Abstract  Cinnamomum tamala (CT) Linn. (Lauraceae) is a component of Indian spices and is also used as antidiabetic agent. Its antioxidant potential was reported by other authors and recently our group has reported its immune-suppressive property. Here, CT leaves were extracted with methanol (CTT) and also with various organic solvents of increasing polarity such as hexane (CTH), ethyl acetate (CTEA), and methanol (CTE) in successive manner by continuous Soxhlet extractor. The active compounds of CTT and CTH were analyzed by GC-MS and most abundant compound (eugenol) was further analyzed by HPLC. These extracts were tested for their free radical (FR) scavenging potential for different FR species, hypoglycemic potential on alloxan-induced hyperglycemia, and anti-inflammatory property in carrageenan-induced paw edema and lipopolysaccharide (LPS)-induced nitric oxide (NO) production in rat peritoneal macrophage culture. Result showed that CTH was the most active fraction toward these parameters, which was parallel to its eugenol and total phenolic content concentration.

Abstract  To elucidate a novel anti-inflammatory mechanism of myrrh against lipopolysaccharide (LPS)-induced inflammation.

RAW264.7 macrophages were cultured in DMEM and then cells were treated with LPS or LPS plus a myrrh methanol extract (MME) for 24h. The culture medium was collected for determination of nitric oxide (NO), prostaglandin (PG)E(2) , interleukin (IL)-1β, and tumour necrosis factor (TNF)-α, and cells were harvested by lysis buffer for Western blot analysis.

Our data showed that treatment with the MME (1∼100µg/ml) did not cause cytotoxicity or activate haem oxygenase-1 (HO-1) protein synthesis in RAW264.7 macrophages. Furthermore, the MME inhibited LPS-stimulated NO, PGE(2) , IL-1β and TNF-α release and inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 protein expression. Zn(II) protoporphyrin IX, a specific inhibitor of HO-1, blocked the inhibition of iNOS and COX-2 expression by the MME.

These results suggest that among mechanisms of the anti-inflammatory response, the MME inhibited the production of NO, PGE(2) , IL-1β and TNF-α by downregulating iNOS and COX-2 gene expression in macrophages and worked through the action of HO-1.

Abstract  Tetrafluoro-4-nitropyridine derivatives have been synthesized and separated successfully by HPLC. The resulting fluorinated amines and 4-amino3-chlorotrifluoropyridine have also been diazotized and the resulting diazonium ions coupled to mesitylene giving the corresponding azo-compounds: 2,3,4,6-tetrafluoro-4-(2,4,6-trimethylphenylazo)pyridine (9) (80%), 3-chloro-2,5,6-trifluoro-4-(2,4,6-trimethylphenylazo)pyridine (23) (83%), 2,3,6-trifluoro-4-nitro-5-(2,4,6-trimethylphenylazo)pyridine (20) (80%): 2,3,5-trifluoro-4-nitro-6-(2,4,6-trimethylphenylazo)pyridine (21) (84%). Treatment of these azo-compounds mentioned earlier with sodium methoxide in methanol/tetrahydro furan gave 3,6-difluoro-2-methoxy-4-nitro- 5-(2,4,6-trimethylphenyl azo)pyridine (24) (37%), 3-fluoro-2,5dimethoxy-4-nitro-6-(2,4,6-trimethylphenylazo)pyridine (26) (49%), 2,3-difluoro-4,5-dimethoxy-6-(2,4,6-trimethylphenylazo)pyridine (25) (32%), 3-chloro-2,3,5-trifluoro-6-methoxy-4-(2,4,6-trimethylphenylazo) pyridine 24 (87%), 3-chloro-3,5-difluoro-2,6-dimethoxy4-(2,4,6-trimethylphenylazo)-pyridine 23 (83%). The two diazepines 25 and 26 were successfully separated by HPLC. The thermolysis of the synthesized azocompounds in boiling mestylene gave the corresponding diazepines: 1,2,4-trifluoro-7,9-dimethyl-11-H-pyrido[4,3-c]benzo[1,2]diazepine (15) (75%), -1,4-difluoro-3-methoxy-7,9-dimethyl-11-H-pyrido[4,3-c]benzo[1,21diazepi ne (32) (80%) and 3,4-difluoro-l-methoxy-7,9-dimethyl-11-H-pyrido[4,3-c]benzo[1,2]diazepin e (33) (9%). The structural diazepine-isomers 32 and 33 were also separated by HPLC.

