ABSTRACT
INTRODUCTION: The lifestyle product 'Eezup!' appeared on the German market and promised to normalize energy metabolism. Among vitamins (B1, B2, B6, C, E and zinc), rice protein and fructose the addition of alcohol dehydrogenase and catalase enzymes is a novel approach. The product was advertised as capable of boosting the rate of alcohol elimination. METHODS: Seventeen subjects (11 men, 6 women, 19-58 years old), participated in a two-way crossover drinking study. Unfiltered wheat beer (4.4g% alcohol content) was drank within one hour to reach blood alcohol concentrations of 1 (1g/kg whole blood). On one day "Eezup!" was taken according to the manufacturer's instructions before and after drinking which was substituted for a placebo on the second test day. Blood samples were taken during 9h and ethanol and congener alcohols were determined. A comparison of Cmax, tmax, area under the curve (AUC) for ethanol and congener alcohols, and the hourly elimination rate of ethanol (ß60) was performed to investigate an effect of Eezup!. RESULTS: Ethanol concentrations (Cmax) were in the range of 0,63-1,00 (median 0,85) and 0.62-1.22 (median 0.84) in the placebo and "Eezup!" condition, respectively, and not statistically different. Also tmax (1-2.5h) and AUCs did not differ. The ethanol elimination rates were 0.16/h (0.14-0.19/h) and 0.17/h (0.14-0.22 /h) in the placebo and "Eezup!" condition without significant difference. The pharmacokinetic parameters of the congener alcohols (1-propanol, isobutanol, 3-methyl-1-butanol, 2-methyl-1-butanol) as well as of methanol did also not differ. CONCLUSIONS: The results of the present study failed to show any effect of the sobering product "Eezup!" on the amount of ethanol and congener alcohols absorbed (Cmax, tmax, AUC) and on the ethanol elimination rate (ß60).
Subject(s)
Alcoholic Intoxication/prevention & control , Beverages , Central Nervous System Depressants/pharmacokinetics , Ethanol/pharmacokinetics , 1-Propanol/blood , Adult , Beer , Butanols/blood , Central Nervous System Depressants/blood , Ethanol/blood , Female , Humans , Male , Middle Aged , Pentanols/blood , Young AdultABSTRACT
Butane is an addictive volatile substance like toluene. We report three forensic autopsy cases of sudden death that occurred while sniffing n-butane and isobutane from portable gas cartridges. n-Butane and isobutane were detected in all three cases. In cases 1-3, n-butane concentrations in heart blood were 54.3, 25.5, and 30.7µg/mL, respectively. These concentrations were considered fatal according to the previous reports. In addition, n-butane metabolites (2-butanol and 2-butanone) were detected in cases 1 and 3 but not in case 2. Blood levels of 2-butanol and 2-butanone were 6.5 and 1.8µg/mL, respectively, in case 1, and 6.3 and 5.6µg/mL, respectively, in case 3. According to the police investigation, the decedent in case 1 had misused butane gas for more than 6 months in the period leading up to death. The decedent in case 3 also had a history of chronic misuse of butane gas. There was no history of chronic misuse of butane gas by the decedent in case 2. It was suspected that he attempted suicide via inhalation of butane gas using a plastic bag, leading to a rapid death. The presence or absence of n-butane metabolites might reflect the way of butane inhalation, such as the frequency and duration. Although additional experimental and case studies are necessary to establish the forensic applications of n-butane metabolite detection, it may be a useful method to understand the decedents' pattern of butane sniffing before death.
