Toxicology Commons^™

Effects Of Antiepileptic Drugs On Immune Function In Human Subjects And Mice, Nadine C. Margaretten

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

A number of immune abnormalities have been found in epileptic patients treated with antiepileptic drugs (AED). The alterations seen range from mild suppression of immunoglobulins to severly impaired humoral and cellular immunities. There is evidence for both drug effects and genetic or acquired factors as contributors to these abnormalities. In order to examine the basis for immune abnormalities in patients with epilepsy, a number of experimental designs were employed: clinical studies, in vitro studies, and use of an animal model.

Peripheral blood mononuclear cells (PBMC) isolated from epileptic patients currently receiving AED were found to have a reduced OKT4+/0KT8+ ratio. …

Microbial Characteristics Of An Activated Sludge And Three Commercial Preparations After Exposure To Phenolics, Laurie Gneiding

Theses

The biological characteristics of four microbial mixtures were examined after successive exposure to phenol and 2-chlorophenol at room temperature. One of the microbial mixtures was an activated sludge from the Livingston, NJ municipal wastewater treatment plant. The other three mixtures were commercial preparations sold by Polybac Corp.(Hydrobac), Sybron Corp. (BI-CHEM DC 1006/1007), and General Environmental Sciences(LLMO).

The characteristics examined were relative counts and species of gram negative/gram positive bacteria, yeast and fungi, protozoa, and higher organisms. For the gram negative bacteria and yeasts, culturing techniques and diagnostic tubes were used to determine the predominant species. Biochemical tests were done on …

Toxicological Studies On Aquatic Contaminants Originating From Coal Production And Utilization: The Induction Of Tolerance To Silver In Laboratory Populations Of Fish And The Chronic Toxicity Of Nickel To Fish Early Life Stages, Wesley J. Birge, Jeffrey A. Black, James F. Hobson, Albert G. Westerman

KWRRI Research Reports

Aquatic toxicity studies were performed on two important coal-derived contaminants, silver and nickel. Silver was investigated with regard to metal-induced tolerance in laboratory populations of the fathead minnow (Pimephales promelas). Fish were exposed to acute silver concentrations following acclimation to sublethal exposures of this metal. Based on median lethal times (LT50), animals which had received 14 days prior exposure to 1.5 and 15 μg Ag/L were three to four times more resistant to silver than were previously unexposed organisms. This metal-induced resistance was not a sustained response. After organisms which had been acclimated to 15 μg/L had been transferred to …

The Effects Of Tri-O-Cresyl Phosphate On 2',3'-Cyclicnucleotide-3'-Phosphohydrolase Activity In Neural And Non-Neural Tissue Of The Rat, Mark K. Schlager

Chemistry & Biochemistry Theses & Dissertations

A total of 44 Long-Evans rats received 5.7 g/kg tri-O-cresyl phosphate (TOCP) orally every 3 days for 6 days. A second group of 13 rats received 4.6 g/kg orally every 3 days for 6 days. Animals were administered atropine sulfate (10 mg/kg) intraperitoneally every 6 hours or as needed to alleviate cholinergic symptoms. Ten control animals were given corn oil orally. Eight rats (18%) survived the 5.7 g/kg dose regimen and 5 rats (38%) survived the 4.6 g/kg dose regimen. Surviving rats were killed at 30-33 days post-dose. Signs of delayed neuropathy included ataxia and motor impairment.

The CNP activity …

Analysis Of Selected Volatile Organic Substances Associated With Residential Kerosene Heater Use And The Health Implications, Catherine Coombs Bobenhausen

Theses

Volatile organic species (aliphatic hydrocarbons from hexane to dodecane, cyclohexane and aromatic species including benzene, toluene, ethyl benzene, m,p, and o—xylenes, nitrobenzene, styrene and naphthalene) associated with residential kerosene heater emissions were measured at two sites. One was a small room having a total volume of 23.66 cubic meters and an air change rate of 2.71 air changes per hour, and the other, a living/dining room area having a combined volume of 79.30 cubic meters and an estimated air change rate of .7 air changes per hour. The analytical procedure involved collection of a series of air samples in stainless …

Investigations Into Rates And Mechanisms Of Mercury Depuration In The Killifish, Fundulus Heteroclitus, Joanne A. Korpanty

