Toxicity of ethanol-barbiturate mixtures.
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Amobarbital↗
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Biodesulfurization in biphasic systems containing organic solvents.
Biphasic systems can overcome the problem of low productivity in conventional media and have been exploited for biocatalysis. Solvent-tolerant microorganisms are useful in biotransformation with whole cells in biphasic reactions. A solvent-tolerant desulfurizing bacterium, Pseudomonas putida A4, was constructed by introducing the biodesulfurizing gene cluster dszABCD, which was from Rhodococcus erythropolis XP, into the solvent-tolerant strain P. putida Idaho. Biphasic reactions were performed to investigate the desulfurization of various sulfur-containing heterocyclic compounds in the presence of various organic solvents. P. putida A4 had the same substrate range as R. erythropolis XP and could degrade dibenzothiophene at a specific rate of 1.29 mM g (dry weight) of cells(-1) h(-1) for the first 2 h in the presence of 10% (vol/vol) p-xylene. P. putida A4 was also able to degrade dibenzothiophene in the presence of many other organic solvents at a concentration of 10% (vol/vol). This study is a significant step in the exploration of the biotechnological potential of novel biocatalysts for developing an efficient biodesulfurization process in biphasic reaction mixtures containing toxic organic solvents.
Bacterial Proteins↗
Evidence that the mechanisms of fungitoxicity of 8-quinolinol and its bischelate with copper(II) are different.
The copper(II) contents of the growth media, Sabouraud dextrose and Czapek-Dox broths, and of the spore inocula of Aspergillus niger (ATCC 1004), Aspergillus oryzae (ATCC 1011), Trichoderma viride (ATCC 8678), and Myrothecium verrucaria (ATCC 9095) were determined by atomic absorption spectrophotometry in a graphite furnace. The test systems composed of Sabouraud dextrose broth and spore inocula of the four fungi contained only a little over 3% of the copper(II) required to form a minimal inhibitory concentration of bis(8-quinolinolato)copper(II). The test system of Czapek-Dox broth and A. oryzae contained slightly less than 65% of the copper(II) required to form a minimal inhibitory concentration of the bischelate of 8-quinolinol with copper(II). When the minimal inhibitory concentrations of 8-quinolinol and bis(8-quinolinolato)copper(II) were added simultaneously to the test system of Czapek-Dox broth and A. oryzae, 10% of the combined mixture of toxicants caused complete inhibition of growth indicating synergism between the toxicants. These results together with the observation that alpha-lipoic acid as well as small aliphatic thiol-containing compounds (cysteine, glutathione, dithioerythritol, and dithiothreitol) reversed the toxicity of 8-quinolinol but not the toxicity of bis(8-quinolinolato)copper(II) led to the conclusion that the mechanisms of fungitoxicity of both toxicants are different.
Aspergillus↗
Characterization of metal-resistant soil eubacteria by polymerase chain reaction--denaturing gradient gel electrophoresis with isolation of resistant strains.
Contamination of soils with heavy metal ions is a major problem on industrial and defense-related sites worldwide. The bioavailability and mobility of these contaminants is partially determined by the microbial biomass present at these sites. In this study, we have assessed the effect of the addition of a mixture of toxic metal salts on the prokaryotic community of microcosms consisting of sandy-loam soil using direct molecular analysis of the recoverable eubacterial 16S rDNA molecules by polymerase chain reaction--denaturing gradient gel electrophoresis (PCR-DGGE) and limited phospholipid fatty acid analysis (PLFA). Addition of toxic metals (nonradioactive surrogates of Sr, Co, Cs, Cd) resulted in rapid (ca. 1 week) changes in the DGGE profile of the indigenous eubacterial community when compared with pristine controls. These changes were stable over the course of the experiment (8 weeks). No changes in the eubacterial population of control microcosms were detected. The major changes in community structure in metal-contaminated microcosms consisted of the appearance of four novel bands not detected in controls. Sequence analysis of these bands suggested that two organisms related to the genus Acinetobacter and two related to the genus Burkholderia carried a selective advantage over other indigenous eubacteria under heavy metal induced stress. The Burkholderia spp. were then cultured and further characterized using lipid analysis.
