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PubMed1998

[Concepts for the regulation of mixtures of toxic pollutants in environmental hygiene].

In view of the increasing accumulation of large-scale livestock production facilities in the western parts of Lower Saxony the question rises how ecology and economy can be conciliated and how the protection of human health can be assured. Based on existing legislation this is hard to achieve because of the weak legal position of the administration when trying to prohibit the further expansion of livestock production as opposed to the strong legal position of owners and investors. Presently there is no agreement within the scientific community on safe limits for airborne pathogens and it is quite obvious that thresholds for peak concentrations do not solve the problem of background level exposures. Apart from the unsatisfactory current practise to licence farm animal units in the outskirts of existing villages only, in future the introduction of the EC Environmental Management and Auditing Scheme (EMAS) in animal production may improve the situation. This management system is intended to permanently reduce the environmental impact of a production site and implements the ALARA-PRINCIPLE (as low as reasonably achievable) which is known from protection measures against radiation. As the implementation of the EMAS so far works only on a voluntary basis, an incentive is needed. If dealers and consumers give preference to products from producers having adopted the EMAS, this would be a very efficient incentive. Before this could be put into practise, however, the EMAS criteria originally designed for industrial production sites will have to be adapted to the special conditions of animal production.

Animal Husbandry↗
PubMed1997

Additivity in microbial toxicity of nonuniform mixtures of organic chemicals.

Microbial toxicity of nonuniform mixtures of selected synthetic organic chemicals in several proportion is evaluated. Toxicity is quantified by the inhibition of oxygen uptake rate of a surrogate microbial text culture as measured by a respirometer. The joint toxic effects of the chemicals are analyzed for simple addition using toxic units (TU) and similarity parameters (lambda). A new approach is proposed to assign acceptance limits to sigma(TU)i and lambda to account for experiment errors and variances. Based on this approach, the joint toxic effects of 16 chemicals evaluated in this study in 14 different mixtures were found to be simply additive. Predictions of component concentration based on simple additivity agreed with the measured values within an average factor of error of 1.4.

Bacteria↗
PubMed2006

Predictive models attribute effects on fish assemblages to toxicity and habitat alteration.

Biological assessments should both estimate the condition of a biological resource (magnitude of alteration) and provide environmental managers with a diagnosis of the potential causes of impairment. Although methods of quantifying condition are well developed, identifying and proportionately attributing impairment to probable causes remain problematic. Furthermore, analyses of both condition and cause have often been difficult to communicate. We developed an approach that (1) links fish, habitat, and chemistry data collected from hundreds of sites in Ohio (USA) streams, (2) assesses the biological condition at each site, (3) attributes impairment to multiple probable causes, and (4) provides the results of the analyses in simple-to-interpret pie charts. The data set was managed using a geographic information system. Biological condition was assessed using a RIVPACS (river invertebrate prediction and classification system)-like predictive model. The model provided probabilities of capture for 117 fish species based on the geographic location of sites and local habitat descriptors. Impaired biological condition was defined as the proportion of those native species predicted to occur at a site that were observed. The potential toxic effects of exposure to mixtures of contaminants were estimated using species sensitivity distributions and mixture toxicity principles. Generalized linear regression models described species abundance as a function of habitat characteristics. Statistically linking biological condition, habitat characteristics including mixture risks, and species abundance allowed us to evaluate the losses of species with environmental conditions. Results were mapped as simple effect and probable-cause pie charts (EPC pie diagrams), with pie sizes corresponding to magnitude of local impairment, and slice sizes to the relative probable contributions of different stressors. The types of models we used have been successfully applied in ecology and ecotoxicology, but they have not previously been used in concert to quantify impairment and its likely causes. Although data limitations constrained our ability to examine complex interactions between stressors and species, the direct relationships we detected likely represent conservative estimates of stressor contributions to local impairment. Future refinements of the general approach and specific methods described here should yield even more promising results.

Animals↗
PubMed2001

Development of quantitative structure activity relationships in toxicity prediction of complex mixtures.