Abstract  Novel [3+3]-additions and water (methanol)-incorporated additions were observed in the photoreactions of N-methyl-1,8-naphthalimide with methylbenzenes, such as xylenes, mesitylene, and durene, in acetonitrile. A mechanism for the reactions is proposed on the basis of the fluorescence quenching examinations, calculations of de associated with the electron transfer, and deuteration studies.

Abstract  The application of sulfur-nanoparticle-loaded alumina as an efficient adsorbent for the solid-phase extraction (SPE) and determination of trace amounts of Cd, Cu, Zn, and Pb ions was investigated in marine samples using flame atomic absorption spectrometry (FAAS). The nanometer-sized sulfur particles were synthesized in situ, physically loaded onto alumina microparticles, and the parameters influencing the preconcentration of the analytes, such as the pH, solution flow rate and volume, eluent solution, and interfering ions, were examined. The results showed that the optimal conditions for quantitative recovery of the metal ions by adsorption and elution on the sulfur nanoparticles (SNPs) was achieved by employing a flow rate of 15 mL min(-1), a pH of 8.5 for the sample solutions, and an eluent composed of 3.0 mol L(-1) HNO(3) in methanol. The detection limits of this method for Cd, Zn, Cu, and Pb ions were 0.30, 0.21, 0.24, and 0.63 μg L(-1) (n=10), respectively. Application of the proposed method to the analysis of fish certified reference material (DORM-3) produced results that were in good agreement with the certified values. The proposed method was also successfully applied to the determination of analytes in marine samples, including seawater, fish, and oysters.

Abstract  Parsley (Petroselinum crispum) leaves were macerated with a mixture of methanol: water: acetic acid to produce a crude extract which was then defatted with (40 degrees-60 degrees) petrol. Antioxidant activity of the extract was evaluated using a battery of in vitro assays, viz., iron(III) reduction, iron(II) chelation and free radical scavenging assays. Evaluation of the pro-oxidant activity of the extract was based upon its effects upon DNA fragmentation and protein carbonylation. Cytotoxicity and apoptotic effects of the extract were determined in non-cancerous CV1-P fibroblast and cancerous A375 melanoma cells using MTT and LDH tests and caspase 3-like activity assay. The highest concentration, 2.0 mg ml(-1), decreased the viability of both cell lines, however, the cancerous melanoma cells were slightly susceptible to the effects. The observed cytotoxicity was not due to the caspase 3 activity. In conclusion, the toxicity might be explained by the pro-oxidative activity of components within the extract against proteins and/or DNA but it is not related to caspase 3-dependent apoptosis within cells.

Abstract  Liquid electrode plasma atomic emission spectrometry (LEP-AES) is a compact elemental-analysis method, which requires no plasma gas and no high-power source, and is suitable for on-site portable analysis. In this paper, the LEP-AES is combined with the concentration method using liquid organic ion associate extraction, and a concentration/simultaneous determination method for trace metals (Cu, Mn, Pd, Zn, Cd and Pb) in water is developed. Metals were converted into a complex with a chelating reagent in a 40 mL sample solution, and were extracted into a liquid ion associate during phase formation. The volume of the ion associate was mu L-scale. The ion associate was dissolved with 400 mu L of a 50 vol% methanol + 0.1 M HNO(3) solution, followed by detection by LEP-AES using 40 mu L of the sample. As a results, a liquid organic ion associate extraction enabled a 100-fold enrichment of trace metals, and improved the detection limits (3 sigma) by a few mu L L(-1) - sub mg L(-1). Interestingly, for some metal elements, the magnification of the total sensitivity combined with LEP-AES resulted in more than 1000, which is more than the value of 100-fold for the enrichment. This method was alied to the determinations of Cu, Mn, Zn, Cd and Pb in certified reference materials (Enviro MAT EU-H-1 waste water). The values obtained in this method were nearly equal to the certified values.

Abstract  The title Cu(II) coordination polymer, {[Cu(C(7)H(10)N(6))(2)(H(2)O)(2)](NO(3))(2)·H(2)O}(n), was obtained by the reaction of equimolar Cu(NO(3))(2)·4H(2)O and 1,3-bis-(1,2,4-triazol-1-yl)propane (btp) in a water-methanol solvent. The Cu(II) atom is located on a centre of inversion and has an elongated octa-hedral coordination geometry formed by four N atoms from four symmetry-related btp ligands and two coordinated water mol-ecules. Adjacent Cu(II) atoms are connected by btp ligands, generating a double-stranded chain. The nitrate anion is disordered over two positions in a 0.828 (7):0.172 (2) ratio.

