Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Methanol”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 127 records · Page 7Linked to original sources
PubMed1992

Physiologically based pharmacokinetic model for methanol in rats, monkeys, and humans.

The pharmacokinetics of methanol and formate were characterized in male Fischer-344 rats and rhesus monkeys exposed to methanol vapor concentrations between 50 and 2000 ppm for 6 hr. End-of-exposure blood methanol concentrations were not directly proportional to the atmospheric concentration. The methanol exposures did not cause an elevation in blood formate concentrations. After an intravenous dose of [14C]methanol in rats, metabolism, exhalation, and renal excretion contributed 96.6, 2.6, and 0.8%, respectively, to the elimination of blood methanol concentrations. These values and the calculated renal methanol extraction efficiency (0.007) are nearly identical to those for humans after low doses of methanol. A physiologically based pharmacokinetic model was developed to simulate the in vivo data. In order to simulate the observed blood methanol concentrations in the inhalation studies in rats, a double pathway for methanol metabolism to formaldehyde was used. One path used rodent catalase Km and Vmax values and the other used a smaller Km and Vmax to simulate an enzyme with a higher affinity and lower capacity. The lack of proportionality observed in end-of-exposure blood methanol concentrations may be due to saturation of an enzyme with higher affinity and lower capacity than catalase. The physiologically based pharmacokinetic model was modified to simulate the monkey data and was scaled-up for humans. In order to simulate the monkey blood methanol concentrations, the use of rodent catalase parameters for methanol metabolism was required. This finding suggests that primates and rodents may be similar in the initial step of methanol metabolism after low methanol doses. Previously published human urinary methanol excretion data was successfully simulated by the model. The models were used to predict the atmospheric methanol concentration range over which the laboratory species exhibit quantitative similarities with humans. Below 1200 ppm, all three species exhibit similar end-of-exposure blood methanol concentrations and a linear relationship between atmospheric and blood methanol concentrations. At higher atmospheric concentrations, external and internal methanol concentrations increase desparately, suggesting that delivered dose rather than exposure concentration should be used in interpreting data from high-dose studies.

Administration, Inhalation↗
PubMed1985

Growth substrate effects on acetate and methanol catabolism in Methanosarcina sp. strain TM-1.

When Methanosarcina sp. strain TM-1 is grown in medium in which both methanol and acetate are present, growth is biphasic, with methanol used as the primary catabolic substrate during the first phase. To better understand this phenomenon, we grew cells on methanol or on acetate or on both and examined the abilities of anaerobically washed cells to catabolize these substrates. Washed acetate-grown cells incubated with 10 mM acetate, 10 mM methanol, or both substrates together produced methane at initial rates of 325, 3, and 315 nmol min-1 mg of protein-1, respectively. Although the initial rate of methanogenesis from both substrates was nearly identical to the rate for acetate alone, after several hours of incubation the rate was greater for cells provided with both substrates. Studies with 14C-labeled methanol indicated that methanol was catabolized to methane at increasing rates by acetate-grown cells in a manner reminiscent of an induction curve, but only when cells were provided with acetate as a cosubstrate. Acetate was presumably providing energy and carbon for induction of methanol-catabolic enzymes. Methanol-grown cells showed a pattern of substrate utilization significantly different from that of acetate-grown cells, producing methane from 10 mM acetate, 10 mM methanol, or both substrates at initial rates of 10, 280, and 450 nmol min-1 mg of protein-1, respectively. There was significant oxidation of the methyl group of acetate during metabolism of both substrates. Cells grown on methanol-acetate and harvested before methanol depletion (methanol phase) showed catabolic patterns nearly identical to those of methanol-grown cells, including a low rate of methanogenesis from acetate. Cells harvested from methanol-acetate cultures in the acetate phase were capable of significant methanogenesis from either methanol or acetate alone, and the rate from both substrates together was nearly equal to the sum of the rates for the single substrates. When both 10 mM methanol and 10 mM acetate were presented to the acetate-phase cells, there was a preference for the methanol. These results are consistent with a model for regulation in Methanosarcina sp. strain TM-1 in which methanol represses acetate catabolism while methanol catabolism is inducible.

Acetates↗
PubMed2002

American Academy of Clinical Toxicology practice guidelines on the treatment of methanol poisoning.

