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At least 91 records · Page 5Linked to original sources
PubMed1991

Chlorine gas toxicity from mixture of bleach with other cleaning products--California.

From October 1987 through November 1989, five episodes of chlorine gas exposure with toxicity to at least 14 persons occurred at two state hospitals in California. Each hospital provides inpatient treatment to approximately 1000 forensic psychiatric patients. As part of their rehabilitation programs, selected patients perform cleaning duties under the supervision of janitors or nursing staff. Each incident occurred during the performance of these duties and involved the mixture of bleach (sodium hypochlorite) and a phosphoric acid cleaner by inpatients. This mixture produced chlorine gas and other chemical byproducts (Figure 1a and 1b) and resulted in temporary illness in exposed persons.

Chlorine↗
PubMed2005

Comparative and mixture sediment toxicity of trinitrotoluene and its major transformation products to a freshwater midge.

The explosive trinitrotoluene (TNT) is a prevalent contaminant in many military installations worldwide. Limited knowledge of the comparative toxicity of sediment-associated TNT and related compounds contributes to uncertainty when assessing ecological risks in contaminated sites. Trinitrotoluene undergoes transformation when associated with soils and sediments and typically occurs as a mixture dominated by its reduction products. The objective of this study was to comparatively evaluate the single-compound toxicity of TNT and its major transformation products to the freshwater midge Chironomus tentans in 10-day exposures to sediment spiked with TNT, 2-aminodinitrotoluene (2-ADNT), 2,4-diaminonitrotoluene (2,4-DANT), or trinitrobenzene (TNB). In addition, the nature of the toxicological interactions of the latter compounds in a mixture was evaluated. Upon spiking to sediment, TNT and TNB rapidly degraded to reduced products, and disappearance of extractable compounds suggested irreversible binding to sediment particles. The high degree of transformation and reactivity occurring during 10 days at spiking concentrations as high as 4000 micromol/kg dry weight suggests that TNT and related compounds are unlikely to be encountered in fine-grained sediments at contaminated sites. Similar to previous investigations, the high reactivity of the spiked compound hampered determination of accurate toxic concentrations of TNT and related compounds, and of the nature of toxicological interaction of compounds in a mixture in this study. Sediment concentrations associated with decreased survival were similar for all four compounds, with the 10-d median lethal concentrations (LC50s) determined using initial concentrations ranging from 175 (2-ADNT) to 605 (2,4-DANT) micromol/kg dry weight. Sublethal decrease in growth was not observed for any compound. Results from the mixture experiment suggest additive interaction among TNT and related compounds in sediment exposures.

Animals↗
PubMed2002

Toxicity of flare and crude hydrocarbon mixtures.

The toxicity of whole, saturate, and aromatic hydrocarbon mixtures from flare pit and crude oil sources were evaluated using Lumbricus terrestris. Body burden analysis was used to analyze the intrinsic toxicity of the six hydrocarbon mixtures. The major fractions of the whole mixtures, the saturate, and aromatic fractions had different intrinsic toxicities; the aromatics were more toxic than the saturates. The toxicity of the saturate and aromatic fractions also differed between the mixtures. The flare saturate mixture was more toxic than the crude saturate mixture, while the crude aromatic mixture was more toxic than the flare aromatic mixture. The most dramatic difference in toxicity of the two sources was between the flare whole and crude whole mixtures. The crude whole mixture was very toxic; the toxicity of this mixture reflected the toxicity of the crude aromatic fraction. However, the flare whole mixture was not toxic, due to a lack of partitioning from the whole mixture into the lipid membrane of the exposed worms. This lack of partitioning appears to be related to the relatively high concentrations of asphaltenes and polar compounds in the flare pit whole mixture.

Animals↗
PubMed1981

Fish toxicity tests with mixtures of more than two chemicals: a proposal for a quantitative approach and experimental results.

The problem of the toxic action of mixtures of many chemicals has been studied. Starting with the classification of Plackett and Hewlett, the types of mixtures for which toxicity can be predicted is discussed. A Mixture Toxicity Index (MTI) has been proposed as a quantification of the result of mixture toxicity experiments. Toxicity experiments with guppies have been conducted, using 6 mixtures of 3--50 chemicals. The toxicity of mixtures of simple similarly acting chemicals could be predicted by Concentration Addition. The concentrations of the separate chemicals in a mixture of 50 compounds giving 50% mortality, were 0.02 X LC50.