Abstract  The anti-inflammatory and anticancer activities of a methanol extract of the rhizome of Cnidium officinale were investigated. Four compounds, namely falcarindiol (1), 6-hydroxy-7-methoxy-dihydroligustilide (2), ligustilidiol (3), and senkyunolide H (4) were isolated from the extract of the rhizome of Cnidium officinale and their structures were elucidated by analysis of their spectroscopic data and by comparison with previously reported data. These compounds showed anti-inflammatory activities, measured as inhibition of nitric oxide (NO) release in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage cells, with IC(50) values of 4.31 ± 5.22, 152.95 ± 4.23, 72.78 ± 5.13, and 173.42 ± 3.22 μM, respectively. They also inhibited inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) mRNA expression induced by LPS. Among these compounds, falcarindiol (1) was found to have anti-proliferative effect against MCF-7 human breast cancer cells by induction of a G(0)/G(1) cell cycle block of the cells, with an IC(50) value of 35.67 μM. Typical apoptotic effects were observed by phase contrast microscopy and were also exhibited in fluorescence microscopy with Hoechst 33342 staining. In addition, falcarindiol induced apoptosis through strongly increased mRNA expression of Bax and p53, and slightly reduced Bcl-2 mRNA levels in a dose dependent manner. This study suggested that C. officinale extract and its components would be valuable candidates in therapeutic applications for anti-inflammatory and anti-cancer agents.

Abstract  1. In the rat hepatic artery, the SK(Ca) inhibitors UCL 1684 (300 nM) completely blocked, and scyllatoxin (1 microM) and d-tubocurarine (100 microM) partially inhibited EDHF relaxations when each of them was combined with charybdotoxin (300 nM). 2. The IK(Ca) inhibitors clotrimazole (3 microM) and 2-chlorophenyl-bisphenyl-methanol (3 microM) strongly depressed EDHF relaxations when each of them was combined with apamin (300 nM). The cytochrome P450 mono-oxygenase inhibitor ketoconazole (10 microM) had no effect in the presence of apamin. 3. Ciclazindol (10 microM), which abolishes EDHF relaxations in the presence of apamin, almost completely prevented the calcium ionophore (A23187) stimulated (86)Rb(+) influx via the Gardos channel (IK(Ca)) in human erythrocytes. 4. The Na(+)/K(+) ATPase inhibitor ouabain (500 microM) and the K(IR) blocker Ba(2+) (30 microM) neither alone nor in combination inhibited EDHF relaxations. Ba(2+) was also without effect in the presence of either apamin or charybdotoxin. 5. In contrast to EDHF, an increase in extracellular [K(+)] from 4.6 mM to 9.6, 14.6 and 19.6 mM inconsistently relaxed arteries. In K(+)-free physiological salt solution, re-admission of K(+) always caused complete and sustained relaxations which were abolished by ouabain but unaffected by Ba(2+). 6. The present study provides pharmacological evidence for the involvement of SK(Ca) and IK(Ca) in the action of EDHF in the rat hepatic artery. Our results are not consistent with the idea that EDHF is K(+) activating Na(+)/K(+) ATPase and K(IR) in this blood vessel.

Abstract  ABSTRACT. The demographics, sources and outcomes of methanol poisoning have not been described in Turkey. Our study identified the profile of acute methanol exposures reported to Drug and Poison Information Center (DPIC) in lzmir, Turkey, from 1993 to 2002. Data analysis included patient demographics. sources of methanol, reason for the exposure, clinical effects and outcomes of methanol poisoning. The DPIC recorded 30,485 calls concerning poisoning: 996 (3.3 %) alcohol poisonings were recorded and 113 (11.3%) of them were methanol poisonings. There were 91 (80.5%) males and 22 (19.5 %) females with a mean age of 34.7±1.3y (range 19-65) and 4.8 ± 0.9y (range 1-18) in adults and children, respectively. The sources of methanol were eu de cologne (72.6 %), spirits (10.6%) and antifreeze (2.7%). Accidental poisoning occurred in all children between 0 and 12 y old, abuse (55.7%) and intentional poisoning (27.3%) were predominant in adults. Clinical signs in all cases were central nervous system symptoms (45.1 %).metabolic acidosis (23.0 %), visual symptoms (21.2%) and gastrointestinal symptoms (10.6 %). Sixteen patients (14.1%) died, 63(55.8%) had complete recovery and 1 (0.9%) had irreversible visual problems. Most patients with methanol poisoning may die or present serious morbidity without appropriate treatment in a health care facility. Methanol for producing cheap eu de colognes in Turkey is the principal reason for severe poisoning and deaths. Public education about colognes and legislative control of cologne production are important in preventing methanol poisoning.

