Search

Saccharomyces cerevisiae genetically engineered to enhance butanol production will be used in a manufacturing process similar to that of fuel ethanol production, including co-production of distillers products for animal feed. A poultry feeding trial was conducted with simulated isobutanol-derived dried distillers grains with solubles (bDDGS), comprising non-fermentable corn solids and heat-inactivated Butamax modified yeast (BMY), to determine potential health effects. Simulated dried distillers grains were produced in 2 variants: bDDGS containing 10% (B10) or 50% (B50) BMY. The BMY concentrations were selected based on a conservative estimate from ethanol-derived distillers grains (eDDGS) approximating 2.5 and 12-fold margins of exposure. The B10 and B50 DDGS were evaluated in a 42-day feeding trial using male Ross 708 broiler chickens fed diets containing eDDGS, B50 DDGS, or B10 DDGS without or with isobutanol, 2,3-butanediol, and isobutyric acid metabolites each at target concentrations of 2 (B10-2), 5 (B10-5), or 10 (B10-10) times the anticipated specification limit in the commercial product. Diets were fed (n = 50 broilers/treatment) in 3 phases: starter phase with 8% DDGS and grower and finisher phases each with 15% DDGS. No statistically significant differences or diet-related effects on mortality, clinical pathology, or organ weights, and no microscopic observations associated with consumption of diets containing B10, B50, or B10 supplemented with metabolites at any targeted exposure level were observed. A lower (P < 0.05) mean absolute bursa of Fabricius weight in the B10-10 group compared to the B10 group was considered to be within the range of biological variability. A non-significant trend toward lower weight, gains, and feed intake, and higher feed:gain ratio was observed in the B10-10 group, and was considered a non-adverse palatability effect of consuming high concentrations of metabolites. These results demonstrate that consumption of phase diets containing simulated DDGS from a novel isobutanol production process was well-tolerated., Competing Interests: K.S. Reidinger is an employee of Butamax Advanced Biofuels, LLC, the funding entity for the work presented within the manuscript, and the producer of Butamax Modified Yeast. A. Chen is an employee of DuPont Industrial Biosciences, a related entity to Butamax Advanced Biofuels, LLC. J.M. Roper and J.M. Caverly Rae are employees of DuPont Haskell Global Center for Health Sciences (DuPont Haskell). B.L. Smith, E. Huang, and C.A. Walker are employees of DuPont Pioneer. J.L. McNaughton is an employee of AHPharma, Inc. DuPont Pioneer, DuPont Haskell, and AHPharma, Inc. received financial support from Butamax Advanced Biofuels, LLC for materials, resources and consulting expertise related to the design, conduct, analysis and interpretation of the studies presented within this manuscript. These disclosed commercial affiliations do not alter the authors’ adherence to PLOS ONE policies on sharing data and materials. The authors declare no additional potential competing interests.

Background: Rhododendrol (rhododenol), an inhibitor of tyrosinase activity, is used as a skin-whitening component. Many cases of leukoderma after the application have been reported, termed rhododenol-induced leukoderma (RIL). The aim of this study was to clarify the pathogenesis of RIL morphologically through comparison with vitiligo., Methods: We examined 14 cases of RIL and 15 cases of vitiligo using routine histopathology and immunohistochemistry. Thirteen cases of RIL, six cases of vitiligo and specimens of the RIL mouse model were evaluated by electron microscopy., Results: There were common findings in RIL and vitiligo at the light-microscopic level: (a) vacuolar changes in the dermo-epidermal junction, (b) melanophages in the papillary dermis, (c) perifollicular lymphocyte infiltration, (d) loss or decrease of basal melanin pigment and (e) decrease of melanocytes in the lesions. The ultrastructural observations showed specific findings of RIL: (a) remaining melanocytes in depigmented lesions, (b) inhomogeneous melanization in melanocytes and (c) degenerated melanosomes in melanocytes. Some of the findings were observed in a RIL mouse model. Furthermore, it is notable that cell organelles of melanocytes were intact in our RIL cases., Conclusion: Morphological changes of RIL targeting melanosomes in melanocytes without degeneration of organelles reflect the reversible clinical course of most cases., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Cosmetics containing rhododendrol (RD) were voluntarily recalled after incidents of leukoderma related to their use. Users reported using up to five different RD-containing products by layered application. In this study, we investigated the effects of layered application, formulations, and their components on the skin permeation of cosmetics containing RD. Experiments were designed to simulate actual in-use conditions, such as varying application volumes, physical mixing of formulations, sequence of cosmetics application and time interval between applications, to establish their effect on the skin permeation of RD. Milk and lotion RD-containing cosmetics (2%), 1% aqueous RD, and preparations of formulation components were applied as the first or second layers as finite doses of 10 or 20 µL/cm 2 . Permeation experiments were performed through excised porcine ear skin using Franz diffusion cells with an effective diffusion area of 1.77 cm 2 . Cosmetics applied by layered application exhibited lower skin permeation of RD compared with a single application despite having the same application dose. High initial volume (20 µL at 0 or 5 sec) did not exhibit any significant reduction in the permeation of RD. Formulations and their components caused varying reductions in RD permeation, probably due to changes in thermodynamic activity of the active component. Layered application, formulation components, application volume, time interval and sequence of application had significant influences on the skin permeation of the active component. Moreover, this study established a method of investigating the influence of formulations and their components on the skin permeation of actives after layered application.

