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At least 685 records · Page 38Linked to original sources
PubMed2000

Relationship between arterial, mixed venous, and internal jugular carboxyhemoglobin concentrations at low, medium, and high concentrations in a piglet model of carbon monoxide toxicity.

OBJECTIVE: This study tested the hypothesis that mixed venous carboxyhemoglobin concentrations (V-COHb) and internal jugular carboxyhemoglobin concentrations (I-COHb) accurately predict arterial carboxyhemoglobin concentrations (A-COHb). In addition, this study tested the hypothesis that there is a high correlation at low (COHb, 0% to 10%), moderate (COHb, >10% to 40%), and high (COHb, >40%) concentrations between V-COHb, I-COHb, and A-COHb. DESIGN: The study was a prospective comparison of A-COHb, V-COHb, and I-COHb concentrations in piglets exposed to increasing concentrations of carbon monoxide over 6 hrs to achieve a concentration of > or =60% COHb. Carboxyhemoglobin measurements were evaluated by analysis of variance and correlation analysis. Agreement between V-COHb and A-COHb concentrations was examined by using a plot of arteriovenous differences against the mean of the two measurements. INTERVENTION: We simultaneously sampled arterial, mixed venous, and internal jugular blood every 30 mins over the 6-hr study period. RESULTS: Two hundred fifty arterial and mixed venous COHb concentrations were obtained, and 214 internal jugular COHb concentrations were obtained. One hundred additional arterial, mixed venous, internal jugular, and peripheral COHb concentrations were obtained. Correlation between samples at each concentration revealed r2 > = .94. CONCLUSION: Venous COHb concentrations predict arterial COHb concentrations with a high degree of accuracy and are correlated at low, moderate, and high concentrations of carbon monoxide exposure. Arterial or venous samples can be used to accurately measure COHb concentrations.

Animals↗
PubMed2003

Experimental model to study reproductive toxicity of chemicals using induced ovulation in immature F344 rats.

We investigated a simple method using induced ovulation in immature rats to detect ovarian injury due to chemicals. We investigated the influence of di-(2-ethylhexyl) phthalate (DEHP) on ovulation induced by equine chorionic gonadotropin (eCG) in immature F344 rats. Single injections of 15 and 30 iu eCG induced ovulation in 4 of 6 rats and in all of 4 rats, respectively. The mean number of ovulated ova was 12.7 in the 15 iu eCG group and 8.0 in the 30 iu group. When rats received 4 daily doses of DEHP at 500 mg/kg, ovulation occurred in 4 of 6 rats in the 15 iu eCG group and in 1 of 3 rats in the 30 iu group. Mean numbers of ovulated ova were 2.50 and 0.33 ova in the 15 and 30 iu groups, respectively. Changes in ovarian and uterine weights were not found. Inhibition of ovulation by the injection of DEHP indicated the utility of induced ovulation in immature rats to detect reproductive toxicity in females.

Animals↗
PubMed2003

Model of CNS O2 toxicity in complex dives with varied metabolic rates and inspired CO2 levels.

INTRODUCTION: Clinical hyperbaric oxygen (HBO) therapy and the use of pure oxygen or gases having a high partial pressure of oxygen in diving carry a risk of central nervous system (CNS) oxygen toxicity. Previously, we solved the power equation K = t2(PO2/101.3)C for humans, where t is the exposure time, PO2 is the oxygen pressure, and K is the cumulative oxygen toxicity index. The value of c was 6.76, and a symptom may appear when K reaches a threshold value Kc = 2.31 X 10(8) (Arieli et al. J Appl Physiol 2002; 92:248-56). METHODS AND RESULTS: The calculation of K for a complex exposure profile made it possible to estimate risk from the normal distribution for a metabolic rate of 1.28 L x min(-1), Z = [ln(K0.5)-9.63]/2.02 and for 0.9 L x min(-1), Z = [ln(K0.5)-11.19]/1.35. The predicted risk was in agreement with the reported risk in composite exposures. The parameters c and ln(Kc) in the power equation are linearly related to metabolic rate (M) and inspired CO2 in rats. Due to the assumed similar relationship between the data from rats and humans, the mean time to CNS oxygen toxicity (tc(M)) as a function of metabolic rate may be calculated for humans as follows: tc(M) = [(e(-2.85 M + 31.8))/(PO2/101.3)(-7.45 M + 39.6)]0.5, where M is metabolic rate in units of resting metabolic rate. A parallel equation for the mean time to toxicity as a function of PCO2 was derived for the rat. This equation can be transformed to express the latency in humans, once the parameters for humans are known. CONCLUSIONS: The power equation that predicts oxygen toxicity in humans was extended to include a complex diving profile as well as the effects of metabolic rate and CO2.

