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At least 649 records · Page 36Linked to original sources
PubMed2003

Inhalation toxicity of dimethyl piperidinone.

A mixture of 1,3-dimethyl-2-piperidinone and 1,5-dimethyl-2-piperidinone (DMPD) (approximately 63-37 parts by weight) was tested for its inhalation toxicity in rats following 90-day repeated exposures. Male and female rats were exposed whole-body to either 0, 51, 230, or 310 mg/m(3) DMPD for 6 h/day, 5 days/weak for 90 days. Clinical signs, growth, clinical pathology, tissue pathology, neurobehavior, neuropathology, and semen quality were evaluated. No compound-related adverse effects were noted in clinical signs, body weights, food consumption, clinical laboratory evaluations, neurobehavioral evaluations, neuropathology, or sperm counts. Laryngeal changes consisting of minimal squamous epithelial hyperplasia and degeneration/necrosis of the cartilage were present in male and female rats exposed to 310 mg/m(3) both immediately following exposure and after the 1-month recovery period Male rats exposed to DMPD had increased relative kidney weights, increased formation of hyaline droplets and granular casts, and increased incidence of chronic progressive nephropathy. These kidney effects are consistent with increased accumulation of the urinary protein alpha(2 mu)-globulin, which has been well essential for several xenobiotics. The subsequent increased incidence of progressive nephropathy was specific to male rats with the alpha(2 mu) syndrome. Male and female rats exposed to 230 or 310 mg/m(3) had centrilobular hepatocellular hypertrophy, and male rats exposed to 310 mg/m(3) had increased relative liver weights. These liver changes were reversible following the recovery period and were considered not to represent adverse toxicological effects of treatment. Since the male rat-specific renal findings do not connote adversity for man and are net considered relevant to human hazard assessment, the no-observed-effect level in male and female rats was 230 mg/m(3), based on the microscopic changes in the larynx exposed to 310 mg/m(3).

Animals↗
PubMed2006

Effects-directed analysis of organic toxicants in wastewater effluent from Zagreb, Croatia.

The organic toxicants present in the effluent of the main sewer of the city of Zagreb, Croatia were isolated and identified through the use of effects-directed characterisation techniques. At the time of investigation, the wastewater effluent received no treatment and was comprised of a mixture of effluent from domestic and industrial sources. The organic load of the wastewater was isolated by solid phase extraction and toxicity profiles obtained using reverse-phase HPLC. All procedures were evaluated through the analysis of a series of reference compounds of widely differing polarity. Toxicity profiles for EROD activity (CYP1A induction), vitellogenin induction (estrogenic activity), cytotoxicity (membrane stability and metabolic inhibition) were obtained using a rainbow trout (Oncorhynchus mykiss) primary hepatocyte bioassay. The suite of bioassays showed biological responses after exposure to the raw extracts for all the endpoints tested. However, a combination of mixture toxicity and cytotoxicity in the complex raw extract had some masking effect on the sub-lethal responses of vitellogenin and EROD induction. Bioassay testing of the fine fractions obtained by HPLC produced a range of endpoint-specific toxicity profiles for each sample. A number of compounds were identified by the use of GC-MS and LC-MS/MS as responsible for the observed effects. The steroid estrogens 17 beta-estradiol and estriol were identified by LC-MS/MS as estrogen receptor agonists in two of the estrogenic fractions. In addition, GC-MS analysis identified different alkylphenols, benzophenone and methylparaben which also contributed to the estrogenic activity of the sample. Polycyclic aromatic hydrocarbons (PAHs), alkyl substituted PAHs, nitro-polycyclic aromatic compounds (nitro-PACs), carbazoles and alkyl substituted carbazoles and other known CYP1A inducers were identified by GC-MS analysis as responsible for some of the observed EROD activity. Some active compounds remain unidentified.

Animals↗
PubMed2006

Testing for additivity at select mixture groups of interest based on statistical equivalence testing methods.

