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Toxicity of formaldehyde and acrolein mixtures: in vitro studies using nasal epithelial cells.

In vitro studies with human and rat nasal epithelial cells were carried out to investigate the combined toxicity of formaldehyde and acrolein and the role of aldehyde dehydrogenases in this process. These studies showed that the toxic effect of mixtures of aldehydes was additive. In addition, aldehyde dehydrogenases were inhibited by disulfiram and acrolein in S9 incubation but disulfiram did not influence the toxicity in vitro (cell culture). This study does not support the idea that aldehyde dehydrogenases play a major role in the detoxification of exogenous aldehydes.

Acrolein↗

Acute urinary bladder toxicity of a polyurethane foam catalyst mixture: a possible new target organ for propionitrile derivative.

The toxicity of the mixture NIAX-ESN which contains 95% dimethylaminopropionitrile was evaluated in male rats. Large doses (2.0 ml/kg ip) rapidly produced CNS excitation followed by depression and death. The mixture (given orally as two doses of 0.31 or 0.62 ml/kg respectively) induced acute urinary bladder lesions in 3 days. The changes consisted of massive transmural edema, acute ulcers and inflammation and, occassionally hemorrhagic necrosis of the bladder wall.

Aminopropionitrile↗

Temporal analysis of airborne particulate matter reveals a dose-rate effect on mortality in El Paso: indications of differential toxicity for different particle mixtures.

One of two topics explored is the limitations of the daily average in summarizing pollutant hourly profiles. The daily average of hourly measurements of air pollutant constituents provides continuity with previous studies using monitoring technology that only provided the daily average. However, other summary statistics are needed that make better use of all available information in 24-hr profiles. The daily average reflects the total daily dose, obscuring hourly resolution of the dose rate. Air pollutant exposures with comparable total daily doses may have very different effects when occurring at high levels over a few hours as opposed to low levels over a longer time. Alternative data-based choices for summary statistics are provided using principal component analysis to capture the exposure dose rate, while preserving ease of interpretation. This is demonstrated using the earliest hourly particle concentration data available for El Paso from archived records of particulate matter (PM)10. In this way, a significant association between evening PM10 exposures and nonaccidental daily mortality is found in El Paso from 1992 to 1995, otherwise missed using the daily average. Secondly, the nature and, hence, effects of particles in the ambient aerosol during El Paso sandstorms is believed different from that of particles present during still-air conditions resulting from atmospheric temperature inversions. To investigate this, wind speed (ws) is used as a surrogate variable to label PM10 exposures as Low-ws (primarily fine particles), High-ws (primarily coarse particles), or Mid-ws (a mixture of fine and coarse particles). A High-ws evening is significantly associated with a 10% lower risk of mortality on the succeeding third day, as compared with comparable exposures at Low- or Mid-ws. Although this analysis cannot be used to form firm conclusions because it uses a very small data set, it demonstrates the limitations of the daily average and suggests differential toxicity for different particle compositions.

Air Pollutants↗

Assessment of toxic interactions of heavy metals in a multicomponent mixture using Lepidium sativum and Spirodela polyrrhiza.

The toxicities of copper, chromium, cadmium, nickel, manganese, zinc, and lead ions and various concentrations of mixtures of them were studied using the aquatic plant Spirodela polyrrhiza and the terrestrial plant Lepidium sativum. The composition of the model mixture was based on average analytical data of the annual amounts of representative heavy metals (HM) in wastewater discharged from the Ignalina Nuclear Power Plant (Lithuania) during 1996. The observed and predicted effects of the HM mixture on tested plants were evaluated and compared with the prediction models used in describing the toxic interactions of heavy metals in the mixture. The type of toxic interaction at each tested concentration of the mixture was assessed by a statistical approach that tested the null hypothesis of additive toxicity (Ince et al., 1999) and the mixture toxicity index (MTI; Könemann, 1981). For both plant organisms the effect of the HM mixture calculated using the MTI was synergistic. However, assessment of the HM interaction type at 50% effect concentrations using the hypothesis of additive toxicity showed a synergistic effect for Spirodela polyrrhiza and an additive effect for Lepidium sativum. Though the results obtained using both prediction models for assessing the HM mixture's toxicity were similar, in our opinion, the additive toxicity model is more suitable than the MTI model because the former allows evaluation of the impact of various mixture concentrations, not only those with a 50% effect.

Araceae↗

Combination ecotoxicity and testing of common chemical discharges to sewer using the Vibrio fischeri luminescence bioassay.