Acinetobacter↗
Tarantula (Eurypelma californicum) venom, a multicomponent system.
The venom of the tarantula Eurypelma californicum was analysed biochemically, the components were isolated and characterized. The pH value of the crude venom is 5.3 +/- 0.3. After dilution with distilled water, UV-absorption spectra showed a single maximum at 258 nm (pH ca. 7.0). A second maximum at 328 nm emerged above pH 8.0. Protein concentration of the venom is ca. 65 mg/ml. After Coomassie staining SDS-PAGE patterns show three major bands with apparent molecular masses around 40 kDa, 4.3 kDa and 1.3 kDa besides some weak high molecular protein bands. The following low-molecular mass constituents were determined in the crude venom: ATP, ADP, AMP, glutamic acid, aspartic acid, gamma-aminobutyric acid, glucose and the ions potassium, sodium, calcium, magnesium and chloride; the osmolality was 361 micro0smol/ml. The LD50 value for female cockroaches was 0.15 microliters venom per g body weight and for male cockroaches 0.4 microliters venom per g body weight. Separation of the crude venom by gel chromatography yielded four elution peaks. Peak I contains the enzyme hyaluronidase. The activity is 200-900 U/microliters. Peak II contains a mixture of toxic peptides. Peak III contains the 1.3-kDa components of SDS-PAGE and peak IV mainly contains ATP. Venom proteins including the enzyme hyaluronidase were precipitated by 5% trichloroacetic acid. The supernatant was separated by HPLC into 13 fractions. Fraction 1 contains glutamic acid, aspartic acid, gamma-aminobutyric acid and ATP; fraction 2 contains ATP, ADP and AMP as well as a component 2' visible in SDS-PAGE as 1.3-kDa band and consisting of spermine and tryptophan; fraction 3 contains ATP and an unknown component 3'; fractions 4-6 also show a 1.3-kDa band in SDS-PAGE, fraction 4 being tyrosylspermine and fractions 5 and 6 containing compounds of spermine and aromatic molecules; fraction 7 contains a peptide which lacks aromatic amino acids, it was sequenced from the N-terminus; fractions 8-13 contain very similar toxic peptides. The peptides in fractions 11 and 12, labeled ESTX for Eurypelma spider toxin, were cleaved with different enzymes and sequenced. They differ in one amino acid in position 26. Homologies with scorpion toxins and with a toxin of the spider Segestria florentina were found.
Adenosine Triphosphate↗
Endocrine disruptive effects of polychlorinated biphenyls on the thyroid gland in female rats.
Polychlorinated biphenyls (PCBs) are persistent environmental pollutants. Aroclor 1221 (A1221) and Aroclor 1254 (A1254) are commercial PCB mixtures with low and high number of chlorination, respectively. We have comparatively investigated effects of A1221 and A1254 on serum levels of thyroid hormones and thyroid gland histology in adult female Wistar rats. Animals were subcutaneously injected with A1221 (10 mg/kg) or A1254 (10 mg/kg) for six weeks. One group of animals served as control. At the end, all animals were decapitated and trunk blood collected. Serum levels of triiodothyronine (T3) and thyroxine (T4) were measured by the electrochemiluminescence immunoassay method. Thyroid glands were removed for histopathological examination under light microscopy. Serum total T4 levels were significantly increased in A1221- and A1254-treated rats (p < 0.05). Serum free T4 levels were significantly increased in the A1254-treated rats (p < 0.01), but not in the A1221-treated rats. In contrast, the treatment with A1221 caused a significant increase in serum free T3 concentrations (p < 0.05) but not with A1254. Notably, either A1221 or A1254 caused distinct histopathological changes, such as formation of many microfollicles in the thyroid gland, which mimic the changes seen in thyrotoxicosis. In conclusion, both PCB mixtures induce toxic effects in the thyroid gland regardless of their degree of chlorination. We suggest that these environmental contaminants may disrupt thyroid hormone homeostasis in exposed individuals and thus pose a threat to human health.