Subject(s)
Butanes/blood , Butanes/poisoning , Butanols/blood , Butanones/blood , Inhalant Abuse/blood , Adolescent , Adult , Brain Edema/pathology , Female , Forensic Toxicology , Gas Chromatography-Mass Spectrometry , Humans , Male , Pulmonary Edema/pathology , SuicideABSTRACT
PURPOSE: Neurokinin 1 (NK1) receptors have been implicated in depression, anxiety, and pain perception. Recently, it was shown that, in the human brain, a specific NK1 receptor-related signal was obtained with the novel radioligand, [¹¹C]R116301, using positron emission tomography. The purpose of this study was to evaluate various methods for quantifying specific [¹¹C]R116301 binding. METHODS: Two dynamic 90-min [¹¹C]R116301 scans, separated by 5 h, were performed in 11 healthy volunteers. In three patients, the second scan was performed after an oral blocking dose of 125 mg of aprepitant, whereas in the other eight, no intervention was performed (test-retest). Whole striatum was used as the tissue of interest, as it has the highest density of NK1 receptors. Cerebellum was used as the reference tissue. RESULTS: Reference tissue models were stable with the simplified reference tissue model (SRTM) performing best. Average (± standard deviation) SRTM-derived mean nondisplaceable binding potential (BP(ND)) of all (first) baseline scans was 0.64±0.31 (n=11), which reduced to -0.01±0.03 (n=3) after aprepitant administration. Test-retest results showed low variability (14.0±10.7%) and excellent reliability, as indicated by the intraclass correlation coefficient (0.93). The ratio of standardized uptake values of striatum and cerebellum minus 1, an approximation of BP(ND), showed very low variability (6.2±3.1%) with excellent reliability (intraclass correlation coefficient=0.98), and correlated well with SRTM-derived BP(ND) (R²=0.96). CONCLUSION: SRTM is the model of choice for quantifying [¹¹C]R116301 binding. Semiquantitative tissue ratios hold promise for routine clinical applications.
Subject(s)
Butanols/metabolism , Receptors, Neurokinin-1/metabolism , Adult , Butanols/blood , Carbon Radioisotopes , Cerebellum/diagnostic imaging , Cerebellum/metabolism , Female , Humans , Kinetics , Ligands , Malates , Male , Middle Aged , Neostriatum/diagnostic imaging , Neostriatum/metabolism , Piperidines , Positron-Emission Tomography , Protein Binding , Reference Standards , Substrate Specificity , Young AdultABSTRACT
Valone is a chronic anticoagulant rodenticide that has come into wide use in China. Current literature lacks analytical methods for the determination of valone. In this paper, a sensitive and selective assay was established for the identification and quantification of valone in serum by liquid chromatography-tandem mass spectrometry. After addition of the internal standard, warfarin, serum samples were extracted with 10% methanol in acetonitrile and cleaned using Oasis HLB solid-phase extraction (SPE) cartridges. The compounds were separated on an Agilent SB C18 column with a mobile phase of methanol/acetic acid-ammonium acetate (5 mmol/L, pH 6.3) (75:25, v/v). Detection was performed by electrospray ionization ion trap mass spectrometry in the negative multiple reaction monitoring mode. The transition ions of m/z 229 --> 145 and m/z 307 --> 161 were selected for quantification of valone and the internal standard, respectively. The overall extraction efficiency was between 81.1% and 91.1%. The limit of quantification was 0.5 ng/mL. Regression analysis of the calibration data revealed good correlation (r(2) > 0.99) for valone. Intra- and interday precisions for quality-control samples were less than 7.8% and 12.8%, respectively. This method combines a rapid SPE procedure with an extremely fast chromatographic analysis, which is especially advantageous or clinical laboratories.
Subject(s)
Butanols/blood , Chromatography, High Pressure Liquid/methods , Indenes/blood , Rodenticides/blood , Tandem Mass Spectrometry/methods , Adult , Butanols/poisoning , Female , Humans , Indenes/poisoning , Male , Poisoning/blood , Reference Standards , Reproducibility of Results , Rodenticides/poisoning , Sensitivity and Specificity , Time Factors , Young AdultABSTRACT
The second part of this review describes the principles and practice of forensic congener analysis as an alternative way to evaluate claims of drinking alcohol after driving. Congener analysis was developed, perfected and practised in Germany as a way to evaluate hip-flask defences. This kind of defence challenge arises frequently when the drunk driving suspect is not apprehended at the wheel and especially after hit-and-run incidents. Besides ethanol and water, alcoholic beverages contain trace amounts of many other low-molecular substances, known collectively as the congeners, which impart the characteristic smell and taste to the drink. Importantly, the congener profile can be used to identify a particular kind of alcoholic beverage. Forensic congener analysis entails making a qualitative and quantitative analysis of ethanol, methanol, n-propanol and the isomers of butanol in blood and urine from the apprehended driver and comparing the results with the known congener profile of the alcoholic beverage allegedly consumed after driving. Interpreting the results of congener analysis requires knowledge about the absorption, distribution and elimination pattern of the congener alcohols, including their oxidation and conjugation reactions, and any metabolic interactions with ethanol. Complications arise if drinks with widely different congener profiles are consumed or if the same beverage was ingested both before and after driving. Despite these limitations, congener analysis can furnish compelling evidence to challenge or support claims of drinking alcohol after driving.
