Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Mixture toxicity”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 271 records · Page 15Linked to original sources
PubMed2003

Evaluation of an in vitro hsp70 induction test for toxicity assessment of complex mixtures: comparison with chemical analyses and ecotoxicity tests.

The aim of this study was to assess the potential of a human cell line containing the hsp70 promoter linked to the chloramphenicol acetyltransferase reporter gene in evaluating the toxic potential of complex mixtures. Cells were exposed to eluates of industrial wastes and the cellular responses were compared with the metal contents of the samples and with standardized aquatic (microalgal growth inhibition, daphnia Immobilization, bacterial luminescence inhibition, Ceriodaphnia dubia reproduction inhibition) and terrestrial (earthworm lethality, plant growth inhibition) tests. The hsp70 promoter was significantly induced by 11 of 14 samples, with different dose-response patterns. Significant correlations of in vitro induction potency with aquatic ecotoxicity, especially with chronic tests, and with the metal contents of the samples were observed. Our study provides new information on the relevance of hsp70 gene induction as a criterion of toxicity and suggests its usefulness for the detection of toxicity associated with metallic pollution in complex mixtures.

Animals↗
PubMed2005

Confirmation of cause-effect relationships using effect-directed analysis for complex environmental samples.

The establishment of causal links between chemical contamination and observed ecotoxic effects of environmental samples is a major challenge in ecotoxicology. Effect-directed analysis is an approach combining fractionation with toxicity testing before chemical nontarget analysis to separate and subsequently identify toxic compounds in environmental samples. A final confirmation step in this procedure evaluates how much of the observed toxicity in the environmental sample can be attributed to the mixture of identified toxicants. The aim of the present study is to advance the methodology for the confirmation of mixtures in effect-directed analysis by using tools for the assessment of mixture toxicity accounting for unknown modes of action and heterogeneity of concentration-response curves. For this purpose, toxicants were identified in sediment extracts from two different sites. All identified compounds were tested both individually as pure compounds and in mixtures at ratios equal to those found in the sediment extracts. The observed extract toxicity was then compared with the expected combined effects calculated according to the models of concentration addition and independent action as well as with the observed toxicity of the synthetic mixture. Drawbacks of the established approach using toxic unit summation are demonstrated, and the Index of Confirmation Quality, an easy-to-read representation that allows a quantitative measure of confirmation over a range of different effect levels, is introduced.

Chemical Fractionation↗
PubMedDate not supplied

Toxicological investigations in the semiconductor industry: I. Studies on the acute oral toxicity of a complex mixture of waste products from the aluminium plasma etching process.

In dry etching processes--one of the sources of potential exposure to toxic wastes in the semiconductor industry--complex mixtures of inorganic and organic compounds arise from reactions between feed stock gases (BCl3/Cl2), top layers (aluminium photoresist), and the carrier gas (N2). Two different fractions of the complex mixture--one an ethanolic solution (ES) and the other an insoluble liquid residue (LR)--were examined for acute oral toxicity in rats. Analytical data showed that the ethanol soluble fraction contained mainly inorganic compounds, whereas the residue contained various halogenated hydrocarbons. Neither death nor behavioral changes occurred after oral administration and observation up to 23 days. ES caused a lower mean arterial blood pressure in both sexes, increased P-R-intervals in male rats, and caused some mild biochemical and hematological alterations and changes in relative organ weights compared to the control groups. Exposure to LR influenced food and water intake, and caused a significant decrease in body weights, signs of polyurie, as well as changes in various relative organ weights and biochemical and hematological parameters. The blood pressure of the male animals fell and the heart rates of both sexes decreased.

Aluminum↗
PubMedDate not supplied

DNA-protein crosslink and DNA strand break formation in HL-60 cells treated with trans,trans-muconaldehyde, hydroquinone and their mixtures.

