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PubMed1981

Blood methanol concentrations in normal adult subjects administered abuse doses of aspartame.

Blood methanol concentrations were measured in 30 normal adult subjects administered aspartame, a dipeptide methyl ester. The doses studied included the 99th percentile of projected daily ingestion (34 mg/kg body weight) and three doses considered to be in the abuse range (100, 150, and 200 mg/kg body weight). Methanol concentrations were below the level of detection (0.4 mg/dl) in the blood of the 12 normal subjects who ingested aspartame at 34 mg/kg. They were significantly elevated (p less than or equal to 0 .001) after ingestion of each abuse dose, with the mean peak blood methanol concentrations and the areas under the blood methanol concentration-time curve increasing in proportion to dose. Mean (+/- SD) peak blood methanol concentrations were 1.27 +/- 0.48 mg/dl at the 100 mg/kg dose, 2.14 +/- 0.35 mg/dl at the 150 mg/kg dose, and 2.58 +/- 0.78 mg/dl at the 200 mg/kg dose. Blood methanol concentrations returned to predosing levels by 8 h after administration of the 100 mg/kg dose. Methanol was still detected in the blood 8 h after the subjects had ingested aspartame at 150 or 200 mg/kg. Blood formate analyses were carried out in the 6 subjects who ingested aspartame at 200 mg/kg, since recent studies indicate that the toxic effects of methanol are due to formate accumulation. No significant increase in blood formate concentrations over predosing concentrations was noted. No changes were noted in any of the blood chemistry profile parameters measured 24 h after aspartame ingestion, compared to values noted before administration. Similarly, no differences were noted in ophthalmologic examinations carried out before and after aspartame loading.

Adult↗
PubMed2001

A biologically based dynamic model for predicting the disposition of methanol and its metabolites in animals and humans.

A multicompartment biologically based dynamic model was developed to describe the time evolution of methanol and its metabolites in the whole body and in accessible biological matrices of rats, monkeys, and humans following different exposure scenarios. The dynamic of intercompartment exchanges was described mathematically by a mass balance differential equation system. The model's conceptual and functional representation was the same for rats, monkeys, and humans, but relevant published data specific to the species of interest served to determine the critical parameters of the kinetics. Simulations provided a close approximation to kinetic data available in the published literature. The average pulmonary absorption fraction of methanol was estimated to be 0.60 in rats, 0.69 in monkeys, and 0.58-0.82 in human volunteers. The corresponding average elimination half-life of absorbed methanol through metabolism to formaldehyde was estimated to be 1.3, 0.7-3.2, and 1.7 h. Saturation of methanol metabolism appeared to occur at a lower exposure in rats than in monkeys and humans. Also, the main species difference in the kinetics was attributed to a metabolism rate constant of whole body formaldehyde to formate estimated to be twice as high in rats as in monkeys. Inversely, in monkeys and in humans, a larger fraction of body burden of formaldehyde is rapidly transferred to a long-term component. The latter represents the formaldehyde that (directly or after oxidation to formate) binds to various endogenous molecules or is taken up by the tetrahydrofolic-acid-dependent one-carbon pathway to become the building block of synthetic pathways. This model can be used to quantitatively relate methanol or its metabolites in biological matrices to the absorbed dose and tissue burden at any point in time in rats, monkeys, and humans for different exposures, thus reducing uncertainties in the dose-response relationship, and animal-to-human and exposure scenario comparisons. The model, adapted to kinetic data in human volunteers exposed acutely to methanol vapors, predicts that 8-h inhalation exposures ranging from 500 to 2000 ppm, without physical activities, are needed to increase concentrations of blood formate and urinary formic acid above mean background values reported by various authors (4.9-10.3 and 6.3-13 mg/liter, respectively). This leaves blood and urinary methanol concentrations as the most sensitive biomarkers of absorbed methanol.

Air Pollutants, Occupational↗
PubMed2001

Effects of acetone, methanol, or paraformaldehyde on cellular structure, visualized by reflection contrast microscopy and transmission and scanning electron microscopy.

