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A comparison of toluene and ethanol (EtOH) induced changes in central nervous system (CNS) function and symptoms were evaluated in two studies, and when possible the effects of toluene were expressed in EtOH equivalent units. The toluene concentrations were 0, 75, and 150 ppm, bracketing the American Conference of Governmental Industrial Hygienists threshold limit value (ACGIH TLV) of 100 ppm. The socially relevant EtOH doses were 0.00, 0.33, and 0.66 g EtOH/kg body weight, equivalent to two and four 3.5% 12 ounce beers. Forty two paid college students were used in each study. In the first study, subjects were exposed to toluene and an odour masking agent menthol (0.078 ppm) for seven hours over three days. In the second study EtOH or a placebo was administered at 1530 across three days also in the presence of menthol. Verbal and visual short term memory (Sternberg, digit span, Benton, pattern memory), perception (pattern recognition), psychomotor skill (simple reaction time, continuous performance, symbol-digit, hand-eye coordination, finger tapping, and critical tracking), manual dexterity (one hole), mood (profile on mood scales (POMS), fatigue (fatigue checklist), and verbal ability were evaluated at 0800, 1200, and 1600. Voluntary symptoms and observations of sleep were collected daily. A 3 x 3 latin square design evaluated solvent effects simultaneously controlling for learning and dose sequence. An analysis of variance and test for trend were performed on am-pm differences reflecting an eight hour workday and on pm scores for each solvent, in which subjects were their own control Intersubject variation in absorbance was monitored in breath. A 5 to 10% decrement was considered meaningful if consistent with a linear trend at p less than 0.05. At 150 ppm toluene, losses in performance were 6.0% for digit span, 12.1% for pattern recognition (latency), 5% for pattern memory (number correct), 6.5% for one hole, and 3% for critical tracking. The number of headaches and eye irritation also increased in a dose-response manner. The greatest effect was found for an increasing number of observations of sleep. A range of 2 to 7% decrements suggest the ACGIH TLV of 100 ppm toluene may be a good estimate of the biological threshold supporting a re-evaluation of the TLV. At 0.66 g EtOH/kg body weight symptoms and performance decrements were 6.6% for digit span, 9.2% for pattern recognition, 4.0% for continuous performance, 7.9% for symbol-digit, 16.5% for finger tapping, 6.2% for critical tracking, and 5.2% for the one hole test. The EtOH equivalents at 150 ppm toluene for digit span (0.56g EtOH/kg/body weight), the latency for pattern recognition (0.66 g EtOH kg body weight), and the one hole element "move" (0.37 g EtOH kg body weight) show that the first two measures would be affected at or above the 50 mg% blood alcohol concentration. This concentration is recognised as the lowest alcohol concentration associated with increased numbers of automobile accidents. The results suggest that EtOH may be a useful acute standard to compare the effects of various industrial solvents and support investigating an association between exposure to solvents and increased risk to safety in industry.
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PMID:Acute behavioural comparisons of toluene and ethanol in human subjects. 195 53

We recently reported that alcoholic rat diaphragm develops greater contractile force than diaphragm of pair-fed control animals. The present experiment examines whether alcohol or dietary restriction is the more likely cause of this surprising finding. We conditioned 10 rats using a liquid diet containing ethanol as 36% of calories. Ten pair-fed control animals received an equal amount of isocaloric, ethanol-free liquid diet. Ten ad libitum control animals had unrestricted access to lab chow and water. Rats were killed after 30 weeks. Left costal diaphragm strips were studied in vitro at optimal length using direct stimulation at supramaximal voltage. Isometric force was measured and divided by muscle cross-section to compute stress. Maximal tetanic stresses developed by muscle from pair-fed controls were systematically less than alcoholic and ad libitum control values (p less than 0.0001); this did not depend on temperature (25 degrees vs. 37 degrees; p greater than 0.50). Pair-feeding increased twitch half-relaxation times (p less than 0.03) and shifted the tetanic stress-stimulation frequency relationship leftward by 10 Hz (p less than 0.01). Diaphragm of pair-fed rats continued to generate lower stresses during the fatigue caused by repeated contractions (p less than 0.01). We conclude that dietary restriction associated with pair-feeding compromises diaphragm performance in rats. Chronic alcohol consumption prevents or reverses these changes, since diaphragm function of alcoholic and ad libitum control animals was not different.
Alcohol Clin Exp Res 1990 Aug
PMID:Alcohol protects the diaphragm during dietary restriction. 222 Dec 85