The toxicity of benzene, a human leukemogen and ubiquitous environmental pollutant, is mediated in part by ring-hydroxylated metabolites including hydroquinone (HQ) and ring-opened metabolites including trans,trans-muconaldehyde (muconaldehyde, MUC), and their interactions. DNA-protein crosslinks (DNAPC) and DNA strand breaks (DNASB) are toxic lesions associated with the mechanism(s) of toxicity of carcinogenic compounds. In the present studies, we examined the hypothesis that individual and interactive effects of MUC and HQ are involved in the formation of DNAPC and DNASB. We extended our previous studies on DNAPC induction by MUC in HL-60 cells to HQ and mixtures of MUC and HQ, and determined DNASB levels, including 3'OH DNASB. Treatment of HL-60 cells with 25 to 100 microM HQ followed by incubation for 4 hours resulted in 1.3- to 2.8-fold increases in DNAPC levels compared with control, as determined by a K+/sodium dodecyl sulfate (SDS) precipitation assay. At 25 and 100 microM, MUC was 1.8 and 4.9 fold more effective at inducing DNAPC than HQ. Treatment with equimolar mixtures of 25 or 50 microM MUC and HQ resulted in higher DNAPC formation relative to the DNAPC levels expected if the effects were only additive. 3'OH DNASB levels as determined by the TUNEL assay showed a significant concentration-dependent increase 1 hour after treatment with 5 to 25 microM MUC, whereas HQ treatment had no effect. Cotreatment with 25 and 50 microM MUC/HQ mixtures resulted in significant decreases in TUNEL labeling relative to treatment with MUC alone. HL-60 cells treated with 1 to 50 microM MUC or HQ exhibited concentration- and time-dependent increases in DNASB as determined by the FADU assay, which measures a variety of single- and double-strand breaks and alkali labile sites. Exposure to 10 microM MUC gave QDNASB values (1 QDNASB approximately equals 100 DNASB/cell) of 7.5 +/- 1.2 and 15.4 +/- 1.4 at the 1- and 2-hour time points respectively, compared with 0.1 +/- 3.8 and 0.0 +/- 1.5 for the corresponding time controls. The QDNASB values after treatment with 10 microM HQ were 4.4 +/- 0.7 and 17.7 +/- 2.1 at the 1- and 2-hour time points, respectively, compared with 0.0 +/- 0.5 and 0.0 +/- 1.3 for the corresponding time controls. Induction of DNASB was additive 1 hour after treatment with equimolar MUC/HQ mixtures of 5 to 50 microM. These in vitro findings are significant in that DNAPC and DNASB lesions induced by MUC and HQ as well as their interactions could contribute to benzene-induced hematotoxicity and leukemogenesis.

Aldehydes↗
PubMed1981

Mixtures of local anesthetics are no more toxic than the parent drugs.

Mixtures of local anesthetics can combine the best features of both components. The authors assayed the systemic toxicity of local anesthetic mixtures given subcutaneously to mice. Convulsions regularly preceded death. The median convulsant dose (CD50) of bupivacaine was one-fourth that of lidocaine, and one-seventh that of chloroprocaine. The median lethal dose (LD50) of chloroprocaine was twice the CD50, whereas the LD50 of bupivacaine was but little greater than the CD50. Hence, the more potent the agent, the greater is the chance of death from a convulsant dose of local anesthetic. Conversion to lidocaine-equivalent doses permitted comparisons between mixtures. None of the mixtures were more convulsant or more lethal than their parent components; lidocaine-containing mixtures were significantly less lethal than the lidocaine norm. Mixing increased the distance between convulsant and lethal doses, with survival from convulsions induced by bupivacaine-containing mixtures enhanced in particular. It is concluded that local anesthetic toxicity is essentially additive.

Anesthetics, Local↗
PubMed1991

Joint toxic action of binary mixtures of osteolathyrogens at malformation-inducing concentrations for Xenopus embryos.