The authors recently showed variable subcellular immunoreactivity of the Bcl-2 and Bax proteins after fixation of cell monolayers with acetone, methanol, or paraformaldehyde (PF) followed by methanol (PF/methanol). Here, the authors demonstrate by reflection contrast microscopy and transmission electron microscopy that acetone or methanol fixation result in complete loss of integrity of intracellular structures in contrast with PF or glutaraldehyde fixation. Scanning electron microscopy revealed poor preservation of plasma membrane integrity after fixation in acetone or methanol. Fixation with PF before methanol reduced damage to intracellular and plasma membranes. In addition, Western blot analysis demonstrated loss of Bcl-2 and Bax protein during acetone or methanol fixation, whereas PF fixation before methanol permeabilization markedly reduced this loss. For studies on the intracellular localization of soluble or unknown types of antigen, the authors discourage the use of acetone and methanol as single fixatives.

Acetone↗
PubMed1993

Identification of methanol-regulated promoter sequences from the facultative methylotrophic bacterium Methylobacterium organophilum XX.

A promoter-probe vector (pHX200) was constructed using the broad-host-range cosmid pLA2917 and a promoterless xylE gene of Pseudomonas as the reporter gene. Insertion of the cloned promoter fragment of the methanol dehydrogenase large subunit gene moxF (methanol oxidation) in front of the xylE gene in pHX200V-47 resulted in high-level expression of the xylE gene product--catechol 2,3-dioxygenase--in Methylobacterium organophilum XX. The specific activity of the enzyme was four times higher in methanol-grown M. organophilum XX culture than in succinate-grown culture. Interestingly, the insertion of the same fragment in the opposite orientation in front of the xylE gene (pHX200V-74) also led to elevated catechol 2,3-dioxygenase activity. This promoter activity was also methanol regulated. A total of 21 methanol-regulated promoter clones were identified that originate from three gene clusters (groups V, VI and VII) on the M. organophilum XX chromosome involved in methanol oxidation. Vector pHX200 and its derivatives were successfully mobilized into cells of three phylogenetically diverse methylotrophic bacteria: Methylophilus methylotrophus AS1, Methylobacterium extorquens AM1 and Methylobacterium sp. DM4. The reporter gene (xylE) was functionally expressed in all three bacteria with the aid of a proper promoter. Transcriptional fusions of methanol-regulated promoters with the xylE gene were mobilized into Mox- mutants of M. organophilum XX and M. extorquens AM1 to study the roles of methanol oxidation genes, especially regulatory genes. It appeared that vector pHX200 is an efficient promoter probe with wide host-range and an excellent tool for studies of structure and function of promoters/regulators.

Base Sequence↗
PubMed1988

The transmembrane electrochemical gradient of Na+ as driving force for methanol oxidation in Methanosarcina barkeri.

A sodium ion gradient (inside low) across the cytoplasmic membrane of Methanosarcina barkeri was required for methanogenesis from methanol. This could be concluded from the following results. (a) Inhibition of the Na+/H+ antiporter by K+ or amiloride led to an inhibition of methanogenesis from methanol. (b) Upon addition of the sodium ionophore monensin the Na+ gradient was abolished and at the same time methanogenesis from methanol was inhibited. (c) Methanogenesis was impaired when the Na+ gradient had the opposite orientation (inside high). All these inhibitory effects were not observed when H2 was present in addition to methanol indicating that the oxidation of methanol to CO2 was driven by a sodium-motive force. In accordance with this, a methanol-dependent influx of Na+ and a corresponding decrease of the membrane potential could be observed, when the Na+/H+ antiporter was inhibited by amiloride. This influx was indicative of the presence of a Na+ transport system which was functional when the oxidation of methanol had to be driven, but was not functional when H2 was present for reduction of methanol to methane.

Amiloride↗
PubMed1980

Methanol toxicity: treatment with folic acid and 5-formyl tetrahydrofolic acid.

After methanol administration to monkeys, an accumulation of formate in blood occurs coincident with the development of metabolic acidosis and a depletion of blood bicarbonate. Formate metabolism in monkeys depends upon and is regulated by a folate-dependent system; therefore, the effect of folic acid pretreatment and 5-formyl tetrahydrofolic acid administration on methanol toxicity was investigated. Treatment of monkeys with repetitive doses of either sodium folate (48, 24, 12, and 4 hr prior to methanol) or 5-formyl tetrahydrofolic acid (2 mg/kg at 0, 4, 8, 12, and 18 hr after methanol) resulted in a marked decrease in the levels of blood formate and an absence of both metabolic acidosis and depletion of blood bicarbonate following methanol administration. Also, 5-formyl tetrahydrofolic acid reversed methanol toxicity once it was established in the monkey. The results indicate that folate compounds decrease formate accumulation after methanol by stimulating formate oxidation or utilization and suggest a possible use for folates in the treatment of certain cases of human methanol poisoning.