The genus Passiflora is popularly used to treat anxiety. Recent studies showed antidepressant-like effects of two varieties of P. edulis (edulis and flavicarpa) in mice. However, the mechanisms of antidepressant actions are still unknown. Here, the effects of P. edulis fo. edulis aqueous extract (AE, 100-300mg/kg, po), and ethyl acetate (AcOEt, 25-50mg/kg, po), butanol (BuOH, 25-50mg/kg, po) and residual aqueous (25-100mg/kg, po) fractions were investigated in the mouse forced swimming test. In addition, the involvement of monoamines in the P. edulis fractions-induced antidepressant actions was approached. HPLC analyses showed that AcOEt and BuOH, but not residual, fractions shared with AE the main peaks between 25 and 70min (UV 340nm), which are suggestive of flavonoids. Nortriptyline and fluoxetine reduced the immobility time and similar results were observed for AE, AcOEt and BuOH but not residual fractions. PCPA (inhibitor of 5-HT synthesis), AMPT (inhibitor of catecholamine synthesis) and sulpiride (selective D2 receptor antagonist), but not DSP-4 (noradrenergic neurotoxin), blocked the antidepressant actions of AcOEt and BuOH. In conclusion, AcOEt and BuOH fractions shared with AE similar phytochemical composition and antidepressant actions. Preserved 5-HT and dopamine transmissions were required for the antidepressant effects of P. edulis fractions., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The studies evaluating the effect of smoking on olfaction reveals opposite results. In vitro and animal studies and epidemiological evidence from volunteers and patients, demonstrated the association between olfaction and erectile functions. In smoking man the reduction of olfactory acuity could adversely affect sexuality. The aim of the present study was to investigate the relationship between erectile dysfunction (ED) and olfactory dysfunction (OD) by comparing a group of healthy adult men with a group of smoking adult men. This prospective study involved 62 volunteers, who were recruited and divided into two groups; one consisted of 35 smoking adult men, and the other included 27 healthy non-smoking men. All participants in both groups were examined in detail for any condition with the potential to cause OD. They all had a normal genitourinary system suffered from no circulatory diseases, diabetes mellitus, hypertension, coronary artery disease nor hyperlipidemia; they had no history of medication affecting genitourinary system. Butanol threshold test and sniffin' stick® (Burghart, Wedel; Germany) screening test was used to asses olfactory functions in both groups. Participants' sexual desire was assessed using an International Index of Erectile Function (IIEF-5) scale. The means of sniffin' sticks scores, butanol threshold scores and IIEF-5 scores were statistically higher in non-smoking group. Butanol threshold scores and sniffin' sticks scores are correlated statistically with IIEF-5 in non-smoking and smoking groups. This study found an association between olfaction and erectile function in smoking and non-smoking men. As far as we know this study is the third published study to show the relationship olfactory and erectile function. In the future studies electrophysiological olfactory methods could be used to confirm in large cohorts the results obtained by the psychophysical approach., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Miracle fruit (Synsepalum dulcificum) belongs to the Sapotaceae family. It can change flavors on taste buds, transforming acidic tastes to sweet. We evaluated various miracle fruit extracts, including water, butanol, ethyl acetate (EA), and hexane fractions, to determine its antioxidant effects. These extracts isolated from miracle fruit exerted potential for reduction of uric acid and inhibited xanthine oxidase activity in vitro and in monosodiumurate (MSU)-treated RAW264.7 macrophages. Moreover, we also found that the butanol extracts of miracle fruit attenuated oxonic acid potassium salt-induced hyperuricaemia in ICR mice by lowering serum uric acid levels and activating hepatic xanthine oxidase. These effects were equal to those of allopurinol, suggesting that the butanol extract of miracle fruit could be developed as a novel anti-hyperuricaemia agent or health food.

Background: Rhododendrol, 4-(4-hydroxyphenyl)-2-butanol, Rhododenol(®) (RD), a naturally occurring phenolic compound, was developed as a tyrosinase inhibitor for skin-lightening/whitening cosmetics. In 2013, skin depigmentation was reported in consumers using RD-containing skin-brightening cosmetics; this condition is called RD-induced leukoderma., Objective: The etiology of RD-induced leukoderma is still largely unknown. Here, to assess the depigmentation potential of RD, we developed a new mouse model of leukoderma by topically applying RD., Methods: Hairless hk14-SCF Tg mice with melanocytes distributed in the epidermis were used for this study. RD was applied on the dorsal skin of the mice daily for 28 days. Then, immunohistological, biochemical, and electron microscopic analyses were performed on biopsy samples taken from these mice., Results: The depigmentation in the RD-treated sites appeared on Day 14. Histological examination indicated a loss of epidermal melanocytes at Day 7. On the other hand, the melanocyte number did not decrease in the albino mice having the same background as the hairless hk14-SCF Tg, but without tyrosinase activity. Biochemical analyses showed that the eumelanin content decreased in the RD-treated sites and metabolites of RD-quinone, i.e., non-protein thiol adducts and protein-SH adducts, were produced. Electron microscopic analyses revealed double-membrane-walled structures containing electron-dense material, which might be typical for melanin-containing autophagosomes and a dilated endoplasmic reticulum (ER), which would indicate ER stress., Conclusions: These data suggested that RD exerted tyrosinase-dependent melanocyte cytotoxicity and that tyrosinase-dependent accumulation of ER stress from activation of the autophagy pathway contributed to melanocyte cytotoxicity., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

The aim of this study was to investigate whether there are differences between women and men in how chemosensory stimuli are processed. Event-related potentials from 36 participants (18 men) showed that women had larger P3 amplitudes when attending, but not when ignoring CO(2) and amyl acetate stimuli compared with men. Conversely, auditory P3 was reduced by the same degree in women and men. No gender differences were found in magnitude estimations over time. Women had lower detection thresholds for CO(2), but not for n-butanol, compared with men. The main finding was that women and men differ in cognitive measures of chemosensory processing., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Purpose: NK1 receptors have been implicated in various neuropsychiatric and other disorders. R116301 is a selective NK1 receptor antagonist. In this pilot study, [(11)C]R116301 was evaluated as a potential positron emission tomography (PET) ligand for the NK1 receptor., Procedures: Two dynamic PET studies were performed in three normal volunteers before and after a blocking dose of aprepitant. Data were analyzed using striatum to cerebellum standardized uptake value (SUV) ratios., Results: Baseline SUV ratios at 60-90 min after injection ranged from 1.22 to 1.70. Following aprepitant administration, this specific signal was completely blocked. Aprepitant administration did not significantly affect uptake in cerebellum, confirming the absence of NK1 receptors in cerebellum., Conclusion: These preliminary results indicate that [(11)C]R116301 has potential as a radioligand for in vivo assessment of NK1 receptors in the human brain.