EPIDEMIOLOGY: Almost all cases of acute methanol toxicity result from ingestion, though rarely cases of poisoning have followed inhalation or dermal absorption. The absorption of methanol following oral administration is rapid and peak methanol concentrations occur within 30-60minutes. MECHANISMS OF TOXICITY: Methanol has a relatively low toxicity and metabolism is responsible for the transformation of methanol to its toxic metabolites. Methanol is oxidized by alcohol dehydrogenase to formaldehyde. The oxidation of formaldehyde to formic acid is facilitated by formaldehyde dehydrogenase. Formic acid is converted by 10-formyl tetrahydrofolate synthetase to carbon dioxide and water. In cases of methanol poisoning, formic acid accumulates and there is a direct correlation between the formic acid concentration and increased morbidity and mortality. The acidosis observed in methanol poisoning appears to be caused directly or indirectly by formic acid production. Formic acid has also been shown to inhibit cytochrome oxidase and is the prime cause of ocular toxicity, though acidosis can increase toxicity further by enabling greater diffusion of formic acid into cells. FEATURES: Methanol poisoning typically induces nausea, vomiting, abdominal pain, and mild central nervous system depression. There is then a latent period lasting approximately 12-24 hours, depending, in part, on the methanol dose ingested, following which an uncompensated metabolic acidosis develops and visualfunction becomes impaired, ranging from blurred vision and altered visual fields to complete blindness. MANAGEMENT: For the patient presenting with ophthalmologic abnormalities or significant acidosis, the acidosis should be corrected with intravenous sodium bicarbonate, the further generation of toxic metabolite should be blocked by the administration of fomepizole or ethanol and formic acid metabolism should be enhanced by the administration of intravenous folinic acid. Hemodialysis may also be required to correct severe metabolic abnormalities and to enhance methanol and formate elimination. For the methanol poisoned patient without evidence of clinical toxicity, the first priority is to inhibit methanol metabolism with intravenous ethanol orfomepizole. Although there are no clinical outcome data confirming the superiority of either of these antidotes over the other, there are significant disadvantages associated with ethanol. These include complex dosing, difficulties with maintaining therapeutic concentrations, the need for more comprehensive clinical and laboratory monitoring, and more adverse effects. Thus fomepizole is very attractive, however, it has a relatively high acquisition cost. CONCLUSION: The management of methanol poisoning includes standard supportive care, the correction of metabolic acidosis, the administration of folinic acid, the provision of an antidote to inhibit the metabolism of methanol to formate, and selective hemodialysis to correct severe metabolic abnormalities and to enhance methanol and formate elimination. Although both ethanol and fomepizole are effective, fomepizole is the preferred antidote for methanol poisoning.

Ethanol↗
PubMed1998

Differential effects of methanol on rat aortic smooth muscle.

The effects of methanol on isolated segments of rat aorta were investigated. In the absence of any vasoactive agent, methanol (5-675 mM) failed to alter basal tension. In rat aortic rings precontracted with high K+ (30 mM), methanol elicited a concentration-related relaxation at concentrations of from 5 to 675 mM. The K+-induced contraction in the presence of endothelium was more strongly inhibited by methanol than in the absence of endothelium. The effective concentration producing approximately 50% of the maximal relaxation response (ED50) to methanol was about 96 mM. Methanol-induced relaxations could not be abolished either by 5 x 10(-5) M N-nitro-L-arginine methyl ester (L-NAME) or NG-nitro-L-arginine (L-NNA), both selective inhibitors of nitric oxide (NO) formation; these relaxations were not potentiated by addition of excess L-arginine. An inhibitor of prostanoid synthesis, indomethacin (10(-5) M), had no effects on methanol-induced relaxation. Removal of extracellular Ca2+ ([Ca2+]o) resulted in almost complete inhibition of the relaxant effects of methanol on rat aortic ring segments. Marked attenuation of the relaxation responses of intact arteries to methanol was obtained after buffering intracellular Ca2+ ([Ca2+]i) with 10 microM BAPTA-AM. In 5-hydroxytryptamine (5-HT, 2.5 microM)- or phenylephrine (PE, 0.1 microM)-precontracted rat aortic rings, methanol amplified contractile responses to 5-HT and PE; these increased responses were concentration dependent. No significant differences in these methanol potentiated responses were found between aorta with or without endothelial cells. The amplified rat aortic smooth muscle responses induced by methanol after PE could be modified only by phentolamine, an antagonist of PE, while responses to 5-HT could be inhibited by methysergide (an antagonist of 5-HT) and by phentolamine, diphenhydramine, and haloperidol. Pretreatment with 50, 200, and 500 mM methanol increased rat aortic contractile responses induced by 5-HT and PE. Our results suggest that: (a) acute methanol exposure relaxes rat aortic smooth muscle contractile responses induced by high K+, leading to vessel relaxation. This relaxation effect of methanol is endothelium-dependent, clearly Ca2+ dependent, and independent of endogenous vasodilators such as acetylcholine, histamine, catecholamines, serotonin, or PG. (b) Methanol seems to increase potassium current by shifting the potential towards more negative values in depolarized vascular muscle cell membranes, probably inducing hyperpolarization of the cell membranes leading to a repolarization. (c) In contrast to the relaxant responses, methanol potentiates contractile response of rat aorta to 5-HT and PE.