Animals↗
PubMed2005

H nuclear magnetic resonance spectroscopic investigation of urine for diagnostic and clinical assessment of methanol intoxication.

Occasional or suicidal methanol intoxications are a permanent problem for most Poisoning Centers around the World. Therefore it is important to look for new diagnostic and clinical prognostic methods. In the present paper 5 cases of methanol intoxication were analyzed. At first the methanol concentrations in blood and urine were estimated with headspace gas chromatography technique. Next the urine samples were examined with 1H NMR spectroscopy, then the levels of ethanol, methanol and its metabolite, formate, lactate and trimethylamine-N-oxide with dimethylamine were evaluated. The concentrations of the above compounds were correlated with the patient's clinical status, the level of ethanol and methanol and biochemical parameters. The results indicate the correlation between clinical course of intoxication, prognostication and lactate level. There were no significant parallels for formate level as acidosis causing metabolite and initial methanol levels. In the urine samples of intoxicated patients the increased trimethyl-N-oxide and dimethylamine levels were observed, which may indicate renal cortex damage. Contrary to the opinion of some clinicians, methanol intoxication may be connected with renal functional disturbances. 1H NMR examination of urine appears to be an excellent tool to evaluate the clinical course of methanol intoxication.

Dimethylamines↗
PubMed1994

Importance of cobalt for individual trophic groups in an anaerobic methanol-degrading consortium.

Methanol is an important anaerobic substrate in industrial wastewater treatment and the natural environment. Previous studies indicate that cobalt greatly stimulates methane formation during anaerobic treatment of methanolic wastewaters. To evaluate the effect of cobalt in a mixed culture, a sludge with low background levels of cobalt was cultivated in an upflow anaerobic sludge blanket reactor. Specific inhibitors in batch assays were then utilized to study the effect of cobalt on the growth rate and activity of different microorganisms involved in the anaerobic degradation of methanol. Only methylotrophic methanogens and acetogens were stimulated by cobalt additions, while the other trophic groups utilizing downstream intermediates, H2-CO2 or acetate, were largely unaffected. The optimal concentration of cobalt for the growth and activity of methanol-utilizing methanogens and acetogens was 0.05 mg liter-1. The higher requirement of cobalt is presumably due to the previously reported production of unique corrinoid-containing enzymes (or coenzymes) by direct utilizers of methanol. This distinctly high requirement of cobalt by methylotrophs should be considered during methanolic wastewater treatment. Methylotroph methanogens presented a 60-fold-higher affinity for methanol than acetogens. This result in combination with the fact that acetogens grow slightly faster than methanogens under optimal cobalt conditions indicates that acetogens can outcompete methanogens only when reactor methanol and cobalt concentrations are high, provided enough inorganic carbon is available.

Anaerobiosis↗
PubMed2006

Differential regulation of the three methanol methyltransferase isozymes in Methanosarcina acetivorans C2A.

Genetic analysis of the three methanol-specific methyltransferase 1 operons (mtaCB1, mtaCB2, and mtaCB3) in Methanosarcina acetivorans led to the suggestion that each of them has a discrete function during growth on methanol, which might be reflected in differential gene regulation (Pritchett and Metcalf, Mol. Microbiol. 56:1183-1194, 2005). To test this suggestion, reporter gene fusions were constructed for each of the three operons, and their expression was examined under various growth conditions. Expression of the mtaCB1 and mtaCB2 fusions was 100-fold and 575-fold higher, respectively, in methanol-grown cells than in trimethylamine (TMA)-grown cells. The mtaCB3 fusion was expressed at low levels on methanol, TMA, and dimethylamine but was significantly upregulated on monomethylamine and acetate. When TMA- or acetate-grown cultures were shifted to methanol, the mtaCB1 fusion was expressed most highly during exponential phase, whereas the mtaCB2 fusion, although strongly induced prior to mtaCB1 expression, did not reach full expression levels until stationary phase. The mtaCB3 fusion was transiently expressed prior to entry into exponential phase during a TMA-to-methanol substrate shift experiment. When acetate-grown cells were shifted to medium containing both TMA and methanol, TMA utilization commenced prior to utilization of methanol; however, these two substrates were consumed simultaneously later in growth. Under these conditions expression of the mtaCB2 and mtaCB3 fusions was delayed, suggesting that methylamines may repress their expression.

