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PubMed1990

Correlation between 'on admission' blood toluene concentrations and the presence or absence of signs and symptoms in solvent abusers.

For 1 year, from June 1987 to June 1988, toluene concentrations in blood samples of patients admitted to a psychiatric hospital after inhaling solvent vapor, collected on admission and 4 h later, were analyzed by gas chromatograph. Toluene levels in the first urine samples collected after admission were also analyzed and case histories were kept listing age, sex and physical and psychiatric effects. In all, 51 cases were studied--34 males and 17 females. (1) The average age of the males was 21.4 years and of the female 16.2 years. (2) The toluene concentrations in the blood collected on admission ranged from 0.3 to 22.8 micrograms/g. (3) Physical signs were observed in 9 patients with an "on admission" blood toluene concentrations of more than 3.0 micrograms/g; twice as many subjects (18), however, with blood toluene concentration greater than 3.0 micrograms/g were without physical signs. (4) The blood toluene concentrations of three cases in the condition known as twilight state were more than 10.0 micrograms/g. (5) In 24 cases with blood toluene concentrations below 3.0 micrograms/g, there were no physical signs. (6) Five subjects with blood toluene concentrations in the 0.8-5.2 micrograms/g range showed neuropsychiatric effects; however, 23 subjects in the same blood toluene concentration range did not exhibit psychiatric effects, and none of the subjects with blood toluene concentrations greater than 5.2 micrograms/g, 15 in all, had such effects.

Adolescent↗
PubMed2006

Determination of toluene in brain of freely moving mice using solid-phase microextraction technique.

For the purpose of measuring the pharmacokinetics of inhaled toluene in the brain of mice, we developed a method for the direct detection of toluene by gas chromatography/mass spectrometry (GC/MS). The method uses a solid-phase microextraction (SPME) fiber inserted into the mouse' hippocampus (CA1) through a cannula fixed onto the animal. BALB/c mice were exposed to 0, 0.9, 9, 50 and 90 ppm toluene for 30 min. The toluene level detected near the hippocampus by this method after exposure to 0.9 ppm toluene in air showed no significant difference from the level found in the non-exposure control group; however, the toluene level increased significantly after exposure to concentrations of 9, 50 and 90 ppm. These increases were concentration-dependent. In addition, the pharmacokinetics of toluene in the brain of mice exposed to 50 ppm toluene showed that the toluene level decreased rapidly after the exposure, and returned to control levels after 60 min. This study describes the method which has successfully detected toluene levels in the brain of conscious, free-moving mice for the first time.

Animals↗
PubMed2002

Toluene inhibits muscarinic receptor-mediated cytosolic Ca2+ responses in neural precursor cells.

Toluene is widely used as a component in industrial solvents and many toluene-containing products are abused via inhalation. While many studies have demonstrated its inhibitory effects on neuronal activity, the effects of toluene on receptor signaling in proliferating and differentiating neural precursor cells are presently unclear. Here, using digital video microscopy and Ca2+ imaging, we investigated the effects of acute exposure to toluene on the function of muscarinic acetylcholine receptors (mAChRs) expressed in neural precursor cells. The neural precursor cells were isolatedfrom embryonic day 13 (E13) rat cortex and expanded in serum-free medium containing basic fibroblast growth factor (bFGF). We found that the acetylcholine (ACh) analog carbachol (CCh) induced a dose-dependent increase in cytosolic Ca2+, which was blocked by the muscarinic receptor antagonist atropine in a reversible manner. Toluene was added to the perfusion medium and concentrations of toluene in the medium were determined by gas chromatographic analysis. Following imaging, the cells were fixed and processed for 5-bromo-2'-deoxyuridine (BrdU, cell proliferation marker) and beta-tubulin (TuJ1, neuronal marker) immunostaining. In the 5 day culture, most cells continued to divide (BrdU+), while afew cells differentiated into young neurons (TuJ1-). The CCh-induced Ca2+ elevations in proliferating (BrdU+TuJ1-) neural precursor cells were significantly reduced by acute exposure to 0.15 mM toluene and completely blocked by 10 mM toluene. Toluene's inhibition of muscarinic receptor-mediated Ca2+ signaling was rapid, reversible and dose-dependent with an IC50 value 0.5 mM. Since muscarinic receptors mediate cell proliferation and differentiation during neural precursor cell development, these results suggest that depression of muscarinic signaling may play a role in toluene's teratogenic effect on the developing nervous system.