Subject(s)
1-Propanol/blood , Alcoholic Intoxication/blood , Automobile Driving/legislation & jurisprudence , Butanols/blood , Ethanol/blood , Forensic Medicine/methods , 1-Propanol/metabolism , Alcohol Drinking , Alcoholic Intoxication/diagnosis , Alcoholic Intoxication/metabolism , Butanols/metabolism , Chromatography, Gas , Ethanol/metabolism , HumansABSTRACT
OBJECTIVE: To test the effect of the neurokinin-1 receptor antagonist hydroxybutanedioate (R116301) in human hand veins in vivo. METHODS: In a randomized, double-blind, placebo-controlled crossover study we used the hand vein compliance method to evaluate the inhibition of the response to substance P by R116301. RESULTS: In hand veins preconstricted with phenylephrine to 21% +/- 2.6% (mean +/- SEM, placebo) and 25% +/- 3.0% (R116301) of the initial diameter, substance P resulted in a mean venodilation of 84% +/- 7% and 87% +/- 13% (P = .8) before administration of placebo and R116301, respectively. Oral administration of 300 mg R116301 resulted in peak plasma concentrations of 1.16 +/- 0.1 microg/mL within 128 +/- 14 minutes. With increasing R116301 plasma concentrations, substance P-induced venodilation decreased significantly (P < .001), whereas placebo had no effect. Mean substance P-induced venodilation was markedly reduced to 8% +/- 7%. CONCLUSION: This study confirms the presence of neurokinin-1 receptors in human veins and the effectiveness of the neurokinin-1 receptor antagonist R116301 in human hand veins.
Subject(s)
Butanols/pharmacology , Neurokinin-1 Receptor Antagonists , Substance P/pharmacology , Vasoconstriction/drug effects , Vasoconstrictor Agents/pharmacology , Vasodilation/drug effects , Vasodilator Agents/pharmacology , Administration, Oral , Adult , Area Under Curve , Butanols/administration & dosage , Butanols/blood , Cross-Over Studies , Double-Blind Method , Hand/blood supply , Humans , Malates , Male , Piperidines , Reference Values , Substance P/administration & dosage , Vasoconstrictor Agents/administration & dosage , Vasoconstrictor Agents/blood , Vasodilator Agents/administration & dosage , Veins/drug effectsABSTRACT
Methyl tertiary-butyl ether (MTBE) and its metabolite tertiary-butanol (TBA) both cause renal tumors in chronically exposed male rats. Knowledge of the kinetic behavior of MTBE and TBA in rats and its comparison to the kinetics of these chemicals in humans will aid in assessing human risk. The objective of this study was to develop a physiologically based pharmacokinetic (PBPK) model for MTBE and TBA in rats that will form the basis for a human model. Physiological parameters such as blood flows, tissue volumes, and alveolar ventilation were obtained from the literature. Chemical-specific parameters such as the solubility of MTBE and TBA in blood and selected tissues and metabolic rate constants to describe whole-body metabolism of MTBE in rats were measured using vial equilibration and gas uptake techniques, respectively. MTBE metabolism was described in the model as occurring through two saturable pathways. The model was able to predict gas uptake data (100 to 2000 ppm starting concentrations) and levels of MTBE in blood of rats exposed to MTBE by inhalation (400 to 8000 ppm, 6 hr), i.v. (40 mg/kg), and oral (40 or 400 mg/kg) administration. Two different models to describe the dosimetry of TBA in a rat were tested for their ability to predict TBA blood levels after MTBE exposure. TBA blood levels were predicted best at low MTBE exposure concentrations using a two-compartment model. The pharmacokinetics of TBA appear to be far more complex than those of MTBE, and additional experimental data on TBA distribution and elimination will be necessary to refine the submodel. With a quantitative description of the important determinants of MTBE and TBA dosimetry understood, a better assessment of the potential toxic and cancer risk for humans exposed to MTBE can be made.