Theses

Metallothionein (MT) and glutathione (GSH) have been shown in mammalian research to play a role in the sequestration and depuration of mercury. The sulfhydryl groups on both these peptides have a strong affinity for mercury, MT for Hg²⁺ and GSH for CH₃Hg⁺. In this study, killifish (Fundulus heteroclitus) were force-fed one piece of squid laced with labelled mercuric nitrate to give a final food concentration of 20 ppm ²⁰³Hg²⁺ and 0.03 -0.05 µg g-1 Hg²⁺ total dose. Most of the mercury, 84.1 ± 12.1% (mean ± standard deviation), is depurated within the …

Acrylamide Effects On Nerve Terminal Enzymes, Christopher S. E. Marlowe

Theses

Acrylamide causes a peripehral neuropathy. The biochemical mechanism by which it does so is the subject of intense investigation. One of the principal hypotheses for this mechanism centers on acrylamide's ability to inhibit glycolysis. This study examines the effects of in vivo exposure to acrylamide on the enzymes of the nerve terminal particle, the synaptosome.

A method for measuring glycolytic enzyme inhibition in the synaptosome was developed. Acrylamide (500 mg/kg) was administered to rats intraperitoneally. Synaptosomes were prepared by the method of Dodd et al, and lysed by sonication. GAPDH activity and NSE concentration were measured. GAPDH inhibition measured in …

Effects Of 3, 5, 6-Trichloro-2-Pyridinol On Thyroid Function, Charles Franklin Luke

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

3,5,6-trichloro-2-pyridinol, when administered in the diet, increases the feed efficiency (the ratio of weight gain to feed consumed) in various species of domestic animals and also appears to be retained in the liver at low concentrations, possibly by binding to a specific macromolecule. Because of its structural similarities to the outer ring of the thyroid hormones, trichloropyridinol and three structural analogs (2,4,5-trichlorophenol, 4-bromo-2,5-dichlorophenol, or 4-iodo-2,5-dichlorophenol) were tested for ability to compete in vitro with 3,5,3'-triiodothyronine (T₃) for nuclear receptors specific for the thyroid hormones. All four of the halogenated compounds were found to be weakly competitive for the …

Natural Killer Cell Activity And Beta-Endorphin In The Mink (Mustela Vison) And The In Vitro Effect Of Beta-Endorphin In Immunologic Assays, Nancy Cathleen Pace

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

The purpose of this study was to investigate natural killer cell activity and the possible role of beta- endorphin in a natural model of autoimmune orchitis, the dark mink.

An assay was developed to study natural killer cell activity in the mink and base-line levels of activity in this specie were determined. Natural killer cell activity was assessed in fertile mutation mink, primary infertile dark mink and secondary infertile Utah dark mink with autoimmune orchitis. The study included three sampling times: November, March and April. Natural killer cell activity was significantly lower in mink studied in April than it was …

Lead Poisoning Of Sandhill Cranes (Grus Canadensis), R. M. Windingstad, S. M. Kerr, L. N. Locke, J. J. Hurt

Papers in Ornithology

Two wild and two captive sandhill cranes (Grus canadensis) were diagnosed by National Wildlife Health Laboratory personnel as having died from lead toxicity. Ingestion of lead fishing weights by the wild cranes and of unspent .22 caliber shell cartidges by the captive cranes were responsible for these deaths. One crane force-fed lead pellets showed an increase of blood lead levels from 0.77 ppm to 23.8 ppm (wet weight) just before its death 15 days following exposure. Liver lead concentrations of sandhill cranes dying of causes other than lead toxicity are presented.

How Rabbit Poisoning Methods Work, S H. Wheeler

Journal of the Department of Agriculture, Western Australia, Series 4

While the "rabbit plauges" of the past are a distant memory for most farmers, rabbit numbers must still be controlled in many parts of Western Australia. Rabit control techniques rely heavily on poisoning, which given the right conditions can kill a high percentage of rabbits at risk.

Recent research by the Agricultural Protection Board has been aimed at determining how different poisons, baits and poisoning methods work. By knowing in detail how each method works and what influences its results, we can choose the best control method for a particular place and time, avoid costly failures, and increase the effectiveness …

1080 : A Selective Poison For Pests, D R. King

Journal of the Department of Agriculture, Western Australia, Series 4

Since the 1960s, the control programmes for rabbits and dingoes in Western Australia have relied heavily on the use of sodium monofluoroacetate, more commonly known as compound 1080. Large quantaties are used each year as it is a valuable substance for the control of vertebrate pests.