Animals↗
PubMed2001

Multicenter field trial on possible health effects of toluene. III. Evaluation of effects after long-term exposure.

In rotogravure industry, contributing considerably to mass color printing of catalogues and magazines, toluene is still extensively used as paint solvent, and many printers have been exposed to this chemical for several decades. Information on adverse health effects associated with long-term toluene exposure is still controversial. In a multi-center study, adverse health effects possibly associated with long-term toluene exposure were evaluated. In 12 rotogravure factories, 1226 male volunteers were recruited, and sufficient information on exposure and on medical data was compiled for about 1077 of them. Evaluations included: physical examination, standard tests of psycho-physiological and psycho-motoric performances, self-report of subjective symptoms, and data on a variety of laboratory blood tests. The medical data were correlated with the length (months) of toluene exposure, and a rough estimate of the extent of exposure (i.e. highly exposed printers and their helpers versus employees working at locations with low or negligible toluene exposure). A small reference group (n=109) was selected from companies of the paper industry. When linear regression curves were calculated (test results versus duration of exposure), extremely low overall coefficients of determination (r(2) adj.) of a few percent were estimated within the data clouds, with sometimes statistically significant P-values. Closer analyses revealed a strong influence of the confounding factor age, no clustering of abnormal values of highly toluene-exposed volunteers, and the vast majority or all values of the highly and long-term toluene-exposed participants staying within the reference ranges. Thus, no medical relevance of P-values <0.05 could be recognized in this evaluation, and there may have been some border-line deviations or results largely occurring by chance in the large trial. In a small cluster of the many rotogravure printers toluene-exposed for more than 20 years, the highest systolic blood pressure values of the study were found, but many possible confounding factors were not taken into account. Data on acute exposure and possible effects are presented in accompanying papers (Neubert et al., 2001a, Neubert et al., 2001b). Restricting the conclusions to the end points evaluated as well as the apparent limitations of the evaluation, no evidence was found that long-term occupational toluene exposure extending over several decades in the rotogravure industry in the Western part of Germany was convincingly associated with chronic adverse health effects or convincingly altered surrogate markers in still working male volunteers. Several peculiarities and pitfalls arising when interpreting medical data associated with such a type of environmental exposure must be considered. Reversibility of alterations previously induced at higher levels of toluene-exposure, as well as a healthy workers effect, cannot be excluded for some of the medical end points evaluated.

Adult↗
PubMedDate not supplied

Color vision and occupational toluene exposure.

We examined the relationship between acquired color vision loss and exposure to toluene and total hydrocarbons among 125 male workers. Seventy-two toluene-exposed printers were compared with 34 workers from the same photogravure plant with ambient background exposure, and with 19 workers from a bookbinding plant located in the same town (nonexposed). Environmental mean toluene exposure level at workstation was estimated from individual 8-h sampling. Historic exposure data from the last 30 years were used to construct two cumulative exposure indices, one for toluene and one for total hydrocarbons. Airborne toluene levels were overall lower than the current Threshold Limit Value (TLV) of 50 ppm. Color vision was assessed by the Lanthony D-15 desaturated panel. Color vision loss was quantitatively established by the Color Confusion Index (CCI) and classified by type of acquired dyschromatopsia according to Verriest's classification. CCI was positively related to current airborne toluene levels, and cumulative exposure indices for toluene and total hydrocarbons (.18< or =r< or =.35). Odds ratios of acquired dyschromatopsia were significant for current airborne toluene, toluene, and total hydrocarbon past exposure (1.27 [1.02-1.58], 1.21 [1.04-1.39], 1.15 [1.02-1.31], respectively). In conclusion, this study suggests that the Lanthony D-15 desaturated panel detects early neurotoxic effects among workers exposed to toluene.

Adult↗
PubMed1995

Purification and characterization of toluene 2-monooxygenase from Burkholderia cepacia G4.