Dimethylamines↗
PubMed2003

Permeation and toxicity of ethylene glycol and methanol in larvae of Anopheles gambiae.

In this study, we applied proton NMR to measure the permeation of two cryoprotective agents (CPAs), ethylene glycol (EG) and methanol, into 1st instar Anopheles larvae. Calibration with standard solutions of EG or methanol (0-10 mol l(-1)) confirmed the reliability of the NMR measurements for determining the concentration of these solutes. To assess permeation, larvae were immersed in 1.5 mol l(-1) EG or 1.5 mol l(-1) methanol for different periods of time at 22 degrees C. The concentration of both CPAs in the larvae was then measured as a function of exposure time using (1)H-NMR spectroscopy. Results show that after a 6 h exposure to 1.5 mol l(-1) EG, the larval concentration of EG reaches a maximum value of 1.44 mol l(-1), which is 96% of the theoretical maximum. By contrast, after just 1 h exposure to 1.5 mol l(-1) methanol, the larval methanol concentration reaches its maximum, which, however, is only 75% of the theoretical maximum. Toxicity data show that larval survival remains 91% and 95% after 4 h and 1 h exposure to 1.5 mol l(-1) EG and 1.5 mol l(-1) methanol, respectively, at which time the larval concentration of EG and methanol has risen to 1.21 mol l (-1) and 1.13 mol l(-1), respectively. These results suggest that CPAs such as EG and methanol do permeate Anopheles larvae to up to 81% and 75% of equilibrium, respectively, before the exposure becomes toxic.

Animals↗
PubMed2003

Independent exponential feeding of glycerol and methanol for fed-batch culture of recombinant Hansenula polymorpha DL-1.

As a novel feeding strategy for optimizing human epidermal growth factor (hEGF) production with a recombinant Hansenula polymorpha DL-1 using the methanol oxidase (MOX) promoter in H. polymorpha DL-1, independent exponential feeding of two substrates was used. A simple kinetic model considering the cell growth on two substrates was established and used to calculate the respective feeding rates of glycerol and methanol. In the fedbatch culture with methanol-only feeding, the optimal set point of specific growth rate on methanol was found to be 0.10 h-1. When the fed-batch cultures were conducted by the independent feeding of glycerol and methanol, the actual specific growth rate on glycerol and methanol was slightly lower than the set point of specific growth rate. By the uncoupled feeding of glycerol and methanol the volumetric productivity of hEGF increased from 6.4 to 8.0 mg/(L.h), compared with methanol-only feeding.

Alcohol Oxidoreductases↗
PubMed2006

Methanol-induced oxidative stress in rat lymphoid organs.

Methanol is primarily metabolized by oxidation to formaldehyde and then to formate. These processes are accompanied by formation of superoxide anion and hydrogen peroxide. This paper reports data on the effect of methanol on antioxidant status and lipid peroxidation in lymphoid organs such as the spleen, thymus, lymph nodes and bone marrow of rats. Male Wistar albino rats were intoxicated with methanol (2.37 g/kg b.w intraperitoneally) for detecting toxicity levels for one day, 15 d and 30 d, respectively. Administration of methanol at 15 and 30 d significantly (p<0.05) increased lipid peroxidation and decreased the enzymatic (superoxide dismutase, catalase, glutathione peroxidase) and non-enzymatic antioxidants (reduced glutathione and vitamin C) in lymphoid organs. However, lipid peroxidation and enzymatic and non-enzymatic antioxidants in the acute methanol exposed group animals were found to be significantly (p<0.05) increased. In one day methanol intoxication, the levels of free radicals initially increased, and to remove these free radicals, antioxidants levels were elevated, which generally prevented oxidative cell damage. But in longer periods of intoxication, when the generation of reactive free radicals overwhelmed the antioxidant defense, lipid peroxidation increased. Further, decreased antioxidants in 15 and 30 d methanol intoxication may have been due to overutilization of non-enzymatic and enzymatic antioxidants to scavenge the products of lipid peroxidation. In addition, the liver and kidney markers of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), urea and creatinine significantly increased. This study concludes that exposure to methanol causes oxidative stress by altering the oxidant/antioxidant balance in lymphoid organs of the rat.