Once in the animal's body 1080 is converted to fluorocitrate, a poison which is highly toxic to most mammals. Fluorocitrate blocks the Krebs cycle, a fundamental pathway of energy exchange in animals and plants. The animal dies as a result of damage to the heart, or to the brain and central nervous system, or …

Covalent Binding And Other Mechanisms Of Primaquine Toxicity, Lucille S. K. Chau Yau

Loma Linda University Electronic Theses, Dissertations & Projects

A dose-dependent covalent binding of primaquine to mouse liver microsomal protein was found in both in vitro and in vivo studies. The binding in vitro was linear during the first 90 minutes of incubation and dependent on the concentration of mouse liver microsomal protein. The in vitro covalent binding was markedly enhanced by cofactors. Pretreatment of mice with phenobarbital, a cytochrome P450 inducer, increased the microsomal cytochrome P450 content and the in vitro covalent binding significantly. Binding was markedly inhibited when microsomal metabolism inhibitors (SK&F-525A, metyrapone and piperonyl butoxide), and sulfhydryl-contai ni ng compounds were added to the incubation system. …

The Induction Of Tolerance To Heavy Metals In Natural And Laboratory Populations Of Fish, Wesley J. Birge, William H. Benson, Jeffrey A. Black

KWRRI Research Reports

Aquatic toxicity studies were performed on two natural populations of fathead minnows. One group of organisms was taken from a metal-contaminated flyash pond associated with a coal-fired power plant and the other group was collected from relatively uncontaminated hatchery ponds. Acute tests indicated that flyash pond fish were significantly more tolerant to cadmium and copper than were hatchery fish. At an exposure concentration of 6.0 mg Cd/L in moderately hard water, the median period of survival for flyash pond fish was 50.0 hr compared to 6.8 hr for hatchery fish. Both groups of organisms were about equally sensitive to zinc. …

Residual Phytotoxicity Of Mon-097 In Sludge Enriched Soils, Jennifer A. Woods

Masters Theses

Aerobically and anaerobically digested sludges were added to soil at concentrations of 0, 1, 5, and 10% (v/v). Dry weights of Avena sativa var. Noble plants, harvested 28 days after planting, were greater with increased sludge concentrations. Plant dry weights were consistently greater with aerobically than with anaerobically digested sludge. MON-097, an acetanilide herbicide, was applied to these soil/sludge mixtures at concentrations of 0, 0.5, 1, 2, 4, 8, 16 and 32 ppm. Residual phytotoxicity of MON-097 was not significantly affected by sludge concentration. These results suggest that increased concentrations of sludge in the soil do not contribute to detoxification …

Evaluation Of Allergic Hypersensitivity To 2,4-D, Malathion, And Captafol In Mice, Janette R. Cushman

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

2,4-D-specific IgE antibodies were detected in serum of BALB/c mice using the rat passive cutaneous anaphylaxis (PCA) test following the second intraperitoneal immunization with 1, 10, or 100 ug of 2,4-D0keyhole limpet hemocyanin (KLH) conjugate administered with aluminum hydroxide adjuvant. The groups that received 1 ug of 2,4-D conjugate had the highest antibody titers (geometric mean of 60). A paper radioallergosorbent test (PRAST) was developed for determination of 2,4-D-specific IgE. The PRAST was equally as sensitive as and showed a positive correlation with the PCA assay.

The anhydride of the diacid metabolite of malathion (MMA) coupled to KLH elicited MMA-specific …

Pharmacokinetic Assessment Of The Influence Of Dietary Fiber On The Absorption And Disposition Of Selected Model Xenobiotics As It Relates To Colon Cancer, Joseph Donald Debethizy

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

Selected drugs are being utilized as models of putative colon carcinogens in a study of the influence of major types of dietary fiber upon drug pharmacokinetics. Adult, male Wistar rats were pretreated with standardized, isocaloric hydrated gelatin diets containing no fiber or 15% (w/w) cellulose, lignin, hemicellulose (metamucil), or pectin for 30 days. An additional group was fed lab chow ad libitum as a reference control.

The pharmacokinetics of acetaminophen, FD & C Red No. 2 and mirex were examined following oral administration in three separate experiments. Among fiber types, pectin and hemicellulose (Metamucil) caused higher peak plasma concentrations of …

Blood Levels Of 5-Bromo-2'-Deoxyuridine In Intraperitoneal Infusion For Determination Of Sister Chromatid Exchange Induction Using Hplc, Angelo Turturro, Narendra P. Singh, Johnny Bazare Jr., Ronald W. Hart