Animals↗
PubMed1978

[Proposed model for evaluation of toxicity in antineoplastic chemo-hormonotherapy].

A detailed code for the evaluation of side-effects due to antiblastics in accordance with clinical, pharmacological and chronobiological parameters is described. Eight types of toxicity are recognised: systemic or local, cutaneous and adnexal, gastroenteric, haematochemical, cardiovascular, respiratory, genital and urinary, and nervous. Improvement of the objectivity and comparability of results in clinical oncology is proposed by means of a balanced points system for the expression of such effects, and methods for the summary expression of the toxicity of a single case or a uniform group of cases. The method of evaluation proposed also permits statistical comparison between different treatment protocols.

Alopecia↗
PubMed1988

Lysosomal enzyme release from macrophages: a model of food yeast toxicity evaluation.

The role of lysosomal enzyme released by macrophages was examined in relation to the toxic effect caused by food yeast. Mouse peritoneal macrophages exposed to yeast in culture showed marked release of N-acetyl glucosaminidase, beta-galactosaminidase and beta-glucuronidase below the median lethal dose (LD50). LD50 was measured from the dose response curves of the cytoplasmic lactate dehydrogenase enzyme. Saccharomyces cerevisiae showed the highest LD50 followed by Kluyveromyces fragilis and Candida utilis yeast. LD50 values obtained as well as the in vitro lysosomal release by mouse peritoneal macrophages may be relevant to assess the toxic capacity of food yeast intended for human consumption.

Animals↗
PubMed1998

Structure- and property-activity relationship models for prediction of microbial toxicity of organic chemicals to activated sludge.

Two quantitative structure-activity relationship (QSAR) and two quantitative property-activity relationship (QPAR) models reported in the literature for predicting toxicity of synthetic organic chemicals to activated sludge microorganisms are summarized and compared. The QSAR models were developed using solvatochromic parameters and molecular connectivity indices; the QPAR models, using octanol-water partition coefficient and aqueous solubility. Experimental data on 16 chemicals not used in developing the above models are used to compare and evaluate the predictive ability of these QSAR/QPAR models. Based on the quality of the original models, their predictions, ease of application, and availability of model parameters, molecular connectivity indices and log P appear to be the most suitable in toxicity predictions.

1-Octanol↗
PubMedDate not supplied

Central nervous system and cardiac effects from long-acting amide local anesthetic toxicity in the intact animal model.

With the development of the newer long-acting amide local anesthetics,ropivacaine and levobupivacaine, numerous animal studies of LA systemic toxicity have emerged. Because of the complex nature of the human response to LA intoxication, the task of designing and interpreting these animal studies of LA toxicity can be difficult. Accordingly, this report will review the selection of an animal model for the study of LA toxicity; examine the pertinent in vivo animal studies that compare the central nervous system toxicity, cardiovascular toxicity, and the ease of resuscitation of the single enantiomer local anesthetics to racemic bupivacaine; and extrapolate these findings to the clinical setting.

Amides↗
PubMed2002

The biotic ligand model and a cellular approach to class B metal aquatic toxicity.

The biotic ligand model (BLM) and a cellular molecular mechanism approach represent two approaches to the correlation of metal speciation with observed toxicity to aquatic organisms. The two approaches are examined in some detail with particular reference to class B, or soft metals. Kinetic arguments are presented to suggest situations that can arise where the BLM criterion of equilibrium between all metal species in the bulk solution and the biotic ligand may not be satisfied and what might the consequences be to BLM predictive capability. Molecular mechanisms of toxicity are discussed in terms of how a class B metal might enter a cell, how it is distributed in a cell, and how the cell might respond to the unwanted metal. Specific examples are given for copper as an organism trace essential metal, which is toxic in excess, and for silver, a non-essential metal. As class B metals all bind strongly to sulfur, regulation of these metals requires that all S(II-) species be accounted for in aquatic systems, even under oxic conditions.