In order to investigate possible synergistic or antagonistic (more or less than additive) toxicity effects, mixtures of chemicals were tested in water using a microbial bioassay. Ten toxicants (3,4-dichloroaniline, 3,5-dichlorophenol, cadmium, chromium, copper, Lindane, linear alkylbenzene sulphonate, pentachlorophenol, toluene, zinc) were chosen on the basis of their common occurrence in industrial effluents within local waste water treatment plants. These toxicants also cover a wide range of modes of toxic action, namely, polar and non-polar narcosis, membrane disruption, respiratory disruption, uncouplers of oxidative phosphorylation, biochemical disruption and enzyme inhibition. Efficient screening for possible combination toxicity between toxicants involved testing the chemicals both singly and in triplet combinations. The triplets were based on four replicates of a balanced incomplete block design (BIB). A standardised Vibrio fischeri rapid toxicity bioluminescence assay was used. The combinations tested showed that only one mixture was found to be significantly more toxic than expected from the pure single-toxicant results. Two triplets were significantly less toxic. Further tests on the more toxic triplet showed that the effect was due to only one of the 45 pairs originally screened. It is concluded that synergistic effects in combinations of toxicants are rather rare in bioluminescence systems utilising common effluents discharged to sewer.

Biological Assay↗

Diethylaminoethyl-cellulose clean-up of a large volume naphthenic acid extract.

The Athabasca oil sands of Alberta, Canada contain an estimated 174 billion barrels of bitumen. During oil sands refining processes, an extraction tailings mixture is produced that has been reported as toxic to aquatic organisms and is therefore collected in settling ponds on site. Investigation into the toxicity of these tailings pond waters has identified naphthenic acids (NAs) and their sodium salts as the major toxic components, and a multi-year study has been initiated to identify the principal toxic components within NA mixtures. Future toxicity studies require a large volume of a NA mixture, however, a well-defined bulk extraction technique is not available. This study investigated the use of a weak anion exchanger, diethylaminoethyl-cellulose (DEAE-cellulose), to remove humic-like material present after collecting the organic acid fraction of oil sands tailings pond water. The NA extraction and clean-up procedure proved to be a fast and efficient method to process large volumes of tailings pond water, providing an extraction efficiency of 41.2%. The resulting concentrated NA solution had a composition that differed somewhat from oil sands fresh tailings, with a reduction in the abundance of lower molecular weight NAs being the most significant difference. This reduction was mainly due to the initial acidification of tailings pond water. The DEAE-cellulose treatment had only a minor effect on the NA concentration, no noticeable effect on the NA fingerprint, and no significant effect on the mixture toxicity towards Vibrio fischeri.

Aliivibrio fischeri↗

Toxic effects of chemical mixtures.

Exposures to chemical mixtures have reportedly produced unexpected effects. Examination of new case studies, as well as those previously reported, shows that when the human body is exposed to mixtures of chemicals that include lipophilic and hydrophilic species, the lipophiles facilitate the absorption of the hydrophiles at enhanced levels and produce effects that are not expected from an individual chemical. These effects include enhanced acute and chronic responses, low-level concentration response, and unexpected target organ attack. Octanol:water partition coefficients are predictive of relative lipophilicity and hydrophilicity. The findings have implications for safe drinking water standards, air quality standards, safe industrial and environmental exposure levels, product formulation, product labeling, and protocols for toxicity testing of chemical products.

Air Pollutants↗

Metalworking fluid--the toxicity of a complex mixture.

Various chemicals are used in the manufacture of cooling and lubricating fluids and fall into the classes of straight, soluble, semisynthetic, and synthetic metalworking fluids. The diversity of chemicals and in-use contaminants makes the risk assessment of metalworking fluids quite difficult. Toxicologists have used a number of methods to evaluate the component(s) responsible for the adverse pulmonary effects of metal working fluid aerosols encountered in the workplace. Although investigators have studied the adverse effects of metalworking fluid chemicals alone and in combination, the majority of evidence strongly suggests that the microbial changes that occur in fluid composition, during use and storage in the workplace, are responsible for the pulmonary effects reported for workers exposed to metalworking fluid aerosols. This review discusses the methodologies used to examine the toxicity of the complex nature of modern metalworking fluids and the findings that point toward bacterial endotoxin as a major contributor to their adverse effects.

Aerosols↗

Efficacy of histopathology in detecting petrochemical-induced toxicity in wild cotton rats (Sigmodon hispidus).

A variety of chemical mixtures exist in the soil of petrochemical waste sites, and many of these compounds are known immunotoxicants that have been observed to induce immune alterations in wild rodents inhabiting many of these petrochemical waste sites. Conventional histopathological assessments have been widely used with considerable success to investigate immunotoxicity of various agents under laboratory conditions. We hypothesized that histopathologic assessments would be equally sensitive for detecting exposure to complex mixtures of toxicants in cotton rats (Sigmodon hispidus) residing in contaminated habitats. Histopathological parameters were examined from a total of 624 cotton rats that were seasonally collected from 13 petrochemical-contaminated waste sites and 13 ecologically matched reference sites in Oklahoma over a 3-year period. Histopathological examination did not reveal any lesion associated with exposure to petrochemical wastes except renal inclusion bodies. Prevalence and severity of histologic lesions in liver and kidneys of cotton rats were significantly influenced by season, where prevalence and severity were lower in winter than summer on all study sites. These results suggest that the evaluation of toxicity from exposure to contaminants in the soil of industrial waste sites using histopathological assessments is not sensitive enough to detect exposure to the low levels of environmental contaminants present on most waste sites.