The joint action of binary mixtures of the osteolathyrogens semicarbazide (SC), beta-aminopropionitrile (beta APN) and penicillamine (PNC) were determined at malformation-inducing concentrations for Xenopus embryos. Tests were static with renewal every 24 h for the 96-h test period. Simultaneous tests on each individual component of the binary mixtures alone gave baseline malformation data (EC50) for joint action analyses. Toxic unit analysis and isobole diagrams were used to determine the type of joint action for 3:1, 1:1 and 1:3 mixtures of each combination. The joint action was concentration additive (strictly additive) for SC with beta APN and response additive (less-than-additive) for SC with PNC and beta APN with PNC. The joint actions were not changed when only osteolathyrogenic lesions, rather than all types of malformations, were considered. The different specific location and character of PNC lesions, as opposed to those for SC and beta APN, may signify a different type of osteolathyrogenic effect for PNC. The mixture testing approach has potential value in determining compounds that act similarly.

Abnormalities, Drug-Induced↗
PubMed1992

Joint actions of developmental toxicants in Xenopus embryos: binary mixtures of DNA synthesis inhibitors.

The joint toxic action for each of three binary combinations of DNA synthesis inhibitors was examined at concentrations that induce malformations in Xenopus laevis embryos. The three compounds, hydroxyurea, cytosine arabinoside, and 5-fluorouracil, which each inhibit a different enzyme involved in DNA synthesis, were selected for joint action testing to help determine whether joint action types are related to general modes of action (e.g., inhibit DNA synthesis) or to specific biochemical/molecular mechanisms. Three mixtures were tested, in 96-hr static-renewal tests, for each combination. Each combination was tested on three separate occasions. Using toxic unit analysis, the joint action for induction of malformations was generally antagonism, although response addition was observed for certain mixtures. An antagonistic joint action represents the phenomenon of interaction. Therefore, the tests were ineffective in determining whether a concentration addition joint action depicts two compounds that induce malformations by the same general mode of action or by the same specific mechanism of action.

Animals↗
PubMed1986

[Microscopic fungi in chicken feed mixtures, their toxigenicity and toxicity for the chick embryo].

Contamination with microscopic fungi was studied in broiler complete feed mixtures in 1983-1984. The contamination levels ranged from 10(1) to 10(5) of fungus units per gram of feed (mostly around 10(3) units per gram). Sixty species of microscopic fungi of sixteen genera were isolated from the feeds. The genera Aspergillus and Penicillium occurred most frequently (97% of samples), followed by Mucor (93%), Cladosporium (79%), Rhizopus (52%) and Fusarium (41%). Of the 64 isolates of ten species of microscopic fungi, 42 (66%) were toxicogenic, and out of 49 such strains, 27 (55%) were toxic.

Animal Feed↗
PubMed2005

Effects of metal and organophosphate mixtures on Ceriodaphnia dubia survival and reproduction.

The toxicity of mixtures of copper, zinc, and diazinon were determined for Ceriodaphnia dubia using 7-d survival and reproduction tests. Fifteen treatments, including combinations of the chemicals at 0, 25, 50, 75, and 100% of their individual median lethal concentrations, adding up to one toxic unit (TU) were tested. The TU was then used to classify each mixture response as additive, greater than additive, or less than additive. For survival, additive responses occurred in the 75% zinc plus 25% diazinon and the 50% copper plus 25% zinc plus 25% diazinon treatments. For reproduction, additive responses occurred in the 75% copper plus 25% zinc, 75% copper plus 25% diazinon, and 75% zinc plus 25% diazinon treatments. Copper and zinc played a greater role in toxicity than diazinon did. Less-than-additive interactions were found in all remaining mixtures, perhaps because of differences in mode of action between diazinon and metals. Consideration of dose-response curves can help to explain inconsistencies regarding toxic response in treatments with different ratios of the same chemicals. As TU percentages changed, mixture components were taken from different locations on differently shaped dose-response curves. Because most responses were less than additive, however, water-quality criteria based on individual concentrations probably are protective for most metal-organophosphate mixtures.

Animals↗
PubMed2002

Toxicity of cadmium and zinc mixtures to Diplostomum spathaceum (Trematoda: Diplostomidae) cercarial survival.