Recent in vivo studies indicate that ring monooxygenation is a widespread mechanism by which bacteria metabolize aromatic hydrocarbons and obtain carbon and energy. In this study, toluene 2-monooxygenase from Burkholderia (formerly Pseudomonas) cepacia G4 was purified to homogeneity and found to be a three-component enzyme system. The reconstituted enzyme system oxidized toluene to o-cresol and o-cresol to 3-methylcatechol, an important intermediate for growth of the bacterium on toluene. Steady-state kinetic parameters measured for the water-soluble substrate o-cresol were a Km of 0.8 microM and a Vmax of 131 nmol min-1 (mg of hydroxylase protein)-1. The three protein components were (1) a 40 kDa polypeptide containing one FAD and a [2Fe2S] cluster, (2) a 10.4 kDa polypeptide that contained no identifiable metals or organic cofactors, and (3) a 211 kDa alpha 2 beta 2 gamma 2 component containing five to six iron atoms. The 40 kDa flavo-iron-sulfur protein oxidized NADH and transferred electrons to cytochrome c, dyes, and the alpha 2 beta 2 gamma 2 component. It is analogous to other NADH oxidoreductase components found in a wide range of bacterial mono- and dioxygenases. The 10.4 kDa component, added to the other two components and NADH, increased toluene oxidation rates 10-fold. The alpha 2 beta 2 gamma 2 component was indicated to contain the site for toluene binding and hydroxylation by the following observations: (1) tight binding to a toluene affinity column; (2) oxidation of toluene after reduction of the protein with dithionite and adding O2; (3) H2O2-dependent toluene oxidation and catalase activity; and (4) spectroscopic studies of the iron atoms in the component. The alpha 2 beta 2 gamma 2 component had no significant absorbance in the visible region. EPR spectroscopy yielded a signal at g = 16 upon addition of > 2 equiv of electrons per 2 Fe atoms. Taken with the quantitation of five to six iron atoms, the data suggest that the alpha 2 beta 2 gamma 2 component contains two binuclear iron centers. In total, the structural, spectroscopic, and catalytic features of toluene 2-monooxygenase are reminiscent of soluble methane monooxygenase obtained from methanotrophic bacteria. The two enzyme systems also differ in many subtle ways; for example, they oxidize toluene with completely different regiospecificity.

Burkholderia cepacia↗
PubMed2003

Oxidative DNA damage induced by toluene is involved in its male reproductive toxicity.

Toluene is widely used as an organic solvent in various industries and commercial products. Recent investigations have shown that toluene may induce male reproductive dysfunctions and carcinogenicity. To clarify whether the toxicity results from the interference of endocrine systems or direct damage to reproductive organs, we examined the effects of toluene on the male reproductive system in rats, comparing to those of diethylstilbestrol (DES), a potent synthetic estrogen. Toluene (50, 500 mg/kg) or DES (2 mg/kg) injected subcutaneously to male Sprague-Dawley rats once a day for 10 days decreased the epididymal sperm counts and the serum concentrations of testosterone. The mRNA level for gonadotropin-releasing hormone receptor in the pituitary was decreased by DES, but not by toluene. On the contrary, 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) formation in testes, the biological marker for oxidative DNA damage, was increased by toluene but not by DES. These results suggest that toluene induces reproductive toxicity via direct oxidative damage of spermatozoa, whereas DES affects endocrine systems via the hypothalamo-pituitary-gonadal axis. Morphological findings supported the idea. To determine the mechanism of 8-oxodG formation in vivo, we examined DNA damage induced by toluene metabolic products in vitro. Minor toluene metabolites, methylhydroquinone and methylcatechols, induced oxidative DNA damage, and the methylcatechols induced NADH-mediated 8-oxodG formation more efficiently than methylhydroquinone did. We propose that oxidative DNA damage in the testis plays a role in reproductive toxicity induced by toluene.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2002

Use of real-time breath analysis and physiologically based pharmacokinetic modeling to evaluate dermal absorption of aqueous toluene in human volunteers.