Abstract  BACKGROUND: Methanol poisoning during human pregnancy rarely has been described. We report the first human newborn with a documented methanol concentration resulting from maternal exposure. CASE REPORT: A 28-year-old pregnant woman EGA 30 weeks with HIV infection and asthma presented to the emergency department in respiratory distress. She was acidotic (pH 7.17) with an anion gap of 26, and fetal bradycardia was noted. Her son was delivered by emergent C-section (birthweight 950 g, Apgars 1 and 3) and required aggressive resuscitation. During his hospital course, acidosis (initial pH 6.9) persisted despite fluid, blood, and bicarbonate administration. His mother also had persistent metabolic acidosis despite fluids, bicarbonate, and dopamine. Results of other laboratory tests on the mother included undetectable ethanol and salicylates and an osmolar gap of 41. An ethanol drip was initiated for the mother 36 h after admission when a methanol level of 54 mg/dL was reported. When consulted on hospital day 3, our regional poison center recommended hemodialysis for the mother and administering fomepizole and testing the methanol level of the newborn (61.6 mg/dL). Because the infant developed a grade 4 intraventricular bleed, no further therapy was offered, and he died on day 4. His mother died on day 10. CONCLUSION: Fatal neonatal methanol toxicity can result from transplacental exposure.

Abstract  To obtain insight into the identity of chemicals associated with the mutagenicity of United States National Institute of Standards and Technology (NIST) Standard Reference Materials SRM 1649 (urban dust) and SRM 1650 (diesel particulate), parallel mutagenicity tests and chemical analyses were performed on dichloromethane and sequential organic extracts of these samples. SRM 1649 and 1650 were sequentially extracted with five organic solvents of increasing polarity, in order to partition mutagenic components into discrete fractions. The solvents (with associated polarity index) were as follows: (1) hexane (0.0); (2) hexane:diethyl ether 9:1 (0.29); (3) hexane:diethyl ether 1:1 (1.45); (4) diethyl ether (2.9); (5) methanol (6.6). 0.9270 g of SRM 1649, and 0.0510 g of SRM 1650 were each extracted three times with 8 ml of each of the solvents, the three aliquots were pooled, and analysed for target organics or solvent-exchanged into DMSO for mutagenicity testing in Salmonella typhimurium strains TA98 and TA100. The dichloromethane extracts of SRM 1649 and SRM 1650 contained direct-acting mutagens in Salmonella strains TA98 and TA100; SRM 1650 was significantly more potent than SRM 1649 in either strain. Addition of S9 caused a large decrease in mutagenicity of each extract, although SRM 1650 remained more potent. An interesting pattern of mutagenicity was observed for the sequential extracts of SRM 1649 and SRM 1650: the mutagenic potency of SRM 1649 extracts increased with increasing polarity of the extraction solvent while the response of the SRM 1650 extracts was the opposite. This suggests that the direct-acting mutagens in SRM 1650 are unlike those in SRM 1649. The response, though diminished, was largely unchanged when S9 was included in the test mixture. Chemical analyses on the various extracts were performed using a Hewlett-Packard model 5890 gas chromatograph equipped with a model 5970B mass selective detector (GC-MSD), and a 0.3 microns film thickness cross-linked methyl silicone capillary column (HP 1909A-101). Selected ion monitoring (SIM) methods were used to analyze for 105 target compounds including PAHs and nitro-PAHs. Chemical analysis of the dichloromethane extracts of SRM 1649 and SRM 1650 identified three main classes of compounds: polyaromatic hydrocarbons (PAH), nitro-polyaromatic hydrocarbons (NO2-PAHs) and heterocyclics. The concentration of target compounds and the proportion of nitro-PAHs and heterocyclic compounds were considerably greater in SRM 1650 than in SRM 1649, consistent with the observed differences in their mutagenic potency. However, the different responses of the dichloromethane extracts in TA98 and TA100 suggest the presence of different (unidentified) compounds.(ABSTRACT TRUNCATED AT 400 WORDS)