Several assumptions, defined and undefined, are used in the toxicity assessment of chemical mixtures. In scientific practice mixture components in the low-dose region, particularly subthreshold doses, are often assumed to behave additively (i.e., zero interaction) based on heuristic arguments. This assumption has important implications in the practice of risk assessment, but has not been experimentally tested. We have developed methodology to test for additivity in the sense of Berenbaum (Advances in Cancer Research, 1981), based on the statistical equivalence testing literature where the null hypothesis of interaction is rejected for the alternative hypothesis of additivity when data support the claim. The implication of this approach is that conclusions of additivity are made with a false positive rate controlled by the experimenter. The claim of additivity is based on prespecified additivity margins, which are chosen using expert biological judgment such that small deviations from additivity, which are not considered to be biologically important, are not statistically significant. This approach is in contrast to the usual hypothesis-testing framework that assumes additivity in the null hypothesis and rejects when there is significant evidence of interaction. In this scenario, failure to reject may be due to lack of statistical power making the claim of additivity problematic. The proposed method is illustrated in a mixture of five organophosphorus pesticides that were experimentally evaluated alone and at relevant mixing ratios. Motor activity was assessed in adult male rats following acute exposure. Four low-dose mixture groups were evaluated. Evidence of additivity is found in three of the four low-dose mixture groups. The proposed method tests for additivity of the whole mixture and does not take into account subset interactions (e.g., synergistic, antagonistic) that may have occurred and cancelled each other out.

Animals↗
PubMed2003

Mammary gland morphology in Sprague-Dawley rats following treatment with an organochlorine mixture in utero and neonatal genistein.

In a related reproductive toxicology study designed to investigate the effects of in utero exposure to environmental toxicants and potential interaction with postnatal genistein, gross enlargement of thoracic mammary glands was observed in female offspring at 200 days of age. Therefore, the objective of this study was to analyze the effect of in utero exposure to a mixture of toxicants on mammary gland morphology. Time-mated Sprague-Dawley rats were treated on days 9-16 of gestation with vehicle or a mixture of environmental toxicants at 1x the acceptable daily intake. Furthermore, it is unclear whether postnatal exposure to phytoestrogens in soy formulas poses breast cancer benefit or risk, and potential interactions with environmental toxicants are unknown. Therefore, half the female pups from each treatment group received either subcutaneous vehicle or genistein (10 microg/g body weight [bw]/day) on postnatal days 2-8. Following necropsy at 200 days of age, a pathologist, blinded to treatment groups, examined mammary gland histopathology. Only mild histological changes were found in mammary glands of rats exposed to the mixture in utero while pronounced ductal hyperplasia, lactational changes, and fibrosis were observed in mammary glands from the genistein group and were more prominent in the mixture + genistein group. Mammary glands of the control group were histologically normal. Collectively, our results reveal that postnatal exposure to pharmacological levels of genistein induces profound morphological changes in the mammary glands of adult female rats, and that high levels of phytoestrogens possess the potential to modulate the toxicological effects of toxicant mixtures.

Administration, Oral↗
PubMed1999

Toxicity of formulated glycol deicers and ethylene and propylene glycol to lactuca sativa, lolium perenne, selenastrum capricornutum, and lemna minor

Laboratory studies were conducted to determine the toxicity of ethylene glycol (EG) and propylene glycol (PG) as well as two formulated glycol aircraft deicing/anti-icing fluids (ADAFs) to lettuce (Lactuca sativa), perennial ryegrass (Lolium perenne), a green alga (Selenastrum capricornutum), and duckweed (Lemna minor). Seedling emergence, root length, and shoot length were measured in lettuce and ryegrass; cell growth of the alga and frond growth, chlorophyll a, and pheophytin a of the duckweed were measured. While both the ADAFs and pure glycols were toxic to the test species, there were substantial differences in how the organisms responded to the test materials. ADAFs affected emergence in ryegrass more than in lettuce. However, when considering the sublethal endpoints of root and shoot length, the ADAFs were significantly more toxic to lettuce. The root length 120-h IC25s for lettuce were 2,710 and 21, 270 mg EG/L for the ADAF and pure EG compound, respectively; the root length 120-h IC25s for ryegrass were 4,150 and 3,620 mg EG/L for the ADAF and pure EG compound, respectively. EG and PG ADAFs were more toxic than pure EG or PG to L. minor. To S. capricornutum, EG ADAF toxicity was similar to EG toxicity, however, PG ADAF was substantially more toxic to the alga than pure PG. The greater toxicity of ADAFs is reflective of other studies using animals and suggests that although glycols no doubt contribute to toxicity in deicer formulations, other compounds in the mixtures also contribute to the toxicity of the deicers. However, differences in responses between the four plant species suggest differences in modes of action and/or how the plants metabolize the compounds.http://link. springer-ny.com/link/service/journals/00244/bibs/37n1p29.html

Journal Article↗
PubMed1977

Respiratory effects of exposure to ozone plus sulfur dioxide in Southern Californians and Eastern Canadians.