Animals↗
PubMed1996

Methanol inhalation: site and other factors influencing absorption, and an inhalation toxicokinetic model for the rat.

PURPOSE: This investigation was conducted to identify the site and characteristics of methanol absorption and to develop an inhalation model relating methanol absorption, blood concentration, and elimination. METHODS: Rats were exposed to methanol in chambers that allowed measurement of methanol uptake, ventilation, and blood concentrations; anesthetized rats with a tracheal cannula were examined to determine tracheal concentrations. In separate experiments, methanol exposed rats received an iv methanol bolus to examine the effect of blood methanol on ventilation and absorption; ventilation also was manipulated by CO(2) or pentobarbital to assess the effect of ventilation rate on methanol absorption. These data were combined to construct a semi-physiologic model of methanol uptake. RESULTS: Only 1-3 percent of inhaled methanol reached the trachea, primarily from systemic methanol partitioning into the trachea; blood methanol did not alter methanol absorption. Manipulation of ventilation and application of the pharmacokinetic model indicated that ventilation was less significant than environmental methanol concentration in determining the fraction of inhaled methanol absorbed, although both parameters were important determinants of the total mass absorbed. CONCLUSIONS: These data indicate that methanol uptake is a complex process that depends upon several parameters. Despite these complexities, a relatively simple semi-physiologic model was capable of describing methanol uptake over a wide range of exposure concentrations in the rat.

Administration, Inhalation↗
PubMed1995

Chloroform degradation in methanogenic methanol enrichment cultures and by Methanosarcina barkeri 227.

The effects of methanol addition and consumption on chloroform degradation rate and product distribution in methanogenic methanol enrichment cultures and in cultures of Methanosarcina barkeri 227 were investigated. Degradation of chloroform with initial concentrations up to 27.3 microM in enrichment cultures and 4.8 microM in pure cultures was stimulated by the addition of methanol. However, methanol consumption was inhibited by as little as 2.5 microM chloroform in enrichment cultures and 0.8 microM chloroform in pure cultures, suggesting that the presence of methanol, not its exact concentration or consumption rate, was the most significant variable affecting chloroform degradation rate. Methanol addition also significantly increased the number of moles of dichloromethane produced per mole of chloroform consumed. In enrichment cultures, the number of moles of dichloromethane produced per mole of chloroform consumed ranged from 0.7 (methanol consumption essentially uninhibited) to 0.35 (methanol consumption significantly inhibited) to less than 0.2 (methanol not added to the culture). In pure cultures, the number of moles of dichloromethane produced per mole of chloroform consumed was 0.47 when methanol was added and 0.24 when no methanol was added. Studies with [14C]chloroform in both enrichment and pure cultures confirmed that methanol metabolism stimulated dichloromethane production compared with CO2 production. The results indicate that while the addition of methanol significantly stimulated chloroform degradation in both methanogenic methanol enrichment cultures and cultures of M. barkeri 227, the prospects for use of methanol as a growth substrate for anaerobic chloroform-degrading systems may be limited unless the increased production of undesirable chloroform degradation products and the inhibition of methanol consumption can be mitigated.

Biodegradation, Environmental↗
PubMed2005

Infrared spectroscopy of acetone-methanol liquid mixtures: hydrogen bond network.

