Terry W Schultz

Structure-activity relationships for osteolathyrism: IV. Para-substituted benzoic acid-hydrazides and alkyl carbazates

D.A. Dawson — Mon, 25 Oct 2010 11:12:13 PDT

Structure-activity relationship for methyl and/or chloro substituted anilines and the polar narcosis mechanism of toxicity

L.M. Arnold — Mon, 25 Oct 2010 11:05:44 PDT

The relative toxicity of 32 methyl- and/or chloro-substituted anilines was assessed in the 48-h sublethal, static Tetrahymena pyriformis population growth assay. Quantitative structure-activity relationships (QSARs) were examined. Regression analysis of toxicity (log IGC₅₀⁻¹) versus the 1-octanol/water partition coefficient (log K_OW) showed excellent correlation as revealed by the equation log IGC₅₀⁻¹ = 0.698 (log K_OW) −1.190; n= 23, r-square= 0.931, s= 0.136, f= 282.47, Pr > f= 0.0001. This equation is considered to represent the polar narcosis mode of action. Nine derivatives were not included in the model. The parent compound aniline and the 4-chloro derivative were observed to be more toxic than predicted. The seven di- and trimethyl derivatives were observed to be less toxic than predicted. The latter seven derivatives could be included in the model with the addition of the summation of the Hammett sigma constants (∑σ) as a second descriptor, log IGC₅₀⁻¹ = 0.428 (log K_OW) + 0.733 (∑σ) −0.828; n= 30, r-square= 0.919, s= 0.169, f= 153.60, Pr > f= 0.0001. Abiotic loss was not considered to be a factor in the observed toxicities.

Structure-toxicity relationships for selected weak acid respiratory uncouplers

M. Cajina-Quezada — Mon, 25 Oct 2010 10:56:33 PDT

The relative biological response (log BR) for each of 30 select substituted phenols and anilines was evaluated using the 48-h Tetrahymena pyriformis population growth test system. Simple linear regression analysis of log BR versus log Kow (1-octanol/water partition coefficient) was used to formulate a quantitative structure-activity relationship (QSAR). The equation, log BR = 0.438 (log Kow) + 0.157; n=27, r2 =0.933, s = 0.151, f=348.02, is a highly predictive model. An evaluation of data on fathead minnow mortality for these same compounds shows a similar QSAR, log LC50= −0.590 (log Kow)− 3.247; n = 11, r2 = 0.917, s = 0.287, f=99.04. These relationships are the respective QSARs for the respiratory uncoupling mechanism of action of selected weak acids. Moreover, the toxic response in the two systems are highly correlated (r2 = 0.915).

Comparative toxicity of selected nitrogen-containing aromatic compounds in the Tetrahymena pyriformis and Pimephales promelas test systems

Terry W. Schultz — Mon, 25 Oct 2010 10:50:20 PDT

Structure-toxicity relationships for selected benzyl alcohols and the polar narcosis mechanism of toxicity

Terry W. Schultz — Mon, 25 Oct 2010 10:43:38 PDT

The relative toxicity of 20 ortho-, meta-, and para-position monoalkylated or monohalogenated benzyl alcohols has been determined as 50% population growth inhibition (log BR; biological response) to Tetrahymena pyriformis. Linear relationships are observed between log BR and the 1-octanol/water partition coefficient (log Kow) for both the alkylated and the halogenated series. Regression analysis of the combined data results in poor correlation with the model, log BR = 0.7085(log Kow) − 1.3018; n = 20, r2 = 0.644, s = 0.323. However, the predictability of this quantitative structure-activity relationship (QSAR) is sharply enhanced by the addition of the Hammett sigma constant (σ) as a second molecular descriptor, log BR = 0.8395(log Kow) + 1.4322 (σ) − 1.6823; n = 20, r2 = 0.923, s = 0.154. This latter QSAR uses the para-position σ as an estimator of ortho-position effects and compares well with previous work with alkyl- or halogen-substituted phenols. It is thought to model the polar narcosis mode of toxic action.