AIM: To predict the toxicity of mixtures of halogenated benzenes (narcotics). METHODS: Acute toxicity test of single chemicals and mixtures was performed using Photobacterium phosphoreum. Partition coefficients of mixtures were calculated by a special equation. Quantitative structure-activity relationship (QSAR) studies were carried out based on results of toxicity tests, n-octanol/water partition coefficient (Kow), and partition coefficient of mixtures (Kmix). RESULTS: 1) There was a good relationship between toxicity and lgKow for single compounds. 2) QSAR analysis showed a perfect correlation between the calculated Kmix and the mixture toxicity for binary mixtures. 3) Using the QSAR model of binary mixtures, the toxicity of other related mixtures containing different composition and fraction was predicted very well. CONCLUSION: The toxicity of halogenated benzene mixtures (narcotics) was predicted by QSAR. This kind of study is helpful for assessing the toxicity of narcotic mixtures.

Benzene Derivatives↗
PubMed2001

Toxicity of cadmium and zinc to miracidia of Schistosoma mansoni.

The specific objectives of this study were to elucidate metal toxicity to hatching, survival and avoidance behaviour of Schistosoma mansoni miracidia. The toxicity of cadmium, zinc, and cadmium/zinc mixtures at concentrations ranging from 10000 to 10 microg/l was investigated. Metal mixture toxicity investigation was undertaken with equal concentrations of the metals. The hatching of miracidia from eggs was inhibited by concentrations of 1000-10000 microg/l of single metals. Metal mixtures had no effect on egg hatching. Survival of miracidia was reduced by increasing metal concentration except at concentrations of 10 microg/l for single metal toxicity where survival was increased above the control. Miracidia demonstrated a rapid avoidance behaviour when briefly exposed to heavy metals. The mechanisms of metal toxicity to miracidia are briefly discussed.

Animals↗
PubMed2005

Algal toxicity of nitrobenzenes: combined effect analysis as a pharmacological probe for similar modes of interaction.

An analysis regarding the effects of the mixture toxicity of different nitrobenzenes on the reproduction of the green alga Scenedesmus vacuolatus was undertaken using the concepts of concentration addition and response addition. Using lipophilicity-based quantitative structure-activity relationship (QSAR) modeling for nitrobenzenes, the assumption is held that mononitrobenzenes may exert narcotic effects as a common type of action, whereas dinitrobenzenes show a somewhat greater toxicity. From the literature, QSARs based on quantum chemical parameters suggest that some mononitrobenzenes may be effective through additional other modes of action. The toxicity of a mixture of 14 nitrobenzenes clearly exceeds the predicted combined effects, as expected for the sum of toxic units from a uniform narcotic mode of action. Moreover, the observed combined effect is smaller than that predicted from similarly acting compounds calculated on the basis of the parameterized dose-response functions using concentration addition. Further modeling of the combined effect, joining the models of concentration addition for components with anticipated similar modes of action and of response addition for those with independent action, led us to propose that not all nitrobenzenes follow the same mode of action. This idea is in line with the hypothesis derived from quantum chemical QSAR considerations. Most interestingly, the methodology introduced here uses combined effect analysis as a pharmacological probe to test for similarity in the mode of action of mixture components.

Animals↗
PubMed1975

Toxicity of paired mixtures of candidate forest insecticides to rainbow trout.

The toxicities of Zectran, Dylox, Volaton, Guthion, pyrethrum extract, and the synthetic pyrethroids SBP-1382, and RU-11679 were determined individually and in paired mixtures against rainbow trout. The carbamate Zectran was the least toxic, and the synthetic pyrethroids were the most toxic. Nine of the mixtures produced less than additive toxicity (antagonism), nine produced additive toxicity, and two produced greater than additive toxicity (synergism). None of the mixture toxicities deviated markedly from additive,and only two pairs of mixtures would pose a greater toxicological hazard to fish than the respective individual chemicals.