The toxicity of cadmium and zinc mixtures at concentrations ranging from 0.1 to 10,000 microg/L was investigated against the survival of the free-living cercarial stage of the parasitic fluke Diplostomum spathaceum. Cercariae were exposed to metal mixtures of equal concentration, metal mixtures of unequal concentration, and low-dose pretreatment followed by high-dose exposure mixtures. Under all exposures cercarial survival was increased compared to that achieved with single metals. At exposures with metal mixture of equal concentration in the range 0.1-100 microg/L survival was increased compared to that achieved by controls. The mechanism of metal toxicity and their effects on cercarial survival are discussed.

Animals↗
PubMed2002

Toxicity of single and mixed contaminants in seawater measured with acute toxicity bioassays.

Different types of organic pollutants commonly detected in seawater have been evaluated by acute toxicity bioassays. Vibrio fischeri, Daphnia magna, and Selenastrum capricornotum were selected to test toxic effects of individual compounds and mixtures of these compounds, obtaining EC50 values in the range of 0.001 to 28.9 mg/l. In the case of mixtures, synergistic toxic responses were seen for a clear majority of the cases (>60%). Mixtures containing methyl-tertiary-butyl ether (MTBE) exhibit accelerated processes that result in a change in concentration required to produce a toxic effect; for example, in the case of mixtures containing MTBE and Diuron and Dichlofluanid.

Animals↗
PubMed1999

Assessment of toxic interactions of heavy metals in binary mixtures: A statistical approach

Toxicity of zinc, copper, cobalt, and chromium ions and their binary interactions were studied at varying test levels by using a battery of two tests, Microtox and duckweed with Vibrio fisheri and Lemna minor as test organisms, respectively. The type of toxic interaction at each test combination was assessed by a statistical approach based on testing the null hypothesis of "additive toxicity" at 95% confidence level. The interactions were called "antagonistic," "additive," or "synergistic" in accordance with the statistical significance and the sign of the difference between the tested hypothesis and the value of the observed toxicity at the binary test level concerned. In the majority of the combinations studied by the two bioassays, the interactions were of antagonistic nature. Additive toxicity was the next frequently predicted interaction in both test results, the frequency being much higher in Microtox responses than in those of duckweed. Finally, synergism was found to be a rare interaction in Microtox results, but totally unlikely in duckweed within the selected test combinations.

Journal Article↗
PubMed2003

A comparison of two methods for fractionating complex mixtures in preparation for toxicity analysis.

Chemical fractionation is a widely used tool for the chemical and toxicological characterization of complex mixtures. The objective of this research was to compare two frequently employed methods for fractionating a wood preserving waste (WPW) containing polycyclic aromatic hydrocarbons (PAHs) and pentachlorophenol (PCP). The first method involved fractionation of the WPW into acid, base, and neutral fractions using a liquid-liquid acid/base/neutral (A/B/N) technique. The second method utilized alumina column chromatography to produce two fractions, A1 and A2. Gas chromatography and mass spectrometry were used to quantify the chemical components in all fractions. The alumina method recovered 473,338 mg of total PAHs (tPAHs) per kilogram crude, while the A/B/N method yielded only 193,379 mg tPAHs/kg crude. In contrast, the A/B/N method recovered 13.7 mg PCP/kg crude while the alumina method yielded only 0.5 mg PCP/kg crude. Three bioassays were used to determine the toxicity of the crude extract and fractions. The neutral and A1 fractions contained the highest levels of tPAHs and benzo[a]pyrene (BaP) but failed to induce a positive response in the Salmonella/microsome assay with concentrations containing as much as 1800 and 2500 ng BaP/plate, respectively. In the Escherichia coli prophage induction assay, the acid fraction, which contained 472 mg PCP/kg fraction, induced a positive response, as did the base fraction, which did not contain detectable PCP. Significant reduction of gap junctional intercellular communication in hepatic cells occurred with the crude extract and acid, base, and neutral fractions. Overall, the results of these bioassays suggest that PCP genotoxicity was expressed in the acid fraction, whereas the cumulative genotoxicity of genotoxic PAHs appeared to be masked in the isolates from either fractionation method. The optimal fractionation method for a mixture of chlorophenols and PAHs may involve a refined hybrid method.

Animals↗
PubMed2004

B6C3F1 mice exposed to ozone with 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone and/or dibutyl phthalate showed toxicities through alterations of NF-kappaB, AP-1, Nrf2, and osteopontin.