Toluene is a ubiquitous chemical that is commonly used for its solvent properties in industry and manufacturing, and is a component of many paint products. Although human exposure to toluene is most likely to be through inhalation, toluene is also found in well and surface water. Therefore, an assessment of the dermal contribution to total toluene uptake is useful for understanding human exposures. To evaluate the significance of these exposures, the dermal absorption of toluene was assessed in human volunteers using a combination of real-time exhaled breath analysis and physiologically based pharmacokinetic (PBPK) modeling. Human volunteers wearing swimsuits were submerged in warm tap water to neck level in a stainless steel hydrotherapy tub containing an initial concentration of approximately 500-microg/l toluene. Volunteers were provided purified breathing air to eliminate inhalation exposures, and exhaled breath was continually analyzed before, during, and post exposure to track the absorption and subsequent elimination of the compound in real time. A PBPK model was used to estimate the dermal permeability coefficient (K(p)) to describe each set of exhaled breath data from 4-6 human volunteers. An average K(p) value of 0.012 +/- 0.007 cm/h was found to provide a good fit to all data sets. Volunteers also participated in a second study phase, in which the subject was allowed to breathe the room air during immersion, thus both dermal and inhalation exposures to toluene occurred. Exhaled breath analyses revealed that concurrent inhalation of volatilized toluene resulted in a transient increase in the peak exhaled-breath level by 100 ppb, or an approximate 50% increase over breath levels observed in dermal-only studies. For perspective, the total intake of toluene associated with oral consumption of 2 liters of water containing toluene at bath water concentrations were estimated to be more than 30 times greater than the dermal contribution due to bathing.

Administration, Cutaneous↗
PubMed1989

Effects of toluene on protein synthesis and the interaction with ethanol in hepatocytes isolated from fed and fasted rats.

The effects of three different concentrations (about 10, 100 and 1000 microM) of toluene on protein synthesis were studied in hepatocytes isolated from fed and fasted rats after 60 and 120 min. of incubation. The interaction between ethanol (60 mM) and the low and high toluene concentrations were also tested. To measure protein synthesis, 14C-valine was used as the precursor amino acid. Total valine concentration was 2 mM to ensure near-constant specific radioactivity of precursor. Toluene concentrations were measured by head-space gas chromatography. Protein synthesis was unchanged in the presence of low toluene concentrations. Intermediate toluene concentration decreased protein synthesis by about 20% and high toluene concentration decreased protein synthesis by about 60%. Protein synthesis was similar in cells from fed and fasted rats. Ethanol alone inhibited protein synthesis by 20-30%, more in fasted than in fed rats. Toluene and ethanol in combination inhibited protein synthesis additively. The high toluene concentration with or without ethanol appeared to inhibit synthesis/secretion of export proteins in hepatocytes from fasted rats. In conclusion, our study indicates that toluene in relatively high concentrations inhibits general protein synthesis in isolated rat hepatocytes. Toluene and ethanol seems to inhibit protein synthesis additively.

Animals↗
PubMed2003

Genetic engineering of a highly solvent-tolerant Pseudomonas putida strain for biotransformation of toluene to p-hydroxybenzoate.

The solvent-tolerant strain Pseudomonas putida DOT-T1E has been engineered for biotransformation of toluene into 4-hydroxybenzoate (4-HBA). P. putida DOT-T1E transforms toluene into 3-methylcatechol in a reaction catalyzed by toluene dioxygenase. The todC1C2 genes encode the alpha and beta subunits of the multicomponent enzyme toluene dioxygenase, which catalyzes the first step in the Tod pathway of toluene catabolism. A DOT-T1EdeltatodC mutant strain was constructed by homologous recombination and was shown to be unable to use toluene as a sole carbon source. The P. putida pobA gene, whose product is responsible for the hydroxylation of 4-HBA into 3,4-hydroxybenzoate, was cloned by complementation of a Pseudomonas mendocina pobA1 pobA2 double mutant. This pobA gene was knocked out in vitro and used to generate a double mutant, DOT-T1EdeltatodCpobA, that was unable to use either toluene or 4-HBA as a carbon source. The tmo and pcu genes from P. mendocina KR1, which catalyze the transformation of toluene into 4-HBA through a combination of the toluene 4-monoxygenase pathway and oxidation of p-cresol into the hydroxylated carboxylic acid, were subcloned in mini-Tn5Tc and stably recruited in the chromosome of DOT-T1EdeltatodCpobA. Expression of the tmo and pcu genes took place in a DOT-T1E background due to cross-activation of the tmo promoter by the two-component signal transduction system TodST. Several independent isolates that accumulated 4-HBA in the supernatant from toluene were analyzed. Differences were observed in these clones in the time required for detection of 4-HBA and in the amount of this compound accumulated in the supernatant. The fastest and most noticeable accumulation of 4-HBA (12 mM) was found with a clone designated DOT-T1E-24.

