. Validation is performed either in comparison with in vivo assays or in comparison with other in vitro assays of established validity. Biostatistical methods are presented which are of potential use and benefit for the validation of alternative methods for the risk assessment of chemicals, providing at least an equivalent level of protection through in vitro toxicity testing to that obtained through the use of current in vivo methods. Characteristic indices are developed and determined. Qualitative outcomes are characterised by the rates of false-positive and false-negative predictions, sensitivity and specificity, and predictive values. Quantitative outcomes are characterised by regression coefficients derived from predictive models. The receiver operating characteristics (ROC) technique, applicable when a continuum of cut-off values is considered, is discussed in detail, in relation to its use for statistical modelling and statistical inference. The methods presented are examined for their use for the proof of safety and for toxicity detection and testing. We emphasise that the final validation of toxicity testing is human toxicity, and that the in vivo test itself is only a predictor with an inherent uncertainty. Therefore, the validation of the in vitro test has to account for the vagueness and uncertainty of the "gold standard" in vivo test. We address model selection and model validation, and a four-step scheme is proposed for the conduct of validation studies. Gaps and research needs are formulated to improve the validation of alternative methods for in vitro toxicity testing.

Animal Testing Alternatives↗

Toxicity testing in environmental monitoring: the role of enzymatic biosensors.

Biological toxicity testing is a rapidly expanding field involving numerous bioanalytical techniques. The enzymatic biosensors are valuable screening tools to identify pollutants and/or toxic agents in the environment and/or in food matrices, thus representing a valid alternative to animal testing in analytical toxicology. Inhibition based biosensors here presented have been proved to represent alternative assays for the toxicity evaluation of warfare agents and endocrine disrupting chemicals as well as algal toxins (phycotoxins) in the contamined sea foods (mainly clams and other mollusks). Results obtained by inhibition studies performed by means of several enzymatic biosensors indicate the reliability of the proposed method and the possibility to extend such an experimental approach to other toxicants as a simple, rapid and cheap biotest, to be used easily also "on the spot".

Animals↗

Toxicity testing and derivation of the ADI.

The ADI is an estimate of the amount of a chemical that can be ingested daily over a lifetime without appreciable health risk. It is derived from No-Observed-Adverse-Effect-Levels (NOAELs) determined in a battery of toxicity tests in animals and augmented by human data where available. The toxicity tests are intended (with a few exceptions) to embrace all the circumstances of human exposure to dietary chemicals. Hence these tests include chronic studies, sometimes with prior exposure in utero, and reproduction tests covering the reproductive phase including effects on the parental animals and the offspring. The tests should also cover the rapid growth phase from weaning to maturing. The ADI is calculated from the lowest NOAEL in the most sensitive test and the most sensitive species, unless other data indicate otherwise, and if the reproductive, neonatal or rapid growth phases indicate particular periods of sensitivity this should drive the numerical derivation of the ADI. In calculating the ADI, the NOAEL is divided by appropriate arbitrary or data-derived safety or uncertainty factors. Care in selecting the pivotal test, the NOAEL and the safety factors should ensure that the ADI does apply to children (or other age groups). However, because of the higher food intake of children on a body weight basis, specific risk management measures may be needed to ensure that the ADI is not exceeded.

Animals↗

[Is the abnormal toxicity test still relevant for the safety of vaccines, sera and immunoglobulins?]

The German Pharmacopoeia (DAB) requires the abnormal toxicity test (ATT) using mice and guinea pigs as a non-specific safety test for vaccines, sera and immuno-globulines. The purpose of this project was to investigate the relevance of ATT after the introduction of GMP- and GLP-principles in the manufacturing of biological products. A great variability in the test performance became evident for the different test laboratories, involving the animal number as well as the vaccine dosage administration and test duration. The retrospective analysis of ATT results reveals reasons for the incompatibility of particular preparation groups, vaccine components or additives with the animal species used. There were highly significant differences between the manufacturers and the PEI regarding the frequency of deviating test results for identical test batches. Positive ATT"s never resulted from the insufficient quality of a batch. On the other hand vaccines causing adverse reactions in the target species were not identified by the ATT. For these reasons the abnormal toxicity test is unsuitable to detect harmful batches. The results of the analysis of data show that finally the ATT has always been passed, i.e. there was no retention by the vaccine manufacturers and no refusal by the controlling authorities due to the ATT-results. Considering the present animal model and the questionable transferability of the test results to the target species only a poor reliability is evident. Taking into account aspects of drug safety and animal welfare it is recommended to the DAB to omit the ATT.