Animals↗
PubMed1986

Reliability in determination of methanol concentration.

Two sampling methods for reliable determination of methanol concentration were studied. Methanol vapor stored in glass container was found to be decomposed on the glass surface. The decomposition increased as the surface area of the glass container was extended. The proportion of the decomposition in the glass container was relatively high, especially when the concentration of methanol vapor was low. Therefore, a reliable determination by the above sampling method was impossible. In the solid sorbent sampling by silica gel, the collected methanol was also decomposed, but the decomposed amount was negligibly small compared to the collected methanol when the amount of methanol was more than 0.1 microliter of the liquid methanol. It could be concluded from the foregoing findings that the determination of methanol concentration by this method is reliable.

Air Pollutants, Occupational↗
PubMed2003

Effects of methanol on photosynthetic processes and growth of Lemna gibba.

Effects of methanol on growth and photosynthetic activity of Lemna gibba exposed under continuous illumination were examined. As a higher plant, L. gibba appeared to be much more sensitive to methanol inhibitory effect compared with some algae (Theodoridou et al. [2002] Biochim. Biophys. Acta, 1573, 189-198). We found that stimulatory or inhibitory effects were strongly dependent on the methanol concentration and the time of exposure. When the exposure was up to 0.2% methanol, the growth rate of biomass was improved by 50%. However, stimulatory effect of methanol appeared to be smaller when plants were exposed for 48 h compared with 24 h. Increase in biomass induced by methanol was not based on the increase in primary photosynthetic process but rather on accommodation of energy dissipation during photosynthesis. Inhibitory effect on the growth of L. gibba already observed for 0.5% methanol was strongly associated with the increase in the nonphotochemical energy dissipation. The ratio between biomass and methanol concentration appeared to determine the stimulatory or the inhibitory effect. Suggested explanations for the stimulatory and the inhibitory effects are presented.

Methanol↗
PubMed2003

[Determination of methanol in gardenia red and gardenia blue].

The natural food color gardenia red is manufactured through the hydrolysis of the methyl ester of iridoid glucoside. Gardenia blue is also made from iridoid glucoside. Therefore, there is a possibility that the commercial products contain methanol. To determine methanol in gardenia red and gardenia blue, a headspace GC method with standard addition was developed. In the case of gardenia blue with the methyl ester, methanol may be formed during the analytical procedures for methanol. Thus, conditions in which methanol would not be produced in the headspace-GC method were investigated. Vials containing 1 g of the color preparation, 1 mL of water, and a standard solution were sealed. Equilibrium temperature was an important factor among the conditions for analyzing methanol in gardenia blue. Although at room temperature and 50 degrees C, the contents of methanol were equal, the content increased 1.2 times at 80 degrees C. Methanol contents determined at 50 degrees C were 8 and 9 micrograms/g in two gardenia red products and 25-34 micrograms/g in three gardenia blue products, which were below the residual limit of 50 micrograms/g set for many other natural food additives.

Amino Acids↗
PubMed1999

Time course and reproducibility of urinary excretion profiles of ethanol, methanol, and the ratio of serotonin metabolites after intravenous infusion of ethanol.

BACKGROUND: The aim of this study was to determine the time course and reproducibility of urinary excretion profiles of ethanol, methanol, and ratio of serotonin metabolites, 5-hydroxytryptophol (5HTOL) to 5-hydroxyindoleacetic acid (5HIAA), under strictly controlled conditions. METHODS: Nine healthy volunteers (6 women and 3 men) received 0.40 g of ethanol/kg of body weight on two occasions by constant rate intravenous infusion 30 min. Urine was voided before administration of ethanol and thereafter every 60 min for a total of 8 hr. Concentrations of ethanol and methanol in urine were determined by headspace gas chromatography, and the serotonin metabolites 5HTOL and 5HIAA were measured by gas chromatography-mass spectrometry and high-performance liquid chromatography, respectively. RESULTS: The peak concentration of ethanol in urine occurred at 30 or 60 min after the infusion ended. The peak concentration of methanol and the 5HTOL/5HIAA ratio developed more gradually, reaching a plateau at 213 to 220 min and 200 to 220 min postinfusion, respectively. The concentration-time profiles of ethanol and the 5HTOL/5HIAA ratio varied more between subjects than within subjects (p < 0.001), whereas the inter- and intraindividual variation in the pharmacokinetics of methanol were not significantly different (p > 0.05). The concentration of methanol and the 5HTOL/5HIAA ratio remained above the endogenous levels at 8-hr postinfusion despite the fact that urinary ethanol was no longer measurable (<0.01 g/liter) after 5 to 6 hr. CONCLUSIONS: Measuring the concentrations of methanol and the ratio of serotonin metabolites (5HTOL/5HIAA) in urine is a more sensitive way to monitor recent drinking, compared with analysis of ethanol in body fluids. Moreover, the concentration-time profiles of methanol and the 5HTOL/5HIAA ratio showed a good test-retest stability. The present intravenous infusion experiment confirms previous work on these markers when ethanol was given perorally. The urinary methanol and the 5HTOL/5HIAA ratio have applications in forensic and clinical medicine as indicators of acute alcohol consumption.