Toxic effects of ozone, 4-(N-methyl-N-nitrosamino)-1-(3- pyridyl)-1-butanone (NNK), and/or dibutyl phthalate (DBP) were examined through NF-kappaB, AP-1, Nrf2, and osteopontin (OPN) in lungs and livers of B6C3F1 mice. Electrophoretic mobility shift assay (EMSA) indicated that mice treated with combination of toxicants induced high NF-kappaB activities. Expression levels of p105, p65, and p50 proteins increased in all treated mice, whereas IkB activity was inhibited in NNK-, DBP-, and combination-treated ones. All treated mice except ozone-treated one showed high AP-1 binding activities. Expression levels of c-fos, c-jun, junB, jun D, Nrf2, and OPN proteins increased in all treated mice. Additive interactions were frequently noted from two-toxicant combination mice compared to ozone-treated one. These results indicate treatment of mixture of toxicants increased toxicity through NF-kappaB, AP-1, Nrf2, and OPN. Our data could be applied to the elucidation of mechanism as well as the risk assessment of mixture-induced toxicity.

Animals↗
PubMed2000

Assessing the aquatic toxicity of complex hydrocarbon mixtures using solid phase microextraction.

Assessing the ecotoxicity of hydrocarbon mixtures is complicated by the complex nature of these mixtures. Traditional analytical methods for characterizing hydrocarbon contamination are not good predictors of potential ecotoxicity because these methods fail to characterize the bioavailability of individual hydrocarbon components. Recent research indicates that hydrocarbons act by a common narcotic mode of action and that ecotoxicity occurs when the molar concentration in organism lipid exceeds a critical threshold. Since the ecotoxicity of narcotic mixtures appears to be additive, ecotoxicity thus depends upon the partitioning of individual hydrocarbons from the environment to lipids and the total molar sum of individual hydrocarbons in lipids. These insights have led previous investigators to advance the concept of 'biomimetic' extraction as a novel analytical tool for assessing narcosis-type or 'baseline'. Drawing from this earlier work, a simple method to quantify bioavailable petroleum hydrocarbons (BPHs) in hydrocarbon-contaminated aqueous and soil/sediment samples was developed. The proposed method combines the essential features of biomimetic extraction for simulating the bioconcentration process with the analytical advantages of solid phase microextraction (SPME). The procedure for determining BPH involves two steps. The sample is first equilibrated with a SPME fiber that serves as a surrogate for organism lipids. The total moles of hydrocarbons that partition to the SPME fiber is then quantified using GC/FID. The capability of this method to predict ecotoxicity was assessed by comparing BPH measurements for hydrocarbon contaminated aqueous samples to corresponding toxicity test results for rainbow trout. Results indicate that BPH analyses correlate to the observed acute toxicity. Consequently, BPH analyses offer a promising, cost-effective screening tool for predicting aquatic toxicity of complex hydrocarbon mixtures.

Animals↗
PubMed1992

Inhalation toxicity of an isomeric mixture of hydrochlorofluorocarbon (HCFC) 225 in male rats.

A blend of the hydrochlorofluorocarbon isomers HCFC-225ca and HCFC-225cb has been proposed as a potential substitute for CFC-113, an important solvent and cleaning agent. The toxicity following repeated inhalation of an HCFC-225 isomer mixture was assessed in male Crl:CDBR rats. Three groups of 10 male rats were exposed to the test compound in air at design concentrations of 500, 5000, and 13,000 ppm. Rats were exposed 6 hr/day, 5 days/week for 2 weeks. A control group of 10 male rats was exposed to air only. Decreased serum cholesterol, triglycerides, and glucose; dose-related increased mean absolute and relative liver weights; and microscopic hepatocellular hypertrophy were present at all exposure concentrations. Hepatocellular hypertrophy correlated ultrastructurally to proliferation of peroxisomes. Clinical chemical parameters and organ weight and morphologic changes in the liver were reversible following 14 days of recovery.