Journal of the Arkansas Academy of Science

A new technique was developed to measure the amount of 5-bromo-2 '-deoxyurdine (BrdUrd), a thymidine analogue, rapidly and conveniently in blood, and it was applied to measure the concentration of BrdUrd during the initiation of a paradigm for the labeling of DNA to measure the induction of sister chromatid exchanges (SCE) by genotoxic agents. Radio labelled BrdUrd was used and blood was drawn from the abdominal aorta in pregnant Sprague-Dawley derived D rats. Using the hplc, the BrdUrd peak was easily identifiable and separable from its metabolites. The BrdUrd level in the blood stabilized in 30 minutes, and a level …

Inhibitors Affecting Bacterial Action In Reaerated Activated Sludge, Alice M. Dunn

Masters Theses

Inhibition of reaerated activated sludge was assessed using reduction of dissolved oxygen uptake by the microbial population as a criterion. Oxygen uptake is essential to biodegradation of the organic components in the activated sludge process; therefore, a decrease in dissolved oxygen uptake is an indication of reduced efficiency in wastewater treatment.

The irihibitors tested were cadmium, copper, lead, mercury, silver, 2,4-Dichlorophenoxyacetic acid (2,4-D), Terbacil and Zectran. The IIC₅₀, determined by extrapolation of plotted data, for each inhibitor in mg/l was Hg (20), Cu (50), Ag (43), Cd (115), Pb (550), and 2,4-D (430). The IIC₅₀ was determined …

Influence Of Lipophilicity On The Accumulation And Distribution Of Halogenated Phenols And A Pyridinol As Metabolites Of Pesticides In The Rat, Assed A. Attumi

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

Exposure to halogenated phenols and pyridinols is of increasing concern because of their wide use and distribution. This research was initiated to determine the distribution, accumulation, and depletion of a group of halogenated phenols and a pyridinol in selected tissues of male weanling rats at different time intervals following a single oral dose of 0.33 or 1.66 m moles per kg body weight. The halogenated phenols and pyridinol were distributed differently in every tissue sampled following their administration, even though the amount administered was the same in each case. The concentrations in tissue were found in the order: 2,4,5-trichlorophenol > 4-bromo-2,5-dichlorophenol …

Alterations In Rat Brain Norepinephrine And Dopamine Levels And Synthesis Rates In Response To Five Neurotoxic Chemicals: Acrylamide, 2,5-Hexanedione, Tri-O-Tolyl Phosphate, Leptophos, And Methyl Mercuric Chloride, Charles N. Aldous

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

Acrylamide, 2,5-hexanedione, Tri-o-tolyl phosphate and leptophos belong to three fundamentally different chemical classes but all four chemicals cause central-peripheral distal axonopathy. Some of these compounds have been shown to alter brain steady state levels of neurotransmitters or to inhibit the activities of adenosine triphosphatases which are involved in the uptake and storage of biogenic amines. Tests were performed to determine alterations in steady state levels of rat brain norepinephrine and dopamine in response to doses of the above chemicals and of the central nervous system toxin, methyl mercuric chloride sufficient to cause ataxia. Catecholamine synthesis rate constant estimations were performed. …

Inhibition Of Synaptosomal Biogenic Amine Transport By A Diverse Group Of Neurotoxic Chemicals, William M. Bracken

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

Synaptosomal membrane functions were monitored, after in vitro exposure to select environmental pollutants, in synaptosomal preparations originating from rat cerebral cortices. The uptake of NE and 5HT into the synaptosomes was monitored as was the K⁺-dependent phosphate activity of the membrane. CH₃HgCl, Hg(NO₃)₂, CdCl₂, diisopropylfluorophosphate (DFP), paraoxon, acrylamide and Kepone were the test chemicals whose effects were studied.

CH₃HgCl, Hg(NO₃)₂ and Kepone had the greatest inhibitory effects on NE and 5HT uptake. The concentrations producing 50 percent inhibition (IC₅₀) were 1.4 x 10 …

The Effects Of Tri-O-Tolyl Phosphate (Totp) On The Immune System Of Mice, Craig R. Brinkerhoff

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

TOTP is a prevalent industrial and environmental contaminant which has been shown to be a neurotoxic agent. This study was undertaken to investigate the effects of this compound on the immune system. Several techniques were employed to test the humoral as well as cellular effects. Male Swiss Webster mice were administered by gastric gavage with three doses of TOTP (5, 50, and 500 mg/kg) and one dose TMTP (50 mg/kg) in corn oil once a week for 13 weeks. Control animals were given corn oil alone.