Acetone and methanol mixtures covering the whole solubility range are studied by Fourier transform infrared attenuated total reflectance spectroscopy. The strong bathochromic shifts observed on methanol OH and acetone CO stretch IR bands are related to hydrogen bonds between these groups. Factor analysis separates the spectra into four acetone and four methanol principal factors. A random molecular model developed for the acetone-water system [Max and Chapados, J. Chem. Phys. 119, 5632 (2003); 120, 6625 (2004)] was modified for the acetone-methanol system. This model, which takes into account H bonds accepted by methanol and acetone, is made up of 12 methanol and 11 acetone species. The 23 species abundances are regrouped according to evolving patterns or spectral similarities to compare them to the eight experimental factors. Methanol acetone mixtures are almost but not exactly random: the methanol oxygen atoms have stronger capacities than acetone to accept H bonds from methanol in the proportion 1.5 to 1. Since oxygen atoms are in excess, all labile hydrogen atoms will form H bonds. As acetone is added to methanol, its OH stretch band blueshifts as the number of accepted H bonds decreases. When methanol gives one H bond and accepts one, an H-bonding network is formed that was coined "chained organization." However, the acetone molecules do not sequester any methanol molecules by breaking or increasing the H-bond methanol network. Similarly, the methanol molecules do not sequester any acetone molecules. Consequently no acetone-methanol complex is formed in the mixtures. Gaussian simulation of the four principal factors in the methanol OH stretch region gave three distinct absorption regimes consisting of the OH stretch bands and their satellites that are identified as MeOH(1), MeOH(2), and MeOH(3) (subscript indicates the number of H, covalent and H bond, which surround the oxygen). These regimes are related to those identified in the water-acetone system as OH(2), OH(3), and OH(4).

Journal Article↗
PubMed2005

Treatment of dilute clusters of methanol and water by ab initio quantum mechanical calculations.

Large molecular clusters can be considered as intermediate states between gas and condensed phases, and information about them can help us understand condensed phases. In this paper, ab initio quantum mechanical methods have been used to examine clusters formed of methanol and water molecules. The main goal was to obtain information about the intermolecular interactions and the structure of methanol/water clusters at the molecular level. The large clusters (CH(4)O...(H(2)O)(12) and H(2)O...(CH(4)O)(10)) containing one molecule of one component (methanol or water) and many (12, 10) molecules of the other component were considered. Møller-Plesset perturbation theory (MP2) was used in the calculations. Several representative cluster geometries were optimized, and nearest-neighbor interaction energies were calculated for the geometries obtained in the first step. The results of the calculations were compared to the available experimental information regarding the liquid methanol/water mixtures and to the molecular dynamics and Monte Carlo simulations, and good agreement was found. For the CH(4)O...(H(2)O)(12) cluster, it was shown that the molecules of water can be subdivided into two classes: (i) H bonded to the central methanol molecule and (ii) not H bonded to the central methanol molecule. As expected, these two classes exhibited striking energy differences. Although they are located almost the same distance from the carbon atom of the central methanol molecule, they possess very different intermolecular interaction energies with the central molecule. The H bonding constitutes a dominant factor in the hydration of methanol in dilute aqueous solutions. For the H(2)O...(CH(4)O)(10) cluster, it was shown that the central molecule of water has almost three H bonds with the methanol molecules; this result differs from those in the literature that concluded that the average number of H bonds between a central water molecule and methanol molecules in dilute solutions of water in methanol is about two, with the water molecules being incorporated into the chains of methanol. In contrast, the present predictions revealed that the central water molecule is not incorporated into a chain of methanol molecules, but it can be the center of several (2-3) chains of methanol molecules. The molecules of methanol, which are not H bonded to the central water molecule, have characteristics similar to those of the methane molecules around a central water molecule in the H(2)O...(CH(4))(10) cluster. The ab initio quantum mechanical methods employed in this paper have provided detailed information about the H bonds in the clusters investigated. In particular, they provided full information about two types of H bonds between water and methanol molecules (in which the water or the methanol molecule is the proton donor), including information about their energies and lengths. The average numbers of the two types of H bonds in the CH(4)O...(H(2)O)(12) and H(2)O...(CH(4)O)(10) clusters have been calculated. Such information could hardly be obtained with the simulation methods.

Computer Simulation↗
PubMed2003

NTP-CERHR Monograph on the Potential Human Reproductive and Developmental Effects of Methanol.

