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At least 451 records · Page 25Linked to original sources
PubMed1998

Selective identification by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry of different types of gluten in foods made with cereal mixtures.

The gluten toxic fractions responsible for the mucosal damage in coeliac disease (CD), so-called gliadins, hordeins, secalins and avenins from a large number (30-40) of wheat, barley, rye and oats cultivars respectively, have been mass analyzed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). Gliadin, secalin and avenin characteristic mass profiles are nearly identical amongst distinct cultivars from the corresponding cereal, while hordeins profiles show more variability depending on the particular barley cultivar. On the basis of these four distinguishable characteristic mass patterns spreading within the 20,000-40,000 Da range, MALDI-TOF-MS has permitted the direct and simultaneous visualization of gliadins, hordeins, secalins and avenins in foods elaborated with cereal mixtures of wheat, barley, rye and oats. This capacity has been demonstrated by mass analyzing foods made with these four cereals in varying ratios. Thus MALDI-TOF-MS can be preliminarily established as a unique system with the ability to discriminate the specific type of gluten toxic fractions present in food samples.

Avena↗
PubMedDate not supplied

Assessing the environmental impact of wastewaters.

The conventional approach for assessing the environmental impact of wastewaters uses a set of global physicochemical and ecotoxicological parameters and is well adapted to the vast majority of wastewaters. When some chemicals may be particularly harmful for the environment, a specific approach based on a comparison between the predicted environmental concentration (PEC) and the predicted no-effect concentration (PNEC) may be used. The four steps of extrapolation required for PNEC evaluation are discussed and the importance of the interspecies extrapolation is highlighted. It may also be useful to use an integrated approach relating the characteristics of the wastewater to that of specific compounds. For physicochemical parameters, a simple addition is adequate, whereas, for ecotoxicity, the problem is more complex. The toxicity of a mixture of compounds acting by the same mechanism is often described by the concentration addition model. Although this model is very useful for practical applications owing to its simplicity, a statistical evaluation of its performance indicates that it slightly over-predicts the toxicity of mixtures. A new model derived from the statistically sound "independence action" principle and based on a precise mathematical description of the dose-response relationship is proposed. Applications of this model to mixtures tested with algae demonstrate the accuracy of this model with the experimental data.

Animals↗
PubMed2005

Evaluation of cocoa- and coffee-derived methylxanthines as toxicants for the control of pest coyotes.

Methylxanthines were quantified in coffee, tea, and chocolate products. Tarajuilie tea from India, cocoa powder, and cocoa nibs contained the highest levels of methylxanthines. Theobromine, caffeine, and theophylline combined in the ratios observed in tea and chocolate were ingested by coyotes. Although both mixtures induced acute toxicity, the symptoms accompanying the chocolate methylxanthine mimic were preferable. Manipulation of the ratios of methylxanthines in the chocolate mimic led to the identification of a 5:1 theobromine/caffeine mixture as a promising coyote toxicant. This mixture was then administered to coyotes using the coyote lure operative device (CLOD). Mortality occurred in every coyote that ingested any portion of the CLOD contents. These results indicate that mixtures of theobromine and caffeine have the potential to be developed into a selective, effective, and socially acceptable toxicant for the control of pest coyotes.

Animals↗
PubMed2006

Impact of atrazine on chlorpyrifos toxicity in four aquatic vertebrates.

Atrazine has been shown previously to potentiate chlorpyrifos toxicity in selected invertebrates. This study examined interactions of atrazine and chlorpyrifos in four aquatic vertebrates. Organisms were exposed to binary mixtures of atrazine and chlorpyrifos during toxicity bioassays. Inhibition of cholinesterase (ChE) enzyme activity and chlorpyrifos uptake kinetics were also examined with and without atrazine exposure. Atrazine alone did not affect organisms at concentrations up to 5000 microg/L; however, the presence of atrazine at 1000 microg/L did result in a significant increase in the acute toxicity of chlorpyrifos in Xenopus laevis. Mixed results were encountered with Pimephales promelas; some bioassays showed greater than additive toxicity, while others showed an additive response. No effect of atrazine on chlorpyrifos toxicity was observed for Lepomis macrochirus and Rana clamitans. Atrazine did not affect ChE activity or chlorpyrifos uptake rates, indicating that these toxicodynamic and toxicokinetic parameters may not be related to the mechanism of atrazine potentiation of chlorpyrifos toxicity. Based on the results of this study, it does not appear that a mixture toxicity of atrazine and chlorpyrifos at environmentally relevant concentrations presents a risk to the vertebrate organisms examined in this study.