Animals↗
PubMed1990

Disposition and toxicity of amphotericin-B in the hyperlipidemic Zucker rat model.

The pharmacokinetics and toxicity of the lipophilic antifungal agent, amphotericin-B (AmpB), were studied in the hyperlipidemic obese rat model and compared with lean litter-mates. Serial blood samples were obtained for 36 h following a single intravenous infusion of AmpB (1.2 mg/kg) with pre- and post-drug measurements of renal function. Although triglyceride, cholesterol, HDL-cholesterol and LDL + VLDL-cholesterol levels were elevated in the obese compared with lean rats, protein: lipoprotein ratios were similar. There was a 2-fold increase in the area under the serum concentration-time curve of AmpB in obese rats compared to lean litter-mates (15,600 +/- 6900 v. 7800 +/- 2900 ng. h/ml; P less than 0.05); no differences in elimination rate constants were found between groups. Weight-corrected volume of distribution and total body clearance were significantly lower in obese compared with lean rats; no differences were found in absolute clearance or volume. Kidney levels of AmpB were markedly increased in obese versus lean rats. Similarly, kidney to serum ratios of AmpB were greater in obese compared with lean rats (152 +/- 113 v. 41 +/- 23; P less than 0.001). There was a significant decline in the creatinine clearance from baseline in the obese rats coupled with a rise in serum creatinine; no differences were found in lean rats. Similarities in absolute pharmacokinetic variables and protein: lipoprotein ratios suggest differences in AmpB disposition and toxicity are a result of differences in lipoprotein-mediated transport mechanisms between obese and lean rats.

Amphotericin B↗
PubMed2006

Bioenergetics-based matrix population modeling enhances life-cycle toxicity assessment of tilapia Oreochromis mossambicus exposed to arsenic.

The objective of this study was to integrate a bioenergetics-based modeling approach into a population stage structure to enhance life-cycle toxicity assessments of the effects of waterborne arsenic (As) on the population dynamics of the tilapia Oreochromis mossambicus. The proposed mathematical model links a Leslie matrix population model and a universal ontogenetic growth model embedding the population-level growth rate and stage-specific modes of toxic action. We present data analyses of key parameters and distributions and discuss the processes of data capture and analysis and the impact of acute/chronic As toxicity responses on population-level effects. We employed a three-parameter Hill equation model to describe the relationship between tilapia whole-body burden and mortality in order to estimate the probability of stage-specific vital rate of survival. Using the DEBtox theory, we distinguished three modes of toxic action (MOA): direct effects on growth and indirect effects via maintenance and food consumption on inhibition by arsenic of the growth of a tilapia population. The asymptotic population growth rate decreased from lambda = 1.0027 for the control group to lambda = 0.9935 for tilapia population exposed to 4 microg mL(-1) As, indicating a potential risk of population intrinsic growth rates for tilapia exposed to higher levels of waterborne As. Our results estimated that an As concentration of 1.02 microg mL(-1) would cause a 50% reduction in the tilapia population. We found that the interplay between external stressors of waterborne As concentration and internally generated modes of action decreasing feeding in the juvenile stage and increasing the maintenance cost in the adult stage had a pronounced influence on the population stage structure of tilapia.

Animals↗
PubMedDate not supplied

A rodent model for studying four well defined toxic endpoints during bupivacaine infusion.

