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Biomedical subjects

T W Schultz

Publications and source records attributed to T W Schultz.

At least 109 records · Page 6Linked to original sources
PubMed1985

Correlations for the acute toxicity of multiple nitrogen substituted aromatic molecules.

Twenty-nine compounds, including amino and nitro derivatives of aromatic hydrocarbons as well as azaarenes and indole analogs, were assayed. The biological activity was monitored as population growth to axenic cultures of the ciliate Tetrahymena pyriformis. Structure-activity relationships were examined by linear regression analysis of log biological activity (Y) and log 1-octanol/water partition coefficient (X). Partition coefficients were determined by linear regression analysis of the retention time index of HPLC data. Attempts to generate linear predictive correlations for all the test compounds (n = 29; r2 = 0.325; P greater than 0.0013) and groups, subdivided based on the following chemical classes: aromatic hydrocarbons (n = 13; r2 = 0.122; P greater than 0.2417), azaarenes (n = 9; r2 = 0.348; P greater than 0.0946) and indole analogs (n = 7; r2 = 0.743; P greater than 0.0126), met with little success. Similarly, subdivisions based on the presence of a single (n = 14; r2 = 0.514; P greater than 0.0039) or multiple H-polar groups, i.e., NO2, NH2 (n = 15; r2 = 0.195; P greater than 0.0996), met with little success also. However, if one segregates the compounds which have para oriented H-polar substituents one gets a strong linear predictive correlation (n = 11; r2 = 0.889; P greater than 0.0001). A subdivision of the remaining data set leads to two models (n = 11; r2 = 0.845; P greater than 0.0001) and (n = 7; r2 = 0.965; P greater than 0.0001). An examination of the toxicity partitioning product values suggests the three-line predictive correlation model of these data is valid.

Animals↗
PubMed1985

Structure-activity relationships of selected pyridines. I. Substituent constant analysis.

Twenty-two four-position derivatives of pyridine (C5H5N) were tested following an acute static regime with biological response being monitored as population growth of Tetrahymena pyriformis. The vinyl derivative was the most active and the hydroxy derivative was the least active. Structure-activity relationships were examined using substituent constants as molecular descriptors. Size/shape parameters and hydrophobic/hydrophilic parameters were found to be more important descriptors than electronic parameters. Following the deletion of the outliers, 4-vinylpyridine and 4-nitropyridine, molar refractivity was found to be the best single descriptor explaining 62.5% of the variability in biological response. Based on highest adjusted r2 value the best model is log BR = 0.0055 (MR) - 0.3699 (Ha) - 1.0124, r2 = 0.709 (BR, biological response; MR, molar refractivity; Ha, hydrogen acceptance). Models using Pi (hydrophobic substituent constant) as the descriptor and comparisons with previously assayed naphthalenes are discussed.

Animals↗
PubMed1985

The embryotoxic and osteolathyrogenic effects of semicarbazide.

The osteolathyrogenic agent semicarbazide was assayed for its toxicity and teratogenicity using early embryos of the frog Xenopus laevis. The 96-h LC50 is 1504.20 mg/l while the 96-h EC50 is 76.28 mg/l. Embryo length is altered prior to the onset of other effects indicated by a reduction in stage of development. The major malformation is associated with the notochord where the notochordal sheath is reduced owing to the disruption in the maturation and/or deposition of the connective tissue fibers.

Abnormalities, Drug-Induced↗
PubMed1985

Predictive correlations for the toxicity of alkyl- and halogen- substituted phenols.

The structure-activity relationships between toxicity (log BR), monitored as cell population growth, and the log 1-octanol/water partition coefficient (log Kow) for a series of 20 alkyl- and halogen-substituted phenols have been examined. The equation log BR = 0.9455 log Kow -1.9190 has been found to be an excellent linear model for these compounds. It explains 93.8% of the variability in toxicity. Subdivision of the tested derivatives based on substituent field electronic effects reveals that those with electron-releasing effects, e.g. methyl or ethyl groups, are slightly less toxic than those with electron-withdrawing effects, e.g. halogen groups.

Electrons↗
PubMed1985

Changes in leukocyte populations in pulmonary lavage fluids of calves after inhalation of Pasteurella haemolytica.