Abstract  NA

Abstract  In the rural troposphere, the nonmethane hydrocarbon compounds (NMHCs) play a significant role in establishing the absolute, as well as, the relative concentration of the odd-hydrogen radicals. In order to provide data which could be used to estimate OH reactive loss rates with hydrocarbons directly, and to broaden our understanding of the production of biogenic NMHCs in and the transport of anthropogenic NMHCs into the Colorado mountains, in situ hydrocarbon measurements were made during the Tropospheric OH Photochemistry Experiment in the fall of 1993. NMHC measurements were made using an automated gas chromatographic system that was capable of quantifying alkanes C3 (propane) through C10 (decane), alkenes C4(butene) through C10 (decene), light alcohols from C1 (methanol) through C5 (pentanol), light ketones from C3 (acetone) through C5 (pentanone), aromatics from C6 (benzene) through C9 (trimethylbenzenes), C10 monoterpenes, and acetaldehyde. During periods of influx of urban air masses, the NMHCs appeared to be the dominant sink for OH radicals.

Abstract  SUP17O Nuclear magnetic resonance (NMR) spectroscopy allows exclusive detection and direct quantification of oxygenates in gasoline unaffected by its hydrocarbon content, using the internal standard quantitative NMR (QNMR) method. Chemical shifts of 24 oxygen-containing compounds as potential additives and contaminants have been measured in gasoline and corrected values of deltaSUBO 18.1 and 3.9 determined for neat methyl tert-butyl ether (MTBE) and neat di-n-butyl ether, respectively. Quantification of ethanol in gasoline can be readily achieved by SUP17O QNMR with dimethyl sulfone as an internal standard reference material, at the levels currently used in retail gasolines (1-20%). In addition, the simultaneous detection and quantification of the oxygenates methanol, ethanol, 2-propanol, tert-butyl alcohol, and MTBE in gasoline has been established to further demonstrate the specificity of the method. SUP17O NMR has distinct advantages over SUP1H and SUP13C QNMR methods, and although it cannot reliably differentiate 1-propanol, 1-butanol, 1-pentanol, and isopentyl alcohol, SUP17O NMR does allow the rapid and unambiguous identification of unexpected oxygenates such as acetates and ketones found as contaminants in some retail gasoline.

Abstract  A biologically based approach was taken to developing an inhalation Reference Concentration (RfC) for methanol, a high production volume chemical with many commercial applications, including use as an alternative fuel for motor vehicles and as a hydrogen source for fuel cells. Benchmark Dose methodology was applied to the most sensitive toxic endpoint for assessing potential health risks in humans, cervical rib malformation data obtained using CD-1 mice. The concentration of methanol in circulating blood was employed as the dose metric, and the maximum likelihood estimate of the blood methanol increment causing a 10% extra risk of these malformations, was 215.4 mg/L, with a lower 95% confidence bound of 97.4 mg/L. A "Reference Increment" for blood methanol was then determined by dividing this value by a 3-fold factor for residual pharmacodynamic uncertainty between species and a 10-fold factor for interindividual variation in human sensitivity to methanol. The resulting Reference Increment in blood methanol was then converted to an equivalent inhalation Reference Concentration with a physiologically based pharmacokinetic model evaluated for continuous exposure conditions. The resulting maximum likelihood estimate for the inhalation RfC was 298 mg/m3, with a 95% lower confidence bound of 135 mg/m3.

Abstract  There has been a significant evolution in the clinical management of the poisoned patient over the last decade. Interventions that were once the cornerstone of treating the poisoned patient have become passÚ or have come under intense scrutiny. The advent of evidence-based medicine has forced clinical scientists to re-evaluate standard therapies. Gastrointestinal decontamination with either emesis or gastric lavage was the foundation of the initial management of most poisoned patients. Examination of the published literature demonstrated that neither emesis nor lavage changed the ultimate outcome of poisoned patients, and most poison centers have abandoned their use. Even the use of activated charcoal has been questioned. A multitude of studies demonstrated that the effectiveness of activated charcoal diminished significantly 30û60 min after the ingestion of a poison. No study has demonstrated that charcoal changed patient outcome. Cathartics have been deemed to be ineffective and potentially dangerous and are never indicated. Whole bowel irrigation should not be used routinely in the management of the poisoned patient. Multiple dose activated charcoal and urinary alkalinization, commonly used to enhance the elimination of some poisons, have limited usefulness. While these `old' and more general methods of `detoxification' have thus failed in most cases to improve or change patient outcome, the use of more specific antidotes, tailored to the exact cause of intoxication is to be considered. Very few antidotes, however, are used on a consistent basis in the management of poisoned victims. The indiscriminate use of antidotes may even be harmful to the patient and incur an inordinate expense. In addition to the commonly known antidotes N-acetylcysteine (acetaminophen, paracetamol), naloxone (opioids) and flumazenil (benzodiazepines), new antidotes include fomepizole to treat ethylene glycol and methanol poisoning and Crotalidae Polyvalent Immune Fab (Ovine) for pit viper envenomation.