Subject(s)
Butanols/pharmacokinetics , Carcinogens/pharmacokinetics , Methyl Ethers/pharmacokinetics , Administration, Inhalation , Animals , Butanols/blood , Humans , Male , Methyl Ethers/blood , Models, Biological , Rats , Rats, Inbred F344 , Risk Assessment , Solvents/pharmacokinetics , tert-Butyl AlcoholABSTRACT
We developed an isotope-dilution method for measuring methyl tert-butyl ether (MTBE) and tert-butyl alcohol (TBA) in whole human blood using a purge-and-trap gas chromatographic-mass spectrometric method. The labeled analogues for MTBE and TBA were [2H12]methyl tert-butyl ether and [2H9]-tert-butyl alcohol, respectively. Volatiles were removed from the blood by direct helium purging of the liquid; were trapped on a Tenax trap; and were desorbed, cryofocused, and chromatographed on a DB-624 capillary column that was connected directly to the ion source of a mass spectrometer. Detection was by mass analysis using a double-focusing magnetic-sector mass spectrometer operating in the full-scan mode at the medium mass resolution of 3000. For the isotope-dilution method, the minimum detection limits in blood (5-10 mL) are 0.01 microgram/L for MTBE and 0.06 microgram/L for TBA. The isotope-dilution method proved to be a big improvement in recovery, reproducibility, and sensitivity over our previous analytical method, which used the labeled ketone, [4-2H3]-2-butanone, as the internal standard for both MTBE and TBA. The isotope-dilution method has sufficient sensitivity for monitoring blood levels of MTBE and TBA in populations exposed to oxygenated fuels containing MTBE.
Subject(s)
Butanols/blood , Ethers/blood , Methyl Ethers , Butanols/urine , Ethers/urine , Gas Chromatography-Mass Spectrometry/instrumentation , Gas Chromatography-Mass Spectrometry/methods , Humans , tert-Butyl AlcoholABSTRACT
A simple method for the extraction of 5 thinner components from human whole blood and urine, using the headspace solid-phase microextraction (SPME) method is presented. After heating a vial containing the samples with 5 compounds (toluene, benzene, n-butyl acetate, n-butanol and n-isoamyl acetate) at 80 degrees C, a polydimethylsiloxane-coated SPME fiber was exposed to the headspace of the vial to allow adsorption of the compounds. The fiber needle was then injected into a capillary gas chromatography (GC) port. The headspace SPME-GC gave intense peaks for each compound and a low level of background noise was seen only for whole blood. Recovery rates of the 5 compounds by use of the headspace SPME-GC were 50-70%. Reproducibility for headspace SPME-GC data were excellent for both body fluids. The calibration curves showed linearity in the range 2-100 ng/0.5 ml whole blood or urine. The detection limits of each compound were 1.1-2.4 ng/0.5 ml sample. The present results on the analysis of 5 thinner components by headspace SPME-GC suggest its applicability to a number of other volatile compounds in forensic toxicology.
Subject(s)
Chromatography, Gas/methods , Solvents/analysis , Substance Abuse Detection/methods , 1-Butanol , Acetates/blood , Acetates/urine , Benzene/analysis , Butanols/blood , Butanols/urine , Forensic Medicine , Humans , Pentanols/blood , Pentanols/urine , Reproducibility of Results , Toluene/blood , Toluene/urineABSTRACT
The levels of m-xylene and n-butyl alcohol in blood of rats during single and combined inhalation exposure to m-xylene and n-butyl alcohol at the concentrations of 100 + 100 ppm were investigated. We found that levels of n-butyl alcohol and m-xylene in blood of animals during single exposure did not differ as compared to coexposure. It has been shown that less than additive neurotoxic and irritating respiratory tract effects of m-xylene and n-butyl alcohol mixture, observed earlier under acute and subchronic inhalation study, cannot be explained by their metabolic interaction.
Subject(s)
Butanols/blood , Xylenes/blood , 1-Butanol , Administration, Inhalation , Analysis of Variance , Animals , Butanols/pharmacokinetics , Dose-Response Relationship, Drug , Male , Rats , Rats, Wistar , Xylenes/pharmacokineticsABSTRACT
Residents of Fairbanks, Alaska reported health complaints when 15%, by volume, methyl tertiary butyl ether (MTBE) was added to gasoline during an oxygenated fuel program. We conducted an exposure survey to investigate the effect of the program on human exposure to MTBE. We studied 18 workers in December 1992 during the program and 28 workers in February 1993 after the program was suspended. All workers were heavily exposed to motor vehicle exhaust or gasoline fumes. In December, the median post-shift blood concentration of MTBE in the workers was 1.8 micrograms/l (range, 0.2-37.0 micrograms/l), and in February the median post-shift blood concentration of MTBE in the 28 workers was 0.24 micrograms/l (range, 0.05-1.44 micrograms/l; p = .0001). Blood MTBE levels were measurably higher during the oxygenated fuel program in Fairbanks than after the program was suspended.