The distribution of leukocytes in bovine bronchoalveolar lavage fluids was determined in 15 calves at various times after aerosol exposure to Pasteurella haemolytica. For comparison, 10 calves were exposed to aerosols of phosphate-buffered saline solution; 15 calves, to Staphylococcus epidermidis; and 10 calves, to Salmonella typhimurium endotoxin. At 10 minutes after inhalation exposure for each group, the predominant cell type was the macrophage. Macrophages remained the predominant cell type throughout each lavage interval for calves exposed to phosphate-buffered saline solution and Staph epidermidis. For calves exposed to P haemolytica, there was a decrease in the percentage of macrophages detectable by 30 minutes after exposure, with a corresponding increase in the percentage of neutrophils. Sixty minutes after the inhalation exposure to P haemolytica, the percentages of macrophages and neutrophils in the lavage fluid were equal. By 240 minutes after exposure to P haemolytica, greater than 90% of the cells in the lavage fluids was neutrophils. The increase in the percentage of neutrophils in lavage fluids from calves exposed to S typhimurium endotoxin was similar to that seen for the calves exposed to P haemolytica.

Animals↗
PubMed1984

Percutaneous absorption: a new physicochemical predictive model for maximum human in vivo penetration rates.

A diffusion model for stratum corneum-limited percutaneous absorption based on the interaction of the diffusate with the stratum corneum was derived. Two types of interactions were proposed, ion-dipole and lipid-lipid, based on current knowledge of the stratum corneum and on irreversible thermodynamic arguments. The resulting flux equations predict a linear dependence of flux on the dipole moment and ln X of the diffusates , where X is the mole fraction solubility. These flux equations were tested on 21 different diffusates whose human percutaneous absorption rates in vivo had been previously determined. A solubility method was used to classify the interaction pathway for each diffusate . Correlation of the maximum absorption rate for the lipid and polar pathways give correlation coefficients of 0.946 and 0.998, respectively. It is believed that these studies provide a starting point for the ultimate goal of percutaneous absorption research: to be able to bypass in vivo and in vitro studies and to predict absorption solely on the basis of the physicochemical properties of the diffusates .

Chemical Phenomena↗
PubMed1984

Growth phase-dependent phagocytosis of Pasteurella haemolytica by bovine pulmonary macrophages.

The ability of the bovine pulmonary macrophage (PM) to phagocytize Pasteurella haemolytica in its logarithmic and declining phases of growth was characterized. Pulmonary macrophages were harvested from bovine lungs before and after their in vivo exposure to P haemolytica. The PM from each lavage period phagocytized P haemolytica in the declining phase of growth. However, P haemolytica in the log phase of growth was not phagocytized by PM from any of the lavage periods. Instead, PM exposed to P haemolytica in the log phase of growth had altered cellular morphologic features and were cytolytic. Pasteurella haemolytica in the log phase also inhibited phagocytosis of Saccharomyces cerevisiae by PM. This inhibition of phagocytosis, as well as morphologic alterations, was evident in PM cultures exposed to P haemolytica for less than 1 minute.

Animals↗
PubMed1983

Structure activity relationships of selected naphthalene derivatives.

Twenty-two derivatives of naphthalene were assayed under an acute static regime with biological activity being monitored as population growth of Tetrahymena pyriformis. Activity varied over one log unit. Substituent constant structure-activity analyses revealed the model, log BR = 0.282Ha + 0.352 pi + 0.692F + 0.3341Xvsub - 0.326R + 0.027, to be best and to account for 85% of the variation in log BR (BR, biological response; Ha, hydrogen acceptance; pi, hydrophobic substituent constant; F, polar electronic substituent constant, 1Xvsub, substituent molar connectivity index; R, resonance electronic substituent constant). The Ha and pi parameters are the most important, accounting for 71% of the log BR variability.

Animals↗
PubMed1983

Toxic and teratogenic effects of chemical class fractions of a coal-gasification electrostatic precipitator tar.

Dimethyl sulfoxide slurries of a coal gasifier electrostatic precipitator tar and its chemical class fractions were assayed for their toxicity and teratogenicity using early embryos of the frog Xenopus laevis. Of the 5 tar fractions the ether-soluble base and polyaromatic were found to be the most teratogenic and the ether-soluble acid and ether-soluble base were the most toxic. The teratogenic effects of the raw tar suggest synergism. The toxic effects to newly metamorphosed froglets is 1-2 orders of magnitude less than those observed for embryos. Chemical analysis shows dihydroxybenzenes and organonitrogen compounds to be the major components of the acid and base fractions, respectively. The neutral fractions contain mainly alkyl-substituted two-ring hydrocarbons.

Abnormalities, Drug-Induced↗
PubMed1982

Embryotoxic and teratogenic effects of aqueous extracts of tar from a coal gasification electrostatic precipitator.