Indigofera tinctoria is a perennial shrub, which belongs to the family Papilionaceae. As a part of our drug discovery program we have investigated the antidyslipidemic activity of the alcoholic extract from Indigofera tinctoria as well as its three other components, that is, chloroform, butanol and aqueous fractions in dyslipidemic hamsters that were fed a high fat diet. The chloroform fraction showed a significant decrease in the plasma triglycerides (TG, 52%) (P < 0.001), total cholesterol (TC, 29%) (P < 0.05), glycerol (Gly, 24%) and free fatty acids (FFA, 14%). This decrease was also accompanied by an increase in high density lipoproteins (HDL) by 9% and an increased HDL-C/TC ratio of 52% at the dose of 250 mg/kg of body weight.

The butanolic fraction of dried leaves of Acacia pennata (Mimosaceae) was tested for analgesic and anti-inflammatory activities in animal models. It showed significant protective effects against chemical stimuli (acetic acid and formalin) in the mouse. It also produced a significant increase of the threshold of sensitivity to pressure-induced pain in the rats. The extract revealed an inhibitory effect in carrageenin-induced rat paw oedema in the late phase. The results suggested that a peripheral mechanism is involved in the analgesic, associated to anti-inflammatory effect (NSAIDs-like). Among the class of compounds characterized in this fraction, flavonoids may be mainly responsible for the pharmacological activities.

The antioxidant activities of Acanthopanax senticosus stems were evaluated in CCl4-intoxicated rats. The n-butanol fraction from the water extract of the stems, when pretreated orally at 200 mg/kg/day for 7 consecutive days in rats, was demonstrated to exhibit significant increases in antioxidant enzyme activities such as hepatic cytosolic superoxide dismutase, catalase and glutathione peroxidase by 30.31, 19.82 and 155%, respectively. The n-butanol fraction whereas showed a significant inhibition of serum GPT activity (65.79% inhibition) elevated with hepatic damage induced by CCl4-intoxication. Eleutheroside B, a lignan component, isolated from the n-butanol fraction was found to cause a moderate free radical scavenging effect on DPPH, its scavenging potency as indicated in IC50 value, being 58.5 microM. These results suggested that the stems of A. senticosus possess not only antioxidant but also hepatoprotective activities.

The recent development of selective NK(1) receptor antagonists that are active in vivo provides an important research tool to examine the role of substance P in the regulation of circadian rhythmicity. First, we tested whether R116301 [(2R-trans)-4-[1-[3,5-bis(trifluoromethyl)benzoyl]-2-(phenylmethyl)-4-piperidinyl]-N-(2,6-dimethylphenyl)-1-acetamide (S) hydroxybutanedioate], a new selective NK(1) antagonist, alters the phase-shifting effects of light. Hamsters housed in constant darkness were injected with different doses of R116301, just before being exposed to a light pulse during the subjective night. The results were compared with those obtained with the NK(1) antagonist L-760,735 [2-(R)-(1-(R)-3,5-bis(trifluoromethyl)phenyl)ethoxy)-4-(5-(dimethylaminomethyl)-1,2,3-trioazol-4-yl)methyl-3-(5)-phenyl)morpholine]. Second, the effects of the NK(1) antagonists R116301 or L-760,735 injected immediately after exposure to a light pulse were similarly determined. Third, we investigated whether R116301 or L-760,735 injected during the mid-subjective day or the late subjective night can phase-shift the circadian rhythm of locomotor activity in hamsters housed in constant light. Both compounds reduced, by more than 30%, the phase-advancing effects of a light pulse in hamsters otherwise maintained in constant darkness, only when the drugs were administered before the light pulse. Under constant light conditions, both NK(1) receptor antagonists induced significant phase-advances when injected during the subjective day, but not during the subjective night. The present results indicate that tachykinergic neurotransmission modulates the photic responses of the circadian system upstream of phase resetting mechanisms and suggest that an inhibition of the NK(1) receptor signals "darkness" to the circadian clock.

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.

Lifibrol (4-(4'-tert-butylphenyl)-1-(4'carboxyphenoxy)-2-butanol), a new hypocholesterolemic drug, effectively reduces total cholesterol (CH), low density lipoprotein (LDL)-CH, and apolipoprotein (apo) B in experimental animals and in humans. The impact of Lifibrol on the metabolism of apoB-100 containing lipoproteins in patients with hyperlipoproteinemia using endogenous labeling with stable isotopes is examined. Kinetic studies were performed in four male hypercholesterolemic individuals (type IIa) before and on treatment with 450 mg of Lifibrol daily for 4 weeks, and in five male individuals suffering from mixed hyperlipidemia (type IIb) before and on therapy for 12 weeks. Kinetic parameters were estimated by multicompartmental modeling. Lifibrol therapy reduced total CH by 16% (P = 0.012) in all patients, increased triglycerides (TG) by 11% (not significant) in type IIa patients and decreased TG by 34% (P = 0.059) in type IIb patients. During Lifibrol therapy, LDL apoB-100 concentrations decreased by 19% (P = 0.011) in all patients. The decrease in LDL apoB concentrations with Lifibrol therapy was due to an overall increase (75%, P = 0.006) of the fractional catabolic rates (FCR) of LDL apoB. This increase was partially attenuated by a 33% increase in LDL apoB production rate (PR) (P = 0.041). The overall production of apoB increased only slightly. Our data suggest that the major mechanism by which Lifibrol lowers LDL-CH is an increase in receptor-mediated catabolism of LDL rather than a decrease in hepatic apoB production.

Objectives: To investigate the possibility of applying diffusive air sampling and urinalysis (for mother compound and metabolites) to the monitoring of exposure of factory workers to 1-butanol., Methods: The performance of carbon cloth in adsorbing 1-butanol vapor in air was studied by experimental exposure of the cloth to 1-butanol at 50, 100, 200 or 400 ppm for up to 10 h. 1-Butanol in the exposed cloth was extracted with carbon disulfide and this was followed by gas-chromatographic (GC) analysis. Urine samples were collected from factory workers occupationally exposed to 1-butanol and from rats exposed experimentally to 1-butanol vapour (up to 200 ppm). The urine samples were analyzed by GC without any pretreatment, or after treatment with hydrochloric acid or hydrolase preparation., Results: The performance of the carbon cloth was such that it adsorbed 1-butanol in proportion to the concentration (up to 400 ppm) and the duration (up to 10 h) of exposure, and responded quantitatively to a 15-min exposure up to 400 ppm. The amount of 1-butanol (after enzymic or acid hydrolysis) in post-exposure urine samples from rats was proportional to the exposure intensity. The proportion of free 1-butanol in total 1-butanol (i.e., free+conjugated) in urine was higher after 100 or 200 ppm exposure (35-40%) than after 50 ppm exposure (about 8%). There was a significant increase in total 1-butanol concentration (but not in free 1-butanol) in shift-end urine samples of workers exposed to 1-butanol at concentrations up to 3 ppm., Conclusions: Diffusive sampling with carbon cloth as an adsorbent can be applied to ambient air monitoring of exposure to 1-butanol. Urinalysis for 1-butanol after hydrolysis is sensitive enough to detect occupational 1-butanol vapour exposure at 3 ppm.