Pulmonary lesions induced by Pasteurella haemolytica in neutrophil sufficient and neutrophil deficient calves

M.A. Breider — Mon, 25 Oct 2010 08:26:23 PDT

The role of neutrophils in the development of peracute lung lesions of bovine pneumonic pasteurellosis was investigated. Eight calves were divided into two groups of four calves each. Group I was treated with intravenous phosphate-buffered saline and served as the neutrophil sufficient calves. Group II was treated with intravenous hydroxyurea which produced a state of neutropenia. When peripheral blood neutrophil numbers dropped below 300 cells/microL in group II, all calves were challenged with an intrabronchial bolus of Pasteurella haemolytica in the log phase of growth. An acute inflammatory process occurred in both groups of calves indicated by a rise in body temperature. While pulmonary lesions occurred in both groups by six hours postinoculation, they varied in pathological characteristics. Pulmonary lesions in the neutrophil sufficient calves consisted of fibrinopurulent alveolitis-bronchiolitis with associated alveolar septal necrosis, interlobular edema, and intravascular thrombi. The neutrophil deficient calves had extensive intra-alveolar edema, interlobular edema, intraalveolar hemorrhage, atelectasis, and focal areas of alveolar septal necrosis. These results show that P. haemolytica can induce severe pulmonary tissue damage through both neutrophil dependent and neutrophil independent mechanisms.

Structure-activity relationships for osteolathyrism: I. Effects of altering the semicarbazide structure.

Terry W. Schultz — Mon, 25 Oct 2010 08:04:30 PDT

The toxic and osteolathyrogenic effects of 15 chemicals reflecting modifications of semicarbazide [H2N-N(H)-C(=O)-NH2] were evaluated using the Frog Embryo Teratogenesis Assay: Xenopus (FETAX). Osteolathyrism, the failure of connective tissue fibers to cross-link correctly, is expressed as gross alterations in the long axis of the embryo and a sinusoidal configuration of the notochord. Alteration (addition or subtraction) at the hydrazino (H2NNH-) end of the molecule sharply reduces osteolathyrogenic activity. Alteration at the amino (H2N-) end of the molecule results in a graded response. The replacement of oxygen with sulfur causes no loss of osteolathyrogenic activity.

Teratogenic effects of benzoyl hydrazine on the frog embryo

Terry W. Schultz — Fri, 22 Oct 2010 12:01:25 PDT

The toxic and osteolathyrogenic effects of benzoyl hydrazine were evaluated using the Frog Embryo Teratogenesis Assay: Xenopus (FETAX), a rapid and inexpensive in vitro test system. Osteolathyrism, a connective tissue lesion associated with decreased intermolecular bonding in collagen and elastin, is manifested in early embryos as alterations in the long axis of the animal. Morphological examination, including electron microscopy, reveals that gross effects were produced by changes in connective tissue fibers of the notochordal sheath. The effects of benzoyl hydrazine were concentration-, and to a lesser extent developmental stage- (incubation temperature), dependent. The 25C 96- hour LC50 and EC50 values were determined to be 113.68 mg/liter and 58.58 mg/liter, respectively. The 20C 96-hour LC50 and EC50 values were determined to be 671.55 mg/ liter and 85.37 mg/liter, respectively. The 25C and 20C 96-hour teratogenic indices (LC50/EC50) of 1.9 and 7.9, respectively, suggest that benzoyl hydrazine is a developmental hazard.

Comparisons of several structure-activity relationships for chlorophenols

M.P. Moulton — Fri, 22 Oct 2010 11:54:27 PDT

We compared the toxic response of chlorophenols from 10 different test systems. These systems used various experimental protocols including phylogenetically diverse test species. The best statistical model for explaining variation in toxic response (log TR) with changes in hydrophobicity (log Kow) was a traditional analysis of covariance model. This model consists of a set of parallel lines corresponding to the different test systems. The y-intercepts for these lines fell into four clearly defined subgroups. In general, the toxic response of a given chlorophenol in one system could be used to predict its toxic response in other systems.