Abstract  Wild female and male white sucker (Catostomus commersoni) inhabiting an area receiving pulp mill effluent had reduced hepatic levels of retinol, didehydroretinol, retinyl esters, and didehydroretinyl esters, while vitamin F levels were unaffected. This disruption of the retinoid system led us to test methanol and dichloromethane extracts from the effluent of 11 pulp mills from across Canada for their ability to bind to rainbow trout (Oncorhynchus mykiss) retinoic acid receptors (RARs) from the gill and retinoid X receptors (RXRs) from the liver. Concentrated extracts of the final effluent from 6 of the 11 pulp mills were able to displace greater than 25% of the receptor-bound [3H]all-trans retinoic acid (RA) or [3H]9-cis RA from trout RARs and RXRs, respectively. The ability of the extracts to displace retinoic acid did not appear to be linked to the pulping or treatment processes. Moreover, extracts with the greatest activity came from thermomechanical mills, suggesting the compounds may originate from the wood furnish. In addition, extracts prepared from wood furnish (wood chips: white spruce [50%], lodgepole pine [47%], and balsam fir [3%]) from one mill were able to displace [3H]RA from the RARs and RXRs. The 4-hydroxy RA, a metabolite of RA that has been shown to be generated in greater quantities in fish exposed to P450-inducing xenobiotics, was able to displace [3H]all-trans RA from trout RARs as effectively as unlabeled all-trans RA. These results suggest that pulp mill effluent may impact the retinoid system of fish at multiple sites, either by decreasing hepatic retinoid stores or through contributing additional ligands (from the wood furnish) that can bind to RA receptors.

Abstract   Methanol has been proposed as an alternative automotive fuel to reduce pollution in the urban environment. Utilization of methanol will increase exposure to low levels of methanol vapors for the general public and in occupational settings. Information on absorption by inhalation and serum concentrations after low-level exposure would be important in evaluating the health impact of generalized methanol exposure. During a randomized double-blind study of the potential neurobehavioral effects of inhaled methanol at 200 ppm for 4 hours, 15 timed specimens from 22 subjects were obtained for methanol analysis by head-space gas chromatography. Methanol was rapidly absorbed by inhalation (absorption rate constant = 0.87 ? 0.60 hours-1). Serum methanol concentrations were increased by more than fourfold at the end of the exposure period (6.5 ? 2.7 vs 0.9 ? 0.6 mg/L), as were urinary methanol excretion rates, although formate concentrations were not increased over background concentrations. The overall (n = 22) elimination half-life was 3.2 ? 2.3 hours. Elimination from plasma fit a monoexponential model for only half of the subjects during the 4-hour postexposure follow-up period (mean half-life = 2.2 hours). Subjects with poor fits either showed greater variability or apparent slow (nonsignificant) declines in serum methanol concentrations, possibly because of the offsetting contributions of dietary intake or endogenous production, but more likely as a result of the limited number of sampling times and limited follow-up period.

Abstract  ABSTRACT Blood methanol concentrations were measured in 24 1-year-old infants administered aspartame, a dipeptide methyl ester sweetener. The doses studied included a dose projected to be the 99th percentile of daily ingestion for adults (34 mg/kg bodyweight), a very high use dose (50 mg/kg body weight) and a dose considered to be in the abuse range (100 mg/kg body weight). Blood methanol values in infants were compared to values observed previously in adults administered equivalent doses of aspartame. Methanol concentrations were below the level of detection (0.35 mg/dl) in the blood of 10 infants administered aspartame at 34 mg/kg body weight, but were significantly elevated (P ½= 0.05) after ingestion of aspartame at 50 and 100 mg/kg body weight. At the latter doses, mean peak blood methanol concentrations and the area under the blood methanol concentration-time curve increased in proportion to dose. Mean (?SEM) peak blood methanol concentration was 0.30 ? 0.10 mg/100 ml at a 50mg/kg body weight aspartame dose (n = 6) and 1.02 ? 0.28 mg/ml at the 100 mg/kg body weight dose (n = 8). Blood methanol values in infants were similar to those observed in normal adults.