Olfactory threshold was investigated in patients with verified allergic rhinitis to birch pollen. In 20 patients the olfactory threshold was measured before and after challenge with topically applied birch pollen allergen during a non-symptomatic period. After provocation a statistically significant impaired detection sensitivity was found. The change in olfactory threshold was correlated with the measured amount of nasal secretions but not with subjectively or objectively registered nasal obstruction. A pronounced allergic reaction after allergen challenge is accompanied by an elevated olfactory threshold.

Post mortem diffusion of paint thinner (toluene/ethyl acetate/isobutanol 8:1:1 v/v) from gastric residue (25 ml or 100 ml) and airways contamination (25 ml) was assessed in a human cadaver model, with sampling after 24 h at room temperature. Four torso blood samples showed less toluene diffusion after gastric instillation (0.5-3.8 micrograms/ml) than after tracheal instillation (10.5-421 micrograms/ml). Isobutanol diffused more readily than toluene with four torso blood samples 1.8-256 micrograms/ml after gastric instillation and 26-576 micrograms/ml after tracheal instillation. Following 25 ml gastric instillation, toluene concentrations (microgram/ml or microgram/mg) were: pericardial fluid 0.7-4.0; bile 0.5-0.6; urine 0-0.6; brainstem 1.1; lung 0.4-4.4; liver 0-162; spleen 0.6-0.7; kidneys 0.4-0.6; peri-renal fat 0.3-30.3; psoas muscle 0.3-0.8; concentrations of toluene and isobutanol were markedly higher in the left lobe of the liver than the right. Ethyl acetate was mostly undetectable in tissue samples but variably present in five blood samples: 0-21.2 micrograms/ml following 25 ml or 100 ml gastric instillation and 0-198 micrograms/ml following 25 ml tracheal instillation. Ethyl acetate was always detectable in pericardial fluid but not always detectable in gastric contents. We conclude that post mortem diffusion of toluene from gastric residue or airways contamination is unlikely to compromise the analytical validity of femoral venous blood samples, brain, or liver from deep within the right lobe. Analysis of pericardial fluid and gastric contents allows identification of ethyl acetate and isobutanol thus implicating thinner solution.

Tertiary butyl alcohol and trichloroacetic acid (TCA) are known to be contaminants in drinking water. In order to evaluate the interactive toxicity of t-butyl alcohol (TBA) with TCA, young male Wistar rats were dosed through water at a dose level of TBA (0.5% v/v), 25 ppm TCA and a combined dose of TBA+TCA (0.5% v/v TBA, 25 ppm TCA) for a period of 10 weeks ad libitum and were maintained on normal diet. The control animals received plain water and normal diet. There was remarkable loss of body weight and significantly decreased liver triglycerides in the treatment groups in the order of TBA+TCA, TCA, TBA and increased liver weights were observed. Serum succinate dehydrogenase (SDH) levels were significantly increased in TCA- and TBA+TCA-treated groups. There was no significant change in serum alanine (GPT), aspartate (GOT) aminotransferase, serum alkaline (ALP) and acid (ACP) phosphatase levels as well as liver glutathione (GSH) and liver and serum cholesterol levels in the treated groups. But serum triglycerides, liver glycogen, serum glucose (only in TBA- and TCA-treated animals) were significantly high in the treated groups. Lipid peroxidation measured by diene conjugation was significant in TBA+TCA-treated group and kidney GSH levels were significantly low in the treated groups. These results show that interaction of TBA+TCA does bring about alteration in biochemical parameters which may play a pivotal role in toxic responses on long-term exposure.

3-Methyl-1-butanol (MEB) and 2-methyl-1-propanol (MEP) were tested for their prenatal inhalation toxicity in pregnant Wistar rats or Himalayan rabbits. Twenty-five female rats and 15 female rabbits per group were exposed to MEB and MEP vapors at concentrations of 10, 2.5, or 0.5 mg/liter, 6 hr/day. The rats were exposed on Days 6-15 postcoitum (pc) and the rabbits were exposed on Days 7-19 postinsemination (pi). Control groups were exposed to clean air. The body weights of the animals of either species were determined several times throughout the studies. All rats and all rabbits were killed on Day 20 pc and Day 29 pi, respectively. The fetuses were removed from the uterus and examined for compound-related effects. The high concentration of 10 mg/liter caused a slight retardation of body weight gain in the dams of either species exposed to MEB and in the dams of rabbits exposed to MEP during the first days of the exposure period. Eye irritation was observed only in the MEB-treated rabbits during the period of exposure to 10 mg/liter. The fetuses of either species exhibited no signs of embryo-/fetotoxicity or teratogenic effects caused by MEP or MEB. Under the experimental conditions, 2.5 mg/liter was found to be a no-observable-adverse-effect level (NOAEL) for the dams of either species exposed to MEB and for the does exposed to MEP, whereas 10 mg/liter MEP was the NOAEL for the maternal rats. For both substances 10 mg/liter was defined as the NOAEL for the conceptuses of either species.

Three microsomal enzyme inducers, ethanol, phenobarbital (PB), and beta-naphthoflavone (beta NF), were compared for their effects on butanol oxidase activity in rat hepatic and pulmonary microsomes. Four concentrations of 2-butanol (1.0, 5.0, 10, and 33 mM) were used to determine if the effects of induction on 2-butanol metabolism were substrate concentration dependent. Ethanol induced at all substrate concentrations in the liver while PB induced at only the high substrate concentrations (5.0, 10, and 33 mM). beta NF did not induce at any substrate concentration. 2-Butanol oxidation in the lung was not induced by any of the treatments. Thus, both ethanol and phenobarbital induce hepatic enzymes capable of 2-butanol oxidation, and the isozyme(s) induced by the latter has a somewhat lesser affinity for this alcohol.