Structure-activity relationships of selected pyridines

M.P. Moulton — Fri, 22 Oct 2010 11:46:34 PDT

Principal components analysis was used in conjunction with linear regression analysis to examine the structure-activity relationships of a diverse group of 20 para-substituted pyridines. Eight substituent constants were used as initial molecular descriptors. Principle components analysis was used to define four new orthogonal variables which in turn were used as independent variables to describe the biological activity of the pyridines. These results agree with previously completed multiple regression analyses and reveal that shape/size and hydrophobic factors are more important than electronic factors in predicting the toxicity of para-substituted pyridines.

Structure-activity relationships for nitrogen-containing aromatics

Terry W. Schultz — Fri, 22 Oct 2010 11:27:37 PDT

Twenty-four nitrogen-containing aromatic molecules, mono- and dicyclic homologs from each of 12 different analog sets, were studied to determine their relative acute static toxicities, monitored as population growth impairment to the ciliate Tetrahymena pyriformis. Quantitative structure-activity correlations between the molecular descriptors log l-octanol/water partition coefficient (log Kow) and log toxicity are reported. Using the complete data set the descriptor does not provide an adequate model for predictability. A scatter plot of log Kow versus log toxicity suggests two parallel linear correlations: one consisting of the more complex multiple H-polar nitrogen-containing compounds and the other with the single H-polar and in-ring substituted nitrogen-containing compounds.

The mitigation of acute toxicity of coal-derived liquids by hydrotreatment

Terry W. Schultz — Fri, 22 Oct 2010 11:18:37 PDT

Acute toxicity of 12 coal derived liquids representing 3 different technologies and 4 different severities of hydrotreatment has been examined with the Tetrahymena population growth bioassay. Tetrahymena were exposed to various concentrations of the organic materials and growth impairment was monitored. In addition, analyses of the major organic elements in the coal liquids are presented. Coal-derived liquids have a greater heteroatom and aromatic content than do natural crude oils. Hydrotreatment, the catalytic addition of hydrogen, concomitantly reduces toxicity as well as heteroatom content and aromaticity. Regression analysis of log toxicity vs % weight of the major organic elements suggests hydrogen content may be a good indicator of relative toxicity of coal-derived liquids.

Teratogenicity and embryotoxicity of monosodium methanearsonate herbicide

Terry W. Schultz — Fri, 22 Oct 2010 10:25:44 PDT

The teratogenicity and embryotoxicity of the herbicide monosodium methanearsonate (MSMA) to early embryos of Xenopus laevis has been studied. The 96-hour LC50 (concentration that causes 50% lethality) and EC50 (concentration that causes 50% survivors to be abnormal) values for embryos are 225 and 46 mg/liter, respectively. This is in contrast to adult 96-h LC50, which is 1,132 mg/liter. Sublethal effects on early embryos include stunted development and malformations. The severity of these effects is directly dependent upon concentration, length of exposure, and time of initial exposure. Major malformations include optic and musculature defects.

Structure activity relationships of selected naphthalene derivatives

Terry W. Schultz — Fri, 22 Oct 2010 10:17:07 PDT

Acute cytotoxicity of fossil energy-related comparative research materials.

Terry W. Schultz — Fri, 22 Oct 2010 10:13:20 PDT

Aqueous extracts of five fossil-energy-related comparative research materials have been examined under acute static conditions for toxic effects by use of the Tetrahymena assay system. Cells were exposed to various concentrations of extracts, and cytolysis and population growth impairment were monitored. In addition, chemical class fractionation and major organic elemental analysis were performed. Synthetic fossil fuel materials are more toxic than conventional petroleum crude oils and coal-derived materials are more toxic than crude shale oil. Synthetic fossil-fuel-related materials have a higher nitrogen and oxygen content and a greater aromaticity than do natural crude oils. Acute toxicity appears to be correlated with ether-soluble acid (phenolic) content, mono- and diaromatic hydrocarbon content, and ether-soluble base (primary aromatic amines and azaarenes) content.