Volunteer subjects were exposed in an environmentally controlled chamber in Los Angeles to SO2 and O3, separately and in combination, to study the enhanced toxicity of the O3 + SO2 mixture observed in a previous study in Montreal. Toxic responses to O3 + SO2 were less severe than observed previously, and only slightly more severe than with O3 alone. Sulfur-containing aerosols formed by chemical reactions within the chamber air may have contributed to the O3 + SO2 responses in the Montreal study. Adaptation of Los Angeles residents to ambient O3 may also contribute to response variability.

California↗
PubMedDate not supplied

Effects of an ethanol-gasoline mixture: results of a 4-week inhalation study in rats.

The inhalation toxicity of an ethanol-gasoline mixture was investigated in rats. Groups of 15 male and 15 female rats were exposed by inhalation to 6130 ppm ethanol, 500 ppm gasoline or a mixture of 85% ethanol and 15% gasoline (by volume, 6130 ppm ethanol and 500 ppm gasoline), 6 h a day, 5 days per week for 4 weeks. Control rats of both genders received HEPA/charcoal-filtered room air. Ten males and ten females from each group were killed after 4 weeks of treatment and the remaining rats were exposed to filtered room air for an additional 4 weeks to determine the reversibility of toxic injuries. Female rats treated with the mixture showed growth suppression, which was reversed after 4 weeks of recovery. Increased kidney weight and elevated liver microsomal ethoxyresorufin-O-deethylase (EROD) activity, urinary ascorbic acid, hippuric acid and blood lymphocytes were observed and most of the effects were associated with gasoline exposure. Combined exposure to ethanol and gasoline appeared to exert an additive effect on growth suppression. Inflammation of the upper respiratory tract was observed only in the ethanol-gasoline mixture groups, and exposure to either ethanol and gasoline had no effect on the organ, suggesting that an irritating effect was produced when the two liquids were mixed. Morphology in the adrenal gland was characterized by vacuolation of the cortical area. Although histological changes were generally mild in male and female rats and were reversed after 4 weeks, the changes tended to be more severe in male rats. Brain biogenic amine levels were altered in ethanol- and gasoline-treated groups; their levels varied with respect to gender and brain region. Although no general interactions were observed in the brain neurotransmitters, gasoline appeared to suppress dopamine concentrations in the nucleus accumbens region co-exposed to ethanol. It was concluded that treatment with ethanol and gasoline, at the levels studied, produced mild, reversible biochemical hematological and histological effects, with some indications of interactions when they were co-administered.

Administration, Inhalation↗
PubMed1986

Toxic pneumonitis from mixing household cleaners.

In the past year we have seen three cases of life-threatening toxic pneumonitis caused by exposure to mixtures of household ammonia and bleach. This particular mixture forms intermediary chloramine compounds that cause toxic pneumonitis. Each patient had a prolonged hospitalization and was left with symptomatic residual roentgenographic changes. Exposure to mixtures of household ammonia and bleach may be a frequent cause of acute pneumonitis that is not well recognized.

Aged↗
PubMed2005

Interactive toxic effects of heavy metals and humic acids on Vibrio fischeri.

The effect of humic acids (HAs) on the toxicity of copper, zinc, and lead was investigated using the photobacterium Vibrio fischeri (Microtox test) as a test organism. The effects of HAs on metal toxicity were evaluated as functions of time and concentration in pure compound solutions. The toxicities of copper and lead were generally comparable, while the toxicity of zinc was lower than those of the other two metals. The toxicity of copper decreased with the addition of HAs, while the toxicity of zinc remained almost constant. On the other hand, the toxicity of lead increased, depending on the concentration of HAs. The interactive effects between copper and zinc and between lead and zinc were synergistic, while the interactive effect between copper and lead on the bioluminescence of V. fischeri was additive. The presence of HAs caused relatively high toxicity reduction in the binary mixtures of zinc and copper or zinc and lead, while the toxicity reduction in the case of the binary mixture of copper and lead was negligible.