Animals↗
PubMed1998

Effects of combinations of methanol and formic acid on rat embryos in culture.

Acute human exposure to methanol (MeOH) results in elevated serum concentrations of both MeOH and formic acid. In order to better assess the risk of adverse developmental effects of MeOH exposure in humans, the effects of the combination of formate and MeOH, in addition to the individual toxicity profiles for MeOH and formate, need to be established. Gestational day 9 rat embryos were exposed to various concentrations of MeOH and formate in whole embryo culture (WEC) for 48 hr and the degree of embryotoxicity was evaluated using developmental score (DEVSC) as the parameter of comparison across exposure combinations. After establishing embryo toxicity of the individual compounds in previous studies, concentrations of MeOH and formate were chosen which would produce similar DEVSCs, and isoboles were plotted joining the equivalently toxic doses. These mixtures would be expected to have similar toxicity to the MeOH or formate concentrations according to a dose-addition model. The responses of embryos to the selected concentrations along each isobole were measured and tested for linearity to determine the nature of any interaction between the two agents. The concentrations of MeOH and formate used separately and in combination ranged from 0 to 8.75 mg/ml MeOH and 0 to 1.51 mg/ml formate. Increasing concentrations of either MeOH or formate resulted in significant decreases in DEVSC. Exposure to combinations of MeOH and formate had less effect on DEVSC than would be expected based on simple toxicity additivity. This observation was also true for embryonic crown-rump length, head length, and somite number. These results suggest that the embryotoxicity observed following low level exposure to MeOH is mechanistically different from that observed following exposure to formate.

Abnormalities, Drug-Induced↗
PubMed1994

Toxic interactions among environmental pollutants: corroborating laboratory observations with human experience.

Combined exposures to multiple chemicals may result in interactions leading to a significant increase or decrease in the overall toxicity of the mixture compared to the summation of the toxicity of the components. A large number of chemical interactions have been described in animal studies by administering high doses of chemicals by routes and scenarios often different from anticipated human exposures. Though limited, there is some evidence for the occurrence of several supra-additive (the combined effects are greater than the simple summation of the individual effects) and infra-additive (the combined effects are smaller than the simple summation of the individual effects) chemical interactions in humans. For example, toxicokinetic interactions between several solvents have been found to occur in the workplace, whereas those involving pesticides have been reported less frequently, especially during accidental exposures. Toxic interactions involving nutritionally important metals and metalloids appear to occur more frequently, since several of them have an important role in a variety of physiological and biochemical processes. On the contrary, there is not much evidence to confirm the occurrence of toxic interactions among the commonly encountered inorganic gaseous pollutants in humans. Overall, the majority of chemical interactions observed in animal studies have neither been investigated in humans nor been extrapolated to humans based on appropriate mechanistic considerations. Future research efforts in the chemical interactions arena should address these issues by focusing on the development of mechanistically and biologically based models that allow predictions of the extent of interactions likely to be observed in humans.

Air Pollutants↗
PubMed1991

Joint action of t-retinoic and valproic acids on Xenopus embryo development.

The joint action of all-trans retinoic acid (RA) with valproic acid (VPA) was examined at malformation-inducing concentrations for Xenopus embryos. The compounds were selected for testing to evaluate malformation as an endpoint for the developmental toxicity of chemical mixtures and to help assess whether joint action types can be related to modes or mechanisms of chemical toxicity for Xenopus. Three mixtures (3:1, 1:1, and 1:3 RA:VPA) were tested in 96 hr static-renewal exposures. Three separate tests were conducted on each mixture. Positive controls were also tested (i.e., 1:0 and 0:1 solutions). Using toxic unit analysis, the joint action for induction of malformations of all types, craniofacial malformations, and microcephaly was response addition, indicating the chemicals are dissimilar and non-interactive. The results support recent joint action studies in providing evidence that similar acting chemicals might be defined as chemicals with the same biochemical/molecular mechanism of action in inducing malformations in Xenopus embryos.

Abnormalities, Drug-Induced↗
PubMed1995

Use of bioassays in assessing health hazards from complex mixtures: a rash analysis.

The Finney harmonic mean model for joint toxicity of ingredients in mixtures can be used to estimate the toxicity of the neat compound if each component can be substituted in potency-adjusted-doses for any of the other components. Chemical analysis of constituent substances and their associated concentrations and relative toxicological potency values (computed according to the RApid Screening of Hazard (RASH) method) were used to compare the toxicities as predicted from ingredients of cigarette smoke, PAHs in diesel exhaust, asphalt, coal tar, pitch, and creosote with the measured toxicities of the corresponding neat mixtures. Accuracy for cigarette smoke condensate, coal tar, pitch, and creosote were within a factor of three based on the PAH fraction; asphalt was within a factor of 18; but the PAH fraction of diesel particulate was again found to be inadequate to describe the composite toxicity of diesel emissions.