Subject(s)
Ethers/blood , Gasoline/analysis , Methyl Ethers , Occupational Exposure , Adult , Air Pollutants, Occupational/analysis , Alaska , Butanols/blood , Female , Gas Chromatography-Mass Spectrometry , Humans , Male , Surveys and Questionnaires , Vehicle Emissions/analysis , tert-Butyl AlcoholABSTRACT
1. A continuous 5 h-exposure to approximately 440 ppm tert-butyl acetate in air (via a tracheal canule) resulted in continuously increasing concentrations of tert-butyl acetate and tert-butyl alcohol (metabolite of tert-butyl acetate) in the blood of rats. 2. This accumulation of tert-butyl acetate and tert-butyl alcohol was reproduced during a continuous exposure to about 900 ppm tert-butyl acetate in air over a period of 4 h and 15 min. After the inhalation approximately 50% of the blood level of tert-butyl acetate decreased within 45 min, but that of tert-butyl alcohol remained unchanged at a high level. 3. The accumulation of tert-butyl acetate and tert-butyl alcohol should be relevant for the health risk assessment at the workside.
Subject(s)
Acetates/metabolism , Butanols/blood , Solvents/metabolism , Acetates/blood , Administration, Inhalation , Animals , Female , Rats , Rats, Sprague-Dawley , tert-Butyl AlcoholABSTRACT
Lifibrol, a new drug for the treatment of hypercholesterolemia, contains a stereogenic center bearing a secondary alcohol group. A normal-phase achiral-chiral HPLC separation of the enantiomers of lifibrol and two of its metabolites was developed and validated for quantitation in dog plasma. A silica and a Chiralcel OD-H column were operated in series and all six enantiomeric components and internal standard were directly separated. An initial solid-phase extraction (phenyl) clean-up step and a column-switching step to eliminate late-eluting compounds were also utilized. The solid-phase extraction step was automated using a robotic system. Assay development, validation, and application of the method to a bioavailability study of the racemate and enantiomers of lifibrol in dogs are described. The lower limit of quantitation was 0.0125 microgram/ml for each enantiomer of lifibrol using 200 microliters of dog plasma with UV detection (255 nm). In dog plasma following oral or intravenous administration of the racemate, the (R)/(S) ratio of the enantiomers of lifibrol was greater than one and increased with time. Following administration of the individual enantiomers, chiral inversion of the (S)-enantiomer but not the (R)-enantiomer was observed.
Subject(s)
Butanols/blood , Hydroxybenzoates/blood , Hypolipidemic Agents/blood , Administration, Oral , Animals , Autoanalysis , Biological Availability , Butanols/pharmacokinetics , Chromatography, High Pressure Liquid , Dogs , Female , Hydroxybenzoates/pharmacokinetics , Hypolipidemic Agents/pharmacokinetics , Injections, Intravenous , Male , Robotics , Spectrophotometry, Ultraviolet , StereoisomerismABSTRACT
The development of cross-tolerance to various alcohols and pentobarbital was examined in ethanol (EtOH)-treated mice. Chronic EtOH treatment (dosage rising in steps from 3.5-4.5 g/kg i.p. daily during a 23-day period) produced tolerance to its hypnotic effect. Such tolerance was seen as a reduction in the duration of loss of righting reflex (LRR), as well as higher blood EtOH levels at the offset of LRR, in EtOH-treated mice as compared to saline-treated controls. Cross-tolerance was shown by shifts in dose-response curves for the LRR induced by n-propanol and t-butanol. Such treatment, however, did not confer functional cross-tolerance to n-butanol and pentobarbital. Because n-butanol and pentobarbital are more lipid-soluble, whereas EtOH, n-propanol and t-butanol have low degrees of lipid solubility, the development of cross-tolerance among these sedative-hypnotic drugs might be related to their relative degrees of lipid solubility.