Aliivibrio fischeri↗
PubMed1995

Characterization of endothelial cell injury by cholesterol oxidation products found in oxidized LDL.

The present study describes the toxicity of oxidized LDL towards rabbit aortic endothelial cells in terms of its lipid components with specific attention to the cholesterol oxidation products (ChOx) found in oxidized LDL isolated from human plasma. Measurements of the major ChOx associated with freshly isolated unmodified LDL, those found in oxidized LDL isolated from human plasma and LDL subjected to oxidation in vitro are described. We have confirmed previous findings that most of the cytotoxicity of freshly isolated human LDL may be attributable to a minor fraction that appears to be oxidatively modified by several criteria. Moreover, this plasma-derived oxidized LDL (referred to as LDL) is highly enriched in ChOx, whereas the content of lipid peroxides or derived products (measured as conjugated dienes and thiobarbituric acid reacting products) are much lower, particularly when compared to copper-induced LDL oxidation. Much of the ChOx found in plasma are associated with LDL, however, the levels and proportions of the various ChOx found in LDL differ from those produced after extensive copper-induced oxidation but resemble those produced after moderate oxidation with copper. The species and concentrations of ChOx found in LDL when applied as a mixture exhibit considerably more toxicity than any individual ChOx alone. At non-toxic levels this ChOx mixture causes an increased influx of several ions, including calcium, an effect not seen with individual ChOx at comparable doses. Perturbations in ionic homeostasis, and particularly the sustained increase in intracellular calcium concentrations, are associated with much of the cytotoxicity, an effect attributable to the membrane disruptive action of ChOx leading to altered ion transporter activity. The effect of the ChOx mixture (but not any individual ChOx) on sodium and potassium flux appears to be due to enhanced Na+/K(+)-ATPase activity based on the complete inhibition produced by ouabain under all treatment conditions. These findings also show that the levels of cholesterol oxidation products found in normal LDL are not cytotoxic whereas those present in oxidized LDL exceed the toxic threshold for endothelial cells and account for most of the cytotoxicity produced by this modified lipoprotein.

Animals↗
PubMed2005

A unifying concept for assessing toxicological interactions: changes in slope.

Robust statistical methods are important to the evaluation of toxicological interactions (i.e., departures from additivity) among chemicals in a mixture. However, different concepts of joint toxic action as applied to the statistical analysis of chemical mixture toxicology data or as used in environmental risk assessment often appear to conflict with one another. A unifying approach for application of statistical methodology in chemical mixture toxicology research is based on consideration of change(s) in slope. If the slope of the dose-response curve of one chemical does not change in the presence of other chemicals, then there is no interaction between the first chemical and the others. Conversely, if the rate of change in the response with respect to dose of the first chemical changes in the presence of the other chemicals, then an interaction is said to exist. This concept of zero interaction is equivalent to the usual approach taken in additivity models in the statistical literature. In these additivity models, the rate of change in the response as a function of the i(th) chemical does not change in the presence of other chemicals in a mixture. It is important to note that Berenbaum's (1985, J. Theor. Biol. 114, 413-431) general and fundamental definition of additivity does not require the chemicals in the mixture to have a common toxic mode of action nor to have similarly shaped dose response curves. We show an algebraic equivalence between these statistical additivity models and the definition of additivity given by Berenbaum.

Complex Mixtures↗
PubMed2005

Growth inhibition as indicator of stress because of atrazine following multiple toxicant exposure of the freshwater macrophyte, Juncus effusus L.