Animals↗
PubMed2002

A mathematical algorithm to identify toxicity and prioritize pollutants in field sediments.

In order to evaluate sediment toxicity, a mathematical algorithm was developed to compute the toxicity of multiple component mixtures acting in an additive manner. A statistical approach was devised to determine the presence of potential interactive effects among mixture components. The algorithm uses three kinds of data to obtain an integrative approach to sediment toxicity assessment: Microtox toxicity data (EC50 values), sediment pollutant concentration measurements, and sequential extraction (SEQ) data to investigate metal partitioning. To simplify the analysis of complex mixtures using a prioritization scheme based on intrinsic toxicity and relative abundance, a toxicity index (TI) was employed as an indicator of adverse ecological impact. In general, the ranking of contaminants using the TI approach was found to be most efficient in reducing computational time, and concentrations using bioavailability data from SEQ was found to be the best theoretical predictor of the experimental mixture toxicity value. Only a few pollutants that were present at the greatest abundance were needed to provide a good approximation of the calculated EC50 found when all components were included. Not only does this substantially reduce the computational time needed to determine the EC50, it could in some cases dramatically reduce the pollutant monitoring effort required to track toxicity effectively. This approach would have substantial implications for both risk assessment and for remediation strategies, making them more efficient by focusing on the priority pollutants identified.

Algorithms↗
PubMed2001

Toxicity of cadmium and zinc to encystment and in vitro excystment of Parorchis acanthus (Digenea: Philophthalmidae).

The toxicity of cadmium, zinc and cadmium/zinc mixtures at concentrations ranging from 1000 to 50000 microg/l were investigated against cercariae and metacercariae of Parorchis acanthus obtained from the dog whelk Nucella lapillus. Cercarial encystment at concentrations of 25000 microg/l or higher was significantly impaired by all test metals; however, at lower concentrations only zinc demonstrated toxicity. Mixtures of cadmium and zinc had a synergistic effect compared with single metal toxicity but only at 50000 microg/l. Excystment in vitro was only significantly affected by cercariae exposed to cadmium/zinc mixtures whilst encysting. Twenty-four h exposures of fully formed cysts had no effect on excystment in vitro. Effects on in vitro excystment rates over a 2 h period demonstrated widespread effects for cercariae-exposed P. acanthus. No effects were evident on excystment rates of cyst-exposed parasites.

Animals↗
PubMed1992

Reproductive and developmental toxicity studies of a linear alkylbenzene mixture in rats.

Alkylate 215, a mixture of linear decyl- to tridecylbenzenes, is an intermediate in the manufacture of detergent sulfonates. A two-generation reproduction study and a developmental toxicity study were conducted using single daily doses given by gastric intubation in a corn oil vehicle. In the reproduction study, groups of 30 rats/sex/group were given doses of 0, 5, 50, or 500 mg/kg/day. F0 animals received a 10-week premating treatment period and were then mated to produce a single litter; F1 adults were selected from the F1 litters. F1 animals were dosed for 11 weeks before mating to produce a single litter. Adults and weaned pups received a gross postmortem examination. Histopathology studies were conducted on reproductive tissues, tissues with gross lesions, and the pituitary gland taken from each adult in the control and high dose groups. In the developmental toxicity study, groups of 24 mated female rats were given 0, 125, 500, or 2000 mg/kg/day on Days 6 through 15 of gestation. Dams were terminated on gestation Day 20 and fetuses were examined for external, soft tissue, and skeletal defects. Results of the reproduction study were as follows. At 50 mg/kg/day, pup weights were decreased at Day 7 in the F1 litter. At 500 mg/kg/day, decreases were found in the F0 females in premating and early lactation weight gains; in both generations in premating weight gains in males and in weight gains during gestation in females; and in litter size, pup viability at birth, Day 0-4 survival, and pup weights on Days 14 and 21. The NOAEL for reproductive effects was 5 mg/kg/day. The developmental toxicity study found effects on several parameters.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1982

Short-term oral toxicity of a 2,4,6-trinitrotoluene and hexahydro-1,3,5-trinitro-1,3,5-triazine mixture in mice, rats, and dogs.