Abstract  This paper reports on an experimental study of dermal exposure to neat methanol in human volunteers for the purposes of estimating percutaneous absorption rates, permeation kinetics, baseline (pre-exposure) levels of methanol in blood, and inter- and intrasubject variability. A total of 12 volunteers (seven men and five women) were exposed to methanol via one hand for durations of 0 to 16 min in a total of 65 sessions, making this the largest controlled study of percutaneous absorption for this common solvent. In each session, 14 blood samples were collected sequentially and analyzed for methanol. These data were used to derive absorption rates and delivery kinetics using a two compartment model that accounts for elimination and pre-exposure levels. The pre-exposure methanol concentration in blood was 1.7 +/- 0.9 mg 1(-1), and subjects had statistically different mean concentrations. The maximum methanol concentration in blood was reached 1.9 +/- 1.0 h after exposure. Delivery rates from skin into blood lagged exposure by 0.5 h, and methanol continued to enter the systemic circulation for 4 h following exposure. While in vitro studies have reported comparable lag times, the prolonged permeation or epidermal reservoir effect for such miscible solvents has not been previously measured. The mean derived absorption rate, 8.1 +/- 3.7 mg cm-2 h-1, is compatible with that found in the other in vivo study of methanol absorption. Both in vivo absorption rate estimates considerably exceed in vitro estimates. The maximum concentration of methanol in blood following an exposure to one hand lasting approximately 20 min is comparable to that reached following inhalational exposures at a methanol concentration of 200 ppm, the threshold limit value-time weighted average (TLV-TWA). While variability in blood concentrations and absorption rates approached a factor of two, differences between individuals were not statistically significant. The derived absorption and permeation rates provide information regarding kinetics and absorbed dose that can help to interpret biological monitoring data and confirm mathematical models of chemical permeation.

Abstract  Using proton transfer reaction-mass spectrometry for trace gas analysis of the human breath; the concentrations of methanol and ethanol have been measured for various test persons consuming alcoholic beverages and various amounts of fruits, respectively. The methanol concentrations increased from a natural (physiological) level of ~0.4 ppm up to ~2 ppm a few hours after eating about ¢ kg of fruits, and about the same concentration was reached after drinking of 100 ml brandy containing 24% volume of ethanol and 0.19% volume of methanol.

Abstract  Alcohols are widely used as industrial solvents. In spite of the fact that ethanol is a human teratogen, there has not been systematic investigation of the potential teratogenic effects of other alcohols, particularly using the inhalation route of exposure, as would be appropriate in assessing occupational and environmental types of experience. As part of a large teratological examination of industrial alcohols, methanol and ethanol were administered by inhalation to groups of approximately 15 pregnant Sprague-Dawley rats. Methanol was administered at 20,000 ppm (20ME), 10,000 ppm (10ME), 5000 ppm (5ME), and 0 ppm (MECO) for 7 hr/day on Days 1-19 of gestation (Days 7-15 for 20ME). Ethanol was administered at 20,000 ppm (20ET), 16,000 ppm (16ET), 10,000 ppm (10ET), and 0 ppm (ETCO) for 7 hr/day on Days 1-19 of gestation. Dams were sacrificed on Day 20 (sperm = Day 0). One-half of the fetuses were examined using the Wilson technique for visceral defects, and the other half were examined for skeletal defects. The highest concentration of methanol (20ME) produced slight maternal toxicity and a high incidence of congenital malformations (p less than 0.001), predominantly extra or rudimentary cervical ribs and urinary or cardiovascular defects. Similar malformations were seen in the 10ME group, but the incidence was not significantly different from controls. No adverse effects were noted in the 5ME group. Dams in the 20ET group were narcotized by the end of exposure, and maternal weight gain and feed intake were decreased during the first week of exposure. The 16ET dams had slightly depressed weight gain (p less than 0.01) during the first week of exposure, but there were no significant effects on feed consumption. There was no definite increase in malformations at any level of ethanol, although the incidence in the 20ET group was of borderline significance.