Atrazine is a herbicide used most frequently in North America, but it usually is encountered in mixtures of agrochemicals. Few atrazine exposure studies have been conducted using mixed pesticides; therefore, little data are available to suggest reliable means of discerning effects attributable to atrazine. The common freshwater macrophyte, Juncus effusus L., was exposed in 66 mesocosms to atrazine at two nominal concentrations (96 and 192 microg/L) with varying concentrations of chlorpyrifos, monosodium methanearsonate, and monomethylmercury. Exposure levels represented typical levels that might follow runoff or direct-spray application in enclosed waterbodies. Using shoot density and number of shoots shorter than 25 cm per unit area as response measurements, the growth effects of atrazine, even in varying pesticide mixes, could be detected as early as 16 d after initial exposure. Further growth effects specifically caused by atrazine also could be detected following a second exposure to the same toxicant mixture. Mesocosm tests offer greater control of natural variability than would be found in the natural environment and offer more realistic conditions than traditional laboratory/greenhouse studies. Therefore, in field testing, growth measurements should be accompanied by other confirmatory tests, such as pesticide concentrations in tissue and, possibly, chlorophyll concentrations, for measuring specific toxic effects of atrazine and other pesticides.

Animals↗
PubMed1996

Enzyme induction and acute endocrine effects in prepubertal female rats receiving environmental PCB/PCDF/PCDD mixtures.

Air, subsurface soil, and superficial dust from a National Priorities List landfill located in southern Illinois were sampled to determine their potential toxicities. The major components of these landfill extracts were polychlorinated biphenyls (PCBs), with significant amounts of polychlorinated dibenzofurans (PCDFs) and small amounts of polychlorinated dibenzodioxins (PCDDs). The 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) toxic equivalency factor approach has been proposed to estimate the toxic potency of complex mixtures of chlorinated aromatics for environmental risk assessment. However, most components of environmental residues are nonplanar and do not act as aryl hydrocarbon (Ah) receptor agonists, so there is a great risk of not identifying adverse responses that are not dioxinlike. We used a 2-day prepubertal female rat bioassay to examine multiple biological responses, including both dioxinlike and nondioxinlike effects from these landfill extracts. As expected, both types of effects were detected. The soil and dust extracts produced similar dose-response relationships for 7-ethoxyresorufin O-deethylase, 7-pentoxyresorufin O-depentylase, 7-benzyloxyresorufin O-debenzylase, and 4-nitrophenol UDP-glucuronyltransferase induction; the dose response for the air extract deviated from the other two extracts. Soil, dust, and air extracts effectively reduced serum total thyroxine (T4) with similar dose-response relationships, despite the significantly different TCDD toxic equivalent (TEQ) values of these three extracts. Both soil (346 mg PCB/kg) and air (175 mg PCB/kg) extracts caused a greater than 30% increase in uterine wet weight. This study suggests that a more comprehensive approach is required to improve current risk assessment of environmental mixtures. TCDD TEQs reflect only a portion of effects and may especially underpredict effects on T4.

Air Pollutants↗
PubMed1981

Toxicity of endosulfan and manganese chloride: cumulative toxicity rating.

There has been, in general, no accepted comparable way to express the effects of repeated doses. This study was designed to provide information on cumulative toxicity of manganese chloride (MnCl2), endosulfan, and a mixture of these compounds and to suggest cumulative toxicity rating. Male mice were given the test compound i.p. 6 days/week for a minimum for 10 weeks and until the cumulative LD50 remained constant for 3 consecutive weeks. Using a ratio between a single dose and weekly cumulative LD50 (CLD50), cumulative toxic factors (CTF) were determined. The CTF for weeks 1-13 for MnCl2 ranged from 0 to 3.48; endosulfan LD50 and CLD50 values for a mixture of MnCl2 and endosulfan were higher than the expected values, indicating a greatly reduced toxicity of a mixture, when given either in a single dose or repeated doses. Using the CLD50 criterion as laid down in this study, the cumulative toxicity rating, class 1 to 6, has been suggested so as to have a comparative assessment of th cumulative potential of several compounds.

Animals↗
PubMed1991

[Hygienic evaluation of hazardous materials].

The appearance of the toxicity phenomenon in the mixture with the simultaneous analysis of the characters of the combined actions of the elements were studied in experiments using as a model incredop composition to determine the significance of each components and quantitative interactions. It was found, that elimination from this mixture even of a single element or changing in the quantitative interactions between elements caused the changes in the toxicity, levels of the sumulation and characters of the combined actions of the components. Therefore the mixtures must be studied as the single object with the establishment of according standards which may not correlate with that in the individual compounds.