Journal Article↗

Estimation of the critical effect level for pollution prevention based on oyster embryonic development toxicity test: the search for reliability.

In spite of the consideration that toxicity testing is a reduced approach to measure the effects of pollutants on ecosystems, the early-life-stage (ELS) tests have evident ecological relevance because they reflect the possible reproductive impairment of the natural populations. The procedure and validation of Crassostrea rhizophorae embryonic development test have shown that it meets the same precision as other U.S. EPA tests, where EC(50) is generally used as a toxicological endpoint. However, the recognition that EC(50) is not the best endpoint to assess contaminant effects led U.S. EPA to recently suggest EC(25) as an alternative to estimate xenobiotic effects for pollution prevention. To provide reliability to the toxicological test results on C. rhizophorae embryos, the present work aimed to establish the critical effect level for this test organism, based on its reaction to reference toxicants, by using the statistical method proposed by Norberg-King (Inhibition Concentration, version 2.0). Oyster embryos were exposed to graded series of reference toxicants (ZnSO(4) x 7H(2)O; AgNO(3); KCl; CdCl(2)H(2)O; phenol, 4-chlorophenol and dodecyl sodium sulphate). Based on the obtained results, the critical value for C. rhizophorae embryonic development test was estimated as EC(15). The present research enhances the emerging consensus that ELS tests data would be adequate for estimating the chronic safe concentrations of pollutants in the receiving waters. Based on recommended criteria and on the results of the present research, zinc sulphate and 4-chlorophenol have been pointed out, among the inorganic and organic compounds tested, as the best reference toxicants for C. rhizophorae ELS-test.

Animals↗

Using population-based serum drug concentration cutoff values to predict toxicity: test performance and limitations compared with Bayesian interpretation.

The use of population-based serum drug concentration cutoff values for several commonly monitored drugs as tests to distinguish toxicity from nontoxicity was studied. Serum drug concentration and response data published in studies of theophylline, digoxin, aminoglycosides, vancomycin, and procainamide were analyzed to determine the prevalence of toxicity in each group of patients. Serum drug concentration cutoff values were then varied, and the following performance characteristics of the cutoffs as tests for predicting toxicity were calculated for each value: sensitivity, specificity, likelihood ratio, predictive value, and ratio of net consequences. At commonly accepted cutoff values, sensitivity was lower than desirable, positive predictive values were less than negative values, and the ratio of net consequences indicated that false-negative errors are implicitly weighted as more risky than false-positive errors. As the cutoff for each drug was increased, specificity increased but sensitivity decreased, positive predictive values increased but negative predictive values decreased, and the ratio of net consequences increased. Therapeutic drug monitoring would improve if practitioners and laboratorians collaborated to (1) conduct prospective studies of the test performance characteristics of drug concentrations, (2) estimate the pretest probability of toxicity for each patient, (3) combine the pretest estimate with the test characteristics to make a posttest estimate, and (4) develop a more patient-specific, Bayesian approach.

Aminoglycosides↗

Early life-stage toxicity test methods for gulf toadfish (Opsanus beta) and results using chlorpyrifos.

Gulf toadfish (Opsanus beta) were continuously exposed as embryos, sac fry, and juveniles to technical chlorpyrifos in two 49-day early life-stage toxicity tests. Survival was significantly (alpha = 0.05) reduced only in 150 micrograms/liter. However, toadfish exposed to chlorpyrifos concentrations from 3.7 to 150 micrograms/liter weighted significantly less than control fish: 9% lower in 3.7 micrograms/liter to 62% lower in 150 micrograms/liter. The 96-hr LC50 for juvenile fish was 520 micrograms/liter. Concentrations of chlorpyrifos in toadfish and bioconcentration factors increased with increasing exposure concentration, a condition not generally observed with other marine fishes and other test chemicals. These results demonstrated the procedures for, and the practicality of, early life-stage tests with this marine species. We recommend the use of the gulf toadfish for comparative toxicity testing and for evaluating the toxicity of substances in conjunction with ontogenetical, physiological, and histological investigations of this considerably studied genus. We do not recommend it for routine effects testing.