The National Toxicology Program (NTP) Center for the Evaluation of Risks to Human Reproduction (CERHR) conducted an evaluation of the potential for methanol to cause adverse effects on reproduction and development in humans. Methanol was selected for evaluation because it is a high production volume chemical with high potential for occupational, consumer, and environmental exposure. Methanol is used in chemical syntheses and as an industrial solvent. It is found in a variety of consumer products such as paints, antifreeze, cleaning solutions, and adhesives and is a by-product of sewage treatment, fermentation, and paper production. Methanol is used in racecar fuels, and there is the potential for the expanded use of methanol as a vehicle fuel or fuel additive. Methanol occurs naturally in a variety of fresh fruits and vegetables, alcoholic beverages, and cigarette smoke. The results of this evaluation on methanol are published in an NTP-CERHR monograph which includes: 1) the NTP Brief, 2) the Expert Panel Report on the Reproductive and Developmental Toxicity of Methanol, and 3) public comments received on the Expert Panel Report. As stated in the NTP Brief, the NTP reached the following conclusions regarding the possible effects of exposure to methanol on human development and reproduction. First, there is concern for adverse developmental effects in fetuses if pregnant women are exposed to levels of methanol that result in high blood concentrations, such as with acute methanol poisoning. Although there is insufficient evidence to determine if a human fetus is more or less sensitive than rodents to the adverse effect of methanol, humans suffering acute methanol poisoning may have blood levels similar to those resulting in developmental toxicity in rodents. Second, for exposures that result in low blood methanol concentrations (below approx. 10 mg/L blood), there is minimal concern for adverse developmental effects , and negligible concern for adverse male reproductive effects. There is insufficient evidence to assess the effects of methanol on female reproduction. Data available to the expert panel were not sufficient to rule out the possibility of male reproductive effects at toxic exposure levels. The panel judged that blood levels >/=10 mg/L are not expected to result from normal dietary or occupational exposures. NTP-CERHR monographs are transmitted to federal and state agencies, interested parties, and the public and are available in electronic PDF format on the CERHR web site (http://cerhr.niehs.nih.gov) and in printed text or CD-ROM from the CERHR (National Institute of Environmental Health Sciences, P.O. Box 12233, MD EC-32, Research Triangle Park, NC; fax: 919-316-4511).

Journal Article↗
PubMedDate not supplied

Developmental toxicity interactions of methanol and radiofrequency radiation or 2-methoxyethanol in rats.

This research was undertaken to determine potential interactions among chemical and physical agents. Radiofrequency (RF) radiation is used in numerous workplaces, and many workers are concurrently exposed to RF radiation and various chemicals. The developmental toxicity of RF radiation is associated with the degree and duration of hyperthermia induced by the exposure. Previous animal research indicates that hyperthermia induced by an elevation in ambient temperature can potentiate the toxicity and teratogenicity of some chemical agents. We previously demonstrated that combined exposure to RF radiation (10 MHz) and the industrial solvent, 2-methoxyethanol (2ME), enhanced teratogenicity in rats. Interactions were noted at even the lowest levels of 2ME tested, but only at hyperthermic levels of RF radiation. The purpose of the present research is to investigate if the interactive effects noted for RF radiation and 2ME are unique to these agents, or if similar interactions might be seen with other chemicals. Because methanol is widely used as a solvent as well as fuel additive, and, at high levels, is teratogenic in animals, we selected methanol as a chemical to address generalizability. Based on the literature and our pilot studies, 0, 2, or 3 g/kg methanol (twice, at 6-hour intervals) were administered on gestation day 9 or 13 to groups of 10 Sprague-Dawley rats. Dams treated on day 9 were given methanol and exposed to RF radiation sufficient to maintain colonic temperature at 41 degrees C for 60 minutes (or sham). Those treated on day 13 were given methanol plus either 0 or 100 mg/kg 2ME. Because we observed that methanol produced hypothermia, some groups were given the initial dose of methanol concurrently with the RF or 2ME, and others were given the first dose of methanol 1.5 hours prior to RF or 2ME. Dams were sacrificed on gestation day 20, and the fetuses were examined for external malformations. The results indicate that RF radiation or methanol on day 9 increased the incidence of resorbed fetuses, but no interactive effects were observed. The resorptions were highest in groups given the experimental treatments 1.5 hours apart. The higher dose of methanol also reduced fetal weights. Administration of 2ME or methanol on day 13 increased the rate of malformations, and there was evidence of a positive interaction between 2ME and methanol. Fetal weights were reduced by 2ME and methanol alone, but no interaction was observed. Also, separation of the dosing with the teratogens did not affect the results. These results point out that interactions in developmental toxicology, such as those of RF radiation, 2ME, and methanol that we have studied, are complex, and such interactions cannot be fully understood or predicted without more research. It is important that combined exposure effects be considered when developing both physical agent and chemical agent exposure guidelines and intervention strategies.