Biotransformation↗
PubMed1975

Permanent loss of chromosome initiation in toluene-treated Bacillus subtilis cells.

Initiation of deoxyribonucleic acid replication is absent in Bacillus subtilis cells made permeable by toluene. The absence of initiation may be (i) a temporary removal of toluene, or (ii) irreversibly lost due to damage by toluene treatment to a cellular structure or a process required for chromosome initiation. Washed cells, previously treated with toluene and subsequently washed free of detectable amounts of toluene, have the same characteristics of toluene-treated cells in which toluene is not removed. The continued absence of initiation in the washed cells indicates a permanent loss of initiation in cells treated with toluene. Protein synthesis is also inhibited irreversibly by toluene treatment, indicating damage to translation as a possible mechanism for loss of initiation of toluene-treated cells.

Bacillus subtilis↗
PubMed2005

Proteomic analysis reveals the participation of energy- and stress-related proteins in the response of Pseudomonas putida DOT-T1E to toluene.

Pseudomonas putida DOT-T1E is tolerant to toluene and other toxic hydrocarbons through extrusion of the toxic compounds from the cell by means of three efflux pumps, TtgABC, TtgDEF, and TtgGHI. To identify other cellular factors that allow the growth of P. putida DOT-T1E in the presence of high concentrations of toluene, we performed two-dimensional gel analyses of proteins extracted from cultures grown on glucose in the presence and in the absence of the organic solvent. From a total of 531 spots, 134 proteins were observed to be toluene specific. In the absence of toluene, 525 spots were clearly separated and 117 proteins were only present in this condition. Moreover, 35 proteins were induced by at least twofold in the presence of toluene whereas 26 were repressed by at least twofold under these conditions. We reasoned that proteins that were highly induced could play a role in toluene tolerance. These proteins, identified by matrix-assisted laser desorption ionization-time of flight mass spectrometry, were classified into four categories: 1, proteins involved in the catabolism of toluene; 2, proteins involved in the channeling of metabolic intermediates to the Krebs cycle and activation of purine biosynthesis; 3, proteins involved in sugar transport; 4, stress-related proteins. The set of proteins in groups 2 and 3 suggests that the high energy demand required for solvent tolerance is achieved via activation of cell metabolism. The role of chaperones that facilitate the proper folding of newly synthesized proteins under toluene stress conditions was analyzed in further detail. Knockout mutants revealed that CspA, XenA, and Tuf-1 play a role in solvent tolerance in Pseudomonas, although this role is probably not specific to toluene, as indicated by the fact that all mutants grew more slowly than the wild type without toluene.

Bacterial Proteins↗
PubMed1994

Toluene abuse: physical basis for hypointensity of the basal ganglia on T2-weighted MR images.

PURPOSE: To explain the hypointensity in the basal ganglia on T2-weighted magnetic resonance (MR) images of brains of toluene abusers. MATERIALS AND METHODS: Eight patients with histories of toluene abuse underwent MR imaging. A bilayered model of dipalmitoylphosphatidylcholine (DPPC; 100 mmol/L concentration) and varying concentrations of toluene was formed. The DPPC control and toluene-mixed bilayers underwent MR imaging. T1 and T2 were measured as a function of toluene and lipid concentrations. RESULTS: T2-weighted images of patients who had abused toluene showed marked hypointensity in the thalami and moderate hypointensity in the basal ganglia. Measurements of the DPPC-toluene phantom indicated that toluene-tainted lipid bilayers dramatically shortened T2 and had little effect on T1. By comparison, DPPC itself had little discernible effect on either T1 or T2. CONCLUSION: This model suggests that partitioning of toluene into the lipid membranes of cells in cerebral tissue may be responsible for the hypointensity of basal ganglia noted on T2-weighted MR images of brains of toluene abusers.

Adult↗
PubMed2000

Prenatal exposure to toluene results in abnormal neurogenesis and migration in rat somatosensory cortex.