Animals↗
Exposure-related effects on Cd bioaccumulation explain toxicity of Cd-phenanthrene mixtures in Hyalella azteca.
Little is known regarding mixture effects of metals and polynuclear aromatic hydrocarbon (PAHs) under environmentally relevant exposure regimes. Standard U.S. Environmental Protection Agency (U.S. EPA) procedures were applied and extended to test effects of phenanthrene (Phen) on sediment-Cd uptake, aqueous-Cd uptake, and Cd-elimination kinetics in the amphipod Hyalella azteca. In sediment exposures, Phen increased the projected equilibrium-tissue concentration of Cd from 47.2 (36.2-58.3) to 221.1 microg/g ([117.8-324.3], 95% confidence intervals [CI] in parentheses). Although Cd bioaccumulation increased markedly in sediment exposures, dissolved Cd concentrations and physical-chemical parameters indicative of Cd bioavailability were unaffected by Phen. Further, in water-only exposures, Phen had no effect on Cd bioaccumulation or Cd-elimination kinetics. These results indicate that increased Cd bioaccumulation in Cd-Phen mixtures occurred via a sediment-mediated process and was likely a function of increased uptake associated with feeding (i.e., Phen-induced alterations in ingestion and/or digestive processes). Observed increases in H. azteca lethality when exposed to Cd-Phen mixtures in sediment, but not in water-only exposures, likely resulted from increased Cd bioaccumulation rate rather than a true toxicological synergism. Thus, apparent synergisms and antagonisms may result from exposure-mediated effects in sediment that are unrelated to toxicological interactions. Implications of these findings regarding sediment-quality assessment and suggestions for future studies are discussed.
Amphipoda↗
Acute lung injury, acute respiratory distress syndrome and inhalation injury: an overview.
Acute Lung Injury (ALI) and the Acute Respiratory Distress Syndrome (ARDS) are severe respiratory diseases that have a very poor prognosis and have numerous causes. Despite a great deal of research and investigation since the initial description of ARDS 30 years ago many questions about the pathogenesis, treatment and outcome of the disease remain unanswered. Although there is evidence to suggest that outcome of ALI and ARDS is improving, the reasons why are unknown and there is not yet a well developed treatment for these diseases. Inhalation injury resulting from exposure to pyrolysis and combustion atmospheres is among the causes of ALI/ARDS. Little is known of the mechanisms of fire related inhalation injury that results in the development of ALI/ARDS. There is a paucity of information about fire atmosphere exposure response relationships for smoke-induced inhalation injury. Although there is considerable information about the pulmonary toxicity of many of the more common constituents of fire atmospheres, little is known about the pulmonary toxicity of mixtures of these constituents. Fire related pulmonary health risks are of particular concern to the Navy due to the limited opportunity to escape the inhalation hazards posed by shipboard fires. Consequently the Naval Medical Research Institute Detachment (Toxicology) has undertaken a research program to develop research models of combustion atmosphere induced ALI/ARDS which can be exploited to systematically address some of the questions surrounding fire related ALI/ARDS. ALI/ARDS has been the topic of a vast amount of research, numerous symposia, working groups and their published proceedings, book chapters, and books. Less information is available regarding experimental models of smoke induced lung damage, however the literature on the subject is extensive. Consequently this article is intended to provide the reader with a primer or cursory "overview" of ALI and ARDS from a toxicological perspective and should not be considered comprehensive.
Animals↗
[Effects of chemical mixtures on embryonic development: examples of experimental models and problems in risk assessment].
Toxicological risk deriving from the exposure to mixtures of toxic substances, the study of possible interactions among them and their mechanisms of action are of special interest in prenatal toxicology. In fact, embryo is a dynamic complex system whose gradual development substantially modulates the extent and type of damages to which it may be sensitive, through specific, critical periods of sensitivity. In this paper, a number of types of interactions among toxic substances which show the same mechanisms of action and/or the same target site, are analysed. Besides, pharmacokinetic interactions among teratogenic agents and substances modulating their metabolism, need specific evaluations because of the wide variability of possible events. In conclusion, risk assessment in prenatal toxicology has to put greater attention to the various types of effect and pharmacokinetic interaction since they might result in an increasing risk at low doses.