Most previous reports of ototoxicity following exposure to several volatile organic solvents have restricted testing to the low- and mid-frequencies (2-20 kHz) of the hearing range in the rat (0.25-80 kHz). We report here that inhalation exposure to styrene, mixed xylene, toluene, and 1,1,2-trichloroethylene resulted in hearing dysfunction only in the mid-frequency range and spared function at lower and higher frequencies. Adult male Long Evans rats were exposed via inhalation (whole body) in flow-through chambers. The following exposures were used: styrene, 1600 ppm; 1,1,2-trichloroethylene, 3500 ppm; toluene, 2500 ppm; mixed xylenes, 1800 ppm (N = 7-8 per group, 8 h/day for 5 days), and n-butanol, 4000 ppm (N = 10/group, 6 h/day for 5 days). Testing of auditory function was conducted 5 to 8 weeks after exposure using reflex modification audiometry (RMA). RMA thresholds were determined for frequencies from 0.5 to 40 kHz. Results indicated increased RMA thresholds for the mid-frequency tones (e.g., 8 and 16 kHz), but not higher or lower tones, for all solvents except n-butanol. Toluene and xylene also increased thresholds at 24 kHz. These data indicate that for those solvents reported thus far to cause hearing loss, the deficit is restricted to mid-frequencies in rats.

The effects of combined exposure to n-butyl alcohol and n-butyl acetate on rotarod performance and hot plate behaviour in rats and respiratory rate in mice were investigated in the condition of an acute inhalation experiment. Rotarod performance and hot-plate behaviour were tested in rats exposed to various concentrations of n-butyl alcohol, n-butyl acetate and their mixture consisting of 50 Vol-% n-butyl alcohol and 50 Vol-% n-butyl acetate immediately after termination of a 4-hour exposure period. The respiratory rate in mice was recorded continuously before the exposure to solvents, during 6 min of exposure and 6 min after termination of exposure using whole body plethysmographic method. Mice were exposed to vapours of single solvents and their 50:50 Vol-% mixture. Both solvents and their mixture caused concentration-dependent disturbances of rotarod performance in rat. The medial effective concentration (EC50) for the effect amounted to 7559 ppm, 8339 ppm and 10672 ppm for n-butyl alcohol, n-butyl acetate and their mixture, respectively. Both solvents and their mixture decreased sensitivity to the pain and changes were concentration-dependent. In condition of combined exposure the results obtained in rotarod and hot-plate behaviour test indicate the summation of individual solvent effects. The tested solvents resulted in concentration-dependent decrease in respiratory rate in mice. n-Butyl alcohol produced maximal decrease in respiratory rate in the first minute of exposure whereas n-butyl acetate in the sixth minute.(ABSTRACT TRUNCATED AT 250 WORDS)

Female rats were given aqueous solutions of n-butanol containing 0.24, 0.8 and 4% n-butanol (0.3; 1.0 and 5.0 g/kg/day) for 8 weeks before and during gestation. The control animals received tap water. The experiment was performed in two stages. The first comprised of the assessment of the oestrous cycle before exposure and then during 4-5 and 7-8 weeks of exposure, and the second stage of the fertility of female rats and their foetal development. The duration of the cycle and its individual stages in the control and the exposed females were similar. It was found that n-butanol alcohol is a foetotoxic agent and produces developmental anomalies in a foetus's skeleton and central nervous system.

Tert-butyl alcohol, an important commodity chemical, additive to unleaded gasoline, and contaminant of drinking water, was evaluated for toxicity and was found to enhance nephropathy in male Fischer 344 rats. Because male rats treated with t-butyl alcohol for 2 years had a low incidence of renal cortical tumors, additional renal sections for the 90-day toxicity study were examined for the presence of hyaline droplet accumulation, nephropathy, and evidence of replicative DNA synthesis (S-phase nuclei) to indirectly and retrospectively investigate a possible role of alpha-2 mu-globulin in the pathogenesis of the nephropathy. Dose levels for t-butyl alcohol were 0, 0.25, 0.5, 1, 2, and 4% (w/v) administered in drinking water. Significant body weight gain depressions were observed in all treated males, and there was an absolute weight loss in the 4% male group, none of which survived to the end of the study. Except for the 4% dose group, there was a treatment-related increase in hyaline droplet accumulation in the renal proximal tubules with crystalline, rectangular, and rhomboid forms of the protein evident. The severity of nephropathy was enhanced in treated rats, except for the 4% dose group. Replicative DNA synthesis, as measured by immunohistochemical staining for proliferating cell nuclear antigen, was increased in proximal tubules of rats dosed with 2% t-butyl alcohol. It is concluded that t-butyl alcohol exacerbated nephropathy in male Fischer 344 rats and increased renal accumulation of hyaline protein material consistent with alpha-2 mu-globulin deposition.