Animals↗
PubMed1998

Estimation of toxicity of chemical mixtures through modeling of chemical interactions.

The Agency for Toxic Substances and Disease Registry (ATSDR), in collaboration with the Dutch Organization for Applied Scientific Research (TNO) Nutrition and Food Research Institute, is conducting studies to evaluate the role of chemical interactions in the expression of toxicity from low-level exposure to combinations of chemicals. The goal of this collaborative effort is to use a weight-of-evidence (WOE) approach to estimate joint toxicity of some simple chemical mixtures and to compare the estimations with test results from animal toxicity studies. The WOE approach uses individual chemical dose-response assessments and algorithms that incorporate various assumptions regarding potential chemical interactions. Qualitative evaluations were prepared for binary combinations of chemicals for the effect of butyl hydroxyanisole on di(2-ethylhexyl)phthalate, the effect of stannous chloride on Cd chloride (CdCl2), and the effect of CdCl2 on loperamide. Analyses of these evaluations and their comparison with the conclusions of laboratory animal experiments indicate that the WOE approach can be used to estimate qualitatively the joint toxicity of such simple mixtures. To further test the utility of the WOE approach, qualitative and semiquantitative evaluations were prepared for two chemical mixtures--one with similarly acting halogenated aliphatics (trichloroethylene, tetrachloroethylene, hexachloro-1,3-butadiene[HCBD], and 1,1,2-trichloro-3,3,3-trifluoropropene [TCTFP]) and the other with dissimilarly acting nephrotoxic components (mercuric chloride, lysinolalanine, D-limonene, and HCBD). These two sets of data were used to estimate the overall toxicities of the mixtures using the WOE algorithm for the mixture. The comparison of the results of the estimated toxicity with experimentally determined toxicity of the mixture of similarly acting nephrotoxicants demonstrated that the WOE approach correctly adjusted for the observed interactions in experimental animal studies. However, this was not true for the mixture of dissimilarly acting nephrotoxicants. This could be attributed to the fact that WOE evaluations are based on dose additivity that postulates that all chemicals in a given mixture act in the same way--by the same mechanism--and differ only in their potencies. In these cases the WOE approach evaluations, based on consideration of common mechanisms for simple chemical mixtures, can lead to better estimates of joint toxicity of chemical mixtures than the default assumption of dose additivity. The results also show that the WOE evaluations should be target-organ specific because none of the models tested could approximate the observed responses in organs other than the target organs in the laboratory animal studies.

Algorithms↗
PubMed2004

Effects of advanced oxidation processes (AOPs) on the toxicity of a mixture of pharmaceuticals.

The possibility of applying main AOP techniques, namely ozonation, H2O2/UV photolysis and TiO2 photocatalysis to provide a significant reduction of toxicity of pharmaceutical mixtures has been evaluated. For the preparation of the mixture six pharmaceuticals were chosen among those found at highest concentrations in Sewage Treatment Plant effluents, namely carbamazepine, clofibric acid, diclofenac, sulfamethoxazole, ofloxacin and propranolol. The blue-green alga Synechococcus leopoliensis and the rotifer Brachyonus calyciflorus were utilised to assess the toxicity of the mixtures after AOP treatments. All the toxicity tests were performed using chronic standardized bioassays. The best results were obtained with ozonation. With this type of treatment a complete removal of mixture toxicity on S. leopolensis was obtained even after the shortest time of application (1 min). The ozonation treatment leads also to removal of all the pharmaceutical mixture toxicity on B. calyciflorus, by applying the oxidizing agent for at least for 2 minutes.

Animals↗
PubMed2002

New technique for estimating thresholds of toxicity in ecological risk assessment.