Animals↗
Bauxite manufacturing residues from Gardanne (France) and Portovesme (Italy) exert different patterns of pollution and toxicity to sea urchin embryos.
This study was designed to investigate the composition and toxicity of solid residues from bauxite manufacturing plants. Soil and dust samples were collected in the proximity of two bauxite plants (Gardanne, France, and Portovesme, Italy). Samples were analyzed for their content of some selected inorganic contaminants by means of inductively coupled plasma optical emission spectroscopy (ICP-OES) either following acid digestion procedures or by seawater release of soluble components. Toxicity was tested by sea urchin bioassays to evaluate a set of toxicity endpoints including acute embryotoxicity, developmental defects, changes in sperm fertilization success, transmissible damage from sperm to the offspring, and cytogenetic abnormalities. Inorganic analysis showed two distinct sets of inorganic contaminants in Gardanne versus Portovesme, including Al, Cr, Cu, Fe, Mn, Pb, Ti, and Zn; sample composition (seawater-soluble contaminants) and toxicity showed a noteworthy association. The most severe toxicity to embryogenesis and to sperm fertilization success was exerted by some Portovesme samples (0.03-0.5% w/v), with a significant association between toxicity and dose-related seawater release of Zn, Pb, and Mn. Seawater extraction of a toxic dust sample (G20) from the Gardanne factory showed increasing seawater release of Al, Fe, and Mn; the G20 sample, at the level of 0.5%, affected both developing sea urchin embryos and sperm (offspring quality). Soil samples around the Gardanne factory showed the highest frequency of toxic soil sites eastward from the factory. The present data point to solid deposition from bauxite plants as a potential subject of environmental health concern. The results suggest that extraction methods for evaluating the toxicity of complex mixtures should be based on the environmental availability of mixture components. The differences in sample toxicity among the tested sites, however, suggest possible site-to-site variability in geochemical and/or technological parameters.
Aluminum Oxide↗
Toxicity and mutagenicity of a mixture of 25 chemicals found in contaminated groundwater.
A defined mixture of 25 chemicals that are often found in contaminated groundwater was prepared as an aqueous solution and studied for mutagenicity in bacteria, for prophage induction in bacteria, for palatability and effect on weight-gain in rats and mice, and for cytogenetic effects in bone marrow cells of rats and mice. The bacterial mutation and prophage induction tests were negative. Exposure to the mixture in drinking water for two weeks resulted in a concentration-related decrease in water consumption in male and female rats and mice. Concentration-related decreases in weight gain were observed in male and female mice; in rats, only the high-dose groups showed decreased weight gains. A small but significant increase in sister chromatid exchanges was seen in male mice and a similar weak effect on micronucleated polychromatic erythrocytes (PCE) in the bone marrow of males and females. Also in bone marrow of male and female mice, an increase in mitotic index and a decrease in average cell generation time was observed. The %PCE in bone marrow was decreased in female mice only, while the %PCE in peripheral blood was increased in both sexes. In rats, the only effects observed in the cytogenetic studies were increased PCE frequencies in the peripheral blood of males and in the bone marrow of males and females. These results indicate that the 25-chemical mixture studied is not genotoxic in bacteria and that a concentration-dependent effect on its palatability to rodents leads to reduced water consumption, food consumption and weight gain. Although the bone marrow effects may be associated with disruptions of normal erythropoiesis that, in turn, alter the cytogenetic end-points reported, elevations of SCE and MN-PCE in mice suggest the 25-chemical mixture, under the conditions of administration, leads to cytogenetic damage in the bone marrow. Such damage may indicate a potential health hazard.
Animals↗
Silicate pneumoconiosis of farm workers.
