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Toxic Interactions (toxic + interaction)
Selected AbstractsDevelopmental toxicity of indium: Embryotoxicity and teratogenicity in experimental animalsCONGENITAL ANOMALIES, Issue 4 2008Mikio Nakajima ABSTRACT Indium, a precious metal classified in group 13 (IIIB) in the periodic table, has been used increasingly in the semiconductor industry. Because indium is a rare metal, technology for indium recycling from transparent conducting films for liquid crystal displays is desired, and its safety evaluation is becoming increasingly necessary. The developmental toxicity of indium in experimental animals was summarized. The intravenous or oral administration of indium to pregnant animals causes growth inhibition and the death of embryos in hamsters, rats, and mice. The intravenous administration of indium to pregnant animals causes embryonic or fetal malformation, mainly involving digit and tail deformities, in hamsters and rats. The oral administration of indium also induces fetal malformation in rats and rabbits, but requires higher doses. No teratogenicity has been observed in mice. Caudal hypoplasia, probably due to excessive cell loss by increased apoptosis in the tailbud, in the early postimplantation stage was considered to account for indium-induced tail malformation as a possible pathogenetic mechanism. Findings from in vitro experiments indicated that the embryotoxicity of indium could have direct effects on the conceptuses. Toxicokinetic studies showed that the embryonic exposure concentration was more critical than the exposure time regarding the embryotoxicity of indium. It is considered from these findings that the risk of the developmental toxicity of indium in humans is low, unless an accidentally high level of exposure or unknown toxic interaction occurs because of possible human exposure routes and levels (i.e. oral, very low-level exposure). [source] Assessment of the toxicity of mixtures of nickel or cadmium with 9,10-phenanthrenequinone to Daphnia magna: Impact of a reactive oxygen-mediated mechanism with different redox-active metalsENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 7 2007Fangli Xie Abstract Recently, we showed that reactive oxygen species (ROS) formation was involved in the toxicity of the redox-active metal Cu and mixtures of Cu plus a photomodified polycyclic aromatic hydrocarbon (PAH), phenanthrenequinone (PHQ), to Daphnia magna. It is unknown, however, if similar results can be observed for metals with lower or no redox activity and their mixtures with PHQ. In the present study using D. magna, the toxicity of Ni, a weakly redox-active metal, and of Cd, a non-redox active metal, was examined with or without PHQ. The abilities of Ni, Cd, PHQ, and binary mixtures of metal plus PHQ to generate ROS were measured using a 2,,7,-dichlorofluorescein fluorescence assay. The results were compared with the results of Cu and mixtures of Cu plus PHQ from a recent study by our group. The order of metal toxicity to D. magna was found to be Cd , Cu > Ni. As with Cu/PHQ mixtures, synergistic toxicity was observed for mixtures of Ni and PHQ, whereas additive toxicity was observed for mixtures of Cd and PHQ. Alone, PHQ had no impact on ROS levels in D. magna. Nickel alone caused elevated ROS, which was further enhanced in the presence of PHQ. Neither Cd nor Cd/PHQ mixtures increased ROS production. Attenuation of toxicity and ROS production was observed in response to treatment with low concentrations of L -ascorbic acid. These results indicate potential toxic interactions between metals and modified PAHs. With redox-active metals, such as Cu and Ni, and modified PAHs, such as PHQ, these interactions can involve ROS formation. [source] Comparison of synthetic surfactants and biosurfactants in enhancing biodegradation of polycyclic aromatic hydrocarbonsENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 10 2003Randhir S. Makkar Abstract Polycyclic aromatic hydrocarbon (PAH) contamination of the environment represents a serious threat to the health of humans and ecosystems. Given the human health effects of PAHs, effective and cost-competitive remediation technologies are required. Bioremediation has shown promise as a potentially effective and low-cost treatment option, but concerns about the slow process rate and bioavailability limitations have hampered more widespread use of this technology. An option to enhance the bioavailability of PAHs is to add surfactants directly to soil in situ or ex situ in bioreactors. Surfactants increase the apparent solubility and desorption rate of the PAH to the aqueous phase. However, the results with some synthetic surfactants have shown that surfactant addition can actually inhibit PAH biodegradation via toxic interactions, stimulation of surfactant degraders, or sequestration of PAHs into surfactant micelles. Biosurfactants have been shown to have many of the positive effects of synthetic surfactants but without the drawbacks. They are biodegradable and nontoxic, and many biosurfactants do not produce true micelles, thus facilitating direct transfer of the surfactant-associated PAH to bacteria. The results with biosurfactants to date are promising, but further research to elucidate surfactant,PAH interactions in aqueous environments is needed to lead to predictive, mechanistic models of biosurfactant-enhanced PAH bioavailability and thus better bioremediation design. [source] Protein aggregation in motor neurone disordersNEUROPATHOLOGY & APPLIED NEUROBIOLOGY, Issue 6 2003J. D. Wood Toxicity associated with abnormal protein folding and protein aggregation are major hypotheses for neurodegeneration. This article comparatively reviews the experimental and human tissue-based evidence for the involvement of such mechanisms in neuronal death associated with the motor system disorders of X-linked spinobulbar muscular atrophy (SBMA; Kennedy's disease) and amyotrophic lateral sclerosis (ALS), especially disease related to mutations in the superoxide dismutase (SOD1) gene. Evidence from transgenic mouse, Drosophila and cell culture models of SBMA, in common with other trinucleotide repeat expansion disorders, show protein aggregation of the mutated androgen receptor, and intraneuronal accumulation of aggregated protein, to be obligate mechanisms. Strong experimental data link these phenomena with downstream biochemical events involving gene transcription pathways (CREB-binding protein) and interactions with protein chaperone systems. Manipulations of these pathways are already established in experimental systems of trinucleotide repeat disorders as potential beneficial targets for therapeutic activity. In contrast, the evidence for the role of protein aggregation in models of SOD1-linked familial ALS is less clear-cut. Several classes of intraneuronal inclusion body have been described, some of which are invariably present. However, the lack of understanding of the biochemical basis of the most frequent inclusion in sporadic ALS, the ubiquitinated inclusion, has hampered research. The toxicity associated with expression of mutant SOD1 has been intensively studied however. Abnormal protein aggregation and folding is the only one of the four major hypotheses for the mechanism of neuronal degeneration in this disorder currently under investigation (the others comprise oxidative stress, axonal transport and cytoskeletal dysfunctions, and glutamatergic excitotoxicity). Whilst hyaline inclusions, which are strongly immunoreactive to SOD1, are linked to degeneration in SOD1 mutant mouse models, the evidence from human tissue is less consistent and convincing. A role for mutant SOD1 aggregation in the mitochondrial dysfunction associated with ALS, and in potentially toxic interactions with heat shock proteins, both leading to apoptosis, are supported by some experimental data. Direct in vitro data on mutant SOD1 show evidence for spontaneous oligomerization, but the role of such oligomers remains to be elucidated, and therapeutic strategies are less well developed for this familial variant of ALS. [source] | ||||||||||