Animals↗
PubMed2004

Using factorial experiments to study the toxicity of metal mixtures.

Two-level factorial experiments were employed in this study for understanding and predicting the toxicity of binary and ternary metal mixtures. Toxicity of metal mixtures with concentrations between the respective EC10 and EC80 values was experimentally measured. Models were fit to the experimental data and the resultant models were of high quality as reflected by R2 (coefficient of determination). Interactions between mixture components were indicated by the existence of statistically significant interaction terms in the models. Toxicity predictions based on the models were compared with observed toxicity for binary and ternary metal mixtures. The models developed did not assume additivity between metals, were simple and interpretable, and gave satisfactory predictions of the toxicity of metal mixtures in aqueous solutions without requiring knowledge on synergism or antagonism.

Bacterial Proteins↗
PubMed2004

Developmental toxicity of mixtures: the water disinfection by-products dichloro-, dibromo- and bromochloro acetic acid in rat embryo culture.

The chlorination of drinking water results in production of numerous disinfection by-products (DBPs). One of the important classes of DBPs is the haloacetic acids. We have previously shown that the haloacetic acids (HAs), dichloro (DCA), dibromo (DBA) and bromochloro (BCA) acetic acid are developmentally toxic in mouse whole embryo culture. Human exposure to these contaminants in drinking water would involve simultaneous exposure to all three HAs. This study explores the question of developmental toxicity interactions between these compounds. Gestational day (GD) 9.5 rat embryos were exposed to various concentrations of the three HAs (singly or in combination) for 48 h and then evaluated for dysmorphology. The embryonic effects from exposure to the single compounds and mixtures were evaluated using developmental score (DEVSC) as the parameter of comparison. Concentrations of individual compounds and mixtures were chosen (based on a dose-additivity model) which were predicted to produce scores 10 or 20% lower than control levels. Evaluations were performed on all possible combinations of the three HAs. The HAs were dysmorphogenic and resulted in primarily rotation and heart defects and to a lesser extent prosencephalic, visceral arch, and eye defects. The percent anomalies in the rat were comparable to those previously published for the mouse at comparable toxicant concentration. There was a low incidence of neural tube defects in the rat following exposure to the HAs. The rat neural tube appeared less sensitive to the HAs than did the mouse resulting in a higher rate of neural tube dysmorphology in the mouse. Following exposures to BCA and DBA, alone and in combination, there was a significant incidence of delayed embryonic caudal development with apparent normal development anterior to the second visceral arch. The developmental scores for embryos exposed to combinations of the three compounds, when compared to scores for embryos exposed to the single compounds, indicated that the dose-additivity model adequately predicted the observed toxicity and that the developmental toxicity of these water disinfection by-products appears to be additive in whole embryo culture (WEC).

Abnormalities, Drug-Induced↗
PubMed2002

Biochemical and toxicological evaluation of agent-cofactor reactivity as a mechanism of action for osteolathyrism.

In vitro reactivity for each of four osteolathyrogens with a model compound for the lysyl oxidase (LO) cofactor was evaluated and coupled with mixture toxicity testing to evaluate agent-cofactor reactivity as a potential mechanism of action for osteolathyrism. Reactivity of the model cofactor (mLTQ: 4-butylamino-5-methyl-o-quinone), with each of two ureides, semicarbazide (SC) and thiosemicarbazide (TSC), and each of two aminonitriles, aminoacetonitrile (AAN) and beta-aminopropionitrile (betaAPN), was assessed using UV-vis spectrophotometry; both in the absence and presence of Cu(II)-bipyridine (bipy) complex. Two sets of mixture toxicity experiments were conducted using a frog embryo assay that assessed the incidence of osteolathyrism in the notochord of tadpoles after 96-h exposure. The resulting concentration-response curves for each set were evaluated (chi(2) goodness-of-fit test) against theoretical curves for two combined effects models: dose-addition and independence, to determine the combined effect of each osteolathyrogen combination. The agents SC, TSC and AAN each showed rapid, irreversible reactivity with mLTQ, both in the absence and presence of Cu(II)-bipy complex, as indicated by bleaching of the mLTQ peak (504 nm) and formation of an adduct at 350 nm. betaAPN showed no apparent reactivity in the absence of prolonged incubation with mLTQ, whether Cu(II)-bipy complex was present or not. After prolonged incubation (24-144 h) a new peak formed at 350 nm, suggesting that betaAPN reacts weakly with the cofactor, but in a manner different from the other agents examined. The toxicity tests indicated a dose-additive combined effect for the SC:TSC, AAN:SC and AAN:SC:TSC mixtures (0.1<P<0.9; with slope and EC(50) additivity quotient values between 0.93-1.14), suggesting these agents induce osteolathyrism via a common mechanism. The betaAPN:SC and betaAPN: SC:TSC mixtures showed a greater-than dose-additive combined effect (P<0.001; slope and EC(50) additivity quotient values from 0.74 to 0.89), suggesting a different or additional mechanism of osteolathyrism for betaAPN. Taken together the results indicate that SC, TSC and AAN induce osteolathyrism primarily, if not completely, by binding to the LO cofactor, thereby inhibiting proper connective tissue fiber cross-linking. While betaAPN also has the potential to react with the cofactor, the nature of the reactivity observed suggests that betaAPN-cofactor binding is, at best, a secondary mechanism for induction of osteolathyrism in vivo.