An animal model with four well defined endpoints for studying the cardiotoxicity and neurotoxicity of bupivacaine is described. Five male Wistar rats (264-324 g) were anesthetized, tracheostomized and ventilated, and ECG and EEG leads were placed. Femoral arteries and veins were then cannulated. Twenty minutes before bupivacaine infusion, 0.1 mg/kg pancuronium was given intravenously, and anesthesia was adjusted to halothane 0.5%, 30% O2 and 70% N2O. Bupivacaine infusion was then begun at 2 mg/kg/minute. Bupivacaine doses producing the following endpoints were then determined: (1) first ventricular arrhythmia (ARR), (2) seizures (SZ), (3) isoelectric EEG (ISO EEG), and (4) asystole (ASYS). The doses of bupivacaine (in mg/kg +/- SD) precipitating AAR, SZ, ISO EEG and ASYS were 4.22 +/- 1.87, 7.08 +/- 1.55, 11.05 +/- 5.15 and 20.4 +/- 6.49 mg/kg, respectively. These endpoints were present and readily determined in all animals. The doses of bupivacaine producing ARR and SZ were not significantly different (p greater than 0.05). The doses producing SZ, ISO EEG and ASYS were significantly different from each other (p greater than 0.05, ANOVA and the Duncan test). These results indicate that it is possible to study, in the anesthetized and paralyzed rat that is intensely monitored, many of the variables associated with local anesthetic toxicity currently of clinical interest. The use of a constant local anesthetic infusion allows ready observation of the progression of toxic signs.

Animals↗
PubMed2006

Estimating the combined toxicity by two-step prediction model on the complicated chemical mixtures from wastewater treatment plant effluents.

The toxicities of chemical mixtures containing 10 compounds, detected in wastewater treatment plant (WWTP) effluents, were investigated using Daphnia magna in a two-step prediction (TSP) model. The 10 chemicals determined by gas chromatography/ mass spectrometry in WWTP effluents included three groups: Three acetylcholinesterase inhibitors, six narcosis inhibitors, and one seedling root inhibitor. In the first step, a concentration addition (CA) model was used to predict the mixture toxicities for the three component groups with similar modes of action; in the second step, an independent action (IA) model was used for the newly developed concentration-response curves from the three CA predictions. The CA predictions did not show a statistically significant difference from the observed results with respect to the three groups of chemicals, whereas the IA model did not conform to the experimental results. Therefore, the concentration-response curves obtained from the mixture toxicity tests in each group was considered as a single curve and applied in the next step of the mixture toxicity prediction. However, the observed toxicity of the 10-chemical mixture showed large differences from the results of the IA and CA model predictions, whereas the TSP model predicted the toxicity well and with statistical significance (p = 0.0501, n = 17). This suggests that the TSP model would provide a valid prediction for a randomly selected chemical mixture having various modes of action if the concentration-response function for an individual component is obtained.

Animals↗
PubMed1991

Lead enhances lipopolysaccharide and tumor necrosis factor liver injury.

Lead markedly augments the lethality of endotoxin lipopolysaccharide (LPS) in rats. In this model of LPS toxicity, the liver is severely injured. Much of the tissue injury produced by LPS is thought to be mediated by the cytokine tumor necrosis factor (TNF). Tumor necrosis factor recently has been speculated to be a mediator of several models of liver injury such as that produced by galactosamine. To investigate the possible role of TNF in the lead-enhanced LPS toxicity model, we administered doses of lead acetate (15 mg/kg), LPS (100 micrograms/kg), or TNF (6.25 x 10(6) U/kg) that produced minimal changes in liver enzymes. However, when lead was administered simultaneously with either LPS or TNF, serum aspartate transaminase, alanine transaminase, alkaline phosphatase, glutamyl transpeptidase, and plasma triglyceride levels were markedly increased. Lead + LPS treatment increased both peak serum TNF concentrations and TNF "area under the curve" as compared with LPS alone. We conclude that lead not only enhances LPS lethality but also LPS liver injury. Furthermore, lead enhances TNF liver injury and increases LPS-stimulated serum TNF levels. These data suggest that the lead-enhanced LPS model offers a system for studying TNF-induced liver injury.

Alanine Transaminase↗
PubMed1991

Mathematical modeling of reproductive and developmental toxic effects for quantitative risk assessment.

A new mathematical dose-response model for reproductive and developmental risk assessment is proposed. The model includes the possibility of an exposure threshold as well as a litter-size effect. Correlation of responses of offspring from the same litter is taken into account through the use of the beta-binomial distribution. Confidence limits for low-dose extrapolation are based on the asymptotic distribution of the likelihood ratio. An empirical comparison of the proposed procedure to that of Rai and Van Ryzin demonstrates the improvement that can be achieved with the new procedure.

Animals↗