Toxicity of Santa Barbara, California, USA seep oil to starfish (Patiria miniata) embryos. 2. The growth bioassay

P.H. Davis — Fri, 22 Oct 2010 09:36:38 PDT

The asteroid Patiria miniata was used to develop a static bioassay for various crude oil water-soluble fractions (WSF). The criterion used is the size of 48-h exposed embryos. The reasons for choosing this species and the growth criterion are discussed. Experiments show that the body length of 48-h exposed embryos is inversely proportional to hydrocarbon concentration of the WSF and the time of exposure. It is also shown that the toxicity of the WSF decreases with the age of the preparation and that the first 12 h following fertilisation are most sensitive to the effects of WSF.

Cytotoxicity of acridine, a synfuel component, to Tetrahymena

Terry W. Schultz — Fri, 22 Oct 2010 09:32:34 PDT

Histochemical analysis of the goblet cell matrix in the larval midgut of Manduca sexta

Terry W. Schultz — Fri, 22 Oct 2010 09:29:39 PDT

Experimental analyses were made to histochemically determine the composition of the goblet cell matrix material in the larval midgut of the tobacco hornwormn, Manduca sexta. Techniques employed following fixation in Carnoy fluid were the periodic acid-Schiff reaction and the alcian blue stain at pH 1.0 and pH 2.5 and following inethylation and subsequent saponification. The cumulative evidence suggests that the plug material is an acid mucosubstance.

Effects of coal gasification sour water on Xenopus laevis embryos

J.N. Dumont — Fri, 22 Oct 2010 09:24:31 PDT

The untreated sour water from a coal-gasification process has been examined for toxic and teratogenic effects on the embryos of the amphibian Xenopus laevis. Embryos were exposed to varying concentrations of sour water, and the number of deaths and abnormals as well as motility, pigmentation, and stage of development were monitored. Increases in toxicity and teratogenicity were directly related to both concentration and time of exposure. The sour water also caused a reduction in motility, pigmentation, and rate of embryonic development.

Cytotoxicity of untreated coal liquefaction process water (and a comparison with gasification process water)

Terry W. Schultz — Thu, 21 Oct 2010 12:34:39 PDT

The untreated scrubber water from the Char Oil Energy Development coal liquefaction process was examined for pernicious effects on the protozoan Tetrahymena pyriformis. Cells were exposed to varying concentrations of process water; their behavior, oxygen uptake, and population growth were monitored. Reduction in cell number and motility are directly related to both concentration and length of exposure with concentrations up to 5% and exposures up to 24 hr. The product water causes a nonlinear, dose-dependent reduction in oxygen uptake over a 2 to 5% concentration range. Population growth is reduced by concentrations as low as 0.2% process water. Both the growth rate and the final density of the test populations are inversely related to concentration over the range of 0.2 to 1%. Comparisons with the coal gasification product water are discussed.

Structure of the ephippium of Daphnia pulex (Crustacea: Cladocera)

Terry W. Schultz — Thu, 21 Oct 2010 12:30:09 PDT

The external surface of the ephippium of Daphnia pulex bears numerous, randomly distributed pits which are formed by the thickening of the brood chamber cuticle. The internal surface is covered by a thin amorphous sheet below which lies a polygonal matrix or lattice. In section, the wall of the ephippium is shown to be formed by several layers. The exterior is the thing epicuticle. The second or middle layer, the procuticle, is subdivided into an outer, thick laminated or banded region, a middle polygonal matrix of varying thickness, and an inner, thin, irregular lattice region. Innermost is an amorphous noncellular later within which are observed bacteria-like particles.

