Toxicity and Environmental Health Hazards of Petroleum Products in Wells Used for Drinking Water in the Intermountain West

Introduction: Groundwater is aprimary source of drinking water for about 50 percent of the population in the U.S. This source of drinking water has been generally regarded as safe from contamination. Several papers indicate that numerous underground storage tanks containing petroleum products may be leaking and contaminating public water supply wells across the U.S. (Matis, 1971; Ferguson, 1979; Woodhull, 1981; Burmaster and Harris, 1982; Lehman, 1984; Dowd, 1984; OTA, 1984). A study conducted by the Utah Cureau of Solid and Hazardous Wastes in 1985 concluded that there are at least 2,314 underground steel tanks, most of which are used to store gasoline and diesel fuel, in Utah which are more than 20 years old and may be leaking. Contamination of well water by petrolium products from leaking underground storage tanks (LUST) is a matter of increasing concern. LUST pose a serious threat to the groundwater and public health. Leaks of petroleum products from LUST at industrial plants, commercial establishments (e.g., automobile service stations), and other operations could be expected to increase the types and concentrations of petroleum products in groundwater used for drinking and exposure of humans to the toxic effects of these chemical compounds. Petroleum products are persistent and highly mobile contaminatns which are difficult to remove from groundwater. In addition, many of these chemicals are known or suspected carcinogens or mutagens which can pose undesireable human health risks (e.g., cancer, birth defects, and other chronic conditions) at 10 ppb and below (Council on Environmental Quality, 1980). There is a need for more research on the types and concentrations of petroleum products (e.g., benzene, toluene, ethylbenzene) found in public water supply wells used for drinking water and the immunotoxic and neurotoxic effects of these organic compounds. The objectives of this research project were: 1. To characterize petroleum products in raw water from wells used for drinking water in selected areas (industrial, commercial, and other) of Utah. 2. To evaluate the toxicity of selected petroleum products in experimental animals, with emphasis on the following: a. Immunotoxic and hypersensitivity effects. b. Neurotoxic and behavioral effects

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Neurobiochemical Alterations Induced by the Artificial Sweetener Aspartame (NutraSweet®)

The dipeptide aspartame (NutraSweet) is a newly approved and widely used artificial sweetener in foods and beverages. Consumption of aspartame (ASM) has been reported to be responsible for neurologic and behavioral disturbances in sensitive individuals. Unfasted male CD-1 mice were dosed orally with 13, 130, or 650 mg/kg ASM in corn oil, while control animals received corn oil alone. Three hours after dosing, the animals were killed, and the concentrations of the catecholamines norepinephrine (NE) and dopamine (DA), catecholamine metabolites 3-methoxy-4-hydroxymandelic acid (VMA), homovanillic acid (HVA), and dihydroxyphenylacetic acid (DOPAC), the indoleamine serotonin (5-HT), and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) were determined by electrochemical high-performance liquid chromatography in six brain regions. ASM exerted its primary effect on adrenergic neurotransmitters in various brain regions. In the hypothalamus, the region richest in NE, increases in NE concentrations of 12, 49, and 47% were found in the low, medium, and high dose groups, respectively, relative to control. Significant increases of NE in the medulla oblongata and corpus striatum were also observed. Increases of the catecholamine DA and catecholamine metabolites VMA, HVA, and DOPAC were seen in various regions. The indoleamine serotonin and its metabolite 5-HIAA were unaffected by ASM treatment. These findings are consistent with ASM-induced increases in the brain catecholamine precursor amino acids phenylalanine and tyrosine, as reported earlier. Such observed alterations in brain neurotransmitter concentrations may be responsible for the reported clinical and behavioral effects associated with ASM ingestion

Effect of Repeated Dietary Exposure of Aflatoxin B1 on Brain Biogenic Amines and Metabolites in the Rat