Recently, we reported that the ingestion of alcohol in rats reduced the mechanical strength of femurs. Our results showed that, as the dose exceeded 0.012 g of ethanol per gram of body weight, a significant (p less than 0.001) loss of "strength" occurred that was independent of sex according to the relationship, Strength (N) = 140.4 - 6003 dose (g/g). In the present effort, the same flexure tests were reevaluated to include the parameters of stiffness, toughness, and ductility. These latest results confirm that the femurs of rats fed an ethanol liquid diet for 4 weeks are not only weaker but also more compliant and less energy absorbing. Although the femurs of rats fed ethanol are more ductile, the bones are more prone to fracture in fatigue and impact circumstances as well as under simple loading situations. The rat may be an appropriate model to study the mechanisms that lead to the higher incidence of fractures in the alcoholic human.
Alcohol Clin Exp Res 1989 Apr
PMID:Influence of ethanol on stiffness, toughness, and ductility of femurs of rats. 265 53

Young adult sons of alcoholic fathers (HR) were compared with matched young men from families without alcoholic relatives (LR) with respect to perceived mood, perceived intoxication, and plasma prolactin responses to oral challenge with two doses of alcohol and a placebo drink. HR subjects were found to have a qualitatively and quantitatively different mood response than controls to all three beverage conditions. HR subjects endorsed greater tension, depression, and fatigue across beverage conditions independent of alcohol dose. Alcohol dose interacted with risk status for perceived anger, vigor, and confusion. HR subjects reported less perceived intoxication on the descending limb of the alcohol concentration-time curve across all three conditions. These differential responses could not be explained by the occurrence of personality subtypes determined through administration of the Tridimensional Personality Questionnaire. A significantly reduced prolactin response to alcohol in HR subjects could not be confirmed. Perceived mood effects of alcohol could have etiological significance in the development of alcoholism among HR individuals.
Alcohol Clin Exp Res 1989 Apr
PMID:Responses by sons of alcoholic fathers to alcoholic and placebo drinks: perceived mood, intoxication, and plasma prolactin. 265 66

The ergogenic potential of drugs used by athletes to enhance performance is reviewed, and areas of involvement for pharmacists interested in the problem of drug abuse in athletics are described. Athletes use drugs for therapeutic and recreational purposes, as supposed ergogenic aids, and to mask the presence of other drugs during testing. Because many athletes train for competition and not for health, they may view the risk-to-benefit ratio of ergogenic drugs as favorable and may begin using them at an early age. Alcohol is the drug most commonly used by student athletes. Although alcohol has no ergogenic benefit, it is viewed as a caloric source and an anxiolytic. Amphetamines do not prevent exhaustion but may mask fatigue, which can have dangerous consequences. Anabolic steroids appear to increase strength but frequently cause adverse reactions, primarily involving the hepatic and endocrine systems. Beta-blocking agents have been shown to reduce anxiety, hand tremor, and heart rate in precision sports like archery, but susceptible persons may experience serious adverse effects. Caffeine improves the efficiency of fuel use and reduces fatigue; its use has been banned by several athletic organizations. Neither cocaine nor marijuana causes any increase in strength. Secretion of human growth hormone may be stimulated by a variety of agents, but evidence that any subsequent increases in size and weight occur is lacking. Other substances tried by athletes include vitamins and minerals, naloxone, albuterol, and human recombinant erythropoietin. Opportunities in sports pharmacy exists in the areas of information retrieval and interpretation, drug testing, legislation to reclassify drugs, education, and research.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Abuse of drugs used to enhance athletic performance. 268 62

In 1985, 30 rotogravure printers exposed to toluene for 4-43 years (median 29) were examined by means of interviews and psychometric testing. They were 33-61 years of age (mean 50). Comparisons were made with a reference group of 72 men aged 27-69 (mean 47). The referents had never been exposed to solvents and were all in good health. The printers were employed by two Swedish companies. The mean exposure levels were 43 and 157 mg/m3 of toluene, respectively, at the two printing shops. Before 1980 the exposure levels had exceeded 300 mg/m3. On Monday mornings, before psychometric testing at the department of occupational medicine, toluene was measured in venous blood samples from most of the exposed subjects. A high proportion of the printers reported fatigue (60%), recent short-term memory problems (60%), concentration difficulties (40%), mood lability (27%), and other neurasthenic symptoms. In the psychometric tests their performance was poorer than the reference group's in most of the tests applied. Even performance on the synonyms test, usually considered resistant to mild brain affliction, was worse in the group of printers. Adjusting for this difference in the group comparisons reduced the group differences substantially. Alcohol consumption above 200 g/week was found to reduce the subjects' psychometric function more than toluene exposure. The printers' sum of neurasthenic complaints correlated negatively with their score in several tests. Exposure variables showed only weak associations with test results. Blood toluene levels were positively correlated with scores in spatial tests. The direction of the correlations suggests that the influence of acute pharmacologic effects is undetectable on Monday mornings before work. In conclusion, we found that exposure to toluene at levels below 157 mg/m3 following long-term exposure did induce neurasthenic problems and might reduce psychometric test performance.
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PMID:Neurasthenic complaints and psychometric function of toluene-exposed rotogravure printers. 275 Jul 52