Toluene inhalant abuse during pregnancy may result in growth-retarded microcephalic newborns who subsequently demonstrate developmental impairment. By using a rat model of toluene-abuse embryopathy, we studied the effects of prenatal toluene exposure on the generation and migration of cortical neurons. Dams were exposed by gavage to either corn oil or toluene diluted in corn oil on d 6-21 of gestation. The time of origin of cortical neurons was determined in the mature pups of dams injected with the thymidine analogue 5'-bromodeoxyuridine on 1 d during the period from d 13-21 of gestation. 5'-Bromodeoxyuridine-labeled neurons were identified by immunohistochemistry in a 400-microm-wide column of somatosensory cortex. The brains of the toluene-exposed pups had a significant reduction in the number of neurons within each cortical layer (p < 0.001). Depending on the cortical layer, the generation of neurons in the toluene-exposed pups was delayed by 1 or 2 d. In addition, the brains of the toluene-exposed pups also showed evidence of abnormal neuronal migration. However, there were no differences in either brain weight or body weight between the control and toluene-exposed pups. These observations suggest that although prenatal toluene exposure results in abnormal neuronal proliferation and migration, brain weight in the toluene-exposed pups may be preserved by enhanced development of glia or the neuropil.

Animals↗
PubMed2000

Elevation of steroid 5 alpha-reductase mRNA levels in rat cerebellum by toluene inhalation: possible relation to GFAP expression.

Toluene, a commonly used industrial solvent, is known to be toxic to both neuronal and glial cells, and has been shown to increase the immunoreactivity of glial fibrillary acidic protein (GFAP) in the brain. However, the mechanism of toluene-induced GFAP expression is poorly understood. Recently, GFAP mRNA expression in cultured astrocytes has been shown to be modulated by various steroid hormones, such as progesterone, testosterone, and their 5 alpha-reduced metabolites. Therefore, it seems possible that steroid hormones may play a potential role in the enhancement of GFAP expression observed following toluene exposure. To address this possibility, the effect of toluene inhalation on the expression of mRNAs encoding GFAP and steroidogenic enzymes in rat brain was examined. Toluene exposure increased GFAP protein contents without any significant alteration in GFAP mRNA levels in the hippocampus. In contrast, the elevation of both GFAP protein contents and its mRNA levels was observed in the cerebellum following toluene exposure. Further studies indicated that toluene exposure increased steroid 5 alpha-reductase (5 alpha-R) mRNA levels prior to the elevation of GFAP mRNA in the cerebellum, whereas neither 5 alpha-R nor GFAP mRNA levels in the hippocampus were significantly affected by toluene exposure. These results suggest that toluene inhalation may enhance GFAP gene expression in the rat cerebellum, and propose the possibility that the elevation of 5 alpha-R expression, and hence 5 alpha-reduced metabolites of steroid hormones, is presumably related to toluene-induced GFAP mRNA expression.

3-Hydroxysteroid Dehydrogenases↗
PubMed1999

Temperature effects and substrate interactions during the aerobic biotransformation of BTEX mixtures by toluene-enriched consortia and Rhodococcus rhodochrous.

A microbial consortium derived from a gasoline-contaminated aquifer was enriched on toluene (T) in a chemostat at 20 degrees C and was found to degrade benzene (B), ethylbenzene (E), and xylenes (X). Studies conducted to determine the optimal temperature for microbial activity revealed that cell growth and toluene degradation were maximized at 35 degrees C. A consortium enriched at 35 degrees C exhibited increased degradation rates of benzene, toluene, ethylbenzene, and xylenes in single-substrate experiments; in BTEX mixtures, enhanced benzene, toluene, and xylene degradation rates were observed, but ethylbenzene degradation rates decreased. Substrate degradation patterns over a range of BTEX concentrations (0 to 80 mg/L) for individual aromatics were found to differ significantly from patterns for aromatics in mixtures. Individually, toluene was degraded fastest, followed by benzene, ethylbenzene, and the xylenes. In BTEX mixtures, degradation followed the order of ethylbenzene, toluene, and benzene, with the xylenes degraded last. A pure culture isolated from the 35 degrees C-enriched consortium was identified as Rhodococcus rhodochrous. This culture was shown to degrade each of the BTEX compounds, individually and in mixtures, following the same degradation patterns as the mixed cultures. Additionally, R. rhodochrous was shown to utilize benzene, toluene, and ethylbenzene as primary carbon and energy sources. Studies conducted with the 35 degrees C-enriched consortium and R. rhodochrous to evaluate potential substrate interactions caused by the concurrent presence of multiple BTEX compounds revealed a range of substrate interaction patterns including no interaction, stimulation, competitive inhibition, noncompetitive inhibition, and cometabolism. In the case of the consortium, benzene and toluene degradation rates were slightly enhanced by the presence of o-xylene, whereas the presence of toluene, benzene, or ethylbenzene had a negative effect on xylene degradation rates. Ethylbenzene was shown to be the most potent inhibitor of BTEX degradation by both the mixed and pure cultures. Attempted quantification of these inhibition effects in the case of the consortium suggested a mixture of competitive and noncompetitive inhibition kinetics. Benzene, toluene, and the xylenes had a negligible effect on the biodegradation of ethylbenzene by both cultures. Cometabolism of o-, m-, and p-xylene was shown to be a positive substrate interaction.