The oral toxicity of a mixture of 2,4,6-trinitrotoluene and hexahydro-1,3,5-trinitro-1,3,5-triazine (1:0.62, w/w) compounds typically found in munitions plant effluents, was evaluated in mammalian species. Single-dose oral LD50s of the mixture were 574 and 594 mg/kg in male and female rats and 947 and 1130 mg/kg in male and female mice, respectively. Long dispersion periods during preparation or ultraviolet irradiation of the mixture lowered the LD50s. In repeated-exposure studies, dogs were given 0.50, 5.0 or 50 mg/kg X d by capsule for up to 90 d. Rats and mice were fed the mixture in the diet at 0.005, 0.05, or 0.5% for 90 d; mice were also fed at 0.25%. Mortality resulted at the highest dose level in each species. All three species showed depression of body weight or body weight gain, depressed food intake, moderate to severe anemia, and alterations in the spleen (hemosiderosis), liver (hepatomegaly), and testes (atrophy) at the highest dose levels. Cholesterol was elevated in rats and dogs after 90 d. Several species differences were also noted. Uric acid values were elevated in rats but not in dogs, serum glutamic-pyruvic transaminase (SGPT) activity was low in dogs but unchanged in rats, and rats developed hypoplasia of the uterus but dogs did not. Signs of anemia were present at the intermediate dose levels. The lowest dose level in all three species was designated at a "no observable effects" level, based on the absence of clearly treatment-related effects. In a 4-wk study, the irradiated mixture fed to rats at 0.003, 0.03, or 0.3% in the diet was less toxic than the unirradiated mixture.

Anemia↗
PubMed1988

A nine-month chronic toxicity study of tegafur-uracil mixture (UFT) in dogs.

In order to evaluate the long-term-safety of UFT which contained tegafur [1-(2-tetrahydrofuryl)-5-fluorouracil, FT-207] and uracil in molar ratio of 1:4, a nine-month chronic toxicity study was performed in dogs. In doses of 9.7 (as FT-207: 3 mg/kg), 16.2 (as FT-207: 5 mg/kg) and 24.3 (as FT-207:7.5 mg/kg) mg/kg, UFT was administered orally in both sexes of dogs once a day for 9 months and withdrawn for 1 month. Three control drugs, FT-207, uracil and 5-FU, were also included in present experiment at doses of 7.5, 420.0 and 5.0 mg/kg, respectively. In this study, the two types of toxic behaviors and symptoms were observed in UFT, FT-207 and 5-FU. The first type was the acute and/or dynamic signs and the other type was the chronic and/or static signs. Slight decrease in food consumption was observed in males at the dose levels of 24.3 mg/kg of UFT group and in both sexes of 5-FU group. In the ECG test, high T-wave was observed in some males treated with UFT, FT-207 and 5-FU. Histopathologically, micro-vacuolizations were observed in various portions of the cerebrum in both survived and dead animals treated with UFT, FT-207 and 5-FU. After one month recovery period, significant changes were not observed in various examinations, but morphological changes in the cerebrum had been remained. In conclusion, it seemed that the maximum safety dose of UFT in dogs were the 9.7 mg/kg for males and less than 9.7 mg/kg for females.

Administration, Oral↗
PubMed1988

Genotoxicity of complex mixtures: strategies for the identification and comparative assessment of airborne mutagens and carcinogens from combustion sources.

Two strategies for assessment of the toxicity of complex mixtures are described and illustrated with examples from genotoxicity studies of complex combustion mixtures. The first, a strategy for identifying biologically active compounds or compound classes in complex mixtures, is called bioassay-directed fractionation and characterization. The identification and assessment of mutagens and potential carcinogens in complex mixtures has been significantly advanced by the use of short-term genetic bioassays. Bioassay-directed fractionation coupled with new analytical characterization methods has provided the tools needed to more efficiently identify potential carcinogens in complex combustion emissions and urban air samples. These studies have shown that a significant portion of the mutagenicity in combustion emissions and urban air is found in fractions more polar than polynuclear aromatic hydrocarbons (PAHs). A second strategy, the comparative potency method, provides an approach to evaluating the relative toxicities of a series of mixtures. The comparative mutagenicity and carcinogenicity of a series of combustion emissions has been assessed using dose-response studies in bacteria, mammalian cells, and rodents. Comparative mutagenic and tumorigenic emission rates or emission factors provide a means to directly compare the relative hazard of the sources. This data base has also been used to develop a comparative risk assessment methodology for combustion emissions.

Air Pollutants↗
PubMed1999

Quantitative component analysis of mixtures for risk assessment: application to eye irritation.