Abnormalities, Drug-Induced↗
PubMed2004

Toxicity of binary mixtures of cadmium-copper and carbendazim-copper to the nematode Caenorhabditis elegans.

For ecological risk assessment, the additive model may be used to empirically predict toxic mixture effects. Detailed toxicity tests were performed to determine whether effects of mixtures of copper-cadmium and copper-carbendazim on Caenorhabditis elegans were similar to the effects of the individual compounds. Effects on the course of reproduction, the length of the juvenile period, the length of the reproductive period, and body length were analyzed. Dose-response data were compared to the additive model and tested for four deviation patterns from additivity: No deviation, synergistic/antagonistic deviation, dose ratio-dependent deviation, dose level-dependent deviation. During the exposure, the cadmium-copper effect on reproduction changed from a synergistic, to a dose ratio-dependent deviation from additivity. More cadmium in the mixture decreased the toxicity and more copper increased the toxicity. The effect of copper-carbendazim on reproduction was synergistic at low dose levels and antagonistic at high dose levels and independent of time. Mixture effects on the juvenile and reproductive period were similar to single component effects. It was concluded that the observed time-dependence of toxic interactions was small and that interactions on the timing of reproduction were not found. The additive model underestimated mixture effects on reproduction and body length.

Animals↗
PubMed2004

Toxicity of a mixture of dissimilarly acting substances to natural algal communities: predictive power and limitations of independent action and concentration addition.

Predictive studies of chemical mixtures are typically based on experiments with single species. To study the applicability of the concepts of independent action (IA) and concentration addition (CA) on a multispecies level, the carbon fixation of natural algal communities under toxicant exposure was studied. The presented study focused on a mixture of six dissimilarly acting substances. Conceptual reasoning as well as empirical evidence from single-species tests suggest that IA is more appropriate for this type of mixture. Nonetheless, the potential of CA was also investigated, to assess whether this concept may be applicable as a reasonable worst case prediction of mixture toxicities also on a community level. IA predicted the experimental EC50 precisely. CA underestimated the EC50 by a factor of only 1.4, although the shape of the predicted concentration-response curve was clearly different from experimental data. Hence, it can be concluded that the applicability of the concepts is not restricted to the level of single species. However, some limitations of both concepts became apparent, when stimulating (hormesis-like) effects were observed fo rtwo of the mixture components. These effects were also seen in the experimental mixture toxicity data but cannot be adequately modeled by either concept.

Complex Mixtures↗
PubMed1987

Mixtures of toxic agents and attributable risk calculations.

Calculations of attributable risks have attracted increasing interest recently. However, these efforts have been limited to mostly one agent, radiation, and no interactions with effects of other toxic agents have been taken into account. This paper outlines a generic approach to the calculation of attributable risks for an exposure to several toxic agents and interaction effects associated with them. In this calculation, the partition of interaction terms between the agents responsible is of particular importance. At present, there are no rules on how to assign equitable shares, so one methodology will be proposed and others discussed briefly. For one example of an assignment, the standard errors of the attributable risks are determined in terms of the uncertainties of the input parameters, thus setting the stage for a comparison of the different shares of responsibility.

Drug Interactions↗