Abnormalities, Drug-Induced↗
PubMed1989

Effects of methanol on the growth of gastrointestinal anaerobes.

The effects of methanol on the growth of representative, predominant, anaerobic gut bacteria were studied. Growth yields and rates were determined in a base medium to which methanol was added to produce media with methanol concentrations varying, in twofold steps, over a concentration range of 0.01 to 25%, by volume. The growth of many of the organisms was completely inhibited by a methanol concentration equal to, or less than, 6.2%. Isolates representing cellulolytic species were completely inhibited at a methanol concentration of 3.1%, and inhibitory effects on the yield of some cellulolytic isolates were found at a methanol concentration as small as 0.01%. Although most of the organisms studied were inhibited at relatively small methanol concentrations, isolates of Selenomonas ruminantium, Bacteroides ovatus, and Fusobacterium necrophorum were relatively methanol resistant. A methanol concentration of 12.5% was required to completely inhibit S. ruminantium. Substantial growth of B. ovatus was obtained in media containing 12.5% methanol, and for F. necrophorum, substantial growth occurred in media containing 25% methanol. The yields of F. necrophorum strain B85 and S. ruminantium strain PC18 were enhanced by relatively small methanol concentrations and reduced with further methanol concentration increase Anaerobic, nonsporing gut bacteria exhibit a diversity of responses to methanol.

Animals↗
PubMed2005

Methanol and formate kinetics during treatment with fomepizole.

OBJECTIVE: Methanol is metabolized by alcohol dehydrogenase to formaldehyde, and further to formic acid, which is responsible for the toxicity in methanol poisoning. Fomepizole (4-methylpyrazole) is a potent competitive inhibitor of alcohol dehydrogenase and is used as an antidote to treat methanol poisonings. We report serum methanol kinetics in eight patients treated with bicarbonate and fomepizole only. METHODS: Prospective case series study of eight patients with methanol poisoning, who were selected to fomepizole and bicarbonate treatment only, because of moderate metabolic acidosis. Three of the patients were later dialyzed, because of high serum methanol concentrations and very slow methanol elimination. RESULTS: Upon admission the median pH was 7.27 (range 7.12-7.50), median base deficit was 15 mmol/L (5-22 mmol/L) and median serum methanol was 20.4 mmol/L (65 mg/dL) (range 8.4-140.6 mmol/L). The kinetics of methanol during fomepizole treatment in six patients was best described by a first-order elimination one-compartment model. The mean correlation coefficient (R2) describing the first-order elimination model in all eight patients was 0.95 (range 0.90-0.99). The mean plasma half-life (t(1/2)) of methanol during fomepizole treatment was 52 h (range 22-87); the higher the serum methanol, the longer the T(1/2). Mean half-life of serum formate was 2.6 h, when methanol metabolism was assumed blocked by fomepizole and no folinic acid was given. This rapid formate elimination in nonacidotic patients may be explained by high renal excretion of formate. CONCLUSION: Based on our data, methanol-poisoned patients with moderate metabolic acidosis and methanol levels up to 19 mmol/L (60 mg/L) may safely be treated with bicarbonate and fomepizole only, without dialysis.

Acidosis↗
PubMed2006

Influence of ethanol on methanol-induced oxidative stress and neurobehavioral deficits.

The present study examines the efficacy of ethanol as an antidote in methanol neurotoxicity in terms of its effect on antioxidant defense system and behavior. It was observed that acute methanol exposure (7.5 g/kg body weight) led to an increase in lipid peroxidation in various regions of brain. Ethanol administration (7.5 g/kg body weight), on the other hand, was found to accentuate methanol-induced lipid peroxidation. Glutathione levels in brain were significantly reduced in methanol-exposed animals. However, in the coexposed animals, the levels of glutathione were comparable to those observed in controls. The activities of superoxide dismutase and catalase were decreased in the brain following methanol exposure, whereas in methanol- and ethanol-coexposed animals there was no significant effect on these enzymes as compared to methanol-exposed animals. The activity of acetylcholinesterase was significantly reduced in the methanol-exposed animals. On the other hand, acetylcholinesterase activity was not affected in the coexposed animals in comparison to methanol-treated group. Neurobehavioral studies revealed impaired motor and cognitive functions following methanol exposure. In contrast, ethanol exposure ameliorated the behavioral deficits induced by methanol. The findings from the present study suggest the beneficial effect of ethanol on neurobehavioral deficits induced by methanol along with intensification of methanol-induced oxidative stress.