Disturbances of movement and other motor functions can result from exposure to toxicants and drugs. Sometimes, as with acute exposure to ethanol or solvents, these effects disappear when exposure ends. Other times, as with manganese, haloperidol, or chronic ethanol, motor disturbances are irreversible and may even lie undetected until after exposure has ended. Motor disturbances can take on many guises, including tremor, difficulty in positioning, fatigue, or rigidity. Techniques for measuring these different endpoints in primates will be addressed. One preparation that enables the simultaneous monitoring of positioning, tremor, and operant behavior in nonhuman primates is described, and tactics for obtaining spectral estimates of tremor from a positioning task are outlined. The spectra obtained from this preparation are reliable and valid: they are stable over a period of a year, they correspond to spectra obtained from accelerometers, and are altered by acute administration of ethanol or oxotremorine. These two drugs had opposite effects on tremor but affected bar positioning in a similar manner.
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PMID:Quantification of motor function in toxicology. 314 Apr 29

The influence on the kinetics of toluene from long-term occupational exposure, cigarette smoking, and ethanol consumption was studied in 26 male spray painters. A group of spray painters with reported subjective symptoms such as concentration deficits, fatigue, and dizziness due to the solvent exposure did not differ in the uptake and disposition of toluene from a group of spray painters with no symptoms. In occupationally exposed workers, a tendency for an enhanced clearance of toluene from the blood was observed in relation to personal habits such as smoking and/or moderate chronic ethanol intake. Long-term occupational exposure to a mixture of organic solvents does not exert any effect on the metabolic rate of toluene as compared with that of an unexposed group.
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PMID:Toxicokinetics of toluene in occupationally exposed volunteers. 382 7

Thirteen healthy male volunteers ingested a single 0.25 mg dose of the thienodiazepine hypnotic, brotizolam, on two occasions: once with a typical social cocktail (containing 60 ml of vodka), and in a second trial with an 'ethanol-placebo' cocktail. Brotizolam kinetics were determined from multiple plasma concentrations measured during the 24 h after dosage. Coadministration of brotizolam with ethanol, as opposed to the placebo cocktail, slightly imparied brotizolam clearance (1.85 vs 2.19 ml min-1 kg-1 P less than 0.005), increased peak plasma concentrations (5.3 vs 4.3 ng ml-1, P less than 0.05), and prolonged elimination half-life (5.2 vs 4.4 h, P less than 0.05). There was evidence of impairment of performance, although not statistically significant, for the first 4-6 h after brotizolam dosage in the reaction time test, the digit-symbol substitution test, and a tracking task. None of these was enhanced by ethanol. In both trials, brotizolam produced significant increases in self-rated perceptions of sedation, fatigue, feeling 'spaced-out', and thinking slowed down. These effects were more intense during the brotizolam-ethanol as compared to brotizolam-placebo. In both trials, recovery was essentially complete by 6-8 h after dosage. Coadministration of brotizolam with ethanol produces a small but significant impairment of brotizolam clearance. Brotizolam produced self-rated perceptions of sedation and fatigue during 4-6 h after dosage, but objective impairment of psychomotor performance was minimal. Subjective perceptions of sedation were enhanced by ethanol coadministration, but the effects on psychomotor performance were not.
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PMID:Kinetic and dynamic interaction of brotizolam and ethanol. 395 36

Twelve healthy male volunteers were treated (double-blind crossover design) with tofisopam (a new 3,4-benzodiazepine), diazepam, or placebo, on 2 consecutive days each. Psychomotor skills were impaired after a single dose of diazepam (10 mg) given on day 1. Measurements on day 2 showed that some tolerance had developed to the diazepam-induced impairment of reactive and coordinative skills, but not to its effects on flicker fusion or on the extraocular muscle balance. Tofisopam failed to impair performance both as a single dose (100 mg) and after repeated doses (100 + 50 + 50 + 100 mg). The subjects felt more fatigue, dizziness, calmness, and passiveness after diazepam than after tofisopam. When either drug was given together with 0.8 g/kg ethanol on day 2, the breath ethanol concentrations were 0.7--1.0 mg/ml and all psychomotor skills were impaired. Diazepam + ethanol particularly impaired memory and learning as well. After this combination the subjects were classified (time anticipation test) as 'disqualified drivers' more often than after placebo. It is concluded that diazepam, as well as either benzodiazepine with ethanol, may reduce the ability to drive vehicles or operate machinery.
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PMID:Tofisopam, a novel 3,4-benzodiazepine: multiple-dose effects on psychomotor skills and memory. Comparison with diazepam and interactions with ethanol. 610 45


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