The effects of combined exposure to m-xylene and n-butyl alcohol on rotarod performance and motor activity in rats and respiratory rate in mice were investigated in the condition of an acute inhalation experiment. Rotarod performance and motor activity were tested in rats exposed to various concentrations of m-xylene, n-butyl alcohol and their mixture consisting of 50 Vol-% m-xylene and 50 Vol-% n-butyl alcohol immediately after termination of a 4-hour exposure period. The respiratory rate in mice was recorded in short 6 min duration exposures to individual solvents and their 50:50 Vol-% mixture. Both solvents and mixtures caused concentration-dependent disturbances of rotarod performance in rats. The medial effective concentration (EC50) for the effect amounted 6530 ppm, 1980 ppm and 3080 ppm for n-butyl alcohol, m-xylene and their mixture, respectively. Both solvents and their mixture changed the spontaneous motor activity in the rat. Because of a two-phase effect, the concentration-dependence of the observed changes could not be defined. The evaluation of the combined effect in motor activity test was carried out by comparing experimental values with expected ones assuming the summation of individual solvent effects. The tested solvents resulted in a concentration-dependent decrease in respiratory rate in mice. The concentration which decreased the respiratory rate to 50% (RD50) was 3010 ppm, 1360 ppm and 3140 ppm for n-butyl alcohol, m-xylene and their mixture, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Studies were done to determine if warm n-butyl alcohol vapor might be effective for the destruction of respiratory tract foam bubbles and for alleviation of the arterial hypoxemia accompanying severe acute pulmonary edema. In vitro studies showed that warm butyl alcohol vapors made from 5% and 7% butyl alcohol solutions at 39 degrees C were much more effective in antifoam activity against synthetic foam bubbles than ethyl alcohol vapors, made from 20% and 30% ethyl alcohol at 22 degrees C. Warm butyl alcohol vapor also slowly destroyed in vitro the fine foam bubbles of alveolar lining origin made in rabbit lung post mortem. Evolving lung edema was induced in anesthetized rabbits by aspiration of 1.1 ml/kg of 1.2 molal sorbitol/0.14 molal sodium chloride/0.01 molal hydrochloric acid solution of pH 2.0. After established severe arterial hypoxemia and in the absence of overt foam, inhalation of warm butyl alcohol/H2O vapor-air mixture, made by air humidification from 7% butyl alcohol at 39 degrees C, alleviated promptly the hypoxemia. The improvement was progressive over the first 45 minutes of continued vapor therapy. The lessened hypoxemia occurred without concurrent improvement in the amount of formed lung edema fluid. Control inhalations of warm 100% H2O vapor-air mixture did not improve the hypoxemia. The only noted side effects of warm butyl alcohol vapor treatments were slight hypotension and slight metabolic acidosis which developed very slowly. The results suggest that warm butyl alcohol vapor might prove to be an effective adjuvant agent to lessen critically severe hypoxemia in selective cases of acute pulmonary edema in man.

The short-term course of sea water wet near-drowning was studied in anesthetized rabbits breathing spontaneously. Therapeutic trials were incorporated using warm n-butyl alcohol vapor both in inspired air and in inspired oxygen. The purpose was to determine if butyl alcohol vapor might alleviate the hypoxemia of sea water aspiration, possibly by a defoaming action on the fine foam bubbles of alveolar origin in the lung edema even without tracheal foam being present. The findings from 20 rabbits without overt tracheal foam, that had aspirated 2.05 mL/kg of sea water and were placed 10-minutes postaspirationally into four different inhalational treatment groups, showed remarkable differences. Warm butyl alcohol vapor made by humidification of 7.5% solution at 31 degrees C alleviated the hypoxemia. With vapor treatment for 15 minutes, mean arterial oxygen tension (PaO2) was not significantly changed in the water vapor-air group, but increased significantly to 50.5 +/- 4.6, 70.0 +/- 8.9, and 146.7 +/- 40.7 mm Hg in the butanol/water vapor-air, water vapor-oxygen, and butanol/water vapor-oxygen groups, respectively. With treatment for 30 minutes, mean PaO2 increased to 248.3 +/- 38.0 mm Hg with butanol/water vapor-oxygen inhalations, but only to 91.2 +/- 9.8 mm Hg with 100% water vapor-oxygen inhalations. Thus, the inspired vapor of butanol was much more effective in elevation of arterial blood oxygen pressures when combined with oxygen therapy over the values found when 100% water vapor-oxygen treatments were given. Respiratory and cardiac depressant effects from inspired butanol were not evident.(ABSTRACT TRUNCATED AT 250 WORDS)

Taking a practical forensic case that provided an opportunity, an attempt was made to prove that paint thinner had been ingested by the victim. One ml of standard thinner solution, which was prepared by mixing toluene, ethyl acetate, and isobutanol, was given by gavage to rats, after which, on sacrifice of the animals, the distribution of thinner components in the body tissue and in the gastric contents was examined by gas chromatography, using the salting-out technique and the headspace method. Three thinner components and ethanol, a metabolite of ethyl acetate, were found to be present in the gastric contents, whereas only toluene was found in the blood and in the other tissue. From these results we thus have concluded that paint thinner taken can be proved by detecting the presence of ethyl acetate and isobutanol together with toluene in the stomach, whereas only toluene can be detected in the body fluids and the other tissue.

Long-term treatment of rats with n-butanol leads to a change in in vitro brain protein synthesis which increases the resistance of this process to either ethanol or isopropanol. The change seems to be related to ribosomal events since the synthesis of aminoacyl-tRNA was not affected in the same conditions.

Transfer of the inhibitory neurotransmitter gamma-aminobutyric acid across the normal blood-brain barrier is minimal. One prerequisite for gamma-aminobutyric acid in plasma contributing to the neural inhibition of hepatic encephalopathy would be that increased transfer of gamma-aminobutyric acid across the blood-brain barrier occurs in liver failure. The aim of the present study was to determine if brain gamma-aminobutyric acid uptake is increased in rabbits with stage II-III (precoma) hepatic encephalopathy due to galactosamine-induced fulminant hepatic failure. A modification of the Oldendorf intracarotid artery-injection technique was applied. [3H] gamma-aminobutyric acid, [14C] butanol, and 113mIn-labeled serum protein (transferrin) were injected simultaneously 4 s before decapitation. The ipsilateral brain uptake index of gamma-aminobutyric acid was determined from measurements of the 3 isotopes in 5 brain regions. Uncorrected or simple brain uptake indices of [3H] gamma-aminobutyric acid and [113mIn] transferrin were calculated using [14C] butanol as the highly extracted reference compound. The [113mIn] transferrin data were also used to "correct" the brain uptake index of [3H] gamma-aminobutyric acid for intravascular retention of [3H] gamma-aminobutyric acid. The methodology adopted minimized problems attributable to rapid [3H] gamma-aminobutyric acid metabolism, and slow brain washout and recirculation of the radiolabeled tracers. Both the uncorrected and corrected brain uptake indices of gamma-aminobutyric acid as well as the simple brain uptake index of transferrin were significantly increased in both stage II and III hepatic encephalopathy in all brain regions studied. Moreover, these brain uptake indices were significantly greater in stage III hepatic encephalopathy than in stage II hepatic encephalopathy. These findings indicate that transfer of gamma-aminobutyric acid from plasma to brain extracellular fluid is increased in the model of hepatic encephalopathy studied; hence, they provide support for the hypothesis that plasma-derived gamma-aminobutyric acid may contribute to the neural inhibition of hepatic encephalopathy due to fulminant hepatic failure.