Aerobiosis↗
PubMed1987

Comparisons of some behavioral effects of d-amphetamine and toluene.

The levels of toluene affecting behavior were compared to those with lethal effects, for three different routes of administration. Lethality (LC50 = 13160 ppm; LD50 = 0.47 g/kg i.p., 2.25 g/kg s.c.) consistently occurred at levels 4.5-5.0 times greater than those that reduced FI 60-sec responding 50%, for all routes of administration (2700 ppm, 100 mg/kg, i.p. and 500 mg/kg, s.c.). However, inhalational exposure to toluene had effects different than those of injections of toluene with a nose-poke response. Low-to-intermediate concentrations (approximately 1000 ppm) increased responding and higher concentrations (approximately 3000 ppm) decreased responding while injections of toluene (10-300 mg/kg, i.p. and 10-3000 mg/kg, s.c.) only decreased responding. d-Amphetamine (0.3-30 mg/kg, i.p.) injections increased nose-poke responding to a lesser extent than did inhalational exposure to toluene. When a different type of response, running (one revolution around a circular runway), was maintained under an FI 60-sec schedule, toluene, d-amphetamine, and caffeine (0.3-100 mg/kg, i.p.) only decreased responding. Thus, the behavioral effects of toluene depended upon both the response studied and the route of administration, as toluene inhalation increased nose-poke responding to a greater extent than did injections of amphetamine, caffeine, or toluene. The results characterize important situational-specific factors determining the stimulant properties and behavioral toxicity of toluene which may apply to other volatile organic solvents.

Amphetamine↗
PubMed1998

Effects of the abused solvent toluene on recombinant N-methyl-D-aspartate and non-N-methyl-D-aspartate receptors expressed in Xenopus oocytes.

Previous studies have shown that toluene, which is commonly abused, depresses neuronal activity and causes behavioral effects in both animals and man similar to those observed for ethanol. In this study, the oocyte expression system was used to test the hypothesis that toluene, like ethanol, inhibits the function of ionotropic glutamate receptors. Oocytes were injected with mRNA for specific N-methyl-D-aspartate (NMDA) or non-NMDA subunits and currents were recorded using conventional two-electrode voltage clamp. To enhance the low water solubility of toluene, drug solutions were prepared by mixing toluene with alkamuls (ethoxylated castor oil) at a 1:1 ratio (v:v) and diluting this mixture to the appropriate concentration with barium-containing normal frog Ringer solution. Alkamuls, up to 0.1%, had no significant effects on membrane leak currents or on NMDA-induced currents. Toluene, up to approximately 9 mM, had only minor effects on membrane leak currents but dose-dependently inhibited NMDA-mediated currents in oocytes. The inhibition of NMDA receptor currents by toluene was rapid, reversible and the potency for toluene's effects was subunit dependent. The NR1/2B subunit combination was the most sensitive with an IC50 value for toluene-induced inhibition of 0.17 mM. The NR1/2A and NR1/2C receptors were 6- and 12-fold less sensitive with IC50 values of 1.4 and 2.1 mM, respectively. In contrast, toluene up to approximately 9 mM did not inhibit kainate-induced currents in oocytes expressing GluR1, GluR1(+)R2 or GluR6 subunits. These results suggest that some of the effects of toluene on neuronal activity and behavior may be mediated by inhibition of NMDA receptors.

Anesthetics, Inhalation↗