Acetylcholinesterase↗
PubMed1996

Use of intrauterine microdialysis to investigate methanol-induced alterations in uteroplacental blood flow.

Methanol is teratogenic in rodents; it has been postulated that this teratogenicity may be mediated in part by conceptal hypoxia. To construct a model to predict conceptal risk following maternal methanol exposure, conceptal disposition of methanol must be determined and any effects of such exposure on blood flow must be quantitated. In the present study, these toxicokinetic and toxico-dynamic parameters were evaluated by in vivo intrauterine microdialysis. Microdialysis probes were inserted into the uteri of Gestational Day (gd) 20 rats; methanol was administered as either an iv bolus (100 or 500 mg/kg) or infusion (100 or 1000 mg/kg/hr). In separate experiments, methanol (100 or 500 mg/kg) and 3H2O (20 microCi/kg) were administered iv to gd 20 and 14 rats and gd 18 mice. In both experiments, maternal blood and uterine microdialysate were collected and analyzed for methanol or 3H2O content. The methanol concentration-time data were consistent with saturable maternal elimination and apparent first-order transfer between maternal and conceptal compartments; at distribution equilibrium, conceptal methanol concentrations exceeded those in the dam by approximately 25%. The initial rate of conceptal permeation of methanol was proportional to the reciprocal of maternal blood methanol concentration (r2 = 0.910). Methanol also reduced significantly the rate of 3H2O uptake into the conceptus in a concentration-dependent fashion in gd 14 and 20 rats and gd 18 mice. These data indicate that methanol may decrease uteroplacental blood flow, decreasing methanol presentation to the conceptus and possibly producing conceptal hypoxia.

Administration, Intravaginal↗
PubMed1982

Role of catalase and hydroxyl radicals in the oxidation of methanol by rat liver microsomes.

In view of the presence of adventitious catalase in isolated microsomes, and the requirement for H2O2, it has been suggested that NADPH-dependent oxidation of methanol by rat liver microsomes was mediated exclusively by the peroxidatic activity of catalase. However, H2O2 may also serve as a precursor of the hydroxyl radical, and methanol reacts with hydroxyl radicals to produce formaldehyde. Inhibition of H2O2 production should therefore decrease methanol oxidation by either a hydroxyl radical-dependent pathway or a catalase-dependent pathway. To attempt to clarify some of the controversies concerning the roles of H2O2 and catalase in the microsomal pathway of oxidation of short chain alcohols, studies were carried out to determine the nature of the pathway responsible for methanol oxidation by isolated microsomes. In the absence of the catalase inhibitor azide, methanol may be oxidized primarily by the peroxidatic activity of catalase since there was little effect on methanol oxidation by competing hydroxyl radical scavengers. Azide, which inhibited catalase activity greater than 95%, inhibited NADPH-dependent oxidation of methanol by 30-50%. The azide-insensitive (catalase-independent) pathway of methanol oxidation was inhibited by scavengers of hydroxyl radicals. The inhibition of the scavengers reflected the rate constant for interaction with hydroxyl radicals and was greater at lower concentrations of methanol than at higher concentrations, suggesting competition between the scavengers and methanol. The addition of H2O2 stimulated the oxidation of methanol in the presence of azide; H2O2 may serve as a precursor of the hydroxyl radical. Iron-EDTA, which is known to increase hydroxyl radical production, stimulated the oxidation of methanol in the absence and presence of azide. The stimulation by iron-EDTA was blocked by the competing hydroxyl radical scavengers even in the absence of azide, suggesting that the added iron-EDTA favorably with microsomal catalase for H2O2 to produce hydroxyl radicals (or a species with the oxidizing power of the hydroxyl radical). These results suggest that in microsomes, depending on the absence or presence of azide, methanol may be oxidized by two primary pathways, one involving the peroxidatic activity of catalase, and the other in which hydroxyl radicals, generated from microsomal electron transfer, play a role. In view of the crucial role played by H2O2 in both pathways, inhibition of H2O2 formation should not be interpreted solely as evidence for a role for catalase in the microsomal oxidation of alcohols.

Animals↗
PubMed2005

Structure of methanol confined in MCM-41 investigated by large-angle X-ray scattering technique.