Administration, Inhalation↗
PubMed2004

Baseline toxicity of a chlorobenzene mixture and total body residues measured and estimated with solid-phase microextraction.

Body residues of compounds with a narcotic mode of action that exceed critical levels result in baseline toxicity in organisms. Previous studies have shown that internal concentrations in organisms also can be estimated by way of passive sampling. In this experiment, solid-phase microextraction (SPME) fibers were used as a tool to estimate the body residues, which were then compared to measured levels. Past application of SPME fibers in the assessment of toxicity risk of samples has focused on separate exposure of fibers and organisms, often necessitated by the amount of agitation needed in order to achieve steady state in the fibers within a convenient time period. Uptake kinetic studies have shown that in SPME fibers with thin coatings, equilibrium concentrations can be reached without agitation within the time frame of a toxicity test. In contrast to toxicity experiments to date, the SPME fibers in the current study were exposed concomitantly to the test water with the organisms, ensuring an exposure under the exact same conditions. Fibers and two aquatic invertebrate species were exposed to a mixture of four chlorobenzenes with a narcotic mode of action. The total body residue of these compounds in the organisms was determined, as was the acute toxicity resulting from the accumulation. The total body residues of both species were correlated to the total concentrations in SPME fibers. It was concluded that toxicity could be predicted based on total body residue (TBR) estimates from fiber concentrations.

Animals↗
PubMed2005

In vivo evaluation of three biomarkers in the mosquitofish (Gambusia yucatana) exposed to pesticides.

In this study, the acute toxicity and the in vivo effects of commercial chlorpyrifos, carbofuran and glyphosate formulations on cholinesterase (ChE), glutathione S-transferase (GST) and lactate dehydrogenase (LDH) activities of the mosquitofish (Gambusia yucatana) were investigated. In a first phase of the study, head and muscle ChE were characterized with different substrates (acetylthiocholine iodide, s-butyrylthiocholine iodide and propionylthiocholine iodide) and the selective inhibitors eserine hemisulfate, 1,5-bis(4-allyldimethylammoniumphenyl)-pentan-3-one dibromide (BW284C51), and N,N'-diisopropylphosphorodiamic acid (iso-OMPA). The results obtained suggest that the enzyme present in both head and muscle of G. yucatana is mainly acetylcholinesterase (AChE). Acute toxicity was evaluated by exposing fish to several concentrations of single pesticides and of a mixture of chlorpyrifos/glyphosate. LC50 values were determined after 96 h of exposure, except in the case of carbofuran for which LC50 was calculated after 24 h since almost all the fish died within this period. LC50 values were 0.085 mg/l for chlorpyrifos, 17.79 mg/l for glyphosate, 0.636 mg/l for carbofuran and 0.011 mg/l for the chlorpyrifos/glyphosate mixture. A Toxic Unit approach was used to compare the toxicity of chlorpyrifos and glyphosate when occurring in a mixture with their toxicities as single compounds. Synergistic effects of chlorpyrifos and glyphosate when present in a mixture were found. At the end of each bioassay (24 h for carbofuran, 96 for the other substances/mixture), effects on biomarkers were analyzed. Muscle LDH activity was not altered by any of the three pesticides tested. Gill GST activity was significantly inhibited (40%) by carbofuran after 24 h of exposure to concentrations equal or higher than 0.06 mg/l. ChE muscle and head activity were significantly inhibited (50% and 30%, respectively) by carbofuran at concentrations equal or higher than 0.25 mg/l. Chlorpyrifos induced a significant inhibition of both muscle and head ChE (80% and 50%, respectively) after 96 h of exposure to concentrations equal or higher than 0.05 mg/l. Carbofuran did not induce significant alterations of fish ChE. The ChE EC50 determined for chlorpyrifos/glyphosate mixture (0.070 mg/l) was higher than the correspondent value calculated for chlorpyrifos alone (0.011 mg/l) suggesting an antagonistic effect of glyphosate on ChE inhibition by chlorpyrifos. ChE activity of G. yucatana seems to be a good biomarker to diagnose the exposure of wild populations of this species exposed to anticholinesterase pesticides.

Animals↗