Animals↗

Methods used for testing toxicity of industrial chemicals and the need of their international unification.

The work presented here provides a demonstration of approaches in testing chemical substances in the world, comparison of various guidelines, shows differences in them with the aim to unify them as much as possible and thus to achieve their international comparability. First chapter includes a comparison of American and European approaches to Good Laboratory Practice (GLP). Some parts of American GLP seem to be specific for the USA only and thus they are not suitable for application on the international level where countries having different systems of government and various levels of their economy would have to observe them. GLP published in OECD and ECETOC guidelines seem to be most beneficial for needs of socialist countries. OECD, EEC, EPA/FIFRA, EPA/TSCA, Japan/MAFF and UK/HSC guidelines are compared in subsequent chapters and recommendations given by ECETOC and the authors of this work for unification of the guidelines are presented as well. Some parts of OECD guidelines are specified in detail there especially those which are most suitable for CMEA countries. Differences or supplements contained in CMEA recommendations are presented in the end of each chapter. Acute, subchronic and chronic toxicity tests were compared as well as carcinogenicity, combined carcinogenicity/chronic toxicity studies and reproductive toxicity tests.

Animals↗

Investigations into using the nematode Caenorhabditis elegans for municipal and industrial wastewater toxicity testing.

This investigative study assesses the ease and usefulness of the nematode Caenorhabditis elegans for identifying contributors to effluent toxicity within an industrial and municipal wastewater treatment plant (WWTP) system. Several different types of industries, including fiberglass manufacturing, paper packaging, and yarn dyeing, discharge effluent into the municipal wastewater treatment plant, which in turn discharges into a local creek. A major objective of this study was to identify primary sources of toxicity throughout the system with a nematode toxicity test. Twenty-four-hour composite water samples were taken periodically over a ten-month period at five strategic points within the system: (1) at the point of discharge at each of the three industries, (2) at the combined industrial influent of the wastewater treatment plant, (3) at the effluent of the WWTP, (4) upstream of the WWTP discharge, and (5) downstream of the WWTP discharge. Samples were analyzed for basic water chemistry, and each sample was tested for whole effluent toxicity using a 72-h nematode test with mortality as the end point. Results suggest that interactions between the wastewaters of certain industries may increase the overall nematode toxicity in the wastewater treatment facility's composite influent and effluent. Nematode mortality trends indicate relatively high toxicity levels in wastewater entering the WWTP from contributing industries. High WWTP influent toxicity may potentially be due to varying flow rate ratios of industrial discharges, release of varying toxic constituents in wastewaters, and toxic interactions between chemical constituents of industrial wastewaters. The evaluation of toxicity within the treatment system may pinpoint locations where pollution prevention strategies may be implemented to reduce overall toxicity at the point of discharge.

Animals↗

A new early life-stage toxicity test using the California grunion (Leuresthes tenuis) and results with chlorpyrifos.

California grunion were continuously exposed as embryos and fry to technical chlorpyrifos in two toxicity tests conducted in the same exposure apparatus. The first test, a 35-day early life-stage (ELS) test, began with approximately 2.5-day-old embryos that were exposed in flow-through aquaria in darkness until hatching was stimulated on Day 9 of exposure. The second toxicity test, a fry test, began with newly hatched fry and lasted 26 days. Test water temperature ranged from 23 to 26 degrees C and salinity from 24.5 to 34.0%. Results of the two tests were similar, indicating that exposure of embryos added little to the overall toxicity of chlorpyrifos to grunions. Percentage hatch of embryos was unaffected by the chlorpyrifos concentrations tested. Fry survival was apparently reduced in nominal concentrations greater than or equal to 1.0 micrograms/liter in both tests, but significantly so in concentrations greater than or equal to 1.0 micrograms/liter in the ELS test and greater than or equal to 2.0 micrograms/liter in the fry test. When compared with carrier controls, mean fish weights were significantly reduced in nominal chlorpyrifos concentrations greater than or equal to 0.5 micrograms/liter in the ELS test and greater than or equal to 1.0 micrograms/liter in the fry exposure. Mean bioconcentration factors were 770X for fish that survived the ELS test and 190X for those that survived the fry test. Results demonstrate the practicality of conducting ELS tests for the first time with a marine fish from the Pacific coastal waters of the United States.