Lymphocyte transformation was determined on cultures of splenic cells obtained from animals sacrificed at …

Accumulation Of Formaldehyde And Its Relation To Postmortem Aging Of Non-Gadoid Fish Species, Mohamad A. Al-Kanhal

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

Three non-gadoid fish species, trout (Cynoscion regalis), English sole (Paraophyrys vetulus) and Pacific red snapper (Scomber japonicus) have been tested for the recovery of trimethylamine oxide (TMAO), trimethylamine (TMA), dimethylamine (DMA), and formaldehyde (FA) during postmortem storage at 4°C and -5°C. TMAO, TMA, and DMA content was determined by measuring them as the salt derivative of picric acid. FA was determined by using the 3-Methyl-2-Benzothiazolinone hydrazone test.

In muscle tissue of red snapper and English sole, it was clear that initially TMAO decreased during storage at 4°C, while the amounts of TMA, DMA, and …

Pesticide Exposure Studies: Direct And Indirect Detection Of Absorption Of 2,4-D And Pronamide Herbicides In The Guinea Pig And Occupationally Exposed Workers, Ibrahim A.R. Al-Jabery

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

A simple high pressure liquid chromatography procedure was used to determine 2,4-D and pronamide exposure in spraymen and their dermal absorption and excretion in guinea pigs.

Results of dermal application of these herbicides to guinea pigs demonstrated a strong correlation between the applied dermal dose and the urinary residue excretion over the dosage range tested. As the dosage was increased, the urinary excretion of residues was also increased. However, the excretion of 2,4-D amine mixture following dermal treatment of guinea pigs was prolonged as compared to that of pronamide.

Residue levels of these compounds were also determined to estimate skin …

A Computer Simulation Study Of Blood Cholinesterase Inhibition In Parathion Treated Rats, Scott Christopher Hennes

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

A computer simulation model of blood cholinesterase inhibition in rats resulting from a single oral or dermal dose of parathion was developed and tested. The model consists of a set of non-linear differential equations describing the absorption, distribution and metabolism of parathion and the kinetics of inhibition and reactivation of erythrocyte and plasma cholinesterase. The equations are numerically integrated to produce the time-course of each of the cholinesterase activities of the blood. The model was tested for validity by a comparison of the activities predicted by the model to values determined experimentally in male rats. The model successfully simulated plasma …

Leptophos Metabolism In The Rat: An In Vivo Study Of Oxidative Versus Conjugative Modes Of Metabolism, David Richard Hampson

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

The objectives of this research were to examine the metabolism in vivo of the pesticide leptophos in the rat under normal conditions and during inhibition of the mixed-function oxidases and during depletion of glutathione. Glutathione is a cofactor in the conjugation reactions of the glutathione-S-transferases. Both the mixed-function oxidase system and the glutathione-S-transferases have been shown to be important in the biotransformation of other organophosphate pesticides.

Urinary metabolites of leptophos were extracted, derivatized and subsequently analyzed by gas-liquid chromatography. The methods used to analyze for alkyl phosphonates were subject to several shortcomings and modifications of the original procedure were necessary. …

Effects Of Organic Compounds On Amphibian Reproduction, Wesley J. Birge, Jeffrey A. Black, Robert A. Kuehne

KWRRI Research Reports

Aquatic toxicity tests were conducted with atrazine, carbon tetrachloride, chloroform, methylene chloride, trisodium nitrilotriacetic acid (NTA), and phenol. Each compound was administered to developmental stages of three to five amphibian species. Exposure was initiated at fertilization and maintained through 4 days posthatching. Test responses included lethality and teratogenesis. Different amphibian species exhibited varying degrees of tolerance to the selected compounds. Greatest tolerance usually was observed for the more broadly adapted semi-aquatic and terrestrial species (e.g., Bufo americanus, Bufo fowleri). The more sensitive amphibians usually included those species which normally are restricted to aquatic or moist habitats (e.g., Rana …

Metals In Apple Cider Produced And Marketed In Connecticut, Dennis W. Hill, Thomas R. Kelley, Gale R. Morrow, Sylvia W. Matiuck

Storrs Agricultural Experiment Station

No abstract provided.

Bulletin 3967 - Cyanogenetic Plants Of Western Australia, T E H Aplin

Bulletins - 3000 - 3999

This article deals with those native, naturalized and cultivated plants, which by virtue of contained cyanogenetic glycosides, are known to be poisonous or potentially poisonous to livestock in Western Australia.

Cyanogenetic glycosides are chemical compounds which contain a cyanogen (cyanide) radical combined with a sugar molecule. The sugar moiety may differ in glycosides obtained from different plants, and as a consequence glycosides from different plants, containing different sugar moieties, may be given different names.

When a cyanogenetic glycoside is broken down by enzyme action, through injury to the plant or by microbial action in the digestive system of the animal, …