Threshold concentrations of olfactory sensation of odorants change due to adaptation to polluted atmosphere. The study was aimed at determination of trimethylamine and n-butanol threshold concentrations of olfactory sensation under standard laboratory conditions. The results were analysed from two viewpoints: the role of odour as a warning against chemical hazard, a possibility of using the shift of sensation threshold of appropriately selected reference standards as a measure of discomfort created by odours in working environment.

By the method of tissue culture, it is established that the capron threads stained by brilliant green, coated with the chemosorbed substances on the base of titanium alkoxides, polyalkylhydridsiloxanes and polyorganilsiloxanes have no histotoxic properties and can be used in microsurgical practice.

The antiarrhythmic activity of diphenidol, an antiemetic, has been demonstrated both in electrophysiologic studies of patiens and in experimental arrhythmias in animals. Accordingly, 18 patients with tachyarrhythmias were treated with intravenous diphenidol in doses of 0.5 to 1.5 mg/kg. In six patients with atrial arrhythmias, there was no notable effect. Similarly, 12 patients with premature ventricular contractions were treated and studied. In six of them, ectopic beats were abolished, at least transiently; in three the number of ventricular premature contractions decreased; in two there was no effect; and in one, the number of premature beats was increased. Of the total number of 18 patients, 14 suffered adverse effects related to the central nervous system. These adverse effects were of such severity as to suggest that further studies with diphenidol as an antiarrhythmic are not warranted.

In the framework of the development of drug delivery systems for locally administered contraceptive drugs, a reliable method that can afford quantitative evaluation of drug absorption behavior was explored using the rabit doe. A system was constructed based upon perfusing the drug solution in the vaginal tract. For this purpose, a "rib-cage" type cell was constructed and surgically implanted in the rabbit prior to an experiment. The primary purpose of the present paper is to evaluate the method, including the surgical operation and the perfusion system. The absorption experiments were carried out using n-butanol-1minus 14C as the model solute to survey the reproducibility of the absorption behavior. Experiments were conducted with a number of rabbits on several successive days to determine the day-to-day and animal-to-animal variations. The drug disappearance in the reservoir followed first-order kinetics from which the apparent permeability coefficient was calculated. The results indicated that a set of experiments may be carried out on a single animal and that the method generally affords rather high precision.

The olfactory epithelia of the bullfrog and the carp were stimulated with various odorants in the gaseous and/or aqueous phases. Some ionic solutions were also applied. 1. By recording the induced waves in the olfactory bulb, it was shown that the bullfrog responds to odorants in the two phases, but the carp can respond only to odorants in the aqueous phase. 2. Comparison of the stimulative effects of the same odorants in the two phases were made in the bullfrog. Although various response patterns to gaseous and aqueous stimuli of single cells in the olfactory bulb were found in most cases, a difference in the application methods of vapors and solutions made such comparison difficult. 3. The same single cells in the olfactory bulb usually responded to various odorous vapors and solutions as well as to ions in different patterns. When the responses to the vapors and solutions of the same odorants of different concentrations were compared, different patterns were also found.

No method has been reported for measuring CBF, repeatedly and noninvasively, in the rat brain. A new method is described, which is noninvasive to the brain, skull, or cervical large vessels. Two pairs of coincidence detectors were positioned, one over the rat brain and the other at the loop of a catheter inserted into the femoral artery. The coincidence head curve and arterial curve were recorded after intravenous injection of 1-[11C]butanol in 15 rats. CBF was calculated by one-compartment curve fitting ( CBFo ) from 1-min data and with the recirculation corrected height/area method from 3-min data ( CBFh X 3 min) and 5-min data ( CBFh X 5 min). CBFo agreed well with CBFh X 5 min, although a slight overestimation was observed in CBFh X 3 min. The normal CBFo in the normocapnic group (n = 6, paCO2 36.7 +/- 2.3 mm Hg) was 1.76 +/- 0.49 ml/g min (mean +/- SD). A good correlation was observed between CBFo (y) and PaCO2 (x), and the regression line was y = 0. 0629x -0.715 (r = 0.88, p less than 0.0001). We concluded that this method gives the stable blood flow values noninvasively and with a minimum loss of blood (less than 0.28 ml per measurement). Applications of this method include activation studies, studies on the effect of drugs and treatments, and water and oxygen extraction fraction studies using different tracers in the same rat.

A new method was developed and used in rat to measure regional and whole-brain blood flow and blood-brain glucose transfer simultaneously and in 20 s. This simple method consisted of i.v. bolus injection of labeled butanol and tracer glucose, determination of the average arterial tracer concentration and subsequent assay of cerebral tissue activity 20 s after bolus injection. The whole-brain blood flow rate averaged 129 ml (100 g)-1 min-1. The unidirectional blood-brain glucose transfer was twice as high as previously estimated in similar studies on rat, or 144 mumol (100 g)-1 min-1 at 10 mM glucose in plasma. The magnitude is sufficient to explain the high cerebral glucose consumption rates recently determined by means of autoradiographic 2-deoxy-D-glucose method of Sokoloff et al. (1977).

The choleretic and the general pharmacological properties of dihydroxy-dibutyl ether (Discinil) were investigated in several animal species. Discinil (DHBE) increased the bile flow in conscious rats and dogs, after both oral and i.v. administration. A choleretic effect was also observed after i.v. injection into anaesthetized rats and guinea pigs. A dose-response relationship was always obtained, the threshold dose being 25--100 mg/kg. No evidence of tachyphylaxis was observed in rats after repeated treatments. The bile hyperflow was generally accompanied by an increased excretion of the total dry residue in guinea pigs and dogs. The choleretic effect in rats was still present after pretreatment with either DL-ethionine (causing parenchymal liver damage) or atropine (blocking the cholinergic control of bile production). At low doses (25--100 mg/kg i.v.) eliciting a definite choleretic response, DHBE did not show spasmogenic and spasmolytic effects in vivo on the smooth muscles of the gallbladder of guinea pigs and dogs, neither on the stomach and intestine of mice and dogs; while it constricted the pylorus sphincter of rats. At larger doses (200--400 mg/kg i.v.) the compound showed a mild relaxing activity on Oddi's sphincter of guinea pigs and a weak spasmogenic activity either on gall bladder or on small intestine. In vitro, it caused an unspecific antagonism against the spasm induced by acetylcholine, barium chloride, histamine, 5-hydroxytryptamine and norepinephrine. In anaesthetized rats, rabbits and dogs, DHBE caused a moderate and short-lasting hypotension, and tachycardia. The threshold doses for these effects were 2--4 times superior to those being choleretic. In conscious dogs, the compound was slightly hypertensive. DHBE did not provoke important respiratory and ECG changes, neither showed diuretic nor antiphlogistic effects.