Male Sprague-Dawley rats were treated po twice weekly for 3 weeks with a low (32.8 μg/kg) and high dose (327.9 μg/kg) of aflatoxin B1 (AFB1) in corn oil. A control group received corn oil only. At the end of the experiment the rats were killed, and the concentrations of the brain catecholamines, norepinephrine (NE) and dopamine (DA), catecholamine metabolites, 3-methoxy-4-hydroxymandelic acid (VMA), homovanillic acid (HVA), and dihydroxyphenylacetic acid (DOPAC), and the indoleamine serotonin (5-HT) and its metabolite, 5-hydroxyindoleacetic acid (5-HIAA), were determined by high-pressure liquid chromatography in five brain regions. The major effects were found in striatal dopamine and serotonin concentrations, with decreases of 37 and 29%, respectively. A corresponding decline was observed in the dopamine metabolites, homovanillic acid (44%) and dihydroxyphenylacetic acid (30%). Concentrations of these neurotransmitters and metabolites were only marginally altered in cerebral cortex, cerebellum, hypothalamus, and medulla oblongata. It appears that a major effect of AFB1 is on dopaminergic pathways, possible by selectively perturbing the conversion of tyrosine to biogenic catecholamine neurotransmitters

Effects of Dietary Vanadium Exposure on Levels of Regional Brain Neurotransmitters and Their Metabolites

Adult male CD-1 mice were treated with various levels of vanadate in drinking water for 30 days. The levels of catecholamine and indoleamine neurotransmitters and their major metabolites were measured in six different brain regions. Vanadium caused a dose-related decrease in norepinephrine (NE) levels in hypothalamus, the region rich in this biogenic amine. Levels of the NE metabolite, vanillylmandelic acid (VMA), correspondingly decreased in the same region. Although hypothalamic dopamine (DA) also snowed a significant decline, vanadium had little effect on DA metabolites. Levels of 5-hydroxytryptamine (5-HT) and its metabolite, 5-hydroxyindoleacetic acid (5-HIAA), were not influenced. Levels of DA were not affected in the corpus striatum, where the highest levels of this amine are observed. Effects of vanadium on various biogenic amines and their metabolites were only marginal in other brain regions. Results suggest that vanadium has a selective effect on adrenergic pathways, and effects on other hypothalamic amines appear to be secondary. These observations support the prooxidant potential of vanadate ion on catecholamines suggested earlier

Pharmacokinetics of the Antiviral Agent 3-Deazaneplanocin A

The pharmacokinetics of 3-deazaneplanocin A (c3Nep), a competitive inhibitor of S-adenosyl-L-homocysteine (AdoHcy) hydrolase and novel antiviral agent, was investigated in female BALB/c mice. Animals were given a single intravenous dose of [3H]-c3Nep (0.1 mg/kg; 10 microCi), and blood and selected tissues were collected at various intervals thereafter for up to 72 h. The plasma concentration versus time data for c3Nep was best approximated by a two-compartment open model with first order elimination. The elimination half-life was 12.8 min, the area-under curve (AUC) was 3.38 micrograms.min.ml-1. The distribution of c3Nep into tissues was not extensive. Following 30, 120 min, and 24 h after dosing, the kidneys and the liver contained the highest amount of drug, but this amount did not exceed 1 microgram/g tissue. At these time periods, the majority of activity in the tissues represented labeled derivatives of c3Nep indicating that this compound was converted to stable metabolites. The presence of labeled conversion products in the blood confirmed that this drug is metabolized in vivo. The fact that c3Nep bound to plasma proteins in vitro may explain this drug\u27s limited tissue distribution. The half-life and tissue distribution of c3Nep were different from those of carbocyclic 3-deazaadenosine, a related adenosine nucleoside antiviral drug and AdoHcy hydrolase inhibitor

Diurnal Alterations of Catecholamines, Indoleamines and Their Metabolites in Specific Brain Regions of the Mouse

1. The diurnal variations of regional brain concentrations of dopamine (DA), norepinephrine (NE), serotonin (5-HT) and metabolites were determined in unperturbed male CD-1 mice. Determinations were made every 4 hr for 24 hr. 2. The most striking and significant variations in biogenic amines were seen in the hypothalamus, where concentrations of NE, DA and 5-HT varied in a rhythmic pattern and as much as two-fold during this period. 3. In some cases, daily alterations in parent biogenic amines were reflected by concurrent changes in their metabolites. 4. Since concentrations of neurotransmitters in the brain are often used as an indicator of stress and/or toxicity, these data should provide an accurate data base allowing for more accurate interpretation of results