The use and utility of the no observed effect concentration (NOEC) in ecological risk assessment is a contentious issue. One concern is that the NOEC is not representative of a concentration at which no biologically significant effect is occurring. A new method has been developed to estimate the threshold of toxicity, or a true NOEC, for aquatic plants. The method involves determining the effective concentration (ECx) of a number of endpoints from one species. These ECx values are plotted on a log-probability scale. The x-intercept, or a low centile, of the distribution can be interpreted as the threshold of toxicity for that plant at that response level. This threshold is the concentration at which no effects should be observed for any endpoint above that response level. It is based on the assumptions that multiple effect measures from a single species will be log-normally distributed and thatthe distribution contains all possible endpoints for that species. The thresholds and the distributions can then be used as a substitute for the NOEC or ECx in risk assessment techniques, such as hazard quotients and probabilistic ecological risk assessment. This new method of estimating toxicitythresholds is more realistic than the use of arbitrary uncertainty factors, is more conservative than current probabilistic risk assessment methods, allows for simple comparison between species and exposure duration to a toxicant, and may be useful for assessing mixture toxicity. This technique was applied to field derived data with Lemna gibba, Myriophyllum spicatum, and M. sibiricumto assess potential risks from monochloroacetic acid (MCA). Using this new risk assessment method, we conclude that MCA does not appear to pose a risk to aquatic macrophytes under field conditions at current environmental concentrations.

Acetates↗
PubMed2026

From molecular responses to environmental monitoring: advances and translational gaps in omics approaches in fish environmental toxicology.

Fish occupy a central position in aquatic ecosystems and serve as important bioindicators for environmental monitoring, as well as powerful translational models for understanding toxic mechanisms conserved across higher vertebrates. In recent years, omics techniques have proven to be powerful tools to address complex environmental questions that conventional toxicology methods cannot answer. Despite this potential, a critical translational gap remains between molecular findings and their use in ecological risk assessment frameworks. This review critically synthesizes advances across omics techniques including epigenomics, transcriptomics, metabolomics and proteomics and their integration. Special emphasis is placed on methodological considerations and practical aspects of these techniques in fish environmental toxicology and environmental monitoring. Evidence from single-omics studies suggests conserved biomarker signatures across species while characterizing complex phenomena like non-monotonic dose-response relationships, mixture toxicity and transgenerational and stereoselective effects with implications for population level monitoring. Multi-omics studies, especially those involving triple omics, further enhance mechanistic resolution by reconstructing adverse outcome pathways. We further evaluate using case studies when additional molecular layers provide critical insight and when they offer limited advantage, a strategic distinction with direct implications in environmental monitoring programmes. Finally, current limitations and future directions that will ultimately bridge the translational gap and hold promise for advancing mechanistic ecotoxicology and predictive environmental monitoring are discussed.

Animals↗
PubMed2005

An integrated addition and interaction model for assessing toxicity of chemical mixtures.

The high propensity for simultaneous exposure to multiple environmental chemicals necessitates the development and use of models that provide insight into the toxicity of chemical mixtures. In this study, we developed a mathematical model that combines concepts of concentration addition, response addition, and toxicokinetic chemical interaction to assess toxicity of chemical mixtures. A ternary mixture of acetylcholinesterase inhibiting organophosphates (malathion and parathion) and the P450 inhibitor piperonyl butoxide was used to model toxicity. Concentration-response curves were generated for individual chemicals as well as for mixtures of the chemicals using acute toxicity tests with Daphnia magna. The toxicity of binary combinations of malathion and parathion adhered to the principles of concentration addition. The contribution of piperonyl butoxide to mixture toxicity was integrated using a model for response addition. Piperonyl butoxide also modified the toxicity of the organophosphates by inhibiting their metabolic activation. The antagonistic effects of piperonyl butoxide towards the organophosphates were quantified as coefficients of interactions (K-functions) and incorporated into the mixture model. Finally, toxicity of the ternary mixture was modeled at 30 different mixture formulations using three additive models that assumed no interaction (concentration addition, response addition, and integrated addition) and using the integrated addition and interaction (IAI) model. Toxicity of the 30 mixtures was then experimentally determined and compared to model results. Only the IAI model accurately predicted the toxicity of the mixtures. The IAI model holds promise as a means for assessing hazard of complex chemical mixtures.

Acetylcholinesterase↗