Animals↗
PubMed1999

[The toxicity of combination of selenium, fluoride and arsenic on rat embryos].

Whole embryo rotated culture technique was used to investigate the toxicity of combination of selenium, fluoride and arsenic on rat embryos at day 9.5 of gestation. The result of factorial analysis (3 x 3 x 3) showed that the main effect of combination of selenium, fluoride and arsenic on the developmental toxicity was synergistic. The mixtures with different level of these three chemicals in combination could result in different developmental toxicity. The low level combinations mainly caused teratogenic effect, and the high level combinations(selenium 2.0 micrograms + fluoride 10 micrograms + arsenic 1.0 microgram/ml culture media) caused lethal effect. The results suggested that the disorders of yolk-sac placenta in structure and function were one of teratogenic mechanisms for the combination of selenium, fluoride and arsenic.

Animals↗
PubMed1998

A study of the lethal and sublethal toxicity of polyphase P-100, an antisapstain fungicide containing 3-iodo-2-propynyl butyl carbamate (IPBC), on fish and aquatic invertebrates.

The acute toxicity of Polyphase P-100, an antisapstain wood preservative that contains 97% 3-iodo-2-propynyl butyl carbamate (IPBC), was determined for three species of fish (coho salmon, rainbow trout, and starry flounder) and three species of aquatic invertebrates (Daphnia magna, Hyalella azteca, and Neomysis mercedis). The 96-h LC50 values for the various fish species exposed to Polyphase P-100 ranged from 95 ppb for coho smolts (Oncorhynchus kisutch) to 370 ppm for juvenile starry flounder (Platichthys stellatus). The sensitivity of coho to Polyphase P-100 was altered by their developmental stage. Coho embryos were six to nine times more tolerant of Polyphase P-100 than coho alevins, which were twice as tolerant as coho smolts. The 48-h LC50 values for the invertebrates D. magna, H. azteca, and N. mercedis were 40 ppb, 500 ppb, and 2,920 ppb, respectively. In addition to a wider range of sensitivity to Polyphase P-100 compared with the fish species, the invertebrate species were characterized by a shallower concentration-response. In acute, 24-h sublethal tests with juvenile starry flounder and rainbow trout, there was no primary or secondary stress response (changes in hematocrit, leucocrit, hemoglobin concentration, plasma lactate concentration, and plasma cortisol concentration) at concentrations up to 50% of the 96-h LC50 value. The acute toxicity of a 1:8 mixture of Polyphase P-100 and Bardac 2280 (another antisapstain compound that contains didecyldimethylammonium chloride [DDAC] as the active ingredient) was close to additive for fish, but not for invertebrate species. The acute toxicity of the mixture was seven to eight times more than additive for H. azteca, but two to three times less than additive for D. magna. Some sublethal stress responses were revealed with the mixture that were not observed with the test chemicals alone.

Animals↗
PubMedDate not supplied

Neurotoxicity of organic solvent mixtures: embryotoxicity and fetotoxicity.

The toxicity of organic solvents at different concentrations was examined to determine their effect on pregnant rats and their offspring. A very serious effect which inhalational exposure to n-hexane, methyl-ethyl-ketone and a mixture of the two organic solvents produced in pregnant rats was a concentration-dependent increase of intrauterine mortality. In cases of only prenatal exposure, the persistence of reduced body growth was an important result obtained at all concentrations we investigated (first solvent experiment, 500 ppm; second solvent experiment, 800 ppm; and third solvent experiment, 1000 to 1500 ppm; 23 hr day). In these cases, a delay in the maturation of cerebellar cortex was also observed. In cases of pre- and postnatal solvent exposure, the effects of malnutrition were added to the solvent-induced retardation. This resulted in an extreme delay in tissue maturation accompanied by a retarded cell maturation. The solvents examined had no teratogenic effect in pregnant rodents and their offspring. Neurotoxicity was restricted to the known structures of the adult animals, whose axons were damaged. They did, however, show a concentration-dependent embryotoxic and fetotoxic effect.

Administration, Inhalation↗