Animals↗

Biodegradation of naphthenic acids by microbial populations indigenous to oil sands tailings.

Organic acids, similar in structure to naphthenic acids, have been associated with the acute toxicity of tailings produced by the oil sands industry in northeastern Alberta, Canada. Bacterial cultures enriched from oil sands tailings were found to utilize as their sole carbon source both a commercial mixture of naphthenic acids and a mixture of organic acids extracted from oil sands tailings. Gas chromatographic analysis of both the commercial naphthenic acids and the extracted organic acids revealed an unresolved "hump" formed by the presence of many overlapping peaks. Microbial activity directed against the commercial mixture of naphthenic acids converted approximately 50% of organic carbon into CO2 and resulted in a reduction in many of the gas chromatographic peaks associated with this mixture. Acute toxicity testing utilizing the Microtox test revealed a complete absence of detectable toxicity following the biodegradation of the naphthenic acids. Microbial activity mineralized approximately 20% of the organic carbon present in the extracted organic acids mixture, although there was no indication of a reduction in any gas chromatographic peaks with biodegradation. Microbial attack on the organic acids mixture reduced acute toxicity to approximately one half of the original level. Respirometric measurements of microbial activity within microcosms containing oil sands tailings were used to provide further evidence that the indigenous microbial community could biodegrade naphthenic acids and components within the extracted organic acids mixture.

Acinetobacter calcoaceticus↗

Toxicity of binary chemical mixtures: effects on reproduction of zebrafish (Brachydanio rerio).

A complete life-cycle test with zebrafish was carried outwith different concentrations of the binary mixture 3,4-dichloroaniline andlindane under flow-through conditions. Length and weight of fish of theF1-generation were reduced, even in the lowest test concentrationof 2 microg/L 3,4-dichloroaniline and 40 microg/L lindane. The same effects werefound in the early life stage test for the F2-generation. In themixture of 100 microg/L 3,4-dichloroaniline and 40 microg/L lindane, fish whichwere exposed for their whole life time stopped spawning, irreversibly; thefish population will become extinct. In an additional experiment, fish wereexposed to the same xenobiotic concentrations after reaching maturity. Inthis case, egg production was reduced. Cessation of egg production occurs ina concentration of 200 microg/L 3,4-dichloroaniline and 40 microg/L lindane.Nevertheless, effects on spawning are influenced by duration of exposure andthe life stages of exposure.

Aniline Compounds↗

Toxicity of venalot (a mixture of coumarin and troxerutin) in the baboon.

Venalot, a mixture of coumarin and troxerutin, in the proportion 1 to 6 respectively, was given orally to baboons at dosages of 0, 100, 300 and 1000 mg/kg/day for 26 weeks. Vomiting, usually within 3 h of administration and considered to be of central origin, in addition to vomiting immediately after dosing, was noted in animals receiving 1000 mg/kg/day. At this level, collapse on several occasions in two animals, one of which died, was also observed. Another animal receiving 1000 mg/kg/day was killed for humane reasons following a period of weight loss, reduced appetite and deterioration in body condition. However, no adverse effect on body weight gain, food or water consumption, ophthalmoscopic or electrocardiographic examinations were noted in any other animals during this study. Increased levels of liver function (serum leucine amino-peptidase (LAP), and serum ornithine carbamyl transferase (OCT) were noted during the dosing period, together with slightly increased liver weights terminally for animals receiving 1000 mg/kg/day; however, as no morphological or ultrastructural changes were noted, these findings were considered to be attributable to hypertrophy.

Animals↗

Male fertility, sister chromatid exchange, and germ cell toxicity following exposure to mixtures of chlorinated phenoxy acids containing 2,3,7,8-tetrachlorodibenzo-p-dioxin.

Fertility and sperm number, motility, and morphology were analyzed in male C57BL/6 mice exposed to various mixtures of 2,4-dichlorophenoxyacetic acid (2,4-D), 2,4,5-trichlor-ophenoxyacetic acid (2,4,5-T), and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in the diet for 8 wk. Somatic cell (bone marrow) sister chromatid exchange frequencies were also evaluated in mice injected with similar chemical mixtures. The concentration of the test chemicals was such that the average daily feeding dose in the three mixtures or control was 40 mg/kg 2, 4-D, 40 mg/kg 2,4,5-T, and 2.4 micrograms/kg TCDD; 40 mg/kg 2,4-D, 40 mg/kg 2,4,5-T and 0.16 microgram/kg TCDD; 20 mg/kg 2, 4-D, 20 mg/kg 2,4,5-T, and 1.2 micrograms/kg TCDD; or no chemical added (control). No significant dose-related effects were observed in the treated mice compared to the control group.

2,4,5-Trichlorophenoxyacetic Acid↗