Abnormal numbers of birefringent particles have been found in the lungs of seven patients (five vineyard workers, one farmer, and one rural resident) in association with a spectrum of early to late interstitial inflammation and fibrosis. Nodular granulomas of the type seen in silicosis were absent. Scanning electron microscopy and energy dispersive x-ray analysis of 177 individual particles (less than 5 micrometer.) in situ in the lungs of four of the patients showed mostly silicates (notably aluminum, silicon, and potassium), with 5 to 10 per cent silicon dioxide. An analysis of particles less than 5 micrometer. from both vineyard and non-vineyard soil showed lung and soil particles to have a similar composition. The presence of large amounts of silicates in the lung tissues, in association with chronic inflammation and fibrosis, implicates the silicates in the causation of the fibrosis. The silicate deposits may, in large part, be a marker, reflecting a mixture of toxic soil additives or pesticides found in commercial clay silicate products or in dusts from the soil itself. The findings do not exclude lung pathology of a similar nature in regions outside of the farm.
Aged↗
[Importance of butyrous aerosol in creating the toxic effect produced by a mixture of volatile products secondary to thermooxidative decomposition of lubricant oils synthesized on bases of esters of adipine acid].
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Adipates↗
Attenuation of increased vascular permeability and toxicity of a radioprotective chemical mixture by chlorpromazine in mice.
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Animals↗
[Experimental studies on the chronic toxicity of a new analgetic mixture. Comparison with analgetic pills containing phenacetin].
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Amides↗
[Comparative characteristics of the toxicity of slag-forming mixtures].
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Animals↗
Potentiation and antagonism of 2,3,7,8-tetrachlorodibenzo-p-dioxin effects in a complex environmental mixture.
There is increasing need to understand the toxicity of complex environmental mixtures. The organic phase of a leachate (OPL) from the Love Canal chemical dump site is a complex mixture that contains over 100 organic compounds, including 0.74 ppm 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Mice congenic at the Ah locus were used to evaluate several toxic effects of the OPL, including immune function and hepatic enzyme induction. OPL toxicity was compared with that of pure TCDD in both C57BL/6J Ahb/b and congenic C57BL/6 Ahd/d (B6.D2) mice. Mice were given single oral doses of up to 2 g OPL/kg or 100 micrograms TCDD/kg, immunized, and evaluated after 7 days. The TCDD equivalent of the OPL was determined to be 3.9 and 5.0 ppm in C57BL/6J and B6.D2 mice, respectively. This is six times the TCDD content. The Ah phenotype-dependent response ratio was calculated by dividing the dose required to cause an effect in the B6.D2 strain by the dose causing the same effect in the C57BL/6J strain. Ratios based on both ED50s and the lowest observed adverse effect levels were used to determine whether each adverse effect was Ah phenotype-dependent, the extent to which TCDD contributed to the effect, whether there were interactive effects between the AhR ligands and nonligands and if they were additive, antagonistic, or synergistic, and whether the response was predictable based on the known chemical composition of the mixture. It was concluded that the non-TCDD component potentiated TCDD immune suppression, and possibly thymic atrophy, through AhR mechanisms. In contrast, this analysis indicated that the non-TCDD component of the OPL antagonized the ability of the TCDD component to induce hepatic AHH activity whereas OPL hepatomegaly was caused primarily by the non-TCDD component of the OPL. This study demonstrates that the toxicity of mixtures containing TCDD may not be accurately predicted based on the TCDD content alone and that this approach could be useful in the toxicologic assessment and management of environmental contamination.
Animals↗
[Are combinations of local anesthetics dangerous?].
Although local anaesthetic mixtures are often used, there is often no scientific basis for this. Interactions between the local anaesthetics in the mixture can even increase their toxicity. Such interactions may be due to the physical chemical properties of each constituent (this is not a real problem for amide local anaesthetics), to a mutual displacement from the binding sites on the plasma proteins or to an additional effect on membrane receptors. This displacement would seem to benefit the least toxic drug: the toxicity of local anaesthetic mixtures may therefore be reduced; for example, lidocaine and mepivacaine are displaced by bupivacaine. Moreover, the fraction of drug which leaves the blood vessel is greater than the serum free fraction. During chronic administration, neurological toxicity and free fraction are narrowly linked. When using local anaesthetic mixtures, it must be remembered that potency and toxicity of a local anaesthetic are closely correlated and that the toxic effects are, at least, additive.
Anesthetics, Local↗