Animals↗

Chronic toxicity tests with Daphnia magna for examination of river water quality.

Chronic toxicity tests with Daphnia magna were applied for examination of river water quality. Water was sampled from the Maioka River in Yokohama City on May 14, 20, and 27, 1999, and used for the test after solid-phase extraction. The chronic test was carried out according to the OECD method. The duration was 21 days and the total number of live offspring produced per parent animal was counted. The results of the tests showed, survival rates of 100% using river water sampled on May 14 and 20 and the total numbers of live offspring produced per parent animal did not differ from the control. However, the survival rate of the sample collected on May 27 was 0% and the pesticides, fenitrothion, and thiobencarb were detected in the water. In addition to the river water samples, reconstituted water (Elendt M7) with additions of fenitrothion and thiobencarb was prepared to investigate mortality. When the reconstituted water with thiobencarb was applied to the test, the total number of live offspring produced per parent animal did not differ from the control. In contrast, when reconstituted water with fenitrothion was applied to the test, most parents were alive, but the total number of live offspring produced per parent animal was apparently different. The results of the above tests indicate that D. magna was affected not only by fenitrothion in the river water collected on May 27, but also by other factors that were not clarified in this study.

Animals↗

Salinity tolerance of Daphnia magna and potential use for estuarine sediment toxicity tests.

Daphnia magna Straus, a common organism used for freshwater sediment toxicity tests, was evaluated to determine its tolerance to salinity and suitability for tests with estuarine water and sediments. Daphnids were exposed for 2 to 21 days to salinity in a variety of water-only tests, in tests with freshwater sediment overlain by salt water, and in tests with estuarine sediments overlain by freshwater. Daphnid age, test length, and temperature seemed to have little effect upon the range of LC50, NOAEL, and LOAEL values. LC50s for all tests ranged from 5.10 to 7.81 g/L, with a mean of 6.6 g/L salinity (measured conductivity 10.0 mS/cm) [corrected]. The mean NOAEL and LOAEL values based on production of young were 4.6 and 6.9 g/L salinity (measured conductivity 7.1 and 10.5 mS/cm) [corrected], respectively. The results indicate that D. magna will survive and reproduce well in water with salinities below 4 g/L and demonstrate the potential usefulness of this organism in monitoring sediment toxicity from both freshwater and estuarine wetland sites.

Animals↗

Microbial toxicity tests and chemical analysis as monitoring parameters at composting of creosote-contaminated soil.

Traditionally, chemical analyses are used in the assessment of contaminated soil and in monitoring the efficiency of soil remediation processes. We investigated if chemical analysis could be supported and even partly replaced by biological toxicity tests. In two case studies creosote-contaminated soil was composted outdoors in 5- and 100-m3 windrows. Degradation of polyaromatic hydrocarbons (PAHs) was followed by chemical analysis and toxicity tests. Polyaromatic hydrocarbons were quantified and identified by HPLC. Because the soil was also contaminated by copper-, chromium-, and arsenic-containing fungicides, these elements were analyzed by atomic absorption spectrometry. The toxicity of soil samples was assessed by a soil-contact modification of the luminescent bacteria (Vibrio fischeri) test and in the other case also by enzyme synthesis inhibition (Toxi-ChromoPad test, Escherichia coli). The toxicity of soil water extracts was measured by the standard luminescent bacteria (V. fischeri) test and bacterial (Pseudomonas putida) growth inhibition test. After the first 4 months of the composting period the total amount of PAHs was reduced in all windrows, and in particular, the loss of two- and some three-ring compounds was high, almost 90%. Toxicity decreased concurrently with the decrease in PAH concentration during composting, but after 4 months, one of the piles inoculated with mycobacteria and containing more three- and four-ring compounds was found to be more toxic than at the beginning. After the next summer, total PAH content was further reduced but some four-ring or heavier compounds were demonstrated to be poorly degraded. The toxicity was also reduced to the same level as in the control pile. The total PAH content and the toxicity were both reduced significantly during 5 months of composting.

Biodegradation, Environmental↗