Analyses of the integument and muscle attachment in Daphnia (Crustacea: Cladocera)

Terry W. Schultz — Thu, 21 Oct 2010 12:21:45 PDT

The Cytotoxic effects of the herbicide 3-amino-1,2,4-triazole on Daphnia pulex (Crustacea: Cladocera)

Terry W. Schultz — Thu, 21 Oct 2010 12:08:30 PDT

Zero to 24 hour old specimens of Daphnia were exposed to 10 ppm 3-amino-1,2,4-triazole at 24° C until immobilized. The most consistent alteration in cell structure was expressed by the mitochondria especially those of muscle fibers. Not all muscle cells within a single animal nor all mitochondria within a single cell were affected equally. The most common alteration observed was folding of the outer membrane. This was accompanied by organelle swelling and a reduction in electron density of the ground matrix and number of cristae.In addition other cytotoxic effects were observed. These included general tissue swelling, disarrangement of myofilaments and dissociation of membranes. Mobile 0-24 hr old daphnids which were exposed to the herbicide for up to 15 hr showed no cell or organelle damage regardless of length of exposure.Data from acute static experiments suggest that the time of immobility is closely related to molt for 0-24 hr juveniles.

The ultrastructure of the hepatopancreatic caeca of Grammarus minus (Crustacea: Amphipoda)

Terry W. Schultz — Thu, 21 Oct 2010 12:03:56 PDT

The hepatopancreatic caeca of the freshwater amphipod Gummarus minus are four tapered blind pouches lined with a simple columnar epithelium bearing an apical surface of regular microvilli and resting on a basement membrane. This epithelium is enclosed by a tonic, striated muscularis. Each caecum consists of three regions. The distal zone is formed of embryonic cells having a high nuclear to cytoplasmic ratio and giving rise to the other cell types. The second or differentiation zone consists of regular tall columnar cells of two morphological types:(1) light staining R-cells which have a large number of lipid droplets and few Golgi bodies; (2) basophilic F-cells which have numerous distended Golgi bodies. The more proximal secretory zone forms the majority of each diverticulum. This mature zone is formed from R-cells and large, basophilic, vacuolated B-cells which differentiate from F-cells. The secretory cell sequence appears to be E-cell — F-cell — B-cell with secretion being apocrine in nature. The exact relationship of Rcells to the other cell types is questionable, but the R-, F - and B-cells all appear to be able to absorb and store nutrients. Within the Malacostraca the hepatopancreatic epithelium of Amphipoda more closely approximates that of Decapoda than that of the Isopoda.

Functional Morphology of the Oral Appendages and Foregut of Lirceus Garmani (Crustacea: Isopoda)

Terry W. Schultz — Wed, 20 Oct 2010 08:43:13 PDT

Lirceus garmani illustrates the typical malacostracan arrangement of oral appendages. The mandibles, first maxillae, and second maxillae originate from the cephalon, whereas the maxillipeds are derived from the first thoracic segment.

Digestive Anatomy of Lirceus Fontinalis Rafinesque (Crustacea: Isopoda)

Terry W. Schultz — Wed, 20 Oct 2010 07:55:01 PDT

The fresh-water isopod Lirceus fontinalis has a straight tubular digestive tract which for convenience is divided into a foregut, an intestine, a rectum, and two pair of lateral caeca. The esophagus, cardiac, and pyloric chambers collectively form the foregut. The gastric armature, an elaboration of the chitinous intima, provides the triturating mechanism of the cardiac chamber. The intima of the pyloric chamber forms a pressing and straining apparatus. The intestine, possessing a dorsal longtitudinal typhlosole and intestinal sphincter, is joined anteriorly by the two pair of lateral hepatopancreatic caeca. The rectum is short and terminated by way of the anus. The foregut and rectum are histologically similar, their walls consisting of a chininous intima, a mucosa of columnar epithelium, continuous bands of circular muscle, and scattered strands of longitudinal muscle. Histologically, the intestine is cellular in nature and possesses a chitinous intima. The muscularis of the midgut forms a segmented checkerboard pattern of spaced inner circular bands and spaced outer longitudinal bands, the hepatopancreatic caeca are hollow blind tubes composed of two types of cells.