A methodology called quantitative component analysis of mixtures (QCAM) was used to analyze an existing set of product formulation data to determine if the irritating ingredients in the mixtures could be identified. Eye irritation scores, based on a rat model, for 18 mixtures having a composite total of 37 components, were analyzed by QCAM. QCAM relates a net toxicity measure of a mixture to the toxicities of the individual components of the mixture through linear, quadratic, and pairwise cross-component concentration-dependent interactions. A correlation model is established using a particular genetic algorithm employing either multidimensional linear regression or partial least-squares regression fitting. Cornea eye irritation and average eye irritation are well-explained in terms of a linear model of, at most, three components over the set of mixtures. Moreover, extensive cornea and average eye irritations are due to only one of these three components of the mixtures. Also, one of the three significant components was predicted to decrease the extent of eye irritation, and subsequently identified as an "anti-irritant" in contact lens solutions. A reasonable linear correlation model could also be developed for conjunctiva irritation, but no significant iris irritation model could be constructed. The addition of quadratic and/or cross-component concentration terms to a linear correlation model did not statistically improve the overall resultant model. The QCAM models permit estimation of the intrinsic (self) toxicity of each of the components of a mixture, and may aid in the reduction, and ultimate elimination, of the need for animal eye irritation studies.

Algorithms↗
PubMed2004

A low-toxicity method for the separation of lanosterol and dihydrolanosterol from commercial mixtures.

We describe an inexpensive, low-toxicity and high-yielding method for the production of pure lanosterol and dihydrolanosterol from the commercially available mixture. Optimum conditions are presented for the one-pot production of the intermediate 24,25 vicinal diol of lanosterol acetate (via either epoxidation or hydroxyhalogenation) which is readily separated from the unreacted dihydrolanosterol acetate. The lanosterol diol can then be converted to pure (>97%) lanosterol. Hypophosphorous acid was used for both the conversion of the epoxide to the diol, and as a catalyst for the hydroxyhalogenation by N-halosuccinimides of the olefinic bond.

Acetylation↗
PubMedDate not supplied

One-year dog toxicity study of D-002, a mixture of aliphatic alcohols.

D-002 is a mixture of high-molecular-weight aliphatic alcohols, obtained from bees wax (Apis mellifera), with mild anti-inflammatory properties and effective anti-ulcer activities demonstrated in experimental models. This study investigated the oral toxicity of D-002 administered for 1 year to beagle dogs. Twenty-four beagle dogs (12 males and 12 females) were distributed randomly in three experimental groups (four animals per group): a control and two treated groups received D-002 at 50 and 250 mg kg(-1) (7 days/week) by gastric gavage. Overall, D-002 was well tolerated throughout the study. No signs or symptoms of toxicity were observed, and no mortality occurred during the study. All groups showed similar weight gain and food consumption. No hematological, blood biochemical or histopathological disturbances attributable to treatment were observed. This study shows no drug-related toxicity induced by long-term administration of up to 250 mg kg(-1) D-002 to beagle dogs.

Administration, Oral↗
PubMed2006

Alcoholic fermentation of carbon sources in biomass hydrolysates by Saccharomyces cerevisiae: current status.

Fuel ethanol production from plant biomass hydrolysates by Saccharomyces cerevisiae is of great economic and environmental significance. This paper reviews the current status with respect to alcoholic fermentation of the main plant biomass-derived monosaccharides by this yeast. Wild-type S. cerevisiae strains readily ferment glucose, mannose and fructose via the Embden-Meyerhof pathway of glycolysis, while galactose is fermented via the Leloir pathway. Construction of yeast strains that efficiently convert other potentially fermentable substrates in plant biomass hydrolysates into ethanol is a major challenge in metabolic engineering. The most abundant of these compounds is xylose. Recent metabolic and evolutionary engineering studies on S. cerevisiae strains that express a fungal xylose isomerase have enabled the rapid and efficient anaerobic fermentation of this pentose. L: -Arabinose fermentation, based on the expression of a prokaryotic pathway in S. cerevisiae, has also been established, but needs further optimization before it can be considered for industrial implementation. In addition to these already investigated strategies, possible approaches for metabolic engineering of galacturonic acid and rhamnose fermentation by S. cerevisiae are discussed. An emerging and major challenge is to achieve the rapid transition from proof-of-principle experiments under 'academic' conditions (synthetic media, single substrates or simple substrate mixtures, absence of toxic inhibitors) towards efficient conversion of complex industrial substrate mixtures that contain synergistically acting inhibitors.

Biomass↗