Large-angle X-ray scattering (LAXS) measurements over a temperature range from 223 to 298 K have been made on methanol confined in mesoporous silica MCM-41 with two different pore diameters, 28 A (C14) and 21 A (C10), under both monolayer and capillary-condensed adsorption conditions. To compare the structure of methanol in the MCM-41 pores with that of bulk methanol, X-ray scattering intensities for bulk methanol in the same temperature range have also been measured. The radial distribution functions (RDFs) for the monolayer methanol samples showed that methanol molecules are strongly hydrogen bonded to the silanol groups on the MCM-41 surface, resulting in no significant change in the structure of adsorbed methanol with respect to the pore size and temperature. On the other hand, the RDFs for the capillary-condensed methanol samples showed that hydrogen-bonded chains of methanol molecules are formed in both pores. However, the distance and number of hydrogen bonds estimated from the RDFs suggested that hydrogen bonds between methanol molecules in the pores are significantly distorted or partly disrupted. It has been found that the hydrogen bonds are more distorted in the smaller pores of MCM-41. With decreasing temperature, however, the hydrogen-bonded chains of methanol in the pores were gradually ordered. A comparison of the present results on methanol in MCM-41 pores with those on water in the same pores revealed that the structural change with temperature is less significant for confined methanol than for confined water.

Hydrogen Bonding↗
PubMed2003

Process control and design considerations for methanol-induced denitrification in a sequencing batch reactor.

The primary goal of this research was to determine the effect of methanol-induced denitrification on volatile suspended solids production, settleability, and oxidation-reduction potential in a full-scale sequencing batch reactor. Batch tests were also conducted to determine the influence of mixing and acclimatization on the denitrification of wastewater with methanol. The observed sludge production in the full-scale sequencing batch reactor with methanol addition was 0.21 kg volatile suspended solids l(-1) methanol, versus the calculated stoichiometric sludge production of 0.17 kg volatile suspended solids l(-1) methanol. The settleability in the full-scale sequencing batch reactor, measured by the sludge volume index, increases linearly with increasing denitrification rate. The total change in the oxidation-reduction potential magnitude during a sequencing batch reactor cycle increased linearly with increasing denitrification rate. A minimum of 55% increase in the denitrification rate was observed in a batch reactor with methanol addition and a sludge acclimatized to methanol addition, compared to a batch reactor with methanol addition and a non-acclimatized sludge. The non-acclimatized batch reactor had a negligible denitrification rate without methanol addition. However, significant denitrification rates were observed in the acclimatized batch reactors without methanol addition, potentially caused by microbial storage or an increased population of denitrifiers that scavenge any available carbon. A completely mixed batch reactor, with sludge acclimatized to methanol addition during the anoxic cycle, had an increase in the denitrification rate ranging from 660%, without methanol addition, to 200%, with a methanol dosage of 12.7 mg l(-1), compared to the unmixed batch reactor with an acclimatized sludge. Therefore, mixing appears to be critical to the denitrification process, to realize the best kinetic performance.

Bioreactors↗
PubMed1995

Role of retinal metabolism in methanol-induced retinal toxicity.

Methanol is a toxicant that causes systemic and ocular toxicity after acute exposure. The folate-reduced (FR) rat is an excellent animal model that mimics characteristic human methanol toxic responses. The present study examines the role of the methanol metabolites formaldehyde and formate in the initiation of methanol-induced retinal toxicity. After a single oral dose of 3.0 g/kg methanol, blood methanol concentrations were not significantly different in FR rats compared with folate-sufficient (FS) (control) rats. However, FR rats treated with 3.0 g/kg methanol displayed elevated blood (14.6 mM) and vitreous humor (19.5 mM) formate levels and abnormal electroretinograms (loss of b-wave) 48 h postdose. FR rats pretreated with disulfiram (DSF) prior to 3.0 g/kg methanol treatment failed to display these symptoms. Formaldehyde was not detected in blood or vitreous humor with or without DSF treatment, suggesting that formate is the toxic metabolite in methanol-induced retinal toxicity. Additionally, creating a blood formate profile (14.2 mM at 48 h) similar to that observed in methanol-treated rats by iv infusion of pH-buffered formate does not alter the electroretinogram as is observed with methanol treatment. These data suggest that intraretinal metabolism of methanol is necessary for the formate-mediated initiation of methanol-induced retinal toxicity.

Animals↗