The hypolipemic effect of K12.148, a new hypolipemic compound, was examined in normolipemic rats, marmosets and pigs. It could be demonstrated that this compound reduced serum lipids, and in particular serum cholesterol, very effectively in all tested animal species. The analysis of the lipids of the pig give evidence that the hypocholesterolemic effect is due to a reduction of LDL only. In vitro experiments with rat liver homogenates suggest that the hypocholesterolemic effect is brought about by the inhibition of hepatic cholesterol synthesis.

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.

Bar-press responding of rats was maintained under a 30-response fixed-ratio schedule of food presentation. Responding was characterized by an initial pause followed by a high rate of responding which prevailed until food delivery. Oral administration (15 minutes pre-session) of ethanol (0.25-6.0 g/kg) or tertiary-butanol (0.25-3.0 g/kg) produced dose-related decreases in responding at the higher doses; tertiary-butanol was 1.6 times as potent as ethanol. The 3.0 g/kg dose of ethanol or the 1.0 g/kg dose of tertiary-butanol decreased responding by about twenty percent when given either 15, 30, or 60 minutes prior to the experimental session. Overall response rate and response rate exclusive of the initial pause were decreased similarly.

As part of an ongoing study of the developmental toxicology of industrial alcohols, this report presents the results of the teratology assessments of 1-butanol, 2-butanol, and t-butanol administered by inhalation to rats. Groups of approximately 15 Sprague-Dawley rats were exposed at 8000, 6000, 3500, or 0 ppm 1-butanol, 7000, 5000, 3500, or 0 ppm 2-butanol, or 5000, 3500, 2000, or 0 ppm t-butanol for 7 hr/day on Gestation Days 1-19 (sperm = 0). In each case, the highest concentration was selected to produce maternal toxicity. Dams were sacrificed on Gestation Day 20, and fetuses were individually weighed, tagged, and examined for external malformations. One-half of the fetuses were stained and examined for skeletal abnormalities, and the other half were examined for visceral defects using the Wilson technique. For each butanol isomer examined, the highest concentration (and the intermediate in some cases) was maternally toxic, as manifest by reduced weight gain and feed intake. Even at a maternally toxic dose, and in spite of a dose-dependent reduction in fetal weights for each isomer, the only teratogenicity observed was a slight increase in skeletal malformations (primarily rudimentary cervical ribs), seen with the highest concentration of 1-butanol. Thus, although teratogenicity was observed at 8000 ppm 1-butanol, and developmental toxicity was observed with each of the butyl alcohol isomers studied, concentrations 50 times the current permissible exposure limits for these three butanol isomers do not produce teratogenicity in rats.

The rate at which odorous vapor flows over the receptor surface is reflected in olfactory nerve activity, but the evidence for a corresponding effect on odor strength is scant and inconsistent. A perceptual constancy model for odor strength resolves this apparent contradiction: The effect of flow rate at the receptor site may be perceptually discounted when there is sensory feedback, in the form of perceived effort, from the action of sniffing responsible for changes in flow rate. Previous evidence shows that observers experience change in perceived effort when sniffing at various pressures against fixed resistance but not when sniffing with fixed pressure against varying resistance. Thus the model predicts both that odor strength varies when flow rate is manipulated by changes in olfactory resistance and that odor strength is invariant when flow rate is manipulated by changes in sniff pressure. In the present study, in which subjects made magnitude estimates of the odor strength of pyridine and n-butanol, an earlier finding for the effects of resistance change was confirmed and extended. Further, within the framework of a single experiment in which both pressure and resistance were independently manipulated, the odor strength of n-butanol conformed to the predictions of the constancy model.

Sprague-Dawley rats were given 15, 70 and 140 min exposures to 15 mg/l 3,3-dimethyl-2-butanol, pinacolyl alcohol (PA), or 6-hour exposures to 0.2, 1.0 and 5.0 mg/l PA (1 mg/l = 240 ppm). A 50% mortality rate was obtained at the longest exposure to 15 mg/l. Sex related differences in the blood levels of PA and pinacolone were noted, and the surviving male rats failed to gain weight normally in the first week after exposure. In rats exposed to 5.0 mg/l for 6 hours, there were reductions in horizontal and vertical activity and the minute volume was 55% of controls at the end of exposure. Like many secondary alcohols, PA poses only a possible inhalation hazard; however, male rats may be somewhat more susceptible than females.

Pretreatment with n-butanol (10 mmol/kg i.p.) 30 minutes before alloxan (100 mg/kg) protects mice from the permanent hyperglycemic effects (measured at 72 hours) of the diabetogenic agent. This dose of n-butanol caused an elevation of serum glucose at 30 minutes, the time of alloxan administration. Since glucose administration can protect animals from alloxan, the possibility that alcohol-induced hyperglycemia protected mice from alloxan was investigated. Mannoheptulose, an antagonist of glucose action at the pancreatic beta-cell, when given 24 minutes after n-butanol and 6 minutes before alloxan, eliminated the alcohol-induced protection. Fasted mice did not exhibit n-butanol-induced hyperglycemia at 30 minutes and alloxan given at that time produced diabetes. No protection was observed in fed animals when n-butanol was given 5 minutes before alloxan. The high serum levels of butanol and normal serum glucose which were observed at 5 minutes after alcohol administration indicated that the lack of protection was not due to a lack of circulating alcohol but resulted from an absence of hyperglycemia. The results indicate that pretreatment with n-butanol protects mice from alloxan-induced diabetes by the indirect mechanism of producing hyperglycemia at the time of alloxan administration.