Subject(s)
Ethanol/administration & dosage , Hypnotics and Sedatives/administration & dosage , 1-Butanol , 1-Propanol/blood , 1-Propanol/pharmacology , Analysis of Variance , Animals , Butanols/blood , Butanols/pharmacology , Drug Tolerance , Ethanol/blood , Ethanol/pharmacology , Male , Mice , Pentobarbital/blood , Pentobarbital/pharmacology , Reflex/drug effects , Sleep/drug effectsABSTRACT
As shown by others, ethanol and methanol appear in the breath of normals, and endogenous methanol becomes detectable also in the blood after intake of ethanol. In this study I have investigated whether low-molecular-weight volatile organics, other than methanol, arise in the blood of drunk drivers who had imbibed alcoholic beverages. To this end a method for searching for such compounds in the blood is described. It was based on headspace extraction, gas chromatographic separation on a DB-WAX capillary, and ion trap detection in the mass range 29-99 u. Detection limits, as defined by the analyte concentration that gives a signal equal to three times the standard deviation of the baseline noise, were estimated for the different mass numbers used in the substance search. Given the detection limits, presented as mmoles per litre (numbers within parentheses), in every drunk driver's blood with more than 10 mmol l-1 of ethanol between seven and nine different volatile substances were spotted. These were ethanol (0.15), 2-propanone (0.015), ethyl acetate (0.0005), 2-butanone (0.006), methanol (1.5), 2-propanol (0.06), ethanol (0.7), 2-butanol (0.03), and 1-propanol (0.03).
Subject(s)
Alcoholic Intoxication/blood , Automobile Driving , 1-Propanol/blood , Acetaldehyde/blood , Acetates/blood , Acetone/blood , Butanols/blood , Butanones/blood , Ethanol/blood , Gas Chromatography-Mass Spectrometry/methods , Humans , In Vitro Techniques , Methanol/bloodABSTRACT
n-Butanol appears in large quantities in the blood of a drowned person and a correlation exists between its quantity (concentration) and the time the body lay in water. This correlation depends on the temperature of the water but not on whether it is fresh or salt water. The time of death can be fixed within the span of 0-26 days after the event, as we have found out in our research (no longer period has been examined).
Subject(s)
Butanols/blood , Drowning/blood , 1-Butanol , Forensic Medicine/methods , Humans , Seasons , Time FactorsABSTRACT
The kinetics of inhaled methyl ethyl ketone (MEK) at a concentration of 200 ppm for four hours were studied in volunteers after swallowing ethanol at a dose of 0.8 g/kg. Ethanol was given either before or at the end of the exposure to MEK. The blood concentrations of MEK, 2-butanol, and 2,3-butanediol were monitored during and after the exposure. MEK concentrations in exhaled air and MEK and 2,3-butanediol concentrations in urine were also measured. Ethanol inhibited the primary oxidative metabolism of MEK and caused an increase in the blood concentrations of MEK and 2-butanol after ingestion. Ethanol ingestion, through higher blood MEK concentrations, also increased the elimination of MEK in the urine and exhaled air. Ethanol taken before exposure to MEK reduced the serum concentration of 2,3-butanediol initially but there was an increase about eight hours after the exposure. Urinary excretion of 2,3-butanediol followed the same pattern. Prior ingestion of ethanol thus seemed to interfere with the metabolism of 2,3-butanediol during and after exposure to MEK.
Subject(s)
Butanones/pharmacokinetics , Ethanol/pharmacology , Lung/metabolism , Adult , Butanols/blood , Butanones/blood , Butylene Glycols/blood , Butylene Glycols/urine , Humans , MaleABSTRACT
For a more sensitive detection of paint thinner components in body fluids, we made use of a salting-out technique, with sodium chloride added to blood samples followed by gas chromatography, using the headspace method. The detection of ethyl acetate and isobutanol was considerably enhanced using these approaches.
Subject(s)
Acetates/blood , Butanols/blood , Toluene/blood , Ammonium Sulfate , Carbonates , Chromatography, Gas , Gas Chromatography-Mass Spectrometry , Humans , Mutagens/blood , Potassium , Reproducibility of Results , Sodium ChlorideABSTRACT
The influence of "accelerants" on the percutaneous absorption of 3 organic solvents (butanol, toluene, 1,1,1-trichloroethane) was investigated in the guinea pig. DMSO in binary and ternary mixtures with various concentrations, the result of adding 0.1 M C18 fatty acids, and of pretreatment with DMSO and olive oil, were studied. Addition of DMSO (binary solutions) resulted in increased or decreased absorption of the solvents related to their water solubility. There was reduced absorption of toluene and trichloroethane in binary mixtures with DMSO, while DMSO in binary mixture with butanol gave a marked increase, with concentrations of 50 and 75%. Pretreatment with DMSO resulted in a decrease in the absorption of toluene and a marked increase in the absorption of butanol. The same tendency was seen when skin was pretreated with olive oil under occlusion. The results indicate that the effect of DMSO is related to the water solubility of the penetrant.