Aqueous extracts of tar from a coal gasification electrostatic precipitator were tested for its toxic and teratogenic potential in vitro on embryos of the amphibian Xenopus laevis. The 96-h LC50 and EC50 were determined to be 0.83% and 0.48%, respectively. The developmental stage of normal-appearing exposed embryos is not affected by increasing concentrations of the extract. Embryo growth, however, is significantly reduced at concentrations as low as 0.25%. Motility and pigmentation were effectively reduced relative to controls by extract concentrations of 0.5% and greater. Exposed embryos are shorter and stockier than controls. Malformations of head, eyes, viscera, and spine are common, and cartilage formation is abnormal. The epidermis is often hyperplastic, and large blisters occur over the somatic surface. The severity of abnormal development is directly related to the concentration of the toxicant to which the embryos are exposed. Chemical analysis shows that the aqueous extracts contain phenols, furans, monoaromatic and diaromatic hydrocarbons, and mono- and diazaarenes and/or monoaromatic amines.

Abnormalities, Drug-Induced↗
PubMed1981

Toxic and teratogenic effects of selected aromatic amines on embryos of the amphibian Xenopus laevis.

Evaluations of the toxic and teratogenic effects of four aromatic amines, acridine, aniline, pyridine, and quinoline, have been made on amphibian (Xenopus laevis) embryos. For toxicity testing, the embryos were divided into three groups according to stage of development: Group I were mid-blastulae, Group II were tailbud embryos, and Group III were swimming larvae. Of the amines tested, acridine and quinoline were the most toxic, followed by aniline and pyridine. Ninety six hr LC50 values for acridine, quinoline, aniline, and pyridine were 4.5, 95, 150, and 1090 mg/L, respectively, for Group III larvae. Except for acridine, where embryos in all three groups were about equally affected, those in Group II were less sensitive to the other amines than those in Groups I and III. Group I embryos were exposed to all four amines to determine their teratogenicity. The amines were ranked in order to decreasing teratogenicity: acridine, quinoline, aniline, and pyridine having 96-hr EC50 values of 2.4, 29, 370, and 1200 mg/L, respectively. Electron microscopic examination of Group III larvae exposed to these amines reveals pathology of the spinal cord and musculature. This damage was correlated with immobility of the larvae. The uptake of acridine was followed in larvae (Group III) exposed to 5 mg/L and was found to reach a maximum level of about 85 mg/g wet weight in about one hr. Depuration kinetics were characterized by a rapid loss of 70% of the total acridine within 45 min. Acridine was undetectable after two hr. These data suggest that acridine, aniline, and quinoline have toxic and teratogenic effects at sufficiently low concentrations as to make them potential environmental hazards.

Acridines↗
PubMed1980

Uptake, depuration, and distribution of selenium in Daphnia and its effects on survival and ultrastructure.

Selenium is an important essential nutritional trace element which has been shown to provide protection against certain other metal poisoning. However, it is a suspected carcinogen and teratogen. The uptake, depuration, and toxicity of selenium in Daphnia pulex have been examined. The LC50 at 48 and 96 hr for juvenile animals is 0.6 mg/L and 0.1 mg/L respectively, and for adults it is 1.3 mg/L and 0.5 mg/L respectively. Uptake in adult unfed animals is rapid, reaching a maximum at about 12 hr, but depuration is slow. In fed animals, uptake is slower, reaching a maximum at 96 hr, but initial depuration is followed by a slower prolonged loss. Localization in cells is primarily in the cytoplasmic compartment although evidence is presented which suggests nucleolar localization. Ultrastructural damage is detected by 16 hr after exposure and is initially confined to the mitochondria. Dense deposits accumulate in the mitochondrial matrices. The nature of these deposits is unknown; they may represent a calcium- or phosphate-selenium complex. With time, the mitochondria degenerate. It is clear that relatively low concentrations of selenium are toxic to these aquatic organisms and render them incapable of survival in the natural environment. Concentrations higher than those lethal to Daphnia can be expected, at least in local areas, from the burning or conversion of fossil fuels.

Animals↗
PubMed1980

Structure-toxicity relationships of selected nitrogenous heterocyclic compounds.

A series of eleven nitrogen-containing heterocyclic compounds, which may be potentially associated with aqueous effluents from coal conversion technologies, were examined to determine the relationships between their n-octanol/H2O partition coefficients, molecular weights, boiling points, and their toxicity monitored as reproduction impairment to Tetrahymena pyriformis. Toxicity increases linearly with increased partition coefficient, molecular weight, and boiling point. All of these parameters increase with increased alkyl and ring addition.

Animals↗