Adult↗
PubMed2001

Differential recovery of retinal function after mitochondrial inhibition by methanol intoxication.

PURPOSE: The authors' laboratory has previously documented formate-induced retinal toxicity in a rodent model of methanol intoxication. These studies determined functional, bioenergetic, and structural recovery of the retina after methanol intoxication. METHODS: Rats were intoxicated with methanol, and retinal function was assessed by electroretinography 72 hours after the initial dose of methanol and after a 72-hour recovery period. Retinal energy metabolites, glutathione (GSH) concentrations, and histology were determined at the same time points. RESULTS: Both rod-dominated and UV-cone-mediated electroretinogram responses were profoundly attenuated in methanol-intoxicated rats. In rats allowed to recover from methanol intoxication, there was significant, although incomplete, recovery of rod-dominated retinal function. However, there was no demonstrable improvement in UV-cone-mediated responses. Retinal adenosine triphosphate (ATP), adenosine diphosphate (ADP), and GSH concentrations were significantly reduced after intoxication. Although retinal energy metabolites returned to control values after the recovery period, retinal GSH remained significantly depleted. Histopathologic changes were apparent in the photoreceptors after methanol intoxication, with evidence of inner segment swelling and mitochondrial disruption. In animals allowed to recover from methanol intoxication, there was no evidence of histopathology at the light microscopic level; however, ultrastructural studies revealed subtle photoreceptor mitochondrial alterations. CONCLUSIONS: These findings support the hypothesis that formate inhibits retinal mitochondrial function and increases oxidative stress. They also provide evidence for a differential sensitivity of photoreceptors to the cytotoxic actions of formic acid, with a partial recovery of rod-dominated responses and no recovery of UV-cone-mediated responses.

Adenosine Diphosphate↗
PubMed1996

Developmental neurotoxicity of methanol exposure by inhalation in rats.

The possibility of widespread methanol exposure via inhalation stemming from its adoption as an automotive fuel or fuel component arouses concerns about the potential vulnerability of the fetal brain. This project was designed to help address such concerns by studying the behavior of neonate and adult rats following perinatal exposure to methanol vapor. Four cohorts of pregnant Long-Evans hooded rats, each cohort consisting of an exposure and a control group, were exposed to 0 parts per million (ppm) (control) or 4,500 ppm methanol vapor for six hours daily beginning on gestation day (GD) 6 with dams and pups then being exposed postnatal day (PND) 21. Exposures took place in 2-m3 Rochester-type inhalation chambers while the animals remained in their plastic breeder cages. Prenatal and postnatal blood methanol concentrations were determined by gas chromatography. Blood methanol concentrations of the dams, measured immediately following a six-hour exposure, were approximately 500 to 800 micrograms/mL throughout gestation and lactation. Average blood methanol concentrations of the pups were about twice those of the dams. Because such results appeared consistently across the other cohorts, we decided to obtain additional data with Cohort 4. Once it had undergone the standard exposure protocol, we selected sets of extra pups from those that had not been assigned previously to the adult phase of behavioral testing. Each set was exposed once, at ages that extended out to PND 52, for one additional six-hour session of exposure to 4,500 ppm methanol. The blood methanol concentrations of these pups declined until about PND 48, at which time they approximated those of the dams. These findings might be accounted for by a process of metabolic maturation in the pups that remains to be identified.

Animals↗